TOHOKU UNIVERSITY Researchers

Details of the Researcher

Home

日本語 English

Yoko Tsukita

Section

Tohoku University Hospital

Job title

Assistant Professor

Degree

researchmap

https://researchmap.jp/YokoTsukita

J-GLOBAL ID

201901015875324104

Research History 7

2020/05 - Present

東北大学呼吸器内科助教
2020/04 - 2020/05

東北大学呼吸器内科特任助手
2018/04 - 2020/03

東北大学呼吸器内科医員
2012/10 - 2015/03

宮城県立がんセンター呼吸器内科
2011/10 - 2012/09

東北厚生年金病院呼吸器内科レジデント
2011/04 - 2011/09

国立病院機構仙台医療センター後期臨床研修医
2009/04 - 2011/03

国立病院機構仙台医療センター初期臨床研修医

Show all Show first 5

Education 2

Tohoku University　Graduate School of Medicine

2014/04 - 2018/03
Yamagata University　Faculty of Medicine　School of Medicine

2003/04 - 2009/03

Professional Memberships 7

THE JAPANESE CANCER ASSOCIATION
米国臨床腫瘍学会
THE JAPAN SOCIETY FOR RESPIRATORY ENDOSCOPY
日本臨床腫瘍学会
THE JAPAN LUNG CANCER SOCIETY
THE JAPANESE RESPIRATORY SOCIETY
THE JAPANESE SOCIETY OF INTERNAL MEDICINE

︎Show all ︎Show first 5

Research Interests 3

胸部腫瘍学
臨床試験
肺癌

Research Areas 1

Life sciences / Respiratory medicine /

Awards 3

日本肺癌学会若手奨励賞

2020
ATS Young Investigator

2019　日本呼吸器学会
東北大学医学系研究科女子大学院学生奨励賞（七星賞）優秀賞

2019

Papers 95

Efficacy and safety of first-line lenvatinib in patients with advanced or recurrent thymic carcinoma in the real-world setting. International-journal Peer-reviewed

Ryosuke Tsugitomi, Kento Takagi, Go Saito, Motoko Tachihara, Hironori Ashinuma, Takehito Shukuya, Shinnosuke Takemoto, Shinya Sakata, Atsuto Mouri, Hideki Miwa, Yosuke Tamura, Takaaki Tokito, Yoko Tsukita, Yoshihito Kogure, Takeshi Masuda, Hiroshi Tanaka, Sousuke Kubo, Takaaki Sasaki, Tomohiro Oba, Nobuaki Mamesaya, Taro Yamanaka, Hiromi Nagashima, Motohiro Tamiya, Hiroaki Kanemura, Takehiro Tozuka, Megumi Furuta, Hayato Kawachi, Takashi Ninomiya, Yoshiaki Nagai, Hirokazu Ogino, Kentaro Ito, Masashi Ishihara, Takuji Suzuki

Lung cancer (Amsterdam, Netherlands)　214　109309-109309　2026/02/07

DOI： 10.1016/j.lungcan.2026.109309 　

More details Close

BACKGROUND: Thymic carcinoma is a rare thoracic malignancy with limited first-line treatment options. Lenvatinib has shown efficacy and tolerability in previously treated patients, but its role in chemotherapy-naive patients is unclear. METHODS: We conducted a retrospective, multicentre observational study across 31 Japanese institutions. Patients with advanced or recurrent thymic carcinoma who received lenvatinib between 23 March 2021 and 31 October 2022 were included. Data cut-off was 13 November 2024. Outcomes for chemotherapy-naive patients included objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), time to treatment failure (TTF), overall survival (OS), and adverse events (AEs). Subgroup analyses were stratified by age. RESULTS: Of 107 patients, 20 received lenvatinib as first-line therapy. Median observation was 23.6 months (interquartile range, 12.5-27.1). ORR was 50% (90% confidence interval [CI], 27.2-72.8%), and DCR 85% (95% CI, 62.1-96.8%). Median PFS, TTF, and OS were 10.9 months (95% CI, 5.6-17.1), 8.9 months (95% CI, 5.3-17.8), and 25.0 months (95% CI, 21.2-not reached). AEs occurred in 95% (Grade ≥ 3 in 60%); dose reductions and discontinuations occurred in 85% and 25%. Safety was consistent with prior reports. Older patients showed higher rates of Grade ≥ 3 AEs and discontinuation. CONCLUSIONS: In this real-world cohort, first-line lenvatinib demonstrated favourable efficacy and manageable safety, supporting its use in advanced or recurrent thymic carcinoma.
Durvalumab, carboplatin, and etoposide in patients who are treatment-naive with extensive-stage small-cell lung cancer and poor performance status (NEJ045A): a single-arm phase 2 trial. International-journal

Tetsuhiko Asao, Yu Saida, Satoshi Watanabe, Akira Kisohara, Kazuma Kishi, Ryo Morita, Taku Nakagawa, Yoko Tsukita, Naoki Furuya, Taichi Miyawaki, Nobuhisa Ishikawa, Tadaaki Yamada, Takahiro Tanaka, Satoshi Morita, Toshiaki Kikuchi, Makoto Maemondo, Kunihiko Kobayashi

The Lancet. Respiratory medicine　13　(12)　1057-1066　2025/12

DOI： 10.1016/S2213-2600(25)00240-1 　

More details Close

BACKGROUND: Treating patients with extensive-stage small-cell lung cancer (SCLC) with poor performance status poses considerable challenges. We aimed to evaluate the combination of an immune checkpoint inhibitor with platinum-based therapy in this population. METHODS: This open-label, single-arm phase 2 NEJ045A trial enrolled untreated patients with extensive-stage SCLC with performance status 2 or 3. Participants received four cycles of durvalumab, carboplatin, and etoposide, followed by durvalumab maintenance. A dose adjustment strategy was used, with initial reductions in carboplatin-etoposide dosages, subsequently adjusted based on adverse events, allowing for potential escalation. The primary endpoint was tolerability, assessed by the proportion of patients completing induction therapy. A key secondary endpoint was 1-year survival rate. This trial is registered at the Japan Registry of Clinical Trials (jRCTs031200319) and has been completed. FINDINGS: Between April 8, 2021, and Oct 3, 2023, 57 patients (performance status 2 n=43 and performance status 3 n=14) were enrolled with a median age of 73·5 years (IQR 69·0-77·5), 44 (79%) of 56 were male. 26 (67%; 80% CI 55·2-76·7; p<0·0001) of 39 patients with performance status 2 and five (50%; 26·7-73·3; p=0·0088) of ten with performance status 3 completed induction therapy, exceeding the pre-specified threshold. Grade 3 or higher adverse events occurred in 52 (93%) of 56 patients, and 12 (21%) of 56 discontinued due to adverse events. The 1-year survival rates were 43·4% (80% CI 34·1-53·1) overall (p<0·0001), 50·0% (39·1-60·9) in performance status 2 (p<0·0001), and 18·2% (5·0-41·5) in performance status 3. INTERPRETATION: Durvalumab, carboplatin, and etoposide showed tolerability and promising efficacy as a first-line treatment for patients with untreated extensive-stage SCLC with poor performance status, supporting the integration of immune checkpoint inhibitors in this therapeutically challenging population. FUNDING: AstraZeneca KK.
原発部位が生存転帰と再発形式に与える影響 III期非小細胞肺がん患者の後方視観察研究

岩崎史, 宮内栄作, 山本貴也, 田中寿志, 布村恭仁, 畑山佳臣, 守田亮, 福井伸, 伊藤辰徳, 突田容子, 渋谷里紗, 杉浦久敏

肺癌　65　(5)　435-435　2025/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
進行非小細胞肺癌患者に対するイピリムマブ+ニボルマブ療法と放射線照射の第II相試験(NEJ053B)

中川拓, 宮内栄作, 梅澤玲, 牧口友紀, 坂田能彦, 守田亮, 柳澤悟, 角俊行, 松本啓孝, 杉坂淳, 齋藤良太, 田中智, 荒井大輔, 突田容子, 井上彰, 杉浦久敏, 前門戸任

肺癌　65　(5)　484-484　2025/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
肺癌診療におけるAI技術の活用有害事象対応提案AIの開発日本肺癌学会AI開発小委員会による産学連携プロジェクト

藤本大智, 柴木亮太, 齋藤合, 坂田能彦, 突田容子, 塩山善之

肺癌　65　(5)　351-351　2025/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
特発性肺線維症における組織常在性マクロファージの分子プロファイルと前腫瘍微小環境形成機序の解明

藤野直也, 齋藤拓矢, 今野周一, 小野祥直, 伊藤辰徳, 突田容子, 渋谷里紗, 宮内栄作, 山田充啓, 杉浦久敏

肺癌　65　(5)　443-443　2025/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
進行非小細胞肺癌患者に対するイピリムマブ+ニボルマブ療法と放射線照射の第II相試験(NEJ053B)

中川拓, 宮内栄作, 梅澤玲, 牧口友紀, 坂田能彦, 守田亮, 柳澤悟, 角俊行, 松本啓孝, 杉坂淳, 齋藤良太, 田中智, 荒井大輔, 突田容子, 井上彰, 杉浦久敏, 前門戸任

肺癌　65　(5)　484-484　2025/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
肝門部リンパ節病変により閉塞性黄疸をきたしたサルコイドーシスの一例

杉山初美, 村上康司, 佐野寛仁, 突田容子, 東出直樹, 藤野直也, 塩谷梨沙子, 有竹秀美, 玉田勉, 杉浦久敏

日本サルコイドーシス/肉芽腫性疾患学会雑誌　45　(サプリメント号)　70-70　2025/10
Publisher: 日本サルコイドーシス
ISSN： 1883-1273

eISSN： 1884-6114
腎細胞癌術後37年目に肺,縦隔リンパ節転移を認めた1例

宮内栄作, 成田大輔, 小野寺賢, 山崎有人, 佐野寛仁, 突田容子, 東出直樹, 村上康司, 藤野直也, 山田充啓, 岡田克典, 杉浦久敏

気管支学　47　(5)　497-497　2025/09
Publisher: (一社)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
腎細胞癌術後37年目に肺,縦隔リンパ節転移を認めた1例

宮内栄作, 成田大輔, 小野寺賢, 山崎有人, 佐野寛仁, 突田容子, 東出直樹, 村上康司, 藤野直也, 山田充啓, 岡田克典, 杉浦久敏

気管支学　47　(5)　497-497　2025/09
Publisher: (一社)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
Investigation of cardiotoxicity in patients treated with osimertinib: findings from the OSI-FACT study. International-journal

Asuka Okada, Yoshihiko Sakata, Yuko Oya, Shinya Sakata, Teppei Yamaguchi, Motohiro Tamiya, Hidekazu Suzuki, Ryota Shibaki, Toshihide Yokoyama, Hirotaka Matsumoto, Taiichiro Otsuki, Yuki Sato, Junji Uchida, Go Saito, Yoko Tsukita, Megumi Inaba, Hideki Ikeda, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Takuro Sakagami

Lung cancer (Amsterdam, Netherlands)　204　108589-108589　2025/06

DOI： 10.1016/j.lungcan.2025.108589 　

More details Close

INTRODUCTION: Osimertinib is a highly effective first-line treatment for advanced epithelial growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). With its expanded perioperative use, the long-term risk of cardiotoxicity merits investigation. We assessed the occurrence and risk factors of QT prolongation and cardiac dysfunction in patients with NSCLC treated with first-line osimertinib across multiple institutions. METHODS: This retrospective cohort study, a part of the OSI-FACT study, included 538 patients who started first-line osimertinib treatment between August 2018 and December 2019. Patients receiving concurrent anticancer therapies were excluded. Clinical data, including patient characteristics, EGFR mutation status, and tumor stage, were analyzed. Cardiotoxicity graded per Common Terminology Criteria for Adverse Events version 5.0 was monitored via ECG and echocardiography over a median follow-up of 37 months. RESULTS: QT prolongation occurred in 23 patients (4.3 %), with eight reaching Grade ≥3. The median time to onset was 246 days. No significant risk factors for QT prolongation were identified. Cardiac dysfunction was reported in 14 patients (2.6 %), with five cases of Grade ≥3. The median onset was 171 days, with cases occurring after six months. Multivariate analysis identified poor performance status as a risk factor for cardiac dysfunction (HR 2.24, p = 0.005). CONCLUSION: Osimertinib-related cardiotoxicity, while rare, has important clinical implications, particularly for older patients and those with comorbidities. Regular monitoring, beyond the first year, is essential to ensure patient safety.
肺癌患者におけるFoundationOne検査の現状と提出検体の違いによる治療提案率の検討

宮内栄作, 山本友梨, 成田大輔, 木村望, 伊藤辰徳, 突田容子, 渋谷里紗, 杉浦久敏

気管支学　47　(Suppl.)　S244-S244　2025/05
Publisher: (一社)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
Phase 2 Trial of Combination Radiotherapy and Pembrolizumab Plus Chemotherapy in Patients With Previously Untreated Metastatic NSCLC: NJLCG 1902. International-journal

Yoko Tsukita, Rei Umezawa, Taku Nakagawa, Akira Anbai, Tomonori Makiguchi, Hisashi Tanaka, Yosuke Horii, Aya Suzuki, Ryo Morita, Hitomi Nogawa, Hiroshi Yokouchi, Nozomu Kimura, Keiichi Jingu, Akira Inoue, Hisatoshi Sugiura, Eisaku Miyauchi

