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Tetsuya Kodama

Section

Graduate School of Biomedical Engineering

Job title

Professor

Degree

博士（医学）（東北大学）
博士（工学）（東北大学）

researchmap

https://researchmap.jp/read0184510

J-GLOBAL ID

200901001553249540

Research History 8

2008 -

Tohoku University　Graduate School of Biomedical Engineering　教授
2004 -

Tohoku University　Biomedical Engineering Research Organization　助教授
2002 -

Imperial College London　Faculty of Medicine　Reseacrh Associate
2000 -

Department of Medicine, Harvard Medical School　Brigham and Women's Hospital　Research Associate
1998 -

Department of Dermatology, Harvard Medical School　Massachusetts General Hospital　Instructor
1994 -

Tohoku University　Institute of Fluid Science　助手
1993 -

St. Thomas’ Hospital, London　Medical Physics Department　Visiting Scientist
1992 -

Oxford University　Physical Chemistry Laboratory　Visiting Scientist

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Committee Memberships 34

Science Advances　reviewer

2022/07 - Present
Nature Reviews Materials　学術雑誌校閲員

2018/09 - Present
Scientific Reports　校閲委員

2015/04 - Present
日本超音波医学会　工学フェロー

2014/10 - Present
日本DDS学会　評議員

2014/08 - Present
PlosONE　学術雑誌校閲員

2014/04 - Present
日本癌学会　評議員

2014/01 - Present
日本超音波医学会東北地方会運営委員会　運営委員

2009/04 - Present
International Journal of Emerging Multidisciplinary Fluid Sciences　校閲委員

2009/01 - Present
IEEE Transactions on Biomedical Engineering　委員

2009/01 - Present
Applied Physics Letters　学術雑誌校閲員

2005/04 - Present
日本生体医工学会専門別研究会「分子デリバリー研究会」　会長

2008/04 - 2012/03
Advisory Editorial Board on Ultrasound in Medicine and Biology　顧問

2008/04 - 2010/03
平成19-20年度独立行政法人日本学術振興会科学研究費委員会専門員　外部資金申請書審査委員委嘱

2007/04 - 2009/03
衝撃波シンポジウムプログラム委員会　委員

1994/04 - 1998/03
日本エム・イー学会専門別研究会「衝撃波医療法研究会」　幹事

1994/04 - 1998/03
日本機会学会　論文校閲員

1995/04 - 1997/03
事業管理支援法人三菱ＵＦＪリサーチ＆コンサルティング株式会社　外部資金申請書審査員

2012/04 -
日本生体医工学会専門別研究会「分子デリバリー研究会」　幹事

2012/04 -
National Research Foundation, South Africa　reviewer

2010/11 -
平成20年度厚生労働科学研究費補助金申請課題ナノメディシン分野審査員　外部資金申請書審査委員

2008/01 -
平成18年度厚生労働科学研究費補助金申請課題ナノメディシン分野審査員　外部資金申請書審査委員

2006/03 -
日本生体医工学会専門別研究会「分子デリバリーのME研究会」　幹事

2005/04 -
Circulation　学術雑誌校閲員

2005/04 -
Experimental Thermal and Fluid Science　学術雑誌校閲員

2005/04 -
Shock Waves　学術雑誌校閲員

2005/04 -
Ultrasound in Medicine and Biology　学術雑誌校閲員

2005/04 -
International Journal of Emerging Multidisciplinary Fluid Sciences　学術雑誌校閲員

2005/04 -
Journal of Applied Physics　学術雑誌校閲員

2005/04 -
Journal of Controlled Release　学術雑誌校閲員

2005/04 -
Journal of Fluid Mechanics　学術雑誌校閲員

2005/04 -
Journal of Japan Society of Mechanical Engineers　学術雑誌校閲員

2005/04 -
平成17年度厚生労働科学研究費補助金申請課題ナノメディシン分野審査員　外部資金申請書審査委員

2005/02 -
2004年度Israel Science Foundation (ISF)　外部資金申請書審査委員

2004/04 -

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Professional Memberships 9

Japanese Cancer Association

2005 - Present
The Japanese Society of Lymphology

2016 - Present
Japanese Society of Oral and Maxillofacial Surgeons

2008 - Present
Japan Society of Drug Delivery System

2005 - Present
Japan Society of Ultrasonics in Medicine

2004 - Present
Japan Society of Mechanical Engineers

2004 - Present
日本生体医工学会

2008 - 2015
日本口腔外科学会

2009 - 2012
Biophysical Society

2005 - 2008

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Research Interests 5

diagnosis
treatment
DDS
cancer
lymphatic metastasis

Research Areas 3

Life sciences / Biomaterials /
Life sciences / Biomedical engineering /
Life sciences / Medical systems /

Awards 33

Nanoscale Oral Presentation Award

2025/06　The 41st Annual Meeting of the Japan Society of Drug Delivery System
新人賞

2025/06　日本超音波医学会第98回学術集会（JSUM 2025）　造影超音波クラッタフィルタ法による転移リンパ節の血管構造可視化
バイオフロンティア若手優秀講演表彰

2024/12　日本機械学会　新規血管炎モデルMcH/Mo-lpr/lpr-RA1マウスにおける造影エックス線 µCTおよび病理組織学的解析を用いた血管炎評価
優秀ポスター発表賞

2024/11　公益社団法人日本口腔外科学会　Radioimmunotherapy by Lymphatic Drug Delivery System (LDDS) for the treatment of lymph node metastasis
奨励賞

2024/09　日本超音波医学会第68回東北地方会学術集会　超音波RF信号を用いたクラッタフィルタ再構成による転移リンパ節の血管抽出
Rising Scientist賞

2024/07　第78回NPO法人日本口腔科学会学術集会　抗 CTLA4 抗体を用いたリンパ行性薬物送達法によるがん免疫療法に関する実験病理学的検討
Journal Award

2024/07　Lymphatic Drug Delivery System of Single Dose Anti-CTLA4 Enhance by Local X-Ray Irradiation Treatment for Lymph Node Metastatic
優秀論文発表賞

2023/12　日本生体医工学会関東支部　転移リンパ節に対する磁性ナノ粒子Resovist® を用いた磁気温熱療法の開発
Oustanding Student Presentation

2022/06
Oustanding Student Presentation

2022/01　Japan Society of Mechanical Engineers
Encouragement Prize

2020/09　The 60th Annual Meeting of The Japan Society of Ultrasonics in Medicine　A study on the evaluation of treatment efficacy of metastatic lymph nodes associated with changes in drug osmotic pressure in the lymphatic drug delivery system
Oral Presentation 1st Place

2017/08/03　3rd Annual Data Science in Life Science and Engineering Collaboration and Symposium　New insights on Lymph node metastasis : the benefit of using our mouse model in cancer metastasis
CyPos賞 Silver medal

2017/04/13　第76回日本医学放射線学会総会　Quantitative analysis of contrast-enhanced ultrasound for diagnosis of early lymph node metastasis of breast cancer．
学術奨励賞

2016/10/01　第67回仙萩会総会　Direct Delivery of a Cytotoxic Anticancer Agent into the Metastatic Lymph Node Using Nano/Microbubbles and Ultrasound.
第５回新人賞

2016/05/28　日本超音波医学会　ソノポレーションを利用したVasohibin-1 遺伝子導入による抗腫瘍効果の評価
第17回奨励賞

2016/05/28　日本超音波医学会第89回学術集会　乳癌における造影超音波を用いた血管密度定量法
Oral Presenation Award

2014/03/13　The 8th East Asian Consortium on Biomedecal Engineering　Study of diagnosis of lymph node metastasis by Micro-CT
学生奨励賞

2014/03/13　第76回情報処理学会全国大会　超音波画像診断における微小気泡造影剤の検出手法の検討
The Presentation Award

2014/03/12　8th Student Workshop East Asia Consortium on Biomedical Engineering　Inhibition of tumor growth in lymph nodes by lymphatic administration od frugs and nano/microbubbles with ultrasound exposure.
Young Endourologist Award（ポスター部門）

2013/11/09　第27回日本泌尿器内視鏡学会総会　リンパ節担がんマウスに対する超音波と微小気泡をもちいた抗がん剤治療に関する研究
優秀講演発表賞

2013/10/01　第58回日本口腔外科学科総会・学術大会　ナノバブルと高周波超音波による微小リンパ節転移画像診断法の検討
Oral Presenation Award

2013/03/24　The 6th East Asian Pacific Student Workshop on Nano-Biomedical Engineering　Early diagnosis of lymph node metastasis by micro-CT.
Oral Presenation Award

2013/03/23　The 7th East East Asian Consortium on Biomedecal Engineering　Development of a method for doxorubicin delivery through lymphatic vessel into a metastatic lymph node using nano/micro bubbles and ultrasound
IADR/AADR William J. Gies Award

2011/03/16　IADR/AADR　Periodontal gene transfer by ultrasound and nano-/microbubbles
第25回日本DDS学会ベストポスター賞

2009/07/07　第25回日本DDS学会　124I を使用したNIS遺伝子発現イメージング法の開発:超音波とナノバブルを利用した遺伝子デリバリー
第46回日本癌治療学会総会優秀演題賞

2008/10/30　日本癌治療学会　高周波超音波イメージングシステムを用いた所属リンパ節転移画像診断システムの開発
ゴールドリボン賞

2008/10/20　第53回日本口腔外科学会総会　ナノバブルと超音波を用いた腫瘍血管造影法による口腔癌診断システムモデルの開発
ゴールドリボン賞

2008/10/20　第53回日本口腔外科学会総会　ナノバブルと超音波を用いた抗癌剤および抗腫瘍分子導入による新たな癌治療法の開発
日本実験力学会2008年度年次講演会優秀講演賞受賞

2008/06/30　日本実験力学会　歯周組織への遺伝子導入を目指した新しい非ウイルス法の開発
日本超音波医学会第8回奨励賞

2007/05　日本超音波医学会　ソノポレーションによる遺伝子導入効率：気泡特性に対する検討
Paper Presenter Award

2006/06/01　The 11th Congress of the world federation for ultrasound in Medicine and Biology.　Delivery of sodium/iodide symportter therapy using nanobubbles with ultrasound.
Paper Presenter Award

2006/06/01　The 11th Congress of the world federation for ultrasound in Medicine and Biology. WFUM’B 2006　HSV-tk/GCV Cytotoxic Gene Therapy using ultrasound and nanobubbles
Paper Presenter Award

2006/06/01　The 11th Congress of the world federation for ultrasound in Medicine and Biology. WFUM’B 2006　Effects of anti-cancer drug of cisplatin using nanobubbles and ultrasound

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Papers 294

Attenuation Estimation and Acoustic Characterization of Mouse Lymph Node Tumor Using High-frequency Ultrasound

Masaaki Omura, Kazuki Maeda, Kazuki Tamura, Kenji Yoshida, Ariunbuyan Sukhbaatar, Tetsuya Kodama, Tadashi Yamaguchi

Molecular Imaging and Biology　27　379-388　2025/05/12
Publisher: Springer Science and Business Media LLC
DOI： 10.1007/s11307-025-02007-2 　

ISSN： 1536-1632

eISSN： 1860-2002

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Abstract Purpose Lymph node (LN) biopsy is the gold standard for diagnosing metastasis. While ultrasound imaging is a non-invasive method for real-time LN metastasis diagnosis and tumor assessment, its accuracy depends on operator skill and system settings. Quantitative ultrasound can characterize tissue microstructure changes due to tumors, offering operator-independent parameters, and one of the quantitative ultrasound methods, the backscatter coefficient, is necessary to compensate for tissue attenuation. However, the change in the attenuation coefficient (AC) in the tumor growth is uncertain. Using in vivo high-frequency ultrasound (25 MHz) measurement and scanning acoustic microscopy (80 and 300 MHz) for ex vivo samples, we aim to investigate how tumor growth is linked to the attenuation and acoustic properties such as acoustic impedance and speed of sound related to ultrasonic wave propagation. Procedures FM3 A-Luc mammary carcinoma cells were inoculated into the subiliac LNs of mice, and tumor progression was monitored over time. Bioluminescence imaging was used to assess tumor growth, while ultrasound measurements focused on estimating AC and other acoustic properties. Results Results indicated that the mean of AC decreased, and its standard deviation increased as tumors grew, correlating with bioluminescence intensity. Furthermore, acoustic impedance and speed of sound varied between normal and tumor tissues, revealing differences in tissue microstructure from the histopathological images. Conclusions The finding of a decrease in AC observed with tumor growth may play a crucial role in enhancing the accuracy of quantitative ultrasound on attenuation compensation, potentially improving the differentiation between metastatic and non-metastatic LNs.
Optimization of lymphatic drug delivery system with carboplatin for metastatic lymph nodes

Miriu Miyatsu, Ariunbuyan Sukhbaatar, Radhika Mishra, Arunkumar Dorai, Shiro Mori, Tetsuya Kodama

Scientific Reports　15　(1)　2025/05/08
Publisher: Springer Science and Business Media LLC
DOI： 10.1038/s41598-025-99602-8 　

eISSN： 2045-2322
Positive sentinel lymph node biopsy on promotion of metastasis: An unexpected effect?

Lenan Shao, Ariunbuyan Sukhbaatar, Tsuyoshi Sugiura, Tetsuya Kodama

Medical Hypotheses　111624-111624　2025/04
Publisher: Elsevier BV
DOI： 10.1016/j.mehy.2025.111624 　

ISSN： 0306-9877
Development of an intranodal drug delivery system using a mouse model with lymphadenopathy: novel discoveries and clinical application

Tetsuya Kodama, Ariunbuyan Sukhbaatar

Expert Opinion on Drug Delivery　22　(4)　555-564　2025/02/24
Publisher: Informa UK Limited
DOI： 10.1080/17425247.2025.2471982 　

ISSN： 1742-5247

eISSN： 1744-7593
Ultrasound irradiation in the presence of microbubbles may enhance the antitumor effect of chemotherapeutic agents against bladder cancer. International-journal

Takehiro Suzuki, Takuma Sato, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama, Akihiro Ito

Journal of Cancer　16　(2)　368-381　2025

DOI： 10.7150/jca.100846 　

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Intravesical instillation of chemotherapy has been performed to reduce the risk of intravesical recurrence of bladder cancer. However, its antitumor effect is not necessarily sufficient, which may be partially due to inadequate delivery of intravesically administered chemotherapeutic agents to bladder tumors. Ultrasound irradiation to target tissues in the presence of microbubbles is a technique to transiently enhance cell membrane permeability and achieve efficient drug delivery to the desired sites without damage to non-target areas; this technique has been used in chemotherapy, immunotherapy, gene therapy, and radiotherapy for the treatment of various cancers. However, the effectiveness of combining intravesical instillation of chemotherapy and this strategy for the treatment of bladder cancer has not been fully investigated. This report shows that mitomycin C combined with ultrasound and microbubbles has a higher antitumor effect than mitomycin C alone against mouse bladder cancer cells. Next, the antitumor effect of intravesical instillation of chemotherapy combined with ultrasound and microbubbles was demonstrated using an orthotopic mouse bladder cancer model. In vivo experiments showed that ultrasound irradiation in the presence of microbubbles enhanced the local delivery of fluorescent molecules and had the potential to enhance the antitumor effect of intravesical instillation of chemotherapy without visible damage to the surrounding normal tissues. The results of the present study demonstrate that intravesical chemotherapy combined with ultrasound and microbubbles is potentially a safe and effective treatment for bladder cancer.
Development of LDDS for lymph node metastasis of the head and neck cancer

Shiga K., Kusaka T., Katagiri K., Saito D., Kodama T.

Japanese Journal of Lymphology　47　(2)　87-90　2024/12
Development of lymphatic drug delivery system (LDDS)

Kodama T., Sukhbaatar A., Mori S., Shiga K.

Japanese Journal of Lymphology　47　(2)　84-86　2024/12
Modeling of scattering coefficient for biological tissues exposed to near-infrared laser irradiation

Akiyoshi Obonai, Takuma Kogawa, Yuki Kanda, Tetsuya Kodama, Atsuki Komiya

Applied Thermal Engineering　256　123990-123990　2024/11
Publisher: Elsevier BV
DOI： 10.1016/j.applthermaleng.2024.123990 　

ISSN： 1359-4311
A combination of lymphatic drug delivery of anti-CTLA-4 antibody and local radiotherapy for solid-tumor treatment. Peer-reviewed

Takagi K, Sukhbaatar A, Mori S, Kodama T

Cancer Science　2024/10

DOI： 10.1111/cas.16369 　
Facile green synthesis of dual stabilized near-infrared CuInSe/ZnS quantum dots as fluorescent probes for cancer-bacteria imaging Peer-reviewed

Vuyelwa Ncapayi, Neethu Ninan, Thabang C. Lebepe, Sundararajan Parani, Aswathy Ravindran Girija, Richard Bright, Krasimir Vasilev, Rodney Maluleke, Ncediwe Tsolekile, Olanrewaju A. Aladesuyi, Tetsuya Kodama, Oluwatobi S. Oluwafemi

Inorganic Chemistry Communications　167　112795-112795　2024/09
Publisher: Elsevier BV
DOI： 10.1016/j.inoche.2024.112795 　

ISSN： 1387-7003
Photothermal Depth Profiling of Gelatin-Stabilised Gold Nanorods-Trastuzumab Conjugate as a Potential Breast Cancer Photothermal Agent Peer-reviewed

Gracia It Mwad Mbaz, Thabang Calvin Lebepe, Rodney Maluleke, Akiyoshi Obonai, Nande Mgedle, Olanrewaju A. Aladesuyi, Rajendran Kalimutu, Tetsuya Kodama, Atsuki Komiya, Oluwatobi Samuel Oluwafemi

Journal of Inorganic and Organometallic Polymers and Materials　2024/07/03
Publisher: Springer Science and Business Media LLC
DOI： 10.1007/s10904-024-03151-y 　

ISSN： 1574-1443

eISSN： 1574-1451

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Abstract Gold nanorods (AuNRs) are powerful photothermal agents (PTAs) in cancer treatment due to their near-infrared laser light absorption ability. However, the cytotoxicity of AuNRs caused by the presence of cationic surfactants often used and their lack of specificity affect their application in photothermal therapy. Thus, we herein developed a bioconjugate obtained from the functionalisation of AuNRs to gelatin (Gel@AuNRs), followed by the conjugation of the as-synthesised material to a breast cancer antibody, trastuzumab (Trast-Gel@AuNRs) to address these issues. The optical and structural characterization of the as-synthesized indicated no significant changes in the optical properties of AuNRs after their functionalisation with gelatin and conjugation with the antibody. The photothermal profiling of the as-synthesised materials showed that AuNRs still have an excellent photothermal conversion efficiency (PCE) after their functionalisation (20%) and their conjugation to an antibody (19%). In addition, the In vitro photothermal depth response showed that Trast-Gel@AuNRs is a promising photothermal agent for HER2-positive breast cancer treatment. Graphical Abstract
Docetaxel administered through a novel lymphatic drug delivery system (LDDS) improved treatment outcomes for lymph node metastasis Peer-reviewed

Ariunbuyan Sukhbaatar, Shiro Mori, Tsuyoshi Sugiura, Tetsuya Kodama

Biomedicine & Pharmacotherapy　171　116085-116085　2024/02
Publisher: Elsevier BV
DOI： 10.1016/j.biopha.2023.116085 　

ISSN： 0753-3322
Large-scale synthesis of CISe/ZnS core-shell quantum dots and its effects on the enzymatic activity of recombinant human furin (an activator of SARS-COV-2 S1/S2 spike proteins) Peer-reviewed

Vuyelwa Ncapayi, Oladoyin Famutimi, Thabang Calvin Lebepe, Rodney Maluleke, Sam Masha, Nande Mgedle, Sundararajan Parani, Tetsuya Kodama, Isaac Olusanjo Adewale, Oluwatobi Samuel Oluwafemi

Colloid and Interface Science Communications　56　100737-100737　2023/09
Publisher: Elsevier BV
DOI： 10.1016/j.colcom.2023.100737 　

ISSN： 2215-0382
An electrochemical immunosensor on a carbon nanofiber/gold nanoparticles platform for the detection of alpha-feto protein cancer biomarker Peer-reviewed

Foluke O.G. Olorundare, Dimpo S. Sipuka, Tsholofelo I. Sebokolodi, Sesethu Makaluza, Nyasha Midzi, Tetsuya Kodama, Omotayo A. Arotiba, Duduzile Nkosi

Sensing and Bio-Sensing Research　100574-100574　2023/08
Publisher: Elsevier BV
DOI： 10.1016/j.sbsr.2023.100574 　

ISSN： 2214-1804
Intralymphatic injection of chemotherapy drugs modulated with glucose improves their anticancer effect. International-journal Peer-reviewed

Ariunbuyan Sukhbaatar, Shiro Mori, Kiyoto Shiga, Tetsuya Kodama

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie　165　115110-115110　2023/07/06

DOI： 10.1016/j.biopha.2023.115110 　

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Lymph node metastasis (LNM) has a significant impact on cancer prognosis, emphasizing the need for effective treatment strategies. This study investigated the potential use of high osmotic pressure drug solutions with low viscosity administration using a lymphatic drug delivery system (LDDS) to improve LNM treatment outcomes. The hypothesis was that injection of epirubicin or nimustine at high osmotic pressure but without altered viscosity would enhance drug retention and accumulation in LNs, thereby improving the efficacy of treatment. Biofluorescence analysis revealed enhanced drug accumulation and retention in LNs after administration using LDDS compared to intravenous (i.v) injection. Histopathological results demonstrated minimal tissue damage in the LDDS groups. Pharmacokinetic analysis revealed an improved treatment response with higher drug accumulation and retention in LNs. The LDDS approach offers the potential for greatly reduced side effects of chemotherapy drugs, lower dosage requirements and crucially increased drug retention in LNs. The results highlight the promise of high osmotic pressure drug solutions with low viscosity administrated using the LDDS for enhancing the treatment efficacy of LN metastasis. Further research and clinical trials are warranted to validate these results and optimize the clinical translation of this novel treatment technique.
NIR-II window absorbing graphene oxide-coated gold nanorods and graphene quantum dot-coupled gold nanorods for photothermal cancer therapy Peer-reviewed

Thabang C. Lebepe, Sundararajan Parani, Rodney Maluleke, Vuyelwa Ncapayi, Olanrewaju A. Aladesuyi, Atsuki Komiya, Tetsuya Kodama, Oluwatobi S. Oluwafemi

Nanotechnology Reviews　12　(1)　2023/06/07
Publisher: Walter de Gruyter GmbH
DOI： 10.1515/ntrev-2022-0541 　

eISSN： 2191-9097

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Abstract The graphene-based materials have been used as a potential coating material for nanoparticles due to their excellent passivation. Herein, we report for the first time the colloidal stability, photothermal profile, thermal stability, cytotoxicity, and photo-cytotoxicity of graphene quantum dots (GQDs) coupled with the second infrared window (NIR-II) absorbing gold nanorods (AuNRs/GQDs) and compare it to graphene oxide (GO)-coated NIR-II absorbing AuNRs (AuNRs/GO). The composites were achieved by electrostatic interaction of the GO or GQDs with AuNRs. The results revealed that (i) AuNRs/GQDs were more stable in the aqueous phosphate buffer and cell culture media than AuNRs/GO and AuNRs; (ii) GO enhanced the photothermal efficiency of the AuNRs, whereas GQDs reduced it; (iii) GQDs enhanced the photothermal stability of AuNRs than GO; (iv) both AuNRs/GO and AuNRs/GQDs were biocompatible with mouse colon carcinoma (C26) cell lines and malignant fibrous histiocytoma‐like, expressing a fusion of the luciferase and enhanced green fluorescent protein genes (KM-Luc/GFP) cell lines; and (v) photo-cytotoxicity of AuNRs/GO and AuNRs/GQDs conducted against C26 cell lines showed significantly improved cell death compared to laser irradiation alone; however, AuNRs/GO exhibited high photo-toxicity than AuNRs/GQDs. This study shows that AuNRs/GO and AuNRs/GQDs composites possess unique properties to improve AuNRs and be utilised in photothermal applications.
Metastatic lymph node targeted CTLA4 blockade: a potent intervention for local and distant metastases with minimal ICI-induced pneumonia. International-journal Peer-reviewed

Radhika Mishra, Ariunbuyan Sukhbaatar, Shiro Mori, Tetsuya Kodama

Journal of experimental & clinical cancer research : CR　42　(1)　132-132　2023/06/01

DOI： 10.1186/s13046-023-02645-w 　

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BACKGROUND: Immune checkpoint blockade (ICB) elicits a strong and durable therapeutic response, but its application is limited by disparate responses and its associated immune-related adverse events (irAEs). Previously, in a murine model of lymph node (LN) metastasis, we showed that intranodal administration of chemotherapeutic agents using a lymphatic drug delivery system (LDDS) elicits stronger therapeutic responses in comparison to systemic drug delivery approaches, while minimizing systemic toxicity, due to its improved pharmacokinetic profile at the intended site. Importantly, the LN is a reservoir of immunotherapeutic targets. We therefore hypothesized that metastatic LN-targeted ICB can amplify anti-tumor response and uncouple it from ICB-induced irAEs. METHODS: To test our hypothesis, models of LN and distant metastases were established with luciferase expressing LM8 cells in MXH10/Mo-lpr/lpr mice, a recombinant inbred strain of mice capable of recapitulating ICB-induced interstitial pneumonia. This model was used to interrogate ICB-associated therapeutic response and immune related adverse events (irAEs) by in vivo imaging, high-frequency ultrasound imaging and histopathology. qPCR and flowcytometry were utilized to uncover the mediators of anti-tumor immunity. RESULTS: Tumor-bearing LN (tbLN)-directed CTLA4 blockade generated robust anti-tumor response against local and systemic metastases, thereby improving survival. The anti-tumor effects were accompanied by an upregulation of effector CD8T cells in the tumor-microenvironment and periphery. In comparison, non-specific CTLA4 blockade was found to elicit weaker anti-tumor effect and exacerbated ICI-induced irAEs, especially interstitial pneumonia. Together these data highlight the importance of tbLN-targeted checkpoint blockade for efficacious response. CONCLUSIONS: Intranodal delivery of immune checkpoint inhibitors to metastatic LN can potentiate therapeutic response while minimizing irAEs stemming from systemic lowering of immune activation threshold.
Photostable fluorescent Near-infrared colloidal Mn-doped CuInSe/ZnS quantum dots for cancer-bacteria dual imaging Peer-reviewed

Vuyelwa Ncapayi, Neethu Ninan, Thabang C. Lebepe, Sundararajan Parani, Aswathy Ravindran Girija, Richard Bright, Rodney Maluleke, Olanrewaju A. Aladesuyi, Tetsuya Kodama, Krasimir Vasilev, Oluwatobi S. Oluwafemi

Journal of Luminescence　258　119785-119785　2023/06
Publisher: Elsevier BV
DOI： 10.1016/j.jlumin.2023.119785 　

ISSN： 0022-2313
マウス膀胱がんモデルに対する、微小気泡と超音波を併用した抗がん剤の膀胱注入療法の治療効果の解析(The combination of vesical instillation of chemotherapy with ultrasound and nanobubbles is efficient against experimental tumors in murine bladder cancer model)

鈴木健大, 佐藤琢磨, アリウンブヤン・スフバートル, 阪本真弥, 森士朗, 小玉哲也, 伊藤明宏

日本泌尿器科学会総会　110回　AOP06-08　2023/04
Publisher: (一社)日本泌尿器科学会総会事務局
A study of temperature distribution using a combination of near-infrared laser, gold nanorods, and surface cooling Peer-reviewed

Akiyoshi Obonai, Takuma Kogawa, Yuki Kanda, Oluwatobi S. Oluwafemi, Tetsuya Kodama, Atsuki Komiya

Applied Thermal Engineering　120579-120579　2023/04
Publisher: Elsevier BV
DOI： 10.1016/j.applthermaleng.2023.120579 　

ISSN： 1359-4311
Wireless temperature monitoring by using magnetic nanoparticles for biomedical applications on magnetic hyperthermia treatment Peer-reviewed

Akihiro Kuwahata, Ryuichi Hirota, Ariunbuyan Sukhbaatar, Tetsuya Kodama, Shin Yabukami

AIP Advances　13　(2)　025142-025142　2023/02/01
Publisher: AIP Publishing
DOI： 10.1063/9.0000557 　

eISSN： 2158-3226

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Magnetic hyperthermia with magnetic nanoparticles (MNPs) has been introduced to selective treatment of tumor and the MNPs also has demonstrated diagnosis. For non-invasive treatment, a therapeutic platform with temperature monitoring that can avoid overheating in normal tissues is of vital importance. In this study, we have developed a wireless temperature monitoring system by utilizing the combination of magnetic harmonic signals of the MNPs for magnetic hyperthermia treatment in laboratory experiments. We achieved an accurate measurement with an error of 0.18 °C. For practical use on breast/oral cancer, a detectable distance of at least 10 mm is required. To demonstrate the feasibility toward future biomedical applications, we investigated the dependency on the amount of Resovist^® and the error is less than 0.5 °C in a 10 mm distance. Our system can measure the correct temperature regardless of Resovist amount. The results indicate that our system can apply for monitoring temperature on magnetic hyperthermia treatment.
An electrochemical immunosensor for an alpha-fetoprotein cancer biomarker on a carbon black/palladium hybrid nanoparticles platform Peer-reviewed

Foluke O. G. Olorundare, Dimpo S. Sipuka, Tsholofelo I. Sebokolodi, Tetsuya Kodama, Omotayo A. Arotiba, Duduzile Nkosi

Analytical Methods　15　(29)　3577-3585　2023
Publisher: Royal Society of Chemistry (RSC)
DOI： 10.1039/d3ay00702b 　

ISSN： 1759-9660

eISSN： 1759-9679

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An electrochemical immunosensor for alpha-fetoprotein.
Combination therapy of lymphatic drug delivery and total body irradiation in a metastatic lymph node and lung mouse model Peer-reviewed

Shota Sora, Ariunbuyan Sukhbaatar, Shinichi Fukushige, Shiro Mori, Maya Sakamoto, Tetsuya Kodama

Cancer Science　114　(1)　227-235　2022/10/18
Publisher: Wiley
DOI： 10.1111/cas.15562 　

ISSN： 1347-9032

eISSN： 1349-7006
Drug formulation augments the therapeutic response of carboplatin administered through a lymphatic drug delivery system. International-journal Peer-reviewed

Radhika Mishra, Ariunbuyan Sukhbaatar, Arunkumar Dorai, Shiro Mori, Kiyoto Shiga, Tetsuya Kodama

Cancer Science　2022/09/28

DOI： 10.1111/cas.15599 　

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Treatment of metastatic lymph nodes (LNs) is challenging due to their unique architecture and biophysical traits. Systemic chemotherapy fails to impede tumor progression in LNs due to poor drug uptake and retention by LNs, resulting in fatal systemic metastasis. To effectively treat LN metastasis, achieving specific and prolonged retention of chemotherapy drugs in the tumor-draining LNs is essential. The lymphatic drug delivery system (LDDS) is an ultrasound-guided drug delivery methodology for administration of drugs to LNs that addresses these requirements. However, early-stage metastatic LNs have an additional set of drug transport barriers, such as elevated intranodal pressure and viscosity, that negatively impact drug diffusion. In the present study, using formulations of elevated osmotic pressure and viscosity relative to saline, we sought to favorably alter the LN's physical environment and study its impact on pharmacokinetics and consequently the therapeutic efficacy of carboplatin delivered using the LDDS. Our study confirmed the capability of a drug formulation with elevated osmotic pressure and viscosity to alter the architecture of LNs, as it caused notable expansion of the lymphatic sinus. Additionally, the study delineated an optimal range of osmotic pressure and viscosity, centered around 1,897 kPa and 11.5 mPa·s, above and below which therapeutic efficacy was found to decline markedly. These findings suggests that formulation osmotic pressure and viscosity are parameters that require critical consideration as they can both hinder and promote tumorigenesis. The facile formulation reported here has wide ranging applicability across cancer spectrums and is thus anticipated to be of great clinical benefit.
Intranodal delivery of modified docetaxel: Innovative therapeutic method to inhibit tumor cell growth in lymph nodes International-journal Peer-reviewed

Ariunbuyan Sukhbaatar, Shiro Mori, Tetsuya Kodama

Cancer Science　113　(4)　1125-1139　2022/01/31
Publisher: Wiley
DOI： 10.1111/cas.15283 　

ISSN： 1347-9032

eISSN： 1349-7006

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Delivery of chemotherapeutic agents into metastatic lymph nodes (LNs) is challenging as they are unevenly distributed in the body. They are difficult to access via traditional systemic routes of drug administration, which produce significant adverse effects and low accumulation of drug into the cancerous LNs. To improve the survival rate of patients with LN metastasis, a lymphatic drug delivery system (LDDS) has been developed to target metastatic LNs by delivering chemotherapy agents into sentinel LNs (SLNs) under ultrasound guidance. The LDDS is an advanced method that can be applied at the early stage of progression of tumor cells in the SLNs, before tumor mass formation has occurred. Here we investigated the optimal physicochemical ranges of chemotherapeutic agents' solvents with the aim of increasing treatment efficacy using the LDDS. We found that an appropriate osmotic pressure range for drug administration was 700 - 3,000 kPa, with a viscosity < 40 mPa⋅s. In these physicochemical ranges, expansion of lymphatic vessels and sinuses, drug retention and subsequent antitumor effects could be more precisely controlled. Furthermore, the antitumor effects depended on the tumor progression stage in the SLNs, the injection rate and volumes of administered drugs. We anticipate these optimal ranges to be a starting point for the development of more effective drug regimens to treat metastatic LNs with the LDDS.
Protocols for the Evaluation of a Lymphatic Drug Delivery System Combined with Bioluminescence to Treat Metastatic Lymph Nodes. International-journal Peer-reviewed

Ariunbuyan Sukhbaatar, Tetsuya Kodama

Methods in molecular biology (Clifton, N.J.)　2524　333-346　2022

DOI： 10.1007/978-1-0716-2453-1_27 　

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Bioluminescence (BL) imaging is a powerful non-invasive imaging modality widely used in a broad range of biological disciplines for many types of measurements. The applications of BL imaging in biomedicine are diverse, including tracking bacterial progression, research on gene expression patterns, monitoring tumor cell growth/regression or treatment responses, determining the location and proliferation of stem cells, and so on. It is particularly valuable when studying tissues at depths of 1 to 2 cm in mouse models during preclinical research. Here we describe the protocols for the therapeutic evaluation of a lymphatic drug delivery system (LDDS) using an in vivo BL imaging system (IVIS) for the treatment of metastatic lymph nodes (LNs) with 5-fluorouracil (5-FU). The LDDS is a method that directly injects anticancer drugs into sentinel LNs (SLNs) and delivers them to their downstream LNs. In the protocol, we show that metastases in the proper axillary LN (PALN) are induced by the injection of luciferase-expressing tumor cells into the subiliac LN (SiLN) of MXH10/Mo-lpr/lpr (MXH10/Mo/lpr) mice. 5-FU is injected using the LDDS into the accessory axillary LN (AALN) to treat tumor cells in the PALN after the tumor cell growth is confirmed in the PALN. The tumor growth and therapeutic effects are evaluated by IVIS. This method can be used to evaluate tumor growth and efficacy of anticancer drugs/particles, radiotherapy, surgery, and/or a combination of these methods in various experimental procedures in the oncology field.
Animal Experiment of PID-based Automatic Temperature Control System for Magnetic Hyperthermia.

Shikano A, Tonthat L, Kuwahata A, Sukhbaatar A, Kodama T, Yabukami S

T. Magn. Soc. Jpn. (Special Issues)　6　(1)　2022

DOI： 10.20819/msjtmsj.22TR519 　
Perfusion defects in non-enlarged metastatic lymph nodes using vessel wall magnetic resonance imaging: Detection performance and diagnostic value International-journal Peer-reviewed

Maya Sakamoto, Ikuho Kojima, Masahiro Iikubo, Koichi Ito, Takafumi Aoki, Shiro Mori, Takenori Ogawa, Yukio Katori, Takaki Murata, Daisuke Ito, Tetsuya Kodama

Clinical & Experimental Metastasis　39　(3)　421-431　2022/01
Publisher: Springer Science and Business Media LLC
DOI： 10.1007/s10585-022-10147-w 　

ISSN： 0262-0898

eISSN： 1573-7276

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A perfusion defect (PD) in non-enlarged lymph nodes (LNs) of oral squamous cell carcinoma (OSCC) is the most reliable radiological criterion for the diagnosis of metastasis. However, conventional contrast-enhanced (CE) T1 weighted images using turbo spin echo (TSE) sequence is limited in detecting PD in non-enlarged LNs due to flow artifacts from cervical blood vessels. Vessel wall (VW) MR imaging with blood vessel flow suppression and high spatial resolution may provide new insights into the detection of PD. However, there are no reports in the literature on the usefulness of VW MR imaging for the diagnosis of LN metastasis. It is demonstrated that PD of non-enlarged LNs in CE VR MR imaging of OSCC patients is useful for the diagnosis of metastatic LNs. VW MR imaging was significantly more sensitive in detecting PD of non-enlarged metastatic LNs than conventional TSE imaging on visual evaluation. Furthermore, it was found that the image contrast between PD and surrounding intranodal tissue in CE VW MR images was higher than that in conventional CE TSE images. In the correlation between imaging and histopathological findings of metastatic LNs, all LNs that exhibited PD on CE VW MR images were at an advanced histopathological metastatic stage. The pathology of PD was necrotic tissue with keratinization. The results indicated that PD in CE VW imaging is useful in diagnosing non-enlarged LNs at an advanced metastasis stage. The addition of VW MR imaging to conventional MR examination achieves higher diagnostic performance for non-enlarged metastatic LNs.
Graphene Oxide-Gold Nanorods Nanocomposite-Porphyrin Conjugate as Promising Tool for Cancer Phototherapy Performance Peer-reviewed

Thabang Calvin Lebepe, Sundararajan Parani, Vuyelwa Ncapayi, Rodney Maluleke, Grace It Mwad Mbaz, Olufunto Tolulope Fanoro, Jose Rajendran Varghese, Atsuki Komiya, Tetsuya Kodama, Oluwatobi Samuel Oluwafemi

Pharmaceuticals　14　(12)　1295-1295　2021/12/11
Publisher: MDPI AG
DOI： 10.3390/ph14121295 　

eISSN： 1424-8247

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The cancer mortality rate has increased, and conventional cancer treatments are known for having many side effects. Therefore, it is imperative to find a new therapeutic agent or modify the existing therapeutic agents for better performance and efficiency. Herein, a synergetic phototherapeutic agent based on a combination of photothermal and photodynamic therapy is proposed. The phototherapeutic agent consists of water-soluble cationic porphyrin (5,10,15,20-tetrakis(N-methylpyridinium-3-yl)porphyrin, TMePyP), and gold nanorods (AuNRs) anchored on graphene-oxide (GO) sheet. The TMePyP was initially synthesized by Adler method, followed by methylation, while GO and AuNRs were synthesized using Hummer’s and seed-mediated methods, respectively. The structural and optical properties of TMePyP were confirmed using UV-Vis, zeta analyzer, PL, FTIR and NMR. The formation of both GO and AuNRs was confirmed by UV-Vis-NIR, FTIR, TEM and zeta analyzer. TMePyP and AuNRs were anchored on GO to form GO@AuNRs-TMePyP nanocomposite. The as-synthesized nanocomposite was stable in RPMI and PBS medium, and, on irradiation, produced high heat than the bare AuNRs, with high photothermal efficiency. In addition, the nanocomposite produced higher singlet oxygen than TMePyP with high biocompatibility in the absence of light. These results indicated that the as-synthesized nanocomposite is a promising dual photodynamic and photothermal agent for cancer therapy.
Diagnosis of Prostate Cancer and Prostatitis Using near Infra-Red Fluorescent AgInSe/ZnS Quantum Dots Peer-reviewed

Vuyelwa Ncapayi, Neethu Ninan, Thabang C. Lebepe, Sundararajan Parani, Aswathy Ravindran Girija, Richard Bright, Krasimir Vasilev, Rodney Maluleke, Ncediwe Tsolekile, Tetsuya Kodama, Oluwatobi S. Oluwafemi

International Journal of Molecular Sciences　22　(22)　12514-12514　2021/11/19
Publisher: MDPI AG
DOI： 10.3390/ijms222212514 　

eISSN： 1422-0067

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The link between the microbiome and cancer has led researchers to search for a potential probe for intracellular targeting of bacteria and cancer. Herein, we developed near infrared-emitting ternary AgInSe/ZnS quantum dots (QDs) for dual bacterial and cancer imaging. Briefly, water-soluble AgInSe/ZnS QDs were synthesized in a commercial kitchen pressure cooker. The as-synthesized QDs exhibited a spherical shape with a particle diameter of 4.5 ± 0.5 nm, and they were brightly fluorescent with a photoluminescence maximum at 705 nm. The QDs showed low toxicity against mouse mammary carcinoma (FM3A-Luc), mouse colon carcinoma (C26), malignant fibrous histiocytoma-like (KM-Luc/GFP) and prostate cancer cells, a greater number of accumulations in Staphylococcus aureus, and good cellular uptake in prostate cancer cells. This work is an excellent step towards using ternary QDs for diagnostic and guided therapy for prostate cancer.
Synthesis of NIR-II Absorbing Gelatin Stabilized Gold Nanorods and Its Photothermal Therapy Application against Fibroblast Histiocytoma Cells Peer-reviewed

Adewale Oladipo, Thabang Calvin Lebepe, Sundararajan Parani, Rodney Maluleke, Vuyelwa Ncapayi, Grace It Mwad Mbaz, Sandile Phinda Songca, Tetsuya Kodama, Oluwatobi Samuel Oluwafemi

Pharmaceuticals　14　(11)　1137-1137　2021/11/09
Publisher: MDPI AG
DOI： 10.3390/ph14111137 　

eISSN： 1424-8247

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The excellent photothermal properties of gold nanorods (Au-NRs) make them one of the most researched plasmonic photothermal nanomaterials. However, their biological applications have been hampered greatly due to surfactant-induced cytotoxicity. We herein report a simple synthesis of highly biocompatible gelatin stabilized Au-NRs (gelatin@Au-NRs) to address this issue. The optical and structural properties of the as-synthesized gelatin@Au-NRs were investigated by Zetasizer, Ultraviolet-Visible-Near Infrared (UV-Vis-NIR) spectroscopy, high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared spectroscopy (FTIR). The as-synthesized gelatin@Au-NRs were highly crystalline and rod-like in shape with an average length and diameter of 66.2 ± 2.3 nm and 10 ± 1.6 nm, respectively. The as-synthesized gelatin@Au-NRs showed high stability in common biological media (phosphate buffer saline and Dulbecco’s Modified Eagle’s Medium) compared to CTAB capped Au-NRs. Similarly, the gelatin@Au-NRs showed an improved heat production and outstanding cell viability against two different cancer cell lines; KM-Luc/GFP (mouse fibroblast histiocytoma cell line) and FM3A-Luc (breast carcinoma cell line) compared to CTAB capped Au-NRs and PEG@Au-NRs. An in vitro photothermal therapy study against KM-Luc/GFP showed that gelatin@Au-NRs effectively destroys the cancer cells.
Characterizing perfusion defects in metastatic lymph nodes at an early stage using high-frequency ultrasound and micro-CT imaging International-journal Peer-reviewed

Teppei Yamaki, Ariunbuyan Sukhbaatar, Radhika Mishra, Ryoichi Kikuchi, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

Clinical & Experimental Metastasis　38　(6)　539-549　2021/10/15
Publisher: Springer Science and Business Media LLC
DOI： 10.1007/s10585-021-10127-6 　

ISSN： 0262-0898

eISSN： 1573-7276

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A perfusion defect in a metastatic lymph node (LN) can be visualized as a localized area of low contrast on contrast-enhanced CT, MRI or ultrasound images. Hypotheses for perfusion defects include abnormal hemodynamics in neovascular vessels or a decrease in blood flow in pre-existing blood vessels in the parenchyma due to compression by LN tumor growth. However, the mechanisms underlying perfusion defects in LNs during the early stage of LN metastasis have not been investigated. We show that tumor mass formation with very few microvessels was associated with a perfusion defect in a non-enlarged LN at the early stage of LN metastasis in a LN adenopathy mouse (LN size circa 10 mm). We found in a mouse model of LN metastasis, induced using non-keratinizing tumor cells, that during the formation of the perfusion defect in a non-enlarged LN, the number of blood vessels ≤ 50 μm in diameter decreased, while those of > 50 μm in diameter increased. The methods used were contrast-enhanced high-frequency ultrasound and contrast-enhanced micro-CT imaging systems, with a maximum spatial resolution of > 30 μm. Furthermore, we found no tumor angiogenesis or oxygen partial pressure (pO2) changes in the metastatic LN. Our results demonstrate that the perfusion defect appears to be a specific form of tumorigenesis in the LN, which is a vascular-rich organ. We anticipate that a perfusion defect on ultrasound, CT or MRI images will be used as an indicator of a non-enlarged metastatic LN at an early stage.
The Therapeutic Effect of Second Near-Infrared Absorbing Gold Nanorods on Metastatic Lymph Nodes via Lymphatic Delivery System Peer-reviewed

Adewale O. Oladipo, Thabang C. Lebepe, Vuyelwa Ncapayi, Ncediwe Tsolekile, Sundararajan Parani, Sandile P. Songca, Shiro Mori, Tetsuya Kodama, Oluwatobi S. Oluwafemi

Pharmaceutics　13　(9)　1359-1359　2021/08/28
Publisher: MDPI AG
DOI： 10.3390/pharmaceutics13091359 　

eISSN： 1999-4923

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Photothermal therapy has been established recently as a non-invasive treatment protocol for cancer metastatic lymph nodes. Although this treatment approach shows efficient tumour ablation towards lymph node metastasis, the monitoring and reporting of treatment progress using the lymphatic delivery channel still need to be explored. Herein, we investigated the anti-tumour effect of pegylated gold nanorods with a high aspect ratio (PAuNRs) delivered via the lymphatic route in a mouse model. In this study, breast carcinoma (FM3A-Luc) cells were inoculated in the subiliac lymph node (SiLN) to induce metastasis in the proper axillary lymph node (PALN). The treatment was initiated by injecting the PAuNRs into the accessory axillary lymph node (AALN) after tumour metastasis was confirmed in the PALN followed by external NIR laser irradiation under a temperature-controlled cooling system. The anti-tumour impact of the treatment was evaluated using an in vivo bioluminescence imaging system (IVIS). The results showed a time-dependent reduction in tumour activity with significant treatment response. Tumour growth was inhibited in all mice treated with PAuNRs under laser irradiation; results were statistically significant (** p < 0.01) even after treatment was concluded on day 3. We believe that this non-invasive technique would provide more information on the dynamics of tumour therapy using the lymphatically administered route in preclinical studies.
McH-lpr/lpr-RA1 mice: A novel spontaneous mouse model of autoimmune sialadenitis. International-journal Peer-reviewed

Keiichi Saito, Shiro Mori, Tetsuya Kodama

Immunology letters　237　3-10　2021/06/24

DOI： 10.1016/j.imlet.2021.06.003 　

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Many studies of the autoimmune disease Sjögren's syndrome have been performed using spontaneous mouse models. In the present study, we describe the characteristics of McH/lpr-RA1 mice and propose their use as a novel murine model of autoimmune sialadenitis. The McH/lpr-RA1 mouse is a recombinant congenic strain derived from generation F54 or more of MRL-Faslpr x (MRL- Faslpr x C3H- Faslpr) F1. We show for the first time that this mouse spontaneously develops autoimmune sialadenitis and vasculitis in submandibular gland tissues. Sialadenitis was accompanied by extensive inflammatory cell infiltration and tissue destruction. Immunohistochemical studies revealed that the salivary gland lesions strongly expressed four sialadenitis-related molecules: SSA and SSB (autoantigens of Sjögren's syndrome), gp91phox (an accelerator of reactive oxygen species production) and single strand DNA (a marker of apoptotic cells). In contrast, expression of aquaporin-5 (AQP5), which stimulates salivary secretion was weak or negligible. Statistical correlation analyses indicated that the apoptosis of salivary gland cells provoked by oxidative stress contributed to the severe sialadenitis and reduced expression of AQP5. Our study has demonstrated that McH/lpr-RA1 mice spontaneously develop the pathognomonic features of autoimmune sialadenitis and thus could be used as a new animal model of Sjögren's syndrome.
Study of the physicochemical properties of drugs suitable for administration using a lymphatic drug delivery system. International-journal Peer-reviewed

Ryoichi Fukumura, Ariunbuyan Sukhbaatar, Radhika Mishra, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

Cancer science　112　(5)　1735-1745　2021/05

DOI： 10.1111/cas.14867 　

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Lymph node (LN) metastasis is thought to account for 20-30% of deaths from head and neck cancer. The lymphatic drug delivery system (LDDS) is a new technology that enables the injection of drugs into a sentinel LN (SLN) during the early stage of tumor metastasis to treat the SLN and secondary metastatic LNs. However, the optimal physicochemical properties of the solvent used to carry the drug have not been determined. Here, we show that the osmotic pressure and viscosity of the solvent influenced the antitumor effect of cisplatin (CDDP) in a mouse model of LN metastasis. Tumor cells were inoculated into the proper axillary LN (PALN), and the LDDS was used to inject CDDP solution into the subiliac LN (SiLN) to treat the tumor cells in the downstream PALN. CDDP dissolved in saline had no therapeutic effects in the PALN after it was injected into the SiLN using the LDDS or into the tail vein (as a control). However, CDDP solution with an osmotic pressure of ~ 1,900 kPa and a viscosity of ~ 12 mPa⋅s suppressed tumor growth in the PALN after it was injected into the SiLN using the LDDS. The high osmotic pressure dilated the lymphatic vessels and sinuses to enhance drug flow in the PALN, and the high viscosity increased the retention of CDDP in the PALN. Our results demonstrate that optimizing the osmotic pressure and viscosity of the solvent can enhance the effects of CDDP, and possibly other anticancer drugs, after administration using the LDDS.
Optimization of the Delivery of Molecules into Lymph Nodes Using a Lymphatic Drug Delivery System with Ultrasound. International-journal Peer-reviewed

Shigeki Kato, Shota Yoshiba, Shiro Mori, Tetsuya Kodama

International journal of pharmaceutics　15　(597)　120324-120324　2021/02/01

DOI： 10.1016/j.ijpharm.2021.120324 　

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Conventional treatment for lymph node (LN) metastasis such as systemic chemotherapy have notable disadvantages that lead to the development of unwanted effects. Previously, we have reported the lymphatic administration of drugs into metastatic LNs using a lymphatic drug delivery system (LDDS). However, prior studies of the LDDS have not attempted to optimize the conditions for efficient drug delivery. Here, we investigated the influence of several factors on the efficiency of drug delivery by a LDDS in conjunction with ultrasound (US). First, the effect of the injection rate on delivery efficiency was evaluated. Fluorescent molecules injected into an upstream LN were delivered more effectively into a downstream LN when a lower injection rate was used. Second, the influence of molecular weight on drug delivery efficiency was determined. We found that molecules with a molecular weight > 10,000 were poorly delivered into the LN. Finally, we assessed whether the administration route affected the delivery efficiency. We found that the delivery efficiency was higher when molecules were administered into an upstream LN that was close to the target LN. These findings revealed the importance of a drug's physical properties if it is to be administered by LDDS to treat LN metastasis.
Cytotoxicity evaluation of graphene oxide against adherent and suspension cancer cells Peer-reviewed

Thabang C. Lebepe, Sundararajan Parani, Ncapayi Vuyelwa, Tetsuya Kodama, Oluwatobi S. Oluwafemi

Materials Letters　279　128470-128470　2020/11
Publisher: Elsevier BV
DOI： 10.1016/j.matlet.2020.128470 　

ISSN： 0167-577X
Importance of drug osmotic pressure and viscosity for enhancing treatment effect using lymphatic drug delivery system(和訳中)

Mishra Radhika, 福村凌一, Sukhbaatar Ariunbuyan, 森士朗, 小玉哲也

日本癌学会総会記事　79回　OE10-3　2020/10
Publisher: 日本癌学会
ISSN： 0546-0476
Improvement of chemotherapy for the lymph node metastasis(和訳中)

Sukhbaatar Ariunbuyan, 小玉哲也, 森士朗

日本癌学会総会記事　79回　OE14-4　2020/10
Publisher: 日本癌学会
ISSN： 0546-0476
マウスの転移リンパ節治療における超選択的放射線治療

空翔太, Sukhbaatar Ariunbuyan, 森士朗, 小玉哲也

日本癌学会総会記事　79回　PJ1-4　2020/10
Publisher: 日本癌学会
ISSN： 0546-0476
複数の転移リンパ節モデルマウスの開発

永松大輝, アリウンブヤン・スフバートル, ラディカ・ミシュラ, 森士朗, 小玉哲也

日本癌学会総会記事　79回　PJ10-6　2020/10
Publisher: 日本癌学会
ISSN： 0546-0476
リンパ行性薬物送達法におけるリンパ節への分子集積の定量解析

鈴木健大, アリウンブヤン・スフバートル, 森士朗, 伊藤明宏, 小玉哲也

日本癌学会総会記事　79回　PE17-5　2020/10
Publisher: 日本癌学会
ISSN： 0546-0476
リンパ行性薬剤送達法を用いた抗がん剤投与時における浸透圧の治療依存性

福村凌一, Mishra Radhika, Sukhbaatar Ariunbuyan, 永松大輝, 森士朗, 小玉哲也

日本癌学会総会記事　79回　PJ17-4　2020/10
Publisher: 日本癌学会
ISSN： 0546-0476
Intranodal pressure of a metastatic lymph node reflects the response to lymphatic drug delivery system International-journal Peer-reviewed

Kato S, Takeda K, Sukhbaatar A, Sakamoto M, Mori S, Shiga K, Kodama T

Cancer Sci　111　(11)　4232-4241　2020/09

DOI： 10.1111/cas.14640 　

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Cancer metastasis to lymph nodes (LNs) almost certainly contributes to distant metastasis. Elevation of LN internal pressure (intranodal pressure, INP) during tumor proliferation is associated with a poor prognosis for patients. We have previously reported that a lymphatic drug delivery system (LDDS) allows the direct delivery of anticancer drugs into the lymphatic system and is a promising treatment strategy for early-stage LN metastasis. However, methods for evaluating the treatment effects have not been established. Here, we used a mouse model of MXH10/Mo-lpr/lpr, which develops a systemic swelling of LNs, and murine malignant fibrous histiocytoma-like (KM-Luc/GFP) cells or murine breast cancer (FM3A-Luc) cells inoculated into the subiliac LN of mice to produce a tumor-bearing LN model. The changes in INP during intranodal tumor progression and after treatment with cis-dichlorodiammineplatinum(II) (CDDP) using an LDDS were measured. We found that tumor progression was associated with an increase in INP that occurred independently of LN volume changes. The elevation in INP was suppressed by CDDP treatment with the LDDS when intranodal tumor progression was significantly inhibited. These findings indicate that INP is a useful parameter for monitoring the therapeutic effect in patients with LN metastasis who have been given drugs using an LDDS, which will serve to manage cancer metastasis treatment and contribute to an improved quality of life for cancer patients.
複数の転移リンパ節モデルマウスの開発

永松大輝, Ariunbuyan Sukhbaatar, Radhika Mishara, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　36回　156-156　2020/08
Publisher: 日本DDS学会
複数の転移リンパ節モデルマウスの開発

永松大輝, Ariunbuyan Sukhbaatar, Radhika Mishara, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　36回　156-156　2020/08
Publisher: 日本DDS学会
In vivo delivery of an exogenous molecule into murine T lymphocytes using a lymphatic drug delivery system combined with sonoporation Peer-reviewed

Kato S, Shirai Y, Motozono C, Kanzaki H, Mori S, Kodama T.

