東北大学研究者紹介 - Sukhbaatar Ariunbuyan

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スフバートル　アリウンブヤン

Sukhbaatar Ariunbuyan

所属

大学院歯学研究科　歯科学専攻　病態マネジメント歯学講座（顎顔面口腔腫瘍外科学分野）

職名

助教

学位

博士（歯学）（東北大学）

researchmap

https://researchmap.jp/Ariunbuyan

J-GLOBAL ID

201901018111045358

e-Rad 研究者番号

20867147

所属学協会 6

日本リンパ学会

2024年4月～継続中
公益社団法人日本口腔外科学会

2023年4月～継続中
Counsellor, Japanese Cancer Association

2021年～継続中
日本DDS学会

2018年～継続中
日本癌学会

2016年～継続中
Mongolian Oral and Maxillofacial Surgeon Association

2013年～継続中

︎全件表示 ︎最初の5件までを表示

研究分野 3

ライフサイエンス / 実験病理学 /
ライフサイエンス / 免疫学 /
ライフサイエンス / 生体医工学 /

受賞 7

「新人賞」受賞

2025年5月　日本超音波医学会第98回学術集会
「バイオフロンティア若手優秀講演表彰」受賞

2024年12月　日本機械学会第35回バイオフロンティア講演会
「優秀ポスター発表賞」受賞

2024年11月　第69回（公社）日本口腔外科学会総会・学術集会
「奨励賞」受賞

2024年9月　日本超音波医学会第68回東北地方会学術集会
「ジャーナル賞」受賞

2024年7月　第40回日本DDS学会学術集会
「Rising Scientist賞」受賞

2024年7月　第78回NPO法人日本口腔科学会学術集会
「優秀論文発表賞」受賞

2023年12月　日本生体医工学会関東支部若手研究者発表会

︎全件表示 ︎最初の5件までを表示

論文 33

Perspective on the use of scraping cytology for jawbone destructive lesions, entamoeba gingivalis, and actinomyces co-infection: a retrospective analysis

Tsuyoshi Kurobane, Sukhbaatar Ariunbuyan, Shiro Mori, Hiroyuki Kumamoto, Tsuyoshi Sugiura

Head & Face Medicine　21　(1)　2025年8月7日
出版者・発行元： Springer Science and Business Media LLC
DOI： 10.1186/s13005-025-00535-4 　

eISSN：1746-160X
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　(3)　379-388　2025年5月12日
出版者・発行元： 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.
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　2025年4月3日

DOI： 10.1080/17425247.2025.2471982 　
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年4月
出版者・発行元： Elsevier BV
DOI： 10.1016/j.mehy.2025.111624 　

ISSN：0306-9877
Ultrasound irradiation in the presence of microbubbles may enhance the antitumor effect of chemotherapeutic agents against bladder cancer. 国際誌

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

Journal of Cancer　16　(2)　368-381　2025年

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.
A combination of lymphatic drug delivery of anti‐CTLA‐4 antibody and local radiotherapy for solid‐tumor treatment 査読有り

Koki Takagi, Ariunbuyan Sukhbaatar, Yohei Inaba, Shiro Mori, Tetsuya Kodama

Cancer Science　2024年12月

DOI： 10.1111/cas.16369 　
Docetaxel administered through a novel lymphatic drug delivery system (LDDS) improved treatment outcomes for lymph node metastasis 査読有り

Ariunbuyan Sukhbaatar, Shiro Mori, Tsuyoshi Sugiura, Tetsuya Kodama

Biomedicine & Pharmacotherapy　171　116085-116085　2024年2月
出版者・発行元： Elsevier BV
DOI： 10.1016/j.biopha.2023.116085 　

ISSN：0753-3322
CDDPによるリンパ行性がん化学療法における薬剤溶媒特性のリンパ節転移治療へ及ぼす影響(Efficacy of a Drug Delivery System Against Lymph Node Metastases with Physicochemically Modificated Cisplatin)

岩間亮介, スフバートル・アリウンブヤン, 黒羽根壮, 梶田倫功, 纐纈衆, 森士朗, 小玉哲也

日本癌学会総会記事　82回　324-324　2023年9月
出版者・発行元： (一社)日本癌学会
ISSN：0546-0476
リンパ行性薬剤送達法の開発のための諸臓器所解剖学的解析ンパネットワークマウスモデルの病理(Physioanatomical analysis of mouse lymphatic network for the lymphatic drug delivery system usage)