JTO clinical and research reports　6　(5)　100817-100817　2025/05

DOI： 10.1016/j.jtocrr.2025.100817 　

More details Close

INTRODUCTION: Treatment strategies that enhance the efficacy of immunotherapy are desired. Radiotherapy can enhance immunity, but the utility of adding radiotherapy to immunotherapy plus platinum-doubled chemotherapy in patients with metastatic NSCLC has not been explored. METHODS: This multicenter, single-arm phase 2 trial evaluated the efficacy and safety of combining radiotherapy with pembrolizumab plus chemotherapy in patients with previously untreated metastatic NSCLC. Patients begin receiving pembrolizumab plus platinum-doublet chemotherapy within 1 week of starting radiotherapy (30 Gy in 10 fractions). The primary end point was the 12-month progression-free survival (PFS) rate. The secondary end points included PFS, overall survival, and toxicity profiles. RESULTS: Forty patients were enrolled. In total, 37 and 38 patients were analyzed for efficacy and safety, respectively. The 12-month PFS rate was 44.3% (90% confidence interval [CI]: 30.3-57.3), which met the primary end point. The median PFS was 8.4 months (95% CI: 5.7-22.2), and the median overall survival was 30.1 months (95% CI: 22.3-not reached). Grade 3 or 4 adverse events occurred in 25 patients (65.8%), and one treatment-related death was reported. Pneumonitis was reported in 10 patients (26.3%), including two cases of grade 3 pneumonitis and one case of grade 5. CONCLUSIONS: Adding radiotherapy to pembrolizumab plus platinum-doublet chemotherapy led to promising efficacy in patients with previously untreated metastatic NSCLC. Although caution should be exercised with regard to pneumonitis, adverse events were tolerable. Further research is needed to confirm the efficacy and safety of this strategy.
いま肺全摘の適応を再考する

渡辺有為, 小野寺賢, 野津田泰嗣, 熊田早希子, 突田容子, 宮内栄作, 東郷威男, 渡邉龍秋, 鈴木隆哉, 大石久, 平間崇, 岡田克典

日本呼吸器外科学会雑誌　39　(3)　PS3-2　2025/04
Publisher: (一社)日本呼吸器外科学会
ISSN： 0919-0945

eISSN： 1881-4158
肺MALTリンパ腫再発と鑑別を要した肺Mycobacteroides abscessus species症の1例

山本友梨, 藤野直也, 佐野寛仁, 京極自彦, 突田容子, 東出直樹, 塩谷梨沙子, 竹田俊一, 山田充啓, 杉浦久敏

結核　100　(2)　41-44　2025/03
Publisher: (一社)日本結核・非結核性抗酸菌症学会
ISSN： 0022-9776

eISSN： 1884-2410
Histological and genetic features and therapeutic responses of lung cancers explored via the global analysis of their metabolome profile

Daisuke Narita, Eiji Hishinuma, Risa Ebina-Shibuya, Eisaku Miyauchi, Naomi Matsukawa, Ikuko N. Motoike, Kengo Kinoshita, Seizo Koshiba, Yoko Tsukita, Hirotsugu Notsuda, Nozomu Kimura, Ryota Saito, Hisatoshi Sugiura

Lung Cancer　108082-108082　2025/01
Publisher: Elsevier BV
DOI： 10.1016/j.lungcan.2025.108082 　

ISSN： 0169-5002
Real-World Outcomes of Subsequent Chemotherapy after Progression Following Chemoradiation and Consolidative Durvalumab Therapy in Locally Advanced Non-small Cell Lung Cancer: An Exploratory Analysis from the CRIMSON Study (HOPE-005). International-journal

Hayato Kawachi, Motohiro Tamiya, Yuko Oya, Go Saito, Yoshihiko Taniguchi, Hirotaka Matsumoto, Yuki Sato, Taiichiro Otsuki, Hidekazu Suzuki, Yasushi Fukuda, Satoshi Tanaka, Yoko Tsukita, Junji Uchida, Yoshihiko Sakata, Yuki Nakatani, Ryota Shibaki, Daisuke Arai, Asuka Okada, Satoshi Hara, Koichi Takayama, Kazumi Nishino

Clinical lung cancer　25　(7)　643-652　2024/11

DOI： 10.1016/j.cllc.2024.07.014 　

More details Close

BACKGROUND: The optimal subsequent treatment strategy for locally advanced non-small cell lung cancer (LA-NSCLC) after chemoradiotherapy (CRT) and consolidative durvalumab therapy remains unknown. We aimed to determine the optimal subsequent treatment strategy for this clinical population. MATERIALS AND METHODS: We retrospectively enrolled 523 consecutive patients with LA-NSCLC treated with CRT and analyzed the treatment outcomes of subsequent therapy after progression following CRT and consolidative durvalumab therapy. Patients who received tyrosine kinase inhibitors as subsequent therapy were excluded. RESULTS: Out of 122 patients who received subsequent chemotherapy, 55% underwent platinum-based, 25% non-platinum-based, and 20% immune checkpoint inhibitor (ICI)-containing therapies. In the platinum-based group, patients with a durvalumab-progression-free survival (Dur-PFS) ≥ 1 year had a significantly longer median subsequent therapy-PFS (SubTx-PFS) than those with Dur-PFS < 1 year (13.2 months vs. 4.7 months; hazard ratio, 0.45; 95% confidence interval, 0.21-0.97; P = .04). Furthermore, among patients receiving non-platinum-based chemotherapy, the median SubTx-PFS was longer in the combined with angiogenesis inhibitor group than in the without group, although the difference was not statistically significant. No significant difference of SubTx-PFS was observed between the reason for durvalumab discontinuation and the outcomes of ICI-containing therapy. CONCLUSION: In clinical practice, platinum-based chemotherapy rechallenge is frequently employed following progression subsequent to CRT and consolidative durvalumab therapy for LA-NSCLC. Optimal treatment strategies may consider Dur-PFS and angiogenesis inhibitor feasibility. Further research is warranted to identify clinical biomarkers that can help identify patients who would benefit from ICI rechallenge.
有害事象対応提案AIの作成事業肺癌学会AI開発小委員会における産学連携事業

藤本大智, 柴木亮太, 齋藤合, 坂田能彦, 突田容子, 矢部道俊, 塩山善之

肺癌　64　(5)　503-503　2024/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
初回治療Osimertinibの多施設実態調査(OSI-FACT)における心毒性の検討

岡田あすか, 坂田能彦, 坂田晋也, 山口哲平, 田宮基裕, 鈴木秀和, 柴木亮太, 横山俊秀, 松本啓孝, 大搗泰一郎, 佐藤悠城, 内田純二, 齋藤合, 突田容子, 稲葉恵, 池田英樹, 荒井大輔, 丸山広高, 原聡志, 津村真介, 坂上拓郎

肺癌　64　(5)　463-463　2024/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
EGFR遺伝子変異陽性非小細胞肺癌に対する初回治療Osimertinibの多施設実態調査(OSI-FACT)OS update

坂田能彦, 坂田晋也, 山口哲平, 田宮基裕, 鈴木秀和, 柴木亮太, 岡田あすか, 横山俊秀, 松本啓孝, 大搗泰一郎, 佐藤悠城, 内田純二, 齋藤合, 突田容子, 稲葉恵, 池田英樹, 荒井大輔, 丸山広高, 原聡志, 津村真介, 坂上拓郎

肺癌　64　(5)　512-512　2024/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
希少ドライバー遺伝子異常を有する高齢肺癌患者の臨床的特徴

仲地一郎, 荒井大輔, 齋藤合, 佐藤悠城, 突田容子, 岡田あすか, 松本啓孝, 田宮基裕, 田中智, 内田純二, 坂田能彦, 原聡志, 横山俊秀, 高岩卓也, 河内勇人, 谷口善彦

肺癌　64　(5)　465-465　2024/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
進行非小細胞肺癌患者に対する免疫療法+化学療法と放射線照射との併用療法の第2相試験

牧口友紀, 突田容子, 梅澤玲, 中川拓, 安倍明, 田中寿志, 堀井洋祐, 鈴木綾, 守田亮, 野川ひとみ, 横内浩, 木村望, 井上彰, 杉浦久敏, 宮内栄作

肺癌　64　(5)　443-443　2024/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
当科における肺癌患者の包括的がんゲノムプロファイリング検査(CGP)症例の現況

成田大輔, 渋谷里紗, 宮内栄作, 突田容子, 伊藤辰徳, 木村望, 玉田勉, 杉浦久敏

肺癌　64　(5)　498-498　2024/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
胸腺腫瘍・まれな腫瘍進行再発胸腺癌患者に対するレンバチニブの一次治療での有効性および安全性の検討

芦沼宏典, 高木賢人, 齋藤合, 次富亮輔, 立原素子, 宿谷威仁, 行徳宏, 坂田晋也, 毛利篤人, 三輪秀樹, 田村洋輔, 時任高章, 突田容子, 小暮啓人, 益田武, 田中洋史, 久保創介, 鈴木拓児

肺癌　64　(5)　426-426　2024/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
初回治療Osimertinibの多施設実態調査(OSI-FACT)における心毒性の検討

岡田あすか, 坂田能彦, 坂田晋也, 山口哲平, 田宮基裕, 鈴木秀和, 柴木亮太, 横山俊秀, 松本啓孝, 大搗泰一郎, 佐藤悠城, 内田純二, 齋藤合, 突田容子, 稲葉恵, 池田英樹, 荒井大輔, 丸山広高, 原聡志, 津村真介, 坂上拓郎

肺癌　64　(5)　463-463　2024/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
EGFR遺伝子変異陽性非小細胞肺癌に対する初回治療Osimertinibの多施設実態調査(OSI-FACT)OS update

坂田能彦, 坂田晋也, 山口哲平, 田宮基裕, 鈴木秀和, 柴木亮太, 岡田あすか, 横山俊秀, 松本啓孝, 大搗泰一郎, 佐藤悠城, 内田純二, 齋藤合, 突田容子, 稲葉恵, 池田英樹, 荒井大輔, 丸山広高, 原聡志, 津村真介, 坂上拓郎

肺癌　64　(5)　512-512　2024/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
進行非小細胞肺癌患者に対するイピリムマブ+ニボルマブ療法と放射線照射の第2相試験(NEJ053B)

宮内栄作, 田中寿志, 中川拓, 坂田能彦, 守田亮, 柳澤悟, 松本啓孝, 齋藤良太, 田中智, 角俊行, 突田容子, 前門戸任

肺癌　64　(5)　612-612　2024/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
Durvalumab with etoposide and carboplatin for patients with extensive-stage small cell lung cancer and interstitial lung disease: A multicenter, open-label prospective trial. International-journal

Ryota Shibaki, Daichi Fujimoto, Eisaku Miyauchi, Yoko Tsukita, Ichiro Nakachi, Daisuke Arai, Yoshihiko Sakata, Naoki Shingu, Toshio Shimokawa, Takashi Kijima, Motohiro Tamiya, Sachiko Kawana, Satoshi Hara, Go Saito, Yuki Sato, Toshihide Yokoyama, Shinya Sakata, Yoshihiko Taniguchi, Akito Hata, Hirotaka Matsumoto, Teppei Yamaguchi, Nobuyuki Yamamoto

Lung cancer (Amsterdam, Netherlands)　196　107958-107958　2024/09/19

DOI： 10.1016/j.lungcan.2024.107958 　

More details Close

OBJECTIVES: Certain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP). METHODS: In this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase), followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate. RESULTS: Twenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3-99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6-6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached). CONCLUSIONS: Chemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP.
Risk and survival of patients with non-small cell lung cancer and pre-existing autoimmune disorders receiving immune checkpoint blockade therapy: Survival analysis with inverse probability weighting from a nationwide, multi-institutional, retrospective study (NEJ047). International-journal

Tetsuhiko Asao, Takehito Shukuya, Kohei Uemura, Rui Kitadai, Gaku Yamamoto, Atsuto Mouri, Meiyo Tamaoka, Ryosuke Imai, Yoko Tsukita, Kazutoshi Isobe, Satoshi Watanabe, Mitsuhiro Kamimura, Ryo Morita, Keita Kudo, Minehiko Inomata, Kazunari Tateishi, Kazutaka Kakinuma, Hiroshige Yoshioka, Yukiko Namba, Issei Sumiyoshi, Taku Nakagawa, Kana Watanabe, Kunihiko Kobayashi, Kazuhisa Takahashi

Lung cancer (Amsterdam, Netherlands)　194　107894-107894　2024/07/14

DOI： 10.1016/j.lungcan.2024.107894 　

More details Close

BACKGROUND: The risk and survival of patients with non-small cell lung cancer (NSCLC) with pre-existing autoimmune disorders (AIDs) receiving immune checkpoint blockade (ICB) therapy have not been clearly established. PATIENTS AND METHODS: This multi-institutional, retrospective cohort study was conducted in collaboration with 20 centers in Japan. RESULTS: In total, 229 patients with advanced or recurrent NSCLC and pre-existing AID, with or without ICB treatment from January 2010-February 2020, were included and analyzed. Among 69 patients who received ICB, 2 received two lines of ICBs with a total of 71 ICB treatments; 57 (80.3 %) and 14 (19.7 %) patients received ICB monotherapy and combination therapy, respectively. AID flares were observed in 18 patients (25.4 %, 95 % confidence interval [CI], 15.8-37.1 %) receiving ICB. AID exacerbations were more likely when NSCLC was diagnosed less than 1 year after the AID diagnosis (odds ratio 5.26 [95 % CI, 1.40-21.61]; P = 0.016). Immune-related adverse events were observed in 32 patients (45.1 %, 95 % CI, 33.2-57.3 %); 17 had grade 3 or higher. The safety profile of combination immunotherapy was not significantly different from that of the monotherapy. After inverse probability weighting, the use of ICB prolonged survival (hazard ratio 0.43 [95 % CI, 0.26-0.70]; P = 0.0006). CONCLUSIONS: These findings revealed a novel risk factor for AID flares following ICB treatment, that is the diagnosis of NSCLC within 1 year of AID diagnosis, and showed that ICBs may improve survival in this population. These results support the utilization of ICB in patients with NSCLC and pre-existing AID.
当院における進行期非小細胞肺癌患者に対する院内AMOY遺伝子変異検査の検査成功率とTurn Around Timeの検討