Biochem Biophys Res Commun　525　(4)　1025-1031　2020/03
Analysis of tumor vascularization in a mouse model of metastatic lung cancer International-journal Peer-reviewed

Sukhbaatar A, Sakamoto M, Mori S, Kodama T

Scientific Reports　9　(1)　16029-16029　2019/11

DOI： 10.1038/s41598-019-52144-2 　

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Therapies targeting tumor vasculature would improve the treatment of lung metastasis, although the early changes in vascular structure are incompletely understood. Here, we show that obstructive metastatic foci in lung arterioles decrease the pulmonary vascular network. To generate a mouse model of lung metastasis activation, luciferase-expressing tumor cells were inoculated into the subiliac lymph node (SiLN) of an MXH10/Mo-lpr/lpr mouse, and metastatic tumor cells in the lungs were activated by SiLN resection. Activation of metastases was monitored by in vivo bioluminescence imaging. Pulmonary blood vessel characteristics were analyzed using ex vivo micro-computed tomography. The enhanced permeability and retention (EPR) effect in neovasculature after tumor cell activation was evaluated from the accumulation of intravenously injected indocyanine green (ICG) liposomes. Metastatic foci in lung arterioles were investigated histologically. Micro-computed tomography revealed decreases in pulmonary blood vessel length, volume and number of branching nodes during the early stage of metastasis caused by metastatic foci. ICG liposome accumulation by the EPR effect was not detected. Histology identified metastatic foci in lung arterioles. The lack of an EPR effect after the formation of metastatic foci in lung arterioles makes conventional systemic chemotherapy ineffective for lung metastasis. Thus, alternative therapeutic methods of drug delivery are needed.
リンパ行性薬剤送達法における浸透圧の重要性(Importance of osmotic pressure for lymphatic drug delivery system)

ミシュラ・ラディカ, 福村凌一, アリウンブヤン・スフバートル, 阪本真弥, 森士朗, 志賀清人, 小玉哲也

日本癌学会総会記事　78回　E-3058　2019/09
Publisher: (一社)日本癌学会
ISSN： 0546-0476
リンパ系薬物送達システムに必要な薬物の浸透圧と粘度の最適範囲(Optimized ranges of osmotic pressure and viscosity of drugs required for lymphatic drug delivery system)

福村凌一, ラディカ・ミシュラ, アリウンブヤン・スフバートル, 阪本真弥, 森士朗, 志賀清人, 小玉哲也

日本癌学会総会記事　78回　P-3359　2019/09
Publisher: 日本癌学会
ISSN： 0546-0476
Use of a lymphatic drug delivery system and sonoporation to target malignant metastatic breast cancer cells proliferating in the marginal sinuses International-journal Peer-reviewed

Kato S, Shirai Y, Sakamoto M, Mori S, Kodama T

Scientific Reports　9　(1)　13242-13242　2019/09

DOI： 10.1038/s41598-019-49386-5 　

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Lymph node (LN) metastasis through the lymphatic network is a major route for cancer dissemination. Tumor cells reach the marginal sinuses of LNs via afferent lymphatic vessels (LVs) and form metastatic lesions that lead to distant metastasis. Thus, targeting of metastatic cells in the marginal sinuses could improve cancer treatment outcomes. Here, we investigated whether lymphatic administration of a drug combined with sonoporation could be used to treat a LN containing proliferating murine FM3A breast cancer cells, which are highly invasive, in its marginal sinus. First, we used contrast-enhanced high-frequency ultrasound and histopathology to analyze the structure of LVs in MXH10/Mo-lpr/lpr mice, which exhibit systemic lymphadenopathy. We found that contrast agent injected into the subiliac LN flowed into the marginal sinus of the proper axillary LN (PALN) and reached the cortex. Next, we examined the anti-tumor effects of our proposed technique. We found that a strong anti-tumor effect was achieved by lymphatic administration of doxorubicin and sonoporation. Furthermore, our proposed method prevented tumor cells in the marginal sinus from invading the parenchyma of the PALN and resulted in tumor necrosis. We conclude that lymphatic administration of a drug combined with sonoporation could exert a curative effect in LNs containing metastatic cells in their marginal sinuses.
The effect of anti-IL-6 receptor antibody for the treatment of McH-lpr/lpr-RA1 mice that spontaneously developed destructive arthritis and enthesitis Peer-reviewed

Takuya Izumiyama, Yu Mori, Shiro Mori, Naoko Mori, Tetsuya Kodama, Eiji Itoi

BMC Musculoskeletal Disorders　20　(1)　2019/06/15

DOI： 10.1186/s12891-019-2664-3 　

eISSN： 1471-2474
早期ステージの転移リンパ節における異なる浸透圧でのリンパ薬剤送達系を用いたepirubicin療法の治療効果の分析(Therapeutic effect of epirubicin at different osmotic pressurein metastatic lymph nodes at the early stage using lymphatic drug delivery system)

Sukhbaatar Ariunbuyan, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　35回　124-124　2019/06
Publisher: 日本DDS学会
マウスにおけるリンパ薬剤送達系の流動力学(Flow dynamics of lymphatic drug delivery system in in mice)

Mishra Radhika, Sukhbaatar Ariunbuyan, 阪本真弥, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　35回　166-166　2019/06
Publisher: 日本DDS学会
A model system for studying superselective radiotherapy of lymph node metastasis in mice with swollen lymph nodes Peer-reviewed

Ryohei Kikuchi, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

Clinical and Translational Radiation Oncology　DOI:10.1016/j.ctro.2019.05.002　2019/05
Treatment of false‐negative metastatic lymph nodes by a lymphatic drug delivery system with 5‐fluorouracil International-journal Peer-reviewed

Fujii H, Horie S, Sukhbaatar A, Mishra R, Sakamoto M, Mori S, Kodama T

Cancer Medicine　8　(5)　2241-2251　2019/05

DOI： 10.1002/cam4.2125 　

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Metastatic lymph nodes (LNs) may be the origin of systemic metastases. It will be important to develop a strategy that prevents systemic metastasis by treating these LNs at an early stage. False-negative metastatic LNs, which are found during the early stage of metastasis development, are those that contain tumor cells but have a size and shape similar to LNs that do not host tumor cells. Here, we show that 5-fluorouracil (5-FU), delivered by means of a novel lymphatic drug delivery system (LDDS), can treat LNs with false-negative metastases in a mouse model. The effects of 5-FU on four cell lines were investigated using in vitro cytotoxicity and cell survival assays. The therapeutic effects of LDDS-administered 5-FU on false-negative metastatic LNs were evaluated using bioluminescence imaging, high-frequency ultrasound (US), and histology in MHX10/Mo-lpr/lpr mice. These experimental animals develop LNs that are similar in size to human LNs. We found that all cell lines showed sensitivity to 5-FU in the in vitro assays. Furthermore, a concentration-dependent effect of 5-FU to inhibit tumor growth was observed in tumor cells with low invasive growth characteristics, although a significant reduction in metastatic LN volume was not detected in MHX10/Mo-lpr/lpr mice. Adverse effects of 5-FU were not detected. 5-Fluorouracil administration with a LDDS is an effective treatment method for false-negative metastatic LNs. We anticipate that the delivery of anticancer drugs by a LDDS will be of great benefit in the prevention and treatment of cancer metastasis via LNs.
Lymph node resection induces the activation of tumor cells in the lungs Peer-reviewed

Sukhbaatar A, Mori S, Saiki Y, Takahashi T, Horii Akira H, Kodama T

Cancer Science　110　(2)　509-518　2019/02

DOI： 10.1111/cas.13898 　

ISSN： 1349-7006
Imaging of the mouse lymphatic sinus during early-stage lymph node metastasis using intranodal lymphangiography with X-ray micro-computed tomography International-journal Peer-reviewed

Iwamura R, Sakamoto M, Mori S, Kodama T

Molecular Imaging and Biology　21　(5)　825-834　2019/01

DOI： 10.1007/s11307-018-01303-4 　

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PURPOSE: Lymph node (LN) metastasis is detected prior to distant metastasis in many types of cancer. Detecting early stage LN metastasis can improve treatment outcomes. However, there are few clinical imaging modalities capable of diagnosing metastatic LNs of clinical N0 status (i.e., before their volume increases) with high precision. Here, we report a new method for diagnosing metastatic LNs of clinical N0 status in a mouse model of LN metastasis. PROCEDURES: The method involved using intranodal lymphangiography with x-ray micro-computed tomography (micro-CT). Contrast agent was injected into an upstream LN to deliver it to a downstream LN, which was then removed and analyzed by micro-CT. RESULTS: We found that using an intranodal injection rate of 10-60 μl/min filled the lymphatic sinus of the downstream LN with contrast agent, although the accumulation of contrast agent in the upstream LN increased with a faster injection rate. Furthermore, breast cancer cells growing in the lymphatic sinus of the downstream LN (which was of clinical N0 status) impeded the flow of contrast agent from the upstream LN, resulting in areas deficient of contrast agent in the metastatic downstream LN. The formation of defect areas in the downstream LN manifested as a difference in position between the centroid of the entire LN area and the centroid of the region that filled with contrast agent. CONCLUSION: The present study indicates that intranodal lymphangiography with micro-CT has the potential to be used as a new method for diagnosing metastatic LNs of clinical N0 status.
Tumor cell invasion from the marginal sinus into extranodal veins during early-stage lymph node metastasis can be a starting point for hematogenous metastasis Peer-reviewed

Kodama T, Mori S, Nose M

J Cancer Metastasis Treat　4　(56)　2018/11

DOI： 10.20517/2394-4722.2018.61 　
肺転移マウスモデルにおける肺血管新生の変化に関するmicro-CTによる評価(Murine pulmonary vascularization changes in a metastatic lung mouse model using micro-CT)

Sukhbaatar Ariunbuyan, 森士朗, 小玉哲也

日本癌学会総会記事　77回　2472-2472　2018/09
Publisher: 日本癌学会
ISSN： 0546-0476
関節強直に至る関節炎を自然発症するMcH-lpr/lpr-RA1マウスに対するIL-6抑制効果の検討

泉山拓也, 森優, 武田航, 堀江佐知子, 森士朗, 小玉哲也, 井樋栄二

日本整形外科学会雑誌　92　(8)　S1987-S1987　2018/08
Publisher: (公社)日本整形外科学会
ISSN： 0021-5325
Optimal range of injection rates for a lymphatic drug delivery system. International-journal Peer-reviewed

Fujii H, Horie S, Takeda K, Mori S, Kodama T

Journal of biophotonics　11　(8)　e201700401　2018/08

DOI： 10.1002/jbio.201700401 　

ISSN： 1864-063X

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The lymphatic drug delivery system (LDDS) is a new technique that permits the injection of drugs into a sentinel lymph node (SLN) at an early stage of tumor metastasis, thereby treating metastasis in the SLN and its secondary lymph nodes (LNs). The quantity of drug required for a LDDS is much smaller than that needed for systemic chemotherapy. However, the relationship between the rate of drug injection into a SLN and the amount of drug reaching the secondary LNs has not been investigated. In this study, we used an MXH10/Mo-lpr/lpr mouse model to show that the optimal rate for the injection of a fluorescent dye by a LDDS was 10 to 80 μL/min. An injection rate of 10 to 80 μL/min was able to fill the downstream LN. However, an injection rate of 100 μL/min drove the fluorescent dye into the efferent lymphatic vessels and thoracoepigastric vein, decreasing the amount of dye retained in the downstream LN. Bolus injection (defined as an injection rate of 2400 μL/min) was unable to deliver fluorescent dye into the downstream LN. These results agree with the impulse values calculated from the injection pressures in the upstream LN. We anticipate that our findings will facilitate the development of a LDDS for use in the clinic.
Superselective Drug Delivery Using Doxorubicin-Encapsulated Liposomes and Ultrasound in a Mouse Model of Lung Metastasis Activation Peer-reviewed

Tomoki Ouchi, Ariunbuyan Sukhbaatar, Sachiko Horie, Maya Sakamoto, Kiyoto Shiga, Shiro Mori, Tetsuya Kodama

Ultrasound in Medicine and Biology　44　(8)　1818-1827　2018/08/01
Publisher: Elsevier USA
DOI： 10.1016/j.ultrasmedbio.2018.04.003 　

ISSN： 1879-291X 0301-5629
Evaluation of metastatic niches in distant organs after surgical removal of tumor-bearing lymph nodes Peer-reviewed

Jinhua Zheng, Limin Jia, Shiro Mori, Tetsuya Kodama

BMC Cancer　18　(1)　608　2018/05/30
Publisher: BioMed Central Ltd.
DOI： 10.1186/s12885-018-4538-8 　

ISSN： 1471-2407
リンパ行性薬剤送達法による抗がん剤送達後のリンパ管評価に関する研究

武田航, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　34回　147-147　2018/05
Publisher: 日本DDS学会
口腔癌頸部リンパ節転移の節外進展診断における3テスラblack-blood MR imaging法の有用性

阪本真弥, 小嶋郁穂, 飯久保正弘, 西岡貴志, 笹野高嗣, 伊藤康一, 青木孝文, 小川武則, 森士朗, 小玉哲也

歯科放射線　58　(増刊)　54-54　2018/05
Publisher: (NPO)日本歯科放射線学会
ISSN： 0389-9705

eISSN： 2185-6311
Novel lipids with three C18-fatty acid chains and an amino acid head group for pH-responsive and sustained antibiotic delivery Peer-reviewed

Mahantesh Jadhav, Rahul S. Kalhapure, Sanjeev Rambharose, Chunderika Mocktar, Sanil Singh, Tetsuya Kodama, Thirumala Govender

Chemistry and Physics of Lipids　212　12-25　2018/05/01
Publisher: Elsevier Ireland Ltd
DOI： 10.1016/j.chemphyslip.2017.12.007 　

ISSN： 1873-2941 0009-3084
Treatment of tumor in lymph nodes using near-infrared laser light-activated thermosensitive liposome-encapsulated doxorubicin and gold nanorods Peer-reviewed

Daisuke Matsuki, Oladipo Adewale, Sachiko Horie, Junnosuke Okajima, Atsuki Komiya, Oluwatobi Oluwafemi, Shigenao Maruyama, Shiro Mori, Tetsuya Kodama

JOURNAL OF BIOPHOTONICS　10　(12)　1676-1682　2017/12

DOI： 10.1002/jbio.201600241 　

ISSN： 1864-063X

eISSN： 1864-0648
Green synthesis of MPA-capped CdTe/CdSe quantum dots at different pH and its effect on the cell viability of fibroblast histiocytoma cells Peer-reviewed

Vuyelwa Ncapayi, Sundararajan Parani, Sandile P. Songca, Tetsuya Kodama, Oluwatobi S. Oluwafemi

MATERIALS LETTERS　209　299-302　2017/12

DOI： 10.1016/j.matlet.2017.08.042 　

ISSN： 0167-577X

eISSN： 1873-4979
Therapeutic effect of cisplatin given with a lymphatic drug delivery system on false-negative metastatic lymph nodes Peer-reviewed

Asuka Tada, Sachiko Horie, Shiro Mori, Tetsuya Kodama

CANCER SCIENCE　108　(11)　2115-2121　2017/11

DOI： 10.1111/cas.13387 　

ISSN： 1349-7006
担がんリンパ節郭清による肺転移誘導マウスモデルの作製

堀江佐知子, 森士朗, 小玉哲也

日本癌治療学会学術集会抄録集　55回　PS-8　2017/10
Publisher: (一社)日本癌治療学会
偽陰性N0リンパ節に対するリンパ行性薬剤送達法の基礎理論と治療評価

小玉哲也, 堀江佐知子, 森士朗

日本癌治療学会学術集会抄録集　55回　P8-1　2017/10
Publisher: (一社)日本癌治療学会
リンパ行性薬剤送達法によるがん治療

堀江佐知子, 森菜緒子, 志賀清人, 森士朗, 小玉哲也

日本癌学会総会記事　76回　J-1050　2017/09
Publisher: 日本癌学会
ISSN： 0546-0476
リンパ行性薬剤送達法を利用した5-FUによる転移リンパ節治療

藤井穂乃香, 武田航, 堀江佐知子, 森士朗, 小玉哲也

日本癌学会総会記事　76回　J-1051　2017/09
Publisher: 日本癌学会
ISSN： 0546-0476
転移偽陰性リンパ節における酸素分圧の評価

菊池凌平, 堀江佐知子, 森士朗, 小玉哲也

日本癌学会総会記事　76回　P-3083　2017/09
Publisher: 日本癌学会
ISSN： 0546-0476
マイクロCTと高周波超音波を用いたリンパ造影によるリンパ節転移の新たな診断手法の開発

岩村亮, 森士朗, 阪本真弥, 小玉哲也

日本癌学会総会記事　76回　P-3084　2017/09
Publisher: 日本癌学会
ISSN： 0546-0476
転移リンパ節の解剖学的な背景に関する研究

武田航, 藤井穂乃香, 堀江佐知子, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　76回　P-3110　2017/09
Publisher: 日本癌学会
ISSN： 0546-0476
解剖学的特徴に基づいたリンパ行性薬剤送達法の開発

武田航, 堀江佐知子, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　33回　182-182　2017/06
Publisher: 日本DDS学会
転移リンパ節に対するリンパ行性薬剤送達法の有効性に関する研究

藤井穂乃香, 岡田裕貴, 武田航, 堀江佐知子, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　33回　183-183　2017/06
Publisher: 日本DDS学会
リンパ節切除にともなう郭清域外リンパ節ならびに肺での転移性腫瘍細胞の治療を目指す新たなリンパ行性薬剤送達法の開発

大内友貴, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　33回　184-184　2017/06
Publisher: 日本DDS学会
Study of fluid dynamics reveals direct communications between lymphatic vessels and venous blood vessels at lymph nodes of mice Peer-reviewed

Kazu Takeda, Shiro Mori, Tetsuya Kodama

JOURNAL OF IMMUNOLOGICAL METHODS　445　1-9　2017/06

DOI： 10.1016/j.jim.2017.02.008 　

ISSN： 0022-1759

eISSN： 1872-7905
Evaluation of the enhanced permeability and retention effect in the early stages of lymph node metastasis Peer-reviewed

Mamoru Mikada, Ariunbuyan Sukhbaatar, Yoshinobu Miura, Sachiko Horie, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

CANCER SCIENCE　108　(5)　846-852　2017/05

DOI： 10.1111/cas.13206 　

ISSN： 1349-7006
A novel treatment for metastatic lymph nodes using lymphatic delivery and photothermal therapy Peer-reviewed

Adewale O. Oladipo, Oluwatobi S. Oluwafemi, Sandile P. Songca, Ariunbuyan Sukhbaatar, Shiro Mori, Junnosuke Okajima, Atsuki Komiya, Shigenao Maruyama, Tetsuya Kodama

Scientific Reports　7　45459　2017/04/03
Publisher: Nature Publishing Group
DOI： 10.1038/srep45459 　

ISSN： 2045-2322
Quantitative Analysis of Contrast-Enhanced Ultrasound Imaging in Invasive Breast Cancer: A Novel Technique to Obtain Histopathologic Information of Microvessel Density Peer-reviewed

Naoko Mori, Shunji Mugikura, Shoki Takahashi, Koichi Ito, Chiaki Takasawa, Li Li, Minoru Miyashita, Atsuko Kasajima, Yu Mori, Takanori Ishida, Tetsuya Kodama, Kei Takase

Ultrasound in Medicine and Biology　43　(3)　607-614　2017/03/01

DOI： 10.1016/j.ultrasmedbio.2016.11.009 　

ISSN： 0301-5629

eISSN： 1879-291X
Simple green synthesis of amino acid functionalised CdTe/CdSe/ZnSe core-multi shell with improved cell viability for cellular imaging Peer-reviewed

Vuyelwa Ncapayi, Sundararajan Parani, Sandile P. Songca, Tetsuya Kodama, Oluwatobi S. Oluwafemi

MATERIALS LETTERS　189　168-171　2017/02

DOI： 10.1016/j.matlet.2016.12.006 　

ISSN： 0167-577X

eISSN： 1873-4979
Vascular structure analysis for fnN0 lymph node using micro-CT imaging

Ishikawa Tomoki, Iwamura Ryo, Tada Asuka, Horie Sachiko, Mori Shiro, Kodama Tetsuya

Transactions of Japanese Society for Medical and Biological Engineering　55　(5)　397-397　2017
Publisher: Japanese Society for Medical and Biological Engineering
DOI： 10.11239/jsmbe.55Annual.397 　
Induction of the EPR effect in a mouse model of lung metastasis

Sukhbaatar Ariunbuyan, Horie Sachiko, Takahashi Tetsu, Mori Shiro, Kodama Tetsuya

Transactions of Japanese Society for Medical and Biological Engineering　55　(4)　377-377　2017
Publisher: Japanese Society for Medical and Biological Engineering
DOI： 10.11239/jsmbe.55Annual.377 　

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<p>The Enhanced Permeability and Retention (EPR) effect is considered to be a landmark principle in systemic tumor-targeting chemotherapy. Chemotherapy is used for the treatment of lung metastasis in clinics. However, the EPR effect in the lung metastasis has not been fully investigated. In this study, we evaluate the EPR effect in a mouse model of lung metastasis.Luciferase expressing tumor cells were inoculated into MXH10/Mo/lpr mice to induce lung metastasis. Lung metastasis was activated by dissecting the subiliac lymph node. The EPR effect in the metastatic lung was quantified by accumulation of intravenously injected ICG liposomes. Luciferase activity as well as fluorescence intensity were measured using bioluminescence and biofluorescence imaging. The harvested tissues were analyzed by HE and anti-CD31 staining. Herein, we found that no ICG liposome accumulation was detected in the metastatic lung and the EPR effect was not observed in the mouse model of lung metastasis.</p>
Evaluation of false-negative metastatic lymph nodes with MR and ultrasound imaging

Kikuchi Ryohei, Horie Sachiko, Sakamoto Maya, Mori Naoko, Mori Shiro, Kodama Tetsuya

Transactions of Japanese Society for Medical and Biological Engineering　55　(5)　408-408　2017
Publisher: Japanese Society for Medical and Biological Engineering
DOI： 10.11239/jsmbe.55Annual.408 　
Monitoring of Blood Vessel Density Using Contrast-Enhanced High Frequency Ultrasound May Facilitate Early Diagnosis of Lymph Node Metastasis Peer-reviewed

Takuma Sato, Tomoaki Takemura, Tomoki Ouchi, Shiro Mori, Maya Sakamoto, Yoichi Arai, Tetsuya Kodama

JOURNAL OF CANCER　8　(5)　704-715　2017

DOI： 10.7150/jca.18027 　

ISSN： 1837-9664
リンパ節内圧を用いたリンパ節転移の新規診断方法

武田航, 多田明日香, 吉羽正太, 堀江佐知子, 森士朗, 小玉哲也

日本癌学会総会記事　75回　P-2128　2016/10
Publisher: 日本癌学会
ISSN： 0546-0476
リンパ造影を用いたリンパ節転移の新たな診断法の開発

岩村亮, 森士朗, 小玉哲也

日本癌学会総会記事　75回　P-2129　2016/10
Publisher: 日本癌学会
ISSN： 0546-0476
転移リンパ節に対するリンパ行性薬剤送達法を用いた時間依存型抗がん剤の治療効果の検討

藤井穂乃香, 岡田裕貴, 多田明日香, 堀江佐知子, 森士朗, 小玉哲也

日本癌学会総会記事　75回　P-3269　2016/10
Publisher: 日本癌学会
ISSN： 0546-0476
超音波とナノ・マイクロバブルを用いたリンパ行性薬剤送達能の評価

吉羽正太, 武田航, 多田明日香, 堀江佐知子, 森士朗, 小玉哲也

日本癌学会総会記事　75回　P-3270　2016/10
Publisher: 日本癌学会
ISSN： 0546-0476
転移リンパ節に対するリンパネットワークを用いた薬剤送達法の開発に関する研究

多田明日香, 堀江佐知子, 森士朗, 小玉哲也

日本癌学会総会記事　75回　P-3271　2016/10
Publisher: 日本癌学会
ISSN： 0546-0476
リンパ節転移モデルマウスにおけるドキソルビシンを用いたリンパ行性薬剤送達法の評価

岡田裕貴, 藤井穂乃香, 多田明日香, 堀江佐知子, 森士朗, 小玉哲也

日本癌学会総会記事　75回　P-3272　2016/10
Publisher: 日本癌学会
ISSN： 0546-0476
New concept for the prevention and treatment of metastatic lymph nodes using chemotherapy administered via the lymphatic network Peer-reviewed

Tetsuya Kodama, Daisuke Matsuki, Asuka Tada, Kazu Takeda, Shiro Mori

SCIENTIFIC REPORTS　6　(32506)　2016/09

DOI： 10.1038/srep32506 　

ISSN： 2045-2322
口腔癌の頸部リンパ節転移診断における3テスラblack-blood MR imagingの有用性について

阪本真弥, 小嶋郁穂, 飯久保正弘, 近藤千裕, 伊藤康一, 青木孝文, 小川武則, 森士朗, 小玉哲也, 笹野高嗣

歯科放射線　56　(増刊)　70-70　2016/06
Publisher: (NPO)日本歯科放射線学会
ISSN： 0389-9705

eISSN： 2185-6311
リンパ節転移の早期におけるEPR効果の評価(Evaluation of EPR effect in the early stages of lymph node metastasis)

Sukhbaatar Ariunbuyan, 多田明日香, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　32回　138-138　2016/06
Publisher: 日本DDS学会
Distinctive role of vasohibin-1A and its splicing variant vasohibin-1B in tumor angiogenesis Peer-reviewed

S. Horie, Y. Suzuki, M. Kobayashi, T. Kadonosono, S. Kondoh, T. Kodama, Y. Sato

CANCER GENE THERAPY　23　(5)　133-141　2016/05

DOI： 10.1038/cgt.2016.13 　

ISSN： 0929-1903

eISSN： 1476-5500
ソノポレーションを利用したVasohibin-1遺伝子導入による抗腫瘍効果の評価

堀江佐知子, 鈴木康弘, 小林美穂, 小玉哲也, 佐藤靖史

超音波医学　43　(Suppl.)　S539-S539　2016/04
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
Early diagnosis of lymph node metastasis: Importance of intranodal pressures Peer-reviewed

Yoshinobu Miura, Mamoru Mikada, Tomoki Ouchi, Sachiko Horie, Kazu Takeda, Teppei Yamaki, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

CANCER SCIENCE　107　(3)　224-232　2016/03

DOI： 10.1111/cas.12873 　

ISSN： 1347-9032

eISSN： 1349-7006
Peritumoral apparent diffusion coefficients for prediction of lymphovascular invasion in clinically node-negative invasive breast cancer Peer-reviewed

Naoko Mori, Shunji Mugikura, Chiaki Takasawa, Minoru Miyashita, Akiko Shimauchi, Hideki Ota, Takanori Ishida, Atsuko Kasajima, Kei Takase, Tetsuya Kodama, Shoki Takahashi

EUROPEAN RADIOLOGY　26　(2)　331-339　2016/02

DOI： 10.1007/s00330-015-3847-4 　

ISSN： 0938-7994

eISSN： 1432-1084
Development of lymphatic drug deliver system Invited Peer-reviewed

多田明日香, 堀江佐知子, 森士朗, 小玉哲也

リンパ学　39　(2)　133-135　2016
Publisher:
ISSN： 0910-4186
Extended Bernoulli equation, friction loss, and friction coefficient for microscopic Jeffery-Hamel flow with small Reynolds number up to O(1) Peer-reviewed

Fujikawa T, Egarashi R, Fujikawa S, Takeda K, Kodama T

Journal of Fluid Scinec and Technology　11　(3)　1-12　2016
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jfst.2016jfst0019 　

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<p>The extended Bernoulli equation is formulated in an exact form for a microscopic and small Reynolds number Jeffery-Hamel flow in a two-dimensional convergent or divergent channel. The friction loss and the friction coefficient derived from the extended Bernoulli equation are also obtained for the purpose of engineering applications. The assumption of microscopic and low Reynolds number flow enables us to make the analysis simple, and the results obtained are expressed in forms easy to use. The zeroth- and first-order approximate solutions of velocity distribution in the channel are obtained by solving the nonlinear ordinary differential equation with the optimal homotopy asymptotic method. The zeroth-order solution is shown to be the same function form as that in the two-dimensional parallel flow, i.e., the two-dimensional Poiseuille flow. The extended Bernoulli equation, the friction loss, and the friction coefficient in a finite region of the channel, which are indispensable for applications, are reasonably derived along a stream line and also expressed by cross-sectional average quantities. The cross-sectional average formulae of the friction loss and the friction coefficient are expressed by the geometry of the channel, i.e., the convergent or divergent angle, the channel length, channel widths at inlet and exit. These formulae include the corresponding well-known ones for the two-dimensional parallel flow as a special case where the angle is zero. The friction coefficient drastically increases according to the increase in the angle, especially in a narrow channel region, and attains more than ten times of the friction coefficient for the parallel flow.</p>
HIGH-ACCURACY ULTRASOUND CONTRAST AGENT DETECTION METHOD FOR DIAGNOSTIC ULTRASOUND IMAGING SYSTEMS Peer-reviewed

Koichi Ito, Kazumasa Noro, Yukari Yanagisawa, Maya Sakamoto, Shiro Mori, Kiyoto Shiga, Tetsuya Kodama, Takafumi Aoki

ULTRASOUND IN MEDICINE AND BIOLOGY　41　(12)　3120-3130　2015/12

DOI： 10.1016/j.ultrasmedbio.2015.07.032 　

ISSN： 0301-5629

eISSN： 1879-291X
Photothermal therapy of tumors in lymph nodes using gold nanorods and near-infrared laser light with controlled surface cooling Peer-reviewed

Tessai Sugiura, Daisuke Matsuki, Junnosuke Okajima, Atsuki Komiya, Shiro Mori, Shigenao Maruyama, Tetsuya Kodama

NANO RESEARCH　8　(12)　3842-3852　2015/12

DOI： 10.1007/s12274-015-0884-x 　

ISSN： 1998-0124

eISSN： 1998-0000
ドキソルビシン内封リポソームを用いたリンパ節内における薬剤分布に関する研究

吉羽正太, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　74回　P-1403　2015/10
Publisher: 日本癌学会
ISSN： 0546-0476
リンパ節転移の新たな診断指標の提案

八巻哲平, 阪本真弥, 森士朗, 志賀清人, 小玉哲也

日本癌学会総会記事　74回　P-1343　2015/10
Publisher: 日本癌学会
ISSN： 0546-0476
基礎研究の外科臨床への応用リンパ節への癌細胞接種後における遠隔臓器の転移評価

鄭金華, 森士朗, 小玉哲也

日本癌学会総会記事　74回　S16-2　2015/10
Publisher: 日本癌学会
ISSN： 0546-0476
廓清外リンパ節治療のための超音波と微小気泡を用いたリンパ行性薬剤送達法の開発

多田明日香, 吉羽正太, 武田航, 森士朗, 小玉哲也

日本癌学会総会記事　74回　P-2303　2015/10
Publisher: 日本癌学会
ISSN： 0546-0476
フォトサーマル効果と表面冷却による低侵襲加熱法を利用したリンパ節転移治療法の開発

松木大輔, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　74回　P-2346　2015/10
Publisher: 日本癌学会
ISSN： 0546-0476
リンパ節内圧によるリンパ節担癌の進行とその化学療法の評価方法の検討

武田航, 森士朗, 阪本真弥, 小玉哲也

日本癌学会総会記事　74回　P-3128　2015/10
Publisher: 日本癌学会
ISSN： 0546-0476
Communication between lymphatic and venous systems in mice Peer-reviewed

Lenan Shao, Kazu Takeda, Shigeki Kato, Shiro Mori, Tetsuya Kodama

JOURNAL OF IMMUNOLOGICAL METHODS　424　100-105　2015/09

DOI： 10.1016/j.jim.2015.05.007 　

ISSN： 0022-1759

eISSN： 1872-7905
リンパ行性薬剤投与とソノポレーションによる腫瘍リンパ節治療法開発

加藤茂樹, 森士朗, 阪本真弥, 小玉哲也

日本DDS学会学術集会プログラム予稿集　31回　160-160　2015/06
Publisher: 日本DDS学会
ソノポレーション法によるリンパ球への遺伝子導入

加藤茂樹, 森士朗, 阪本真弥, 小玉哲也

日本DDS学会学術集会プログラム予稿集　31回　200-200　2015/06
Publisher: 日本DDS学会
Enhanced Ultrasonography Using a Nano/Microbubble Contrast Agent for Islet Transplantation Peer-reviewed

N. Sakata, N. Sax, G. Yoshimatsu, H. Tsuchiya, S. Kato, T. Aoki, M. Ishida, Y. Katayose, S. Egawa, T. Kodama, M. Unno

AMERICAN JOURNAL OF TRANSPLANTATION　15　(6)　1531-1542　2015/06

DOI： 10.1111/ajt.13152 　

ISSN： 1600-6135

eISSN： 1600-6143
ソノポレーションを利用したVasohibin-1遺伝子導入による抗腫瘍効果の評価

堀江佐知子, 鈴木康弘, 小林美穂, 小玉哲也, 佐藤靖史

超音波医学　42　(3)　368-368　2015/05
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
リンパ管への薬剤投与とソノポレーションを組み合わせた担がんリンパ節治療

加藤茂樹, 白井優子, 小玉哲也, 森士朗

超音波医学　42　(3)　374-374　2015/05
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
DELIVERY OF MOLECULES TO THE LYMPH NODE VIA LYMPHATIC VESSELS USING ULTRASOUND AND NANO/MICROBUBBLES Peer-reviewed

Shigeki Kato, Yuko Shirai, Hiroyuki Kanzaki, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

ULTRASOUND IN MEDICINE AND BIOLOGY　41　(5)　1411-1421　2015/05

DOI： 10.1016/j.ultrasmedbio.2014.12.014 　

ISSN： 0301-5629

eISSN： 1879-291X
Activation of latent metastases in the lung after resection of a metastatic lymph node in a lymph node metastasis mouse model Peer-reviewed

Lenan Shao, Tomoki Ouchi, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　460　(3)　543-548　2015/05

DOI： 10.1016/j.bbrc.2015.03.066 　

ISSN： 0006-291X

eISSN： 1090-2104
Direct Delivery of a Cytotoxic Anticancer Agent into the Metastatic Lymph Node Using Nano/Microbubbles and Ultrasound Peer-reviewed

Takuma Sato, Shiro Mori, Maya Sakamoto, Yoichi Arai, Tetsuya Kodama

PLOS ONE　10　(4)　2015/04

DOI： 10.1371/journal.pone.0123619 　

ISSN： 1932-6203
Fluid dynamics in lymphatic vessels and lymph nodes using a mouse modeltest a lymphatic drug delivery

KODAMA TETSUYA

Transactions of Japanese Society for Medical and Biological Engineering　53　S124_01-S124_01　2015
Publisher: Japanese Society for Medical and Biological Engineering
DOI： 10.11239/jsmbe.53.S124_01 　

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Curing/preventing micrometastasis to lymph nodes (LNs) located outside the surgically resected area is essential for improving the morbidity and mortality associated with breast cancer and head and neck cancer. However, no lymphatic therapy system exists that can deliver drugs to LNs located outside the dissection area. Here, we demonstrate proof of concept for a drug delivery system using MXH10/Mo-lpr/lpr mice that exhibit systemic lymphadenopathy, with some peripheral LNs being as large as 10 mm in diameter. We report that a fluorescent solution injected into the subiliac LN (defined as the upstream LN within the dissection area) was delivered successfully to the proper axillary LN (defined as the downstream LN outside the dissection area) through the lymphatic vessels. Our results suggest that this approach could be used before surgical resection to deliver drugs to downstream LNs outside the dissection area. We think that our methodology could be applied clinically, before surgical resection, to cure/prevent micrometastasis in LNs outside the dissection area.
The evaluation of anti-tumor effects in metastatic lymph node by interstitial fluid pressure

TAKEDA KAZU, Yoshiba Shota, Mori Shiro, Kodama Tetsuya

Transactions of Japanese Society for Medical and Biological Engineering　53　S123_03-S123_03　2015
Publisher: Japanese Society for Medical and Biological Engineering
DOI： 10.11239/jsmbe.53.S123_03 　

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Cancer death is mainly caused by metastasis via lymphatic or cardiovasucular system. Normally, solid tumor has a high interstitial fluid pressures (IFP) and it makes difficult to deliver drugs into the tumor region. It has been reported that IFP increases in tumor or pre-tumor regions because of tumor vessels and impaired lymphatic vessels, and high IFP may have correlation with lymph node metastasis. Although it is reported that drugs are delivered to metastatic lymph node via lymphogenous, there is no reliable methods to evaluate chemotherapy-induced treatment effect. Here we show the correlation between intermodal pressure (INP) and tumor-bearing lymph node progression / degression caused by chemotherapy by CDDP. We found that tumor-bearing lymph node was progressed with increasing INP, and chemotherapy decreased. There was no significant change in of blood vessel density in lymph node. Our results demonstrate an importance of INP for assessing tumor-bearing lymph node. We anticipate that this study contributes to develop an evaluation method of diagnosis and treatment for lymph node metastasis.
Temporal effect of inertial cavitation with and without microbubbles on surface deformation of agarose S gel in the presence of 1-MHz focused ultrasound Peer-reviewed

Y. Tomita, T. Matsuura, T. Kodama

ULTRASONICS　55　1-5　2015/01

DOI： 10.1016/j.ultras.2014.07.017 　

ISSN： 0041-624X

eISSN： 1874-9968
Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system Peer-reviewed

Tetsuya Kodama, Yuriko Hatakeyama, Shigeki Kato, Shiro Mori

BIOMEDICAL OPTICS EXPRESS　6　(1)　124-134　2015/01

DOI： 10.1364/BOE.6.000124 　

ISSN： 2156-7085
A Novel Treatment Method for Lymph Node Metastasis Using a Lymphatic Drug Delivery System with Nano/Microbubbles and Ultrasound Peer-reviewed

Shigeki Kato, Shiro Mori, Tetsuya Kodama

JOURNAL OF CANCER　6　(12)　1282-1294　2015

DOI： 10.7150/jca.13028 　

ISSN： 1837-9664
センチネルリンパ節切除後の二次リンパ節転移を予防する薬剤送達法の開発(Development of drug delivery system to prevent metastasis in secondary lymph node after sentinel lymph node removal)

大内友貴, 松木大輔, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　73回　J-2036　2014/09
Publisher: 日本癌学会
ISSN： 0546-0476
マイクロCTを用いた転移リンパ節内の血管構造解析(Vascular structural analysis in metastatic lymph node by Micro-CT)

八巻哲平, 柳沢ゆかり, 阪本真弥, 森士朗, 志賀清人, 小玉哲也

日本癌学会総会記事　73回　P-1143　2014/09
Publisher: 日本癌学会
ISSN： 0546-0476
マイクロCTを用いた転移リンパ節内血管構造解析に関する研究(Study of vascular structure analysis in lymph node metastasis using microCT)

柳沢ゆかり, 八巻哲平, 志賀清人, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　73回　P-1144　2014/09
Publisher: 日本癌学会
ISSN： 0546-0476
転移リンパ節に対する超音波と微小気泡を利用したリンパ行性薬剤送達法の開発(development of intralymphatic drug delivery system for metastatic lymph nodes by sonoporation with nano/micro bubbles)

白井優子, 佐藤琢磨, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　73回　P-3379　2014/09
Publisher: 日本癌学会
ISSN： 0546-0476
リンパ節転移治療におけるドキソルビシン封入温度感受性リポソームと光熱療法の併用(Combined application of doxorubicin-loaded thermosensitive liposomes and photothermal therapy in lymph nodes)

松木大輔, 大内友貴, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　73回　P-1452　2014/09
Publisher: 日本癌学会
ISSN： 0546-0476
Development of novel treatment for tumor-bearing lymph node by lymphatic administration and sonoporation Peer-reviewed

Shigeki Kato, Yuko Shirai, Shiro Mori, Tetsuya Kodama

Transactions of Japanese Society for Medical and Biological Engineering　52　349-O-350　2014/08/17
Publisher: Japan Soc. of Med. Electronics and Biol. Engineering
DOI： 10.11239/jsmbe.52.O-349 　

ISSN： 1347-443X 1881-4379
センチネルリンパ節切除による転移誘導を予防する薬剤送達法の開発

大内友貴, 邵楽南, 松木大輔, 加藤茂樹, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　30回　154-154　2014/07
Publisher: 日本DDS学会
転移リンパ節に対する超音波と微小気泡を利用したリンパ行性薬剤送達法の開発

白井優子, 加藤茂樹, 佐藤琢磨, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　30回　155-155　2014/07
Publisher: 日本DDS学会
マイクロCTを用いた転移リンパ節内血管構造解析に関する研究

柳沢ゆかり, 野呂和正, 伊藤康一, 清水良央, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　30回　182-182　2014/07
Publisher: 日本DDS学会
THE COMBINATION OF INTRALYMPHATIC CHEMOTHERAPY WITH ULTRASOUND AND NANO-/MICROBUBBLES IS EFFICIENT IN THE TREATMENT OF EXPERIMENTAL TUMORS IN MOUSE LYMPH NODES Peer-reviewed

Takuma Sato, Shiro Mori, Yoichi Arai, Tetsuya Kodama

ULTRASOUND IN MEDICINE AND BIOLOGY　40　(6)　1237-1249　2014/06

DOI： 10.1016/j.ultrasmedbio.2013.12.012 　

ISSN： 0301-5629

eISSN： 1879-291X
マウス転移リンパ節モデルに対する低出力超音波と微小気泡を用いた抗がん剤治療に関する研究

佐藤琢磨, 阪本真弥, 森士朗, 荒井陽一, 小玉哲也

日本泌尿器科学会総会　102回　622-622　2014/04
Publisher: (一社)日本泌尿器科学会総会事務局
Detecting Contrast Agents in Ultrasound Image Sequences for Tumor Diagnosis Peer-reviewed

Kazumasa Noro, Koichi Ito, Yukari Yanagisawa, Maya Sakamoto, Shiro Mori, Kiyoto Shiga, Tetsuya Kodama, Takafumi Aoki

2014 ASIA-PACIFIC SIGNAL AND INFORMATION PROCESSING ASSOCIATION ANNUAL SUMMIT AND CONFERENCE (APSIPA)　2014
Photothermal therapy of tumors in lymph nodes using gold nanorods and near-infrared laser light Peer-reviewed

Tatsuki Okuno, Shigeki Kato, Yuriko Hatakeyama, Junnosuke Okajima, Shigenao Maruyama, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

JOURNAL OF CONTROLLED RELEASE　172　(3)　879-884　2013/12

DOI： 10.1016/j.jconrel.2013.10.014 　

ISSN： 0168-3659

eISSN： 1873-4995
Characterization of the Arterial Anatomy of the Murine Hindlimb: Functional Role in the Design and Understanding of Ischemia Models Peer-reviewed

Takashi Kochi, Yoshimichi Imai, Atsushi Takeda, Yukiko Watanabe, Shiro Mori, Masahiro Tachi, Tetsuya Kodama

PLOS ONE　8　(12)　e84047　2013/12

DOI： 10.1371/journal.pone.0084047 　

ISSN： 1932-6203
リンパ節転移早期診断のための間質液圧特性に関する研究(Characterization of the interstitial fluid pressure for diagnosis of lymph node metastasis)

三浦由宣, 三ヶ田護, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　72回　324-324　2013/10
Publisher: 日本癌学会
ISSN： 0546-0476
リンパ節癌細胞移植マウスに対する超音波およびナノマイクロバブルをもちいたドラッグデリバリーに関する研究(Drug delivery to the mouse model of tumor bearing lymphnode with nano/microbubbles and ultrasound)

佐藤琢磨, 阪本真弥, 森士朗, 荒井陽一, 小玉哲也

日本癌学会総会記事　72回　474-474　2013/10
Publisher: 日本癌学会
ISSN： 0546-0476
Contrast-enhanced high-frequency ultrasound imaging of early stage liver metastasis in a preclinical mouse model Peer-reviewed

Sachiko Horie, Rui Chen, Li Li, Shiro Mori, Tetsuya Kodama

CANCER LETTERS　339　(2)　208-213　2013/10

DOI： 10.1016/j.canlet.2013.06.006 　

ISSN： 0304-3835

eISSN： 1872-7980
Imaging of transplanted islets by positron emission tomography, magnetic resonance imaging, and ultrasonography Peer-reviewed

Naoaki Sakata, Gumpei Yoshimatsu, Haruyuki Tsuchiya, Takeshi Aoki, Masamichi Mizuma, Fuyuhiko Motoi, Yu Katayose, Tetsuya Kodama, Shinichi Egawa, Michiaki Unno

Islets　5　(5)　179-187　2013/09

DOI： 10.4161/isl.26980 　

ISSN： 1938-2014 1938-2022
The Keap1/Nrf2 Protein Axis Plays a Role in Osteoclast Differentiation by Regulating Intracellular Reactive Oxygen Species Signaling Peer-reviewed

Hiroyuki Kanzaki, Fumiaki Shinohara, Mikihito Kajiya, Tetsuya Kodama

JOURNAL OF BIOLOGICAL CHEMISTRY　288　(32)　23009-23020　2013/08

DOI： 10.1074/jbc.M113.478545 　

ISSN： 0021-9258

eISSN： 1083-351X
EPR効果による近赤外蛍光粒子封入リポソームの腫瘍集積性に関する研究

三ヶ田護, Sax Nicolas, 阪本真弥, 森士朗, 小玉哲也

日本DDS学会学術集会プログラム予稿集　29回　135-135　2013/06
Publisher: 日本DDS学会
口腔癌所属リンパ節転移の診断・治療法の研究のためのリンパ節腫大リンパ節転移モデルマウスの開発

邵楽南, 森士朗, 柳下陽子, 宮下仁, 高橋哲, 小玉哲也

頭頸部癌　39　(2)　170-170　2013/05
Publisher: (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
Enhanced sonographic imaging to diagnose lymph node metastasis: Importance of blood vessel volume and density Peer-reviewed

Li Li, Shiro Mori, Mizuho Kodama, Maya Sakamoto, Shoki Takahashi, Tetsuya Kodama

Cancer Research　73　(7)　2082-2092　2013/04/01

DOI： 10.1158/0008-5472.CAN-12-4200 　

ISSN： 0008-5472 1538-7445
Lymphatic mapping of mice with systemic lymphoproliferative disorder: Usefulness as an inter-lymph node metastasis model of cancer Peer-reviewed

Lenan Shao, Shiro Mori, Yoko Yagishita, Tatsuki Okuno, Yuriko Hatakeyama, Takuma Sato, Tetsuya Kodama

JOURNAL OF IMMUNOLOGICAL METHODS　389　(1-2)　69-78　2013/03

DOI： 10.1016/j.jim.2013.01.004 　

ISSN： 0022-1759
Mouse Model of Lymph Node Metastasis via Afferent Lymphatic Vessels for Development of Imaging Modalities Peer-reviewed

Li Li, Shiro Mori, Maya Sakamoto, Shoki Takahashi, Tetsuya Kodama

PLoS ONE　8　(2)　e55797　2013/02/06

DOI： 10.1371/journal.pone.0055797 　

ISSN： 1932-6203
Temporal and steady state acoustic field in a cell culture well: Simulation Peer-reviewed

Min Joo Choi, Gwan Suk Kang, Tetsuya Kodama, Andrew J. Coleman

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS　1934-1935　2013

DOI： 10.1109/EMBC.2013.6609905 　

ISSN： 1557-170X
Optimization of Acoustic Liposomes for improved in vitro & in vivo stability Peer-reviewed

Sax N, Kodama T

Pharmaceutical Research　30　218-224　2013

DOI： 10.1007/s11095-012-0864-8 　
プラズモン共鳴を利用した局所的熱療法のリンパ節転移治療への応用

奥野竜希, 長谷川奈保, 畠山友梨子, 加藤茂樹, 阪本真弥, 森士郎, 小玉哲也

日本バイオマテリアル学会大会予稿集　シンポジウム2012　446-446　2012/11
Publisher: 日本バイオマテリアル学会
乳がんにおける腫瘍周辺上皮組織のリンパ管および血管分布に関する研究(The distribution of lymphatic and blood vessels in the peritumoral epithelium tissue in breast cancer)

三浦由宣, 佐藤琢磨, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　71回　492-493　2012/08
Publisher: 日本癌学会
ISSN： 0546-0476
二光子顕微鏡をもちいたEPR効果による腫瘍内ナノ粒子流出の観察(Observation of extravasated nano-particls inside solid tumor caused by EPR effect with two photon microscopy)

三ヶ田護, サックス・ニコラ, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　71回　497-497　2012/08
Publisher: 日本癌学会
ISSN： 0546-0476
リンパ行性薬剤送達システム開発ためのリンパ節およびリンパ管内の流動特性

畠山友梨子, サックス・ニコラ, 奥野竜希, 加藤茂樹, 森士郎, 阪本真弥, 小玉哲也

日本DDS学会学術集会プログラム予稿集　28回　143-143　2012/06
Publisher: 日本DDS学会
Effects of the Liposomal Formulation on the Behavior and Physical Characteristics of Acoustic Liposomes Peer-reviewed

Nicolas Sax, Sachiko Horie, Li Li, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

NONLINEAR ACOUSTICS: STATE-OF-THE-ART AND PERSPECTIVES (ISNA 19)　1474　228-231　2012

DOI： 10.1063/1.4749337 　

ISSN： 0094-243X
Eevaluation of antitumor effects with acoustic liposomes and high-frequency ultrasound Peer-reviewed

Kodama T, Tomita N, Yagishita Y, Horie S, Funamoto K, Hayase T, Sakamoto M, Mori S

Cancer Research.　71　(22)　6957-6964　2012

DOI： 10.1016/j.ultrasmedbio.2010.07.015 　
Evaluation of antitumor effects following tumor necrosis factor-alpha gene delivery using nanobubbles and ultrasound Peer-reviewed

Sachiko Horie, Yukiko Watanabe, Masao Ono, Shiro Mori, Tetsuya Kodama

CANCER SCIENCE　102　(11)　2082-2089　2011/11

DOI： 10.1111/j.1349-7006.2011.02056.x 　

ISSN： 1347-9032
Volumetric and Angiogenic Evaluation of Antitumor Effects with Acoustic Liposome and High-Frequency Ultrasound Peer-reviewed

Tetsuya Kodama, Noriko Tomita, Yoko Yagishita, Sachiko Horie, Kenichi Funamoto, Toshiyuki Hayase, Maya Sakamoto, Shiro Mori

CANCER RESEARCH　71　(22)　6957-6964　2011/11

DOI： 10.1158/0008-5472.CAN-11-2389 　

ISSN： 0008-5472
Shock wave-bubble interaction near soft and rigid boundaries during lithotripsy: numerical analysis by the improved ghost fluid method Peer-reviewed

Kazumichi Kobayashi, Tetsuya Kodama, Hiroyuki Takahira

PHYSICS IN MEDICINE AND BIOLOGY　56　(19)　6421-6440　2011/10

DOI： 10.1088/0031-9155/56/19/016 　

ISSN： 0031-9155
鼠径リンパ節内の圧力上昇にともなう輸出リンパ管への流出特性(Characteristics of the flow to the efferent lymphatic vessel upon increased pressure in the groin lymph node)

畠山友梨子, 李麗, サックス・ニコラ, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　70回　127-127　2011/09
Publisher: 日本癌学会
ISSN： 0546-0476
Monitoring transplanted islets by high-frequency ultrasound Peer-reviewed

Naoaki Sakata, Tetsuya Kodama, Rui Chen, Gumpei Yoshimatsu, Masafumi Goto, Shinichi Egawa, Michiaki Unno

ISLETS　3　(5)　259-266　2011/09

DOI： 10.4161/isl.3.5.17058 　

ISSN： 1938-2014
頭頸部癌遺伝子治療に向けたナノバブルと超音波によるNIS遺伝子導入と124I-PETイメージング

渡邊夕紀子, 森士朗, 堀江佐知子, サックス・ニコラ, 李麗, 李深偉, 柳下陽子, 高地崇, 船木善仁, 菊池洋平, 山崎浩道, 石井慶造, 阪本真弥, 宮下仁, 小玉哲也

頭頸部癌　37　(2)　234-234　2011/05
Publisher: (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
頭頸部癌所属リンパ節転移の診断・治療に向けたリンパ節腫大マウスを用いたリンパ節転移モデルの開発

李麗, 森士朗, 柳下陽子, サックス・ニコラ, 堀江佐知子, 渡邊夕紀子, 高地崇, 李深偉, 宮下仁, 森川秀広, 阪本真弥, 小玉哲也

頭頸部癌　37　(2)　274-274　2011/05
Publisher: (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
Investigating the Effect of Polymeric Approaches on Circulation Time and Physical Properties of Nanobubbles Peer-reviewed

Lisa C. du Toit, Thirumala Govender, Viness Pillay, Yahya E. Choonara, Tetsuya Kodama

PHARMACEUTICAL RESEARCH　28　(3)　494-504　2011/03

DOI： 10.1007/s11095-010-0247-y 　

ISSN： 0724-8741
DEVELOPMENT OF LOCALIZED GENE DELIVERY USING A DUAL-INTENSITY ULTRASOUND SYSTEM IN THE BLADDER Peer-reviewed

Sachiko Horie, Yukiko Watanabe, Rui Chen, Shiro Mori, Yasuhiro Matsumura, Tetsuya Kodama

ULTRASOUND IN MEDICINE AND BIOLOGY　36　(11)　1867-1875　2010/11

DOI： 10.1016/j.ultrasmedbio.2010.07.015 　

ISSN： 0301-5629
マイクロバブル造影剤と超音波を用いた頭頸部癌症例の頸部リンパ節転移の検討

天野雅紀, 志賀清人, 加藤健吾, 小川武則, 小林俊光, 小玉哲也, 阪本真弥

日本癌治療学会誌　45　(2)　668-668　2010/09
Publisher: (一社)日本癌治療学会
ISSN： 0021-4671
口腔癌早期診断のためのナノバブルと高周波超音波による腫瘍血管構築画像の病理的評価