スフバートル・アリウンブヤン, 纐纈衆, 宮下仁, 森士朗, 杉浦剛, 小玉哲也

日本癌学会総会記事　82回　503-503　2023年9月
出版者・発行元： (一社)日本癌学会
ISSN：0546-0476
転移性リンパ節の内圧がCDDPの治療効果を低下させる(Intranodal pressure of metastatic lymph node compromises treatment response of CDDP)

梶田倫功, スフバートル・アリウンブヤン, 黒羽根壮, 岩間亮介, 纐纈衆, 森士朗, 小玉哲也, 杉浦剛

日本癌学会総会記事　82回　1779-1779　2023年9月
出版者・発行元： (一社)日本癌学会
ISSN：0546-0476
CDDPによるリンパ行性がん化学療法における薬剤溶媒特性のリンパ節転移治療へ及ぼす影響(Efficacy of a Drug Delivery System Against Lymph Node Metastases with Physicochemically Modificated Cisplatin)

岩間亮介, スフバートル・アリウンブヤン, 黒羽根壮, 梶田倫功, 纐纈衆, 森士朗, 小玉哲也

日本癌学会総会記事　82回　324-324　2023年9月
出版者・発行元： (一社)日本癌学会
ISSN：0546-0476
リンパ行性薬剤送達法の開発のための諸臓器所解剖学的解析ンパネットワークマウスモデルの病理(Physioanatomical analysis of mouse lymphatic network for the lymphatic drug delivery system usage)

スフバートル・アリウンブヤン, 纐纈衆, 宮下仁, 森士朗, 杉浦剛, 小玉哲也

日本癌学会総会記事　82回　503-503　2023年9月
出版者・発行元： (一社)日本癌学会
ISSN：0546-0476
転移性リンパ節の内圧がCDDPの治療効果を低下させる(Intranodal pressure of metastatic lymph node compromises treatment response of CDDP)

梶田倫功, スフバートル・アリウンブヤン, 黒羽根壮, 岩間亮介, 纐纈衆, 森士朗, 小玉哲也, 杉浦剛

日本癌学会総会記事　82回　1779-1779　2023年9月
出版者・発行元： (一社)日本癌学会
ISSN：0546-0476
Intralymphatic injection of chemotherapy drugs modulated with glucose improves their anticancer effect. 国際誌

Ariunbuyan Sukhbaatar, Shiro Mori, Kiyoto Shiga, Tetsuya Kodama

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie　165　115110-115110　2023年7月6日

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.
Metastatic lymph node targeted CTLA4 blockade: a potent intervention for local and distant metastases with minimal ICI-induced pneumonia. 国際誌

Radhika Mishra, Ariunbuyan Sukhbaatar, Shiro Mori, Tetsuya Kodama

Journal of experimental & clinical cancer research : CR　42　(1)　132-132　2023年6月1日

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.
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年4月
出版者・発行元： (一社)日本泌尿器科学会総会事務局
Wireless temperature monitoring by using magnetic nanoparticles for biomedical applications on magnetic hyperthermia treatment

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

AIP Advances　13　(2)　025142-025142　2023年2月1日
出版者・発行元： 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.
Drug formulation augments the therapeutic response of carboplatin administered through a lymphatic drug delivery system. 国際誌

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

Cancer science　2022年9月28日

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.
Combination therapy of lymphatic drug delivery and total-body irradiation in a metastatic lymph node and lung mouse model. 国際誌

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

Cancer science　2022年9月3日

DOI： 10.1111/cas.15562 　

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Chemotherapy using a lymphatic drug delivery system (LDDS) targeting lymph nodes (LNs) in the early stage of metastasis has a superior antitumor effect to systemic chemotherapy. LDDS produces a higher drug retention rate and tissue selectivity in LNs. To expand the therapeutic coverage of LDDS from local treatment of metastatic LNs to prevention of distant metastases, the combination of treatment with therapies that enhance systemic tumor immune effects is an important therapeutic strategy. Recently, low-dose total-body irradiation (TBI) has been shown to activate immune responses and alter the tumor microenvironment. Here we show that combination therapy with TBI and LDDS improves the antitumor effect of metastatic LNs and lung metastasis. Tumor cells were inoculated into the subiliac LN to induce metastasis into the mouse proper axillary LN (PALN) and lung. Total-body irradiation was conducted on day 4 after inoculation using a gamma irradiator. LDDS was administrated into the accessory axillary LN to treat PALN. In vivo bioluminescence imaging system, high-frequency ultrasound system, and histology showed that combination therapy using TBI (total dose 1.0 Gy once) and the LDDS suppressed tumor growth in LNs and lung metastases and was more effective than using LDDS or TBI alone. Quantitative RT-PCR of spleens after combination therapy revealed increased expression of CD4, CD8, and IL-12b, indicating an activated immune response. The results show that combination therapy with TBI and LDDS is a method to improve the efficacy of LN metastases and distant metastases therapy and is a promising novel approach to treat cancer patients.
Intranodal delivery of modified docetaxel: Innovative therapeutic method to inhibit tumor cell growth in lymph nodes 国際誌