岩崎史, 宮内栄作, 井上千裕, 青山弥生, 小泉照樹, 渋谷里紗, 突田容子, 木村望, 伊藤辰徳, 小野祥直, 松本周一郎, 成田大輔, 遠藤卓人, 鈴木眞奈美, 野津田泰嗣, 小野寺賢, 岡田克典

気管支学　46　(Suppl.)　S292-S292　2024/05
Publisher: (一社)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
当院における進行期非小細胞肺癌患者に対する院内AMOY遺伝子変異検査の検査成功率とTurn Around Timeの検討

岩崎史, 宮内栄作, 井上千裕, 青山弥生, 小泉照樹, 渋谷里紗, 突田容子, 木村望, 伊藤辰徳, 小野祥直, 松本周一郎, 成田大輔, 遠藤卓人, 鈴木眞奈美, 野津田泰嗣, 小野寺賢, 岡田克典

気管支学　46　(Suppl.)　S292-S292　2024/05
Publisher: (一社)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
Peripheral blood biomarkers associated with combination of immune checkpoint blockade plus chemotherapy in NSCLC. International-journal

Nozomu Kimura, Yoko Tsukita, Risa Ebina-Shibuya, Eisaku Miyauchi, Mitsuhiro Yamada, Daisuke Narita, Ryota Saito, Chihiro Inoue, Naoya Fujino, Tomohiro Ichikawa, Tsutomu Tamada, Hisatoshi Sugiura

Cancer biomarkers : section A of Disease markers　2024/03/20

DOI： 10.3233/CBM-230301 　

More details Close

BACKGROUND: Biomarkers predicting clinical outcomes of treating non-small cell lung cancer (NSCLC) with combination of immune checkpoint inhibitors (ICIs) and chemotherapy would be valuable. OBJECTIVE: This study aims to seek predictors of combination of ICI/chemotherapy response in NSCLC patients using peripheral blood samples. METHODS: Patients diagnosed with advanced NSCLC between July 2019 and May 2021 receiving combination of ICI/chemotherapy were included and assessed for partial responses (PR), stable disease (SD) or progressive disease (PD). We measured circulating immune cells, plasma cytokines and chemokines. RESULTS: Nineteen patients were enrolled. The proportions of circulating natural killer (NK) cells within CD45 + cells, programmed death 1 (PD-1) + Tim-3 + T cells within CD4 + cells, and the amount of chemokine C-X-C ligand (CXCL10) in the plasma were significantly elevated in PR relative to SD/PD patients (median 8.1%-vs-2.1%, P= 0.0032; median 1.2%-vs-0.3%, P= 0.0050; and median 122.6 pg/ml-vs-76.0 pg/ml, P= 0.0125, respectively). Patients with 2 or 3 elevated factors had longer progression-free survival than patients with 0 or only one (not reached-vs-5.6 months, P= 0.0002). CONCLUSIONS: We conclude that NK cells, CD4 + PD-1 + Tim-3 + T cells, and CXCL10 levels in pre-treatment peripheral blood may predict the efficacy of combination of ICI/chemotherapy in NSCLC.
Immunotherapy or Chemoimmunotherapy in Older Adults With Advanced Non-Small Cell Lung Cancer. International-journal

Yoko Tsukita, Takehiro Tozuka, Kohei Kushiro, Shinobu Hosokawa, Toshiyuki Sumi, Mao Uematsu, Osamu Honjo, Ou Yamaguchi, Tetsuhiko Asao, Jun Sugisaka, Go Saito, Jun Shiihara, Ryo Morita, Seigo Katakura, Takehiro Yasuda, Kakeru Hisakane, Eisaku Miyauchi, Satoshi Morita, Kunihiko Kobayashi, Hajime Asahina

JAMA oncology　2024/03/07

DOI： 10.1001/jamaoncol.2023.6277 　

More details Close

IMPORTANCE: Immune checkpoint inhibitor (ICI) plus chemotherapy combination treatment (ICI-chemotherapy) is now a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alterations, but there are few data on ICI-chemotherapy for patients 75 years and older. OBJECTIVE: To inform the choice of first-line drugs in clinical practice and assess the safety and efficacy of ICI-chemotherapy combination treatment in older adult patients with previously untreated advanced NSCLC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 58 centers in Japan. The cohort consisted of patients 75 years and older with clinical stage IIIB, IIIC, IV, postoperative or radiotherapy recurrent NSCLC. Patients started first-line systemic therapy between December 2018 and March 2021. Those receiving first-line molecular targeted drugs were excluded. The data were analyzed from February 2022 to October 2022. EXPOSURES: Systemic therapy. MAIN OUTCOMES AND MEASURES: The main outcomes were overall survival (OS), progression-free survival (PFS), and safety. RESULTS: A total of 1245 patients (median [range] age, 78 [75-95] years; 967 [78%] male) with NSCLC were included in the cohort. Programmed death ligand-1 (PD-L1) expression of less than 1% occurred in 268 tumors (22%); 1% to 49% in 387 tumors (31%); 50% and higher in 410 tumors (33%), and unknown expression in 180 tumors (14%). Median OS was 20.0 (95% CI, 17.1-23.6) months for the 354 patients receiving ICI-chemotherapy (28%); 19.8 (95% CI, 16.5-23.8) months for the 425 patients receiving ICI alone (34%); 12.8 (95% CI, 10.7-15.6) months for the 311 patients receiving platinum-doublet chemotherapy (25%); and 9.5 (95% CI, 7.4-13.4) months for the 155 patients receiving single-agent chemotherapy (12%). After propensity score matching, no differences in OS and PFS were found between the patients receiving ICI-chemotherapy vs ICI alone. Each group consisted of 118 patients. For PD-L1 expression of 1% and higher the OS hazard ratio (HR) was 0.98 (95% CI, 0.67-1.42; P = .90), and the PFS HR was 0.92 (95% CI, 0.67-1.25; P = .59). Significance was also not reached when separately analyzed for lower or higher PD-L1 expression (1%-49% or ≥50%). However, grade 3 or higher immune-related adverse events occurred in 86 patients (24.3%) treated with ICI-chemotherapy and 76 (17.9%) with ICI alone (P = .03). CONCLUSIONS AND RELEVANCE: In this study, ICI-chemotherapy combination treatment did not improve survival and increased the incidence of grade 3 and higher immune-related adverse events compared with ICI alone in patients 75 years and older. Based on these results, ICI alone may be recommended for older adult patients with PD-L1-positive NSCLC.
肺癌患者の血漿検体を用いたメタボローム解析による個別化医療への挑戦

成田大輔, 渋谷里紗, 宮内栄作, 突田容子, 木村望, 角藤翔, 杉浦久敏

日本呼吸器学会誌　13　(増刊)　268-268　2024/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
Artemis: A Multicenter, Open-Label, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of First-Line Carboplatin/Paclitaxel/Lenvatinib/Pembrolizumab Combination for Previously Untreated Advanced or Recurrent Thymic Carcinomas. International-journal

Yusuke Okuma, Shogo Nomura, Jun Sakakibara-Konishi, Yoko Tsukita, Shuji Murakami, Yukio Hosomi, Yuichi Tambo, Yoshihito Kogure, Hiroshige Yoshioka, Motohiro Tamiya, Kiichiro Ninomiya, Eiji Iwama

Clinical lung cancer　2024/02/08

DOI： 10.1016/j.cllc.2024.02.002 　

More details Close

BACKGROUND: Thymic carcinoma is a rare cancer with an aggressive clinical presentation and no organotypic symptoms. Despite using platinum-based chemotherapy as first-line treatment, the prognosis remains poor, necessitating a novel therapeutic strategy. METHODS: The artemis trial is a Phase II, single-arm, multicenter study designed to evaluate the efficacy and safety of carboplatin, paclitaxel, lenvatinib, and pembrolizumab as first-line chemotherapy for patients with advanced or recurrent thymic carcinoma. A total of 35 patients will be enrolled in this study and will receive induction therapy every 3 weeks for up to 4 cycles, followed by pembrolizumab every 3 weeks, and daily lenvatinib as maintenance therapy for up to 31 cycles (for 2 years). Lenvatinib will be continued until disease progression or unacceptable toxicity based on the discretion of the attending physician. CONCLUSION: The primary endpoint of the study is the objective response rate, with secondary endpoints including progression-free survival, overall survival, duration of response, disease control rate, and safety profile. TRIAL REGISTRATION: ClinicalTrials.gov NCT05832827 Registered on April 27, 2023, https://classic. CLINICALTRIALS: gov/ct2/show/NCT05832827. Japan Registry of Clinical Trials (jRCT), jRCT2031230114. Registered on May 22, 2023, https://jrct.niph.go.jp/latest-detail/jRCT2031230114.
Corrigendum to "Osimertinib as first-line treatment for elderly patients with advanced EGFR mutation-positive non-small-cell lung cancer in a real-world setting (OSI-FACT-EP)" [Lung Cancer 186 (2023) 107426]. International-journal

Yoshihiko Sakata, Go Saito, Shinya Sakata, Yuko Oya, Motohiro Tamiya, Hidekazu Suzuki, Ryota Shibaki, Asuka Okada, Toshihide Yokoyama, Hirotaka Matsumoto, Taiichiro Otsuki, Yuki Sato, Uchida Junji, Yoko Tsukita, Megumi Inaba, Hideki Ikeda, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Jun Morinaga, Takuro Sakagami

Lung cancer (Amsterdam, Netherlands)　188　107450-107450　2024/02

DOI： 10.1016/j.lungcan.2023.107450 　
Durvalumab after chemoradiotherapy in non-small cell lung cancer with EGFR mutation: A real-world study (HOT2101). International-journal

Kosuke Tsuji, Hidenori Mizugaki, Keiki Yokoo, Maki Kobayashi, Yosuke Kawashima, Nozomu Kimura, Hiroshi Yokouchi, Hajime Kikuchi, Toshiyuki Sumi, Yasutaka Kawai, Kenta Kobashi, Ryo Morita, Kenichiro Ito, Yasuo Kitamura, Hiroyuki Minemura, Keiichi Nakamura, Mari Aso, Osamu Honjo, Hisashi Tanaka, Taichi Takashina, Kyoji Tsurumi, Jun Sugisaka, Yoko Tsukita, Satoshi Konno, Satoshi Oizumi

Cancer science　2024/01/29

DOI： 10.1111/cas.16094 　

More details Close

Durvalumab has been administered to patients with unresectable stage III non-small cell lung cancer (NSCLC). However, it remains unclear whether durvalumab benefits these patients with epidermal growth factor receptor (EGFR) mutation. We conducted a retrospective, multicenter study of patients with EGFR mutation who received chemoradiotherapy (CRT) between June 2018 and March 2021. We assessed patient characteristics, efficacy of durvalumab, and durvalumab safety before and after targeted therapy. We collected data on a total of 673 patients, of whom 401 (59.6%) underwent EGFR mutation testing. Fifty-one patients were EGFR positive and 311 were EGFR negative. In the EGFR-positive group, there were higher proportions of females, never-smokers, and patients with adenocarcinoma histology. Of the 51 patients in the positive group and 311 in the negative group who received CRT, 45 (88.2%) and 247 (79.4%) received durvalumab, with median progression-free survival of 23.0 and 24.2 months in the positive and negative groups, respectively (hazard ratio 1.03; 95% confidence interval: 0.64-1.67). The main adverse event was pneumonitis (positive group: 62.2%; 4.4% grade 3; negative group: 62.3%; 6.9% grade 3). No treatment-related deaths were observed. Of the 45 patients in the positive group who received durvalumab, 14 (31.1%) received targeted therapy after durvalumab at the data cutoff. One patient discontinued targeted therapy after developing pneumonitis. In patients with unresectable stage III NSCLC with EGFR mutation, durvalumab after CRT is potentially safe and effective. This may be a suitable treatment sequence for these patients.
Osimertinib as first-line treatment for elderly patients with advanced EGFR mutation-positive non-small cell lung cancer in a real-world setting (OSI-FACT-EP)

Yoshihiko Sakata, Go Saito, Shinya Sakata, Yuko Oya, Motohiro Tamiya, Hidekazu Suzuki, Ryota Shibaki, Asuka Okada, Toshihide Yokoyama, Hirotaka Matsumoto, Taiichiro Otsuki, Yuki Sato, Uchida Junji, Yoko Tsukita, Megumi Inaba, Hideki Ikeda, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Jun Morinaga, Takuro Sakagami

Lung Cancer　186　107426-107426　2023/12
Publisher: Elsevier BV
DOI： 10.1016/j.lungcan.2023.107426 　

ISSN： 0169-5002
局所進行非小細胞肺癌へのPACIFICレジメン後再発に対する次治療実態調査 CRIMSON試験における探索的研究

河内勇人, 田宮基裕, 大矢由子, 松本啓孝, 佐藤悠城, 大搗泰一郎, 齋藤合, 鈴木秀和, 福田泰, 田中智, 突田容子, 内田純二, 坂田能彦, 中谷有貴, 寺岡俊輔, 荒井大輔, 岡田あすか, 原聡志, 高山浩一