柳下陽子, 森士朗, 高田陽子, 大木宏介, 宮下仁, 森川秀広, 川村仁, 小玉哲也

日本口腔外科学会雑誌　56　(Suppl.)　154-154　2010/09
Publisher: (公社)日本口腔外科学会
ISSN： 0021-5163
ナノバブルと高周波超音波による腫瘍血管構築とVEGFの発現に関する分子学的検討

宮下仁, 森士朗, 柳下陽子, 高田陽子, 大木宏介, 川村仁, 森川秀広, 小玉哲也

日本口腔外科学会雑誌　56　(Suppl.)　155-155　2010/09
Publisher: (公社)日本口腔外科学会
ISSN： 0021-5163
ナノ・マイクロバブルと超音波を用いた口腔癌の遺伝子治療を想定した分子導入法の検討

大木宏介, 森士朗, 宮下仁, 川村仁, 小玉哲也

日本口腔外科学会雑誌　56　(Suppl.)　180-180　2010/09
Publisher: (公社)日本口腔外科学会
ISSN： 0021-5163
三次元高周波超音波およびナノバブルを用いた肝転移の非侵襲的観察(Non-invasive observation of liver metastases by three-dimentional high-frequency ultrasound and nano/microbubbles)

陳鋭, 李麗, 渡邊夕紀子, Sax Nicolas, 堀江佐知子, 柳下陽子, 森士朗, 福本学, 小玉哲也

日本癌学会総会記事　69回　254-254　2010/08
Publisher: 日本癌学会
ISSN： 0546-0476
膀胱がん治療に向けた二重超音波照射法の数値的至適化(Theoretical optimization of a dual intensity ultrasound system for development of bladder cancer treatment)

小島貴則, 堀江佐知子, 渡邊夕紀子, 陳鋭, 李麗, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　69回　285-285　2010/08
Publisher: 日本癌学会
ISSN： 0546-0476
ナノバブルと超音波を用いたTNF-alpha遺伝子導入による抗腫瘍効果の評価(TNF-alpha gene delivery using nanobubbles and ultrasound for cancer therapy)

堀江佐知子, 渡邊夕紀子, 小島貴則, 陳鋭, 李麗, 柳下陽子, サックス・ニコラ, 阪本真弥, 森士朗, 小玉哲也

日本癌学会総会記事　69回　322-322　2010/08
Publisher: 日本癌学会
ISSN： 0546-0476
がん遺伝子治療に向けた新しいPETレポーター/治療遺伝子の開発(Development of new PET reporter/ therapy gene for cancer gene therapy) Peer-reviewed

渡邊夕紀子, 児玉栄一, 堀江佐知子, 高地崇, サックス・ニコラ, 柳下陽子, 陳鋭, 李麗, 服部俊夫, 森士朗, 小玉哲也

日本癌学会総会記事　69回　366-366　2010/08
Publisher: 日本癌学会
ISSN： 0546-0476
Optimum conditions of ultrasound-mediated destruction of bubble liposome for siRNA transfer in bladder cancer Peer-reviewed

Suguru Fujisawa, Hiroshige Arakawa, Ryo Suzuki, Kazuo Maruyama, Tetsuya Kodama, Masahiro Yasunaga, Yoshikatsu Koga, Yasuhiro Matsumura

Therapeutic Delivery　1　(2)　247-255　2010/08

DOI： 10.4155/tde.10.23 　

ISSN： 2041-5990 2041-6008

eISSN： 2041-6008
Self-Organization of a Stable Pore Structure in a Phospholipid Bilayer Peer-reviewed

Kenichiro Koshiyama, Takeru Yano, Tetsuya Kodama

PHYSICAL REVIEW LETTERS　105　(1)　018105-1-018105-5　2010/07

DOI： 10.1103/PhysRevLett.105.018105 　

ISSN： 0031-9007
EVALUATION OF TRANSFECTION EFFICIENCY IN SKELETAL MUSCLE USING NANO/MICROBUBBLES AND ULTRASOUND Peer-reviewed

Tetsuya Kodama, Atsuko Aoi, Yukiko Watanabe, Sachiko Horie, Mizuho Kodama, Li Li, Rui Chen, Noriyoshi Teramoto, Hidehiro Morikawa, Shiro Mori, Manabu Fukumoto

ULTRASOUND IN MEDICINE AND BIOLOGY　36　(7)　1196-1205　2010/07

DOI： 10.1016/j.ultrasmedbio.2010.04.016 　

ISSN： 0301-5629
Delivery of Na/I symporter gene into skeletal muscle using nanobubbles and ultrasound: Visualization of gene expression by PET

Yukiko Watanabe, Sachiko Horie, Yoshihito Funaki, Youhei Kikuchi, Hiromichi Yamazaki, Keizo Ishii, Shiro Mori, Georges Vassaux, Tetsuya Kodama

Journal of Nuclear Medicine　51　(6)　951-958　2010/06

DOI： 10.2967/jnumed.109.074443 　

ISSN： 0161-5505
Morphological study of acoustic liposomes using transmission electron microscopy Peer-reviewed

Tetsuya Kodama, Noriko Tomita, Sachiko Horie, Nicolas Sax, Hiroko Iwasaki, Ryo Suzuki, Kazuo Maruyama, Shiro Mori, Fukumoto Manabu

JOURNAL OF ELECTRON MICROSCOPY　59　(3)　187-196　2010/06

DOI： 10.1093/jmicro/dfp056 　

ISSN： 0022-0744
Ultrasound induced microbubble destruction and cavitation bubble generation Peer-reviewed

Tomita Y, Uchikoshi R, Inaba T, Kodama T

Japanese Journal of multiphase flow　24　(2)　162-168　2010/06/01
Publisher: THE JAPANESE SOCIETY FOR MULTIPHASE FLOW
DOI： 10.3811/jjmf.24.162 　

ISSN： 0914-2843

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Microbubble destruction and the induced cavitation bubble behavior are regarded as key phenomena affecting the enhancement of sonoporation. In the present study an experiment was carried out for investigating the interaction of ultrasound waves with microbubbles. Test liquid was a suspension of Sonazoid ultrasound contrast agent diluted with distilled water with the volumetric concentration of 10 % [v/v], which was set in a cylindrical vessel, i.e. one of a 24 well-plate, conventionally used in in vitro experiments and irradiated by ultrasound waves with the frequency of 1 MHz. It was found that microbubbles were rapidly destroyed and the survival number was reduced to half the original number within 100ms for all the liquid depths examined here. A maximum number of cavitation bubbles was achieved at a certain exposure time less than one second where more than sixty cavitation bubbles were generated, subsequently behaving in the observation volume (= 14 mm³). Although almost the microbubbles were crushed within one second, we occasionally observed a special situation where plenty of cavitation bubbles happened at the exposure time of five seconds due to the circulation flow generated by the acoustic radiation pressure coupled with the flow induced by the free surface fluctuation.
エコー高輝度のペグ化リポソームの開発と性状解析(Development and characterization of echogenic PEGylated liposomes)

Nicolas Sax, 堀江佐知子, 李麗, 陳鋭, 渡邊夕紀子, 阪本真弥, 森司朗, 小玉哲也

Drug Delivery System　25　(3)　288-288　2010/05
Publisher: 日本DDS学会
ISSN： 0913-5006

eISSN： 1881-2732
歯肉癌の遺伝子治療のためのナノ・マイクロバブルと超音波を用いた分子導入法の検討

陳鋭, 森士朗, 千葉美麗, 福本学, 小玉哲也

頭頸部癌　36　(2)　183-183　2010/05
Publisher: (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
口腔癌早期診断のためのナノバブルと高周波超音波を用いた画像診断法に関する組織学的検討

柳下陽子, 森士朗, 李麗, 渡邊夕紀子, 堀江佐知子, 富田典子, 陳鋭, 高田陽子, 大木宏介, 宮下仁, 小玉瑞穂, 川村仁, 森川秀広, 小玉哲也

頭頸部癌　36　(2)　253-253　2010/05
Publisher: (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
ナノバブルと高周波超音波を用いた腫瘍血管構築法の開発

柳下陽子, 森士朗, 李麗, 渡邊夕紀子, 堀江佐知子, 陳鋭, 高田陽子, 川村仁, 小玉哲也

Drug Delivery System　25　(3)　299-299　2010/05
Publisher: 日本DDS学会
ISSN： 0913-5006

eISSN： 1881-2732
ナノバブルと超音波を用いたTNF-α遺伝子導入による抗腫瘍効果の評価

堀江佐知子, 渡邊夕紀子, 陳鋭, サックス・ニコラ, 李麗, 小野栄夫, 森士朗, 小玉哲也

Drug Delivery System　25　(3)　313-313　2010/05
Publisher: 日本DDS学会
ISSN： 0913-5006

eISSN： 1881-2732
J0203-2-6 Experimental Study on Sonazoid Destruction by Focused Ultrasound Waves

TOMITA Yukio, MINAGAWA Ryuichiro, SHIMOMURA Bungo, KODAMA Tetsuya

The proceedings of the JSME annual meeting　2010　185-186　2010
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2010.6.0_185 　

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For destroying Sonazoid microbubbles 1 MHz - ultrasound waves was irradiated by employing a concave ultrasound probe with the vibrating diameter of 40 mm and the arithmetic focal length of 80 mm. The probe was set in distilled water at temperature of 25 ℃. A suspension of Sonazoid ultrasound contrast agent diluted with distilled water with the volumetric concentration of 5 % [v/v] was shut in a cuvette which was positioned at x_<c,b> measured from the bottom of the ultrasound probe. It was found that Sonazoid microbubbles were rapidly destroyed and the survival number was reduced to 40 % of the original number at the exposure time of 100 ms. When a cuvette containing suspension of Sonazoid microbubbles was set at the arithmetic focal point, a limited volume of Sonazoid suspension was exposed to the ultrasound waves, resulting in a relatively larger survival number of Sonazoid microbubbles. Sonazoid destruction was observed by taking snapshots using a nano-pulse light with the pulse duration of 180 ns as a light source.
J0203-1-3 Four-dimensional high-frequency ultrasound imaging for evaluation of liver metastases combined with nanobubbles

CHEN Rui, LI Li, WATANABE Yukiko, SAX Nicolas, HOREI Sachiko, MORI Shiro, KODAMA Tetsuya

The proceedings of the JSME annual meeting　2010　169-170　2010
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2010.6.0_169 　

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Three-dimensional high-frequency ultrasound (HF-US) combined with nanobubbles (NBs) permit detection of vessels in tumor. Description of the vessel density in tumors has recently been used for differentiating benign from malignant disease, but it was rarely reported in detection of liver metastases. In this study, we aimed to evaluate the possibility of detecting liver metastases at a minimum size, by evaluation the vessel density in the preclinical liver metastatic models with three-dimensional HF-US and NBs longitudinally. Tumor cells with luciferase-expressing were injected into the spleen slowly to establish the liver metastases models. Liver metastases were confirmed by luciferase activity located in the mouse liver area which was measured by in vivo bioluminescence system (IVIS). Ultrasound imaging on mice livers was performed by a high-frequency ultrasound system after NBs were administered from the tail vein. Vessels in the liver were constructed and the vessel density in the whole liver was calculated by the contrast mode soft. Contrast ultrasound images showed the change of vessels in normal and metastatic parts of liver with time. Vessel density could used to compare the angiogenesis in the metastatic mouse liver with the normal livers. These results demonstrated a system of HF-US combined with NBs could be useful for detection of liver metastases at a minimum size by evaluation the vessel density.
J0203-2-3 Development and characterization of long-circulating fluorescent liposomes

SAX Nicolas, HORIE Sachiko, WATANABE Yukiko, YAGISHITA Yoko, CHEN Rui, LI Li, MORI Shiro, KODAMA Tetsuya

The proceedings of the JSME annual meeting　2010　179-180　2010
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2010.6.0_179 　

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Newly formed tumor vasculature is usually abnormally leaky due to the extensive angiogenesis induced by the growing tumor, which enables extravasation of particles with a diameter of less than 200 nm: this phenomenon is recognized as the enhanced permeability and retention (EPR) effect. Due to their versatility, liposomes are potential candidates to take advantage of the EPR effect and passively target tumor cells. In this study, liposomes encapsulating fluorescent dye or bearing covalently-bound fluorophores on their surface were prepared and characterized in vitro. DLS and fluorescence measurements respectively showed that they currently display a diameter of less than 200nm and a fluorescence intensity similar to that of commercially available agents. Further research aims at an in vivo observation of the EPR effect through real-time visualization of the accumulation of such liposomes.
VISUALIZATION OF MICROCIRCULATION BASED ON BRIGHTNESS VARIATION IN CONTRAST-ENHANCED ULTRASOUND

Kenichi Funamoto, Toshiyuki Hayase, Tetsuya Kodama

PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE, 2010　219-220　2010

DOI： 10.1115/SBC2010-19349 　
Periodontal Gene Transfer by Ultrasound and Nano/Microbubbles Peer-reviewed

R. Chen, M. Chiba, S. Mori, M. Fukumoto, T. Kodama

JOURNAL OF DENTAL RESEARCH　88　(11)　1008-1013　2009/11

DOI： 10.1177/0022034509346119 　

ISSN： 0022-0345
口腔癌治療のためのナノバブルと超音波を用いた抗腫瘍効果増強法に関する検討

宮下仁, 森士朗, 高田陽子, 大木宏介, 川村仁, 森川秀広, 小玉哲也

日本口腔外科学会雑誌　55　(Suppl.)　91-91　2009/09
Publisher: (公社)日本口腔外科学会
ISSN： 0021-5163
ナノバブルと超音波を用いた高周波超音波画像診断装置による微小転移検出に関する検討

大木宏介, 森士朗, 高田陽子, 宮下仁, 川村仁, 森川秀広, 小玉哲也

日本口腔外科学会雑誌　55　(Suppl.)　94-94　2009/09
Publisher: (公社)日本口腔外科学会
ISSN： 0021-5163
超音波分子イメージングによるリンパ節転移早期診断法の開発(A novel approach to early diagnosis of lymph node metastasis with ultrasonic molecular imaging)

李麗, 堀江佐知子, 陳鋭, 渡邊夕紀子, 阪本真弘, 森士朗, 小玉哲也

日本癌学会総会記事　68回　462-462　2009/08
Publisher: 日本癌学会
ISSN： 0546-0476
表在性膀胱がんに対する新しい遺伝子治療法の開発

堀江佐知子, 渡邊夕紀子, 陳鋭, 李麗, 森士朗, 小玉哲也

超音波医学　36　(4)　525-526　2009/07
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
124Iを使用したNIS遺伝子発現イメージング法の開発超音波とナノバブルを利用した遺伝子デリバリー

渡邊夕紀子, 堀江佐知子, 船木善仁, 菊池洋平, 山崎浩道, 石井慶造, 森士朗, 小玉哲也

Drug Delivery System　24　(3)　364-364　2009/06
Publisher: 日本DDS学会
ISSN： 0913-5006

eISSN： 1881-2732
ナノバブルと超音波を用いた口腔癌リアルタイム画像診断システムの開発に向けての検討

森士朗, 李麗, 堀江佐知子, 渡邊夕紀子, 大木宏介, 宮下仁, 川村仁, 森川秀広, 小玉哲也

頭頸部癌　35　(2)　119-119　2009/05
Publisher: (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
ナノバブルと超音波を用いた抗腫瘍分子導入システムによる抗腫瘍効果に関する検討

宮下仁, 森士朗, 李麗, 堀江佐知子, 渡邊夕紀子, 大木宏介, 川村仁, 森川秀広, 小玉哲也

頭頸部癌　35　(2)　119-119　2009/05
Publisher: (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
ナノバブルと超音波を用いた口腔癌画像診断システムの診断精度に関する検討

大木宏介, 森士朗, 李麗, 堀江佐知子, 渡邊夕紀子, 宮下仁, 川村仁, 森川秀広, 小玉哲也

頭頸部癌　35　(2)　119-119　2009/05
Publisher: (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
ナノ・マイクロバブルと超音波によるシスプラチンの導入および抗腫瘍効果の増強

渡邊夕紀子, 堀江佐知子, 冨田典子, 大澤ふき, 森士朗, 小玉哲也

超音波医学　36　(2)　211-212　2009/03
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
A novel strategy utilizing ultrasound for antigen delivery in dendritic cell-based cancer immunotherapy Peer-reviewed

Ryo Suzuki, Yusuke Oda, Naoki Utoguchi, Eisuke Namai, Yuichiro Taira, Naoki Okada, Norimitsu Kadowaki, Tetsuya Kodama, Katsuro Tachibana, Kazuo Maruyama

JOURNAL OF CONTROLLED RELEASE　133　(3)　198-205　2009/02

DOI： 10.1016/j.jconrel.2008.10.015 　

ISSN： 0168-3659
J0201-2-5 Non-invasive observation of liver metastases in preclinical models

CHEN Rui, WATANABE Yukiko, HOREI Sachiko, MORI Shiro, FUKUMOTO Manabu, KODAMA Tetsuya

The proceedings of the JSME annual meeting　2009　117-118　2009
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2009.6.0_117 　

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Preclinical mouse models are essential to the study of liver metastasis, yet their utility has been limited by difficulty in tracking the progression of metastases through time. In this study, we attempted to applicate some non-invasive methods to study the murine liver metastasis. Livers of mice were observed by camera system termed photo dynamic eye (PDE) with the indocianine green (ICG) injected into the tail vein. Mice received and intrasplenic injection of luciferase-expressing tumor cells. Luciferase activity was measured by in vivo bioluminescence system (IVIS). Ultrasound imaging was performed by a high-frequency ultrasound system (VEVO), after nanobubbles were administered from the tail vein. As the result, murine liver metastases were identified using PDE and IVIS. Two-dimensional and three dimensional images by ultrasound and nanobubbles showed vessels in the liver. These results could be benefit for early diagnosis of liver metastases with a minimum detection size in preclinical model.
J0201-1-3 Developing a local molecular delivery for bladder cancer

HORIE Sachiko, WATANABE Yukiko, CHEN Rui, LI Li, MORI Shiro, KODAMA Tetsuya

The proceedings of the JSME annual meeting　2009　101-102　2009
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2009.6.0_101 　

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Seventy percent of patients with bladder cancer present superficial tumors with high recurrence rate. In order to develop effective superficial bladder cancer gene therapy, effective gene delivery using nanobubbles (NBs) and ultrasound (US) is our ultimate goal. To achieve this goal, we propose localized gene delivery in bladder using NBs and low-high-intensity US (LHUS) while low-intensity US direct NBs proximate to targeted cells in the bladder and high-intensity US collapse NBs to increase cell membrane permeability resulting the entry of exogenouse molecules into proximate cells. In the present study, to demonstrate the effectiveness of NBs and LHUS to localize the gene delivery to a designated bladder wall, we have assessed: i) in vivo local delivery and fragmentation of NBs with high frequency US imaging system; ii) localized molecular delivery of fluorescent molecules and quantification of the transfection efficacy; and iii) transfection of plasmid DNA and quantification of the transfection efficacy.
Cavitation bubbles mediated molecular delivery during sonoporation Peer-reviewed

Tetsuya Kodama, Yukio Tomita, Yukiko Watanabe, Kenichiro Koshiyama, Takera Yano, Shigeo Fujikawa

Journal of Biomechanical Science and Engineering　4　(1)　124-130　2009

DOI： 10.1299/jbse.4.124 　

ISSN： 1880-9863
Low-intensity ultrasound and microbubbles enhance the antitumor effect of cisplatin Peer-reviewed

Yukiko Watanabe, Atsuko Aoi, Sachiko Horie, Noriko Tomita, Shiro Mori, Hidehiro Morikawa, Yasuhiro Matsumura, Georges Vassaux, Tetsuya Kodama

CANCER SCIENCE　99　(12)　2525-2531　2008/12

DOI： 10.1111/j.1349-7006.2008.00989.x 　

ISSN： 1347-9032
Local gene delivery system of nano/microbubbles-enhanced ultrasound aimed for treatment of gingival tumor

Chen R, Chiba M, Watanabe Y, Horie S, Tomita N, Fukumoto M, Nori S, Kodama T

2008 International Conference on Frontiers of Dental and Craniofacial Research　2008/11/01
Production of "no carrier added” iodine-124 from a reusable enriched tellurium-124 dioxide target and its application to an ultra-high resolution animal PET study Peer-reviewed

Yamazaki H, Ishii K, Funaki Y, Kanai Y, Y, Kikuchi Y, Watanabe Y, Kodama T, Hatazawa J, Matsuyama S, Sabet H, Terakawa A

The 16th Pacific Basin Nuclear Conference　P16P1299　2008/10/13
高周波超音波イメージングシステムを用いた所属リンパ節転移画像診断システムの開発

冨田典子, 堀江佐知子, 大澤ふき, 陳鋭, 渡邊夕紀子, 森川秀広, 大木宏介, 森士朗, 小玉哲也

日本癌治療学会誌　43　(2)　837-837　2008/10
Publisher: (一社)日本癌治療学会
ISSN： 0021-4671
Peeling off effect and damage pit formation by ultrasonic cavitation

Tomita Y, Inaba T, Uchikoshi R, Kodama T

The International Conference on Hydraulic Machinery and Equipments　2008/10
高周波超音波を利用した新しいリンパ節内微小転移診断システムの開発(New diagnostic imaging system for lymph node micrometastasis with contrast-enhanced high-frequency ultrasound)

冨田典子, 堀江佐知子, 大澤ふき, 陳鋭, 渡邊夕紀子, 森川秀広, 大木宏介, 福本学, 森士朗, 小玉哲也

日本癌学会総会記事　67回　495-495　2008/09
Publisher: 日本癌学会
ISSN： 0546-0476
各種疾患マウス前脛骨筋でのPETによるNIS遺伝子発現の確認

渡邊夕紀子, 堀江佐知子, 冨田典子, 大澤ふき, 船木善仁, 菊池洋平, 中村賢治, 中沢浩一, 山崎浩道, 石井慶造, 福本学, 森士朗, 小玉哲也

核医学　45　(3)　S204-S204　2008/09
Publisher: (一社)日本核医学会
ISSN： 0022-7854

eISSN： 2189-9932
ナノバブルを用いた肝転移診断に関する三次元高周波超音波イメージング(Three-dementional High-Frequency Ultrasound Imaging for diagnosis of Liver Metastases Combined with Nanobubbles)

陳鋭, 冨田典子, 馬場泰輔, 大澤ふき, 渡邊夕紀子, 堀江佐知子, 森士朗, 福本学, 小玉哲也

日本癌学会総会記事　67回　313-313　2008/09
Publisher: 日本癌学会
ISSN： 0546-0476
癌性疼痛緩和およびPETによるイメージング(Cancer pain control and PET imaging)

渡邊夕紀子, 堀江佐知子, 冨田典子, 陳鋭, 大澤ふき, 船木善仁, 菊池洋平, 山崎浩道, 石井慶造, 小野栄夫, 福本学, 森士朗, 小玉哲也

日本癌学会総会記事　67回　388-388　2008/09
Publisher: 日本癌学会
ISSN： 0546-0476
マウス骨格筋でのNa/I symporter (NIS)遺伝子発現の可視化

渡邊夕紀子堀江佐知子, 冨田典子, 大澤ふき, 陳鋭船木善仁, 菊池洋平, 山崎浩道, 石井慶造, 森士朗, 小玉哲也

日本機械学会2008年度年次大会講演論文集Vol.2 23-24頁　2　23-24　2008/08
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2008.2.0_23 　

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A non-invasive molecular delivery method using nano/microbubbles (NB) and ultrasound (US) is an attractive technique for gene therapy. This method is able to deliver macromolecules such as plasmid DNA to a tissue specific site non-invasively. In addition, a non-invasive quantification method of gene expression has been studied by monitoring ^<124> accumulation caused by the of Na/I symporter (NIS) gene expression with positron emission tomography (PET). In the present study, we delivered NIS gene into the skeletal muscle of vasculitis and muscular dystrophy mice by using the US/NB method, and succeed in visualizing the ^<124>I accumulation caused by NIS gene expression in the muscle with PET. The combination of the US/NB delivery with NIS/PET visualization will be a valuable methodology in gene therapy.
ナノバブルと超音波を利用した炎症疾患モデルマウスでのNa/I sympoter(NIS)遺伝子発現の可視化

渡邊夕紀子, 堀江佐知子, 冨田典子, 大澤ふき, 船木善仁, 菊池洋平, 山崎浩道, 石井慶造, 森士朗, 小玉哲也

超音波医学　35　(4)　469-469　2008/07
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
高解像度超音波イメージングシステムを用いたシスプラチンによる抗腫瘍効果の定量化

冨田典子, 堀江佐知子, 渡邊夕紀子, 大澤ふき, 佐久間基成, 大木宏介, 森川秀広, 森士朗, 小野栄夫, 小玉哲也

超音波医学　35　(4)　469-469　2008/07
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
Molecular dynamics simulation of structural changes of lipid bilayers induced by shock waves: Effects of incident angles Peer-reviewed

Kenichiro Koshiyama, Tetsuya Kodama, Takeru Yano, Shigeo Fujikawa

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES　1778　(6)　1423-1428　2008/06

DOI： 10.1016/j.bbamem.2008.03.010 　

ISSN： 0005-2736
ナノバブル超音波システムを用いた抗癌剤および抗腫瘍分子の導入による新たな癌治療法の開発

宮下仁, 森士朗, 冨田典子, 堀江佐知子, 渡邉夕紀子, 陳鋭, 大澤ふき, 佐久間基成, 大木宏介, 川村仁, 森川秀広, 小玉哲也

頭頸部癌　34　(2)　148-148　2008/05
Publisher: (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
口腔癌の診断・治療のためのナノバブルと超音波を用いた画像診断・分子導入システムの開発

森士朗, 渡邊夕紀子, 堀江佐知子, 冨田典子, 陳鋭, 大澤ふき, 佐久間基成, 大木宏介, 宮下仁, 川村仁, 森川秀広, 小玉哲也

頭頸部癌　34　(2)　165-165　2008/05
Publisher: (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
ナノバブルを用いた腫瘍血管造影法による口腔癌早期診断システムモデルの開発

大木宏介, 森士朗, 堀江佐知子, 冨田典子, 渡邊夕紀子, 陳鋭, 大澤ふき, 佐久間基成, 宮下仁, 川村仁, 森川秀広, 小玉哲也

頭頸部癌　34　(2)　165-165　2008/05
Publisher: (一社)日本頭頸部癌学会
ISSN： 1349-5747

eISSN： 1881-8382
高周波超音波イメージングシステムによるシスプラチン抗腫瘍効果の定量化

小玉哲也, 渡邊夕紀子, 堀江佐知子, 冨田典子, 大澤ふき, 佐久間基成, 陳鋭大木宏介, 森川秀広, 森士朗, 小野栄夫

第46回日本生体医工学会大会プログラム・抄録集　277　2008/05
Herpes simplex virus thymidine kinase-mediated suicide gene therapy using nano/microbubbles and ultrasound Peer-reviewed

Atsuko Aoi, Yukiko Watanabe, Shiro Mori, Masahiko Takahashi, Georges Vassaux, Tetsuya Kodama

ULTRASOUND IN MEDICINE AND BIOLOGY　34　(3)　425-434　2008/03

DOI： 10.1016/j.ultrasmedbio.2007.09.004 　

ISSN： 0301-5629
超音波とナノ/ミクロバブルを用いた歯周組織への遺伝子導入(Periodontal Gene Transfer Using Ultrasound and Nano/Microbubbles)

陳鋭, 千葉美麗, 堀江佐知子, 五十嵐薫, 小玉哲也

超音波医学　35　(1)　78-79　2008/01
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
FDG imaging of 1mm tumor with an ultra high resolution animal PET Peer-reviewed

K. Ishii, Y. Funaki, Y. Kikuch, H. Yamazaki, S. Matsuyama, A. Terakawa, M. Fujiwara, R. Iwata, T. Kodama, Y. Watanabe, N. Tanizaki, D. Amano, T. Yamaguchi

2008 5th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, Proceedings, ISBI　1589-1592　2008

DOI： 10.1109/ISBI.2008.4541315 　
Contrast-Enhanced High-Frequency Ultrasound Imaging of Liver Metastases in Preclinical Models Peer-reviewed

Rui Chen, Noriko Tomita, Taisuke Baba, Fuki Oosawa, Yukiko Watanabe, Sachiko Horie, Shiro Mori, Manabu Fukumoto, Tetsuya Kodama

2008 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 AND APPENDIX　1742-1744　2008

ISSN： 1051-0117
Development of diagnostic imaging system for regional lymph node micrometastasis with high-frequency ultrasound Peer-reviewed

Noriko Tomita, Sachiko Horie, Fuki Oosawa, Yukiko Watanabe, Rui Chen, Kosuke Ohki, Hirohide Morikawa, Manabu Fukumoto, Shiro Mori, Tetsuya Kodama

2008 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 AND APPENDIX　1728-+　2008

ISSN： 1051-0117
ナノバブルと超音波を用いたDDS：骨格筋への応用

小玉哲也, 青井あつ子, 渡邊夕紀子, 小野栄夫, 森士朗

日本機械学会2007年度年次大会講演論文集　2　151-152　2007/09
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2007.2.0_151 　

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In the present study, the kinetics of gene transfer mediated by ultrasound contrast agents (albumin, lipid micelle, and acoustic liposome nano/microbubbles) and ultrasound in the skeletal muscle was investigated with varying bubble concentrations. The gene activity depended on the bubble concentration, therefore, gene transfer efficiency would be improved with increasing bubble concentrations. However, the transient nature of transgene expression combined with the damage to the muscle observed at the peak of expression restricts the potential therapeutic application of this methodology.
シスプラチンを使った抗腫瘍効果：高周波による定量化 Peer-reviewed

冨田典子, 渡邊夕紀子, 堀江佐知子, 小野栄夫, 森士朗, 小玉哲也

日本機械学会2007年度年次大会講演論文集　2　155-156　2007/09
ナノバブルと超音波を用いた自殺遺伝子導入法の開発

青井あつ子, 今野聖絵, 篠原文明, 森川秀広, 森士朗, Vassaux, G, 小玉哲也

日本機械学会2006年度年次大会講演論文集　5　29-29　2007/09
Interaction of shock waves generated by cavitation bubbles with cell membranes during sonoporation. Peer-reviewed

Kodama T, Tomita Y, Aoi A, Koshiyama K, Yano T, Fujikawa S

The 1st International Colloquium on Dynamics, Physics and Chemistry of Bubbles and Gas-Liquid Boundaries　7　2007/09
Molecular mechanisms of cavitation-induced cell membrane permeabilization Peer-reviewed

Koshiyama K, Kodama T, Yano T, Fujikawa S

The 1st International Colloquium on Dynamics, Physics and Chemistry of Bubbles and Gas-Liquid Boundaries　8　2007/09
高周波超音波画像診断による抗腫瘍効果の評価(Evaluation of anfitumor effects using high frequency ultrasound biomicroscopy)

堀江佐知子, 冨田典子, 渡邊夕紀子, 大木宏介, 森川秀広, 森士朗, 小野栄夫, 小玉哲也

日本癌学会総会記事　66回　352-352　2007/08
Publisher: 日本癌学会
ISSN： 0546-0476
ナノバブルと高周波超音波による腫瘍内血管の三次元画像の構築(Construction of three-dimentional image of intratumoral vessel using high-frequency contrast-enhanced micro-ultrasound)

冨田典子, 堀江佐知子, 渡邊夕紀子, 船本健一, 早瀬敏幸, 大木宏介, 森川秀広, 小野栄夫, 森士朗, 小玉哲也

日本癌学会総会記事　66回　353-353　2007/08
Publisher: 日本癌学会
ISSN： 0546-0476
ソノポレーションによる遺伝子導入効率気泡特性に対する検討

小玉哲也, 青井あつ子, 渡邊夕紀子, 堀江佐知子, 冨田典子, 小野栄夫, 森士朗

超音波医学　34　(Suppl.)　S295-S295　2007/04
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
Spinal gene transfer using ultrasound and microbubbles Peer-reviewed

Masahiko Takahashi, Kanta Kido, Atsuko Aoi, Hiroshi Furukawa, Masao Ono, Tetsuya Kodama

JOURNAL OF CONTROLLED RELEASE　117　(2)　267-272　2007/02

DOI： 10.1016/j.jconrel.2006.10.026 　

ISSN： 0168-3659
1530 Mechanisms of Ultrasound-mediated Molecular Transport Across Cell Membranes : Molecular Dynamics Simulations

KOSHIYAMA Kenichiro, KODAMA Tetsuya, YANO Takeru, FUJIKAWA Shigeo

The proceedings of the JSME annual meeting　2007　153-154　2007
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2007.2.0_153 　

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Cell membrane permeabilization technique utilizing ultrasound and micro- nano- bubbles (i.e. sonoporation) is a promising way of drug and gene delivery. The mechanisms of the permeabilization and subsequent molecular transport across the membrane are underlying the development of the technique for clinical applications. We thereby have studied the mechanisms in the molecular level by molecular dynamics (MD) simulations of lipid bilayers, which are fundamental of all biological cell membranes. Firstly, we performed MD simulations of structural changes of the bilayer induced by shock wave and revealed the resulting collapse and rebound of the bilayer followed by water penetration into the hydrophobic region of the bilayer. Next, we studied the water pore formation resulted from the water penetration into the hydrophobic region. It was found that the water pore is formed within several nanoseconds when large amount of water molecules are existed in the hydrophobic region. Finally, we analyzed the diffusion of anti-cancer drug in the water pore and deduced that the water pore induced by the action of shock wave may be one of the processes of drug delivery in the presence of shock waves.
1531 Quantification of cisplatin-induced antitumor effect with high-frequency ultrasound

TOMITA Noriko, WATANABE Yukiko, HORIE Sachiko, ONO Masao, MORI Shiro, KODAMA Tetsuya

The proceedings of the JSME annual meeting　2007　155-156　2007
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2007.2.0_155 　

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In the present study, we quantified antitumor effect by cisplatin with thee-dimensional tumor diagnostic technique using high-frequency ultrasound and nanobubbles. Solid tumors were developed in mice and the antitumor efficacy was compared to a conventional caliper method. It was found that high-frequency ultrasound method was able to evaluate intratumor vascular structure and density as well as tumor volume. The caliper method overestimated tumor volume by a factor of two compared to this technique.
Structural change in lipid bilayers and water penetration induced by shock waves: Molecular dynamics simulations Peer-reviewed

Kenichiro Koshiyama, Tetsuya Kodama, Takeru Yano, Shigeo Fujikawa

BIOPHYSICAL JOURNAL　91　(6)　2198-2205　2006/09

DOI： 10.1529/biophysj.105.077677 　

ISSN： 0006-3495
A non-invasive tissue-specific molecular delivery method of cancer gene therapy Peer-reviewed

Tetsuya Kodama, Atsuko Aoi, Georges Vassaux, Shiro Mori, Hidehiro Morikawa, Keni-Chiro Koshiyama, Takeru Yano, Shigeo Fujikawa, Yukio Tomita

MINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES　15　(4)　226-229　2006/08

DOI： 10.1080/13645700600836059 　

ISSN： 1364-5706

eISSN： 1365-2931
Transfection effect of microbubbles on cells in superposed ultrasound waves and behavior of cavitation bubble Peer-reviewed

Tetsuya Kodama, Yukio Tomita, Ken-ichiro Koshiyama, Martin J. K. Blomley

ULTRASOUND IN MEDICINE AND BIOLOGY　32　(6)　905-914　2006/06

DOI： 10.1016/j.ultrasmedbio.2006.03.004 　

ISSN： 0301-5629

eISSN： 1879-291X
ソノポレーションを用いた薬剤導入と抗腫瘍効果(Win)

佐藤義太郎, 鈴木麻衣子, 青井あつ子, 渡邊夕紀子, 小玉哲也, 篠原文明, 森士朗, 力石秀美

超音波医学　33　(2)　243-244　2006/03
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
716 Diffusion of Anti-cancer Drug near Lipid Bilayer Surface : Molecular Dynamics Simulation

KOSHIYAMA Kenichiro, KODAMA Tetsuya, YANO Takeru, FUJIKAWA Shigeo

The proceedings of the JSME annual meeting　2006　233-234　2006
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2006.5.0_233 　

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The diffusion process of a 5-fuluorouracil (5FU) in the water layer confined by two leaflets of lipid monolayer is elucidated by molecular dynamics simulation. The calculated diffusion constant of 5FU is 1.1×10^<-5>cm^2/s in bulk water with SPC/E water model at 25℃. This is in rather good agreement with that obtained in a recent NMR experiment (1.0×10^<-5>cm^2/s). It is found that the diffusion constant of 5FU in the confined water layer decreases as it moves from the center of the water layer toward the lipid monolayer surface. This decrease may be caused by the effect of the charges of the hydrophilic head groups of the lipid molecules.
Molecular dynamics simulation of water pore formation in lipid bilayer induced by shock waves Peer-reviewed

Ken-ichiro Koshiyama, Tetsuya Kodama, Takeru Yano, Shigeo Fujikawa

THERAPEUTIC ULTRASOUND　829　583-+　2006

DOI： 10.1063/1.2205541 　

ISSN： 0094-243X
Interaction of impulsive pressures of cavitation bubbles with cell membranes during sonoporation Peer-reviewed

Tetsuya Kodama, Ken-ichiro Koshiyama, Yukio Tomita, Maiko Suzuki, Takeru Yano, Shigeo Fujikawa

THERAPEUTIC ULTRASOUND　829　34-+　2006

DOI： 10.1063/1.2205433 　

ISSN： 0094-243X
Delivery of oligodeoxynucleotides into human saphenous veins and the adjunct effect of ultrasound and microbubbles Peer-reviewed

T Kodama, PH Tan, Offiah, I, T Partridge, T Cook, AJT George, MJK Blomley

ULTRASOUND IN MEDICINE AND BIOLOGY　31　(12)　1683-1691　2005/12

DOI： 10.1016/j.ultrasmedbio.2005.08.002 　

ISSN： 0301-5629
マイクロバブルを用いた脊髄への遺伝子導入法の開発

城戸幹太, 高橋雅彦, 青井あつ子, 鈴木麻衣子, 小玉哲也, 森士朗, 古川宏, 小野栄夫

日本歯科麻酔学会雑誌　33　(4)　576-576　2005/09
Publisher: (一社)日本歯科麻酔学会
ISSN： 0386-5835

eISSN： 2433-4480
ナノバブルによるアポトーシス誘導と薬剤感受性増強作用

鈴木麻衣子, 篠原文明, 森士朗, 小玉哲也

日本癌学会総会記事　64回　304-304　2005/09
Publisher: 日本癌学会
ISSN： 0546-0476
ナノバブルを用いたHSV-TK/GCV自殺遺伝子治療法の開発

鈴木麻衣子, 篠原文明, 青井あつ子, 佐藤義太郎, 渡邊夕紀子, 森士朗, Vasaaux G., 小玉哲也

日本バイオレオロジー学会年会抄録集　28回　22-22　2005/06
Publisher: (NPO)日本バイオレオロジー学会
ナノバブルを利用したsonoporationのメカニズム

小玉哲也, 鈴木麻衣子, 冨田幸雄, 高橋史明, 森士朗

Drug Delivery System　20　(3)　343-343　2005/05
Publisher: 日本DDS学会
ISSN： 0913-5006

eISSN： 1881-2732
ナノバブルを用いた薬剤導入と抗腫瘍効果の検討

鈴木麻衣子, 篠原文明, 森士朗, 小玉哲也

超音波医学　32　(Suppl.)　S212-S212　2005/04
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
ナノバブルによる抗腫瘍効果

鈴木麻衣子, 篠原文明, 森士朗, Vassaux, G, 小玉哲也

平成16年度衝撃波シンポジウム講演論文集　383-386　2005/03
Nanobubble enhanced drug susceptibility of cancer cells using ultrasound Peer-reviewed

Suzuki M, Koshiyama K, Shinohara F, Mori M, Ono M, Tomita Y, Yano T, Fujikawa S, Vassaux G, Kodama T

International Congress Series.　1284　338-339　2005/02
Publisher: Elsevier BV
DOI： 10.1016/j.ics.2005.06.090 　

ISSN： 0531-5131
1260 Behavior of nano-scale contrast agents with ultrasound and mechanisms of molecular delivery

KODAMA Tetsuya, Suzuki Maiko, Tomita Yukio

The proceedings of the JSME annual meeting　2005　131-132　2005
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2005.6.0_131 　

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Nano/micro-bubbles are capable of enhancing non-invasive cytoplasmic molecular delivery in the presence of ultrasound. Collapse of the bubbles might generate nano-scale free cavitation bubbles, resulting in transient membrane permeabilization. In the present study, we used two different nano bubbles to investigate the mechanism of molecular delivery into the cytoplasm with theory and experiment.
1261 Molecular Dynamics Simulation of 5-Fluorouracil Delivery into Lipid Bilayer

KOSHIYAMA Kenichiro, KODAMA Tetsuya, YANO Takeru, FUJIKAWA Shigeo

The proceedings of the JSME annual meeting　2005　133-134　2005
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2005.6.0_133 　

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Molecular dynamics (MD) simulations of molecular delivery into a lipid bilayer utilizing shock-wave-based techniques were carried out for 5Fuluorouracil (5FU). Although water penetration into the bilayer hydrophobic region was observed for a shock wave impulse range of 9.5〜57mPa.s, 5FU penetration was not observed. Therefore larger structural changes (e.g. water pore formation) than those observed in current simulations are thought to be required for 5FU penetration.
122 Non-Equilibrium Molecular Dynamics of Structural Changes in Lipid Bilayer for Development of Gene Delivery System

KOSHIYAMA Kenichiro, KODAMA Tetsuya, YANO Takeru, FUJIKAWA Shigeo

Proceedings of the JSME Bioengineering Conference and Seminar　2004　235-236　2005
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmebs.2004.17.0_235 　
225 Microbubble induced cell membrane permeabilization : experimental and theoretical analysis

KODAMA Tetsuya, TOMITA Yukio, KOSHIYAMA Ken-ichiro, Blomley Martin

Proceedings of the JSME Bioengineering Conference and Seminar　2004　265-266　2005
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmebs.2004.17.0_265 　
Molecular delivery into a lipid bilayer with a single shock waves using molecular dynamic simulation

K Koshiyama, T Kodama, MR Hamblin, AG Doukas, T Yano, S Fujikawa

4th International Symposium on Therapeutic Ultrasound　754　104-106　2005

ISSN： 0094-243X
Molecular delivery into a lipid bilayer with a single shock waves using molecular dynamic simulation Peer-reviewed

K Koshiyama, T Kodama, MR Hamblin, AG Doukas, T Yano, S Fujikawa

4th International Symposium on Therapeutic Ultrasound　754　104-106　2005

DOI： 10.1063/1.1901611 　

ISSN： 0094-243X
Optimisation of ultrasound-mediated gene transfer (sonoporation) in skeletal muscle cells Peer-reviewed

HD Liang, QL Lu, SA Xue, M Halliwell, T Kodama, DO Cosgrove, HJ Stauss, TA Partridges, MJK Blomley

ULTRASOUND IN MEDICINE AND BIOLOGY　30　(11)　1523-1529　2004/11

DOI： 10.1016/j.ultrasmedbio.2004.08.021 　

ISSN： 0301-5629
Ultrasound mediated gene expression using microbubbles

Kodama T, Tomita Y, Koshiyama, Blomley M

Proceedings of the fourth international symposium on advanced Fluid information and the first international symposium on transdisciplinary fluid integration　34-35　2004/11
Molecular dynamics simulation of cell permeabilization induced by shock wave impulse

Koshiyama K, Kodama T, Yano T, Fujikawa S

Proceedings of the fourth international symposium on advanced Fluid information and the first international symposium on transdisciplinary fluid integration　36-37　2004/11
Molecular Dynamics Simulations of the Interaction of Shock Waves with a Lipid Bilayer

KOSHIYAMA Kenichiro, KODAMA Tetsuya, YANO Takeru, FUJIKAWA Shigeo

The proceedings of the JSME annual meeting　2004　51-52　2004
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/jsmemecjo.2004.2.0_51 　

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Cell permeabilization using shock waves may be a promising way of introducing macromolecules and small polar molecules into the cytoplasm and may have applications in gene therapy and anticancer drug delivery. The detailed mechanism of the cell permeabilization however is still unclear. To investigate the mechanism, we have performed molecular dynamics (MD) simulations of the interaction of the shock wave impulse with a lipid-bilayer. The MD simulation determined the relationship between the uptake of water molecules into the lipid bilayer and the impulse. The interaction of a shock wave with a lipid bilayer induced a structural change of the bilayer and subsequently increased the fluidity of each molecule. These changes in the bilayer may be an important factor for the mechanism of cell permeabilization using shock waves.
Interaction of laser-induced cavitation bubbles with composite surfaces Peer-reviewed

Y Tomita, T Kodama

JOURNAL OF APPLIED PHYSICS　94　(5)　2809-2816　2003/09

DOI： 10.1063/1.1594277 　

ISSN： 0021-8979
Delivery of ribosome-inactivating protein toxin into cancer cells with shock waves Peer-reviewed

Tetsuya Kodama, Apostolos G. Doukas, Michael R. Hamblin

Cancer Letters　189　(1)　69-75　2003/04

DOI： 10.1016/S0304-3835(02)00503-7 　
Shock wave-mediated molecular delivery into cells Peer-reviewed

Kodama T, Doukas AG, Hamblin MR

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH　1542　(1-3)　186-194　2002/04

DOI： 10.1016/S0167-4889(01)00177-X 　
Interaction of cavitation bubbles with a free surface Peer-reviewed

P. B. Robinson, J. R. Blake, T. Kodama, A. Shima, Y. Tomita

Journal of Applied Physics　89　(12)　8225-8237　2001/06

DOI： 10.1063/1.1368163 　

ISSN： 0021-8979
Some aspects of the motion of two laser-produced cavitation bubbles near a free surface Peer-reviewed

Tomita Y, Kodama T

IUTAM Symposium on "Free Surface Flows"　2000/06

DOI： 10.1007/978-94-010-0796-2_37 　
Cavitation bubble behavior and bubble-shock wave interaction near a gelatin surface as a study of in vivo bubble dynamics Peer-reviewed

Kodama T, Tomita Y

APPLIED PHYSICS B-LASERS AND OPTICS　70　(1)　139-149　2000/04

DOI： 10.1007/s003400050022 　
In vivo transdermal delivery using a shock tube Peer-reviewed

S. Lee, D.J. McAuliffe, T. Kodama, Doukas AG

Shock waves　10　(5)　307-311　2000/04

DOI： 10.1007/s001930000059 　
Cytoplasmic Molecular Delivery with Shock Waves: Importance of Impulse Peer-reviewed

Kodama T, Hamblin, MR, Doukas AG

Biophysical Journal　79　(4)　1821-1832　2000/04

DOI： 10.1016/S0006-3495(00)76432-0 　
Liquid jets, accelerated thrombolysis: A study for revascularization of cerebral embolism Peer-reviewed

Tetsuya Kodama, Masashi Tatsuno, Shinya Sugimoto, Hiroshi Uenohara, Takashi Yoshimoto, Kazuyoshi Takayama

Ultrasound in Medicine and Biology　25　(6)　977-983　1999/07
Publisher: Elsevier Science Ltd
DOI： 10.1016/S0301-5629(99)00050-2 　

ISSN： 0301-5629
Innovative technology for tissue disruption by explosive-induced shock waves Peer-reviewed

Tetsuya Kodama, Hiroshi Uenohara, Kazuyoshi Takayama

Ultrasound in Medicine and Biology　24　(9)　1459-1466　1998/12
Publisher: Elsevier Sci Ltd
DOI： 10.1016/S0301-5629(98)00094-5 　

ISSN： 0301-5629
Dynamic behavior of bubbles during extracorporeal shock-wave lithotripsy Peer-reviewed

Tetsuya Kodama, Kazuyoshi Takayama

Ultrasound in Medicine and Biology　24　(5)　723-738　1998/06
Publisher: Elsevier Sci Ltd
DOI： 10.1016/S0301-5629(98)00022-2 　

ISSN： 0301-5629
前立腺肥大症に対するHo:YAGレーザーを用いた治療 Peer-reviewed

棚橋善克, 豊田精一, 喜屋武淳, 坂井清英, 太田章三, 小玉哲也, 高山和喜

日レ医誌（JJSLSM)　19　(1)　39-45　1998
Publisher: Japan Society for Laser Surgery and Medicine
DOI： 10.2530/jslsm1980.19.1_39 　

ISSN： 0288-6200

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Transurethral prostatectomy is performed using Ho: YAG laser in this study. Prostatic tissue is cut by underwater shockwave induced by Ho: YAG laser irradiation. The advantage of this method compared with transurethral prostatectomy using high frequency electrical current is that bleeding is little and there is no possibility of having hyponatremia. Another advantage of this method compared with transurethral prostatectomy using Nd: YAG laser is that the force of urinary stream greatly improves just after the operation.
Medical application of underwater shock waves

Takayama K, Kodama T

Proceedings of 23rd International Pytotechnics Seminar　1997/09
Research into Shock Wave revasculation Therapy of Acute cerebral embolism Peer-reviewed

Kodama T, Takayama K, Uenohara H

Proceedings of International Conference on Fluid Engineering　97-203　(2)　773-776　1997/04
Revascularization therapy for acute cerebral embolism by the impact of a liquid jet generated by the interaction of a gas bubble with an underwater shock wave Peer-reviewed

Kodama T, Takayama K, N. Nagayasu, Uenohara H, Takahashi N

Proceedings of the 21st International Symposium on Shock Waves　(1)　183　1997/04
衝撃波脳塞栓症血行再建術の基礎研究 Peer-reviewed

小玉哲也, 高山和喜, 永易伸生, 上之原広司, 吉田昌弘

Neurosonology　10　(2)　79-83　1997
Publisher: The Japan Academy of Neurosonology
DOI： 10.2301/neurosonology.10.79 　

ISSN： 0917-074X

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The shock-induced collapse and jet formation of a single air bubble inside a cylinder filled with gelatin and an artificial thrombus were investigated using high-speed photography. A thrombus was prepared in vitro and inserted in a cylinder modeling an artery to establish a treatment for brain embolism by the interaction of an underwater shock wave with an air bubble. When the shock wave was applied to an air bubble of mm in diameter, the liquid jet that formed within the bubble penetrated the thrombus. Liquid jet impact ablation of the for thrombus was found to be very effective, and provided valuable information for the treatment of brain embolism.
A new technology for revascularization of cerebral embolism using liquid jet impact Peer-reviewed

Tetsuya Kodama, Kazuyoshi Takayama, Hiroshi Uenohara

Physics in Medicine and Biology　42　(12)　2355-2367　1997

DOI： 10.1088/0031-9155/42/12/004 　

ISSN： 0031-9155
The dynamics of two air bubbles loaded by an underwater shock wave Peer-reviewed

T. Kodama, K. Takayama, N. Nagayasu

Journal of Applied Physics　80　(10)　5587-5592　1996/11/15
Publisher: American Institute of Physics Inc.
DOI： 10.1063/1.363605 　

ISSN： 0021-8979
脳塞栓症血行再建術の基礎研究：円筒内での気泡崩壊にともなう液体ジェットの形成条件 Peer-reviewed

永易伸生, 小玉哲也, 高山和喜, 上之原広司

火薬学会誌　57　(6)　263-270　1996
Publisher:
ISSN： 1340-2781
Interaction of air bubbles with shock waves:Basic research for medical applications

KODAMA Tetsuya, YAMADA Kiyoshi, TAKAYAMA Kazuyoshi

Transactions of Visualization Society of Japan　15　(1)　19-22　1995
Publisher: The Visualization Society of Japan
DOI： 10.3154/jvs.15.Supplement1_19 　

ISSN： 0916-4731

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This is an experimental study visualizing the interaction of air bubbles with underwater shock waves and is related to the investigation of tissue damage induced during extracorporeal shockwave lithotripsy treatment. Two optical visualization techniques, such as holographic interferometry and conventional photography were intensively used. The result of visualization revealed that various collapse patterns exist depending on properties of surrounding materials and the tissue damage could be generated mainly due to liquid jets formed inside the bubbles.
Mechanism of shock wave generation resulting from the interaction between a shock wave and a gas bubble in a liquid Peer-reviewed

Yamada K, Kodama T, Takayama K

In: Sturtevant B.; Shepherd J. E.; Hornung H. G, eds. Proceedings of the 20th International Symposium on Shock Waves. Pasadena: World Scientific (Singapore, New Jersey, London, Hong Kong)　615-616　1995
水中衝撃波と気泡との相互干渉：脳塞栓治療技術の基礎研究 Peer-reviewed

小玉哲也, 永易伸生, 高山和喜, 吉田晶弘

火薬学会誌　56　(5)　195-200　1995
Publisher:
ISSN： 1340-2781
マイクロバルーンの最適圧壊条件に関する一考察 Peer-reviewed

小玉哲也, 永易伸生, 高山和喜

火薬学会誌　56　201-206　1995
DAMAGE TO RED-BLOOD-CELLS INDUCED BY ACOUSTIC CAVITATION Peer-reviewed

S DANIELS, T KODAMA, DJ PRICE

ULTRASOUND IN MEDICINE AND BIOLOGY　21　(1)　105-111　1995

DOI： 10.1016/0301-5629(94)00089-1 　

ISSN： 0301-5629
THE CAVITATION THRESHOLD OF HUMAN TISSUE EXPOSED TO 0.2-MHZ PULSED ULTRASOUND - PRELIMINARY MEASUREMENTS BASED ON A STUDY OF CLINICAL LITHOTRIPSY Peer-reviewed

AJ COLEMAN, T KODAMA, MJ CHOI, T ADAMS, JE SAUNDERS

ULTRASOUND IN MEDICINE AND BIOLOGY　21　(3)　405-417　1995

DOI： 10.1016/0301-5629(94)00116-U 　

ISSN： 0301-5629
ゼラチン壁に付着した気泡と衝撃波との相互干渉(気泡の崩壊と生体損傷に関する一考察) Peer-reviewed

小玉哲也, 冨田幸雄, 島章

日本機械学会論文集(B編)　59　1431-1435　1993/04

DOI： 10.1299/kikaib.59.1431 　
Interaction of tow bubbles near a free surface Peer-reviewed

T Kodama, Y Tomita, K Sato, A Shima

Proceeding of the 18th International Symposium on Shock Wave　1　(1)　559-562　1992/04
An experimental investigation of the growth and collapse of cavitation bubbles near deformable surfaces Peer-reviewed

Tomita Y, Kodama T, Shima A

Proceedings of the 7th Symposium on cavitation, Tokyo (in Japanese)　93-98　1992
ガス銃におけるパルスウォータージェットの生成と壁面損傷に関する研究 Peer-reviewed

冨田幸雄, 島章, 古田直也, 小玉哲也, 佐藤光太郎

ウォータージェット　9　12-24　1992
Growth and collapse of a laser-produced cavitation bubble near a free surface Peer-reviewed