Ariunbuyan Sukhbaatar, Shiro Mori, Tetsuya Kodama

Cancer Science　113　(4)　1125-1139　2022年1月31日
出版者・発行元： 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 result in low accumulation of drugs into the cancerous LN. To improve the survival rate of patients with LN metastasis, a lymphatic drug delivery system (LDDS) has been developed to target metastatic LN by delivering chemotherapy agents into sentinel LN (SLN) under ultrasound guidance. The LDDS is an advanced method that can be applied in the early stage of the progression of tumor cells in the SLN 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 SLN, the injection rate, and the volumes of administered drugs. We anticipate these optimal ranges to be a starting point for developing more effective drug regimens to treat metastatic LN with the LDDS.
磁気温熱療法の定温加熱制御システムを用いた動物実験

鹿野晃弘, トンタットロイ, 桑波田晃弘, アリウンブヤンスフバートル, 小玉哲也, 薮上信

日本磁気学会論文特集号　6　(1)　2022年

DOI： 10.20819/msjtmsj.22TR519 　
Protocols for the Evaluation of a Lymphatic Drug Delivery System Combined with Bioluminescence to Treat Metastatic Lymph Nodes. 国際誌

Ariunbuyan Sukhbaatar, Tetsuya Kodama

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

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.
Characterizing perfusion defects in metastatic lymph nodes at an early stage using high-frequency ultrasound and micro-CT imaging 国際誌

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

Clinical & Experimental Metastasis　38　(6)　539-549　2021年12月
出版者・発行元： 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.
Study of the physicochemical properties of drugs suitable for administration using a lymphatic drug delivery system. 国際誌

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

Cancer science　112　(5)　1735-1745　2021年5月

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.
Intranodal pressure of a metastatic lymph node reflects the response to lymphatic drug delivery system. 国際誌

Shigeki Kato, Kazu Takeda, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Kiyoto Shiga, Tetsuya Kodama

Cancer science　111　(11)　4232-4241　2020年9月3日

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.
Analysis of tumor vascularization in a mouse model of metastatic lung cancer 国際誌査読有り

Scientific Reports　9　(1)　16029-16029　2019年12月

DOI： 10.1038/s41598-019-52144-2 　

ISSN：2045-2322
A model system for studying superselective radiotherapy of lymph node metastasis in mice with swollen lymph nodes 国際誌査読有り

Clinical and Translational Radiation Oncology　20　53-57　2019年5月

DOI： 10.1016/j.ctro.2019.05.002 　

ISSN：2405-6308
Treatment of false-negative metastatic lymph nodes by a lymphatic drug delivery system with 5-fluorouracil. 国際誌査読有り

Cancer medicine　8　(5)　2241-2251　2019年4月

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. 国際誌査読有り

Cancer science　110　(2)　509-518　2019年1月

DOI： 10.1111/cas.13898 　

ISSN：1349-7006
Superselective Drug Delivery Using Doxorubicin-Encapsulated Liposomes and Ultrasound in a Mouse Model of Lung Metastasis Activation 国際誌査読有り

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

Ultrasound in Medicine and Biology　44　(8)　1818-1827　2018年8月1日
出版者・発行元： Elsevier USA
DOI： 10.1016/j.ultrasmedbio.2018.04.003 　

ISSN：1879-291X 0301-5629
Evaluation of the enhanced permeability and retention effect in the early stages of lymph node metastasis 国際誌査読有り

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

CANCER SCIENCE　108　(5)　846-852　2017年5月

DOI： 10.1111/cas.13206 　

ISSN：1349-7006
A novel treatment for metastatic lymph nodes using lymphatic delivery and photothermal therapy 国際誌査読有り