肺癌　63　(5)　489-489　2023/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
希少ドライバー遺伝子異常をもつ肺癌患者の後方視的観察研究

荒井大輔, 仲地一郎, 齋藤合, 佐藤悠城, 突田容子, 岡田あすか, 松本啓孝, 寺岡俊輔, 田宮基裕, 田中智, 内田純二, 坂田能彦, 原聡志, 横山俊秀, 高岩卓也, 河内勇人, 谷口善彦, 岸川孝之

肺癌　63　(5)　537-537　2023/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
BRAF変異陽性肺癌に見られる臨床的特徴と治療効果について

島佑介, 仲地一郎, 荒井大輔, 齋藤合, 田中智, 横山俊秀, 寺岡俊輔, 内田純二, 突田容子, 岸川孝之, 田宮基裕, 河内勇人

肺癌　63　(5)　540-540　2023/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
HER2異常を有する肺癌に見られる臨床的特徴

田中智, 仲地一郎, 齋藤合, 荒井大輔, 田宮基裕, 原聡志, 内田純二, 突田容子, 河内勇人, 寺岡俊輔

肺癌　63　(5)　660-660　2023/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
間質性肺炎合併小細胞肺癌に対するデュルバルマブ/エトポシド/カルボプラチン療法の多施設前向き介入試験

坂田能彦, 藤本大智, 柴木亮太, 仲地一郎, 荒井大輔, 宮内栄作, 突田容子, 神宮直樹, 木島貴志, 田宮基裕, 川名祥子, 原聡志, 齋藤合, 佐藤悠城, 横山俊秀, 坂田晋也, 谷口善彦, 秦明登, 松本啓孝, 山口哲平

肺癌　63　(5)　474-474　2023/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
非小細胞肺癌患者に対するAMOY遺伝子変異検査の院内導入における利点と今後の課題

宮内栄作, 井上千裕, 青山弥生, 小泉照樹, 渋谷里紗, 突田容子, 木村望, 成田大輔, 野津田泰嗣, 小野寺賢, 岡田克典, 杉浦久敏

肺癌　63　(5)　578-578　2023/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
初回治療Osimertinib多施設実態調査(OSI-FACT)の高齢者解析

齋藤合, 坂田能彦, 坂田晋也, 大矢由子, 田宮基裕, 鈴木秀和, 柴木亮太, 岡田あすか, 横山俊秀, 松本啓孝, 大搗泰一郎, 佐藤悠城, 内田純二, 突田容子, 稲葉恵, 池田英樹, 荒井大輔, 丸山広高, 原聡志, 津村真介, 森永潤, 坂上拓郎

肺癌　63　(5)　518-518　2023/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
初回治療Osimertinib多施設実態調査(OSI-FACT)の高齢者解析

齋藤合, 坂田能彦, 坂田晋也, 大矢由子, 田宮基裕, 鈴木秀和, 柴木亮太, 岡田あすか, 横山俊秀, 松本啓孝, 大搗泰一郎, 佐藤悠城, 内田純二, 突田容子, 稲葉恵, 池田英樹, 荒井大輔, 丸山広高, 原聡志, 津村真介, 森永潤, 坂上拓郎

肺癌　63　(5)　518-518　2023/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
A Case of IgA Vasculitis During Atezolizumab Treatment.

Yoshinao Ono, Yoko Tsukita, Naoya Fujino, Hisatoshi Sugiura

Internal medicine (Tokyo, Japan)　2023/08/02

DOI： 10.2169/internalmedicine.2343-23 　
肺癌効果予測因子非小細胞肺癌に対する殺細胞性抗癌剤・免疫チェックポイント阻害薬併用療法の効果予測因子の探索

木村望, 突田容子, 渋谷里紗, 宮内栄作, 角藤翔, 成田大輔, 斎藤良太, 杉浦久敏

日本呼吸器学会誌　12　(増刊)　194-194　2023/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
Antibody responses to second doses of COVID-19 vaccination in lung cancer patients undergoing treatment. International-journal

Daisuke Narita, Risa Ebina-Shibuya, Eisaku Miyauchi, Yoko Tsukita, Ryota Saito, Koji Murakami, Nozomu Kimura, Hisatoshi Sugiura

Respiratory investigation　61　(2)　247-253　2022/12/15

DOI： 10.1016/j.resinv.2022.11.005 　

More details Close

BACKGROUND: Several reports have revealed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection tends to have more severe outcomes in cancer patients. Although vaccination reduces the risk of severe disease, data on antibody titers achieved by vaccination is scarce in cancer patients. METHODS: We collected 79 blood samples (69 lung cancer patients and 10 control individuals) and conducted an anti-SARS-CoV-2 antibody assay to compare the antibody titer achieved with current treatment. Sixty-eight patients (86%) received the BNT162 mRNA vaccine and 11 (14%) received the mRNA-1273 vaccine. They were categorized according to the current treatment: control individuals without cancer (cohort A), lung cancer patients who were treated with cytotoxic chemotherapy (cohort B), immunotherapy (cohort C), combination of cytotoxic chemotherapy and immunotherapy (cohort D), tyrosine kinase inhibitors (cohort E), and radiation therapy (cohort F). RESULTS: Among 69 lung cancer patients (cohort B-F), 57 (83%) had adenocarcinoma, and 66 (96%) had advanced-stage cancer. In the anti-SARS-CoV-2 antibody assay, the antibody titer was significantly lower in lung cancer patients than in control individuals (p = 0.01). The median antibody titers were 161 AU/ml in control individuals and 59.9 AU/ml in lung cancer patients. CONCLUSIONS: Antibody titers after the second vaccination were lower in cancer patients than those in healthy individuals. Our findings provide essential information for understanding the benefits and necessity of additional vaccination to prevent SARS-CoV-2 infection in lung cancer patients.
Safety and efficacy of osimertinib rechallenge or continuation after pneumonitis: A multicentre retrospective cohort study. International-journal

Mihoko Imaji, Daichi Fujimoto, Yuki Sato, Yoshihiko Sakata, Yuko Oya, Motohiro Tamiya, Hidekazu Suzuki, Hideki Ikeda, Takashi Kijima, Hirotaka Matsumoto, Masaki Kanazu, Aoi Hino, Megumi Inaba, Yoko Tsukita, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Hiroshi Kobe, Hiromitsu Sumikawa, Shinya Sakata, Nobuyuki Yamamoto

European journal of cancer (Oxford, England : 1990)　179　15-24　2022/11/12

DOI： 10.1016/j.ejca.2022.10.029 　

More details Close

INTRODUCTION: Although osimertinib is a standard first-line treatment for patients with advanced-stage non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, the incidence rate of pneumonitis associated with osimertinib is high. However, there are few reports about the safety and efficacy of osimertinib rechallenge after the development of pneumonitis. METHODS: We conducted a retrospective multicentre cohort study of consecutive patients who developed pneumonitis associated with osimertinib as a first-line and received osimertinib rechallenge. The primary outcome was the incidence rate of any grade pneumonitis after osimertinib rechallenge. The secondary outcome was treatment efficacy in patients after osimertinib rechallenge. RESULTS: In total, 33 patients who received osimertinib rechallenge were included. Of them, 26 patients had grade 1, 6 patients had grade 2, and 1 patient had grade 3 initial pneumonitis. The median follow-up period after the osimertinib rechallenge was 16.9 months (interquartile range, 11.1-21.3 months). After the start of osimertinib rechallenge, five patients (15%) experienced mild relapsed pneumonitis. Three of the five patients had similar imaging patterns for initial and relapsed pneumonitis. No significant differences in characteristics were observed between patients with and without relapsed pneumonitis. The median progression-free survival after osimertinib rechallenge was not achieved (95% confidence interval: 10.3 months - not reached). CONCLUSION: Osimertinib rechallenge was feasible and effective for patients who developed initial pneumonitis associated with first-line osimertinib therapy. Osimertinib might be considered a treatment option even after the development of mild initial pneumonitis.
初回治療Osimertinibの実臨床実態調査(OSI-FACT)におけるPS不良例の解析

田宮基裕, 坂田能彦, 池田英樹, 齋藤合, 鈴木秀和, 原聡志, 突田容子, 木島貴志, 松本啓孝, 佐藤悠城, 金津正樹, 丸山広高, 稲葉恵, 荒井大輔, 津村伸介, 大矢由子, 神戸寛史, 岡田あすか, 坂田晋也, 藤本大智

肺癌　62　(6)　634-634　2022/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
EGFR陽性非小細胞肺癌に対する初回治療Osimertinibの多施設実態調査に付随する薬剤性肺障害の検討

佐藤悠城, 澄川裕充, 柴木亮太, 森本剛, 坂田能彦, 大矢由子, 田宮基裕, 鈴木秀和, 松本啓孝, 木島貴志, 橋本和樹, 神戸寛史, 日野葵, 稲葉恵, 突田容子, 池田英樹, 荒井大輔, 丸山広高, 原聡志, 津村真介, 坂田晋也, 藤本大智

肺癌　62　(6)　658-658　2022/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
初回治療オシメルチニブによる薬剤性肺障害発症後リチャレンジの安全性,有効性に関する検討

今地美帆子, 藤本大智, 佐藤悠城, 坂田能彦, 大矢由子, 田宮基裕, 鈴木秀和, 池田英樹, 木島貴志, 松本啓孝, 金津正樹, 齋藤合, 稲葉恵, 突田容子, 荒井大輔, 丸山広高, 原聡志, 津村真介, 神戸寛史, 坂田晋也

肺癌　62　(6)　658-658　2022/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
初回治療Osimertinibの多施設実態調査(OSI-FACT)の追跡調査報告

大矢由子, 坂田能彦, 坂田晋也, 田宮基裕, 鈴木秀和, 柴木亮太, 岡田あすか, 神戸寛史, 松本啓孝, 大搗泰一郎, 佐藤悠城, 金津正樹, 齋藤合, 突田容子, 稲葉恵, 池田英樹, 荒井大輔, 丸山広高, 森永潤, 坂上拓郎

肺癌　62　(6)　658-658　2022/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
Uncommon EGFR mutationに対する初回オシメルチニブの有効性・安全性に関する検討

突田容子, 坂田能彦, 田宮基裕, 柴木亮太, 大矢由子, 金津正樹, 稲葉恵, 坂田晋也, 鈴木秀和, 神戸寛史, 日野葵, 池田英樹, 丸山広高, 坂上拓郎

肺癌　62　(6)　689-689　2022/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
Durvalumab承認後,化学放射線治療を受けた局所進行NSCLCにおける予後予測因子の検討(CRIMSON試験)

大矢由子, 河内勇人, 谷口善彦, 松本啓孝, 佐藤悠城, 大搗泰一郎, 斎藤合, 鈴木秀和, 福田泰, 田中智, 突田容子, 金津正樹, 坂田能彦, 中谷有貴, 寺岡俊輔, 荒井大輔, 岡田あすか, 原聡志

肺癌　62　(6)　583-583　2022/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
初回治療Osimertinibの実臨床実態調査(OSI-FACT)におけるPS不良例の解析

田宮基裕, 坂田能彦, 池田英樹, 齋藤合, 鈴木秀和, 原聡志, 突田容子, 木島貴志, 松本啓孝, 佐藤悠城, 金津正樹, 丸山広高, 稲葉恵, 荒井大輔, 津村伸介, 大矢由子, 神戸寛史, 岡田あすか, 坂田晋也, 藤本大智

肺癌　62　(6)　634-634　2022/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
初回治療Osimertinibの多施設実態調査(OSI-FACT)の追跡調査報告

大矢由子, 坂田能彦, 坂田晋也, 田宮基裕, 鈴木秀和, 柴木亮太, 岡田あすか, 神戸寛史, 松本啓孝, 大搗泰一郎, 佐藤悠城, 金津正樹, 齋藤合, 突田容子, 稲葉恵, 池田英樹, 荒井大輔, 丸山広高, 森永潤, 坂上拓郎

肺癌　62　(6)　658-658　2022/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
EGFR陽性非小細胞肺癌に対する初回治療Osimertinibの多施設実態調査に付随する薬剤性肺障害の検討

佐藤悠城, 澄川裕充, 柴木亮太, 森本剛, 坂田能彦, 大矢由子, 田宮基裕, 鈴木秀和, 松本啓孝, 木島貴志, 橋本和樹, 神戸寛史, 日野葵, 稲葉恵, 突田容子, 池田英樹, 荒井大輔, 丸山広高, 原聡志, 津村真介, 坂田晋也, 藤本大智

肺癌　62　(6)　658-658　2022/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
初回治療オシメルチニブによる薬剤性肺障害発症後リチャレンジの安全性,有効性に関する検討

今地美帆子, 藤本大智, 佐藤悠城, 坂田能彦, 大矢由子, 田宮基裕, 鈴木秀和, 池田英樹, 木島貴志, 松本啓孝, 金津正樹, 齋藤合, 稲葉恵, 突田容子, 荒井大輔, 丸山広高, 原聡志, 津村真介, 神戸寛史, 坂田晋也

肺癌　62　(6)　658-658　2022/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
Uncommon EGFR mutationに対する初回オシメルチニブの有効性・安全性に関する検討

突田容子, 坂田能彦, 田宮基裕, 柴木亮太, 大矢由子, 金津正樹, 稲葉恵, 坂田晋也, 鈴木秀和, 神戸寛史, 日野葵, 池田英樹, 丸山広高, 坂上拓郎

肺癌　62　(6)　689-689　2022/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study. International-journal