Kodama T, Tomita Y, Shima A. Iwata R

ASME　FED　(116)　27-32　1991
自由表面近傍での気泡運動に関する研究 Peer-reviewed

冨田幸雄, 小玉哲也, 島章, 岩田竜治

日本機械学会論文集（B編）　57　(541)　2894-2898　1991
Publisher: The Japan Society of Mechanical Engineers
DOI： 10.1299/kikaib.57.2894 　

ISSN： 0387-5016

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An investigation was made of the motion of a cavitation bubble in the vicinity of a free surface experimentally as well as theoretically. A bubble was produced by focusing a ruby laser into water, and subsequent behavior was observed with a high speed camera. The deformable nature of both a bubble and a free surface becomes significant when a bubble behaves relatively close to the surface. Immediately after the bubble rebound a secondary cavitation occurs, at around zero dynamic pressure region, which was developed in water between a rising free surface and a re-expanding bubble due to lower pressure caused by the interaction of reflected expansion waves from the surface. Some aspects of the bubble motion were compared with image theory with good agreement.
Secondary cavitation due to interaction of a collapsing bubble with a rising free surface Peer-reviewed

Y. Tomita, T. Kodama, A. Shima

Applied Physics Letters　59　(3)　274-276　1991

DOI： 10.1063/1.105619 　

ISSN： 0003-6951

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Misc. 105

腫瘍増殖状態が異なる転移リンパ節に対するLDDSの治療効果

スフバートルアリウンブヤン, スフバートルアリウンブヤン, 宮下仁, 森士朗, 森士朗, 森士朗, 小玉哲也, 小玉哲也, 小玉哲也, 小玉哲也

日本癌学会学術総会抄録集(Web)　80th　2021
X線照射後のICGリポソームリンパ行性送達能の評価

栗生晏暉, スフバートルアリウンブヤン, 森士朗, 小玉哲也

日本癌学会学術総会抄録集(Web)　80th　2021
肺転移およびリンパ節内腫瘍に対する全身照射の効果

空翔太, スフバートルアリウンブヤン, 森士朗, 小玉哲也

日本癌学会学術総会抄録集(Web)　80th　2021
Lymph nodes targeted in novel cancer therapy Invited

KODAMA Tetsuya

Research Outreach　105　22-25　2018/12
Application of a drug delivery system using ultrasound and nano/microbubbles for anti-angiogenic therapy

Horie S, Kodama T, Sato Y

Radiation Biology Research Communications　52　(1)　14-23　2017
Publisher: 放射線生物研究会
ISSN： 0441-747X
3テスラblack‐blood MR imagingが口腔癌患者の頸部リンパ節転移診断に有用であった2症例

小嶋郁穂, 阪本真弥, 飯久保正弘, 小川武則, 渡邉みか, 大田英揮, 村田隆紀, 森士朗, 小玉哲也, 笹野高嗣

歯科放射線　56　51　2016/06/08

ISSN： 0389-9705
Peritumoral apparent diffusion coefficients for prediction of lymphovascular invasion in clinically node-negative invasive breast cancer (vol 26, pg 331, 2016)

Naoko Mori, Shunji Mugikura, Chiaki Takasawa, Minoru Miyashita, Akiko Shimauchi, Hideki Ota, Takanori Ishida, Atsuko Kasajima, Kei Takase, Tetsuya Kodama, Shoki Takahashi

EUROPEAN RADIOLOGY　26　(2)　340-341　2016/02

DOI： 10.1007/s00330-015-3888-8 　

ISSN： 0938-7994

eISSN： 1432-1084
1H11 Study of circulatory system around the mouse lymph node

TAKEDA Kazu, MORI Shiro, KODAMA Tetsuya

2016　(28)　"1H11-1"-"1H11-4"　2016/01/09
Publisher: The Japan Society of Mechanical Engineers

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Cancer is one of the most common causes of death in modern society, and metastasis contributes its high mortality. Some types of cancer metastasize to the lymph node, and trigger to the distant metastasis, resulting in poor prognosis. Immigration of tumor cells to the distant organs via lymph node has not been poorly understood and metastasis route in lymphatic vessel has been considered to be different from blood circulation. Our recent study showed that distant metastasis is caused by invasion into vein on the surface of a lymph node after metastasis into the lymph node in a lymph node metastasis mouse model, MXH10/Mo-lpr/lpr (MXH10/Mo/lpr) mouse and suggested that the "lymph node mediated hematogenous metastasis" should be recognized as the final of lymph node metastasis. However, the circulation system around the lymph node that was observed in MXH10/Mo/lpr mice is not be proved in conventional mice. Here we show the similarity of blood vessel network around the subiliac lymph node (SiLN) in MXH10/Mo/lpr mouse C57BL/6 mouse, BALB/cAJcl mouse and NOD/ShiJic-SCID mice. We found that the surficial vein on SiLN is connected to inferior vena cava, and this connection contributes lymph node mediated hematogenous metastasis. We anticipated our investigation to be a start point for advanced research of lymph node mediated hematogenous metastasis.
1F36 Lymph channel structural analysis in metastatic lymph node by micro-CT

IWAMURA Ryo, YAMAKI Teppei, MORI Shiro, KODAMA Tetsuya

2016　(28)　"1F36-1"-"1F36-3"　2016/01/09
Publisher: The Japan Society of Mechanical Engineers

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Since lymph node metastasis is a major prognostic factor of cancer, the development of early diagnosis system for lymph node metastasis is essential for improving the outcome of cancer treatment. It has been reported that metastatic cancer cells promote lymphngiogenesis. In this study, to test whether detection of lymphangiogenesis in the metastatic lymph node is a useful maker for diagnosis of lymph node metastasis, we analyzed contrast micro-CT imaging of lymphatic vessels in the metastatic lymph node of animal model for lymph node metastasis. The animal model used here was MXH10/Mo-lpr/lpr mice whose lymph nodes are enlarged to 10 mm in diameter. As a results of this study, the missing region of the contrast effect was observed in the contrast micro-CT imaging of the early metastatic lymph node.
1H13 Lymphatic Delivery System for Tumor-bearing Lymph Nodes

YOSHIBA Shota, KATO Shigeki, MATSUKI Daisuke, MORI Shiro, KODAMA Tetsuya

2016　(28)　"1H13-1"-"1H13-4"　2016/01/09
Publisher: The Japan Society of Mechanical Engineers

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Cancer is one of the major diseases that cause death all over the world. One of the first steps of metastasis is lymphatic metastasis. Systemic drug administration, which is major chemotherapeutic approach is of minor benefit for the metastatic lymph nodes and causes strong side effects. In our laboratory, we have studied on a novel drug delivery system, combining nano/microbubbles with ultrasound (US), which shows considerable potential for the delivery of exogenous polymeric molecules into lymph node cells through the lymphatic sinus. In this study, we selected some fluorescent molecules with different molecular weight (MW) as exogenous molecules, and evaluated delivery efficiencies into tumor cells in the metastatic lymph node depending MW. We found that delivery efficacy into lymph node cells has difference between MW.
1H12 A study on a lymphatic drug delivery method for the treatment of metastatic LNs

Tada Asuka, Yoshida Shota, Kato Shigeki, Mori Shiro, Kodama Tetsuya

2016　(28)　"1H12-1"-"1H12-3"　2016/01/09
Publisher: The Japan Society of Mechanical Engineers

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Cancer is the leading cause of death in Japan, and most of the cancer patients die relation to the metastasis. However, there is still no reliable treatment for metastatic lymph nodes (LNs). In the present study, we propose a drug delivery method via lymph network for metastatic LNs using ultrasound and nano/micro bubbles. We used MXH10/Mo-lpr/lpr mice, which develop systemic swelling of lymph nodes up to 10 mm in diameter, similar in size to human lymph node. The tumor cells were injected into the upper stream LN; the subiliac LN (SiLN) and the metastasis was induced into the downstream LN; the proper axillary LN (PALN). A dye or anticancer agent were injected into another upper stream LN; the accessory axillary LN (AALN). We visualized that the dye can be delivered into the metastatic LN via the lymphatic vessel. In addition, the effectiveness of new lymphatic drug delivery method was examined. We anticipate that the present method has a potential to treat metastatic LNs.
Anti-angiogenic Effects by Vasohibin-1

HORIE Sachiko, SUZUKI Yasuhiro, KOBAYASHI Miho, KODAMA Tetsuya, SATO Yasufumi

Proceedings. International Conference on Flow Dynamics (CD-ROM)　13th　2016
今、イメージングで見えているものは何か? 医療現場での未来の応用を考える造影超音波定量解析による乳癌早期リンパ節転移診断

森菜緒子, 嶋内亜希子, 宮下穣, 石田孝宣, 伊藤康一, 工藤由美子, 三木美香, 小玉哲也, 高瀬圭

日本癌学会総会記事　74回　S4-6　2015/10
Publisher: 日本癌学会
ISSN： 0546-0476
J0270104 Lymphatic delivery of exogenous high molecules into lymph nodes via lymphatic network using nano/microbubbles and ultrasound

YOSHIBA Shota, KATO Shigeki, TADA Asuka, MORI Shiro, KODAMA Tetsuya

Mechanical Engineering Congress, Japan　2015　"J0270104-1"-"J0270104-4"　2015/09/13
Publisher: The Japan Society of Mechanical Engineers

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Cancer is one of the major diseases that cause death all over the world, especially via metastasis. Systemic drug administration to treat metastatic lymph nodes are not so effective and cause side effects. In our laboratory, we have studied on a novel drug delivery system, combining nano/microbubbles with ultrasound (US), which shows considerable potential for the delivery of exogenous polymeric molecules into lymph node cells through the lymphatic sinus. In this study, we selected some fluorescent molecules which had different molecular weight (MW) as exogenous molecules, and verified delivery efficiencies depending MW. We found that induction dose into lymph node cells has relationship with molecular weght.
J0270103 Evaluation of anti-tumor effect on tumor-bearing lymph node by intranodal pressure

Taleda Kazu, Tada Asuka, Mori Shiro, Kodama Tetsuya

Mechanical Engineering Congress, Japan　2015　"J0270103-1"-"J0270103-4"　2015/09/13
Publisher: The Japan Society of Mechanical Engineers

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The status of tumor-draining lymph nodes (LNs) is a prognostic factor for determining the cancer stage and thus treatment planning. As treatment of lymph node metastasis (LNM), chemotherapy or radiotherapy has been used. However, there have been no reports of evaluation methods of chemotherapy induced anti-tumor effect on metastatic lymph node (MLN) using non-invasive methods. Here we show intranodal pressure (INP) can evaluate the treatment effect on MLN using the mouse model of LNM, MXH10/Mo-/lpr/lpr mice. We found that INP increases in control while chemotherapy induced reduce INP. These results demonstrate that change in INP is related with the anti-tumor effect on LNM. We anticipate that INP is low invasive and may evaluate the antitumor effect on LNM with radiotherapy as well as chemotherapy.
J0270102 A study on the treatment of metastatic lymph node via the lymphatic network

Tada Asuka, Takeda Kazu, Kato Shigeki, Mori Shiro, Kodama Tetsuya

Mechanical Engineering Congress, Japan　2015　"J0270102-1"-"J0270102-3"　2015/09/13
Publisher: The Japan Society of Mechanical Engineers

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Lymph node (LN) metastasis plays an important role in the development of distant metastasis to vital organs. For LN metastasis, administration of anti-cancer agents is a standard treatment, but it has been a problem about strong side effect and low treatment effect. In the present study, we propose a drug delivery method via lymph network for metastatic LNs. It has a potential to be an effective treatment for targeting LNs and low side effect. We used MXH10/Mo-lpr/lpr mice, which develop systemic swelling of lymph nodes up to 13mm in diameter, similar in size to human lymph node. We demonstrated a molecular can be delivered into the metastatic LN via the lymphatic vessel. Our results may help development of an effective new lymphatic drug delivery method.
肝胆膵膵島移植生着を評価するための画像検査超音波検査の可能性について

坂田直昭, 小玉哲也, 吉松軍平, 青木豪, 石田晶玄, 川口桂, 益田邦洋, 岡田良, 薮内伸一, 深瀬耕二, 大塚英郎, 水間正道, 林洋毅, 中川圭, 岡田恭穂, 森川孝則, 吉田寛, 元井冬彦, 内藤剛, 片寄友, 海野倫明

日本外科学会定期学術集会抄録集　115回　OP-272　2015/04
Publisher: (一社)日本外科学会
移植膵島の生着を評価するための超音波検査研究のこれまでの足取り

坂田直昭, NICOLAS Sax, 青木豪, 石田晶玄, 片寄友, 江川新一, 小玉哲也, 海野倫明

日本膵・膵島移植研究会プログラム・抄録集　42nd　76　2015/02
2B15 Development of diagnosis methods of lymph node metastasis in early stages

TAKEDA Kazu, OUCHI Tomoki, MORI Shiro, KODAMA Tetsuya

2015　(27)　349-350　2015/01/08
Publisher: The Japan Society of Mechanical Engineers
1G31 Development of drug delivery system for inhibition of lung metastasis after lymph node removal

OUCHI Tomoki, Shao LENAN, MATSUKI Daisuke, SAKAMOTO Maya, MORI Shiro, KODAMA Tetsuya

2015　(27)　281-282　2015/01/08
Publisher: The Japan Society of Mechanical Engineers
1G26 Photothermal therapy of lymph node metastasis using gold nanorods and near-infrared laser light

MATSUKI Daisuke, OUCHI Tomoki, SAKAMOTO Maya, MORI Shiro, KODAMA Tetsuya

2015　(27)　279-280　2015/01/08
Publisher: The Japan Society of Mechanical Engineers
1G32 Development of drug delivery system for quasi-metastatic lymph node using nano/microbubbles and ultrasound

YOSHIBA Shota, KATO Shigeki, SHIRAI Yuko, TERAKAWA Atsuki, MORI Shiro, KODAMA Tetsuya

2015　(27)　283-284　2015/01/08
Publisher: The Japan Society of Mechanical Engineers
2F35 Vascular structural analysis in metastatic lymph node by Micro-CT

YAMAKI Teppei, YANAGISAWA Yukari, SAKAMOTO Maya, MORI Shiro, KODAMA Tetsuya

2015　(27)　539-540　2015/01/08
Publisher: The Japan Society of Mechanical Engineers
A novel molecular therapy for hepatocellular carcinoma with BNA-based antisense oligonucleotide targeting vasohibin-2

HORIE Sachiko, SUZUKI Yasuhiro, KOBAYASHI Miho, KODAMA Tetsuya, SATO Yasufumi

日本癌学会学術総会抄録集(Web)　74th　2015
Vasohibin2標的性BNA修飾アンチセンスオリゴヌクレオチドによる肝がん治療法の開発

堀江佐知子, 鈴木康弘, 小林美穂, 小玉哲也, 小比賀聡, 佐藤靖史

日本血管生物医学会学術集会プログラム・抄録集　23rd　2015
Experimental and Numerical Investigations of Local Heating of Biological Tissue for Laser Therapy

T. Sugiura, T. Okabe, J. Okajima, A. Komiya, Y. Nakamura, A. Sakurai, V. Timochenko, T. Kodama, S. Maruyama

Proceedings of the 15th International Symposium on Advanced Fluid Information　64-65　2015
Combined Application of Photo-thermal Therapy and Water-cooling System for Treatment of Tumor-bearing Lymph Nodes

D. Matsuki, J. Okajima, A. Komiya, S. Mori, S. Maruyama, T. Kodama

Proceedings of 12th International Conference on Flow Dynamics　370-371　2015
診断機器

小玉哲也

日本機械学会誌　118　(456)　15-15　2015
Publisher: 日本機械学会
造影超音波検査は移植膵島の生着/機能評価に有効である

坂田直昭, SAX Nicolas, 吉松軍平, 土屋朗之, 畠達夫, 深瀬正彦, 青木豪, 石田晶玄, 岡田恭穂, 林洋毅, 中川圭, 森川孝則, 吉田寛, 元井冬彦, 内藤剛, 片寄友, 江川新一, 小玉哲也, 海野倫明

人工臓器(日本人工臓器学会)　43　(2)　S.51　2014/09/22

ISSN： 0300-0818
W021001 What is Biomedical Engineering for Cancer?

KODAMA Tetsuya

Mechanical Engineering Congress, Japan　2014　"W021001-1"-"W021001-2"　2014/09/07
Publisher: The Japan Society of Mechanical Engineers

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What is Biomedical Engineering for Cancer? The word "Biomedical Engineering for Cancer" is a created word that has not been existed so far. In 2010, more than 800,000 people in Japan were newly diagnosed with cancer, and around half this number die each year. The total expenditure on health, especially for caner, was 1.8 trillion yen in 2011. We have spent a large amount of money for cancer research regardless of whether it is public or private money, however, we are in no situation to expect that the number of cancer patients will be decreased rapidly. There is a growing awareness in Europe and United States that cancer can be completely cured through discovery science in the interdisciplinary field, on the other hand, awareness of discovery science is lacking and not enough measures have been taken in Japan. At this workshop, five researchers in the interdisciplinary field will address their current activities and will offer a new direction to discovery science in Biomedical Engineering for Cancer.
J0260103 Treatment for tumor-bearing lymph node by lymphatic administration and sonoporation

KATO Shigeki, SHIRAI Yuko, MORI Shiro, KODAMA Tetsuya

Mechanical Engineering Congress, Japan　2014　"J0260103-1"-"J0260103-4"　2014/09/07
Publisher: The Japan Society of Mechanical Engineers

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Chemotherapy for cancer plays a significant role in clinical situation. Systemic administration of anti-tumor agents causes drug dispersion in the whole body, however, this leads to poor efficacy in lymph node (LN) metastasis and severe side effects due to cytotoxicity to normal tissues. In this report, our aim is to develop a novel treatment method for LN metastasis. Our findings show that the lymphatic administration of drugs, doxorubicin, with a combination of nano/micro bubbles (NMBs) and ultrasound (US) enhances antitumor effect. When the solution of doxorubicin and NMBs were injected into the subiliac LN, they reached the tumor-bearing proper axillary LN (proper-ALN) through lymphatic vessels. Subsequently, the proper-ALN was also exposed to US. The NMBs with US exposure could increase cell membrane permeability transiently, resulting in the delivery of doxorubicin into the tumor cells in the LN efficiently. Furthermore, lymphatic administration inhibited acute toxicity compared to systemic administration. Our results demonstrate that the lymphatic administration of US with NMBs has a potential for the treatment of metastasis.
ナノバブル造影剤高周波超音波検査による移植膵島生着機能評価

坂田直昭, SAX Nicolas, 片寄友, 江川新一, 小玉哲也, 海野倫明

日本移植学会総会プログラム抄録集　50th　464　2014/08
Enhanced Ultrasonography Using Nanobubble Contrast Agent for Islet Transplantation.

N. Sakata, S. Nicolas, G. Yoshimatsu, H. Tsuchiya, T. Hata, Y. Katayose, S. Egawa, T. Kodama, M. Unno

TRANSPLANTATION　98　678-679　2014/07

ISSN： 0041-1337

eISSN： 1534-6080
Enhanced Ultrasonography Using Nanobubble Contrast Agent for Islet Transplantation.

N. Sakata, S. Nicolas, G. Yoshimatsu, H. Tsuchiya, T. Hata, Y. Katayose, S. Egawa, T. Kodama, M. Unno

AMERICAN JOURNAL OF TRANSPLANTATION　14　678-679　2014/06

ISSN： 1600-6135

eISSN： 1600-6143
A Study of an Ultrasound Contrast Agent Detection Method with Motion Estimation

NORO Kazumasa, ITO Koichi, YAMAGISAWA Yukari, SAKAMOTO Maya, MORI Shiro, SHIGA Kiyoto, KODAMA Tetsuya, AOKI Takafumi

IEICE technical report. Signal processing　114　(39)　15-20　2014/05/22
Publisher: The Institute of Electronics, Information and Communication Engineers
ISSN： 0913-5685

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This paper presents a high-accuracy microbubble detection method for diagnostic ultrasound imaging systems. The proposed method detects ultrasound contrast agents using spatio-temporal analysis of the pixel intensity variation over several frames, where we take into account the motion of the target issue. Through a set of experiments using mice and clinical data, we demonstrate that the proposed method exhibits efficient performance compared with conventional methods.
超音波画像診断における微小気泡造影剤の検出手法の検討

野呂和正, 柳沢ゆかり, 伊藤康一, 阪本真弥, 森士朗, 志賀清人, 小玉哲也, 青木孝文

第76回全国大会講演論文集　2014　(1)　243-244　2014/03/11

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近年，造影効果の弱い血流信号を可視化するため，微小気泡造影剤を用いた超音波画像診断が研究されている．直径数ミクロン程度のマイクロバブルが主成分である造影剤は，がん内部の微小血流を可視化し，がん早期発見や診断支援へ利用することが期待されている．そのためには，血管中を流れているマイクロバブル由来の信号のみを正確に抽出する必要となる．現在使われている超音波画像診断装置には，画像の差分を基本とした手法が実装されている．しかしながら，時間経過によって組織の位置や形状に変化するため，従来手法では，造影剤の未検出や誤検出が数多く生じる．そこで，本研究では，時間方向における造影剤の輝度変動を分析することによって，血管中の造影剤を正確に検出する．マウスを使った性能評価実験を通して，提案手法の有用性を示す．
The Keap1/Nrf2 protein axis plays a role in osteoclast differentiation by regulating intracellular reactive oxygen species signaling (vol 288, pg 23009-23020, 2013)

Hiroyuki Kanzaki, Fumiaki Shinohara, Mikihito Kajiya, Tetsuya Kodama

JOURNAL OF BIOLOGICAL CHEMISTRY　289　(9)　5536-5536　2014/02

DOI： 10.1074/jbc.A113.478545 　

ISSN： 0021-9258

eISSN： 1083-351X
2A15 Development of drug delivery system to the secondary lymph node after dissection

OUCHI Tomoki, LENAN Shao, KATO Shigeki, SHIRAI Yuko, SATO Takuma, SAKAMOTO Maya, MORIKAWA Hidehiro, MORI Shiro, KODAMA Tetsuya

2014　(26)　259-260　2014/01/10
Publisher: The Japan Society of Mechanical Engineers
2A14 Anti-tumoral effects of Vasohibin 1 gene delivery using nano/microbubbles and ultrasound

HORIE Sachiko, KOBAYASHI Miho, SUZUKI Yasuhiro, KODAMA Tetsuya, SATO Yasufumi

2014　(26)　257-258　2014/01/10
Publisher: The Japan Society of Mechanical Engineers
2B24 Application of blood vessel imaging using contrast enhanced high frequency ultrasound to diagnosis of early lymph node metastasis in an early stage

TAKEMURA Tomoaki, SATO Takuma, KATO Shigeki, SAKAMOTO Maya, MORI Shiro, ARAI Youichi, KODAMA Tetsuya

2014　(26)　307-308　2014/01/10
Publisher: The Japan Society of Mechanical Engineers
2A12 Amelioration of bone destructive disease by cell-permeable peptide, 7R-ETGE

Kanzaki Hiroyuki, Shinohara Fumiaki, Kajiya Mikihito, Kodama Tetsuya

バイオエンジニアリング講演会講演論文集　2014　(26)　253-254　2014/01/10
Publisher: The Japan Society of Mechanical Engineers
Anti-angiogenic roles of Vasohibin-1A and Vasohibin-1B

HORIE Sachiko, SUZUKI Yasuhiro, KOBAYASHI Miho, KODAMA Tetsuya, SATO Yasufumi

日本癌学会学術総会抄録集(Web)　73rd　2014
Theoretical and Experimental Studies of Local Heating of Biological Tissue for Laser Therapy

T. Sugiura, T. Okabe, J. Okajima, A. Komiya, V. Timochenko, T. Kodama, S. Maruyama

Proceedings of 14th International Symposium on Advanced Fluid Information　46-47　2014
J023015 Dynamic image of the lymphatic vessel using lymphatic drug delivery system

HATAKEYAMA Yuriko, KATO Shigeki, SAKAMOTO Maya, MORI Shiro, KODAMA Tetsuya

Mechanical Engineering Congress, Japan　2013　"J023015-1"-"J023015-4"　2013/09/08
Publisher: The Japan Society of Mechanical Engineers

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The lymphatic system plays an important, but its mechanism has not been understood. Due to the absence of useful experimental animal models, a lymphatic administration method has not been developed. We have developed a mouse model of the pressure-driven lymph node metastasis (LNM) via the efferent lymphatic vessel (LV). Using this model, we succeeded in measuring the pressures in the LNs and visualizing the lymphatic flow with a real-time pressure measurement system. We also elucidated the characterization of lymphatic flow for lymphatic administration. These results allow a new drug delivery system through the LV.
J023014 Molecular delivery system into lymph nodes using ultrasound and nanobubbles

Shirai Yuko, Kato Shigeki, Sato Takuma, Kanzaki Hiroyuki, Mori Shiro, Kodama Tetsuya

Mechanical Engineering Congress, Japan　2013　"J023014-1"-"J023014-5"　2013/09/08
Publisher: The Japan Society of Mechanical Engineers

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Appropriate treatment of lymph node metastasis is essential to improve the prognosis for patients. Although lymph node dissection is a primary option, it is invasive and associated with adverse effects. The development of novel, non-invasive therapeutic methods in preclinical experiments using mice has been restricted by the small lymph node size (only a few millimeters in diameter) and the limited techniques available for non-invasive monitoring of the progression of lymph node metastasis. Here, we show a local drug delivery using nanobubbles and ultrasound via lymphatic vessels shows potential as a non-invasive treatment for tumors in the proper axillary lymph nodes (proper-ALNs) of MXHIO/Mo-Ipr/lpr mice, which develop systemic swelling of lymph nodes (up to 13 mm in diameter, similar in size to human lymph nodes). Tumor cells were inoculated into the proper-ALNs to develop a model of metastatic lesions, and any anti-tumor effects of therapy were assessed with an in vivo bioluminescence imaging system, a high-frequency ultrasound system, and immunohistochemical analysis. We confirmed the successful noninvasive deliveiy of small molecule (TOTO-3 iodide) into lymphocytes invaded by cancer. Our system has a potential for a novel local delivery system for the treatment of lymph node metastasis.
Imaging of Transplanted Islets by Ultrasonography

Naoaki Sakata, Gumpei Yoshimatsu, Haruyuki Tsuchiya, Takeshi Aoki, Masamichi Mizuma, Fuyuhiko Motoi, Yu Katayose, Tetsuya Kodama, Michiaki Unno

TRANSPLANTATION　96　(6)　S126-S126　2013/09

ISSN： 0041-1337

eISSN： 1534-6080
超音波画像診断のための造影剤検出手法とその性能評価 (メディア工学サマーセミナー2013 : 画像処理の理論と実際)

野呂和正, 柳沢ゆかり, 伊藤康一, 阪本真弥, 森士朗, 志賀清人, 小玉哲也, 青木孝文

映像情報メディア学会技術報告 = ITE technical report　37　(36)　65-68　2013/08
Publisher: 一般社団法人映像情報メディア学会
ISSN： 1342-6893

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本稿では,超音波画像診断を支援するために重要となる高精度な造影剤の検出手法を提案する.提案手法では,時空間領域での輝度値の変動を分析することで,血管を流れている造影剤を正確に検出する.マウスを使った評価実験を通して,従来手法では誤検出となってしまうシーンでも,正確に造影剤が検出できることを示す.
A Study of a High-Accuracy Ultrasound Contrast Agent Detection Method for Diagnostic Ultrasound Imaging Systems

ITO Koichi, NORO Kazumasa, YANAGISAWA Yukari, SAKAMOTO Maya, MORI Shiro, SHIGA Kiyoto, KODAMA Tetsuya, AOKI Takafumi

IEICE technical report.　113　(146)　61-65　2013/07/18
Publisher: The Institute of Electronics, Information and Communication Engineers
ISSN： 0913-5685

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This paper presents a high-accuracy microbubble detection method for diagnostic ultrasound imaging systems. The conventional methods are based on simple subtraction of ultrasound images to detect ultrasound contrast agents. Even if the subject slightly moves, the detection result of the conventional methods includes significant errors. On the other hand, the proposed method employs the spatio-temporal analysis of the pixel intensity variation over several frames. Through a set of experiments using the tail of mice, we demonstrate that the proposed method exhibits efficient performance compared with the conventional methods.
超音波と微小気泡によるリンパ管を介したリンパ節内細胞への外来分子導入法の開発

加藤茂樹, 白井優子, 佐藤琢磨, 菅崎弘幸, 本園千尋, 宮澤正顯, 森士朗, 小玉哲也

超音波医学　40　(3)　307-307　2013/05
Publisher: (一社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
PS-383-5 移植膵島の超音波画像(PS ポスターセッション,第113回日本外科学会定期学術集会)

坂田直昭, 後藤昌史, 小玉哲也, 元井冬彦, 水間正道, 吉松軍平, 青木豪, 深瀬耕二, 大塚英郎, 乙供茂, 岡田恭穂, 中川圭, 林洋毅, 森川孝則, 吉田寛, 内藤剛, 三浦康, 片寄友, 里見進, 海野倫明

日本外科学会雑誌　114　(2)　1058-1058　2013/03/05
Publisher: 一般社団法人日本外科学会
ISSN： 1880-1129
1C07 Application of gold nanorod mediated Photo-thermal therapy to lymph node

Okuno Tatsuki, Okajima Junnosuke, Hatakeyama Yuriko, Kato Shigeki, Maruyama Shigenao, Mori Shiro, Kodama Tetsuya

2013　(25)　91-92　2013/01/08
Publisher: The Japan Society of Mechanical Engineers
超音波を利用した遺伝子治療

Gene therapy using ultrasound

The Japan Society of Ultrasonics in Medicine 50 th Anniversary　2013
Imaging of transplanted islets by positron emission tomography, magnetic resonance imaging, and ultrasonography

Sakata N, Yoshimatsu G, Tsuchiya H, Aoki T, Mizuma M, Motoi F, Katayose Y, Kodama T, Egawa S, Unno M

Islets　5　(5)　1-9　2013

DOI： 10.4161/isl.26980 　
J026012 Development of Lymphatic drug delivery system

HATAKEYAMA Yuriko, NICOLAS Sax, KATO Shigeki, SAKAMOTO Maya, MORI Shiro, KODAMA Tetsuya

Mechanical Engineering Congress, Japan　2012　"J026012-1"-"J026012-5"　2012/09/09
Publisher: The Japan Society of Mechanical Engineers

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Systemic chemotherapy is the most popular therapy, especially for breast cancer metastasis. However, a lymphatic administration method has not been developed due to the absence of useful experimental animal models. We have developed a mouse model of the pressure-driven lymph node metastasis via the afferent lymphatic vessel (LV). We developed a system allowing simultaneous imaging of the FITC flow in LNs, and the pressure measurement inside the LNs of MXH-10 mice. Using this system, we also obtained the FITC flow characteristics through the LV, and investigated the administration induced pressure increase, drug dosage and administration speed to deliver drugs to the axillary lymph node from the inguinal lymph node. This administration method requires less doses to deliver drugs relative to the systemic chemotherapy. These results allow more effective and efficient drug delivery system.
J026014 Quantification of extravasate nano particles due to EPR effect with Window chamber

MIKADA Mamoru, NICOLAS Sax, SAKAMOTO Maya, MORI Shiro, KODAMA Tetsuya

Mechanical Engineering Congress, Japan　2012　"J026014-1"-"J026014-5"　2012/09/09
Publisher: The Japan Society of Mechanical Engineers

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The EPR effect provides a great opportunity for selective targeting of solid tumors. In order to observe the EPR effect, Window chamber (WC) for chronological observation and nano particles that can extravasate from newly-formed tumoral blood vessels have been used. The solid tumor deposition method and the tumor cell injection method are both widely spread of tumor implantation methods into the WC. However, the characteristics of nano particle extravasation dependance on implantation methods have not been reported. Here we show that tumor cell injection method results in a 1.77 higher amount of extravasated particles (per surface area) than solid tumor deposition method by use of fluorescent microscope and fluorescent liposomes with an average diameter of 122 nm. We anticipate our study to help understand the EPR effect in a WC model and gain a better understanding of the EPR effect.
J026023

TOMITA Yukio, TANAKA Shigenori, OKADA Akira, KODAMA Tetsuya

Mechanical Engineering Congress, Japan　2012　"J026023-1"-"J026023-4"　2012/09/09
Publisher: The Japan Society of Mechanical Engineers

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An experiment on the interaction of a 1 MHz focused ultrasound (US) with Sonazoid microbubbles has been carried out in the presence of an agar gel. The survival number of Sonazoid microbubbles was examined by changing the exposure time Tex, the acoustic energy density E and the Sonazoid concentration Cv. High-speed photography with the maximum framing rate of 300,000 frames/s was conducted to observe the behavior of bubbles near an agar gel. It was found that bubble coalescence frequently occurred during an earlier stage after US irradiation. Subsequently a newly created bubble migrated towards the agar gel surface and away from it, behaving a kind of circulation due to an acoustic streaming. A minimum volume of a bubble was reached within a region very close to the gel surface, presumably emitting pressure waves at each rebound which could impact on the gel surface. In fact, a number of depressions in dozens nanometers were found on the agar gel surface which were detected by using an AFM.
J026013 Characteristics of the interstitial fluid pressure in groin lymph node associated with tumor growth

MIURA Yoshinobu, HATAKEYAMA Yuriko, SAKAMOTO Maya, MORI Shiro, KODAMA Tetsuya

Mechanical Engineering Congress, Japan　2012　"J026013-1"-"J026013-5"　2012/09/09
Publisher: The Japan Society of Mechanical Engineers

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Growth of most human tumors leads to elevated interstitial fluid pressure (IFP). The mechanisms underlying the high tumor IFP are still not fully understood, but may include increased vascular permeability and abnormal lymph drainage leading to increased fluid volume, followed by elevated IFP. The resultant IFP may lead to poor and heterogeneous uptake of macromolecular and nanoparticle therapeutic agents, thus leading to resistance to immunotherapy and gene therapy. Here we show that tumor cells were inoculated in groin lymph nodes, and the variation of IFP with time was measured by using MXH/lpr mice with human size lymph nodes. The IFP was increased in tumor bearing mouse. Corresponding changes in lymph vessels area, tumor volume, and IFP suggest that the increased pressure is caused by defective lymph drainage and solid stress generated by tumor cells growing in a low compliant environment. This study suggests a possibility for future studies of cancer metastasis.
膵島移植医療に有用な各種画像モダリティの使用法の確立に向けて

坂田直昭, 吉松軍平, Hathout Eba, 小玉哲也, 江川新一, 力山敏樹, 陳鋭, 石田晶玄, 土屋朗之, 後藤昌史, 海野倫明

日本外科学会雑誌　113　(臨増2)　331-331　2012/03
Publisher: (一社)日本外科学会
ISSN： 0301-4894
7E36 Drug Delivery System for the Lymphatic Metastases.

KATO Shigeki, HORIE Sachiko, SATO Takuma, KODAMA Tetsuya

2012　(24)　"7E36-1"-"7E36-2"　2012/01/06
Publisher: The Japan Society of Mechanical Engineers
7E35 Treatment of lymph node metastasis with NIR-laser beams and Au nanorods.

OKUNO Tatsuki, HORIE Sachiko, Nicolas Sax, KODAMA Tetsuya

2012　(24)　"7E35-1"-"7E35-2"　2012/01/06
Publisher: The Japan Society of Mechanical Engineers
超音波検査による移植膵島の機能評価

坂田直昭, 小玉哲也, 陳鋭, 吉松軍平, 後藤昌史, 江川新一, 海野倫明

移植　46　(6)　622-623　2011/12/10

ISSN： 0578-7947
移植膵島生着に対する超音波検査の有効性

坂田直昭, 小玉哲也, 陳鋭, 吉松軍平, 後藤昌史, 江川新一, 海野倫明

移植　46　207　2011/10

ISSN： 0578-7947
J052011 Characteristics of Flow Dynamics into the Efferent Lymphatic Vessel with Increasing Pressures in the Intra-Groin Lymph Node

HATAKEYAMA Yuriko, KODAMA Tetsuya

Mechanical Engineering Congress, Japan　2011　"J052011-1"-"J052011-3"　2011/09/11
Publisher: The Japan Society of Mechanical Engineers

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Lymph node metastasis (LNM) is the major prognostic factor for cancer survival. We have developed the pressuredriven metastasis of LNM mouse model. In this model, metastasis is induced by injection of tumor cells into the groin lymph node (gLN), followed by induction in the axillary lymph node (aLN). However, the mechanism of metastasis has not been fully elucidated. In this paper, we investigate the characteristics of the flow to the lymphatic vessel (LV) upon increased pressure in the gLN. Following administration of fluorescein isothiocyanate (FITC) to the gLN, FITC flow and pressure inside the LN were simultaneously monitored. We also succeeded in visualizing the FITC flow in the LV. These results show potential of developing an effective therapy of LNM by administration of drugs via the LV.
J052022 Focused Ultrasound Induced Sonazoid Destruction and the Resultant Bubble Generation

TOMITA Yukio, TANAKA Shigenori, KODAMA Tetsuya

Mechanical Engineering Congress, Japan　2011　"J052022-1"-"J052022-3"　2011/09/11
Publisher: The Japan Society of Mechanical Engineers

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Sonazoid microbubbles have been destroyed by the irradiation of a 1 MHz ultrasound (US). Both burst waves and continuous waves of US were radiated by means of a concave ultrasound probe with the arithmetic focal length of 80 mm. A suspension of Sonazoid ultrasound contrast agent with the volumetric concentration of C. was poured into a cuvette which was positioned with its bottom in contact with the free surface and exposed to US with the duration of T. After the interaction between a suspension and an ultrasound, Sonazoid microbubbles were quickly destroyed. The survival number of Sonazoid microbubbles has been examined by changing the exposure time T・, the concentration of a suspension Cs and the duty ratio D. Sonazoid destruction yields several pieces of debris together with gas flowing out which act as nuclei of bubble growth. Snapshots of bubbles were taken by using a Xe flash with the pulse duration of 2 ps as a light source.
マイクロバブルと高周波超音波を用いた三次元イメージング法による転移リンパ節の血管密度の評価

佐藤祥太, 李麗, 柳下陽子, 阪本真弥, 高橋昭喜, 森士朗, 小玉哲也

超音波医学　38　(1)　34-34　2011/01
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
表在性膀胱がんに対する膀胱内注入遺伝子治療(Development of a local gene therapy with ultrasound and babble-liposome against superficial bladder cancer)

藤澤優, 鈴木亮, 丸山一雄, 小玉哲也, 安永正浩, 古賀宣勝, 松村保広

日本癌学会総会記事　69回　285-285　2010/08
Publisher: 日本癌学会
ISSN： 0546-0476
表在性膀胱がんに対する再発防止法の開発

藤澤優, 荒川寛茂, 安永正浩, 小玉哲也, 丸山一雄, 鈴木亮, 松村保広

Drug Delivery System　25　(3)　335-335　2010/05
Publisher: 日本DDS学会
ISSN： 0913-5006
音響性リポソームと超音波を使用した遺伝子薬物デリバリー

Yagishita Y, Kodama T

Vascular Biology & Medicine　10　(4)　91-98　2009/11/01
Publisher: Medical Review
表在性膀胱癌に対する超音波とバブルリポソームを用いた局所的遺伝子療法の解析(Development of local gene therapy with ultrasound and bubble-liposome against superficial bladder cancer)

藤澤優, 鈴木亮, 丸山一雄, 小玉哲也, 安永正浩, 松村保広

日本癌学会総会記事　68回　474-474　2009/08
Publisher: 日本癌学会
ISSN： 0546-0476
高周波超音波を用いたリンパ節早期転移の画像診断システムの開発

李麗, 冨田典子, 森士朗, 大澤ふき, 堀江佐知子, 渡辺夕紀子, 陳鋭, 阪本真弥, 高橋昭喜, 小玉哲也

生体医工学　47　(4)　375-375　2009/08
Publisher: 日本生体医工学会
ISSN： 1347-443X

eISSN： 1881-4379
リンパ節転移早期診断に関する三次元高周波超音波イメージング

李麗, 堀江佐知子, 陳鋭, 渡辺夕紀子, 阪本真弥, 高橋昭喜, 森士朗, 小玉哲也

超音波医学　36　(4)　525-525　2009/07
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
ナノバブルと高周波超音波を用いた血管抽出法の開発

小玉哲也

Drug delivery system　24　(3)　252-252　2009/06/09

ISSN： 0913-5006
表在性膀胱がんに対する膀胱内注入遺伝子治療

藤澤優, 荒川寛茂, 安永正浩, 小玉哲也, 丸山一雄, 鈴木亮, 松村保広

Drug Delivery System　24　(3)　343-343　2009/06
Publisher: 日本DDS学会
ISSN： 0913-5006
ナノバブルを用いた超音波によるリンパ節転移早期診断システムの研究開発

李麗, 堀江佐知子, 陳鋭, 渡邊夕紀子, 阪本真弥, 森士朗, 高橋昭喜, 小玉哲也

Drug Delivery System　24　(3)　363-363　2009/06
Publisher: 日本DDS学会
ISSN： 0913-5006

eISSN： 1881-2732
211 Development of Three-Dimensional High-Frequency Ultrasound Imaging for Early Diagnosis of Lymph Node Metastasis Using Nanobubbles

LI Li, TOMITA Noriko, MORI Shiro, OOSAWA Fuki, HOREI Sachiko, CHEN Rui, WATANABE Yukiko, SAKAMOTO Maya, TAKAHASHI Shoki, KODAMA Tetsuya

2008　(21)　71-72　2009/01/22
Publisher: The Japan Society of Mechanical Engineers
Delivery of Na/I symporter gene into skeletal muscle by using nanobubbles and ultrasound:visualization of gene expression with PET

Watanabe Y, Horie S, Funaki Y, Yohei Kikuchi Y, Yamazaki H, Ishii K, Vassaux G, Mori S, Kodama T

CYRIC annual report　2008　142-147　2009
Publisher: CYRIC Report
ナノバブルと超音波を用いた膀胱がんへの遺伝子導入法の開発

堀江佐知子, 渡邊夕紀子, 陳鋭, 冨田典子, 大澤ふき, 小野栄夫, 福本学, 藤澤優, 松村保広, 森士朗, 小玉哲也

日本癌治療学会誌　43　(2)　765-765　2008/10
Publisher: (一社)日本癌治療学会
ISSN： 0021-4671
膀胱がん治療のための新しい薬剤到達法の開発(Developing a new drug delivery system for bladder cancer)

堀江佐知子, 渡邊夕紀子, 陳鋭, 冨田典子, 大澤ふき, 小野栄夫, 福本学, 藤澤優, 松村保広, 森士朗, 小玉哲也

日本癌学会総会記事　67回　315-315　2008/09
Publisher: 日本癌学会
ISSN： 0546-0476
表在性膀胱がんに対する膀胱内注入遺伝子治療(Development of a local gene therapy with ultrasound and bubble-liposome against superficial bladder cancer)

藤澤優, 鈴木亮, 丸山一雄, 小玉哲也, 安永正浩, 松村保広

日本癌学会総会記事　67回　356-356　2008/09
Publisher: 日本癌学会
ISSN： 0546-0476
表在性膀胱がんに対する膀胱内注入遺伝子治療

藤澤優, 荒川寛茂, 安永正浩, 小玉哲也, 丸山一雄, 鈴木亮, 松村保広

Drug Delivery System　23　(3)　417-417　2008/05
Publisher: 日本DDS学会
ISSN： 0913-5006
301 Gene transfer to periodontal tissues using nanobubbles and ultrasound

CHEN Rui, CHIBA Mirei, HOREI Sachiko, WATANABE Yukiko, MORI Shiro, IGARASHI Kaoru, KODAMA Tetsuya

2007　(20)　79-80　2008/01/24
Publisher: The Japan Society of Mechanical Engineers
オーガナイズドセッション22 物理作用に伴う分子デリバリ:―システムの展開

松村保広, 玉川雅章, 小玉哲也

生体医工学　46　(1)　275-277　2008
Publisher: 公益社団法人日本生体医工学会
ISSN： 1347-443X
ナノ・マイクロバブルと超音波を用いた分子導入システムの開発とがん治療への応用

小玉哲也

日本機械学会雑誌　111　(1070)　51-54　2008
表在性膀胱がんに対する膀胱内注入遺伝子治療(Development of local gene therapy with ultrasound and bubble-liposome against superficial bladder cancer)

藤澤優, 鈴木亮, 丸山一雄, 小玉哲也, 安永正浩, 松村保広

日本癌学会総会記事　66回　448-448　2007/08
Publisher: 日本癌学会
ISSN： 0546-0476
ナノバブルと超音波を用いたシスプラチン導入による抗腫瘍効果の検討

小玉哲也, 青井あつ子, 渡邊夕紀子, 松村保広, 森士朗

超音波医学　34　(4)　476-477　2007/07
Publisher: (公社)日本超音波医学会
ISSN： 1346-1176

eISSN： 1881-9311
表在性膀胱がんに対する膀胱内注入遺伝子治療

藤澤優, 安永正浩, 小泉史明, 小玉哲也, 丸山一雄, 鈴木亮, 滝澤知子, 松村保広

Drug Delivery System　22　(3)　379-379　2007/05
Publisher: 日本DDS学会
ISSN： 0913-5006
Development of molecular delivery system using nanobubbles and ultrasound: Application to cancer therapy

KODAMA Tetsuya

2007　(82)　"2-14"　2007/03/16
Publisher: The Japan Society of Mechanical Engineers
A116 Cell Membrane Permeabilization Induced by Shock Wave : Molecular Dynamics Simulation

KOSHIYAMA Kenichiro, KODAMA Tetsuya, YANO Takeru, FUJIKAWA Shigeo

Proceedings of the ... JSME Conference on Frontiers in Bioengineering　2006　(17)　33-34　2006/11/10
Publisher: The Japan Society of Mechanical Engineers
ISSN： 1348-2939
803 Development of a non-invasive tissue specific molecular delivery method of cancer gene therapy(2)

KODAMA Tetsuya, KOSHIYAMA Ken-ichiro, AOI Atsuko, TOMITA Yukio, YANO Takeru, FUJIKAWA Shigeo

Fluids engineering conference ...　2006　"803-1"-"803-4"　2006/10/28
Publisher: The Japan Society of Mechanical Engineers
ISSN： 1348-2882

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Gene transfer to cancer cells using nanobubbles (NBs) and ultrasound (US) is a non-invasive gene therapy. In order to improve efficacy of gene transfection, the impulsive pressures generated by cavitation bubbles created by the collapse of NBs have to be optimized. In addition, the mechanism of molecular transfer as d as subsequent therapeutic effect has to be investigated. In the present study, we delivered fluorescence molecules into cells with the NB-US method and quantified the intracellular fluorescence molecules. Next we verified the therapeutic effect of suicide gene therapy in vitro using harpes simplex virus thymidine kinase (HSV tk) gene and ganciclovir (GCV), Finally we analyzed the cavitation bubble behavior and the interaction of the shock wave with a lipid bilayer by using theoretical and numerical methods, We attributed the delivery exogenous molecules by the NS-US method to the structural change in the lipid bilayer caused by the interaction of the shock waves from the cavitation bubbles.
803 Development of a non-invasive tissue specific molecular delivery method of cancer gene therapy(1)

KODAMA Tetsuya, KOSHIYAMA Ken-ichiro, AOI Atsuko, TOMITA Yu, YANO Takeru, FUJIKAWA Shigeo

Fluids engineering conference ...　2006　"803-a"　2006/10/28
Publisher: The Japan Society of Mechanical Engineers
ISSN： 1348-2882

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Gene transfer to cancer cells using nanobubbles (NBs) and ultrasound (US) is a non-invasive gene therapy. In order to improve efficacy of gene transfection, the impulsive pressures generated by cavitation bubbles created by the collapse of NBs have to be optimized. In addition, the mechanism of molecular transfer as d as subsequent therapeutic effect has to be investigated. In the present study, we delivered fluorescence molecules into cells with the NB-US method and quantified the intracellular fluorescence molecules. Next we verified the therapeutic effect of suicide gene therapy in vitro using harpes simplex virus thymidine kinase (HSV tk) gene and ganciclovir (GCV), Finally we analyzed the cavitation bubble behavior and the interaction of the shock wave with a lipid bilayer by using theoretical and numerical methods, We attributed the delivery exogenous molecules by the NS-US method to the structural change in the lipid bilayer caused by the interaction of the shock waves from the cavitation bubbles.
746 Suicide gene therapy of cancer using nanobubbles and ultrasound

AOI Atsuko, KONNO Kiyoe, SHINOHARA Humiaki, MORIKAWA Hidehiro, MORI Shiro, VASSAUX George, KODAMA Tetsuya

2006　(5)　291-292　2006/09/15
Publisher: The Japan Society of Mechanical Engineers

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Gene transfection to cancer cells using nanobubbles and ultrasound (NBs-US) is a non-invasive gene therapy. Herpes simplex virus thymidine kinase (HSVtk) gene is a representative suicide gene, and has been demonstrated to have potential of cytotoxic sensitivity by ganciclovir (GCV). In this report, we evaluated the effectiveness of HSVtk/GCV cytotoxic gene therapy on cancer cells using NBs-US. For in vitro studies, HSVtk was trasnfected into five cell lines (A549, EMT6, colon26, HT29 and 293T) with NBs-US (0.6MPa). The effects of HSVtk/GCV gene therapy were evaluated using an MTT assay. For in vivo studies, HT29 cells expressing luciferase gene were trasnsplanted into mice. HSVtk was transfected into tumor with NBs-US and GCV was administrated intraperitoneally. Luciferase activity regarded as tumor size was measured by a bioluminescence imaging system. Both in vitro and in vivo studies, cytotoxixity was obtained only in the treated cells with HSVtk/GCV. These results demonstrated the potential to treat cancer cells by using the NBs-US method combined with suicide gene therapy.
卵巣がん遺伝子・核酸治療法の開発

芹沢由里子, 小泉史明, 黒田順一郎, 小玉哲也, 松村保広

日本癌学会総会記事　65回　428-428　2006/09
Publisher: 日本癌学会
ISSN： 0546-0476
ナノバブルを用いた骨格筋への遺伝子導入:分子イメージング解析

青井あつ子, 渡邊夕紀子, 今野聖絵, 堀江佐知子, 森士朗, 森川秀広, 鈴木亮, 丸山一雄, 小玉哲也

Drug Deliv Syst　21　(3)　291-291　2006/06/20
Publisher: 日本DDS学会
ISSN： 0913-5006

eISSN： 1881-2732
超音波による歯根膜細胞への遺伝子導入の試み (〔日本実験力学会〕2006年度年次講演会)

山崎仁, 千葉美麗, 小玉哲也

日本実験力学会講演論文集　(6)　148-150　2006
Publisher: 日本実験力学会
ISSN： 1346-4922
Molecular Dynamics Simulation of 5-Fluorouracil Delivery Using Shock Waves

KOSHIYAMA Ken-ichiro, KODAMA Tetsuya, YANO Takeru, FUJIKAWA Shigeo

32　S277　2005/04/15

ISSN： 1346-1176
Shock wave generation by nanobubbles : mechanism of molecular delivery

KODAMA Tetsuya, KOSHIYAMA Ken-ichiro, TOMITA Yukio, SUZUKI Maiko, YANO Takeru, FUJIKAWA Shigeo

32　S213　2005/04/15

ISSN： 1346-1176
AM05-17-025 Study on anticancer drug delivery into cancer cells with nanobubbles and ultrasound

Kodama Tetsuya, Suzuki Maiko, Tomita Yukio

2005　316-316　2005
Publisher: 日本流体力学会

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We report on the use of gas-encapsulated nanobubbles (NB) delivered by ultrasound (US) to permeabilize cancer cells and potentiated the cytotoxicity of anti-caner drug (5-FU and cisplatin). We studied 293T (human kidney cells), MCF7 (human breast adenocarcinoma), EMT6 (murine mammary carcinoma) and colon 26 cells (murine rectum carcinoma) using cytotoxicity assays (MTT assay). Plasmid DNA (expressing EGFP or luciferase) was used for optimizing ultrasonic conditions. NB (10% v/v) with US (pressure 0.96MPa) produced significant cytotoxicity not seen with either ultrasound or drug alone. Increasing the duty ratio of US up to 80% further increased cytotoxicity. We proposed a hypothesis that sub-nanobubbles (cavitation bubbles) are produced by collapsed of nanobubbles and shock waves generated by the cavitation bubbles lead to the transient membrane permeability, followed by entry of plasmid DNA and drug. From a theoretical analysis, we obtained the critical shock wave propagation distance from a cavitation bubble that would be necessary for transient membrane permeability.
AM05-17-024 Molecular Dynamics Simulation of Water Pore Formation in Lipid Bilayer Induced by Shockwaves

Koshiyama Kenichiro, Kodama Tetsuya, Yano Takeru, Fujikawa Shigeo

2005　315-315　2005
Publisher: 日本流体力学会

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Molecular dynamics simulations of water pore formation by shock waves in a phospholipid bilayer were conducted under the initial condition where the bilayer contains water molecules in its hydrophobic region [Koshiyama, K., et al., AIP Conf. Proc, 754, 104-106, (2005)]. The water pore formation was found to depend on the initial concentration of water molecules in the hydrophobic region. The water pore formation process and stability of water pore agreed with other simulation results of pore formation [Marrink, S.J., et al., J. Am. Chem. Soc, 123, 8638-8639, (2001)]. In addition, the stable water pore diameter was ca. 1.9nm that is 5 times larger than the size of 5 fluorouracil typically used in sonoporation experiments.
Some aspects of the motion of two laser-produced cavitation bubbles near a free surface

Yukio Tomita, Tetsuya Kodama

Fluid Mechanics and its Applications　62　303-310　2001

DOI： 10.1007/978-94-010-0796-2_37 　

ISSN： 0926-5112
The behavior of a single and two laser-induced cavitation bubbles near a free surface

Tomita Yukio, Kodama Tetsuya

Fluids engineering conference ...　2000　124-124　2000/09/08
Publisher: The Japan Society of Mechanical Engineers
ISSN： 1348-2882
Cytoplasmic molecular delivery with shock waves

T Kodama, MR Hamblin, AG Doukas

FASEB JOURNAL　14　(8)　A1473-A1473　2000/05

ISSN： 0892-6638
気泡と衝撃波干渉を利用する脳血栓血行再建術

高山和喜, 小玉哲也

生命環境と流れに関する研究分科会研究成果報告書　61-62　1999
Dynamic behavior of bubbles during extracorporeal shock-wave lithotripsy (vol 24, pg 723, 1998)

T Kodama, K Takayama

ULTRASOUND IN MEDICINE AND BIOLOGY　24　(8)　1227-1227　1998/10

ISSN： 0301-5629
ガス銃によるパルスウォータージェットの高速衝突と壁面損傷

冨田幸雄, 島章, 古田直也, 松井禎, 小玉哲也, 佐藤光太郎

東北大学流体科学研究所報告書　(Vol.3)　141-150　1992
27a-J-11 Formation of a liquid microjet induecd by the interaction between an air bubble and a shock wave

Kodama Tetsuya, Tomita Yukio, Shima Akira

46　(4)　67-67　1991/09/12
Publisher: The Physical Society of Japan (JPS)

Show all ︎Show first 5

Books and Other Publications 3

Methods Molecular Biology

Sukhbaatar A, Kodama T

Sung-Bae Kim (Eds): Bioluminescence　2022/07

ISBN: 9781071624524
Medical Practice 39巻4号〈リンパ節腫大の診療〉

小玉哲也

文光堂　2022/04/01
Recent technology of microbubbles vol.2

Tetsuya Kodama

NTS　2014/08/08

ISBN: 9784860434076

Presentations 611

Chemoimmunotherapyvia Lymphatic Drug Dlivery System Improves Tumor Inhibition and Reduces irAEs in Metastatic Lymph Nodes

Sukhbaatar A., Mori S., Kodama T.