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

Scientific Reports　7　45459-45459　2017年4月3日
出版者・発行元： Nature Publishing Group
DOI： 10.1038/srep45459 　

ISSN：2045-2322
Induction of the EPR effect in a mouse model of lung metastasis

Sukhbaatar Ariunbuyan, 堀江佐知子, 高橋哲, 森士朗, 小玉哲也

生体医工学　55　(4)　377-377　2017年
出版者・発行元：公益社団法人日本生体医工学会
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>

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MISC 9

磁気エネルギー加熱による低侵襲がん治療とリンパ節転移腫瘍モデル動物実験

鏡味隆行, 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, 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, 桑波田晃弘, 桑波田晃弘, 桑波田晃弘, とんたっとろい, とんたっとろい, 篠原陸, 小玉哲也, 小玉哲也, 小玉哲也, 小玉哲也, 薮上信, 薮上信, 薮上信

日本癌学会学術総会抄録集(Web)　82nd　2023年
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

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(Web)　110th　2023年
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年
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年
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年
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

日本癌学会学術総会抄録集(Web)　79th　2020年
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

日本癌学会学術総会抄録集(Web)　79th　2020年
リンパ行性薬剤送達法における浸透圧の重要性

ミシュララディカ, 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

日本癌学会学術総会抄録集(Web)　78th　2019年
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

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

日本癌学会学術総会抄録集(Web)　78th　2019年

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講演・口頭発表等 31

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
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
リンパ節介在血行性転移理論の実験的検証

志水洸太, Radhika Mishra, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

第81回日本癌学会学術総会
放射線局所照射による遠隔転移の抑制

栗生晏暉, Radhika Mishra, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

第81回日本癌学会学術総会
Lymph node resection induces metastases in the lung

Sukhbaatar A, Mori S, Kodama T

第81回日本癌学会学術総会
Immune checkpoint inhibitor delivered via lymphatic drug delivery system: a curative therapy for metastatic lymph nodes

Mishra R, Sukhbaatar A, Mori S, Sakamoto M, Kodama T

第81回日本癌学会学術総会
抗CTLA-4抗体のリンパ節直接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

第81回日本癌学会学術総会
リンパ行性薬剤送達法および浸透圧・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, Radhika Mishra, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

第81回日本癌学会学術総会
ドキソルビシンを用いたリンパ行性薬剤送達法(LDDS)による転移性リンパ節の治療

田中菜生, Radhika Mishra, Ariunbuyan Sukhbaatar, 森士朗, 小玉哲也

第81回日本癌学会学術総会
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年9月13日
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年8月24日
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年8月24日
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年8月24日
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
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
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
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
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
Novel drug formulation for potentiation of therapeutic response using the lymphatic drug delivery system

Mishra R, Sukhbaatar A, Sakamoto M, Mori S, Kodama T

第40回札幌国際がんシンポジウム(SICS2022)
Targeting lymph node metastasis through lymphatic drug delivery system by administration of docetaxel

Sukhbaatar A, Mori S, Kodama T

第40回札幌国際がんシンポジウム(SICS2022)
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　2020年10月
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　2020年10月
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　2020年10月
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　2020年10月
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　2020年8月
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　2019年9月
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　2019年9月
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　2019年6月
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　2019年6月
Murine pulmonary vascularization changes in a metastatic lung mouse model using micro-CT

Sukhbaatar Ariunbuyan, Mori Shiro, Kodama Tetsuya

CANCER SCIENCE　2018年12月
Systemic chemotherapy validity based on the EPR effect at early stage of lung metastasis

Sukhbaatar A, Horie S, Mori S, Kodama T, Takahashi T

China-Japan-Korea Dental Science Symposium 2016

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共同研究・競争的資金等の研究課題 8

リンパ洞・血管交通亢進性リンパ節を標的とする革新的なLDDS免疫化学療法の開発

小玉哲也, SUKHBAATAR ARIUNBUYAN, 藤井博司, 阿部真也, 西條憲, 片桐克則

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Challenging Research (Pioneering)

研究機関：Tohoku University

2025年6月～ 2029年3月
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

2025年4月～ 2028年3月
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

2025年4月～ 2028年3月
転移リンパ節に対する革新的リンパ行性免疫療法の提案

小玉哲也, 薮上信, SUKHBAATAR ARIUNBUYAN, 藤井博司, 山口匡

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (A)