Yuichiro Takeda, Yusaku Kusaba, Yoko Tsukita, Yukari Uemura, Eisaku Miyauchi, Takaya Yamamoto, Hiroshi Mayahara, Akito Hata, Hidetsugu Nakayama, Satoshi Tanaka, Junji Uchida, Kazuhiro Usui, Tatsuya Toyoda, Motohiro Tamiya, Masahiro Morimoto, Yuko Oya, Takeshi Kodaira, Keiichi Jingu, Hisatoshi Sugiura

Clinical and translational radiation oncology　37　57-63　2022/11

DOI： 10.1016/j.ctro.2022.08.010 　

More details Close

Purpose: Intensity-modulated radiotherapy (IMRT) is currently used more commonly than 3-dimensional conformal radiation for definitive thoracic radiation. We examined the efficacy profiles of concurrent chemoradiotherapy (CCRT) with IMRT after durvalumab became clinically available. Methods: We reviewed the clinical records of patients with stage III non-small cell lung cancer (NSCLC) treated with CCRT and IMRT at seven centers in Japan and investigated relapse and survival from May 2018 to December 2019. The primary endpoint of this report was progression-free survival (PFS). Results: Among 107 patients enrolled in the study, 87 were sequentially administered durvalumab. From CCRT commencement, patients were followed up for a median period of 29.7 months. The median PFS at the end of the CCRT was 20.7 months. Among the 87 patients, 58 experienced disease relapses, of whom 36 (62.1 %) had distant metastases. Multivariate Cox regression analysis revealed that a favorable response to CCRT, a radiation dose ≥ 62 Gy, and stage IIIA NSCLC were associated with prolonged PFS (all P = 0.04). Multivariate logistic regression by landmark analysis revealed that mortality risk factors were durvalumab treatment duration ≤ 11.7 months, a lower maximum grade of immune-related adverse events, FEV1 < 2805 mL, and radiation dose < 62 Gy (P = 0.01, 0.01, 0.03, and 0.04, respectively). Conclusions: In patients with NSCLC receiving CCRT using IMRT, long PFS was associated with a better response to CCRT, stage IIIA NSCLC, and an increased radiation dose. The duration of durvalumab consolidation also played an essential role in the survival of patients receiving CCRT with IMRT. (250 words).
Clinical features of COVID-19 patients with rebound phenomenon after corticosteroid therapy

Koji Murakami, Hirohito Sano, Naoki Tode, Yoko Tsukita, Kei Sato, Daisuke Narita, Nozomu Kimura, Shuichiro Matsumoto, Yoshinao Ono, Chikashi Iwasaki, Hatsumi Sugiyama, Manami Suzuki, Sho Kakuto, Shuichi Konno, Hajime Kanamori, Hiroaki Baba, Kengo Oshima, Kentarou Takei, Koichi Tokuda, Tsutomu Tamada, Hisatoshi Sugiura

BMJ OPEN RESPIRATORY RESEARCH　9　(1)　2022/09

DOI： 10.1136/bmjresp-2022-001332 　

eISSN： 2052-4439
Stereotactic Radiosurgery for Lung Cancer with a Risk-Adapted Strategy Using the Volumetric Modulated Arc Therapy Technique: A Single Arm Phase II Study

Takaya Yamamoto, Yu Katagiri, Yoko Tsukita, Haruo Matsushita, Rei Umezawa, Yoshiyuki Katsuta, Noriyuki Kadoya, Noriyoshi Takahashi, Yu Suzuki, Kazuya Takeda, Keita Kishida, So Omata, Eisaku Miyauchi, Ryota Saito, Keiichi Jingu

Cancers　14　(16)　3993-3993　2022/08/18
Publisher: MDPI AG
DOI： 10.3390/cancers14163993 　

eISSN： 2072-6694

More details Close

Purpose: A phase II study carried out to assess the efficacy of a risk-adapted strategy of stereotactic radiosurgery (SRS) for lung cancer. The primary endpoint was 3-year local recurrence, and the secondary endpoints were overall survival (OS), disease-free survival (DFS), rate of start of systemic therapy or best supportive care (SST-BSC), and toxicity. Materials and Methods: Eligible patients fulfilled the following criteria: performance status of 2 or less, forced expiratory volume in 1 s of 700 mL or more, and tumor not located in central or attached to the chest wall. Twenty-eight Gy was prescribed for primary lung cancers with diameters of 3 cm or less and 30 Gy was prescribed for primary lung cancers with diameters of 3.1–5.0 cm or solitary metastatic lung cancer diameters of 5 cm or less. Results: Twenty-one patients were analyzed. The patients included 7 patients with adenocarcinoma, 2 patients with squamous cell carcinoma, 1 patient with metastasis, and 11 patients with clinical diagnosis. The median tumor diameter was 1.9 cm. SRS was prescribed at 28 Gy for 18 tumors and 30 Gy for 3 tumors. During the median follow-up period of 38.9 months for survivors, 1 patient had local recurrence, 7 patients had regional or distant metastasis, and 5 patients died. The 3-year local recurrence, SST-BSC, DFS, and OS rates were 5.3% (95% confidence interval [CI]: 0.3–22.2%), 20.1% (95% CI: 6.0–40.2%), 59.2% (95% CI: 34.4–77.3%), and 78.2% (95% CI: 51.4–91.3%), respectively. The 95% CI upper value of local recurrence was lower than the null local recurrence probability. There was no severe toxicity, and grade 2 radiation pneumonitis occurred in 1 patient. Conclusions: Patients who received SRS for lung cancer had a low rate of 3-year local recurrence and tolerable toxicity.
Decreased expression of airway epithelial Axl is associated with eosinophilic inflammation in severe asthma. International-journal

Koji Itakura, Naoya Fujino, Yosuke Kamide, Ikuo Saito, Mitsuhiro Yamada, Koji Okutomo, Yoko Tsukita, Takuya Saito, Tomohiro Ichikawa, Tadahisa Numakura, Yorihiko Kyogoku, Hiroyuki Aizawa, Yoshinao Ono, Shuichiro Matsumoto, Tracy Hussell, Masami Taniguchi, Masakazu Ichinose, Hisatoshi Sugiura

Allergology international : official journal of the Japanese Society of Allergology　71　(3)　383-394　2022/07

DOI： 10.1016/j.alit.2022.02.010 　

More details Close

BACKGROUND: Airway epithelium-derived cytokines are critical to provoke and perpetuate type 2 inflammation in asthma. Yet it is poorly understood how this epithelial cell-driven inflammatory response is negatively regulated. We previously reported that Axl receptor tyrosine kinase was expressed by basal cells in the airway epithelium and had a role in defining their stem cell identity. However, whether and how Axl regulates airway type 2 inflammation remains unknown. METHODS: We performed immunofluorescence staining to compare Axl expression in airway epithelium between non-asthmatic subjects, mild-moderate asthma and severe asthma. We confirmed this result by interrogating public databases of global gene expression in endobronchial biopsies. We then quantified eosinophil numbers infiltrating into the trachea of wild-type or Axl-knockout mice that were intranasally treated with house dust mite extracts (HDM). Cell-based assays using siRNA targeting Axl were further performed to identify molecules involved in Axl-mediated regulation of inflammation. RESULTS: Histological assessments and transcriptome analyses revealed decreases in protein and mRNA of Axl in airway basal cells of severe asthmatics. This reduction of Axl expression was correlated with infiltration of eosinophils and mast cells in severe asthmatics. Eosinophil infiltration was more evident in the trachea of Axl-knockout mice in response to repetitive HDM administration. siRNA-mediated knockdown of Axl increased mRNA and protein expression of granulocyte macrophage-colony stimulating factor (GM-CSF) in human bronchial epithelial cells. CONCLUSIONS: Axl kinase expressed by basal cells may suppress excessive eosinophilic inflammation via inhibition of GM-CSF in the airway. Axl reduction has clinical implications for the pathogenesis of severe asthma.
Drug-related pneumonitis induced by osimertinib as first-line treatment for EGFR-positive non-small cell lung cancer: a real-world setting. International-journal

Yuki Sato, Hiromitsu Sumikawa, Ryota Shibaki, Takeshi Morimoto, Yoshihiko Sakata, Yuko Oya, Motohiro Tamiya, Hidekazu Suzuki, Hirotaka Matsumoto, Takashi Yokoi, Kazuki Hashimoto, Hiroshi Kobe, Aoi Hino, Megumi Inaba, Yoko Tsukita, Hideki Ikeda, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Shinya Sakata, Daichi Fujimoto

Chest　162　(5)　1188-1198　2022/06/01

DOI： 10.1016/j.chest.2022.05.035 　

More details Close

BACKGROUND: Osimertinib has demonstrated impressive efficacy as a first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive (m+) lung cancer. Drug-related pneumonitis (DRP) is a potentially lethal complication of osimertinib treatment, but reliable real-world data are currently lacking. RESEARCH QUESTION: What is the prevalence of osimertinib-induced DRP in first-line settings? What are the characteristics, clinical impact, and risk factors of osimertinib-induced DRP? STUDY DESIGN AND METHODS: We conducted a retrospective multicenter cohort study of patients who received osimertinib as a first-line treatment for advanced EGFR m+ non-small cell lung cancer (NSCLC) between August 2018 and December 2019. All chest computed tomography (CT) scans and clinical information during osimertinib exposure were collected until June 2020. The primary endpoint was DRP incidence identified through central review. RESULTS: A total of 452 patients from 18 institutions were evaluated. Eighty patients (18%) were diagnosed with DRP (all grades), and 21 patients (4.6%) had ≥grade 3 DRP. Among the patients with DRP, 46% were identified as having transient asymptomatic pulmonary opacity (TAPO). Regarding the CT patterns, organizing pneumonia, simple pulmonary eosinophilia, hypersensitivity pneumonia, diffuse alveolar damage, and non-specific interstitial pneumonia were found in 30, 21, 18, 9, and 2 patients (38%, 26%, 23%, 11%, and 3%), respectively. In multivariate analysis, smoking history was identified as an independent risk factor for DRP (hazard ratio: 1.72, 95% confidence interval: 1.01-2.89, P=0.046). In the 3-month landmark analysis, DRP was associated with poor treatment efficacy; however, the presence of TAPO did not negatively affect treatment efficacy. INTERPRETATION: For osimertinib treatment in first-line settings, the frequency of DRP was considerably elevated to 18 %, and half of these patients exhibited TAPO features.
Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. International-journal

Takaya Yamamoto, Yoko Tsukita, Yu Katagiri, Haruo Matsushita, Rei Umezawa, Yojiro Ishikawa, Noriyoshi Takahashi, Yu Suzuki, Kazuya Takeda, Eisaku Miyauchi, Ryota Saito, Yoshiyuki Katsuta, Noriyuki Kadoya, Keiichi Jingu

BMC cancer　22　(1)　364-364　2022/04/04

DOI： 10.1186/s12885-022-09354-1 　

More details Close

BACKGROUND: In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan-Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates. RESULTS: A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01). CONCLUSIONS: In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.
修飾核酸一斉定量系を用いたCOPD・肺がん鑑別手法の検討

渡辺匠, 平本航大, 沼倉忠久, 宮内栄作, 突田容子, 杉浦久敏, 松本洋太郎, 富岡佳久

日本薬学会年会要旨集　142年会　26M-pm08S　2022/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
修飾核酸一斉定量系を用いたCOPD・肺がん鑑別手法の検討

渡辺匠, 平本航大, 沼倉忠久, 宮内栄作, 突田容子, 杉浦久敏, 松本洋太郎, 富岡佳久

日本薬学会年会要旨集　142年会　26M-pm08S　2022/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Longitudinal analyses and predictive factors of radiation-induced lung toxicity-related parameters after stereotactic radiotherapy for lung cancer. International-journal

Takaya Yamamoto, Yoshiyuki Katsuta, Kiyokazu Sato, Yoko Tsukita, Rei Umezawa, Noriyoshi Takahashi, Yu Suzuki, Kazuya Takeda, Keita Kishida, So Omata, Eisaku Miyauchi, Ryota Saito, Noriyuki Kadoya, Keiichi Jingu

PloS one　17　(12)　e0278707　2022

DOI： 10.1371/journal.pone.0278707 　

More details Close

BACKGROUND AND PURPOSE: The purpose of this prospective study was to investigate changes in longitudinal parameters after stereotactic radiotherapy for lung cancer and to identify possible pretreatment factors related to radiation-induced lung toxicity and the decline in pulmonary function after radiotherapy. MATERIALS AND METHODS: Protocol-specified examinations, including 4-D CT, laboratory tests, pulmonary function tests (PFTs) and body composition measurements, were performed before SRT and at 1 month, 4 months and 12 months after stereotactic radiotherapy. Longitudinal differences were tested by using repeated-measures analysis of variance. Correlations were examined by using the Pearson product-moment correlation coefficient (r). RESULTS: Sixteen patients were analyzed in this study. During a median follow-up period of 26.6 months, grade 1 and 2 lung toxicity occurred in 11 patients and 1 patient, respectively. The mean Hounsfield units (HU) and standard deviation (SD) of the whole lung, as well as sialylated carbohydrate antigen KL-6 (KL-6) and surfactant protein-D (SP-D), peaked at 4 months after radiotherapy (p = 0.11, p<0.01, p = 0.04 and p<0.01, respectively). At 4 months, lung V20 Gy (%) and V40 Gy (%) were correlated with changes in SP-D, whereas changes in the mean HU of the lung were related to body mass index and lean body mass index (r = 0.54, p = 0.02; r = 0.57, p = 0.01; r = 0.69, p<0.01; and r = 0.69, p<0.01, respectively). The parameters of PFTs gradually declined over time. When regarding the change in PFTs from pretreatment to 12 months, lung V5 Gy (cc) showed significant correlations with diffusion capacity for carbon monoxide (DLCO), DLCO/alveolar volume and the relative change in DLCO (r = -0.72, p<0.01; r = -0.73, p<0.01; and r = -0.63, p = 0.01, respectively). CONCLUSIONS: The results indicated that some parameters peaked at 4 months, but PFTs were the lowest at 12 months. Significant correlations between lung V5 Gy (cc) and changes in DLCO and DLCO/alveolar volume were observed.
リンパ行性転移が示唆された小細胞肺癌術後気管内再発の1例