第41回日本DDS学会学術集会
Molecular mechanism in clinically relevant radioresistant cancer cells

宮下仁, 桑原義和, 森士朗, 小玉哲也, 福本学

第49回日本頭頸部癌学会総会・学術講演会
リンパ行性癌化学療法における標的リンパ節に関する臨床病理学的検討

尾形咲季, 東友太郎, 梶田倫功, Sukhbaatar Ariunbuyan, 纐纈衆, 宮下仁, 西條憲, 志賀清人, 小玉哲也, 杉浦剛

第49回日本頭頸部癌学会総会・学術講演会
A comparative study of Docetaxel and immune checkpoint inhibitors effect on metastatic lymph node.

Sukhbaatar Ariunbuyan, 森士朗, 杉浦剛, 小玉哲也

第49回日本頭頸部癌学会総会・学術講演会
造影超音波クラッタフィルタ法による転移リンパ節の血管構造可視化

前田一伎, 岡田侑弥, 大村眞朗, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

日本超音波医学会第98回学術集会（JSUM 2025）
リンパ行性薬剤送達法の溶媒特性に関する薬物動態に関する研究

宮崎黎飛, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

第49回日本リンパ学会総会
LDDS溶媒の粘度・浸透圧の変化に対するリンパ節における薬物動態，薬物分布および形態学的変化に関する研究

島野大輝, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

第49回日本リンパ学会総会
The Role of Lymph Flow for the Enhancement of Lymphatic Drug Delivery System: Mapping Flow Patterns in a Mouse Model

Ariunbuyan Sukhbaatar, Shiro Mori, Tsuyoshi Sugiura, Tetsuya Kodama
Evaluation of how the distribution of gold nanorods affects the temperature distribution characteristics of biological tissue during near-infrared irradiation

Obonai A., Kogawa T., Kanda Y., Kodama T., Komiya A.

the HTSJ International Heat Transfer Symposium (2025-5)
リンパ行性薬物送達法における薬物動態パラメータと粘度，浸透圧の関係に関する研究

宮崎黎飛, Sukhbaatar Ariunbuyan, 小玉哲也

日本機械学会第35回バイオフロンティア講演会　2024/12/14
新規血管炎モデルMcH/Mo-lpr/lpr-RA1マウスにおける造影エックス線 µCTおよび病理組織学的解析を用いた血管炎評価

岡田侑弥, 森健太郎, Sukhbaatar Ariunbuyan, 森士朗, 藤井博司, 小玉哲也

日本機械学会第35回バイオフロンティア講演会　2024/12/14
臨床的放射線耐性がん細胞における放射線耐性の分子機構

宮下仁, 森士朗, 小玉哲也

第69回（公社）日本口腔外科学会総会・学術集会
Treatment Outcome of Immune Checkpoint Inhibitors for the Metastatic Lymph Node Mouse Model

Sukhbaatar Ariunbuyan, Shiro Mori, Tetsuya Kodama, Tsuyoshi Sugiura

第69回（公社）日本口腔外科学会総会・学術集会
Importance of drug osmolality and viscosity in efficient drug delivery using a lymphatic drug delivery system
Radioimmunotherapy by Lymphatic Drug Delivery System (LDDS) for the treatment of lymph node metastasis

Wilda Septilah Aulia, Ariunbuyan Sukhbaatar, Shiro Mori, Tsuyoshi Sugiura, Tetsuya Kodama

第69回（公社）日本口腔外科学会総会・学術集会　2024/11/22
Pharmacokinetic Analysis in Lymphatic Drug Delivery System

Miyazaki R., Shimano T., Sukhbaatar A., Mori S., Kodama T.

21st International Conference on Flow Dynamics
Treatment of Metastatic Lymph Node by Lymphatic Drug Delivery System Using Carboplatin

Tada E., Miyatsu M., Sukhbaatar A., Mori S., Sugiura T., Kodama T.

21st International Conference on Flow Dynamics
Evaluation of Chemoimmunotherapy using Lymphatic Drug Delivery System

Suzuki R., Sukhbaatar A., Fuji H., Mori S., Ito Y., Kodama T.

21st International Conference on Flow Dynamics
High-frequency Ultrasound Imaging Analysis of Intravascular Flow Dynamics in Metastatic Lymph Nodes

Maeda K., Kuramoto D., Okada Y., Miyazaki R., Omura M., Sukhbaatar A., Mori S., Kodama T.

21st International Conference on Flow Dynamics
Evaluation of a minimally invasive prototype fiber optic probe for breast cancer treatment.

Obonai A., Kogawa T., Kanda Y., Kodama T., Komiya A.

The 34th International Symposium on Transport Phenomena
生体内における磁気異方性を用いた加熱効率の向上

上島優也, 桑波田晃弘, 島野大輝, Ariunbuyan Sukhbaatar, Loi Tontha, 小玉哲也, 薮上信

第48回日本磁気学会学術講演会
Docetaxel, immunecheckpoint inhibitor or combination in metastatic lymph node mouse after resection: efficacy and safety

Ariunbuyan Sukhbaatar, Shiro Mori, Tsuyoshi Suguira, Tetsuya Kodama

The 83rd Annual Meeting of the Japanese Cancer Association
Wilda S. Aulia, Ariunbuyan Sukhbaatar, Shiro Mori, Tsuyoshi Sugiura, Tetsuya Kodama

The efficacy of Radioimmunotherapy, administered by lymphatic drug delivery system for lymph node metastasis

The 83rd Annual Meeting of the Japanese Cancer Association
Polysorbate80の事前投与による磁性ナノ粒子のリンパ節内分布変化リンパ節への新たな薬剤送達法による，磁気温熱療法の治療効果の増強

島野大輝, 宮崎黎飛, 山崎葵, 篠原陸, 上島優也, Ariunbuyan Sukhbaatar, 桑波田晃弘, 森士朗, 薮上信, 小玉哲也

生体医工学シンポジウム2024
Development of Predictive Model for Diagnosis Metastatic Lymph Node by Ultrasound RF Signal Reconstruction using Deep Learning

Maeda K, Omura M, Kodama T

The 43rd JAMIT Annual Meeting (JAMIT 2024)
Enhancing the therapeutic effect of X-ray irradiation on metastatic lymph nodes through the induction of magnetosome@RGD

Shimano T, Miyazaki R, Sukhbaatar A, Prévéral S, Mori S, Faivre D, Vassaux G, Cambien B, Kodama T

Interface Summer Seminar 2024 (The 19th International Workshop on Biomaterials in Interface Science)　2024/08/06
リンパ節腫脹モデルマウスの超音波定量解析と微細血流イメージング

大村眞朗, 前田一伎, 小玉哲也, 吉田憲司, 山口匡

日本超音波医学会基礎技術研究会令和6年（2024年）度第2回研究会　2024/08/02
抗 CTLA4 抗体を用いたリンパ行性薬物送達法によるがん免疫療法に関する実験病理学的検討

多田絵梨香, Ariunbuyan Sukhbaatar, 尾形咲季, 東友太郎, 黒羽根壮, 梶田倫功, 纐纈衆, 宮下仁, 小玉哲也, 杉浦剛

第78回NPO法人日本口腔科学会学術集会
リンパ節転移モデルにおけるリンパ節切除後の肺転移病巣活性化に関する実験病理学的検討

尾形咲季, Ariunbuyan Sukhbaatar, 東友太郎, 黒羽根壮, 梶田倫功, 纐纈衆, 宮下仁, 小玉哲也, 杉浦剛

第78回NPO法人日本口腔科学会学術集会
Lymphatic Drug Delivery System of Single Dose Anti-CTLA4 Enhance by Local X-Ray Irradiation Treatment for Lymph Node Metastatic

Wilda Septilah Aulia, Taiki Shimano, Ariunbuyan Sukhbaatar, Shiro Mori, Tsuyoshi Sugiura, Tetsuya Kodama
HDAC/PI3K 2重阻害剤を用いたリンパ行性薬物送達法による転移リンパ節の治療

多田絵梨香, Ariunbuyan Sukhbaatar, 森士朗, 西條憲, 石岡千加史, 杉浦剛, 小玉哲也

第40回日本DDS学会学術集会
magnetosome@RGDを用いたX線放射線療法による転移リンパ節の治療

島野大輝, 宮崎黎飛, Sandra Prévéral, Ariunbuyan Sukhbaatar, 森士朗, Damien Faivre, Georges Vassaux, Beatrice Cambien, 小玉哲也

第40回日本DDS学会学術集会
Preliminary Study Using Fiber-Optic Laser for the Treatment of Breast Cancer, Track 01-1 Bio and Medical Applications

Obonai A., Kogawa T., Kanda Y., Kodama T., Komiya A.

the third Asian Conference on Thermal Sciences (ACTS2024)
Lymph node metastasis and lymph node targeted therapy

Ariunbuyan Sukhbaatar, 宮下仁, 志賀清人, 杉浦剛, 小玉哲也

第48回日本頭頸部癌学会総会・学術講演会
ISG20 is Overexpressed in clinically relevant radioresistant oral cancer cells

宮下仁, 桑原義和, 森士朗, 小玉哲也, 福本学

第48回日本頭頸部癌学会総会・学術講演会
早期転移リンパ節の造影高周波超音波と造影マイクロCT画像における造影欠損の評価

黒羽根壮, Ariunbuyan Sukhbaatar, 梶田倫功, 岩間亮介, 陳都聖, 纐纈衆, 宮下仁, 志賀清人, 小玉哲也, 杉浦剛

第48回日本頭頸部癌学会総会・学術講演会
リンパ洞造影マイクロCTを用いたリンパ節転移早期診断法の開発

梶田倫功, Ariunbuyan Sukhbaatar, 宮下仁, 黒羽根壮, 岩間亮介, 纐纈衆, 志賀清人, 小玉哲也, 杉浦剛

第48回日本頭頸部癌学会総会・学術講演会
リンパ行性薬物送達法の開発 Invited

小玉哲也

第48回日本リンパ学会総会
Effect of lymph node resection in cancer progression

Ariunbuyan Sukhbaatar, Shiro Mori, Tsuyoshi Sugiura, Tetsuya Kodama

1900
担がんリンパ節に対するHDAC/PI3K 2重阻害剤を用いたリンパ行性薬物送達法の治療

多田絵梨香, Ariunbuyan Sukhbaatar, 森士朗, 西條憲, 石岡千加史, 杉浦剛, 小玉哲也

第48回日本リンパ学会総会
Immune Checkpoint Inhibitor by LDDS Combined Treatment with Low Dose Local Radiotherapy for Lymph Node Metastasis

Wilda Septilah Aulia, Ariunbuyan Sukhbaatar, Shiro Mori, Tsuyoshi Sugiura, Tetsuya Kodama

1900
リンパ行性薬剤送達法(LDDS)を用いた化学療法によるリンパ節の病理解析

貝森花音, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

第48回日本リンパ学会総会　1900
超音波RF信号を用いたリンパ節の血流像生成

前田一伎, 大村眞朗, 小玉哲也

第48回日本リンパ学会総会
転移リンパ節に対するmagnetosome@RGDを用いた放射線療法の開発

島野大輝, 宮崎黎飛, Sandra Prévéral, Ariunbuyan Sukhbaatar, 森士朗, Damien Faivre, Georges Vassaux, Beatrice Cambien, 小玉哲也

第48回日本リンパ学会総会
Localized Docetaxel Therapy for Multiple Metastatic Lymph Nodes using Lymphatic Drug Delivery System (LDDS)

Bridget Namugga, Ariunbuyan Sukhbaatar, Shiro Mori, Tetsuya Kodama
転移リンパ節に対するFeOナノ粒子magnetosome@RGDを用いた放射線療法の開発

島野大輝, 宮崎黎飛, Ariunbuyan Sukhbaatar, 森士朗, Sandra Prévéral, Damien Faivre, Georges Vassaux, Beatrice Cambien, 小玉哲也

日本機械学会第36回バイオエンジニアリング講演会　2024/05/12
転移リンパ節に対するドキソルビシンと抗CTLA4抗体を⽤いたリンパ⾏性薬物送達法の研究

鈴木瑠真, Ariunbuyan Sukhbaatar, 藤井博司, 森士朗, 小玉哲也

日本機械学会第36回バイオエンジニアリング講演会　2024/05/11
HDAC/PI3K 2重阻害剤を用いた担がんリンパ節におけるリンパ行性薬剤送達法(LDDS)治療

多田絵梨香, Ariunbuyan Sukhbaatar, 森士朗, 西條憲, 石岡千加史, 小玉哲也

日本生体医工学会関東支部若手研究者発表会2023　2023/12/09
リンパ行性薬剤送達法を用いた免疫療法と放射線療法の併用による治療

鈴木瑠真, 髙木洸樹, 多田絵梨香, 宮津美里有, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

日本生体医工学会関東支部若手研究者発表会2023　2023/12/09
転移リンパ節に対する磁性ナノ粒子Resovist® を用いた磁気温熱療法の開発

島野大輝, 鏡味隆行, 山崎葵, 篠原陸, 上島優也, 宮津美里有, 髙木洸樹, 田中菜生, Ariunbuyan Sukhbaatar, 桑波田晃弘, 森士朗, 薮上信, 小玉哲也

日本生体医工学会関東支部若手研究者発表会2023　2023/12/09
Suppression of lymph node and lung metastases by combination therapy with lymphatic drug delivery and radiation

The 68th Congress of the Japanese Society of Oral and Maxillofacial Surgeons　2023/11/10
Developing docetaxel-based lymphatic drug delivery system for metastatic lymph nodes

Chen TS, Sukhbaatar A, Kurobane T, Kajita T, Iwama R, Mori S, Kodama T, Sugiura T

The 68th Congress of the Japanese Society of Oral and Maxillofacial Surgeons　2023/11/12
Experimental pathology on lymph node-mediated hematogenous metastasis

Ogata S, Sukhbaatar A, Kurobane T, Kajita T, Iwama R, Kouketsu A, Miyashita H, Mori S, Kodama T, Sugiura T

The 68th Congress of the Japanese Society of Oral and Maxillofacial Surgeons　2023/11/12
Study of lymph node metastasis

Sukhbaatar A, Mori S, Kodama T, Sugiura T

The 68th Congress of the Japanese Society of Oral and Maxillofacial Surgeons　2023/11/12
Preliminary Research in Fiber Optic Laser Therapy for Treatment of Breast, Head and Neck Tumors

Obonai A., Kogawa T., Kanda Y., Kodama T., Komiya A.

the 20th International Conference on Flow Dynamics (20th ICFD)
Evaluation of Therapeutic Efficacy of Cancer Immunotherapy Using Lymphatic Network Compared with Hematogenous Administration.

Takagi K, Sukhbaatar A, Mori S, Sugiura T, Kodama T

20th International Conference on Flow Dynamics　2023/11/06
Investigation of Therapeutic efficacy of Intranodaly Administered Hyperosmotic, High-viscosity Formulation of Carboplatin for the Treatment of Metastatic Lymph Node.

Miyatsu M, Mishra R, Sukhbaatar A, Mori S, Kodama T

20th International Conference on Flow Dynamics　2023/11/06
Lymphatic drug delivery system: treatment strategies for metastatic lymph nodes Invited

Kodama T

2023 International Joint Meeting of the 23rd International Conference on Cytochrome P450 and the 38th Annual Meeting of the Japanese Society for the Study of Xenobiotics in Shizuoka　2023/09/29
Evaluation of optical properties of temperature changes in biological tissues induced by nearinfrared laser irradiation

Obanai A, Kogawa T, Kanda Y, Kodama T, Komiya A

The 33rd International Symposium on Transport Phenomena
Intranodal pressure of metastatic lymph node compromises treatment response of CDDP

Kajita T, Sukhbaatar A, Kurobane T, Iwama R, Kouketsu A, Mori S, Kodama T, Sugiura T

The 82nd Annual Meeting of the Japanese Cancer Association　2023/09/23
Non-invasive treatment of lymph node metastasis with magnetic hyperthermia technology in murine tumor model

Kagami T, Sukhbaatar A, Kuwahata A, Tonthat L, Shinohara R, Kodama T, Yabukami S

The 82nd Annual Meeting of the Japanese Cancer Association　2023/09/23
Study of lymph sinus analysis at the early stage of lymph node metastasis using artificial intelligence

Maeda K, Kao KT, Sukhbaatar A, Mori S, Kodama T

The 82nd Annual Meeting of the Japanese Cancer Association　2023/09/23
Quantitative analysis of morphological changes of lymph sinuses in the early stage of lymph node metastasis

Kaimori K, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 82nd Annual Meeting of the Japanese Cancer Association　2023/09/23
Evaluation of the treatment with direct lymph node administration of anti-CTLA-4 antibody combined with radiotherapy

Takagi K, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 82nd Annual Meeting of the Japanese Cancer Association　2023/09/22
Combination therapy with immune checkpoint inhibitor and anticancer drugs by lymphatic drug delivery system (LDDS)

Tanaka N, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 82nd Annual Meeting of the Japanese Cancer Association　2023/09/22
Efficacy of a Drug Delivery System Against Lymph Node Metastases with Physicochemically Modificated Cisplatin

Iwama R, Sukhbaatar A, Kurobane T, Kajita T, Koketsu A, Mori S, Kodama T, Sugiura T

The 82nd Annual Meeting of the Japanese Cancer Association　2023/09/21
Development of lymphatic drug delivery: Optimization of administration conditions for metastatic lymph nodes

Miyatsu M, Sukhbaatar A, Mori S, Kodama T

The 82nd Annual Meeting of the Japanese Cancer Association　2023/09/21
Docetaxel targeted therapy for multiple metastatic lymph nodes using LDDS

Namugga B, Sukhbaatar A, Mori S, Kodama T

The 82nd Annual Meeting of the Japanese Cancer Association
Physioanatomical analysis of mouse lymphatic network for the lymphatic drug delivery system usage

Sukhbaatar A, Kouketsu A, Miyashita H, Mori S, Sugiura T, Kodama T

The 82nd Annual Meeting of the Japanese Cancer Association
Docetaxel targeted therapy for multiple metastatic lymph nodes using LDDS

Namugga B, Sukhbaatar A, Kodama T

2023/07/27
リンパ行性薬物送達法の開発：転移リンパ節に対する投与条件の最適化

宮津美里有, Ariunbuyan Sukhbaatar, Radhika Mishra, 森士朗, 小玉哲也

第39回日本DDS学会学術集会　2023/07/27
Intranodal injected Docetaxel inhibition depends on drug shot

Sukhbaatar A, Mori S, Kodama T

Second JCA-AACR Precision Cancer Medicine International Conference
人工知能を用いた転移性リンパ節の病理画像解析に関する研究

Maeda K, Kao KT, Sukhbaatar A, Kodama T

The 35th Bioengineering Conference Annual Meeting of BED/JSME　2023/06/04
リンパ節転移初期段階におけるリンパ洞の形態学的変化に関する定量解析

Kaimori K, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 35th Bioengineering Conference Annual Meeting of BED/JSME　2023/06/04
An Innovative Pixel-wise Receiver Operating Characteristic Approach for Evaluating Uncertain Annotations of Lyve-1-stained Whole-Slide Images Lymphatic Sinus in Axillary and Subiliac Lymph Nodes of Mice

Kao KT, Chang RF, Kodama T

The 35th Bioengineering Conference Annual Meeting of BED/JSME　2023/06/03
Docetaxel targeted therapy for multiple metastatic lymph nodes using LDDS

Namugga B, Sukhbaatar A, Mori S, Kodama T

The 35th Bioengineering Conference Annual Meeting of BED/JSME　2023/06/03
Lymph node resection activates tumor cells in the distant organs in a mouse model Invited

Sukhbaatar A, Mori S, Kodama T

The 35th Bioengineering Conference Annual Meeting of BED/JSME　2023/06/03
近赤外線レーザー照射による生体組織変化が光学物性に及ぼす影響の評価

小保内秋芳, 古川琢磨, 神田雄貴, オルワフェミオルワトビ, 小玉哲也, 小宮敦樹

第60回日本伝熱シンポジウム, セッションG121
リンパ行性薬物送達法における薬物動態に関する研究

前田一伎, Bridget Namugga, Radhika Mishra, Ariunbuyan Sukhbaatar, 小玉哲也

日本機械学会第33回バイオフロンティア講演会　2022/12/17
CTLA4 targeted therapy using LDDS for the treatment of metastatic lymph nodes

Mishra R, Sukhbaatar A, Mori S, Kodama T

the AACR Special Conference: Precision Prevention, early detection and interception of Cancer　2022/11/18
Acquisition of anti-tumor immunity by local irradiation and its application to radioimmunotherapy

Kuriu S, Mishra R, Sukhbaatar A, Mori S, Kodama T

19th International Conference on Flow Dynamics　2022/11/11
Comparing the pharmacokinetic parameters of ICG via lymphatic drug delivery and the intravenous injection

Namugga B, Sukhbaatar A, Kodama T

19th International Conference on Flow Dynamics　2022/11/11
リンパ行性薬物送達法を用いた転移リンパ節に対する新たな治療戦略 Invited

小玉哲也

第24回SNNS研究会学術集会　2022/11/05
Wireless temperature monitoring by using magnetic nanoparticles for clinical trials on magnetic hyperthermia treatment.

Kuwahata A, Hirota R, Sukhbaatar A, Kodama T, Yabukami S

MMM 2022 Conference
リンパ節転移に対する新たな治療法－LDDS（lymphatic drug delivery system）の開発

志賀清人, 日下尚裕, 片桐克則, 齋藤大輔, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

第60回日本癌治療学会学術集会
リンパ行性薬剤送達法に最適な溶媒特性に関する考察

小玉哲也, Ariunbuyan Sukhbaatar, 森士朗, 志賀清人

第60回日本癌治療学会学術集会
Experimental verification of lymph node mediated hematogenous metastasis theory

Shimizu K, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 81st Annual Meeting of the Japanese Cancer Association
Suppression of Distant Metastasis by Local Irradiation

Kuriu S, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 81st Annual Meeting of the Japanese Cancer Association
Lymph node resection induces metastases in the lung

Sukhbaatar A, Mori S, Kodama T

The 81st Annual Meeting of the Japanese Cancer Association
Mishra R, Sukhbaatar A, Mori S, Sakamoto M, Kodama T

Immune checkpoint inhibitor delivered via lymphatic drug delivery system, a curative therapy for metastatic lymph nodes

The 81st Annual Meeting of the Japanese Cancer Association
Evaluation of the Antitumor Effect on Metastatic Lymph Nodes Using LDDS with Osmotic and Viscosity-Adjusted Carboplatin

Miyatsu M, Takagi K, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 81st Annual Meeting of the Japanese Cancer Association
Treatment of metastatic lymph nodes by lymphatic drug delivery system with doxorubicin

Tanaka N, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 81st Annual Meeting of the Japanese Cancer Association
リンパ行性薬剤送達法における高浸透圧・高粘度溶媒によるリンパ節内薬剤貯留性の向上に関する超音波画像による解析

志水洸太, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

日本超音波医学会第64回東北地方会学術集会　2022/09/11
Ultrasonographic analysis of enhanced intra lymphatic drug delivery by high osmotic pressure and high viscosity solvent in lymphatic drug delivery

Shimizu K, Sukhbaatar A, Mori S, Kodama T

Interface summer seminar 2022 (The 17th International Workshop on Biomaterials in Interface Science)　2022/08/24
Activation of Anti-tumor Immunity by Local Irradiation

Kuriu S, Mishra R, Sukhbaatar A, Mori S, Kodama T

Interface summer seminar 2022 (The 17th International Workshop on Biomaterials in Interface Science)　2022/08/24
Docetaxel facilitates improved treatment effect for lymph node metastasis by LDDS administration

Sukhbaatar A, Sakamoto M, Mori S, Kodama T

Interface summer seminar 2022 (The 17th International Workshop on Biomaterials in Interface Science)　2022/08/24
Evaluation of convective and radiative heat transfer for the therapeutic development using near-infrared laser and gold nanorods

Obanai A, Kanda Y, Oluwafemi O, Kodama T, Komiya A

The 32nd International Symposium on Transport Phenomena　2022
リンパ節介在血行性転移理論に関する実験的検証

志水洸太, 栗生晏暉, 高木洸樹, 宮津美里有, 空翔太, 永松大輝, アリウンヴヤンスフバートル, 鈴木健大, ラディカミシュラ, 阪本真弥, 森士朗, 小玉哲也

日本機械学会第32回バイオフロンティア講演会　2022/01/13
肺転移がんの長期治療実験を実現するマウスモデルの樹立

髙木洸樹, 宮津美里有, Ariunbuyan Sukhbaatar, 栗生晏暉, Radhika Mishra, 空翔太, 永松大輝, 鈴木健大, 志水洸太, 阪本真弥, 森士朗, 小玉哲也

日本機械学会第32回バイオフロンティア講演会　2022/01/13
X線照射によるリンパ洞の薬剤透過性および貯留性の亢進

栗生晏暉, 高木洸樹, 宮津美里有, 空翔太, Arinnbuyan Sukhbaatar, 阪本真弥, 森士朗, 小玉哲也

日本機械学会第32回バイオフロンティア講演会　2022/01/12
転移リンパ節に対するリンパ行性薬剤送達法によるカルボプラチンおよびフルオロウラシルの併用療法

宮津美里有, 髙木洸樹, 栗生晏暉, アリウンブヤンスフバートル, ラディカミシェラ, 空翔太, 志水洸太, 永松大輝, 鈴木健大, 阪本真弥, 森士朗, 小玉哲也

日本機械学会第32回バイオフロンティア講演会　2022/01/12
Evaluation of Lymphatic Delivery Capacity of ICG Liposomes after X-Ray Irradiation

Kuriu S, Sora S, Ariunbuyan S, Mishra R, Sakamoto M, Mori S, Kodama T

The 11th Asian-Pacific Conference on Biomechanics (AP Biomech 2021)
Can radiation therapy for total body including tumor-bearing lymph nodes control metastasis?

Sora S, Ariunbuyan S, Mori S, Kodama T

The 11th Asian-Pacific Conference on Biomechanics (AP Biomech 2021)
Optimization of drug physicochemical parameters for enhanced anti-tumor response using LDDS

Mishra R, Ariunbuyan S, Sakamoto M, Mori S, Kodama T

The 11th Asian-Pacific Conference on Biomechanics (AP Biomech 2021)
A Potential of Temperature Distribution Control using Near-infrared Laser Irradiation and Gold Nanorods

Obonai A., Kogawa T., Kanda Y., Kodama T., Komiya A.

the 18th International Conference on Flow Dynamics (18th ICFD)
Possibility of total body irradiations for lymph node metastasis and lung metastasis

Shouta Sora, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics　2021/10/07
Possibility of total body irradiations for lymph node metastasis and lung metastasis

Shouta Sora, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics　2020/10/07
Importance of drug osmotic pressure and viscosity for efficient drug delivery using the Lymphatic Drug Delivery System

Radhika MISHRA, Ariunbuyan SUKHBAATAR, Shota SORA, Shiro MORI, Maya SAKAMOTO, Tetsuya KODAMA

AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics　2021/10/07
Lymph node metastasis targeted intranodal delivery of docetaxel improves treatment outcome

Ariunbuyan Sukhbaatar, Shouta Sora, Shiro Mori, Tetsuya Kodama

AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics　2021/10/07
Evaluation of Lymphatic Delivery Capacity of ICG Liposomes after X-Ray Irradiation

Shizuki Kuriu, Ariunbuyan Sukhbaatar, Shiro Mori, Tetsuya Kodama

The 80th Annual Meeting of the Japanese Cancer Association　2021/09/30
Effects of total body irradiation on lung metastasis and tumors in lymph nodes

Shouta Sora, Ariunbuyan Sukhbaatar, Shiro Mori, Tetsuya Kodama

The 80th Annual Meeting of the Japanese Cancer Association　2021/09/30
Improved treatment effect by manipulation of drug physicochemical parameters

Mishra Radhika, Ryoichi Fukumura, Ariunbunyan Sukhbaatar, Shiro Mori, Maya Sakamoto, Tetsuya Kodama

The 80th Annual Meeting of the Japanese Cancer Association　2021/10/02
Effect of LDDS on metastatic lymph nodes at different stages

Ariunbuyan Sukhbaatar, Hitoshi Miyashita, Shiro Mori, Tetsuya Kodama

The 80th Annual Meeting of the Japanese Cancer Association　2021/10/02
Manipulation of drug physicochemical parameters for efficient drug delivery using lymphatic drug delivery system

Mishra Radhika, Sukhbaatar Ariunbuyan, Shouta Sora, Sakamoto Maya, Mori Shiro, Kodama Tetsuya

The 16th International Workshop on Biomaterials in Interface Science　2021/09/28
Micro-CT analysis of lung vascularization in a mouse model of metastatic lung cancer

S Ariunbuyan, Kuriu S, Mori S, Kodama T

1st JCA-AACR Precision Cancer Medicine International Conference　2021/09/11
Optimized window of drug physicochemical parameters for the Lymphatic Drug Delivery System

Mishra R, S Ariunbuyan, Sora S, Mori S, Sakamoto M, Kodama T

1st JCA-AACR Precision Cancer Medicine International Conference　2021/09/11
Lymph node metastasis mouse model and its treatment

S Ariunbuyan, Sakamoto M, Mori S, Kodama T

International Joint Symposium 2020(The 15th International Workshop on Biomaterials in Interface Science, The 11th Symposium on Innovative Dental-Engineering Alliance (IDEA))　2020/12/15
リンパ節転移モデルマウスの3次元in vivo超音波定量評価の基礎検討

Omura M, Nagamatsu D, Kodama T, Sato Y, Yoshida K, Yamaguchi T

The 93rd Annual Meeting of the Japan Society of Ultrasonics in Medicine　2020/12/03
深層学習を用いた乳癌造影超音波定量解析における客観的病変範囲評価

Higuchi K, Mori N, Ito K, Kodama T, Takase K

The 93rd Annual Meeting of the Japan Society of Ultrasonics in Medicine　2020/12/01
Study on the morphological changes of lymph nodes in response to the osmotic pressure

Fukumura R, Mishra R, S Ariunbuyan, Mori S, Kodama T

The 93rd Annual Meeting of the Japan Society of Ultrasonics in Medicine　2020/12/02
Does radiotherapy metastatic lymph nodes induce an abscopal effect? International-presentation

Sora S, S Ariunbuyan, Sakamoto M, Mori S, Kodama T

World Molecular Imaging Congress (WMIC) virtual 2020　2020/10
Optimized fluid parameters for enhanced treatment efficacy for drug delivery using the Lymphatic Drug Delivery System International-presentation

Mishra R, Fukumura R, S Ariunbuyan, Mori S, Kodama T

World Molecular Imaging Congress (WMIC) virtual 2020　2020/10
Imaging of the mouse lymphatic sinus during lymphatic administration of high osmotic pressure solutions using a contrast-enhanced high-frequency ultrasound imaging system International-presentation

Fukumura R, Mishra R, S Ariunbuyan, Mori S, Kodama T

World Molecular Imaging Congress (WMIC) virtual 2020　2020/10
Therapeutic dependence of osmotic pressure when administering anticancer drugs using a lymphatic drug delivery system

福村凌一, ミシュララディカ, スフバートルアリウンブヤン, 永松大輝, 森士朗, 小玉哲也

The 79th Annual Meeting of the Japanese Cancer Association　2020/10/01
Quantitative analysis of molecular accumulation in lymph nodes by lymphatic drug delivery system

Suzuki T, S Ariunbuyan, Mori S, Ito A, Kodama T

The 79th Annual Meeting of the Japanese Cancer Association　2020/10/01
Development of multiple metastatic lymph node model mice

Nagamatsu D, S Ariunbuyan, Mishara R, Mori S, Kodama T

The 79th Annual Meeting of the Japanese Cancer Association　2020/10/01
Superselective local radiation therapy to treat metastatic lymph nodes in mice

Sora S, S Ariunbuyan, Mori S, Kodama T

The 79th Annual Meeting of the Japanese Cancer Association　2020/10/01
Importance of drug osmotic pressure and viscosity for enhancing treatment effect using lymphatic drug delivery system

Mishra R, Fukumura R, S Ariunbuyan, Mori S, Kodama T

The 79th Annual Meeting of the Japanese Cancer Association　2020/10/01
Improvement of chemotherapy for the lymph node metastasis

S Ariunbuyan, Kodama T, Mori S

The 79th Annual Meeting of the Japanese Cancer Association　2020/10/01
A study on the evaluation of treatment efficacy of metastatic lymph nodes associated with changes in drug osmotic pressure in the lymphatic drug delivery system

Fukumura R, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 60th Annual Meeting of The Japan Society of Ultrasonics in Medicine　2020/09/13
Development of multiple metastatic lymph node model mice

Nagamatsu D, Sukhbaatar A, Mishra R, Mori S, Kodama T

The 36th Annual Meeting of Japan Society of Drug Delivery System　2020/08/28
Study on the efficacy of high osmotic agents for lymphatic drug delivery system

Fukumura R, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 36th Annual Meeting of Japan Society of Drug Delivery System　2020/08/29
Optimal Osmotic Pressure for a Lymphatic Drug Delivery System

Mishra R, Fukumura R, Sukhbaatar A, Mori S, Kodama T

The 32th Bioengineering Conference Annual Meeting of BED/JSME　2019/12/21
Correlation between the therapeutic effect of lymphatic drug delivery system and drug osmotic pressure

Fukumura R, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 32th Bioengineering Conference Annual Meeting of BED/JSME　2019/12/20
Effect of drug osmotic pressure on the delivery efficiency for a Lymphatic Drug Delivery System International-presentation

Fukumura R, Mishra R, Sukhbaatar A, Mori S, Kodama T

Tohoku University Forum for Creativity Thematic 2019, Cancer - from Biology to Acceptance　2019/12/03
Optimized Physiochemical Properties for Lymphatic Drug Delivery System International-presentation

Fukumura R, Mishra R, Sukhbaatar A, Yadav N, Shrivastava S, Saurav S, Shiga K, Mori S, Kodama T

16th International Conference on Flow Dynamics　2019/11/08
In-vitro cell viability studies of gold nanorods/graphene oxide nanocomposites for photothermal and drug delivery application International-presentation

Lebepe T, Oluwafemi O, Kodama T

16th International Conference on Flow Dynamics　2019/11/07
Flow Visualization and Lymphatic Vessel Characterization for Lymphatic Drug Delivery System International-presentation

Mishra R, Sukhbaatar A, Shrivastava S, Saurav S, Yadav N, Neetu K, Shiga K, Mori S, Kodama T

M16th International Conference on Flow Dynamics　2019/11/07
Enhancement of Epirubicin Anticancer Activity by LDDS in Metastatic Lymph Node Mouse Model International-presentation

Sukhbaatar A, Mori S, Kodama T

16th International Conference on Flow Dynamics　2019/11/07
Study of the lymphatic drug delivery system Invited

KODAMA Tetsuya

The 41st Symposium hosted by the division of physical sciences, the Pharmaceutical Society of Japan　2019/10/19
Effect of drug osmotic pressure on the therapeutic effect using a lymphatic drug delivery system International-presentation

Fukumura R, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 4th International Symposium on Creation of Life Innovation Materials for Interdisciplinary and International Researcher Development(iLIM-4)　2019/10/03
Facile synthesis of amino acid functionalised CdTe/CdSe/ZnSe core-multi shell with improved cell viability for cellular imaging. International-presentation

Ncapayi V, Songca SP, Kodama T, Oluwafemi SO

The 4th International Symposium on Creation of Life Innovation Materials for Interdisciplinary and International Researcher Development(iLIM-4)　2019/10/03
Effect of Osmotic Pressure of drug on treatment efficacy for a Lymphatic Drug Delivery System. International-presentation

Mishra R, Sukhbaatar A, Mori S, Kodama T

The 4th International Symposium on Creation of Life Innovation Materials for Interdisciplinary and International Researcher Development(iLIM-4)　2019/10/03
Importance of osmotic pressure for lymphatic drug delivery system.

Mishra R, Fukumura R, Ariunbuyan S, Sakamoto M, Mori S, Shiga K, Kodama T

The 78th Annual Meeting of the Japanese Cancer Association　2019/09/28
Optimized ranges of osmotic pressure and viscosity of drugs required for lymphatic drug delivery system

Fukumura R, Mishra R, Ariunbuyan S, Sakamoto M, Mori S, Shiga K, Kodama T

The 78th Annual Meeting of the Japanese Cancer Association　2019/09/28
Removal of lymph nodes increases the incidence of metastasis.

Ariunbuyan S, Takahashi T, Mori S, Kodama T

The 78th Annual Meeting of the Japanese Cancer Association　2019/09/26
Flow dynamics of lymphatic drug delivery system in in mice

Mishra Radhika, Sukhbaatar Ariunbuyan, SAKAMOTO Maya, MORI Shiro, KODAMA Tetsuya

The 35th Annual Meeting of the Japan Society of Drug Delivery System　2019/07/04
Therapeutic effect of epirubicin at different osmotic pressure in metastatic lymph nodes at the early stage using lymphatic drug delivery system.

Suhkbaatar Ariunbuyan, MORI Shiro, KODAMA Tetsuya

The 35th Annual Meeting of the Japan Society of Drug Delivery System　2019/07/04
Lymphatic drug delivery system using nimustine for metastatic lymph node

Tadano K, Ishibashi R, Wamuro K, Mori S, Kodama T

The 31st Bioengineering Conference 2019 Annual Meeting of BED/JSME　2018/12/15
Treatment of lymph node metastasis by lymphatic drug delivery system with Methotrexate

Ishibashi R, Tadano K, Wamuro K, Mori S, Kodama T

The 31st Bioengineering Conference 2019 Annual Meeting of BED/JSME　2018/12/15
Murine pulmonary vascularization changes in metastatic lung mouse model using micro-CT

Ariunbuyan S, Takahashi T, Mori S, Kodama T

2018/09/29
Observation of pulmonary vascularization changes in a metastasis lung mouse model using μ-CT International-presentation

Ariunbuyan S, Takahashi T, Mori S, Kodama T

13th International Workshop on Biomaterials in Interface Science　2018/08/02
μCT analysis of vascular changes in lymph nodes after X-ray irradiation International-presentation

Kikuchi R, Mori S, Kodama T

13th International Workshop on Biomaterials in Interface Science　2018/08/02
Induction of lung metastasis after lymphadenectomy International-presentation

Ariunbuyan S, Mori S, Saiki Y, Ishizawa K, Takahashi T, Horii A, Nose M, Kodama T

The 6th JCA-AACR Special Joint Conference　2018/07/10
Metastatic lymph nodes can serve as a source of systemic metastasis International-presentation

Takeda K, Mori S, Kodama T

AACR Annual Meeting 2018　2018/04/14
Validation of anatomical characteristics of metastatic lymph nodes in mouse model. Lymphatics International-presentation

Takeda K, Kikuchi R, Mori S, Kodama T

Gordon Research Conference 2018　2018/03/11
Validation of anatomical characteristics of metastatic lymph nodes in mouse model International-presentation

Takeda K, Kikuchi R, Mori S, Kodama T

Gordon Research Seminars 2018　2018/03/10
Activation of lung metastasis after lymph node dissection International-presentation

Ariunbuyan S, Takahashi T, Mori S, Kodama T

International Conference on Targeted Anticancer Therapies (TAT 2018)　2018/03/05
Activation of metastatic cells in the lung by dissection of lymph nodes International-presentation

Ariunbuyan S, Takahashi T, Mori S, Kodama T

International Symposium for Multimodal Research and Education in IOHS-Liaison2018　2018/01/13
Therapeutic potentials of the lymphatic drug delivery system with 5-FU for the treatment of metastatic lymph nodes International-presentation

Fujii H, Horie S, Mori S, Kodama T

International Symposium for Multimodal Research and Education in IOHS-Liaison2018　2018/01/13
Flow Dynamics Based on Anatomical Characteristics of Lymph Node International-presentation

Takeda K, Horie S, Mori S, Kodama T

14th International Conference on Flow Dynamics　2017/11/01
Anti-tumor effects of 5-FU with lymphatic drug delivery system in a metastatic lymph node mouse model International-presentation

Fujii H, Horie S, Mori S, Kodama T

14th International Conference on Flow Dynamics　2017/11/01
Simple Green Synthesis of Amino Acid Functionalized CdTe/CdSe/XnSe Core Multi-Shell with Improved Cell Viability against Fibroblast Histiocytoma Cells International-presentation

V Ncapayi, S Parani, SP Songca, Kodama T, OS Oluwafemi

14th International Conference on Flow Dynamics　2017/11/01
Oxygen Partial Pressure in False-negative N0 Lymph Nodes International-presentation

Kikuchi R, Horie S, Mori S, Kodama T

14th International Conference on Flow Dynamics　2017/11/01
A Development of an Early Stage Diagnosis for Lymph Node Metastasis Using Lymphangiography International-presentation

Iwamura R, Horie S, Mori S, Kodama T

14th International Conference on Flow Dynamics　2017/11/01
偽陰性N0リンパ節に対するリンパ行性薬剤送達法の基礎理論と治療評価

小玉哲也, 堀江佐知子, 森士朗

第55回日本癌治療学会学術集会　2017/10/20
担がんリンパ節郭清による肺転移誘導マウスモデルの作製

堀江佐知子, 森士朗, 小玉哲也

第55回日本癌治療学会学術集会　2017/10/20
リンパ行性薬剤送達法によるがん治療

堀江佐知子, 森菜緒子, 志賀清人, 森士朗, 小玉哲也

第76回日本癌学会学術総会　2017/09/28
リンパ行性薬剤送達法を利用した５－ＦＵによる転移リンパ節治療

藤井穂乃香, 武田航, 堀江佐知子, 森士朗, 小玉哲也

第76回日本癌学会学術総会　2017/09/28
転移偽陰性リンパ節における酸素分圧の評価

菊池凌平, 堀江佐知子, 森士朗, 小玉哲也

第76回日本癌学会学術総会　2017/09/28
マイクロCTと高周波超音波を用いたリンパ造影によるリンパ節転移の新たな診断手法の開発

岩村亮, 森士朗, 阪本真弥, 小玉哲也

第76回日本癌学会学術総会　2017/09/28
転移リンパ節の解剖学的な背景に関する研究

武田航, 藤井穂乃香, 阪本真弥, 森士朗, 小玉哲也

第76回日本癌学会学術総会　2017/09/28
The Study of flow dynamics in lymphatic system International-presentation

Takeda K, Horie S, Mori S, Kodama T

World Molecular Imaging Congress 2017 (WMIC 2017)　2017/09/13
Oxygen state in fase-negative N0 lymph node mouse model International-presentation

Kikuchi R, Horie S, Mori S, Kodama T

The 12th International Workshop on Biomaterials in Interface Science　2017/08/04
Lymphatic drug delivery system with 5-FU for metastatic lymph nodes International-presentation

Fujii H, Horie S, Mori S, Kodama T

The 12th International Workshop on Biomaterials in Interface Science　2017/08/04
The effects of cis-diamminedichloroplatinum (II) (CDDP), injected intravenously in MXH10/Mo-lpr/lpr mice, on lymph nodes International-presentation

Lily A. David, Horie S, Mori S, Kodama T

The 12th International Workshop on Biomaterials in Interface Science　2017/08/04
New insights on Lymph node metastasis : the benefit of using our mouse model in cancer metastasis International-presentation

Takeda K, Horie S, Mori S, Kodama T

3rd Annual Data Science in Life Science and Engineering Collaboration and Symposium　2017/08/03
The study of flow dynamics in lymphatic system International-presentation

Takeda K, Horie S, Mori S, Kodama T

3rd Annual Data Science in Life Science and Engineering Collaboration and Symposium　2017/08/03
リンパ節転移モデルマウスを用いた転移リンパ節の解剖学的特徴の検討

武田航, 堀江佐知子, 森士朗, 小玉哲也

第26回日本がん転移学会学術集会・総会　2017/07/27
解剖学的特徴に基づいたリンパ行性薬剤送達法の開発

武田航, 堀江佐知子, 森士朗, 小玉哲也

第33回日本DDS学会学術集会　2017/07/06
転移リンパ節に対するリンパ行性薬剤送達法の有効性に関する研究

藤井穂乃香, 岡田裕貴, 武田航, 堀江佐知子, 森士朗, 小玉哲也

第33回日本DDS学会学術集会　2017/07/06
リンパ節切除にともなう郭清域外リンパ節ならびに肺での転移性腫瘍細胞の治療を目指す新たなリンパ行性薬剤送達法の開発

大内友貴, 森士朗, 小玉哲也

第33回日本DDS学会学術集会　2017/07/06
Induction of the EPR effect in a mouse model of lung metastasis

Ariunbuyan S, Horie S, Takahashi T, Mori S, Kodama T

第56回日本生体医工学会大会　2017/05/03
転移偽陰性リンパ節に対するマイクロCT画像診断を用いた血管構造解析

石川朝生, 岩村亮, 堀江佐知子, 森士朗, 小玉哲也

第56回日本生体医工学会大会　2017/05/03
転移偽陰性リンパ節に対するMRI・超音波画像診断による腫瘍検出能の評価

菊池凌平, 堀江佐知子, 阪本真弥, 森菜緒子, 森士朗, 小玉哲也

第56回日本生体医工学会大会　2017/05/03
リンパ行性薬剤送達法に対するフルオロウラシル投与の有効性に関する研究

藤井穂乃香, 岡田裕貴, 多田明日香, 堀江佐知子, 森士朗, 小玉哲也

日本超音波医学会第53回東北地方会学術集会　2017/03/12
影高周波超音波と造影マイクロＣＴ画像を用いた超早期転移リンパ節診断法の開発

岩村亮, 加藤茂樹, 堀江佐知子, 森士朗, 小玉哲也

日本超音波医学会第53回東北地方会学術集会　2017/03/11
マイクロ CT を用いた転移リンパ節リングエンハンスメント形成に関する研究

石川朝生, 岩村亮, 堀江佐知子, 森士朗, 小玉哲也

日本機械学会第29回バイオエンジニアリング講演会　2017/01/19
リンパ造影を用いた新たなリンパ節転移診断手法の開発に関する研究

岩村亮, 堀江佐知子, 森士朗, 小玉哲也

日本機械学会第29回バイオエンジニアリング講演会　2017/01/19
MRI を用いた転移リンパ節に対する評価法の検討

菊池凌平, 堀江佐知子, 阪本真弥, 森菜緒子, 森士朗, 小玉哲也

日本機械学会第29回バイオエンジニアリング講演会　2017/01/19
リンパネットワークを利用した転移リンパ節治療法の開発

藤井穂乃香, 岡田裕貴, 多田明日香, 堀江佐知子, 森士朗, 小玉哲也

日本機械学会第29回バイオエンジニアリング講演会　2017/01/19
リンパ行性薬剤送達法の転移リンパ節に対する抗腫瘍効果の評価

岡田裕貴, 藤井穂乃香, 多田明日香, 堀江佐知子, 森士朗, 小玉哲也

日本機械学会第29回バイオエンジニアリング講演会　2017/01/19
転移リンパ節モデルにおけるリンパ節内圧についての検証

武田航, 森士朗, 小玉哲也

日本機械学会第27回バイオフロンティア講演会　2016/10/22
Anti-angiogenic Effects by Vasohibin-1 International-presentation

Horie S, Suzuki Y, Kobayashi M, Kodama T

13th International Conferece on Flow Dynamics　2016/10/10
The Novel Diagnosis Method for Lymph Node Metastasis by Lymphangiography International-presentation

Iwamura R, Mori S, Kodama T

13th International Conferece on Flow Dynamics　2016/10/10
The Novel Evaluation Methods for Metastatic Lymph Node using Intranodal Pressure International-presentation

Takeda K, Mori S, Kodama T

13th International Conferece on Flow Dynamics　2016/10/10
Enhanced permeability and retention (EPR) effect in early stage of lung metastasis

Ariunbuyan S, Horie S, Mori S, Kodama T

第75回日本癌学会学術集会　2016/10/06
Novel diagnosis methods for lymph node metastasis using intranodal pressure（リンパ節内圧を用いたリンパ節転移の新規診断方法）

武田航, 多田明日香, 吉羽正太, 堀江佐知子, 森士朗, 小玉哲也

第75回日本癌学会学術集会　2016/10/06
Development of a novel diagnosis method for lymph node metastasis by lymphangiography（リンパ造影を用いたリンパ節転移の新たな診断法の開発）

岩村亮, 森士朗, 小玉哲也

第75回日本癌学会学術集会　2016/10/06
Observation of tumor progression in metastatic lymph nodes

Yves J. Siril, Horie S, Mori S, Kodama T

第75回日本癌学会学術集会　2016/10/06
Use of a drug with time-dependency by a drug delivery system using lymph network for metastatic lymph nodes（転移リンパ節に対するリンパ行性薬剤送達法を用いた時間依存型抗がん剤の治療効果の検討）

藤井穂乃香, 岡田裕貴, 多田明日香, 堀江佐知子, 森士朗, 小玉哲也

第75回日本癌学会学術集会　2016/10/06
Evaluation of lymphatic drug delivery systems using ultrasound and nano/microbubbles（超音波とナノ・マイクロバブルを用いたリンパ行性薬剤送達法の評価）

吉羽正太, 武田航, 多田明日香, 堀江佐知子, 森士朗, 小玉哲也

第75回日本癌学会学術集会　2016/10/06
Study of drug delivery system via Lymphatic network for the treatment of lymph node metastasis（転移リンパ節に対するリンパネットワークを用いた薬剤送達法の開発に関する研究）

多田明日香, 堀江佐知子, 森士朗, 小玉哲也

第75回日本癌学会学術集会　2016/10/06
Evaluation of a drug delivery system with doxorubicin via lymph vessels using a lymphatic metastasis model mouse（リンパ節転移モデルマウスにおけるドキソルビシンを用いたリンパ行性薬剤送達法の評価）

岡田裕貴, 藤井穂乃香, 多田明日香, 堀江佐知子, 森士朗, 小玉哲也

第75回日本癌学会学術集会　2016/10/06
Anti-tumor effects of BNA-based antisense oligonucleotides targeting Vasohibin-2 on liver cancers（Vasohibin-2 標的性 BNA 修飾アンチセンスオリゴヌクレオチドによる肝臓がんに対する抗腫瘍効果の評価）

堀江佐知子, 鈴木康弘, 小林美穂, 乗田理恵, 小玉哲也, 佐藤靖史

第75回日本癌学会学術集会　2016/10/06
リンパ節介在血行性転移に関する研究

武田航, 森士朗, 阪本真弥, 小玉哲也

日本機械学会2016年度年次大会　2016/09/11
リンパ節転移モデルマウスを用いたリンパ行性薬剤送達法の開発

岡田裕貴, 藤井穂乃香, 多田明日香, 堀江佐知子, 森士朗, 小玉哲也

日本機械学会2016年度年次大会　2016/09/11
Evaluation of EPR effect in the early stages of lymph node metastasis (早期段階におけるリンパ節転移および肺転移のEPR効果)

Ariunbuyan Sukhbaatar, Mamoru Mikada, Sachiko Horie, Shiro Mori, Tetsuya Kodama

日本機械学会2016年度年次大会　2016/09/11
リンパ洞造影に基づくリンパ節転移早期診断の開発

岩村亮, 森士朗, 小玉哲也

日本機械学会2016年度年次大会　2016/09/11
A novel lymphatic treatment method for metastatic lymph node using photothermal therapy with controlled temperature cooling system (光温熱療法と表面冷却による低侵襲加熱法を利用したリンパ節転移治療法の開発)

Adewale O. Oladipo, Oluwatobi S. Oluwafemi, Sandile P. Songca, Shiro Mori, Tetsuya Kodama

日本機械学会2016年度年次大会　2016/09/11
リンパネットワークを利用した薬剤送達法の開発

藤井穂乃香, 多田明日香, 堀江佐知子, 森士朗, 小玉哲也

日本機械学会2016年度年次大会　2016/09/11
二次元ミクロチャンネルでの定常な極低Re数ながれの抵抗係数

藤川俊秀, 江頭竜, 藤川重雄, 小玉哲也, 武田航

日本機械学会2016年度年次大会　2016/09/11
ドラッグデリバリーに係るミクロ管内極低Re数ながれのCFD解析

藤川俊秀, 江頭竜, 藤川重雄, 小玉哲也, 武田航

日本機械学会2016年度年次大会　2016/09/11
Investigation of lymphatic network and cancer metastasis International-presentation

Shao L, Mori S, Kodama T

The 11th International Workshop on Biomaterials in Interface Science　2016/08/30
Activation of lung metastasis after dissection of metastatic lymph node International-presentation

Sukhbaatar A, Shao L, Mori S, Kodama T

The 11th International Workshop on Biomaterials in Interface Science　2016/08/30
Photothermal treatment of metastatic lymph nodes using biocompatible gold nanorods and near-infrared laser light International-presentation

Oladipo A, Oluwafemi O, Songca S, Mori S, Kodama T

The 11th International Workshop on Biomaterials in Interface Science　2016/08/30
Characteristics of intranodal pressure in tumor-bearing lymph node International-presentation

Takeda K, Horie S, Mori S, Kodama T

The 11th International Workshop on Biomaterials in Interface Science　2016/08/30
リンパ行性薬剤送達法の開発

小玉哲也, 加藤茂樹, 武田航, 多田明日香, 吉羽正太, 森士朗

第40回日本リンパ学会総会　2016/06/24
口腔癌の頸部リンパ節転移診断における3 テスラblack-blood MR imagingの有用性について

阪本真弥, 小嶋郁穂, 飯久保正弘, 近藤千裕, 伊藤康一, 青木孝文, 小川武則, 森士朗, 小玉哲也, 笹野高嗣

日本歯科放射線学会第57回学術大会　2016/06/18
3 テスラ black-blood MR imaging が口腔癌患者の頸部リンパ節転移診断に有用であった2 症例

小嶋郁穂, 阪本真弥, 飯久保正弘, 小川武則, 渡邉みか, 大田英揮, 村田隆紀, 森士朗, 小玉哲也, 笹野高嗣

日本歯科放射線学会第57回学術大会　2016/06/18
ソノポレーションを利用したVasohibin-1 遺伝子導入による抗腫瘍効果の評価

堀江佐知子, 鈴木康弘, 小林美穂, 小玉哲也, 佐藤靖史

日本超音波医学会第８９回学術集会　2016/05/27
Simple green synthesis of amino acid functionalised CdTe/CdSe/ZnSe core-multi shell with improved cell viability for cellular imaging International-presentation