研究機関：Tohoku University

2023年4月～ 2026年3月
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

2023年4月～ 2026年3月

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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．
リンパ行性薬物送達法の創製: 遠隔転移の制御と免疫関連有害事象の解明

SUKHBAATAR ARIUNBUYAN

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Early-Career Scientists

研究機関：Tohoku University

2022年4月～ 2025年3月

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Immunotherapy using immune checkpoint inhibitors (ICIs) is revolutionizing cancer metastasis treatment. However, few head and neck cancer (HNC) patients respond to ICIs with a high incidence of immune-related Adverse Events (irAEs). Still, a majority of them fail to respond. We created experimental mouse model by injecting luciferase expressing tumor cells and ICIs were injected as mono- or sequentially with combination of docetaxel. Treatment effects were evaluated over time, and final confirmation was made histologically along with irAEs. We found more significant tumor inhibition in the chemo-immunotherapy groups than in mono-immunotherapy.
遠隔転移治療に向けた革新的リンパ行性薬物送達法の創製

小玉哲也, SUKHBAATAR ARIUNBUYAN, 森士朗

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Challenging Research (Pioneering)

研究機関：Tohoku University

2021年7月～ 2024年3月

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本年度は革新的なリンパ行性薬剤送達法の開発を目的に, 以下の課題に取り組んだ. （１）転移リンパ節の病理像に対するAI診断の開発転移リンパ節をパラフィン切片にして, ヘマトキシリン・エオジン(HE)で染色されたスライドを作製した. つぎに, このスライドをバーチャルスライドに取り込み, 腫瘍領域のマーキングをおこなった. Pythonソースコードをもとに,特徴解析およびAI-Histologyの開発をおこなった. （２）リンパ行性薬物送達法併用放射線治療 MXH10/Mo/lprリンパ節腫脹マウスの腸骨下リンパ節に腫瘍細胞を移植し, このリンパ節に対するリンパ行性薬物送達法併用全身放射線治療をおこなった. 腫瘍移植の過程で肺に転移巣が形成される. 線量としてSingleL-TBI (0.2 Gy × 1), Single M-TBI (1.0 Gy ×1), Fractionated M-TBI (1.0 Gy × 2)の3群を考えた. まず, 線量が1Gy以上の全身放射線照射 (Single L-TBI群およびFractionated M-TBI群)では肺転移を抑制できることができた. Fractionated M-TBI群ではSiLNにおいても腫瘍増殖が遅延した. 全身放射線照射によるSiLN, PALNおよび肺における治療効果はFractionated M-TBI > Single M-TBI > Single L-TBIの順であることが明らかとなった．つぎに抗がん剤としてシスプラチンを使用してLDDSとsingle M-TBI (1.0 Gy ×1)との併用実験を実施した. Single M-TBI + LDDSの併用療法は, LDDS単独と比較して, PALNにおける腫瘍の増殖を著しく遅延させた. Single M-TBI + LDDSの併用療法では肺における腫瘍増殖が認められず, 肺転移を抑制できることが明らかになった
超早期転移リンパ節に対するリンパ行性薬物送達法の創製

SUKHBAATAR ARIUNBUYAN

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Early-Career Scientists

研究機関：Tohoku University

2020年4月～ 2022年3月

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ISSUE A. perfusion defects in LNs were observed with each imaging modality, and the LNs were subjected to pathological analyses to determine whether they were cN0 or N1. The present finding was that in the early stage of metastasis, tumor cells replace microvascular areas to form a perfusion defect that is not pathologically necrotic tissue. During perfusion defect formation, replacement of parenchyma with tumor supplied by only a few microvessels occurs, intranodal pressure increased, pO2 remained constant and tumor neovascularization was not induced. Perfusion defects, which are formed by the replacement of LN parenchyma with tumor cells, have also been observed with intranodal lymphangiography in non-enlarged LNs. The characteristics of perfusion defect formation in LNs may explain why metastatic LNs show an inadequate response to hematologic systemic chemotherapy using small-molecule and macromolecular anticancer agents. <BR> Issue B. From this study, we found that optimal osmotic pressure range of LDDS solution for the treatment of metastatic LNs is 695 - 2,780 kPa, and for viscosity less than 40 mPas. Up to this viscosity value, the macroscopic flow dynamics of the drug did not significantly differ.

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