木村望, 突田容子, 宮内栄作, 小室英恵, 齊藤涼子, 佐藤輝幸, 宍倉裕, 野津田泰嗣, 桜田晃, 杉浦久敏

気管支学　44　(1)　69-72　2022/01
Publisher: (NPO)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
リンパ行性転移が示唆された小細胞肺癌術後気管内再発の1例

木村望, 突田容子, 宮内栄作, 小室英恵, 齊藤涼子, 佐藤輝幸, 宍倉裕, 野津田泰嗣, 桜田晃, 杉浦久敏

気管支学　44　(1)　69-72　2022/01
Publisher: (NPO)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
Osimertinib as first-line treatment for advanced epidermal growth factor receptor mutation-positive non-small-cell lung cancer in a real-world setting (OSI-FACT). International-journal

Yoshihiko Sakata, Shinya Sakata, Yuko Oya, Motohiro Tamiya, Hidekazu Suzuki, Ryota Shibaki, Asuka Okada, Hiroshi Kobe, Hirotaka Matsumoto, Takashi Yokoi, Yuki Sato, Takeshi Uenami, Go Saito, Yoko Tsukita, Megumi Inaba, Hideki Ikeda, Daisuke Arai, Hirotaka Maruyama, Satoshi Hara, Shinsuke Tsumura, Jun Morinaga, Takuro Sakagami

European journal of cancer (Oxford, England : 1990)　159　144-153　2021/12

DOI： 10.1016/j.ejca.2021.09.041 　

More details Close

BACKGROUND: Osimertinib is the standard of care in the initial treatment for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, clinical data and reliable prognostic biomarkers are insufficient. METHODS: We performed a retrospective multicentre cohort study for 538 EGFR mutation-positive patients, who received osimertinib as the initial treatment between August 2018 and December 2019. The main outcome was progression-free survival (PFS). RESULTS: The median observation period was 14.7 months (interquartile range 11.4-20.0). The median PFS was 20.5 months (95% confidence interval [CI] 18.6-not reached). Multivariate analysis showed that sex (male) (hazard ratio [HR] 1.99, 95% CI 1.35-2.93, P = 0.001), malignant effusions (HR 1.51, 95% CI 1.11-2.04, P = 0.008), liver metastasis (HR 1.55, 95% CI 1.03-2.33, P = 0.037), advanced unresectable cases (HR 1.71, 95% CI, 1.04-2.82, P = 0.036), mutation type and programmed cell death-ligand 1 (PD-L1) expression were associated with PFS. The L858R (HR 1.55, 95% CI 1.01-2.38, P = 0.043) and uncommon mutations (HR 3.15, 95% CI 1.70-5.83, P < 0.001) were associated with PFS. PD-L1 expression of 1-49% (HR 1.66, 95% CI 1.05-2.63, P = 0.029), ≥50% (HR 2.24, 95% CI 1.17-4.30, P = 0.015) and unknown (HR 1.53, 95% CI 1.05-2.22, P = 0.026) was associated with PFS. The main reasons for treatment discontinuation among 219 patients were disease progression (44.3%), pneumonitis (25.5%) and other adverse events (16.0%). CONCLUSION: During initial treatment with osimertinib, PD-L1 expression is significantly related to PFS. Adverse events are a noteworthy reason for discontinuation.
切除不能III期非小細胞肺癌に対する強度変調放射線治療を用いた化学放射線療法に関しての後方視的研究

草場勇作, 竹田雄一郎, 突田容子, 山本貴也, 宮内栄作, 馬屋原博, 秦明登, 田中智, 内田純二, 臼井一裕, 田宮基裕, 大矢由子

肺癌　61　(6)　592-592　2021/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
Intensity-modulated radiation therapy with concurrent chemotherapy followed by durvalumab for stage III non-small cell lung cancer: A multi-center retrospective study. International-journal

Yoko Tsukita, Takaya Yamamoto, Hiroshi Mayahara, Akito Hata, Yuichiro Takeda, Hidetsugu Nakayama, Satoshi Tanaka, Junji Uchida, Kazuhiro Usui, Tatsuya Toyoda, Motohiro Tamiya, Masahiro Morimoto, Yuko Oya, Takeshi Kodaira, Eisaku Miyauchi, Keiichi Jingu, Hisatoshi Sugiura

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology　160　266-272　2021/05/21

DOI： 10.1016/j.radonc.2021.05.016 　

More details Close

BACKGROUND AND PURPOSE: Intensity-modulated radiation therapy (IMRT) is increasingly applied in concurrent chemoradiotherapy (CCRT) for locally-advanced non-small cell lung cancer (NSCLC), with improvement of target coverage and better sparing of normal tissue. IMRT tends to have a larger low-dose irradiation volume than 3D conformal radiotherapy, but the incidence of and risk factors for pneumonitis remain unclear, especially following the approval of durvalumab. MATERIALS AND METHODS: We retrospectively reviewed the records of NSCLC patients treated by CCRT using IMRT at seven Japanese institutions. Primary outcomes were incidence of symptomatic pneumonitis and progression-free survival (PFS). Multivariate logistic regression analysis was used to identify risk factors for ≥grade 2 pneumonitis. RESULTS: Median follow-up from the start of CCRT was 14.3 months (n = 107 patients; median age 70 years, 29% female). Median lung V5 and V20 was 49.2% and 19.5%, respectively. Durvalumab was administered to 87 patients (81%). Pneumonitis developed in 95 (89%) patients of which 53% had grade 1, 28% grade 2, 6.5% grade 3, and 0.9% grade 4. Durvalumab had been discontinued in 16 patients (18.4%) due to pneumonitis. By multivariate analysis, age ≥70 years, male sex, and V5 ≥58.9% were identified as significantly associated with ≥grade 2 pneumonitis (p = 0.0065, 0.036 and 0.0013 respectively). The median PFS from the start of CCRT was not reached (95% CI, 14.2 months to not reached) in patients receiving durvalumab. CONCLUSION: CCRT using IMRT followed by durvalumab was generally effective and tolerable; V5 <60% would be recommended to avoid symptomatic pneumonitis.
当院におけるIMRTによる根治的放射線化学療法後のデュルバルマブ投与症例の検討

木村望, 突田容子, 斎藤良太, 佐藤輝幸, 宮内栄作, 井上彰, 杉浦久敏

日本呼吸器学会誌　10　(増刊)　139-139　2021/04
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
ALK-IHC陽性肺腺癌に対してアレクチニブを投与したが奏効せず、後にROS1陽性が判明しクリゾチニブが奏効した1例

杉山初美, 宮内栄作, 齋藤勉, 相澤洋之, 突田容子, 齋藤良太, 佐藤輝幸, 宍倉裕, 杉浦久敏, 齊藤涼子

肺癌　60　(7)　1032-1032　2020/12
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
ALK-IHC陽性肺腺癌に対してアレクチニブを投与したが奏効せず、後にROS1陽性が判明しクリゾチニブが奏効した1例

杉山初美, 宮内栄作, 齋藤勉, 相澤洋之, 突田容子, 齋藤良太, 佐藤輝幸, 宍倉裕, 杉浦久敏, 齊藤涼子

肺癌　60　(7)　1032-1032　2020/12
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
Immunotherapy-related hepatitis and thrombocytopaenia induced by the very low dose of only 90 mg of atezolizumab. International-journal

Yoko Tsukita, Eisaku Miyauchi, Masahide Fukudo, Takaaki Sasaki, Masakazu Ichinose

European journal of cancer (Oxford, England : 1990)　133　22-24　2020/07

DOI： 10.1016/j.ejca.2020.04.008 　
Clinical Outcomes of Second-Line Chemotherapy in Patients with Previously Treated Advanced Thymic Carcinoma: A Retrospective Analysis of 191 Patients from the NEJ023 Study. International-journal

Kazunari Tateishi, Ryo Ko, Takehito Shukuya, Yusuke Okuma, Satoshi Watanabe, Shoichi Kuyama, Kyoko Murase, Yoko Tsukita, Hironori Ashinuma, Taku Nakagawa, Kazutsugu Uematsu, Mika Nakao, Yoshiaki Mori, Kyoichi Kaira, Atsuto Mouri, Takao Miyabayashi, Hiroyuki Sakashita, Yoko Matsumoto, Tomoyuki Tanigawa, Tomonobu Koizumi, Satoshi Morita, Kunihiko Kobayashi, Toshihiro Nukiwa, Kazuhisa Takahashi

The oncologist　25　(4)　e668-e674　2020/04

DOI： 10.1634/theoncologist.2019-0593 　

More details Close

BACKGROUND: Owing to the rarity of this tumor, there is limited information about second-line chemotherapy for patients with previously treated advanced thymic carcinoma. MATERIAL AND METHODS: We performed a multi-institutional, retrospective study named NEJ023 for patients with advanced thymic carcinoma. Patients without indications for curative treatment were treated with chemotherapy from 1995 to 2014 at 40 institutions in the North East Japan Study Group. Demographic and clinicopathologic characteristics, data on treatment methods, and outcomes of second-line chemotherapy were obtained from medical records. RESULTS: In total, 191 patients were enrolled in this study. Second-line chemotherapy included platinum-based doublets in 57.6% of patients, other multidrug chemotherapy (e.g., cisplatin, doxorubicin, vincristine, and cyclophosphamide) in 13.6%, and monotherapy in 28.8%. The median follow-up time was 50.5 months, and the median overall survival (OS) from the start of second-line chemotherapy was 22.4 (95% confidence interval, 17.5-26.7) months. The average response rate (RR) was 20.0% overall; it was 21.6% for patients treated with platinum-based doublet chemotherapy, 13.6% for those treated with other multidrug chemotherapy, and 19.6% for those treated with single agent chemotherapy. There was no significant difference in OS between platinum-based doublet chemotherapy, other multidrug chemotherapy, and monotherapy (the median OS was 22.4, 25.7, and 21.4 months, respectively). CONCLUSION: The median OS was 22.4 months in patients with advanced thymic carcinoma treated with second-line chemotherapy. There were no significant differences in RR and OS between monotherapy and multidrug chemotherapy in this study. IMPLICATIONS FOR PRACTICE: Owing to the rarity of this tumor, there is limited information about second-line chemotherapy for patients with previously treated advanced thymic carcinoma. This is the largest data for those patients treated with second-line chemotherapy. This study suggests there is no significant difference in efficacy between monotherapy and multidrug chemotherapy for previously treated advanced thymic carcinoma. This result can support the adequacy to select monotherapy as treatment of those patients.
A case of localized tracheobronchial relapsing polychondritis with positive matrilin-1 staining. International-journal Peer-reviewed

Tomonori Makiguchi, Akira Koarai, Chihiro Inoue, Yayoi Aoyama, Taizo Hirano, Takashi Ohe, Tomohiro Ichikawa, Yutaka Shishikura, Hanae Komuro, Yoko Tsukita, Naoki Tode, Tadahisa Numakura, Tsutomu Saito, Teruyuki Sato, Yoshiya Mitsuhashi, Tsutomu Tamada, Hisatoshi Sugiura, Masakazu Ichinose

BMC rheumatology　4　1-1　2020

DOI： 10.1186/s41927-019-0103-6 　

More details Close

Background: Relapsing polychondritis (RPC) is a rare progressive autoimmune disease characterized by inflammation in the cartilage of multiple organs. Tracheobronchial involvement appears in nearly half of RPC patients during the course of their disease and represents the main cause of death. Localized tracheobronchial RPC is much rarer, and the pathogenesis remains unclear. Matrilin-1 is a non-collagenous cartilage matrix protein and has been suggested to be a potent autoantigen that induces the airway disease of RPC in animal models. However, the expression of matrilin-1 in tracheobronchial tissue in human remains unclear. Therefore, we examined the expression of matrilin-1 in the tracheal and auricular tissues in a localized tracheobronchial RPC patient. Case presentation: A 62-year-old man with systemic sclerosis presented with cough and dyspnea on exertion. The lung function test showed an expiratory flow limitation and chest computed tomography showed diffuse thickness from the trachea to the bronchiole. No other tests showed abnormal findings. To evaluate further, bronchoscopy was performed and endobronchial ultrasonography showed thickness in the fourth-marginal echo layer suggesting inflammation of the cartilage. However, the tracheal biopsy showed no specific findings. The subsequent surgical tracheal biopsies showed inflammatory cell infiltration with destruction of the cartilage. Neither auricular nor nasal deformity, except for a tracheobronchial lesion, was detected. Biopsy from the left auricular cartilage also did not show any inflammatory changes. Finally, we diagnosed the patient with localized tracheobronchial RPC. To address the hypothesis that autoimmunity against matrilin-1 is involved in the pathogenesis of localized tracheobronchial RPC, we evaluated the expression level of matrilin-1 in a tracheal and auricular specimen from this patient. Immunohistochemical staining with anti-matrilin-1 antibody showed matrilin-1 in the tracheal but not in the auricular cartilage. Conclusions: We first demonstrated the expression of matrilin-1 in tracheal but not in auricular cartilage in a localized tracheobronchial RPC patient. This result supports the possibility that matrilin-1 is involved in the pathogenesis of localized tracheobronchial RPC. However, this is only one case report and further observations will be needed to confirm this result.
強度変調放射線治療による根治的化学放射線療法後のデュルバルマブ使用経験の報告