The Minerals, Metals & Materials Society (TMS) 145th Annual Meeting and Exhibition　2016/02/14
マイクロ CTを用いた転移リンパ節内の管構造解析

岩村亮, 八巻哲平, 森士朗, 小玉哲也

第２８回バイオエンジニアリング講演会　2016/01/09
マウスリンパ節周囲の循環系に関する研究

武田航, 森士朗, 小玉哲也

第２８回バイオエンジニアリング講演会　2016/01/09
転移リンパ節に対する行性薬剤送達法に関する研究

多田明日香, 吉羽正太, 加藤茂樹, 森士朗, 小玉哲也

第２８回バイオエンジニアリング講演会　2016/01/09
担がんリンパ節へのリンパ行性薬剤送達法に関する研究

吉羽正太, 加藤茂樹, 松木大輔, 森士朗, 小玉哲也

第２８回バイオエンジニアリング講演会　2016/01/09
Vasohibin2標的性BNA修飾アンチセンスオリゴヌクレオチドによる肝がん治療法の開発

堀江佐知子, 鈴木康弘, 小林美穂, 小玉哲也, 小比賀聡, 佐藤靖史

第23回日本血管生物医学会学術集会　2015/12/10
Simple green synthesis of CdTe/CdSe/ZnSe core-multi shell with reduced cytotoxicity for bio imaging International-presentation

Ncapayi Vuyelwa, Oluwafemi Oluwatobi, Songca Sandile, Kodama Tetsuya

4th Nano Today Conference　2015/12/06
Intranodal chemotherapy for tumor-bearing lymph node and its evaluation by using intranodal pressure International-presentation

Takeda K, Mori S, Kodama T

South Africa / Japan Bilateral Sympossium　2015/11/04
Lymphatic Delivery of Exogenous Molecules into Lymph Nodes via Lymphatic Vessels with ano/microbubbles and Ultrasound International-presentation

Yoshiba S, Kato S, Mori S, Kodama T

South Africa / Japan Bilateral Sympossium　2015/11/04
Evaluation Methods of Metastatic Lymph Node and Its Treatment using Intranodal Pressures International-presentation

Takeda K, Mori S, Kodama T

12th International Confefence on Flow Dynamics　2015/10/27
Lymphatic Delivery of Exogenous Molecules into Lymph Nodes via Lymphatic Vessels with ano/microbubbles and Ultrasound International-presentation

Yoshiba S, Kato S, Mori S, Kodama T

12th International Confefence on Flow Dynamics　2015/10/27
Drug Delivery System via Lymphatic Network using Nano/microbubbles and Ultrasound International-presentation

Tada A, Yoshiba S, Kato S, Mori S, Kodama T

12th International Confefence on Flow Dynamics　2015/10/27
Photo-thermal therapy of tumors in lymph nodes using gold nanorods and near-infrared laser light with controlled surface cooling International-presentation

Matsuki D, Okajima J, Komiya A, Mori S, Maruyama S, Kodama T

13th International Symposium on Advanced Biomedical Ultrasound　2015/10/19
Perfusion defect in metastatic lymph node using micro CT International-presentation

Yamaki T, Sakamoto M, Mori S, Shiga K, Kodama T

13th International Symposium on Advanced Biomedical Ultrasound　2015/10/19
Intranodal chemotherapy for tumor-bearing lymph node and its evaluation by using intranodal pressure International-presentation

Takeda K, Mori S, Kodama T

13th International Symposium on Advanced Biomedical Ultrasound　2015/10/19
Lymphatic Delivery of Exogenous Molecules into Lymph Nodes via Lymphatic Vessels with Sonoporation International-presentation

Yoshiba S, Kato S, Mori S, Kodama T

13th International Symposium on Advanced Biomedical Ultrasound　2015/10/19
Visualization of Flow Dynamics in Lymphatic Channels in Lymph Node International-presentation

Tada A, Takeda K, Mori S, Kodama T

13th International Symposium on Advanced Biomedical Ultrasound　2015/10/19
リンパ節転移の新たな診断指標の提案

八巻哲平, 阪本真弥, 森士朗, 志賀清人, 小玉哲也

第74回日本癌学会学術総会　2015/10/08
ドキソルビシン内封リポソームを用いたリンパ節内における薬剤分布に関する研究

吉羽正太, 阪本真弥, 森士朗, 小玉哲也

第74回日本癌学会学術総会　2015/10/08
廓清外リンパ節治療のための超音波と微小気泡を用いたリンパ行性薬剤送達法の開発

多田明日香, 吉羽正太, 武田航, 森士朗, 小玉哲也

第74回日本癌学会学術総会　2015/10/08
フォトサーマル効果と表面冷却による低侵襲加熱法を利用したリンパ節転移治療法の開発

松木大輔, 阪本真弥, 森士朗, 小玉哲也

第74回日本癌学会学術総会　2015/10/08
リンパ節内圧によるリンパ節担癌の進行とその化学療法の評価方法の検討

武田航, 森士朗, 阪本真弥, 小玉哲也

第74回日本癌学会学術総会　2015/10/08
リンパネットワークを介した転移リンパ節の治療法に関する研究

多田明日香, 武田航, 加藤茂樹, 森士朗, 小玉哲也

日本機械学会2015年度年次大会　2015/09/13
ナノ・マイクロバブルと超音波を用いたリンパネットワークによるリンパ節内への高分子導入に関する研究

吉羽正太, 加藤茂樹, 多田明日香, 森士朗, 小玉哲也

日本機械学会2015年度年次大会　2015/09/13
リンパ節内圧を用いたリンパ節内腫瘍の評価とその治療

武田航, 多田明日香, 森士朗, 小玉哲也

日本機械学会2015年度年次大会　2015/09/13
Simple green synthesis of CdTe/CdSe/ZnSe core-multi shell with reduced cytotoxicity for bio imaging. International-presentation

Vuyelwa Ncapayi, Oluwatobi S. Oluwafemi, Sandile P. Songca, Tetsuya Kodama

1st UNIVEN – WSU International Research Conference　2015/09/02
Simple green synthesis of CdTe/CdSe/ZnSe core-multi shell with reduced cytotoxicity for bio imaging International-presentation

Ncapayi V, Oluwafemi S, Songca SP, Kodama T

IUPAC-2015　2015/08/06
Intraymphatic chemotherapy for metastatic lymph node: evaluation by intranodal pressure International-presentation

Takeda K, Mori S, Kodama T

The 10th Anniversary International Workshop on Biomaterials in Interface Science　2015/08/04
Simple green synthesis of water-souble type II CdTe/CdSe nanoparticles and their use in cellular imaging International-presentation

Ncapayi V, Oluwafemi OS, Songca SP, Kodama T

9th international conference of society of free radical research – Africa/ 4th International conference of international association of medical & biomedical researchers　2015/07/27
リンパ行性薬剤投与とソノポレーションによる腫瘍リンパ節治療法開発

加藤茂樹, 森士朗, 阪本真弥, 小玉哲也

第31回日本DDS学会学術集会　2015/07/02
ソノポレーション法によるリンパ球への遺伝子導入

加藤茂樹, 森士朗, 阪本真弥, 小玉哲也

第31回日本DDS学会学術集会　2015/07/02
間質液圧を用いた転移リンパ節に対する抗腫瘍効果の検討

武田航, 吉羽正太, 森士朗, 小玉哲也

第54回日本生体医工学会大会　2015/05/07
リンパ行性薬剤送達法の開発：マウスモデルを用いたリンパ管およびリンパ節内の流れの解明

小玉哲也

第54回日本生体医工学会大会　2015/05/07
Evaluation of Cisplatin-Induced Anti-Tumor Effect with Interstitial Fluid Pressure International-presentation

Takeda K, Ouchi T, Mori S, Kodama T

2015 International Congress on Chemical, Biological and Environmental Sciences (ICCBES)　2015/05/07
Optical and imaging properties of highly luminescent water soluble type II CdTe/CdSe nanoparticles synthesised via a green method International-presentation

Vuyelwa Ncapayi, Oluwafemi Oluwatobi, Sandile Songca, Tetsuya Kodama

TMS 144th Annual Meeting and Exhibition, Walt Disney World　2015/03/15
Lymphatic Adminstration and Soporation Enhanced Antitumor Effects against Tumor-bearing Lymph Node International-presentation

Kato S, Shirai Y, Mori S, Kodama T

The Joint Symposium of 9th International Symposium on Medical, Bio- and Nano-Electronics, and 6th International Workshop on Nanostructures & Nanoelectronics　2015/03/02
Evaluation of chemotherapy for cancer by interstitial fluid pressure International-presentation

Takeda K, Mori S, Kodama T

The Joint Symposium of 9th International Symposium on Medical, Bio- and Nano-Electronics, and 6th International Workshop on Nanostructures & Nanoelectronics　2015/03/02
金ナノロッドと近赤外レーザー光を用いたリンパ節転移治療法の開発

松木大輔, 大内友貴, 阪本真弥, 森士朗, 小玉哲也

日本機械学会第27回バイオエンジニアリング講演会　2015/01/09
リンパ節切除にともなう肺転移を阻害する薬剤送達法の開発

大内友貴, 邵楽南, 松木大輔, 阪本真弥, 森士朗, 小玉哲也

日本機械学会第27回バイオエンジニアリング講演会　2015/01/09
ナノ・マイクロバブルと超音波を用いた疑似転移リンパ節への薬剤送達法の開発

吉羽正太, 加藤茂樹, 白井優子, 寺川貴樹, 森士朗, 小玉哲也

日本機械学会第27回バイオエンジニアリング講演会　2015/01/09
間質液圧を用いたリンパ節転移早期診断法の開発

武田航, 大内友貴, 森士朗, 小玉哲也

日本機械学会第27回バイオエンジニアリング講演会　2015/01/09
マイクロCTを用いた転移リンパ節内の血管構造解析

八巻哲平, 柳沢ゆかり, 阪本真弥, 森士朗, 小玉哲也

日本機械学会第27回バイオエンジニアリング講演会　2015/01/09
Detecting Contrast Agents in Ultrasound Image Sequences for Tumor Diagnosis International-presentation

Noro K, Ito K, Yanagisawa Y, Sakamoto M, Mori S, Shiga K, Kodama T, Aoki T

Asia-Pacific Signal and Information Processing Asscoaition Annual Summit and Conference 2014　2014/12/09
リンパ節転移治療におけるドキソルビシン封入温度感受性リポソームとフォトサーマル療法の併用

松木大輔, 大内友貴, 杉浦鉄宰, 圓山重直, 森士朗, 小玉哲也

分子デリバリー研究会（2014年度研究会：物理と薬学のコラボレーション）　2014/12/05
Optical and cytotoxicity properties of water soluble type II CdTe/CdSe nanoparticles synthesised via a green method International-presentation

Vuyelwa Ncapayi, Samuel. O. Oluwafemi, Sandile .P. Songca, Tetsuya Kodama

Material Research Society (MRS) Fall Meeting　2014/11/30
Optical and biological properties of highly fluorescent CdTe/CdSe nanoparticles synthesized via a facile green method. International-presentation

Vuyelwa Ncapayi, Oluwatobi S Oluwafemi, Sandile P Songca, Tetsuya Kodama

International Symposium on Macro- and Supra-Molecular Architectures and Materials　2014/11/23
キャビテーション援用超音波加熱治療におけるエコー信号の非相関と病理学的観察による組織変性の解析

松浦景子, 高木亮, 柳沢ゆかり, 吉澤晋, 小玉哲也, 梅村晋一郎

第13回日本超音波治療研究会(JSTU 2014)　2014/11/15
リンパ管への薬剤投与とソノポレーションを組み合わせた担がんリンパ節治療

加藤茂樹, 白井優子, 森士朗, 小玉哲也

JSTU2014/超音波分子診断治療研究会共同セッション　2014/11/15
音響性リポソームと超音波を用いたVasohibin-1遺伝子導入による抗血管新生効果の評価

堀江佐知子, 鈴木康弘, 小林美穂, 小玉哲也, 佐藤靖史

JSTU2014/超音波分子診断治療研究会共同セッション　2014/11/15
膵島移植における超音波検査の有効性

坂田直昭, Sax Nicolas, 小玉哲也, 海野倫明

第13回日本超音波治療研究会(JSTU 2014)　2014/11/15
Combined Application of Doxorubicin-Encapsulated Thermosensitive Liposomes and Photothermal Therapy for Treatment of Tumor-Bearing Lymph Nodes International-presentation

Matsuki D, Ouchi T, Mori S, Kodama T

9th East Asian Consortium on Biomedical Engineering　2014/10/11
Diagnosis of Early-stage Lymph Node Metastasis using Interstitial Fluid Pressure International-presentation

Takeda K, Ouchi T, Mori S, Kodama T

9th East Asian Consortium on Biomedical Engineering　2014/10/11
Evalution of Lymph Node Metastasis by Interstitual Fluid Pressure International-presentation

Takeda K, Ouchi T, Kodama T

Eleventh International Conference on Flow Dynamics　2014/10/08
Theoretical and Experimental Studies of Local Heating of Biomedical Tissue for Laser Therapy International-presentation

Sugiura T, Okabe T, Okajima J, Komiya A, Victoria T, Kodama T, Maruyama S

Fourteenth International Symposium on Advanced Fluid Information　2014/10/08
センチネルリンパ節切除後の二次リンパ節転移を予防する薬剤送達法の開発

大内友貴, 松木大輔, 阪本真弥, 森士朗, 小玉哲也

第73回日本癌学会学術総会　2014/09/25
転移リンパ節に対する超音波と微小気泡を利用したリンパ行性薬剤送達法の開発

白井優子, 佐藤琢磨, 阪本真弥, 森士朗, 小玉哲也

第73回日本癌学会学術総会　2014/09/25
マイクロCTを用いた転移リンパ節内の血管構造解析

八巻哲平, 柳沢ゆかり, 阪本真弥, 森士朗, 志賀清人, 小玉哲也

第73回日本癌学会学術総会　2014/09/25
マイクロCTを用いた転移リンパ節内血管構造解析に関する研究

柳沢ゆかり, 八巻哲平, 志賀清人, 阪本真弥, 森士朗, 小玉哲也

第73回日本癌学会学術総会　2014/09/25
抗血管新生効果におけるVasohibin-1AとVasohibin-1Bの役割

堀江佐知子, 鈴木康弘, 小林美穂, 小玉哲也, 佐藤靖史

第73回日本癌学会学術総会　2014/09/25
リンパ節転移治療におけるドキソルビシン封入温度感受性リポソームと光熱療法の併用

松木大輔, 大内友貴, 阪本真弥, 森士朗, 小玉哲也

第73回日本癌学会学術総会　2014/09/25
リンパ行性薬剤投与とソノポレーションによる腫瘍リンパ節の治療

加藤茂樹, 白井優子, 森士朗, 小玉哲也

日本機械学会2014年度年次大会　2014/09/07
Optical and imaging properties of water soluble typeII CdTe/CdSe nanoparticles synthesized via a green method International-presentation

Ncapayi V, Oluwafemi OS, Songca SP, Kodama T

Second International Conference U6 consortium　2014/09/05
Novel antitumor therapy for tumor bearing lymph node by lymphatic administration and sonoporation International-presentation

Kato S, Shirai Y, Morikawa H, Sakamoto M, Mori S, Kodama T

9th International Workshop on Biomaterials in Interface Science　2014/08/26
Development of liposomal drug for prevention of enhanced metastasis after sentinel lymph node removal International-presentation

Ouchi T, Shao L, Matsuki D, Mori S, Kodama T

9th International Workshop on Biomaterials in Interface Science　2014/08/26
センチネルリンパ節切除による転移誘導を予防する薬剤送達法の開発

大内友貴, 邵楽南, 松木大輔, 加藤茂樹, 森士朗, 小玉哲也

第30回日本DDS学会学術集会　2014/07/30
転移リンパ節に対する超音波と微小気泡を利用したリンパ行性薬剤送達法の開発

白井優子, 加藤茂樹, 佐藤琢磨, 森士朗, 小玉哲也

第30回日本DDS学会学術集会　2014/07/30
マイクロCTを用いた転移リンパ節内血管構造解析に関する研究

柳沢ゆかり, 野呂和正, 伊藤康一, 清水良央, 森士朗, 小玉哲也

第30回日本DDS学会学術集会　2014/07/30
動き推定を伴った超音波造影剤の検出手法に関する検討

野呂和正, 伊藤康一, 柳沢ゆかり, 阪本真弥, 森士朗, 志賀清人, 小玉哲也, 青木孝文

電子情報通信学会医用画像研究会　2014/05/22
Study of diagnosis of lymph node metastasis by microCT International-presentation

Yamaki T, Yanagisawa Y, Kochi T, Mori S, Kodama T

Proceedings of 8th Student Workshop East Asia Consortium on Biomedical　2014/03/12
Study of drug delivery to secondary lymph nodes via sentinel lymph nodes International-presentation

Matsuki D, Ouchi T, Sato T, Mori S, Kodama T

Proceedings of 8th Student Workshop East Asia Consortium on Biomedical　2014/03/12
Inhibition of tumor growth in lymph nodes by lymphatic administration od frugs and nano/microbubbles with ultrasound exposure International-presentation

Kato S, Shirai I, Mori S, Kodama T

Proceedings of 8th Student Workshop East Asia Consortium on Biomedical　2014/03/12
Development of drug delivery system to secondary lymph node after sentinel lymph node dissection International-presentation

Ouchi T, Lenan S, Matsuki D, Sato, T, Mori S, Kodama T

Molecular Mechanisms in Lymphatic Function & Disease (GRS), New Frontiers in Lymphatic Research　2014/03/08
Establishment of a lymph node metastasis model using recombinant inbred mice developing lymphnodepathy. International-presentation

Yagishita Y, Mori S, Shao L, Li L, Takahashi T, Kodama T

Innovative Research for Biosis-Abiosis Intelligent Interface Symposium.　2014/01/20
Development of drug delivery system to secondary lymph node after sentineal lymph node dissection International-presentation

Ouchi T, Lenan S, Matsuki D, Sato T, Mori S, Kodama T

Innovative Research for Biosis-Abiosis Intelligent Interface Symposium.　2014/01/20
Study of drug delivery to secondary lymph nodes via sentinel lymph nodes. International-presentation

Matsuki D, Ouchi T, Dato T, Mori S, Kodama T

Innovative Research for Biosis-Abiosis Intelligent Interface Symposium.　2014/01/20
細胞膜透過性ペプチド7R-ETGEによる骨破壊性疾患の阻止

菅崎弘幸, 篠原文明, 加治屋幹人, 小玉哲也

第26回日本機械学会バイオエンジニアリング講演会　2014/01/11
ナノ・マイクロバブルと超音波を用いたVasohibin-1遺伝子導入による抗腫瘍効果の評価

堀江佐知子, 小林美穂, 鈴木康弘, 小玉哲也, 佐藤靖史

第26回日本機械学会バイオエンジニアリング講演会.　2014/01/11
リンパ節郭清後の二次リンパ節転移への薬剤送達法の開発

大内友貴, 邵楽南, 加藤茂樹, 白井優子, 佐藤琢磨, 阪本真弥, 森川秀広, 森士朗, 小玉哲也

第26回日本機械学会バイオエンジニアリング講演会　2014/01/11
造影高周波超音波を用いた血管イメージングの初期リンパ節転移早期診断への応用

竹村知晃, 佐藤琢磨, 加藤茂樹, 阪本真弥, 森士朗, 荒井陽一, 小玉哲也

第26回日本機械学会バイオエンジニアリング講演会　2014/01/11
リンパ節転移の超早期の診断・治療法の開発

第7回次世代を担う若手医療薬科学シンポジウム　2013/11/23
リンパ節転移の超早期の診断・治療法の開発

東北大学電気・情報東京フォーラム　2013/11/21
超音波とナノマイクロバブルを用いたリンパ節転移の早期診断とDDS

第53回日本癌治療学会学術会　2013/10/24
リンパ節転移早期診断のための間質液圧特性に関する研究

三浦由宣, 三ヶ田護, 阪本真弥, 森士朗, 小玉哲也

第72回日本癌学会学術総会　2013/10/03
スプライシングバリアントVasohibin-1B の抗腫瘍効果

堀江佐知子, 鈴木康弘, 小林美穂, 小玉哲也, 佐藤靖史

第72回日本癌学会学術総会　2013/10/03
超音波とナノバブルを利用したリンパ節への分子導入法の開発

白井優子, 加藤茂樹, 菅崎弘幸, 森士朗, 小玉哲也

日本機械学会2013年度年次大会　2013/09/08
リンパ行性薬剤送達法におけるリンパ管内の薬剤動態の観察

畠山友梨子, 加藤茂樹, 阪本真弥, 森士朗, 小玉哲也

日本機械学会2013年度年次大会　2013/09/08
超音波画像診断のための高精度造影剤検出手法の検討

野呂和正, 柳沢ゆかり, 伊藤康一, 阪本真弥, 森士朗, 志賀清人, 小玉哲也, 青木孝文

平成25年度電気関係学会東北支部連合大会　2013/08/22
超音波画像診断のための造影剤検出手法とその性能評価

野呂和正, 柳沢ゆかり, 伊藤康一, 阪本真弥, 森士朗, 志賀清人, 小玉哲也, 青木孝文

精密工学会画像応用技術専門委員会　2013/08/19
超音波画像診断のための高精度造影剤検出手法の検討

伊藤康一, 阪本真弥, 森士朗, 志賀清人, 小玉哲也, 青木孝文

電子情報通信学会医用画像研究会　2013/07/18
リンパ節転移モデルマウスと

第29回日本DDS学会　2013/07/04
ERP効果による近赤外線蛍光粒子封リポソームの腫瘍集積性に関する研究

三ヶ田護, Nicolas S, 阪本真弥, 森士朗

第29回日本DDS学会　2013/07/04
Temporal and steady state acoustic field in a cell culture well: simulation International-presentation

ChoiMJ, Kang SK, Kodama T, Coleman AJ

The 35th Annual International IEEE EMBS. Conference of the IEEE Engineering in Medicine and Biology　2013/07/03
造影高周波超音波を用いた初期リンパ節転移早期診断法の検討

竹村知晃, 佐藤琢磨, 加藤茂樹, 阪本真弥, 森士朗, 荒井陽一, 小玉哲也

日本超音波医学会第86回学術集会　2013/05/24
転移リンパ節モデルへの微小気泡と超音波をもちいたドラッグデリバリーに関する研究

佐藤琢磨, 竹村知晃, 加藤茂樹, 森士朗, 荒井陽一, 小玉哲也

日本超音波医学会第86回学術集会　2013/05/24
Molecualr delivery into lymph nodes using ultrasound and nano bubbles International-presentation

Shirai Y, Kato S, Kanzaki H, Mori S, Kodama T

The 6th East Asian Pacific Student Workshop on Nano-Biomedical Engineering　2013/03/24
超音波と微小気泡によるリンパ管を介したリンパ節内細胞への外来分子導入法の開発

加藤茂樹, 白井優子, 佐藤琢磨, 菅崎弘幸, 本園千尋, 宮澤正顯, 森士朗, 小玉哲也

日本超音波医学会東北地方会第45回学術集会　2013/03/10
Lymphatic drainage routes mapping in a novel experimental lymph metastasis model of mice.

Shao L, Okuno T, Hatakeyama Y, Kato S, Mori S, Kodama T

第71回日本癌学会学術総会　2012/09/19
二光子顕微鏡をもちいたEPR効果による腫瘍内ナノ粒子流出特性の観察

三ヶ田護, サックスニコラ, 阪本真弥, 森士朗, 小玉哲也

第71回日本癌学会学術総会　2012/09/19
Pressure-driven flow characteristics in the lymphatic vessel for lymphatic drug delivery ststem International-presentation

Hatakeyama Y, Sax N, Kato S, Okuno T, Sakamoto M, Nori S, Kodama T

The 9th International Conference on Flow Dynamics　2012/09/19
Cancer treatment via the lymphatic vessel using nano/microbubbles International-presentation

Kato S, Nicolas S, Hatakeyama Y, Okuno T, Mori S, Sakamoto M, Kodama T

The 9th International Conference on Flow Dynamics　2012/09/19
Thermal therapy using plasmonic nano particles for lymph node metastasis International-presentation

Okuno T, Kato S, Hatakeyama Y, Sato T, Sakamoto M, Mori S, Kodama T

The 9th International Conference on Flow Dynamics　2012/09/19
リンパ行性薬剤送達システムの開発

畠山友梨子, 李麗, サックスニコラ, 奥野竜希, 加藤茂樹, 阪本真弥, 森士朗, 小玉哲也

日本機械学会2012年度年次大会　2012/09/09
腫瘍の成長にともなう鼠径リンパ節内の間質液圧特性に関する研究

三浦由宣, 畠山友梨子, 阪本真弥, 森士朗, 小玉哲也

日本機械学会2012年度年次大会　2012/09/09
腫瘍移植とEPR効果に関する研究

三ヶ田護, サックスニコラ, 阪本真弥, 森士朗, 小玉哲也

日本機械学会2012年度年次大　2012/09/09
超音波作用による寒天近傍でのソナゾイドの破壊と気泡のダイナミックス

冨田幸雄, 田仲慈訓, 岡田昭, 小玉哲也

日本機械学会2012年度年次大会　2012/09/09
Characteristics of Sonazoid destruction and bubble motion caused by focused ultrasound International-presentation

Tomita Y, Tanaka N, Kodama T

The 8th International Symposium on Cavitation　2012/08/14
Drug delivery system with acoustic liposomes via the lymphatic vessels

Kato S, Horie S, Sakamoto M, Mori S, Kodama T

The 8th International Symposium on Cavitation　2012/08/14
金ナノロッドを用いたフォトサーマル療法のリンパ節転移への応用

奥野竜希, サックスニコラ, 加藤茂樹, 畠山梨友子, 小玉哲也

第28回日本DDS学会　2012/07/04
リンパ行性薬剤送達システム開発のためのリンパ節およびリンパ管内の流動特性

畠山梨友子, サックスニコラ, 奥野竜希, 森士朗, 阪本真弥, 小玉哲也

第28回日本DDS学会　2012/07/04
Nrf2 negatively regulates osteoclast differentiation International-presentation

Kanzaki H, Kajiya M, Kodama T

IADR, General Session　2012/06/20
Fluid dynamics in the afferent lymphatic International-presentation

Hatakeyama Y, Kodama T

International Symposium of Biomedical Engineering　2012/06/14
Drug delivery system with acoustic liposomes via the lymphatic vessels International-presentation

Kato S, Kodama T

International Symposium of Biomedical Engineering　2012/06/14
Biophysical characteristics of acoustic liposome International-presentation

Nicolas S, Kodama T

International Symposium of Biomedical Engineering　2012/06/14
Plasmonic photo-thermal therapy for lymph node metastasis International-presentation

Okuno T, Kodama T

International Symposium of Biomedical Engineering　2012/06/14
Flow Characteristics of the Lymphatic Flow to the Axillary Lymph Node driven by Increasing Pressures in the Inguinal Lymph Node International-presentation

Hatakeyama Y, Nicolas S, Li L, Kato S, Okuno T, Miura Y, Shao L, Sakamoto M, Mori S, Fujikawa S, Kodama T

Medical Physics and Biomedical Engineering　2012/05/26
Lymphatic network mapping in a novel lymph node metastasis model of mice International-presentation

Shao L, Okuno T, Hatakeyama Y, Kato S, Mori S, Kodama T

Medical Physics and Biomedical Engineering　2012/05/26
Effects of the liposomal formuilation on the behavior and physical characteristics of acoustic liposomes International-presentation

Sax N, Horie S, Li L, Li S, Kochi T, Chen R, Watanabe Y, Yagishita Y, Sakamoto M, Mori S, Kodam T

The 19th International Symposium on Nonliner Acoustics　2012/05/21
膵島移植医療に有用な各種画像モダリティの使用法の確立に向けて

坂田直昭, 吉松軍平, Hathout, 小玉哲也, 江川, 力山, 陳,石田, 土屋朗之, 後藤昌史, 海野倫明

第112回日本外科学会定期学術集会　2012/04/12
高周波超音波検査による異種膵島の移植後急性期変化

坂田直昭, 小玉哲也, 吉松軍平, 石田晶玄, 土屋朗之, 後藤昌史, 海野倫明

第39回日本膵・膵島移植研究会　2012/03/09
Development of Drug Delivery System Via Lymphatic Metastases Using Ultrasound And Nano/Micro Bubbles International-presentation

The 6th International Symposium on Medical, Bio-and Nano-Electronics　2012/03/08

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Kato S, Nicolas S, Horie S, Sato T, Kochi K, Hatakeyama Y, Okuno T, Mori S, Kodama T
Delivery of gold nanorods via a single lymphatic vessel International-presentation

Okuno T, Horie S, Sax N, Kochi T, Sato T, Kato S, Hatakeyama Y, Mori S, Kodama T

The 6th International Symposium on Medical, Bio-and Nano-Electronics　2012/03/08
Real-time Observation of Lymphatic Flow Characteristics International-presentation

Hatakeyama Y, Nicolas.S, Kato S, Okuno T, Kochi T, Sato T, Mori S, Kodama T

The 6th International Symposium on Medical, Bio-and Nano-Electronics　2012/03/08
Optimization of Acoustic Liposomes for improved in vivo stability International-presentation

Sax N, Kodama T

The 6th International Symposium on Medical, Bio-and Nano-Electronics　2012/03/08
近赤外線レーザー光とターゲット金ナノロッドを用いたリンパ節転移治療法の開発

奥野竜希, 堀江佐知子, Sax Nicolas, 小玉哲也

日本機械学会第24回バイオエンジニアリング部門講演会　2012/01/07
鼠径リンパ節内の圧力上昇にともなう輸出リンパ管への流出特性

畠山友梨子, 李麗, サックスニコラ, 阪本真弥, 森士朗, 小玉哲也

第70回日本癌学会学術総会　2011/10/03
Characteristics of the flow to the efferent lymphatic vessel upon increased pressure in the groin lymph node International-presentation

Hatakeyama Y, Kodama T

Joint Research Program with Korea　2011/09/26
Study of a highly accurate analysis technique with high frequency ultrasound International-presentation

Sato S, Kodama T

Joint Research Program with Korea　2011/09/26
Development of an exogeneous molecular delivery system into the lymph node via lymphatic vessel International-presentation

Kato S, Kodama T

Joint Research Program with Korea　2011/09/26
Treatment of lymph node metastasis with NIR-laser beams and nano partciles International-presentation

Okuno T, Kodama T

Joint Research Program with Korea　2011/09/26
鼠径リンパ節内の圧力上昇にともなう輸出リンパ管への流出特性

畠山友梨子, 小玉哲也

日本機械学会2011年度年次大会　2011/09/11
集束超音波によるソナゾイドの破壊と気泡生成

冨田幸雄, 田仲慈訓, 小玉哲也

日本機械学会2011年度年次大会　2011/09/11
ナノバブルと超音波を使用した分子導入法とPETによる分子イメージング

小玉哲也

第27回日本DDS学会　2011/06/09
頭頸部癌遺伝子治療に向けたナノバブルと超音波によるNIS 遺伝子導入と124I-PET イメージング

渡邊夕紀子, 森士朗, 堀江佐知子, サックスニコラ, 李麗, 李深偉, 柳下陽子, 髙地崇, 船木善仁, 菊池洋平, 山崎浩道, 石井慶造, 阪本真弥, 宮下仁, 小玉哲也

第35回日本頭頸部癌学　2011/06/09
頭頸部癌所属リンパ節転移の診断・治療に向けたリンパ節腫大マウスを用いたリンパ節転移モデルの開発

李麗,森士朗, 柳下陽子, サックスニコラ, 堀江佐知子, 渡邊夕紀子, 高地崇, 李深偉, 宮下仁, 森川秀広, 阪本真弥, 小玉哲也

第35回日本頭頸部癌学　2011/06/09
超音波とナノバブルを使用した遺伝子導入法およびPETを使用した遺伝子発現の可視化法の開発

渡邊夕紀子, 堀江佐知子, 船木善仁, 菊地洋平, 山崎浩道, 石井慶造, 森士朗, 小玉哲也

第50回日本生体医工学会大会プログラム　2011/04/29
超音波検査による移植膵島の機能評価

坂田直昭, 小玉哲也, 陳鋭, 吉松軍平, 後藤昌史, 江川新一, 海野倫明

第38回日本膵・膵島移植研究会　2011/03/04
気泡と波動の, 私の医工学研究

小玉哲也

第21回東北大学形成外科同門会学術集会　2011/02/19
ナノバブルと二重超音波を用いた膀胱がん治療の基礎研究

堀江佐知子, 小玉哲也

第15回キャビテーションシンポジウム　2010/11/22
集束超音波によるキャビテーションの生成と噴霧形成

冨田幸雄, 下村文吾, 皆川隆一郎, 小玉哲也

第15回キャビテーションシンポジウム　2010/11/22
マイクロバブル造影剤と超音波を用いた頭頸部癌症例の頸部リンパ節転移の検討

天野雅紀, 志賀清人, 加藤健吾, 小川武則, 小林俊光, 小玉哲也, 阪本真弥

第48回日本癌治療学会学術集会　2010/10/28
口腔癌早期診断のためのナノバブルと高周波超音波による腫瘍血管構築画像の病理学y的評価

柳下陽子, 森士朗, 高田陽子, 大木宏介, 宮下仁, 森川秀広, 川村仁, 小玉哲也

第55回日本口腔外科学会　2010/10/16
ナノバブルと高周波超音波による腫瘍血管構築とVEGFの発現に関する分子学的検討

宮下仁, 森士朗, 柳下陽子, 高田陽子, 大木宏介, 川村仁, 森川秀広, 小玉哲也

第55回日本口腔外科学会プログラム　2010/10/16
ナノ・マイクロバブルと超音波を用いた口腔癌の遺伝子治療法を想定した分子導入法の検討

大木宏介, 森士朗, 宮下仁, 川村仁, 小玉哲也

第55回日本口腔外科学会プログラム　2010/10/16
マイクロバブルと高周波超音波を用いた三次元イメージング法による転移リンパ節の血管密度の評価

佐藤祥太, 李麗, 柳下陽子, 阪本真弥, 高橋昭喜, 森士朗, 小玉哲也

日本超音波医学会東北地方会第40回学術集会　2010/09/26
音響性リポソームの減衰特性における実験的かつ論理的解析

小島貴則, 藤川重雄, 小玉哲也

日本超音波医学会東北地方会第40回学術集会　2010/09/26
膀胱がん治療に向けた二重超音波照射法の数値的至適化

小島貴則, 堀江佐知子, 渡邊夕紀子, 陳鋭,李麗, 阪本真弥, 森士朗, 小玉哲也

第69回日本癌学会学術総会　2010/09/22
がん遺伝子治療に向けた新しいPETレポーター/治療遺伝子の開発

渡邊夕紀子, 児玉栄一, 堀江佐知子, 髙地崇, サックス・ニコラ, 柳下陽子, 陳鋭, 李麗, 服部俊夫, 森士朗, 小玉哲也

第69回日本癌学会学術総会　2010/09/22
ナノバブルと超音波を用いたTNF-alpha遺伝子導入による抗腫瘍効果の評価

堀江佐知子, 渡邊夕紀子, 小島貴則, 陳鋭,李麗, 柳下陽子, サックス・ニコラ, 阪本真弥, 森士朗, 小玉哲也

第69回日本癌学会学術総会　2010/09/22
In vivo detection of cancer metastases at an early stage by vessel density with ultrasound and nano/microbubbles

陳鋭, 千葉美麗, 森士朗

第52回歯科基礎医学会学術大会・総会　2010/09/20
PET visualization of Na/I symporter gene expression after delivery by nanobubbles and ultrasound International-presentation

Watanabe Y, Horie S, Funaki Y, Kikuchi Y, Yamazaki H, Ishii K, Mori S, Vassaux G, Kodama T

2010 World Molecular Imaging Congress　2010/09/08
Longitudinal three-dimensional noninvasive imaging analysis and quantification of anti-tumor effects of TNF-alpha gene for small tumor International-presentation

Horie S, Watanabe Y, Yagishita Y, Nicolas S, Chen R, Li L, Kojima T, Sakamoto M, Ono M, Mori S, Kodama T

2010 World Molecular Imaging Congress　2010/09/08
長期安定蛍光リポソームの開発

サックスニコラ, 堀江佐知子, 渡邊夕紀子, 森士朗,陳, 小玉哲也

日本機械学会2010年度年次大会　2010/09/05
Visualization of Microcirculation Based on Brightness Variation in Contrast-Enhanced Ultrasound International-presentation

Funamoto K, Hayase T, Kodama T

The 2010 Summer Bioengineering Conference, ASME　2010/06/16
歯肉癌の遺伝子治療のためのナノ・マイクロバブルと超音波を用いた分子導入法の検討

陳鋭, 森士朗, 千葉美麗, 福本学, 小玉哲也

第34回日本頭頸部癌学会　2010/06/10
口腔癌早期診断のためのナノバブルと高周波超音波を用いた画像診断法に関する組織学的検討

柳下陽子, 森士朗, 李麗, 渡邊夕紀子, 堀江佐知子, 冨田典子, 陳鋭, 高田陽子, 大木宏介, 小玉哲也

第34回日本頭頸部癌学会　2010/06/10
Four-Dimensional high - frequency ultrasound imaging system for early detection of lymph node micro-metastasis International-presentation

Li L, Horie S, Rui CHEN, Watanabe Y, Baba T, Sax N, Sakamoto M, Mori S, Takahashi S, Kodama T

The 5th International Symposium onMedical,Bio- and Nano-Electronics　2010/02/24
Volumetric and angiogenetic imaging system by using nanobubbles and high-frequency ultrasound for evaluation of the antitumor effect by cisplatin International-presentation

Yagishita Y, Takata Y, Ohki K, Miyashita H, Morikawa H, Sakamoto M, Mori S, Kawamura H, Kodama T

The 5th International Symposium onMedical,Bio- and Nano-Electronics　2010/02/24
PET imaging of Na/I symporter gene expression International-presentation

Watanabe Y, Horie S, Funaki Y, Kikuchi Y, Yamazaki H, Ishii K, Mori S, Kodama T

The 5th International Symposium onMedical,Bio- and Nano-Electronics　2010/02/24
Targeted Gene Delivery using nanobubble and ultrasound International-presentation

Horie S, Watanabe Y, Chen R, Mori S, Matsumura Y, Kodama T

The 5th International Symposium onMedical,Bio- and Nano-Electronics　2010/02/24
Ultrasound molecular imaging of lymph node metastasis with nano/microbubbles. International-presentation

Li L, Chen R, Horie S, Watanabe Y, Baba T, Sax N, Sakamoto M, Mori S, Takahashi S, Kodama T

International Symposium of AIDS and Tuberculosis (ISAT2010)　2010/01/13
Physical characterization of acoustic liposomes. International-presentation

Sax N, Horie S, Li L, Chen R, Watanabe Y, Mori S, Kodama T

International Symposium of AIDS and Tuberculosis (ISAT2010)　2010/01/13
Three-dimentional High-Frequency Ultrasound Imaging for early diagnosis of lymph node metastasis Combined with Microbubbles. International-presentation

Li L, Horie S, Chen R, Watanabe Y, Sakamoto M, Mori S, Takahashi S, Kodama T

The 3rd East Asian Pacific Student Workshop on Nano-Biomedical Engineering　2009/12/21
ナノバブルと超音波を用いた遺伝子治療法の開発：遺伝子発現イメージング法の新技術

小玉哲也

東北大学イノベーションフェア　2009/10/14
ナノバブルを用いた超音波によるリンパ節転移早期診断システムの開発

東北大学イノベーションフェア　2009/10/14
口腔癌治療のためのナノバブルと超音波を用いた抗腫瘍効果増強法に関する検討

宮下仁, 森士朗, 高田陽子, 大木宏介, 川村仁, 森川秀広, 小玉哲也

日本口腔外科学会　2009/10/09
ナノバブルを用いた高周波超音波診断装置の遠隔地口腔癌診断への応用.

森士朗, 高田陽子, 大木宏介, 宮下仁, 川村仁, 森川秀広, 小玉哲也

日本口腔外科学会　2009/10/09
ナノバブルと超音波を用いた高周波超音波診断装置による微小転移検出に関する検討

大木宏介, 森士朗, 高田陽子, 宮下仁, 川村仁, 森川秀広, 小玉哲也

日本口腔外科学会　2009/10/09
超音波分子イメージングによるリンパ節転移早期診断法の開発.

李麗, 堀江佐知子, 陳鋭, 渡邊夕紀子, 阪本真弥, 森士朗, 小玉哲也

第68回日本日本癌学会学術総会　2009/10/01
表在性膀胱がんに対する膀胱内注入遺伝子療法.

藤澤優, 鈴木亮, 丸山一雄, 小玉哲也, 安永浩, 松村保広

第68回日本日本癌学会学術総会　2009/10/01
発ガンリスクが高い血液透析患者の遺伝子発現解析.

馬場泰輔, 澤井恒治, 小玉哲也, 一石英一郎

第68回日本日本癌学会学術総会　2009/10/01
前臨床試験を目指した肝転移モデルの非侵襲的観察.

陳鋭, 渡邊夕紀子, 堀江佐知子, 森士朗, 福本学, 小玉哲也

日本機械学会2009年度年次大会講演　2009/09/13
表在性膀胱がんに対する薬剤送達法の開発.

堀江佐知子, 渡邊夕紀子, 陳鋭, 李麗, 森士朗, 小玉哲也

日本機械学会2009年度年次大会講演　2009/09/13
Microbubble disruption by ultrasound and induced cavitation phenomena International-presentation

Tomita Y, Uchikoshi R, Inada T, Kodama T

Proceedings of the 7th International Symposium on Cavitation,CAV2009　2009/08/15
超音波の作用によるマイクロバブルの破壊とキャビテーション気泡の挙動.

冨田幸雄, 打越亮介, 稲葉拓也, 小玉哲也

日本混相流学会年会講演会 2009　2009/08/07
Molecular delivery system by nanobubbles and ultrasound International-presentation

International Symposium on HIV/AIDS, Medicinal Plants and Geophagia, Advancing the frontiers of Research on HIV/AIDS　2009/07/22
ナノバブルと高周波超音波を用いた血管抽出法の開発.

第25回日本DDS学会　2009/07/03
ナノバブルを用いた超音波によるリンパ節転移早期診断システムの研究開発.

李麗, 堀江佐知子, 陳鋭, 渡邊夕紀子, 阪本真弥, 森士朗, 高橋昭喜, 小玉哲也

第25回日本DDS学会　2009/07/03
124Iを使用したNIS遺伝子発現イメージング法の開発：超音波とナノバブルを利用した遺伝子デリバリー.

渡邊夕紀子, 堀江佐知子, 陳鋭, 李麗, 船木善仁, 菊地洋平, 酒巻学, 山崎浩道, 石井慶造, 森士朗, 小玉哲也

第25回日本DDS学会.　2009/07/03
超音波分子イメージング法による新しいリンパ節転移早期診断法の開発.

李麗, 堀江佐知子, 陳鋭, 渡邊夕紀子, 森士朗, 阪本真弥, 小野栄夫, 高橋昭喜, 小玉哲也

第6回東北大学バイオサイエンスシンポジウムおよび第14回学際ライフサイエンスシンポジウム　2009/06/16
音響照射圧を用いたターゲッティング分子導入法の開発.

堀江佐知子, 渡邊夕紀子, 陳鋭, 李麗, 森士朗, 小玉哲也

第6回東北大学バイオサイエンスシンポジウムおよび第14回学際ライフサイエンスシンポジウム　2009/06/16
ナノバブルと超音波を利用した遺伝子導入法：マウスを使用したPETによる遺伝子発現の可視化.

渡邊夕紀子, 堀江佐知子, 陳鋭, 李麗, 船木善仁, 菊地洋平, 酒巻学, 山崎浩道, 石井慶造, 森士朗, 小玉哲也

第6回東北大学バイオサイエンスシンポジウムおよび第14回学際ライフサイエンスシンポジウム　2009/06/16
Visualization of NIS gene expression using Fine-PET.

渡邊夕紀子, 小玉哲也

第1回半導体PETカメラワークショップ/ユーザーズミーティング　2009/04/25
表在性膀胱がんへの遺伝子治療法の開発.

堀江佐知子, 渡邊夕紀子, 陳鋭, 李麗, 森士朗, 小玉哲也

第48回日本生体医工学会大会　2009/03/23
リンパ節転移早期診断に関する三次元高周波超音波イメージング.

李麗, 堀江佐知子, 陳鋭, 渡辺夕紀子, 阪本真弥, 高橋昭喜, 森士朗, 小玉哲也

日本超音波医学会東北地方会第37回学術集会　2009/03/15
表在性膀胱がんに対する新しい遺伝子治療法の開発.

堀江佐知子, 渡邊夕紀子, 陳鋭, 李麗, 森士朗, 小玉哲也

日本超音波医学会東北地方会第37回学術集会　2009/03/15
ナノバブルと超音波を用いた高周波超音波三次元画像診断・分子導入システムの開発

小玉哲也

平成20年度厚生労働科学研究費研究成果等普及啓発事業医療機器開発推進研究ナノメディシン研究成果発表会　2009/02/25
ナノバブルと超音波を利用した診断・治療システムの開発

第11回癌治療増感研究シンポジウム　2009/02/14
ナノバブルと超音波を用いた高周波超音波三次元画像診断・分子導入システムの開発

小玉哲也

ナノバイオテクノロジー連携群成果報告会　2009/01/28
ナノバブルを用いたリンパ節転移診断に関する三次元高周波超音波イメージング法の開発.

李麗, 冨田典子, 森士朗, 大澤ふき, 堀江佐知子, 陳鋭, 渡辺タ紀子, 阪本真弥, 高橋昭喜, 小玉哲也

日本機械学会第21回バイオエンジニアリング講演会　2009/01/23
高周波超音波を用いたリンパ節早期転移の画像診断システムの開発.

李麗, 冨田典子, 森士朗, 大澤ふき, 堀江佐知子, 渡邊夕紀子, 陳鋭, 阪本真弥, 高橋昭喜, 小玉哲也

第42回日本生体医工学会東北支部大会講演　2008/12/13
半導体PETによるSodium iodide Sympoter (NIS) 遺伝子発現の可視化：ナノバブルと超音波を利用した遺伝子導入法.

渡邊夕紀子, 堀江佐知子, 冨田典子, 大澤ふき, 船木善仁, 菊池洋平, 酒巻学, 山崎浩道, 石井慶造, 森士朗, 小玉哲也

第29回サイクロトロン共同利用実験研究報告会　2008/11/17

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28頁.
Development of diagnostic imaging system for regional lymph node micrometastasis with high-frequency ultrasound. International-presentation

Tomita N, Horie S, Oosawa F, Rui C, Watanabe Y, Morikawa H, Ohki K, Fukumoto M, Mori S, Kodama T

2008 IEEE International Ultrasonics Symposium　2008/11/02

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Abstract Book p.388.
Contrast-Enhanced High-Frequency Ultrasound Imaging of Liver Metastases in preclinical models. International-presentation

Chen R, Tomita N, Baba T, Oosawa F, Watanabe Y, Horie S, Mori S, Fukumoto M, Kodama T

2008 IEEE International Ultrasonics Symposium　2008/11/02

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Abstract Book p.391.
Local gene delivery system of nano/microbubbles-enhanced ultrasound aimed for treatment of gingival tumor International-presentation

Chiba M, Watanabe Y, Horie S, Tomita N, Fukumoto M, Mori S, Kodama T

2008 International Conference on Frontiers of Dental and Craniofacial Research　2008/11/01
Local gene delivery system of nano/microbubbles-enhanced ultrasound aimed for treatment of gingival tumor. International-presentation

Chen R, Chiba M, Watanabe Y, Horie S, Tomita N, Fukumoto M

2008 International Conference on Frontiers of Dental and Craniofacial Research.　2008/11/01
高周波超音波イメージングシステムを用いた所属リンパ節転移画像診断システムの開発.

冨田典子, 堀江佐知子, 大澤ふき, 陳鋭, 渡邊夕紀子, 森川秀広, 大木宏介, 森士朗, 小玉哲也

第46回日本癌治療学会総会.　2008/10/30
ナノバブルと超音波を用いた膀胱がんへの遺伝子導入法の開発.

堀江佐知子, 渡邊夕紀子, 陳鋭, 冨田典子, 大澤ふき, 小野栄夫, 福本学, 藤澤優, 松村保広, 森士朗, 小玉哲也

第46回日本癌治療学会総会　2008/10/30
膀胱がん治療のための新しい薬剤到達法の開発.

堀江佐知子, 渡邊夕紀子, 陳鋭, 冨田典子, 大澤ふき, 小野栄夫, 福本学, 藤澤優, 松村保広, 森士朗, 小玉哲也

第67回日本癌学会学術総会　2008/10/28
ナノバブルを用いた肝転移診断に関する三次元高周波超音波イメージング

陳鋭, 冨田典子, 馬場泰輔, 大澤ふき, 渡邊夕紀子, 堀江佐知子, 森士朗, 福本学, 小玉哲也

第67回日本癌学会学術総会.　2008/10/28
癌疼痛緩和およびPETによるイメージング.

渡邊夕紀子, 堀江佐知子, 冨田典子, 陳鋭, 大澤ふき, 船木善仁, 菊池洋平, 山崎浩道, 石井慶造, 小野栄夫, 福本学, 森士朗, 小玉哲也

第67回日本癌学会学術総会　2008/10/28
高周波超音波を利用した新しいリンパ節内微小転移診断システムの開発.

冨田典子, 堀江佐知子, 大澤ふき, 陳鋭, 渡邊夕紀子, 森川秀広, 大木宏介, 福本学, 森士朗, 小玉哲也

第67回日本癌学会学術総会　2008/10/28
表在性膀胱がんに対する膀胱内注入遺伝子治療.

藤澤優, 鈴木亮, 丸山一雄, 小玉哲也, 安永正浩, 松村保広

第67回日本癌学会学術総会.　2008/10/28

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Proceedings p.356.
各種疾患マウス前脛骨筋でのPETによるNIS遺伝子発現の可視化.

渡邊夕紀子, 堀江佐知子, 冨田典子, 大澤ふき, 船木善仁, 菊池洋平, 中村賢治, 中沢浩一, 山崎弘道, 石井慶造, 福本学, 森士朗, 小玉哲也

第48回日本核医学会学術総会　2008/10/24
Peeling off Effect and Damage Pit Formation by Ultrasonic Cavitation International-presentation

The International Conference on Hydraulic Machinery and Equipments　2008/10/16
Peeling off effect and damage pit formation by ultrasonic cavitation. International-presentation

Tomita Y, Inaba T, Uchikoshi R, Kodama T

The International Conference on Hydraulic Machinery and Equipments　2008/10/16
ナノ・マイクロバブルと超音波によるシスプラチンの抗腫瘍効果の増強.

渡邊夕紀子, 堀江佐知子, 冨田典子, 大澤ふき, 森士朗, 小玉哲也

日本超音波医学会第36回東北地方会学術集会　2008/09/21
Bladder cancer therapy using nanobubbles and two different intensities of ultrasound. International-presentation

Horie S, Watanabe Y, Chen R, Tomita N, Oosawa F, Fujisawa S, Ono M, MFukumoto M, Mori S, Matsumura Y, Kodama T

The 2008 Nanomedicine Conference.　2008/09/19

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Program, p5.
ソノポレーション法を用いたプラナリアへの高分子物質導入法.

原田千明, 藤原綾二, 江本佑貴, 小玉哲也, 杉山友康

日本生物工学会年会　2008/08/27
マウス骨格筋でのNa/I symporter (NIS)遺伝子発現の可視化.

渡邊夕紀子, 堀江佐知子, 冨田典子, 大澤ふき, 陳鋭, 船木善仁, 菊池洋平, 山崎浩道, 石井慶造, 森士朗, 小玉哲也

日本機械学会2008年度年次大会講演　2008/08/03
歯周組織への遺伝子導入を目指した新しい非ウイルス法の開発.

陳鋭, 千葉美麗, 渡邊夕紀子, 堀江佐知子, 冨田典子, 林治秀, 福本学, 森士朗, 小玉哲也

日本実験力学会2008年度年次講演会.日本実験力学会講演　2008/06/30
ナノバブル超音波システムを用いた抗癌剤および抗腫瘍分子導入による新たな癌治療法の開発.

宮下仁, 森士朗, 冨田典子, 堀江佐知子, 渡邊夕紀子, 陳鋭, 大澤ふき, 佐久間基成, 大木宏介, 川村仁, 森川秀広, 小玉哲也

第32回日本頭頸部癌学会/第29回頭頸部手術技研究会　2008/06/11
口腔癌の診断・治療のためのナノバブルと超音波を用いた画像診断・分子導入システムの開発.

森士朗, 渡邊夕紀子, 堀江佐知子, 冨田典子, 陳鋭, 大澤ふき, 佐久間基成, 大木宏介, 宮下仁, 川村仁, 森川秀広, 小玉哲也

第32回日本頭頸部癌学会/第29回頭頸部手術技研究会　2008/06/11
ナノバブルを用いた腫瘍血管造影法による口腔癌早期診断システムモデルの開発.

大木宏介, 森士朗, 堀江佐知子, 冨田典子, 渡邊夕紀子, 陳鋭, 大澤ふき, 佐久間基成, 宮下仁, 川村仁, 森川秀広, 小玉哲也

第32回日本頭頸部癌学会/第29回頭頸部手術技研究会　2008/06/11
高周波超音波イメージングシステムによるシスプラチン抗腫瘍効果の定量化

小玉哲也, 渡邊夕紀子, 堀江佐知子, 冨田典子, 大澤ふき, 佐久間基成, 陳鋭, 大木宏介, 森川秀広, 森士朗, 小野栄夫

第46回日本生体医工学会大会　2008/05/08
Management of Infectious Diseases- From traditional to innovative techniques. International-presentation

South Africa-Japan Universities Forum (SAJU),　2008/04/29
Roles of osteopontin in infectious diseases and application of nanobubbles for infectious diseases International-presentation

University of Kwazulu-Natal講演　2008/04/26
ヨウ素-124 による抗体標識の検討.

堀内逸智, 石井慶造, 菊池洋平, 酒巻学, 船木善仁, 山崎浩道, 渡邊夕紀子, 小玉哲也

日本原子力学会2008年春の年会　2008/03/26
ナノバブルと超音波を利用した炎症疾患モデルマウスでのNa/I sympoter(NIS)遺伝子発現の可視化

渡邊夕紀子, 堀江佐知子冨田典子, 大澤ふき, 船木善仁, 菊池洋平, 山崎浩道, 石井慶造, 森士朗, 小玉哲也

日本超音波医学会東北地方会第35回学術集会　2008/03/23
高解像度超音波イメージングシステムを用いたシスプラチンによる抗腫瘍効果の定量化.