突田容子, 宮内栄作, 斎藤良太, 佐藤輝幸, 山本貴也, 片桐佑, 井上彰, 一ノ瀬正和

肺癌　59　(6)　674-674　2019/11
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
Phase II study of S-1 in patients with previously-treated invasive thymoma and thymic carcinoma: North Japan lung cancer study group trial 1203. Peer-reviewed

Tsukita Y, Inoue A, Sugawara S, Kuyama S, Nakagawa T, Harada D, Tanaka H, Watanabe K, Mori Y, Harada T, Hino T, Fujii M, Ichinose M

Lung Cancer　18　(139)　89-93　2019/10
免疫療法の効果と耐性 EGFR遺伝子変異陽性/陰性肺癌におけるT細胞受容体レパトア解析(Cancer immunotherapy sensitivity and resistance TCR repertoires in lung adenocarcinomas with and without EGFR mutation)

宮内栄作, 松田達雄, 清谷一馬, Low Siew-Kee, 突田容子, 一ノ瀬正和, 桜田晃, 岡田克典, 齊藤涼子, 中村祐輔

日本癌学会総会記事　78回　S19-1　2019/09
Publisher: (一社)日本癌学会
ISSN： 0546-0476
Significant differences in T cell receptor repertoires in lung adenocarcinomas with and without epidermal growth factor receptor mutations International-journal Peer-reviewed

Miyauchi E, Matsuda T, Kiyotani K, Low SK, Hsu YW, Tsukita Y, Ichinose M, Sakurada A, Okada Y, Saito R, Nakamura Y

Cancer Science　110　(3)　867-874　2019/03

DOI： 10.1111/cas.13919 　

More details Close

Recent clinical trials of non-small cell lung cancer with immune checkpoint inhibitors revealed that patients with epidermal growth factor receptor (EGFR) mutations had more unfavorable outcomes compared with those with wild-type EGFR. However, the underlying mechanism for the link between EGFR mutations and immune resistance remains unclear. We performed T cell receptor (TCR) repertoire analysis of resected lung adenocarcinoma tissues with and without EGFR mutations to investigate the characteristics of TCR repertoires. We collected a total of 39 paired (normal and tumor) lung tissue samples (20 had EGFR mutations) and conducted TCR repertoire analysis as well as whole-exome sequencing (WES) and transcriptome analysis. The TCR diversity index in EGFR-mutant tumors was significantly higher than that in EGFR-wild-type tumors (median [range] 552 [162-1,135] vs 230 [30-764]; P < .01), suggesting higher T cell clonal expansion in EGFR-wild-type tumors than in EGFR-mutant tumors. In WES, EGFR-mutant tumors showed lower numbers of non-synonymous mutations and predicted neoantigens than EGFR-wild-type tumors (P < .01, P = .03, respectively). The number of non-synonymous mutations revealed a positive correlation with the sum of frequencies of the TCRβ clonotypes of 1% or higher in tumors (r = .52, P = .04). The present study demonstrates significant differences in TCR repertoires and the number of predicted neoantigens between EGFR-mutant and wild-type lung tumors. Our findings provide important information for understanding the molecular mechanism behind EGFR-mutant patients showing unfavorable responses to immune checkpoint inhibitors.
Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas Peer-reviewed

Yoko Tsukita, Naoya Fujino, Eisaku Miyauchi, Ryoko Saito, Fumiyoshi Fujishima, Koji Itakura, Yorihiko Kyogoku, Koji Okutomo, Mitsuhiro Yamada, Tatsuma Okazaki, Hisatoshi Sugiura, Akira Inoue, Yoshinori Okada, Masakazu Ichinose

Molecular Cancer　18　(1)　24　2019/02/11

DOI： 10.1186/s12943-019-0953-y 　

eISSN： 1476-4598
Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5. International-journal Peer-reviewed

Yoko Tsukita, Tatsuma Okazaki, Satoru Ebihara, Riyo Komatsu, Mayumi Nihei, Makoto Kobayashi, Taizou Hirano, Hisatoshi Sugiura, Tsutomu Tamada, Nobuyuki Tanaka, Yasufumi Sato, Hideo Yagita, Masakazu Ichinose

Oncoimmunology　8　(2)　e1543526　2019

DOI： 10.1080/2162402X.2018.1543526 　

More details Close

Tumor-associated blood vessels and lymphatics are abnormal and dysfunctional. These are hallmarks of the tumor microenvironment, which has an immunosuppressive nature, such as through hypoxia. Treatment with anti-death receptor5 (DR5) monoclonal antibody MD5-1, which induces tumor cell death, is a potent anti-tumor immunotherapy. Generally, MD5-1 induces cell death mainly via antigen presenting cells (APCs) and generates tumor-specific effector T cells. To date, the effects of a simultaneous functional improvement of abnormal blood vessels and lymphatics on the immune microenvironment are largely unknown. A combination therapy using sunitinib, vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor inhibitor, and MD5-1 substantially inhibited tumor growth. Sunitinib improved pericyte coverage on endothelial cells and the expression levels of regulator of G-protein signaling 5, suggesting blood vessel normalization. Sunitinib also increased lymph flow from tumors to central lymph nodes, suggesting improved lymphatic function. In concordance with improved vasculature functions, sunitinib alleviated the tumor hypoxia, suggesting an improved tumor microenvironment. Indeed, the combination therapy induced strong activation of CD8+ T cells and dendritic cells in draining lymph nodes. The combination therapy reduced the ratio of immune-suppressive T regulatory cells in the tumors and draining lymph nodes. The combination therapy enhanced the numbers and activation of tumor-infiltrating CD8+ T cells. CD4 and/or CD8 depletion, or APC inhibiting experiments showed the contribution of CD8+ T cells and APCs to the combination therapy. These findings suggest that targeting blood vessels and lymphatics may have potential benefits for immunotherapy mediated by CD8+ T cells and APCs.
EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を促進する(Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas)

突田容子, 宮内栄作, 齊藤涼子, 岡崎達馬, 井上彰, 岡田克典, 一ノ瀬正和

日本癌学会総会記事　77回　1885-1885　2018/09
Publisher: (一社)日本癌学会
ISSN： 0546-0476
EGFR遺伝子変異陽性肺腺癌におけるT細胞受容体レパトア解析(T cell receptor repertoire analysis of lung adenocarcinoma harboring EGFR mutations)

宮内栄作, 松田達雄, Hsu Yu-Wen, 突田容子, 一ノ瀬正和, 桜田晃, 岡田克典, 齊藤涼子, 清谷一馬, 中村祐輔

日本癌学会総会記事　77回　2036-2036　2018/09
Publisher: (一社)日本癌学会
ISSN： 0546-0476
Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems. International-journal Peer-reviewed

Riyo Komatsu, Tatsuma Okazaki, Satoru Ebihara, Makoto Kobayashi, Yoko Tsukita, Mayumi Nihei, Hisatoshi Sugiura, Kaijun Niu, Takae Ebihara, Masakazu Ichinose

Journal of cachexia, sarcopenia and muscle　9　(4)　643-653　2018/08

DOI： 10.1002/jcsm.12297 　

More details Close

BACKGROUND: Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase-3, followed by further degradation by the ubiquitin-proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle. For swallowing muscles, it is not clear whether they produce cytokines. The main objective of this study was to determine whether aspiration pneumonia induces muscle atrophy in the respiratory (the diaphragm), skeletal (the tibialis anterior, TA), and swallowing (the tongue) systems, and their possible mechanisms. METHODS: We employed a mouse aspiration pneumonia model and computed tomography (CT) scans of aged pneumonia patients. To induce aspiration pneumonia, mice were inoculated with low dose pepsin and lipopolysaccharide solution intra-nasally 5 days a week. The diaphragm, TA, and tongue were isolated, and total RNA, proteins, and frozen sections were stored. Quantitative real-time polymerase chain reaction determined the expression levels of proinflammatory cytokines, muscle E3 ubiquitin ligases, and autophagy related genes. Western blot analysis determined the activation of the muscle proteolysis pathway. Frozen sections determined the presence of muscle atrophy. CT scans were used to evaluate the muscle atrophy in aged aspiration pneumonia patients. RESULTS: The aspiration challenge enhanced the expression levels of proinflammatory cytokines in the diaphragm, TA, and tongue. Among muscle proteolysis pathways, the aspiration challenge activated caspase-3 in all the three muscles examined, whereas calpains were activated in the diaphragm and the TA but not in the tongue. Activation of the ubiquitin-proteasome system was detected in all the three muscles examined. The aspiration challenge activated autophagy in the TA and the tongue, whereas weak or little activation was detected in the diaphragm. The aspiration challenge resulted in a greater proportion of smaller myofibers than in controls in the diaphragm, TA, and tongue, suggesting muscle atrophy. CT scans clearly showed that aspiration pneumonia was followed by muscle atrophy in aged patients. CONCLUSIONS: Aspiration pneumonia induced muscle atrophy in the respiratory, skeletal, and swallowing systems in a preclinical animal model and in human patients. Diaphragmatic atrophy may weaken the force of cough to expectorate sputum or mis-swallowed contents. Skeletal muscle atrophy may cause secondary sarcopenia. The atrophy of swallowing muscles may weaken the swallowing function. Thus, muscle atrophy could become a new therapeutic target of aspiration pneumonia.
ARDSを合併したChlamydophila pneumoniae感染症の1例

突田容子, 山田充啓, 大江崇, 伊藤俊輔, 小林誠, 玉井ときわ, 小荒井晃, 玉田勉, 杉浦久敏, 一ノ瀬正和

日本内科学会雑誌　105　(12)　2426-2431　2016/12
Publisher:
DOI： 10.2169/naika.105.2426 　

ISSN： 0021-5384

eISSN： 1883-2083
EGFR Mutation Analysis of Circulating Tumor DNA Using an Improved PNA-LNA PCR Clamp Method Peer-reviewed

Kana Watanabe, Tatsuro Fukuhara, Yoko Tsukita, Mami Morita, Aya Suzuki, Nobuyuki Tanaka, Hiroshi Terasaki, Toshihiro Nukiwa, Makoto Maemondo

CANADIAN RESPIRATORY JOURNAL　5297329　2016

DOI： 10.1155/2016/5297329 　

ISSN： 1198-2241

eISSN： 1916-7245
Alternate-day Treatment with Crizotinib for Drug-induced Esophagitis and Liver Damage in a Patient with EML4-ALK Fusion Gene-positive Lung Adenocarcinoma Peer-reviewed

Yoko Tsukita, Tatsuro Fukuhara, Maki Kobayashi, Mami Morita, Aya Suzuki, Kana Watanabe, Tetsuya Noguchi, Yasuko Kurata, Manabu Suno, Makoto Maemondo

INTERNAL MEDICINE　54　(24)　3185-3188　2015

DOI： 10.2169/internalmedicine.54.4996 　

ISSN： 0918-2918

eISSN： 1349-7235
ベバシズマブとエルロチニブの併用療法中に腸管気腫症を発症した肺腺癌の1例 Peer-reviewed

突田容子, 渡邉香奈, 盛田麻美, 綿貫善太, 鈴木綾, 福原達朗, 内海潔, 藤谷恒明, 前門戸任

日本呼吸器学会誌　3　(3)　442-445　2014/05
Publisher:
ISSN： 2186-5876
Large-cell neuroendocrine carcinoma with epidermal growth factor receptor mutation: Possible transformation of lung adenocarcinoma Peer-reviewed

Satoru Yanagisawa, Naoto Morikawa, Yuichiro Kimura, Yoko Nagano, Kazuhiro Murakami, Toshiharu Tabata

RESPIROLOGY　17　(8)　1275-1277　2012/11

DOI： 10.1111/j.1440-1843.2012.02258.x 　

ISSN： 1323-7799

eISSN： 1440-1843

Show all ︎Show first 5

Misc. 43

Safety and efficacy of durvalumab plus carboplatin and etoposide for patients with previously untreated extensive-stage small-cell lung cancer (ES-SCLC) with a poor performance status: The results from phase II single-arm study (NEJ045A study).