冨田典子, 堀江佐知子, 渡邊夕紀子, 大澤ふき, 佐久間基成, 大木宏介, 森川秀広, 森士朗, 小野栄夫, 小玉哲也

日本超音波医学会東北地方会第35回学術集会　2008/03/23
高周波超音波を用いたシスプラチン誘導抗腫瘍効果の定量化.

小玉哲也

日本生体医工学会分子デリバリーME研究会第9回報告会　2008/03/15
Evaluation of cisplatin-induced antitumor effect with contrast-enhanced high-frequency ultrasound. International-presentation

Tomita N, Horie S, Watanabe Y, Oosawa F, Sakuma M, Chen R, Ohki K, Morikawa H, Mori S, Ono M, Kodama T

The 11th International Symposium on Advanced Biomedical Ultrasound.　2008/03/07

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Program pp30-33.
がん遺伝子治療を目指した非侵襲組織標的性分子導入法の開発と応用.

小玉哲也

TUBERO終了シンポジウム.　2008/02/08
ナノバブルと超音波を用いた歯周組織への遺伝子導入.

陳鋭, 千葉美麗, 堀江佐知子, 渡邊夕紀子, 森士朗, 五十嵐薫, 小玉哲也

日本機械学会第20回バイオエンジニアリング部門講演会　2008/01/25
日米英での研究生活の足跡：環境を楽しむ心.

九州工業大学大学院教育改革支援プログラム：第１回もっとグローバルマインド！　2007/12/12
ナノバブルと超音波を用いた高周波超音波三次元画像診断・分子導入システムの開発

小玉哲也

ナノバイオテクノロジー連携群成果報告会・ナノバイオテクノロジーが拓くイノベーションの世界　2007/12/05
Molecular-scale lipid bilayer response to shock wave: molecular dynamics simulations. International-presentation

Koshiyama K, Kodama T, Yano T, Fujikawa S

Third Asian-Pacific Congress on Computational Mechanics (APCOM'07) and the Eleventh International Conference on the Enhancement and Promotion of Computational Methods in Engineering and Science (EPMESC XI). ABSTRACTS of APCOM'07 in conjunction with EPMES　2007/12/03

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pp. 437
Molecular imaging of gene expression induced by delivery of nanobubbles and ultrasound. International-presentation

Watanabe Y, Horie S, Tomita N, Sakuma M, Osawa F, Chen R, Kikuchi Y, Tashiro M, Mori S, Funaki Y, Yamazaki H, Ishi K, Kohama Y, Ono M, Ito M, Kodama T

SMIT 2007.　2007/11/20

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Program p.21.
High frequency ultrasound for analysis of antitumor effects. International-presentation

Horie S, Tomita N, Watanabe Y, Osawa F, Sakuma M, Cehn R, Funamoto K, Fukumoto M, Oki K, Mori S, Hayase T, Kodama T

SMIT 2007.　2007/11/20

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Program. p21.
Three-dimensional image of intratumoral neovascular constructed with high-frequency contrast-enhanced micro-ultrasound. International-presentation

Tomita N, Horie S, Watanabe Y, Funamoto K, Hayase T, Oki K, Morikawa H, Ono M, Mori S, Kodama T

SMIT 2007.　2007/11/20

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Program p21.
Basic experiment on development of physical drug delivery system to inhibit alveolar bone resorption. International-presentation

Chen R, Chiba M, Kodama T, Igarashi K

SMIT 2007.　2007/11/20

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Program p21.
ナノバブルと超音波を利用したマウス骨格筋へのNa/I symporter(NIS)遺伝子発現の可視化

渡邊夕紀子, 堀江佐知子, 冨田典子, 船木善仁, 菊池洋平, 酒巻学, 山崎浩道, 石井慶造, 伊藤正敏, 小玉哲也

第28回サイクロトロン共同利用実験研究報告会　2007/11/19
超音波キャビテーションの発生に及ぼす発振周波数の影響.

冨田幸雄, 福士敏也, 木島悠, 小玉哲也

日本産業技術教育学会北海道支部会第21回大会講演　2007/10/13
Basic experiment for controlling of alveolar bone resorption in periodontitis by physical delivery system.

CHEN Rui, Mirei CHIBA, Kaoru IGARASHI, Tetsuya Kodama

東北大学イノベーションフェア　2007/10/05
ナノバブルと超音波を使用したPositronemission Tomogra-phy(PET)によるNa/I symporter (NIS) 遺伝子発現の可視化

渡邊夕紀子, 堀江佐知子, 冨田典子, 佐久間基成, 大澤ふき, 陳鋭, 菊地洋平, 田代学, 森士朗, 船木善仁, 山崎浩道, 石井慶造, 小濱泰昭, 小野栄夫, 伊藤正敏, 小玉哲也

東北大学イノベーションフェア　2007/10/05
ナノバブルと高周波超音波による腫瘍内血管の三次元画像の構築.

冨田典子, 堀江佐知子, 渡邊夕紀子, 大澤ふき, 佐久間基成, 陳鋭, 船本健一, 福本学, 大木宏介, 森士朗, 早瀬敏幸, 小玉哲也

東北大学イノベーションフェア　2007/10/05
高周波超音波画像診断によるシスプラチン(CDDP)の抗腫瘍効果の評価.

堀江佐知子, 冨田典子, 渡邊夕紀子, 大澤ふき, 佐久間基成, 陳鋭, 船本健一, 福本学, 大木宏介, 森士朗, 早瀬敏幸, 小玉哲也

東北大学イノベーションフェア　2007/10/05
Evaluation of antitumor effects using high frequency ultrasound biomicroscopy.

堀江佐知子, 冨田典子, 渡邊夕紀子, 大木宏介, 森川秀広, 森士朗, 小野栄夫, 小玉哲也

第66回日本癌学会学術総会　2007/10/03
Construction of three-dimentional image of intratumoral vessel using high-fr equency contrast-enhanced micro-ultrasound.

冨田典子, 堀江佐知子, 渡邊夕紀子, 船本健一, 早瀬敏幸, 木宏介, 森川秀広, 小野栄夫, 森士朗, 小玉哲也

第66回日本癌学会学術総会　2007/10/03
Development of local gene therapy with ultrasound and bubble-liposome against

藤澤優, 鈴木亮, 丸山一雄, 小玉哲也, 安永正浩, 松村保広

第66回日本癌学会学術総会　2007/10/03
Visualization of Na/I sympoter gene combined by the delivery method using nanobubbles and ultrasound.

渡邊夕紀子, 青井あつ子, 堀江佐知子, 冨田典子, 山崎浩道, 田代学, 菊池洋平, 石井慶造, 伊藤正敏, 小玉哲也

第66回日本癌学会学術総会　2007/10/03
Periodontal gene transfer using ultrasound and nano/microbubbles.

陳鋭, 千葉美麗, 堀江佐知子, 五十嵐薫, 小玉哲也

日本超音波医学会第34回東北地方会学術集会　2007/09/30
Interaction of shock waves generated by cavitation bubbles with cell membranes during sonoporation. International-presentation

Kodama T, Tomita Y, Aoi A, Koshiyama K, Yano T, Fujikawa S

The 1st International Colloquium on Dynamics, Physics and Chemistry of Bubbles and Gas-Liquid Boundaries.ICBB2007　2007/09/25
Molecular mechanisms of cavitation-induced cell membrane permeabilization International-presentation

Koshiyama K, Kodama T, Yano T, Fujikawa S

The 1st International Colloquium on Dynamics, Physics and Chemistry of Bubbles and Gas-Liquid Boundaries. ICBB2007　2007/09/25
ナノバブルと超音波を用いたDDS：骨格筋への応用.

小玉哲也, 青井あつ子, 渡邊夕紀子, 小野栄夫, 森士朗

日本機械学会2007年度年次大会　2007/09/09
超音波による分子の細胞膜通過機構：分子動力学シミュレーション.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

日本機械学会2007年度年次大会　2007/09/09
シスプラチンを使った抗腫瘍効果：高周波超音波による定量化.

冨田典子, 渡邊夕紀子, 堀江佐知子, 小野栄夫, 森士朗, 小玉哲也

日本機械学会2007年度年次大会.　2007/09/09
ナノバブルと超音波を用いたドラッグおよび核酸デリバリーシステムの開発と応用

小玉哲也

次世代医療システム産業化フォーラム2007.　2007/06/26
ナノバブルと超音波を用いたがん治療法の開発.

日本混相流学会年会講演会2007および第26回混相流シンポジウム.　2007/06/22
ソノポレーションによる遺伝子導入効率：気泡特性に対する検討.

小玉哲也, 青井あつ子, 渡邊夕紀子, 堀江佐知子, 冨田典子, 小野栄夫, 森士朗

日本超音波医学会第80回学術集会　2007/05/18
ソノポレーションによるシスプラチンの導入.

小玉哲也, 青井あつ子, 渡邊夕紀子, 森川広秀, 森士朗

第46回日本生体医工学会大会.　2007/04/25
ナノバブルと超音波を用いた分子導入システムの開発と癌治療への応用.

日本機械学会関西支部の第82期定時総会講演会.　2007/03/16
超音波DDSにおける分子導入機構.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

日本超音波医学会第33回東北地方会学術集会　2007/03/11
ナノバブルと超音波を用いたシスプラチン導入による抗腫瘍効果の検討.

小玉哲也, 青井あつ子, 渡邊夕紀子, 松村保広, 森士朗

日本超音波医学会第33回東北地方会学術集会　2007/03/11
衝撃波による細胞膜の透過性変化機構に関する分子動力学シミュレーション.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

第56回理論応用力学講演会.　2007/03/07
ナノバブルと超音波を用いたドラッグおよび核酸送達システムの開発.

科学技術教育講演会「先端医工学技術を知る・見る」　2007/03/02
がん療法を目指したナノバブルと超音波を用いた分子導入法の開発.

日本機械学会マイクロ・ナノフルイズ調査研究分科会　2007/02/27
ナノバブルと超音波を用いた分子デリバリーシステムの開発.

東京女子医科大学講演　2007/02/16
がん局所療法を目指したナノバブルと超音波を用いたドラッグおよび核酸送達

小玉哲也

東北大学イノベーションフェア　2007/02/01
ナノバブルを用いた遺伝子治療.

みやぎ心エコー研究会　2007/01/26
Molecular mechanisms of cell membrane permeabilization induced by shock waves International-presentation

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

第9回北海道大学+ソウル大学ジョイントシンポジウム　2007/01/25
超音波を利用したsiRNA内包バブルリポゾームのがん局所療法の臨床試験導入.

松村保広, 鈴木亮, 丸山一雄, 小玉哲也

第１回ナノバイオテクノロジー連携群成果報告会　2006/12/21
キャビテーション気泡から発生する衝撃波による細胞膜の透過性変化に関するMDシミュレーション

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

第20回数値流体力学シンポジウム　2006/12/18
Antitumor effectiveness of cisplatin with ultrasound and nanobubbles. International-presentation

Kodama T, Aoi A, Watanabe Y, Konno K, Horie S, Vassaux G, Mori S

The 152nd Meeting (4th joint meeting of the Acoustical Society of America and the Acoustical Society of Japan)　2006/11/28
Formation of Water Pore in a Bilayer Induced by Shock Wave: Molecular Dynamics Simulation International-presentation

Koshiyama K, Kodama T, Yano T, Fujikawa S

The 152nd Meeting (4th joint meeting of the Acoustical Society of America and the Acoustical Society of Japan)　2006/11/28
衝撃波による細胞膜の浸透圧変化に関する分子動力学シミュレーション.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

日本機械学会バイオエンジニアリング部門第17回バイオフロンティア講演会　2006/11/11
ナノバブルと超音波を利用したがん治療法の開発.

青井あつ子, 渡邊夕紀子, 今野聖絵, 堀江佐知子, 冨田典子, 小玉哲也

東北大学イノベーションフェア　2006/10/18
ナノバブルと超音波を用いた自殺遺伝子導入法の開発.

第10回オーガナイズド混相流フォーラム'06-仙台（OMF2006）　2006/10/16

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講演論文集38-43頁
超音波ナノバブルを利用した抗がん剤および遺伝子デリバリー

第65回日本癌学会学術総会.シンポジウム　2006/09/28
卵巣がん遺伝子・核酸治療法の開発.

芹沢由里子, 小泉史明, 黒田順一郎, 小玉哲也, 松村保広

第65回日本癌学会学術総会　2006/09/28
脂質膜近傍での抗がん剤の運動に関するMDシミュレーション

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

日本機械学会2006年度年次大会講演　2006/09/18
ナノバブルと超音波を用いた自殺遺伝子導入法の開発.

青井あつこ, 今野聖絵, 篠原文明, 森川秀広, 森士朗, G. Vassaux, 小玉哲也

日本機械学会2006年度年次大会講演　2006/09/18
ナノバブルを用いた骨格筋への遺伝子導入：分子イメージング解析.

青井あつ子, 渡邊夕紀子, 今野聖絵, 堀江佐知子, 森士朗, 森川秀広, 鈴木亮, 丸山一雄, 小玉哲也

第22回日本Drug Delivery System (DDS)学会　2006/07/07
脂質膜に形成する水孔のMD予測.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

日本膜学会第28年会講演　2006/06/08
5FUの拡散に関する分子動力学シミュレーション.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

第44巻特別号第45回日本生体医工学会大会　2006/06/02
ナノバブルと超音波を用いた細胞への分子導入に関する研究.

小玉哲也, 越山顕一朗, 青井あつ子, 冨田幸雄, 矢野猛, 藤川重雄

第13回キャビテーションに関するシンポジウム　2006/06/02
Delivery of oligodeoxynuceotid-es of into human saphenous veins and the adunct effect of ultra-sound and microbubbles. International-presentation

Kodama T, Tan PH, Georges AJT, Blomley MJR

American Society of Gene Therapy. The 9th Annual Meeting.　2006/05/31

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Molecular Therapy.2006; 13, S212.
ナノバブルと超音波を利用したSodium/Iodide Sympoterの導入.

渡邊夕紀子, 青井あつ子, 今野聖絵, 森士朗, 伊藤正敏, Georges Vassaux, 小玉哲也

第3回東北大学バイオサイエンスシンポジウム　2006/05/29
ナノバブルと超音波による抗がん剤感受性の増強.

青井あつ子, 渡邊夕紀子, 今野聖絵, 堀江佐知子, 森川秀広, 森士朗, 小玉哲也

第3回東北大学バイオサイエンスシンポジウム　2006/05/29
ソノポレーションを用いたHSVtk/GCV自殺遺伝子治療法.

青井あつ子, 渡邊夕紀子, 今野聖絵, 堀江佐知子, 森川秀広, 森士朗, 小玉哲也

第3回東北大学バイオサイエンスシンポジウム　2006/05/29
Delivery of sodium/iodide symportter therapy using nanobubbles with ultrasound. International-presentation

Kodama T, Konno K, Aoi A, Mori S, Ito M, Vassaux G

The 11th Congress of the world federation for ultrasound in Medicine and Bioloy. WFUM’B 2006 Seoul.　2006/05/28

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Ultrasound in Medicine and Biology. 2006; 32:280.
HSV-tk/GCV Cytotoxic Gene Therapy using ultrasound and nanobubbles. International-presentation

Aoi A, Konno K, Shinohara F, Mori S, Vassaux G, Kodama T

The 11th Congress of the world federation for ultrasound in Medicine and Bioloy. WFUM’B 2006 Seoul.　2006/05/28

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Ultrasound in Medicine and Biology. 2006; 32:280.
Effects of Anti-cancer drug of cisplatin using nanobubbles and ultrasound. International-presentation

Aoi A, Konno K, Shinohara F, Mori S, Vassaux G, Kodama T

The 11th Congress of the world federation for ultrasound in Medicine and Bioloy. WFUM’B 2006 Seoul.　2006/05/28

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Ultrasound in Medicine and Biology. 2006; 32:280.
微小気泡超音波破砕による脊髄への遺伝子導入.

青井あつ子, 城戸幹太, 高橋雅彦, 小玉哲也

第44巻特別号第45回日本生体医工学会大会　2006/05/15
超音波場でのナノキャビテーション気泡の挙動.

小玉哲也, 冨田幸雄

第44巻特別号第45回日本生体医工学会大会　2006/05/15
ナノバブルを用いたNIS遺伝子のがん細胞への導入.

渡邊夕紀子, 青井あつ子, 今野聖絵, 伊藤正敏, Georges Vassaux, 小玉哲也

日本超音波医学会東北地方会　2006/03/19
超音波による歯根膜細胞への遺伝子導入の試み.

山崎仁, 千葉美麗, 小玉哲也

日本実験力学会2006年度年次講演会　2006/03/14
ナノバブルと超音波を用いたがん遺伝子治療法の開発と応用

日本機械学会バイオエンジニアリング部門.制御と情報-生体への応用研究会平成17年度第1回研究会.　2006/02/23
ナノバブルを用いた超音波分子導入システムの開発と癌治療への応用.

小玉哲也

東京赤坂プリンスホテルにてポスター発表　2006/02/07
Application of nanobubbles for HSV-tk/GCV cytotoxic gene therapy using ultrasound. International-presentation

Suzuki M, Shinohara F, Aoi A, Sato Y, Watanabe Y, Mori S, G. Vassaux, Kodama T

ECCO 13-the European Cancer Conference　2005/10/30
Molecular dynamics simulation of water pore formation in lipid bilayer Induced by shock waves. International-presentation

Koshiyama K, Kodama T, Yano T, Fujikawa S

5th International Symposium on Therapeutic Ultrasound,　2005/10/27
Interaction of impulsive pressures of cavitation bubbles with cell membranes during sonoporation. International-presentation

Kodama T, Suzuki M, Tomita Y, Koshiyama K, Yano T, Fujikawa S

5th International Symposium on Therapeutic Ultrasound　2005/10/27
マイクロバブルを用いた脊髄への遺伝子導入法の開発.

城戸幹太, 高橋雅彦, 青井あつ子, 鈴木麻衣子, 小玉哲也, 森士朗, 古川宏, 小野栄夫

日本歯科麻酔学会　2005/10/26
ソノポレーションを用いた薬剤導入と抗腫瘍効.

佐藤義太郎, 鈴木麻衣子, 青井あつ子, 渡邊夕紀子, 篠原文明, 力石秀美, 森士朗, 小玉哲也

日本超音波医学会東北地方会第30回学術会　2005/09/28
超音波場におけるナノサイズの超音波造影剤の挙動と分子導入機構のメカニズム.

小玉哲也, 鈴木麻衣子, 冨田幸雄

日本機械学会2005年度年次大会講演　2005/09/19
5-Fluorouracil (5FU) の脂質二重層膜への導入に関する分子動力学シミュレーション.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

日本機械学会2005年度年次大会　2005/09/19
微小気泡による抗癌剤感受性増強作用の検討.

鈴木麻衣子, 篠原文明, 森士朗, 小玉哲也

第64回日本癌学会学術総会　2005/09/14
衝撃波による脂質膜の水孔形成に関するMDシミュレーション.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

日本流体力学会年会講演　2005/09/05
ナノ気泡と超音波によるがん細胞への抗がん剤導入に関する研究.

小玉哲也, 鈴木麻衣子, 冨田幸雄

日本流体力学会年会講演　2005/09/05
ナノバブルを利用したsonoporationのメカニズム.

小玉哲也, 鈴木麻衣子, 冨田幸雄, 高橋史明, 森士朗

第21回日本DDS学会　2005/07/22
ナノ気泡と超音波を使った分子導入のメカニズムと松村班での私の役割.

超音波を利用したsiRNA内包バブルリポゾームのがん局所療法の臨床試験導入」班会議講演　2005/07/19
平成17年度文部科学省がん特定領域研究研究代表者会議.

学術総合センター講演　2005/07/05
ナノバブルを用いたHSV-TK/GCV自殺遺伝子治療法の開発.

鈴木麻衣子, 篠原文明, 青井あつ子, 佐藤義太郎, 渡邊夕紀子, 森士朗, G. Vassux

日本バイオレオロジー学会　2005/07/01
Molecular dynamics simulation of shockwave-induced structural changes of lipid bilayers. International-presentation

Molecular dynamics simulation of shockwave-induced structural changes of lipid, bilayers

The 1st CRIS InternationalSymposium on Computational Science and Neuroscience. The 3rd Hokudai Simulation Salon Workshop　2005/06/20
ナノバブルによる衝撃波発生と分子導入のメカニズム.

小玉哲也, 越山顕一朗, 冨田幸雄, 鈴木麻衣子, 矢野猛, 藤川重雄

日本超音波医学会第78回学術集会　2005/05/20
ナノバブルを用いた薬剤導入と抗腫瘍効果の検討.

鈴木麻衣子, 篠原文明, 森士朗, 小玉哲也

日本超音波医学会第７８回学術集会　2005/05/20
衝撃波による5FU輸送に関するMDシミュレーション.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

日本超音波医学会第78回学術集会　2005/05/20
衝撃波による脂質膜構造変化のMD予測.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

日本膜学会第27年会講演　2005/05/19
ナノバブルによる分子導入のメカニズム：衝撃波と細胞膜との干渉.

小玉哲也, 越山顕一朗, 冨田幸雄, 鈴木麻衣子, 矢野猛, 藤川重雄

平成16年度衝撃波シンポジウム講演　2005/03/17
ナノバブルによる抗腫瘍効果

鈴木麻衣子, 篠原文明, 森士朗, Vassaux G, 小玉哲也

平成16年度衝撃波シンポジウム講演　2005/03/17
脂質二重層膜の構造変化に関する非平衡分子動力学-遺伝子導入を目指して.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

第17回バイオエンジニアリング講演会　2005/01/01
マイクロ気泡による細胞膜透過機構：実験および理論的考察.

小玉哲也, 冨田幸雄, 越山顕一朗, マーティン・ブロンムレイ

日本機械学会第17回バイオエンジニアリング講演会　2005/01/01
超音波とマイクロ気泡を使った遺伝子導入.厚生労働省がん研究助成金野村班指定研究「難治がんの総合的な対策に関する研究」小班「がん治療における薬剤ターゲッティングに関する基礎的, 臨床的研究」班会議.

国立がんセンター研究支所講演　2004/12/09
Ultrasound mediated gene expression using microbubbles International-presentation

Proceedings of the fourth international symposium on advanced Fluid information and the first international symposium on transdisciplinary fluid integration　2004/11/11
微小気泡と超音波を利用した分子導入法のメカニズム

小玉哲也, 冨田幸雄, 越山顕一朗, マーティン・ブロンムレイ

第18回日本エムイー学会秋季大会　2004/11/05
衝撃波による細胞膜透過性変化に関する分子動力学シミュレーション.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

第18回日本エムイー学会秋季大会　2004/11/05
Molecular delivery into a lipid bilayer with a single shock wave using molecular dynamics simulation. International-presentation

The 4th International Symposium on Therapeutic Ultrasound　2004/09/18
衝撃波と脂質二重層膜との干渉関する分子動力学シミュレーション.

越山顕一朗, 小玉哲也, 矢野猛, 藤川重雄

日本機械学会2004年度年次大会講演　2004/09/06
Development and application of a non-invasive tissue-specific molecular delivery method of cancer gene therapy. International-presentation

東北大学講演　2004/01/01
Ultrasound-mediated gene therapy using microbubbles. International-presentation

北海道大学講演　2003/01/01
Cytoplasmic molecular delivery with shock waves. International-presentation

九州工業大学　2003/01/01
Clinical applications of shock waves. International-presentation

George R. Harrison Spectroscopy Laboratory. Massachusetts Institute of Technology講演　2001/01/01
Cavitation bubbles mediated gene delivery. International-presentation

Department of Internal Medicine, University of Nebraska Medical Center講演　2001/01/01
Shock wave-mediated molecular delivery into cells. International-presentation

Schools of Chemical Engineering and Biomedical Engineering, Georgia Institute of Technology講演　2001/01/01
Molecular delivery into the cytoplasma of cells with high-intensity ultrasound. International-presentation

Imaging Sciences Department, Hammersmith Hospital, Imperial College講演　2001/01/01
自由表面近傍での単一および2個のレーザ生成キャビテーション気泡の挙動.

冨田幸雄, 小玉哲也

日本機械学会流体工学部門講演会　2000/09/09
Cytoplasmic molecular delivery with shock waves. International-presentation

Kodama T, Hamblin MR, Doukas AG

American Society for Biochemistry and Molecular Biology & The American Society for Pharmacology and Experimental Therapeutics Joint Meeting with French Pharmacological Society Pharmacological Society of Canada Satellite Meetings.　2000/06/04

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FASEB Journal. 2000; 14(8): A1473.
Ultrasound mediated gene therapy with microbubbles. International-presentation

Veterans Administration Medical Center and The University of Texas, Southwestern Medical Center at Dallas講演　2000/01/01
超微小爆薬で発生する衝撃波と組織損傷.

小玉哲也, 龍野正, 高山和喜, 上之原広司

平成9年度衝撃波シンポジウム講演　1998/03/20
Ultrasound, bubble dynamics, thrombolytic therapy

福岡医科大学講演　1998/01/01
Revascularization of cerebral embolism using liquid jet impact

Japan Society of Mechanical Engineering講演　1998/01/01
衝撃波脳血栓症血行再建術での血栓溶解特性.

龍野正, 小玉哲也, 高山和喜, 杉本真也, 上之原広司, 佐々木啓吾, 高橋昇

平成9年度衝撃波シンポジウム講演　1998/01/01
マイクログラム爆薬と金属被覆導爆線の爆発で発生した衝撃波の可視化.

永易伸生, 小野寺収, 小玉哲也, 高山和喜, 大坪信武

平成9年度衝撃波シンポジウム講演　1998/01/01
体外衝撃波破砕術でのキャビテーション気泡の動力学.

小玉哲也, 高山和喜

高速度撮影とフォトニクスに関する総合シンポジウム　1997/12/16
Collapse of cavitation bubble induced during extracorporeal shock wave lithotripsy. International-presentation

Kodama T, Takayama K

The 134th Meeting of the Acoustical Society of America　1997/12/15

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Journal of Acoustic Society of America. 1997; 102(5): 3154.
体外衝撃波結石破砕術におけるキャビテーション損傷

小玉哲也, 高山和喜

第11回日本ME学会秋季大会　1997/11/20
Cavitation bubble induced tissue damage during extracorporeal shock wave lithotripsy.

Kodama T, Takayama K

Proceedings of the 11th Autumn conference of the Japan Society of Medical Electronics and Biological Engineering　1997/10
Medical application of underwater shock waves International-presentation

Takayama K, Kodama T

Proceedings of 23rd International Pytotechnics Seminar　1997/09/30
Revascularization therapy for acute cerebral embolism by the impact of a liquid jet generated by the interaction of a gas bubble with an underwater shock wave International-presentation

Kodama T, Takayama K, Nagayasu N, Uenohara H, Takahashi N

Proceedings of the 21st International Symposium on Shock Waves　1997/07/20
Research into shock wave revascularization therapy of acute cerebral embolism International-presentation

Kodama T, Takayama K, Uenohara H

Japan Society of Mechanical Engineers, Centennial Grand Congress　1997/07/13
脳塞栓症血行再建術：X線による液体ジェットの可視化観察.

小玉哲也, 高山和喜, 上之原広司, 高橋昇

平成8年度衝撃波シンポジウム講演　1997/03/13
Basic research into shockwave revasucularization for acute cerebral embolism.

Takahashi N, Kodama T, Takayama K, Uenohara H, Yoshimoto T

第12回脳神経血管内手術研究会　1996/11/28
衝撃波脳塞栓症血行再建術の基礎的研究.

小玉哲也, 永易伸生, 高山和喜, 上之原広司, 高橋昇

1996年日本機械学会東北支部八戸地方講演会　1996/10/24
衝撃は脳塞栓症血行再建術の基礎研究－衝撃波発生と気泡崩壊－

小玉哲也, 永易伸生, 高山和喜, 上之原広司, 高橋昇

第10回日本ME学会秋季大会　1996/10/24
衝撃波脳塞栓治療術の実験的研究.

永易伸生, 小玉哲也, 高山和喜, 上之原広司, 高橋昇

日本機械学会流体工学部門講演会　1996/07/23
衝撃波による生体損傷のしきい値.

小玉哲也, 永易伸生, 高山和喜

日本機械学会流体工学部門講演会　1996/07/23
The characteristics of the penetration of a liquid jet communicated to the thrombus.

Nagatasu N, Kodama T, Takayama K, Uenohara H, Ito K, Hahizime T

The Kayaku Gakkai Spring Annual Meeting 1996　1996/05/01
衝撃圧に対する正常組織の損傷しきい値.

小玉哲也, 永易伸生, 高山和喜

平成7年度衝撃波シンポジウム　1996/03/14
人工血栓を充填した円柱内での水中衝撃波と空気泡との相互干渉.

永易伸夫, 小玉哲也, 高山和喜, 上之原広司, 吉田昌弘

平成7年度衝撃波シンポジウム　1996/03/14
衝撃波脳塞栓症血行再建術の研究.

小玉哲也, 高山和喜, 永易伸生, 上之原広司, 吉田昌弘

1996年日本神経超音波医学会　1996/01/01
An experimental research on cerebral embolism therapy using interaction of underwater shock waves and bubbles.

Kodama T, Nagayasu N, Takayama K, Uenohara H, Takahashi N

Proceeding of the 30th Tohoku conference of the Japan Society of Medical Electoronics and Biological Engineering,　1996/01/01
気泡の最適崩壊条件.

小玉哲也, 永易伸生, 高山和喜

高速度撮影とフォトニクスに関する総合シンポジウム　1995/12/07
Analog experiments of tissue damage generated during ESWL treatments. International-presentation

Takayama K, Kodama T, Kuwahara M, Ioritani M

The 130th Meeting of the Acoustical Society of America　1995/11/27

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Journal of Acoustic Society of America. 1995; 98(5): 2942.
体外衝撃波結石破砕術にともなう気泡と衝撃波との相互干渉.

小玉哲也, 永易伸生, 高山和喜

第29回日本ME学会東北支部大会　1995/10/28
衝撃波の生体作用軽減をめざして.

棚橋善克, 太田章三, 坂井清英, 高山和喜, 小玉哲也, 小野寺収

第9回日本ME学会秋季大会.医用電子と生体工学　1995/10/26
脳塞栓症急性期血行再建術に対する衝撃波応用血栓破砕術の基礎的検討.

吉田昌弘, 上之原広司, 吉本高志, 永易伸生, 小玉哲也, 高山和喜

第9回日本ME学会秋季大会　1995/10/26
Condition of liquid jet formation inside a cylinder: basic research of acute cerebral embolism.

Nagayasu N, Kodama T, Takayama K, Uenohara K, Yoshida M, Ito K, Hashizume T

日本火薬学会1995年度秋季発表会　1995/10/10

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39 - 40頁 .
衝撃波と気泡との相互干渉を利用した脳血栓症治療の基礎研究.

小玉哲也, 永易伸生, 高山和喜, 吉田昌弘

第4回日本機械学会バイオエンジニアリングシンポジウム講演　1995/07/25

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論文集；207-208頁
Characteristics of multiple air bubbles collapse impacted by underwater shock waves.

Kodama T, Nagayasu N, Takayama K

日本火薬学会1995年度春季発表会　1995/05/01

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101 - 104頁
Basic research for treatment of cerebral thrombosis by means of interaction of underwater shock waves with air bubbles.

Kodama T, Nagayasu N, Takayama K

日本火薬学会1995年度春季発表会　1995/05/01

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111 - 114 頁
水中衝撃波と生体模擬材料に付着した気泡との相互干渉.

小玉哲也, 山田潔, 南啓次, 高山和喜

社団法人日本機械学会第72回通常総会講演会　1995/03/29
Shock wave generation mechanism associated with bubble motion after shock wave interaction.

Yamada K, Kodama T, Takayama K

The 72nd Japan Society of Mechanical Engineers, Spring Annual Meeting 1995　1995/03/23
衝撃波と気泡の相互干渉で誘起される液体ジェットの諸特性.

冨田幸雄, 山田潔, 小玉哲也, 高山和喜

平成6年度衝撃波シンポジウム　1995/03/16
水中衝撃波とゼラチンに付着した気泡との相互干渉.

小玉哲也, 永易伸生, 高山和喜

平成6年度衝撃波シンポジウム　1995/03/16
血管を模擬した円柱内の気泡と水中衝撃波との相互干渉.

永易伸生, 小玉哲也, 高山和喜, 吉田昌弘

平成6年度衝撃波シンポジウム　1995/03/16
ゼラチンに付着した複数気泡と水中衝撃波との相互干渉.

南啓次, 永易伸生, 小玉哲也, 高山和喜

平成6年度衝撃波シンポジウム　1995/03/16
気泡と衝撃波との干渉(医療応用のための基礎研究).

小玉哲也, 山田潔, 高山和喜

第23回可視化シンポジウム　1995/01/01
The cavitation threshold of human tissue exposed to 0.2 MHz pulsed ultrasound.

Coleman AJ, Kodama T, Choi MJ, Adams T, Saunders JE

第8回日本エム・イー学会秋季大会　1994/10/07
変形壁近傍でのキャビテーション気泡の挙動に関する実験的研究

冨田幸雄, 小玉哲也, 島章

日本学術会議キャビテーションに関するシンポジウム（第7回　1992/10
気泡崩壊による生体組織損傷機構に関する一考察.

小玉哲也, 冨田幸雄, 島章

日本機械学会第4回バイオエンジニアリング部門学術講演　1992/07/23
ゼラチン表面に付着した気泡と衝撃波との相互干渉.

小玉哲也, 冨田幸雄, 島章

日本機械学会第69期全国大会講演会　1991/10/16
気泡と衝撃波との相互干渉で誘起される液体マイクロジェットの形成.

小玉哲也, 冨田幸雄, 島章

日本物理学会第46回年会講演　1991/09/27
ガス銃によるパルスウォータージェットの高速衝突と壁面損傷.

冨田幸雄, 島章, 古田直也, 松井禎, 小玉哲也, 佐藤光太郎

日本ウォータージェット学会第7回研究発表講演会　1991/07/19
ゼラチン近傍での気泡の成長および崩壊.

小玉哲也, 冨田幸雄, 島章

日本機会学会第68期通常総会講演会講演　1991/03/30
複合壁近傍での気泡の挙動に関する実験的研究.

小玉哲也, 冨田幸雄, 島章, 岩田竜治

日本機械学会第68期全国大会講演会講演　1990/09/23
自由表面近傍での気泡の成長と崩壊に関する研究（第1報：レーザー生成気泡の挙動観察と鏡像理論との比較）.

冨田幸雄, 島章, 岩田竜治, 小玉哲也

日本機械学会・精密学会東北支部, 東北支部八戸地方講演会講演　1990/01/01
Evaluation of chemoimmunotherapy using lymphatic drug delivery system

Suzuki R., Sukhbaatar A., Shiro M., Ito Y., Kodama T.

South Africa-France-Nigeria-Japanese quadrilateral symposium 2024
Lymphatic drug delivery system: treatment strategies for metastatic lymph nodes

Kodama T.

South Africa-France-Nigeria-Japanese quadrilateral symposium 2024
超音波RF信号を用いたクラッタフィルタ・再構成による転移リンパ節の血管抽出

前田一伎, 岡田侑弥, 大村眞朗, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

日本超音波医学会第68回東北地方会学術集会　2024/09/15
放射線療法とリンパ行性薬物送達法を用いた免疫療法の併用治療における免疫活性の評価

鈴木瑠真, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

第48回日本リンパ学会総会　2024/06/07
Investigation of the effects on distant metastases treated by direct lymph node administration of anti-CTLA-4 antibodies

Takagi K, Miyatsu M, Mishra R, Sukhbaatar A, Mori S, Kodama T

The 81st Annual Meeting of the Japanese Cancer Association　2022/09/29
Lymphatic drug delivery system: an efficient drug delivery strategy for treatment of metastatic lymph nodes using immune checkpoint inhibitors

Mishra R, Sukhbaatar A, Mori A, Sakamoto M, Kodama T

SelectScience® Virtual Cancer & Immunology Research Summit 2022　2022/07/19
リンパ節転移介在遠隔転移マウスモデルの樹立

髙木洸樹, 宮津美里有, Radhika Mishra, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

第38回日本DDS学会学術集会　2022/06/29
リンパ行性薬剤送達法と浸透圧・粘度調整溶媒を用いたカルボプラチンによる転移リンパ節に対する抗腫瘍効果の評価

宮津美里有, 髙木洸樹, 栗生晏暉, 志水洸太, Radhika Mishra, Ariunbuyan Sukhbaatar, 阪本真弥, 森士朗, 小玉哲也

第38回日本DDS学会学術集会　2022/06/29
転移性リンパ節の治療を目指したドキソルビシンを用いたリンパ行性薬物送達法の開発

田中菜生, Radhika Mishra, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

日本機械学会第34回バイオエンジニアリング講演会　2022/06/25
抗CTLA-4抗体のリンパ節投与がもたらす遠隔転移治療効果の検討

髙木洸樹, 宮津美里有, Radhika Mishra, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

日本機械学会第34回バイオエンジニアリング講演会　2022/06/25
リンパ行性薬剤送達法および粘度・浸透圧調整溶媒を用いたカルボプラチンによる転移リンパ節に対する抗腫瘍効果の評価

宮津美里有, 髙木洸樹, Radhika Mishra, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

日本機械学会第34回バイオエンジニアリング講演会　2022/06/25
Targeting lymph node metastasis through lymphatic drug delivery system by administration of docetaxel

Sukhbaatar A, Mori S, Kodama T

The 40th Sapporo International Cancer Symposium　2022/06/23
Novel drug formulation for potentiation of therapeutic response using the lymphatic drug delivery system

Mishra R, Sukhbaatar A, Sakamoto M, Mori S, Kodama T

The 40th Sapporo International Cancer Symposium　2022/06/23
早期転移リンパ節の診断と治療 Invited

小玉哲也

第46回日本頭頸部癌学会　2022/06/17
Three-dimensional evaluation of the relationship between speed of sound and scattering characteristics of lymph nodes in tumor-bearing mice

Kazuma Noguchi, Masaaki Omura, Takashi Ohnishi, Matsumoto Daiki, Tetsuya Kodama, Hideaki Haneishi, Tadashi Yamaguchi

The 42nd Symposium on UltraSonic Electronics (USE2021)　2021/10/25

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Industrial Property Rights 8

リンパ行性薬剤送達法に有効な薬剤を含む溶液の適正な浸透圧域

小玉哲也, 森士朗

特許第7182794号

Property Type: Patent
リンパ行性薬剤投与法で有効な薬剤

小玉哲也, 森士朗

特許第6960637号

Property Type: Patent
リンパ節転移のリスク評価プログラム及び装置

小玉哲也, 森士朗

特許第6593787号

Property Type: Patent
超音波画像データ処理プログラム及び装置

志賀清人, 伊藤康一, 小玉哲也

Property Type: Patent
超音波発生用プローブ

小玉哲也, 森士朗

Property Type: Patent
がん治療用組成物

小濱泰昭, 小玉哲也

Property Type: Patent
血管の閉塞治療用及びガン治療用装置

高山和喜, 小玉哲也, 永易伸生

Property Type: Patent
エマルション爆薬

小玉哲也, 永易伸生, 高山和喜

Property Type: Patent

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Research Projects 89

転移リンパ節に対するリンパ行性放射線免疫療法の開発

SUKHBAATAR ARIUNBUYAN, 藤井博司, 小玉哲也

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(B)

Institution: 東北大学

2025/04/01 - 2028/03/31
シェーグレン症候群に対する免疫チェックポイント阻害薬投与に関する非臨床試験

森士朗, SUKHBAATAR ARIUNBUYAN, 小玉哲也, 杉浦剛

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(C)

Institution: 東北大学

2025/04/01 - 2028/03/31
Innovative Lymphatic Immunotherapy for Metastatic Lymph Nodes

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

2023/04/01 - 2026/03/31
リンパ行性薬剤送達法による免疫チェック阻害剤を用いた頭頸部癌免疫療法の開発

宮下仁, SUKHBAATAR ARIUNBUYAN, 小玉哲也, 森士朗

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(C)

Institution: 東北医科薬科大学

2023/04/01 - 2026/03/31

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概要免疫チェック阻害剤(ICI)を用いたがん免疫療法は, 頭頸部癌においても標準治療として用いられている. しかしながら, 奏効率, 有害事象, 費用対効果等の観点から改善の余地が未だ大きいのが現状である. われわれは, リンパ節(LN)に薬剤を注入しリンパネットワークを介して薬剤を送達させるリンパ行性薬剤送達法(LDDS)を開発し，このLDDSにより, LN内に長期間薬剤を貯留させ, 微量でも長期間奏効性を持続させることが可能であることを示してきた. 本研究の目的は, 頭頸部癌に対するICIとLDDSを併用した新規がん免疫療法の可能性を転移モデルを用いて検証することである. 2023年度においては，ICIの投与部位について検討した．実験動物としては，腫大LNを有するMXH10/Mo/lprマウスを，腫瘍細胞としては，生体発光関連遺伝子を導入したマウス骨肉腫細胞，LM8-Luc細胞を用いた．腫瘍モデルとしては，腸骨下LN(SiLN)に腫瘍細胞を移植した転移モデル用いた．ICIとしては抗CTLA4抗体を用いた．ICIの投与部位としては，腫瘍細胞を移植したSiLNにICIを投与した群(tbLN群)，腫瘍細胞を移植していない反対側のSiLNにICIを投与した群(ntbLN群)，腹腔内にICIを投与した群(ip群)とした．治療効果は，生体発光画像解析システムや病理組織学的手法を用いて評価した．以上のICIを用いた治療実験の結果，tbLN群において，治療を行っていない対照群に比較し，統計学的に有意な腫瘍抑制効果と生存率の向上がみられた．しかし，ntbLN群やip群においては，有意な治療効果は確認できなかった．以上の結果より，転移LNを薬剤投与部位としたLDDSを用いたICIによる免疫療法が，従来のICIを用いた免疫療法に比較し，良好な治療成績をもたらす可能性が示唆された．
Multimodal cancer therapy and diagnostic system using 256-channel diamond quantum sensor array

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2023/04/01 - 2026/03/31
Research on optimization of low-intensity ultrasonic irradiation conditions for ultrasonic therapy to activate self-healing power

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2023/04/01 - 2026/03/31
Novel Rat Model and Intervention for Elucidating the Molecular Mechanism in Chronic Postsurgical Pain

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2021/04/01 - 2025/03/31
Development of innovative lymphatic drug delivery system for distant metastasis treatment

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Research (Pioneering)

Institution: Tohoku University

2021/07/09 - 2024/03/31
Development of a lymphatic drug delivery system for local control of metastatic lymph nodes to systemic metastatic therapy

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

2020/04/01 - 2023/03/31
Super-early stage diagnosis of the metastatic lymph nodes using the measurement of intra-lymph node pressure and lymphatic drug delivery system

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)

Category: Grant-in-Aid for Challenging Research (Exploratory)

Institution: Iwate Medical University

2019/06/28 - 2022/03/31
Development of multi-scale ultrasound pathological diagnosis method reflecting physical characteristics of living tissue

Tadashi Yamaguchi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Chiba University

2019/04/01 - 2022/03/31

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Echo data of various resolutions were collected by observing the biological tissues to be evaluated in vivo with ultrasound in the frequency band used in clinical practice, and by observing them in the clinical to microscopic level frequency band after removal. We evaluated the speed of sound, backscattering coefficient, and amplitude enveloping characteristics of these data, and developed a protocol to understand the frequency dependence of each acoustic and physical property. To promote this study, we also established a sample preparation protocol to observe excised tissue under conditions similar to those in vivo, improved the accuracy of backscattering property analysis, and proposed a model for evaluating amplitude enveloping properties. In addition, we have constructed a system that can evaluate the movement of blood vessels and blood flow at the same time with high time resolution by fusing ultra-high-speed ultrasonic observation and tissue property evaluation technologies.
An experimental study on the theory of lymph node-mediated hematogenous metastasis

KODAMA Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Research (Exploratory)

Institution: Tohoku University

2019/06/28 - 2021/03/31

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This proposal is to experimentally verify the theory of lymph node-mediated hematogenous metastasis, which considers that the sentinel lymph node can be the origin of systemic metastasis. The results of this study can be summarized in the following two points. (1) A perfusion defect is formed in the early stage of lymph node metastasis. (2) The pathological images of lymph nodes in patients with head and neck cancer were carefully examined, and the presence of perforating branches penetrating the lymph node capsule was confirmed. The lymph node-mediated hematogenous metastasis theory accurately describes hematogenous metastasis in the early stage when tumor cells have metastasized and proliferated in the marginal sinuses of lymph nodes. In the future, it is necessary to accumulate experimental evidence for this theory.
Comprehensive study on precise diagnosis and new chemotherapy for micrometastatic lymph nodes

SAKAMOTO Maya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2018/04/01 - 2021/03/31

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In order to develop a precise diagnostic imaging method and minimally invasive local chemotherapy using lymphatic drug delivery system (LDDS) for early metastatic lymph nodes, we conducted experiments using a mouse model of lymph node metastasis. The results showed that lymphatic sinus contrast imaging using micro-CT was useful as an imaging method for the diagnosis of metastatic lymph nodes in the clinical N0 state, because tumor cells proliferating in the lymphatic sinus blocked the flow of contrast medium from upstream lymph nodes, indicating a focal defect of contrast medium. We also found that the optimal infusion rate of drugs into upstream lymph nodes using LDDS was 10-80 μL/min, and that administration of anticancer agents using LDDS had an antitumor effect on metastatic lymph nodes in the model of clinical N0 stage.
Therapeutic system for metastatic lymph nodes at early stages

Kodama Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

2017/04/01 - 2020/03/31

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The applicant has proposed a theory of lymph node-mediated hematogenous metastasis, which considers clinical N0 lymph nodes (cN0 LNs) as the origin of systemic metastasis via the lymphatic system. The lymphatic drug delivery system (LDDS) is based on this concept. The purpose of this research is the following two points. (1) Development of cN0 LNs diagnostic system. (2) Development of the lymphatic drug delivery system for the treatment of cN0 LNs. The following results were obtained in this study. (a) Perfusion defect was observed at the stage of cN0 LNs. (b) The impulse value that was required for LDDS to deliver from the solution from the upstream LN to the downstream LN was obtained. (c) The efficacy of a combination of LDDS and sonoporation for the treatment of cN0 LNs was demonstrated. (d) The optimum range of viscosity and osmotic pressure, which are the optimal solvent characteristics for LDDS, was determined.
Low operation by siRNA with angiogenetic inductive action and modal nano drug delivery, initiation of hurt repairing procedure

Teramoto Noriyoshi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Saga University

2017/04/01 - 2020/03/31

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This present study is entitled "Hypoxia-Inducible Factor-2α (HIF-2α), which is deeply involved in angiogenesis. It targets "a regulator (Int6) that specifically suppresses HIF-2α. We've developed a new nucleic acid drug, siRNA, based on an entirely new design theory. Sonoporation (acoustic drilling) is used to minimally invade the host cells around the skin and mucous membrane wounds (local induction). As a result, peripheral circulatory blood flow is improved through newly induced and formed microcirculatory pathways and the skin and mucous membranes The process of markedly improving the wound healing process is observed at both the tissue and individual animal level, and the wound healing period is measured. It is the creation of an unprecedented minimally invasive wound healing method that aims to significantly reduce the time required for wound healing.
Early diagnosis and low invasive treatment of cancer by micro/nano thermal engineering

Maruyama Shigenao

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

2016/04/01 - 2020/03/31

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This study measured the effective thermal conductivity of healthy and lesional skin in 11 cancer patients. Clinical studies have shown that when the tumor invades the dermis, the effective thermal conductivity of the lesion is higher than in the healthy area. Complex in-vivo heat transfer analysis during laser treatment was performed considering multiple heat scattering in vivo, plasmon heating by GNR, and combined heat transfer analysis considering blood flow and metabolic heat in the body. As a result, it was found that the GNR can be locally heated with a short irradiation time. We examined the usefulness of low invasive laser treatment by an experimental method. From the experiment, the usefulness of the surface cooling by the Peltier device could be evaluated.
Development of a new radiotherapy using targeted nanobubbles and ultrasound for metastatic lymph nodes

Kodama Tetsuya, MORI Shiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)

Category: Grant-in-Aid for Challenging Research (Exploratory)

Institution: Tohoku University

2017/06/30 - 2019/03/31

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In this study, the aim was to increase the oxygen concentration by ultrasonically destroying oxygen bubbles in the metastatic lymph node with a view to improving the response rate to radiation therapy. During the experiments, we found that the oxygen partial pressure in the metastatic lymph node of an MXH10/Mo mouse was similar to that in adjacent blood vessels. We altered the research strategy to develop a mouse irradiation system capable of applying radiotherapy to treat only one lymph node. We succeeded in treating a single metastatic lymph node with radiation larger than 8 Gy. Also, we confirmed the abscopal effect after the irradiation. It is suggested that there is a relationship between radiation therapy and tumor immunity. We anticipate that this radiation system has potential to open the way for new immunoradiotherapy treatment strategies.
Innovative theranostics system with magnetic carbon nanotube

Saijo Yoshifumi, KODAMA Tetsuya, KATO Toshiaki, SIREGAR Syahril

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)

Category: Grant-in-Aid for Challenging Research (Exploratory)

Institution: Tohoku University

2017/06/30 - 2019/03/31

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The basis of innovative theranostics system with magnetic carbon nanotube (M-CNT) was investigated. In the diagnostic side, M-CNT for photoacoustic (PA) imaging was developed and non-local means denoising was applied to reduce PA noise. In the therapeutic side, vibration of M-CNT caused by pulsed magnetic field was confirmed and M-CNT behavior during heating was simulated. The results indicate the application of M-CNT and PA imaging for innovative theranostics system.
gene delivery into lymphocytes using lymphatic administration and ultrasound

KATO Shigeki, KODAMA tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

Category: Grant-in-Aid for Young Scientists (B)

Institution: Kindai University

2017/04/01 - 2019/03/31

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Our study used MXH10/Mo-lpr/lpr mice, which develop systemic swelling of lymph nodes up to 10mm in diameter. Murine breast cancer cells were inoculated into the subiliac lymph node of these mice to deliver them to the downstream proper axillary lymph node, thereby developing a model of a metastatic lesion. In order to deliver doxorubicin (Dox) to the tumor lesions in the proper axillary lymph node via the lymphatic vessels, solutions containing Dox and nano/microbubbles were injected into the subiliac lymph node. After successful detection of nano/microbubbles in the proper axillary lymph node, the bubbles were destroyed by the application of destruction ultrasound; this resulted in the penetration of Dox into tumor tissues in the marginal sinuses and enhancement of its antitumor effects. This study is unique in that the treatment technique described was able to suppress the intranodal invasion of tumor cells and thereby preserve the lymphatic structure in the tumor-bearing lymph node.
Identification of microRNAs associated with distant metastasis in model mouse

Sagai Shun

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2016/04/01 - 2019/03/31

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Using a metastatic model mouse and luciferase expression tumor cells and bioluminescence image analysis equipment, the activation of the pulmonary micrometastasis lesion was confirmed in ilium lymphadenectomy in a metastatic model mouse. However, the time to activation varied according to the type of tumor cells. Furthermore, the implantation of tumor cells into subiliac lymph nodes (SiLN) inhibited the pulmonary micrometastasis when the tumor cells were administered into a caudal vein. These results indicated that some kind of tumor inhibiting factors occured by a tumor implantation into lymph nodes.
Development of a minimally invasive treatment method using biocompatitive gold nanorods and near-infrared laser light for lymph node metastasis

Offer Organization: JSPS

System: Bilateral Programs

Institution: Tohoku University

2017/04 - 2019/03
Treatment for lymph node metastasis of oral cancer by using lymphatic administration of anticancer agent-encapsulated liposomes

Mori Shiro, KODAMA Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2016/04/01 - 2018/03/31

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In order to develop a minimally invasive treatment for lymph node(LN) metastasis of oral cancer, a lymphogenous anticancer drug administration method using a LN upstream in the lymph network as a drug administration site was examined. In this study, MXH10 / Mo / lpr which is a lymph node swollen mouse was used as an experimental animal. When tumor cells are injected into the subiliac LN(SiLN) of this mouse, it has been known that the metastatic lesion is indced in the proper axillary LN which is a downstream LN of the SiLN. As a result of this study, the following was clarified; when drug administration rate to LN was fast, drug delivery to the downstream LN was not sufficiently done; anticancer agent-encapsulated liposomes having large particle size showed prolonged retention in the target LN; and drug delivery performance of anticancer drugs was improved by ultrasonic irradiation after injecting the anticancer agent-encapsulated liposomes into the metastatic LN.
High-frequency ultrasound diagnostic imaging system to detect niche formation in the lymph nodes in a pre-metastatic phase

Sakamoto Maya, KODAMA Tetsuya, ITO Koichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2015/04/01 - 2018/03/31

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To develop an image analysis system to detect niche formation leading to lymph node (LN) metastasis formation, changes in vascular architecture in the process of LN metastasis formation were analyzed using contrast micro CT imaging and contrast high frequency ultrasound imaging. In the present study, tumor cells were inoculated into the subiliac LN (SiLN) of LN-swollen mouse, MXH10/Mo/lpr, and then metastasis formation process in the proper axillary LN located downstream of SiLN in mouse lymph network was analyzed. The results showed that, in the early stage of LN metastasis, blood vessel density in the LN prior to LN size change was increased. However, angiogenesis in the LN at the early stage of LN metastasis could not be confirmed.
リンパ節転移モデルを用いた転移リンパ節の治療法に関する研究 Competitive

小玉哲也

Offer Organization: 株式会社ヤクルト本社

System: 共同研究費

2016 - 2018
Development of a novel agent for ultrasound which can show engarftment of transplanted islets and eraly discovery of neuroendocrinal tumor.

Sakata Naoaki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2014/04/01 - 2017/03/31

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Islet transplantation is a cellular replacement therapy for severe diabetes mellitus. For the success of islet transplantation, it is important to engraft many transplanted islets. However, there are no examinations to evaluate the conditions of transplanted islets directly. Recently, many trials for evaluating the engraftment of islets using imaging examinations have been done. In this study, we tried to evaluate the engraftment and condition of transplanted islets using enhancement ultrasonography, and clarified that echogenicity of the transplanted mouse islets into diabetic mice was increased after injection of contrast agent, and correlation between the echogenicity and metabolic function of the diabetic mice. These findings revealed the possibility of the enhanced ultrasonography for evaluating the engraftment and condition of transplanted islets.
Development of early diagnosis and treatment for lymph node metastasis

Kodama Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

2014/04/01 - 2017/03/31

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There are few pre-clinical studies of early diagnosis and treatment for lymph node (LNM). The reasons mainly are due to the lack of a noninvasive imaging system capable of monitoring metastasis over time in an appropriate animal model. We developed MXH10/Mo/lpr mice, which develop systemic swelling of LNs up to 10 mm in diameter. Here we show using MXH10/Mo/lpr mice that we developed an ultrasound/micro-CT system which consists of a high-frequency ultrasound system and a micro-CT system, and a lymphatic drug delivery system (LDDS) using acoustic liposomes (ALs) and ultrasound (US). Vascular distribution in the metastatic LNs can qualitatively expressed by the ultrasound/micro-CT system at the early stage of LNM. While, the LDDS using US and ALs delivered doxorubicin into metastatic LNs, resulting in an effective treatment for early metastatic LNs. We anticipate that our methodology could be applied clinically for early metastatic LNs.
Establishment of novel non-invasive therapy for siRNA-induced vasculogenesis using sonoporation techniques, nano-size drug delivery systems

Teramoto Noriyoshi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Saga University

2014/04/01 - 2017/03/31

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Due to an aging population and the increasingly westernized diet of Japanese people, it will be essential to combat the increasing incidence of associated lifestyle-related diseases such as atherosclerosis and type 2 diabetes. For example, it is well known that atherosclerosis produces narrowing of blood vessels in the leg, which may lead to severe symptoms including gangrene. For the medical treatment of impeded blood flow (e.g. arteriosclerosis obliterans, Buerger's disease) both drug treatment and/or invasive surgical interventions （stenting, bypass graft surgery, etc.） are required. Therefore, the aim of the present research project is to establish a novel non-invasive therapy for siRNA-induced vasculogenesis by the use of nano-size drug delivery systems, which is designed to stimulate the collateral circulation in compromised tissues. This technique will also be applicable in organ transplant and regenerative medicine.
Quantification of breast cancer microenvironment by three dimensional integration of micro bubble contrast ultrasound and MRI image

Takasawa Chiaki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2014/04/01 - 2017/03/31

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The quantitative method of contrast ultrasound is currently equipped with time intensity curve analysis in clinical models. Peak intensity and area under the curve are calculated as parameters, and it is reported that these correlate with MVD. As a new method, we focus on a certain pixel, measure how the color of pixel changes in the time axis direction, divide one with a large degree of change and one with a small change by threshold．We developed a method to detect things as detected pixels of the contrast agent. Finally, an area ratio (enhancement area ratio) of the region where the contrast medium is detected is calculated with respect to the region of interest. In this study, we clarified that the enhancement area ratio correlates with the pathological MVD of invasive cancer.
Development of volume registration method for diagnosis of metastatic lymph node of head and neck cancer by ultrasound imaging

Sakamoto Maya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2013/04/01 - 2017/03/31

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To detect lymph node micrometastasis, we developed a volume registration method for analyzing the vessel structure in the lymph node by using Scale-Invariant-Feature-Transform and Phase-Only Correlation methods. The algorithm developed here was for correcting images for evaluation of ultrasound images of the experimental metastatic lymph node, and also for calculating highly accurate information of blood vessel considering the dispersion value due to temporal change of luminance information and those before and after contrast agent administration. As a result, it was possible to eliminate misalignment and noise of the ultrasound images, and also extract the microstructure of the blood vessels in the metastatic lymph node.
頭頸部リンパ節転移モデルマウスを用いた薬剤内封ミセルの動態と効果に関する研究 Competitive

小玉哲也

Offer Organization: ナノキャリア株式会社

System: 共同研究費

2015 - 2017
Diagnostic system using a high-frequency ultrasound with contrast agent to distinguish cancerous area from keratotic lesion of oral mucosa

MORIKAWA HIDEHIRO, TAKAHASHI TETSU, MORI SHIRO, KODAMA TETSUYA

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2013/04/01 - 2016/03/31

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Diagnostic system to distinguish cancerous area from keratotic lesion of oral mucosa was tested in this study. First of all, we examined a procedure using a high-frequency ultrasound with contrast agent in the experimental cancer model of mice. As a result, this procedure was useful in measuring the depth of cancerous lesion, but not so effective to evaluate two dimensional area of the cancer. To evaluate the area of cancer, we made the ICG encapsulated liposomes as a contrast agent, and then observed the experimental cancer model using a fluorescence stereomicroscope. From this observation, it was revealed that the fluorescence imaging using the ICG encapsulated liposomes is useful in the evaluation of the two dimensional area of the cancer.
Drug delivery system using nano-microbubbles and ultrasound applicable to a gene therapy for temporomandibular joint ankylosis

KONDO AYA, MORI SHIRO, KODAMA TETSUYA

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2013/04/01 - 2016/03/31

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In this study, we examined a drug delivery system using nano-microbubbles and ultrasound applicable to a gene therapy for temporomandibular joint ankylosis. As a study model, the kinetics of luciferase gene expression was analyzed in the mice model for the joint ankylosis by using bioluminescence imaging. To improve transfer efficiency of transfection with minimum tissue damage, parameters such as irradiation time of ultrasound, ultrasonic frequency to be irradiated, ultrasonic pressure, the duty ratio, pulse number, structure of the nano-microbubbles, the zeta potential, bubble size, the inner sealing gas, and the proportion of cells and the bubble were tested. As a result, the luciferase gene activity was observed in the skeletal muscle close to the knee joint of the model mouse after the luciferase gene transfection.
高精度超音波画像診断装置の開発 Competitive

Offer Organization: 厚生労働省

2012 - 2016
Development of alveolar bone regenerative therapy using nano/microbubbles with IGF-I plasmid gene.

IIKUBO Masahiro, SASANO Takashi, KOJIMA Ikuho, SAKAMOTO Maya, KODAMA Tetsuya, MORI Shiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2012/04/01 - 2015/03/31

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The purpose of this study was to investigate the longitudinal morphological changes in extraction sockets following sustained IGF-I treatment. Fourteen rats were subjected to right mandibular first molar extraction. Experimental rats received a continuous subcutaneous infusion of IGF-I. Micro-computed tomography scanning was performed immediately after tooth extraction, and at 1, 2, 3 and 6 weeks after extraction. New bone formation was markedly higher in the IGF-I treated group as compared with the control group. The loss in alveolar ridge height in the IGF-I group was significantly lower than that in the control group at each time point after extraction on the buccal side, and at 2, 3 and 6 weeks on the lingual side. In conclusions, IGF-I treatment increases the volume of newly formed bone and reduces the loss in alveolar ridge height following tooth extraction.
Three dimensional structural analysis and functional evaluation of lymphatic network

KODAMA Tetsuya, ONO Masao

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2012/04/01 - 2015/03/31

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The lymphatic system plays a crucial role in tumor formation and metastasis progression. However, its function and structure have not been investigated fully. Here we show characteristics of lymphatic network between the subiliac lymph node (SiLN) and proper axillary lymph node (PALN), and of metastasis induction via lymphatic vessel. We used MXH10/Mo-lpr/lpr inbred mice that exhibit systemic lymphadenopathy. We found that bifurcation patterns for the lymphatic vessel that lies between the SiLN and the PALN. In most cases the lymphatic vessel had at least one bifurcation. Furthermore we found that metastasis was induced in the PALN by injection of tumor cells into the SiLN. The intranodal pressure increased in the SiLN and PALN during the course of LN metastasis. The findings provide new insights relevant to the investigation of the mechanisms of lymph node metastasis and and the development of treatment methods for lymph node metastasis, including drug delivery systems.
Development of real-time image analysis system of cervical lymph node network using nanobubbles

SAKAMOTO Maya, KODAMA Tetsuya, IIKUBO Masahiro, KOJIMA Ikuho, MORI Shiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2012/04/01 - 2015/03/31

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The aim of this study is to develop a new diagnostic imaging technique which can detect the head and neck cancer metastasis routes. In this study, MXH10 / Mo / lpr mice, which develop systemic swelling of lymph nodes up to 10 mm in diameter, were used as a lymph node metastasis model. As a method for visualization of lymph node network in real time, we examined a contrast ultrasound imaging system using nano-microbubbles. As a result, it was suggested that contrast ultrasound image analysis method using a nano-micro-bubbles might be a potential method clinically applicable to detection of lymphatic network.
Development of a Vasohibin gene delivery system using nano/microbubbles and ultrasound

HORIE Sachiko, SATO Yasufumi, KODAMA Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up

Category: Grant-in-Aid for Research Activity Start-up

Institution: Tohoku University

2012/08/31 - 2014/03/31

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Vasohibin-1 (VASH1) is an angiogenesis inhibitor. There are two transcripts of VASH1: one is the full length VASH1A and the other is splicing variant VASH1B. In this study, the anti-antitumor effects of VASH1A and VASH1B have been examined with a mouse solid tumor model using a tissue-specific gene delivery method using nano/microbubbels and ultrasound. Both VASH1A and VASH1B inhibited tumor growth exhibiting anti-angiogenic activity. However, more importantly, VASH1A stabilized neovessels while VASH1B pruned neovessels.
Development of contrast agent of ultrasonography for visualizing pancreatic islets

SAKATA Naoaki, KODAMA Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2012/04/01 - 2014/03/31

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In this study, we attempted to develop a novel contrast agent of ultrasonography aiming to visualizing transplanted pancreatic islets. The contrast agent was made by attachment of octreotide on liposome via polyethylene glycol chain, and was used after infusion of C3F8 gas. Enhanced ultrasonography using this agent for diabetic transplanted syngenetic islets showed increase of echogenicity in transplanted islets. The enhancement was significantly correlated with endocrine function of the mice.
Experimental study towards the development of lymphatic drug delivery system for the treatment of cervical lymph node metastasis

MORI SHIRO, KODAMA Tetsuya, ONO Masao

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2012/04/01 - 2014/03/31

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The present study was performed to examine the possibility of intra-lymphatic chemotherapy with minimally invasiveness for cervical lymph node metastasis by using the lymph node metastasis mouse model showing lymphadenopathy. This study revealed that selective intra-lymphatic administration of anticancer agent is available. Moreover, it became clear that irradiation of ultrasonic waves after the simultaneous administration of nano-microbubbles and anticancer agent into the metastatic lymph node via lymphatic vessel enhanced effective induction of anticancer agent into the cells of the targeted lymph node.
Super-selective molecular delivery system of metastatic lymph node using nanobubbles and ultrasound

KODAMA Tetsuya, FUJIKAWA Shigeo

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2011/04/01 - 2014/03/31

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The purpose of this study was to develop a super-selective molecular delivery system of lymph node metastasis via lymphatic vessels using nanobubbles (NBs) and ultrasound (US). We used MXH10/Mo-lpr/lpr mice exhibiting remarkable systemic lymphadenopathy, with proper axillary lymph nodes (PALNs) and subiliac lymph nodes (SiLNs) that are 6 to 12 mm in diameter. First, we identified 22 different LNs situated in the head and neck, limbs, thoracic and abdominal regions. The metastasis route was found to be via the efferent lymphatic vessels of the SiLN, and metastasis incidence depended on the number of cells injected, the injection duration and the SiLN volume. Next, we investigated drug delivery efficiency to the lymph node metastasis by the molecular delivery method using NBs and US. It was found that exposure to US in the presence of NBs enhanced the delivery of fluorophores into the lymphocytes near the lymphatic channels, compared to the use of US in the absence of NBs.
Development of the novel approaches to diagnose and treat head and neck cancer using nanotechnology

SHIGA Kiyoto, KODAMA Tetuya, MORI Shirou

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Iwate Medical University

2011 - 2013

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It is well known that angiogenic processes in growing tumors promote increased vessel density and structural abnormalities. Lymph node metastasis of the head and neck cancer also showed this neo-vascularization features in active phase of metastasis. The purpose of this study is to evaluate the vascular density and morphology in metastatic lymph nodes by using microbubbles as ultrasound contrast-enhancing agent. On the next stage, we intend to use hybrid nanobubbles to introduce some anti-tumor agents or transformed constructs into cancer cells as drug delivery system. We developed novel image-analyzing software to analyze capillary vessels in lymph nodes of the patients. After they underwent neck dissection, all of the patients who showed contrast-enhancement in their lymph nodes had carcinoma metastases in their lymph nodes by histopathological examination. Contrast ultrasound using our software is useful to detect lymph node metastasis of the head and neck cancer.
流動ダイナミックス知の融合教育研究世界拠点 Competitive

Offer Organization: 東北大学

2008 - 2013
Exploration of Optimum Conditions for Sonoporation Effect by Controlling Multi-Phase Flow Field with Microscopic Visualization

TOMITA Yukio, MATSUURA Toshihiko, KODAMA Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Hokkaido University of Education

2011 - 2012

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A fine liquid jet was produced during the collapse of individual small gas bubbles in the second collapse of an attached Sonazoid microbubble. Evidential pits are found on the gel surface. Nanoscale pits are dominant in 0.01 s < T_<ex> < 1 s, and caused by the collapse of Sonazoid microbubbles, whereas microscale pits in T_<ex> > 1 s mainly resulted from cavitation. We found the maximum number of pits when a moderate pressure amplitude of 0.45 MPa was applied, together with a duty ratio of 0.1 and 20 pulses, a result that nearly equals that obtained by continuous ultrasound at a pressure of 0.75 MPa. These results suggests that more suitable conditions for sonoporation can be determined by systematically exploring the characteristics of ultrasound.
超音波診断・治療技術に関する研究 Competitive

小玉哲也

Offer Organization: パナソニック

2011 - 2012
Development of imaging diagnosis system for oral cancer utilizing lesion-integrated nanobubbles and high frequency ultrasound

MORI Shiro, ONO Masao, KODAMA Tetsuya, ONO Masao

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2010 - 2012

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The purpose of the present study is to develop a real-time imaging system using high frequency ultrasound and nanobubbles for the diagnosis of oral cancer. In order to evaluate the diagnostic accuracy of the high-frequency ultrasonic imaging analysis for oral cancer, we established a recombinant inbred strain of mouse showing a similar size of lymph node swelling as that of human. As a result, in the metastatic lymph nodes,it became clear that nanobubbles leake and integrate into the perivascular region of the lesion by enhanced permeability and retention (EPR) effect. This finding suggests that the image analysis using high-frequency ultrasound and nanobubbles isextremely useful in diagnosis of the metastatic lesions in the lymph node.
Molecular delivery therapy for metastatic liver tumor derived from pancreatic cancer using the nanobubble

AKADA Masanori, EGAWA Shinichi, KODAMA Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2010 - 2012

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In this study, we attempted to develop a novel type of nanobubble anticancer agent for treating metastatic liver tumor derived from pancreatic cancer, and to evaluate the effectiveness. We prepared the mice which were received transplantation of tumor cell line, and performed high frequency ultrasonography to the mice using the agent and evaluated the enhancement of the liver in early stage of the transplantation. The enhancement effect was certified and the effect was similar to a microbubble agent used in clinical (SonazoidR).
An experimental study for developments of a 4D-imaging system and a novel gene therapy for the hemangioma using nanobubbles and ultrasound

SAKAMOTO Maya, IIKUBO Masahiro, MORI Shiro, KODAMA Tetsuya, ONO Masao, KOJIMA Ikuho, SASANO Takashi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2009 - 2012

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The aim of the present study is to develop a diagnostic imaging system and gene therapy system for hemangioma using nanobubbles and ultrasound. In the present study, by using experimental tumor model, we developed a high-resolution diagnostic imaging system utilizing nanobubbles and high-frequency ultrasound image analysis equipment. In addition, we were able to present the possibility of a new gene therapy method for hemangioma by transfer of a plasmid DNA, which inhibited the tumor growth, by utilizing nanobubbles and ultrasound.
超音波計測練成解析による超高精度生体機能計測システム Competitive

Offer Organization: 科学技術振興機構

2006 - 2012
Development of a Simulation Technique for Gene/Cancer Therapy Using Nano/Micro Bubbles

TAKAHIRA Hiroyuki, KODAMA Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Osaka Prefecture University

2010 - 2011

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This study is aimed to develop a technique for gene therapy using bubble collapse. The motion of acoustic liposomes under pressure change is investigated experimentally and a bubble model for acoustic liposomes is developed. The collapse of a bubble near a tissue surface is simulated using the boundary element method or the ghost fluid method. A simulation technique is also developed for the transport of therapeutic molecules using bubble collapse. It is shown that the bubble motion is much affected by the variation of surface tension due to the reduction of phospholipid layers on the bubble surface. The tissue boundary velocity is correlated to the impulse at the tissue due to bubble collapse. The usage of vortex flows generated by the liquid jet accompanied with bubble collapse is effective in transporting the molecules.
Development of the cure by the transgenics using the nano bubble to the Recklinghausen disease

TACHI Masahiro, KODAMA Tetsuya, IMAI Yoshimichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2010 - 2011

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Initially the aim of this study was development of a gene therapy of von Recklinghausen's disease. However, because it became clear that integration of NF-1 gene into the vector was difficult, we have changed the target to Malignant peripheral nerve sheath tumor (MPNST), complicating disease of von Recklinghausen's disease. We have observed a marked decrease in number of cells by transfection of IFN-α and IFN-γ gene into cells delived from MPNST.
Development of study model and medical treatment procedure for the FGFR2-related craniosynostosis syndromes

MORI Shiro, KODAMA Tetsuya, ONO Masao

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2010 - 2011

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The aim of the present study is to develop a study model and medical treatment procedure for the FGFR2-related craniosynostosis syndromes. In the present study, a new recombinant congenic strain of mice, which is a model for the dysplasia of bone and cartilage, was successfully established, and the onset of the disease in the mice was significantly associated with the genetic locus of FGFR2. By using the animal model and gene delivery system to the tissue around bone using nanobubbles and ultrasound, it became to be possible to perform an experimental molecular therapy using the Ig-Fc fusion protein of FGFR2 against the study model for the FGFR-related dysplasia of bone and cartilage.
超音波診断・治療技術に関する研究 Competitive

小玉哲也

Offer Organization: パナソニック

2010 - 2011
An experimental study for development of real time diagnosis system for oral cancer treatment using nanobubbles and ultrasound

MORIKAWA Hidehiro, MORI Shiro, KODAMA Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2009 - 2011

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The aim of the present study is to develop a real time imaging diagnosis system for oral cancer using nanobubbles and high-frequency ultrasound. As a result, the following problems were revealed, halation caused by the ultrasound contrast agent, blurring of the image caused by arterial pulsation, and imaging of the immature angiogenesis of the tumor. On the other hand, the diagnostic accuracy could be improved by analyzing the four-dimentional dynamics of nanobubbles in the blood flow. In this stu dy, to solve the problems, hardware and software of the high frequency-ultrasound imaging system were improved
Development of a real time diagnosis of lymph node metastasis by ultrasound and nanobubbles

KODAMA Tetsuya, HAYASE Toshiyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2009 - 2011

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The aim of the present study is to develop a real time diagnostic method of lymphatic metastasis less than 1cm in diameter. First we developed the color difference based on standard deviation (CDSD)method. Next we succeeded in extracting vascular structures in the tumors of less than 1 cm in diameter by high-frequency ultrasound (HF-US)system, nanobubbles (NBs), and the CDSD method. We applied the methodology to the lymphatic metastasis model, and found that it was applicable to early diagnostic and treatment evaluation of lymphatic metastasis.
An experimental study for a novel gene therapy for the highly malignant tumor of salivary gland using nanobubbles and ultrasound

SAKAMOTO Maya, IIKUBO Masahiro, MORI Shiro, KODAMA Tetsuya, ONO Masao, KOJIMA Ikuho

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2009 - 2011

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The aim of the present study is to develop a novel diagnosis and gene therapy system for the highly malignant tumor of salivary gland using nanobubbles and ultrasound. In the present study, by using experimental tumor model, we developed a high-resolution diagnostic imaging system utilizing nanobubbles and high-frequency ultrasound image analysis equipment. In addition, we were able to present the possibility of a new gene therapy method by transfer of a plasmid DNA, which inhibited the tumor growth, by utilizing nanobubbles and ultrasound.
ナノバブルと超音波を用いた転移性肝がんに対する新たな遺伝子治療法の開発

小玉哲也, CHEN. R.

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特別研究員奨励費

Category: 特別研究員奨励費

Institution: 東北大学

2009 - 2010

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本研究では,転移性肝がんの遺伝子治療法の開発とその治療効果の定量化を目的にしている.本年度は,昨年度に開発したマウス転移性肝がんモデルを使用して,ナノ・マクロバブルを用いた肝臓内血管密度の変化に基づく肝転移早期診断法の開発を目的にした.ナノバブルとして音響性リポソーム,マイクロバブルとしてソナゾイドを使用した.まず.EMT6-Lucルシフェラーゼ発現性細胞をマウスの脾臓に移植し,肝転移がんモデルを作製した.つぎに,バブルをマウスの尾静脈に注射して,血管内を流れるバブルの輝度情報から肝転移内の血管像を実験小動物用超高解像度超音波イメージングシステムで構築した.バブルと周囲組織との超音波輝度値が明確化になるように血液中のバブル濃度を調整した.三次元血管構築により腫瘍組織,腫瘍新生血管の縮退・形状変化,血管密度等の定量化をおこなった.ソナゾイドを用いた場合,肝臓内の血管密度がコントロールに対して有意に増加することが示されたが(P<0.05),ナノバブルでは生体内の寿命が短いために有意差が得られなかった.今後,ナノバブルの安定性を高めることで,EPR効果を利用した腫瘍新生血管のイメージングや遺伝子導入が可能になるものと考えられる.
東北大学医工学研究科研究科長裁量経費 Competitive

小玉哲也

Offer Organization: 東北大学

2009 - 2010
ナノバブルを用いた転移リンパ節遺伝子治療法の開発 Competitive

小玉哲也

Offer Organization: 科学技術振興機構

System: シーズ発掘試験

2009 - 2010
長期安定性ナノバブルの開発とがん治療への応用 Competitive

小玉哲也

Offer Organization: 三菱UFJ信託銀行株式会社

System: 公益信託五峯ライフサイエンス国際基金研究助成

2009 - 2010
Development of gene therapy of liver and bladder cancer by using nanobubbles and ultrasound

KODAMA Tetsuya, FUJIKAWA Shigeo

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2008 - 2010

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The present research was aimed to develop a new gene therapy method of bladder and liver cancer by using nanobubbles (NBs)and ultrasound (US). The former was based on regional cancer therapy, and the later on the enhanced permeability and retention (EPR)effect. We developed acoustic liposome (NBs)(<200nm in diameter)as drug carrier and ultrasound contrast agent, dual ultrasound exposure system with high/low acoustic intensity pulses for effective delivery of fluorescent molecules and naked plasmid DNA to the bladder wall in the presence of NBs. In addition, we achieved therapeutic level by delivering tumor necrosis factor (TNF)-alpha expressing plasmid DNA to solid tumors of mice with NBs and US. Furthermore, we established a two/three-dimensional (2/3D)vascular construction method to evaluate therapeutic effects on liver cancer by using NBs and US. Our results demonstrate that the combination of these established materials and methodology can be used for a new gene therapy of bladder and liver cancer.
Transfection of Kir6. 2 channel genes into native vascular smooth muscle using sonoporation

TERAMOTO Noriyoshi, INAI Tetsuichiro, KODAMA Tetsuya, ITO Hiroyuki

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

2008 - 2010

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The combination of ultrasound and nano-bubbles coated with lipid bilayers(i. e. hybrid nano-bubbles) induces transient membrane permeability, leading to direct delivery of exogenous molecules(such as plasmid, siRNA, anticancer drugs etc.) into cells with minimal invasion. This method is generally termed as to be a sonoporation technique. When Kir6. 2(inwardly-rectifying K^+ channel family 6 subtype 2) genes have transfected into native vascular smooth muscle layers of mouse aorta by use of sonoporation, RT-PCR analysis revealed the expression of Kir6. 2 transcripts in vascular smooth muscle. When Kir6. 2 genes, tagging with Myc-genes, were transfected into native smooth muscle layers using sonoporation, immunohistochemical studies have revealed that Kir6. 2 and Myc proteins were co-expressed in vascular smooth muscle cells. The phenylephrine-induced contraction of mouse aorta was significantly reduced after the treatment of Kir6. 2 gene-sonoporation, hyperpolaring the membrane potentials of vascular smooth muscle. These results suggest that Kir6. 2 genes were functionally expressed in mouse vascular smooth muscles, causing a vascular relaxation due to the activity of Kir6. 2. Thus, we have succeeded to establish the novel gene-transfected method.
Focused Ultrasound Controlled Cavitation Bubble Collapse and Promotion of Sonoporation Effect

TOMITA Yukio, KODAMA Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Hokkaido University of Education

2008 - 2010

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The relation between Sonazoid destruction and the resultant cavitation phenomena has been investigated by employing ultrasound waves with the frequency of 1 MHz which were irradiated from two types of US probes with a flat boundary as well as a curved boundary. It was found that Sonazoid microbubbles were rapidly destroyed and the survival number was reduced to half the original number within 100 ms after ultrasound irradiation. The debris of microbubbles played a role of cavitation nuclei from which a large number of cavitation bubbles grew. A liquid micro-jet and a shock wave occurred during the short period of the bubble collapse. An impact pressure resulting from one of these short term phenomena seems to be an important cause of sonoporation which could make a fine hole in the cell membrane transiently.
ナノバブルと超音波を用いたワクチン療法の開発と若手研究者育成事業 Competitive

小玉哲也

Offer Organization: 東北大学

System: 東北大学アジア・アフリカプログラム

2007 - 2010
ナノバブルと超音波を用いた高周波超音波三次元画像診断・分子導入システムの開発 Competitive

小玉哲也

Offer Organization: 厚生労働省

2007 - 2010
In vivo イメージング技術の開発と生体運動機構の解明. Competitive

Offer Organization: 科学技術振興機構

2006 - 2010
ナノバブルを用いた腫瘍新生血管標的性リアルタイム超音波分子導入システムの開発

小玉哲也

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究

Category: 特定領域研究

Institution: 東北大学

2008 - 2009

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本研究は,EPR(Enhanced and Permeability Retention)効果で固形腫瘍内の血管を流れ,漏出・滞留するナノバブルをコンピューター制御下にある超音波で破壊し,このとき発生するキャビテーション気泡の衝撃圧で血管壁周辺組織に治療性分子を導入し,「血管新生の抑制を目指す実時間超音波分子導入システムの開発」と「がん遺伝子治療」への応用を目的にしている. 従来の血管を介したマイクロ気泡と超音波を利用した遺伝子導入の研究では,プラスミドDNAとマイクロ気泡の混合液が使用されてきた.この方法では,血液中に大量に存在するエンドヌクレアーゼの作用でDNAが急激に分解される確率が高いことが知られている.本年度では,液体とガスが同時に封入されるナノバブルの作製と定量化をおこなった.査型電子顕微鏡観察から,ガスと液体が同時に封入される割合は20%であった.液体だけが内封されるリポソームの場合には,プラスミドDNAの封入率は30%である.実時間での分子導入法の開発では,ナノバブルの移動で得られる超音波の画像の閾植をトリガー信号にして超音波の照射が可能な実時間分子導入法をすでに開発している.この手法を用いることで,ナノバブル集積箇所でナノバブルを破壊してナノバブルに含まれる薬剤を選択的に導入できるシステムの開発が可能になった. 本研究の実施期間2年以内に,当初の目標を達成することができた.本研究を臨床に意味ある手法に展開するために,遺伝子導入後の遺伝子発現を陽電子放出断層撮影(PET)で可視化するイメージング法の開発に着手した.本研究は,今後,このPETイメージング法の開発とともに展開されることになる.
東北大学研究科長裁量経費 Competitive

小玉哲也

Offer Organization: 東北大学

2008 - 2009
非侵襲組織標的性分子導入法を用いたがん確定診断法の開発 Competitive

小玉哲也

Offer Organization: 科学技術振興機構

System: シーズ発掘試験

2008 - 2009
Evaluation of Angiogenesis by High Resolution Three-dimensional Ultrasound Molecular Imaging

SAIJO Yoshifumi, SATO Yasufumi, KODAMA Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2007 - 2009

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High resolution three-dimensional ultrasound molecular imaging was developed for evaluation of angiogenesis in small animals such as mice. The following were achieved ; 1. Three-dimensional ultrasound imaging system with the frequency range up to 150 MHz and the spatial resolution of 10 micron, 2. Image analysis algorithm for classification of vessels and surrounding tissues by correlation of RF signals in the consecutive frames, 3. Portable scanner for easy and repetitive use, 4. Molecular imaging of angiogenesis with labeled nano-bubble.
An imaging and drug delivary system for treatment of oral cancer by using ultrasound and nano-bubbles

MORI Shiro, KODAMA Tetsuya, ONO Masao

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2007 - 2009

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In the present study, we try to develop a three-dementional imaging system and drug delivery system by using nanobubbles and ultrasound for diagnosis and treatment of oral cancer. As a result, we could make three-dementional ultrasound imaging of neovascularization in small tumor, which could not be detectable by using conventional imaging system such as CT or MRI. Moreover, when the treatment experiment of tumor by the drug delivery system that used the nanobubbles and ultrasound was done, the therapeutic gain by this method was able to be confirmed.
臓血管系の計測融合数理モデルとレーザー計測 Competitive

Offer Organization: 日本学術振興会

System: ロシアとの共同研究（RFBR)

2007 - 2009
A feasibility study for the treatment of oral cancer using a new drug delivery system and cell inhibitor

MORIKAWA Hidehiro, MORI Shiro, KODAMA Tetsuya

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2007 - 2008
ナノバブルによる新しい遺伝子導入法の開発と末梢循環障害の治療への応用

寺本憲功, 伊東啓行, 小玉哲也

Offer Organization: 日本学術振興会

System: 科学研究費助成事業萌芽研究

Category: 萌芽研究

Institution: 九州大学

2007 - 2008

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我々は様々な低分子の安定ガスを用いてナノサイズのガス粒子およびGFP発現遺伝子を共に封入させ、さらにその周囲を様々な種類のリン脂質を用いて新規ハイブリッド型ナノバブルを試作した。これらの作成したハイブリッド型ナノバブルを用いてHEK293細胞(培養細胞)へのGFP発現遺伝子の導入効率を指標としGFP蛍光をFACSにて計測しその導入効率を定量化した。その結果、最終的に低分子の安定ガスとしてはC_3F_8ガス、またリン脂質としては (Distearoyl-Phosphocholine)-Distearoyl-Phosphoethanolamine-Poly Ethylene Glycolと(Distearoyl phosphatidylcholine)-Poly Ethylene Glycolを選び、ハイブリッド型ナノバブルを完成した。本ハイブリッド型ナノバブルは下記の優れた特徴を有した。 1)リン脂質から成る脂質2重膜内の液相中に導入遺伝子が内封され、血液(体液)中でも導入遺伝子(cDNA)はエンドヌクレアーゼにて加水分解されない。 2)ハイブリッド型ナノバブル内には液相が存在する。この液相中に水溶性のプラスミドDNAが溶解し、導入遺伝子は長期間、安定した状態でハイブリッド型ナノバブル内に保存される。 3)ハイブリッド型ナノバブル内にはC_3F_8ガスから成るナノサイズの微小ガス粒子が含まれ、封入された導入遺伝子の近傍にてC_3F_8ガスによる有効かつ強力な衝撃波が生じるため、in vivo条件における遺伝子導入効率が極めて高い。 4)ハイブリッド型ナノバブルはリン脂質2重膜にてコートされているため、ゼータ電位がほとんど無い。したがってマイナス電荷に帯電している細胞膜に対しても何ら影響なく接近し細胞内に導入することが可能である。すなわち、本ハイブリッド型ナノバブルはソノポレーション法による低侵襲性遺伝子導入の臨床応用に向け、今後、極めて有用なナノサイズレベルの遺伝子導入ツールに成りうると考えた。現在、本研究成果を基に特許の申請準備および原著論文の執筆中である。
A feasibility study for a new vaccination system using Nanobubbles and ultrasound

HORIE Sachiko, KODAMA Tetsuya, ONO Masao, MORI Shiro

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (Start-up)

Category: Grant-in-Aid for Young Scientists (Start-up)

Institution: Tohoku University

2007 - 2008
超音波を利用したsiRNA内包バブルリポゾームのがん局所療法の臨床試験導入 Competitive

Offer Organization: 厚生労働省

2005 - 2008
ナノバブルによる新しい遺伝子導入法の開発とがん治療への応用

小玉哲也, 小野栄夫, 伊藤正敏, 小濱泰昭

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究

Category: 特定領域研究

Institution: 東北大学

2006 - 2007

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超音波とナノバブルを利用した分子導入法は、任意の組織に遺伝子などの高分子を導入することが可能な手法として注目を集めている。一方で、遺伝子治療では、遺伝子導入後の遺伝子発現プロファイルを非侵襲的にモニターし、患者の効果的な治療計画を立案することが望まれる。本研究では、ヨウ素取込み作用をもつNIS遺伝子に着目して、ヨウ素の集積からNIS遺伝子の発現プロファイルをポジトロン断層法(PET)で定量化することを試みた。PETでは陽電子放出核種であるヨウ素124Iの生成が必要であるが、共同分担者が所属する東北大学ラジオアイソトープセンターでの過去3年間の研究により、日本で初めて124Iの生成が常時可能になった。また、世界初の半導体PETの開発の実績を受けて、マイクロバブルと超音波でマウス骨格筋に導入されたNIS遺伝子の発現プロファイルを世界で初めて半導体PETを使用して定量化することができるようになった。この集積性を124Iの生体分布とオートラジオグラフィで確認をおこなった。さらに臨床応用を念頭に、血管病変マウスに超音波とナノバブルを利用した分子導入法でNIS遺伝子を導入し、その発現をPETで確認することができた。これにより、PETイメージングを基本とした遺伝子治療の臨床応用への可能性が示唆された。
ナノバブルを用いたリアルタイム分子導入法の開発と腫瘍血管新生抑制治療への応用

小玉哲也, 小野栄夫, 早瀬敏幸, 藤川重雄

Offer Organization: 日本学術振興会

System: 科学研究費助成事業萌芽研究

Category: 萌芽研究

Institution: 東北大学

2006 - 2007

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本研究は、EPR効果で固形腫瘍内の血管を流れ、漏出・滞留するナノバブルを超音波で破壊し、このとき発生するキャビテーション気泡の衝撃圧で血管壁周辺組織に治療性分子を導入し、「血管新生の抑制を目指す実時間超音波分子導入システムの開発」と「がん遺伝子治療」への応用を検証することを目的とする。本年度では脂質二重膜からで構成されたナノバブルに、ガスと液体を封入し、脂質二重膜には抗体を組み入れることが可能な、ナノサイズの音響性リポゾームを開発することに成功した。これにより、EPR効果で腫瘍新生血管から漏出・滞留するナノバブルを破壊することで封入された薬剤を局所的に血管壁近傍に導入することが可能な分子導入システムを開発した。またバブルの集積の輝度値で超音波を照射することが可能なトリガーシステムを開発し、当初予定していたスーパーコンピュータを介在させた分子デリバリーシステムが可能なった。バブルの移動軌跡は超音波画像として認識されるので、この移動軌跡を抽出することで二次元および三次元の血管構造を抽出することが可能になった。上記の血管壁への分子導入システムと血管構造抽出システムを併用することで、診断と治療が可能なリアルタイムな分子導入システムを構築することができた。
非侵襲的脊髄遺伝子導入による新たな疼痛治療戦略の開発

高橋雅彦, 小玉哲也, 城戸幹太

Offer Organization: 日本学術振興会

System: 科学研究費助成事業萌芽研究

Category: 萌芽研究

Institution: 東北大学

2006 - 2007

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平成18年度の研究により、プラスミドDNAと微小気泡の混合液をマウス脊髄くも膜下腔へ注入し、超音波を照射することにより脊髄硬膜組織へ目的とする遺伝子を導入ができることを確認した。この結果を踏まえて、19年度は以下のような研究を行った。 1.内因性オピオイドのひとつであるβエンドルフィンの前駆物質プロピオメラノコルチン(POMC)遺伝子を含むプラスミドベクターを作成した(インビトロゲン社製)。このベクターが供与する核酸は以下のとおりである。マウスcDNA(POMC遺伝子)、ヒトゲノムDNA(EFIαプロモーター)、サイトメガロウイルス(CMV)IEプロモーター、ネオマイシン耐性遺伝子、カナマイシン耐性遺伝子、オワンクラゲ緑色蛍光タンパク質(GFP)遺伝子及びその変異体。 2.培養細胞(ヒト胎児腎細胞由来)に作製したプラスミドを上記の方法で物理的に導入し、GFP発光を確認した。 3.マウス(BALB/c雄6〜8週)をペントバルビタール腹腔内麻酔後、L4-5問より27G注射針で髄腔内にプラスミドDNAと微小気泡(診断用超音波造影剤アルブミンバブルOptisonTM)の混合液10μlを経皮的に注入し、直ちに水中で刺入部脊椎に垂直に超音波を照射した。 3.照射3日後に、von Frey線維による痛覚閾値と赤外線熱刺激装置による温覚閾値の測定をマウス後脚で行った。しかし、いずれも閾値も対照マウスとの差が認められなかった。また、摘出脊髄標本でもGFPの発光が確認できなかった。この理由としては、遺伝子導入効率が低い可能性や導入されたPOMCからβエンドルフィンが産生されていない可能性が考えられた。
Development of a high-throughput molecular delivery method using microbubbles and ultrasound and its application to cancer gene therapy

KODAMA Tetsuya, ONO Masao, FUJIKAWA Shigeo, TOMITA Yukio

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2005 - 2007

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Non-invasive, tissue-specific molecular delivery is crucial for the efficiency and reduced side effects of a wide range of treatments. A physical method that combines microbubbles (MB) with ultrasound (US) has been regarded as one of the few methods capable of delivering genes into target sites non-invasively. Applied to cancer gene therapy, this method could efficiently target cancer, and may be more efficient than immune gene therapy, as patients are often immunocompromised. However, several essential aspects remain unexplored. First, cavitation bubbles are believed to be a major cause for molecular delivery; however, the relation between wave characteristics and subsequent generation and collapse of cavitation bubbles has not been elucidated, therefore gene transfer has not been optimized. In addition, molecular delivery and subsequent gene expression have not been quantified in vivo. In the present study, these parameters in vitro and in vivo were optimized, and the mechanism of molecular delivery with theoretical and computer analysis were elucidated. Hypothesizing that free cavitation bubbles were generated from cavitation nuclei created by fragmented MB shells, we estimated the shock wave propagation distance that would induce cell membrane damage from the center of the cavitation bubble. Next, we investigated the structural change of a phospholipid bilayer in water under the action of a shock wave with molecular dynamics simulations. The resulting collapse and rebound of the bilayer followed by the penetration of water molecules into the hydrophobic region of the bilayer induced after the shock wave interaction were demonstrated. Finally, we evaluated the application of this technology to cancer gene therapy using herpes simplex virus thymidine kinase-mediated suicide gene therapy. We observed dramatic reductions of the tumor size by US/MB-mediated transfer. These data demonstrate the potential of US/MB as a new physical gene delivery method for cancer gene therapy.
ナノバブルによる血中ドラッグデリバリーを利用する新しい癌治療技術の研究

吉岡修哉, 小玉哲也, 小濱泰昭, 加藤琢真, 古川剛

Offer Organization: 日本学術振興会

System: 科学研究費助成事業萌芽研究

Category: 萌芽研究

Institution: 東北大学

2005 - 2007

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平成19年度は、1.水中に放出されたバブルの詳細計測、及び2.バブルによる水中への酸素供給能力の評価を行った。これらの結果は今後、ドラッグデリバリー技術や角膜再生用培地技術の開発に活かす。 1.バブルの詳細計測昨年度に実用化した光学計測技術を用い、水中に浮遊するバブルの直径、真円率、移動速度を、水温や水流速をパラメーターとして計測した。その結果、水流速度が速いほど、バブルの直径が小さくなることが明らかとなった。またこの傾向には、有意な温度依存性は認められなかった。また、水流速度が速いほどバブルの真円率は1に近づいた。これは、バブル直径が小さくなることによって表面張力の影響が大きくなることが原因と考えられる。バブルの移動速度は、水槽内の水の流動速度とほぼ一致した。このことから、対象とする微細気泡の浮上速度のスケールは、水の流動速度と比較して小さく、効率よく水中に滞留出来ることがわかった。 2.バブルによる水中への酸素供給能力バブル放出による水中溶存酸素濃度変化を測定した結果、水流速が速いほど酸素濃度は短時間で上昇し、飽和濃度に達することが分かった。これは水流速が早いほどバブルが小さくなり、その分単位空気体積当たりの気液界面面積が大きくなる為、結果として効率よく酸素が溶解したためと考えられる。
Experimental study for development of microbubble applicable to clinical use in oral cancer chemotherapy

MORIKAWA Hidehiro, MORI Shiro, KODAMA Tetsuya, ONO Masao

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: TOHOKU UNIVERSITY

2005 - 2006

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In the present study, we have developed a micro-imaging system using microbubbles as an effective type of ultrasound contrast agent, and a molecular delivery system for oral cancer therapy using microbubbles and ultrasound. As a result, it was clarified that microbubbles of 200nm in diameter, flowing blood vessels, could be visualized by using high-resolution ultrasound micro-imaging system (the highest frequency : 80MHz). In addition, when the nanosized bubbles less than a diameter of 200nm were used as an ultrasound contrast agent, the enhanced permeability and retention effect, that is the property by which the bubbles tend to accumulate in tumor tissue much more than they do in normal tissues, was also visualized by the ultrasound micro-imaging system. On the other hand, to test whether the combined use of microbubbles and ultrasound has a potential to deliver some therapeutic materials into cancer cells, we examined the delivery efficiency of 5-FU and cisplatin, and a suicide gene, herpes simplex virus thymidine kinase (HSVtk) gene. From results of in vitro and in vivo studies using cancer cell lines and experimental mice, microbubbles with ultrasound produced significant cytotoxicity not seen with either ultrasound or drug alone. Moreover, HSVtk gene transfection to cancer cells using microbubbles and ultrasound showed a potential of cytotoxic sensitivity by ganciclovir. These results suggests that simultaneous use of the micro-imaging system and the molecular delivery system by using the microbubbles and ultrasound method combined with anti-cancer agents and/or suicide gene therapy has a potential to treat oral cancer.
口腔癌病巣集積型マイクロバブルの開発と治療への応用

森士朗, 小玉哲也, 小野栄夫, 鈴木麻衣子

Offer Organization: 日本学術振興会

System: 科学研究費助成事業萌芽研究

Category: 萌芽研究

Institution: 東北大学

2005 - 2006

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本研究は、マイクロバブルを口腔癌の治療に応用するための病巣集積型マイクロバブルを開発し、治療への応用を検討することを目的とする。本研究においては、当初マイクロバブルに血小板膜の性質を組み込むことにより、癌症巣への標的性を与えることことを目指し、血小板膜をマイクロバブル被膜に取り込んだ血小板キメラバブルの作成技術を検討した。まずヒト血液から血小板を抽出し、キメラバブルを作製した。しかし、このキメラバブルの作製過程において、将来の臨床応用を想定した場合のキメラバブルの生物学的活性の維持、血小板の供給源、キメラバブル作製のための費用、時間など様々な問題が明らかとなり、本来の本研究の目的を達成することが困難と思われた。しかしその一方で、本研究を遂行する過程において、マイクロバブルの大きさを直径200mm以下にすることにより、バブルが腫瘍血管から漏出し、腫瘍血管周囲に停滞すること、高周波超音波イメージング装置を用いることにより、雌内を流れる直径200mmの一個一個のノミブルの動きが可視化されること、我々が開発した高効率型超音波分子導入装置を用いることにより、細胞への分子導入高率が飛躍的に向上することなど、本研究の本来の目的の達成を可能にするマイクロバブルの腫瘍組織内での物理学的特性が明らかとなった。本研究においては、当初主眼においていた血小板キメラバブルの開発という構想は達成できなかったが、本研究で行った様々な実験結果からマイクロバブルの極めて有用な物理学的特性が明らかとなり、当初想定した目的よりもより汎用性のあるマイクロバブルによる癌組織への分子導入システムの開発への道が開けた。
次世代型・高次超音波・分子導入装置の開発 Competitive

小玉哲也

Offer Organization: 科学技術振興機構

2005 - 2006
マイクロ気泡による新しい分子導入法の開発とがん画像診断への応用

小玉哲也, 小野栄夫, 伊藤正敏, 鈴木麻衣子

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究

Category: 特定領域研究

Institution: 東北大学

2005 - 2005

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超音波造影剤(マイクロ気泡)と超音波を利用した分子導入法は、任意の組織に遺伝子などの高分子を非侵襲的に導入する手法として注目を集めている。この手法は免疫原性や細胞毒性はなく、癌や心臓血管疾患への治療応用が期待されている。一方、遺伝子治療では、遺伝子導入後の遺伝子発現特性を非侵襲的に診断し、患者の効率的な治療計画を立てることが望まれる。NIS遺伝子は甲状腺で恒常的に発現している遺伝子でヨウ素を取り込む働きがある。本研究申請ではこのNIS遺伝子に着目して非侵襲的分子導入法を使って腫瘍組織に遺伝子を導入し、この遺伝子の発現特性を非侵襲的に画像化することを目的としている。まず、in vitroおよびin vivoで癌細胞にレポーター遺伝子を導入し、その発現特性から分子導入法に関わる物理条件を最適化した。つぎに、この最適条件下でNIS遺伝子を癌細胞に導入した。in vitroでは経時変化に対するヨウ素^<125>Iの取込特性と放出特性を明らかにし、また、NIS遺伝子の発現活性が高い細胞株でヨウ素の取込量が高まることをmRNAの転写量から定量的に明らかにした。In vivoでは、ヨウ素^<123>Iを使い、γカメラでNIS遺伝子の発現の可視化を試みた。マウス側腹部で増殖させた異種腫瘍にNIS遺伝子をトランスフェクションさせた後、経口投与でマウスの胃に^<123>Iを導入し、マウス全体をγカメラで経時的に可視化を行った。胃、甲状腺、膀胱でヨウ素の集積が確認されたが、腫瘍ではヨウ素の集積が確認できなかった。この理由としてγカメラのバックグランドノイズが高いこと、および、可視化に必要な高濃度のヨウ素が日本では入手不可能で、実験に供し得なかったことがあげられる。現在、共同研究者である英国がん研究所のVassaux博士と、SPECT/CTを使い、高濃度のヨウ素^<123>Iでin vivoでの可視化実験を行っている。
Inhibition of intracoronary stent-Induced intimal hyperplasia with targeted microbubbles carrying the E2F decoy Competitive

Offer Organization: National Research Initiative

System: The National Research Initiative Competitive Grants Program

2002 - 2003
衝撃波伝播にともなう機能的形態的細胞損傷機構に関する研究 Competitive

小玉哲也

Offer Organization: 細胞科学研究財団

System: 育成助成

1998 - 1999
An Experimental Study of Photdynamic Therapy and Sonodynamic Therapy for Obstructive Cerebrovascular Diseases

IKEDA Hidetoshi, KODAMA Tetsuya, TAKAYAMA Kazuyoshi, YOSHIMOTO Takashi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

1997 - 1998

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In this study we tried photodynamic therappy(PDT) and photodynamic diagnosis(PDD) for experimentally induced or autopsy atheroscleotic plaques using doxycycline chlorate (DC) as a photosensitizer and Nd : YAG laser as a power source. The correlation between fluorescent intensity ratio and pathological grades of atherosclerotic plaques was considered. The result shows that the flnorescent intensity ratio of atheromatous lesions have pathologically a good correlation to the extent of atherosclerotic change. In PDT, we use "laser balloon cathter" consisted of balloon angiopiasty catheter and optic fiber . As a result, after PDT atherosclerotic plaques at irradiated part disappeared histologically in all cases. PDT and PDD would be one of modality of treatment and diagnostic parameter of athromatons lesions. Sonochemically induced cell damage (sonodynamic therapy) has been studied to treat for cancer. However, it is not elucidate that how the drug is excitated by the aoustic cavitation. This study has demonstrated that sonoluminescese photodynamically activaties sonosesitizers. Namely, this part of sonodynamic therapy is indirect photodynamic theapy. Furthermore, In this study we describe a rapid revascularization therapy using liquid jets generated by the interaction of gas bubble with shock waves, which impact on the thrombi. The results shows that liquid jets have the potential to penetrate through thrombi in as little as a few microseconds, and with very efficient ablation.
超微小火薬の医療応用に関する基礎研究 Competitive

小玉哲也

Offer Organization: 火薬学会

System: 火薬工業技術奨励会研究助成金

1997 - 1998
Basic Study of sound-dynamic Therapy for Atherosclerotic Cerebrovascular Disease.

YOSHIMOTO Takashi, IKEDA Hidetoshi, KODAMA Tetsuya, MIZOI Kazuo, TAKAYAMA Kazuyosi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

1995 - 1996

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Concomitantly with the progress of ultrasound technology in recent years, sonochemically induced cell damage (Sound-dynamic therapy) syudied various medical field, especially to treatment for cancer. In this time, these studies have demonstrated utility of sonosensitive materials (sonosensitizer) such as doxycycline (DC), hematoporphyrin and daunorubicine (DR). These results suggests that sonochemically induced cell damage by activated DC is probably mediated via sonoluminescence and by DR is probably mediated via singlet oxygen. Furthermore DC to accumulated in atheromatous plaque was excited by insonation, indicates the capability of Sound-dynamic therapy for atherosclerotic cerebrovascular disease. On the other hand, as the physical effect of ultrasound, we studied the efficacy of a liquid jet generated by the interaction of an underwater shock wave with air bubble to apply to acute fibrinolysis for cerebral embolism. Simulation studies using gelatin as embolus model and a teflon tube as a mimic vascular wall were performed. The penetration depth attained of the liquid jet was visualized by means of a high speed camera. It was suggested that the liquid jet impact induced by interaction between bubble and underwater shock waves had some potentiality as a new modality of revascularization for cerebral occlusive diseases.

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Social Activities 8

全く新しい抗がん剤の投入方法が開発される。副作用を軽減しながら、治療効果を最大化

2016/09/08 -

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ヒトのリンパ節と同じ大きさである特殊なマウスを用いて、新しいガン化学療法を模索する共同研究がおこなわれました。結果、従来の画像診断法では検出できないリンパ節（微小転移）の治療や予防を可能にする「新しい抗がん剤投与法」が提案されています。研究をおこなったのは東北大学大学院医工学らのチームです。
リンパ節転移治療に新抗癌剤投与法

2016/09/07 -

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東北大学は8月31日、従来の画像診断法では検出できないリンパ節の微小転移の治療や予防を可能にする新しい抗がん剤投与法を発表した。この研究は、同大大学院医工学研究科の小玉哲也教授、松木大輔元大学院生、武田航大学院生、同大学院工学研究科の多田明日香大学院生、東北大学病院の森士朗講師らの研究グループによるもの。研究成果は「ScientificReports」に9月1日付けで掲載されている。がん患者における死因の9割は、転移に起因するといわれている。乳がんや頭頸部がんをはじめとする上皮系由来のがんの多く
東北大学、リンパネットワークを介した新しいがん化学療法

2016/09/06 -

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小玉哲也（東北大学大学院医工学研究科教授、松木大輔（同大学院医工学研究科元大学院生）、多田明日香（同大学院工学研究科大学院生）、武田航（同大学院医工学研究科大学院生）、および森士朗（東北大学病院講師）らは、ヒトのリンパ節と同等の大きさを有する特殊なマウスを用いた共同研究から、従来の画像診断法では検出できないリンパ節の微小転移の治療や予防を可能にする、新しい抗がん剤投与法を提案しました。
リンパ節の微小転移の治療や予防を可能にする新たな抗がん剤投与法を発表－東北大

2016/09/06 -

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抗がん剤1滴ほどの量で治療可能に東北大学は8月31日、従来の画像診断法では検出できないリンパ節の微小転移の治療や予防を可能にする新しい抗がん剤投与法を発表した。この研究は、同大大学院医工学研究科の小玉哲也教授、松木大輔元大学院生、武田航大学院生、同大学院工学研究科の多田明日香大学院生、東北大学病院の森士朗講師らの研究グループによるもの。研究成果は「Scientific Reports」に9月1日付けで掲載されている。大
自分の前に道はない, 自分の後ろに道ができる

2013/06/01 -
PET helps visualize gene expression after gene transfer

2010/09/20 -

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WMIC: PET helps visualize gene HealthImaging http://www.healthimaging.com/index.php?option=com_articles&article=24164&publication=10&view=portals
How to Open a Hole in a Cell

2010/07/09 -

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Focus: How to Open a Hole in a Cell Published July 9, 2010 | Phys. Rev. Focus 26, 2 (2010) | DOI: 10.1103/PhysRevFocus.26.2 http://physics.aps.org/story/v26/st2
宮城県塩釜高等学校特別講演会

2007/02/20 -

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宮城県塩釜高等学校特別講演会

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Media Coverage 10

転移リンパ節に直接薬剤

岩手日報

2024/09/05

Type: Newspaper, magazine
抗がん剤転移リンパ節に直接投与

河北新報

2024/09/05

Type: Newspaper, magazine
転移リンパ節に直接薬剤

愛媛新聞

2024/09/05

Type: Newspaper, magazine
【小玉哲也東北大教授】水産加工品製造特区を提案

2011/08/23

Type: Newspaper, magazine

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【小玉哲也東北大教授】水産加工品製造特区を提案
Beyond the Abstract - Development of localized gene delivery using a dual-intensity ultrasound system in the bladder, by Sachiko Horie, et al.

2011/02/24

Type: Newspaper, magazine
Drug delivery: Simulated sonoporation

2010/07/12

Type: Newspaper, magazine

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Drug delivery: Simulated sonoporation Nature Asia-Pacific http://www.natureasia.com/asia-materials/highlight.php?id=757
南アフリカ共和国ダーバンに向かう機内で

東北大学機械系同窓会第12号125-128頁

2008/09/30

Type: Other
分子デリバリーシステムの開発-ナノからマクロへ-

東北大学ウェブマガジン

2007/10/24

Type: Other

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Staff Activity
Miraculous microbubbles keep getting better.

ACCJ Journal. 2007. March p80.

2007/03

Type: Newspaper, magazine
研究に生きる

日経サイエンス

2003/01

Type: Newspaper, magazine

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Other 13

がんワクチン療法に関する研究

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がんワクチン療法に関する研究
Treatment of traumatic brain Injury using laser light

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レーザー光を用いた外傷性脳損傷の治療に関する研究
ナノ粒子を用いたドラッグデリバリー

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ナノ粒子を用いたドラッグデリバリー
Inhibition of lymph node metastasis

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リンパ節転移の抑制
Development and application of a non-invasive tissue-specific molecular delivery method of cancer gene therapy

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遺伝子治療法の開発
ナノ粒子の解析

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ナノ粒子の解析
心筋遺伝子治療

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心筋遺伝子治療
Development of acoustic liposome

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音響性リポソームの開発
超音波場でのバブル群の運動

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超音波場でのバブル群の運動
Development and application of a non-invasive tissue-specific molecular delivery method of cancer gene therapy

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Development and application of a non-invasive tissue-specific molecular delivery method of cancer gene therapy
癌核酸治療への応用

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癌核酸治療への応用
Development of molecular delivery system

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分子導入法の開発
キャビテーション気泡の解析

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キャビテーション気泡の解析

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