Yu Saida, Tetsuhiko Asao, Satoshi Watanabe, Akira Kisohara, Kazuma Kishi, Ryo Morita, Taku Nakagawa, Yoko Tsukita, Naoki Furuya, Taichi Miyawaki, Nobuhisa Ishikawa, Tadaaki Yamada, Takahiro Tanaka, Satoshi Morita, Toshiaki Kikuchi, Makoto Maemondo, Kunihiko Kobayashi

JOURNAL OF CLINICAL ONCOLOGY　42　(16)　2024/06/01

ISSN： 0732-183X

eISSN： 1527-7755
PS不良進展型小細胞肺癌に対するカルボプラチン+エトポシド+デュルバルマブ療法の第II相試験(NEJ045A)

木曽原朗, 才田優, 朝尾哲彦, 岸一馬, 守田亮, 中川拓, 突田容子, 古屋直樹, 宮脇太一, 石川暢久, 山田忠明, 田中崇裕, 森田智視, 菊地利明, 小林国彦, 前門戸任, 渡部聡

日本肺癌学会学術集会号(CD-ROM)　65th　2024

ISSN： 0386-9628
修飾核酸一斉定量系を用いたCOPD早期発見手法の開発検討

渡辺匠, 平本航大, 沼倉忠久, 滝田克也, 宮内栄作, 突田容子, 杉浦久敏, 松本洋太郎, 富岡佳久

日本薬学会東北支部大会講演要旨集　59th　2020
TCR repertoires in lung adenocarcinomas with and without EGFR mutation

宮内栄作, 松田達雄, 清谷一馬, LOW Siew-kee, 突田容子, 一ノ瀬正和, 桜田晃, 岡田克典, 齊藤涼子, 中村祐輔

日本癌学会学術総会抄録集(Web)　78th　2019
胸腔鏡下肺切除術で診断された印環細胞癌様の形態を呈した肺腺癌の1例

宮内栄作, 成田大輔, 相澤洋之, 村上康司, 小林誠, 突田容子, 東出直樹, 齋藤良太, 佐藤輝幸, 杉浦久敏, 一ノ瀬正和, 齊藤涼子, 松田安史, 岡田克典

肺癌(Web)　59　(5)　2019

ISSN： 1348-9992
T cell receptor repertoire analysis of lung adenocarcinoma harboring EGFR mutations

Eisaku Miyauchi, Tatsuo Matsuda, Yu-wen Hsu, Yoko Tsukita, Masakazu Ichinose, Akira Sakurada, Yoshinori Okada, Ryoko Saito, Kazuma Kiyotani, Yusuke Nakamura

CANCER SCIENCE　109　1178-1178　2018/12

ISSN： 1349-7006
EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を促進する(Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas)

突田容子, 宮内栄作, 齊藤涼子, 岡崎達馬, 井上彰, 岡田克典, 一ノ瀬正和

日本癌学会総会記事　77回　1885-1885　2018/09
Publisher: 日本癌学会
ISSN： 0546-0476
EGFR遺伝子変異陽性肺腺癌におけるT細胞受容体レパトア解析(T cell receptor repertoire analysis of lung adenocarcinoma harboring EGFR mutations)

宮内栄作, 松田達雄, Hsu Yu-Wen, 突田容子, 一ノ瀬正和, 桜田晃, 岡田克典, 齊藤涼子, 清谷一馬, 中村祐輔

日本癌学会総会記事　77回　2036-2036　2018/09
Publisher: 日本癌学会
ISSN： 0546-0476
リンパ管を標的とした新規胸膜炎治療の検討

小林誠, 岡崎達馬, 突田容子, 小松理世, 杉浦久敏, 海老原覚, 一ノ瀬正和

日本呼吸器学会誌(Web)　7　209　2018/03/10

ISSN： 2186-5884
EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を制御する

突田容子, 藤野直也, 宮内栄作, 井上彰, 板倉康司, 山田充啓, 岡崎達馬, 桜田晃, 杉浦久敏, 岡田克典, 一ノ瀬正和

日本呼吸器学会誌(Web)　7　267　2018/03/10

ISSN： 2186-5884
リンパ管を標的とした新規胸膜炎治療の検討

小林誠, 岡崎達馬, 突田容子, 小松理世, 杉浦久敏, 海老原覚, 一ノ瀬正和

日本呼吸器学会誌　7　(増刊)　209-209　2018/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を制御する

突田容子, 藤野直也, 宮内栄作, 井上彰, 板倉康司, 山田充啓, 岡崎達馬, 桜田晃, 杉浦久敏, 岡田克典, 一ノ瀬正和

日本呼吸器学会誌　7　(増刊)　267-267　2018/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
EGFR遺伝子変異陽性肺腺癌においてAXLキナーゼは免疫抑制分子を制御する

突田容子, 藤野直也, 宮内栄作, 井上彰, 板倉康司, 山田充啓, 岡崎達馬, 桜田晃, 杉浦久敏, 岡田克典, 一ノ瀬正和

日本呼吸器学会誌　7　(増刊)　267-267　2018/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876
高齢者の誤嚥・肺炎予防up‐to‐date 6.サルコペニアと誤嚥性肺炎の関係

岡崎達馬, 小松理世, 突田容子, 小林誠, 二瓶真由美, 海老原孝枝, 一ノ瀬正和

Geriatric Medicine　55　(11)　1221‐1224-1224　2017/11/01
Publisher: (株)ライフ・サイエンス
ISSN： 0387-1088
スニチニブは腫瘍の微小環境を改善してエフェクターT細胞を浸潤させDR-5を介した抗腫瘍免疫療法の効果を増強する

突田容子, 岡崎達馬, 佐藤靖史, 八木田秀雄, 一ノ瀬正和

日本癌学会総会記事　76回　E-1057　2017/09
Publisher: 日本癌学会
ISSN： 0546-0476
Effects of a combination of antiangiogenic and antilymphangiogenic therapies on a death receptor-5 mediated antitumor immunotherapy in mice. Peer-reviewed

Yoko Tsukita, Tatsuma Okazaki, Riyo Komatsu, Mayumi Nihei, Makoto Kobayashi, Yasufumi Sato, Hideo Yagita, Masakazu Ichinose

JOURNAL OF CLINICAL ONCOLOGY　35　2017/05

DOI： 10.1200/JCO.2017.35.15_suppl.e23001 　

ISSN： 0732-183X

eISSN： 1527-7755
サルコイドーシス診断に有用な因子の検討

光根歩, 佐藤輝幸, 柳澤悟, 突田容子, 東條裕, 小野学, 宮内栄作, 一ノ瀬正和

気管支学　39　(Suppl.)　S274-S274　2017/05/01
Publisher: (NPO)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
Mycobacterium shinjukuense肺感染症の1例

山田充啓, 玉井ときわ, 突田容子, 玉田勉, 杉浦久敏, 一ノ瀬正和, 鹿住祐子

結核　92　(5)　448-448　2017/05
Publisher: (一社)日本結核病学会
ISSN： 0022-9776

eISSN： 1884-2410
誤嚥性肺炎の新規治療標的としてのリンパ管と筋肉:サルコペニアを含めた実験モデルと症例の解析

岡崎達馬, 小松理世, 小林誠, 突田容子, 二瓶真由美, 海老原覚, 海老原孝枝, 一ノ瀬正和

日本老年医学会雑誌　54　(Suppl.)　110-110　2017/05
Publisher: (一社)日本老年医学会
ISSN： 0300-9173
誤嚥性肺炎はマイオカインを誘導しサルコペニアを悪化させる

小松理世, 岡崎達馬, 突田容子, 小林誠, 二瓶真由美, 杉浦久敏, 海老原孝枝, 海老原覚, 一ノ瀬正和

日本老年医学会雑誌　54　(Suppl.)　149-149　2017/05
Publisher: (一社)日本老年医学会
ISSN： 0300-9173
誤嚥性肺炎はマイオカインを誘導し筋肉を萎縮させる

小松理世, 岡崎達馬, 突田容子, 小林誠, 二瓶真由美, 杉浦久敏, 海老原覚, 一ノ瀬正和

日本呼吸器学会誌(Web)　6　116　2017/03/10

ISSN： 2186-5884
誤嚥性肺炎はマイオカインを誘導し筋肉を萎縮させる

小松理世, 岡崎達馬, 突田容子, 小林誠, 二瓶真由美, 杉浦久敏, 海老原覚, 一ノ瀬正和

日本呼吸器学会誌　6　(増刊)　116-116　2017/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
Case Report : A case of infection of Chlamydophila pneumoniae with ARDS

突田容子, 山田充啓, 大江崇, 伊藤俊輔, 小林誠, 玉井ときわ, 小荒井晃, 玉田勉, 杉浦久敏, 一ノ瀬正和

日本内科学会雑誌　105　(12)　2426-2431　2016/12/10
Publisher: 日本内科学会
ISSN： 0021-5384
EBUS-TBNAで診断に至った肺原発血管肉腫の1例

京極自彦, 岡崎達馬, 三浦絵美里, 突田容子, 田中里江, 東條裕, 三橋善哉, 宮内栄作, 杉浦久敏, 一ノ瀬正和, 高橋信

肺癌　56　(5)　406-406　2016/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
気管支鏡検査で菌検出が可能であった好酸球増多を伴う肺接合菌症の1例

突田容子, 平野泰三, 佐藤慶, 高橋秀徳, 村上康司, 玉井ときわ, 山田充啓, 玉田勉, 杉浦久敏, 一ノ瀬正和

肺癌　56　(5)　405-405　2016/10
Publisher: (NPO)日本肺癌学会
ISSN： 0386-9628

eISSN： 1348-9992
抗血管新生と抗リンパ管新生療法の組み合わせは抗腫瘍免疫療法の効果を増強する

突田容子, 岡崎達馬, 八木田秀雄, 一ノ瀬正和

日本癌学会総会記事　75回　P-2126　2016/10
Publisher: (一社)日本癌学会
ISSN： 0546-0476
EBUS‐TBNAで診断に至った肺原発血管肉腫の1例

京極自彦, 岡崎達馬, 三浦絵美里, 突田容子, 田中里江, 東條裕, 三橋善哉, 宮内栄作, 杉浦久敏, 一ノ瀬正和, 高橋信

気管支学　38　(5)　445‐446-446　2016/09/25
Publisher: (NPO)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
気管支鏡検査で菌検出が可能であった好酸球増多を伴う肺接合菌症の1例

突田容子, 平野泰三, 佐藤慶, 高橋秀徳, 村上康司, 玉井ときわ, 山田充啓, 玉田勉, 杉浦久敏, 一ノ瀬正和

気管支学　38　(5)　445-445　2016/09
Publisher: (NPO)日本呼吸器内視鏡学会
ISSN： 0287-2137

eISSN： 2186-0149
Second-line chemotherapy efficacy in patients with previously treated advanced thymic carcinoma: A retrospective analysis of 192 patients from NEJ023 Study.

Shunichiro Iwasawa, Ryo Ko, Takehito Shukuya, Satoshi Watanabe, Yoko Tsukita, Hironori Ashinuma, Taku Nakagawa, Ryo Ito, Kazutsugu Uematsu, Mika Nakao, Yoshiaki Mori, Kyoichi Kaira, Atsuto Moun, Takao Miyabayashi, Hiroyuki Sakashita, Yoko Matsumoto, Tomoyuki Tanigawa, Satoshi Morita, Kazuhisa Takahashi

JOURNAL OF CLINICAL ONCOLOGY　34　(15)　2016/05

DOI： 10.1200/JCO.2016.34.15_suppl.8569 　

ISSN： 0732-183X

eISSN： 1527-7755
誤嚥性肺炎はマイオカイン及び筋萎縮を誘導する~動物モデルを用いた解析~

岡崎達馬, 小松理世, 小林誠, 二瓶真由美, 突田容子, 海老原覚, 一ノ瀬正和

日本老年医学会雑誌　53　(Suppl.)　143-143　2016/05
Publisher: (一社)日本老年医学会
ISSN： 0300-9173
正常及び敗血症モデルマウスの胸膜(横隔膜)のリンパ管の解析

小林誠, 岡崎達馬, 二瓶真由美, 突田容子, 小松理世, 玉井ときわ, 杉浦久敏, 一ノ瀬正和

日本呼吸器学会誌　5　(増刊)　304-304　2016/03/10
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
誤嚥性肺炎は呼吸筋,骨格筋,嚥下筋の萎縮を誘導する

小松理世, 岡崎達馬, 二瓶真由美, 小林誠, 突田容子, 杉浦久敏, 海老原覚, 一ノ瀬正和

日本呼吸器学会誌　5　(増刊)　175-175　2016/03
Publisher: (一社)日本呼吸器学会
ISSN： 2186-5876

eISSN： 2186-5884
alectinib耐性後にc‐Met遺伝子増幅を来しcrizotinibが奏効したALK融合遺伝子陽性肺腺癌の一例

渡辺香奈, 突田容子, 盛田麻美, 鈴木綾, 福原達朗, 玉井恵一, 片山量平, 前門戸任

日本肺癌学会総会号　56th　658　2015/10/05

ISSN： 0386-9628
ガイドシース併用気管支腔内超音波断層法(EBUS‐GS)における擦過回数と診断率の検討

突田容子, 渡邉香奈, 佐藤ひかり, 盛田麻美, 鈴木綾, 福原達朗, 伊藤しげみ, 佐藤郁郎, 前門戸任

気管支学　37　S171　2015/05/01
Publisher: 特定非営利活動法人日本呼吸器内視鏡学会
DOI： 10.18907/jjsre.37.Special_S171_2 　

ISSN： 0287-2137
高感度EGFR遺伝子変異解析を用いた非小細胞肺癌血漿中循環DNAの測定

渡辺香奈, 福原達朗, 突田容子, 盛田麻美, 鈴木綾, 寺崎浩司, 前門戸任

日本呼吸器学会誌　4　131　2015/03/10

ISSN： 2186-5876
高感度改良型PNA‐LNAクランプ法を用いた非小細胞肺癌血漿中循環DNAのEGFR遺伝子変異測定によるEGFR‐TKI効果予測

渡辺香奈, 福原達朗, 突田容子, 盛田麻美, 鈴木綾, 田中伸幸, 寺崎浩司, 前門戸任, 貫和敏博

日本臨床腫瘍学会学術集会(CD-ROM)　13th　ROMBUNNO.O2-13-2　2015
ACTH産生腫瘍が疑われた肺小細胞癌の1例

盛田麻美, 福原達朗, 鈴木綾, 渡邉香奈, 前門戸任, 突田容子, 伊藤しげみ, 佐藤郁郎

肺癌(Web)　55　(4)　288(J‐STAGE)　2015

ISSN： 1348-9992
高感度EGFR遺伝子変異解析を用いた非小細胞肺癌血漿中循環DNAの測定とEGFR‐TKI効果との関連性の検討

渡辺香奈, 福原達朗, 小林真紀, 突田容子, 盛田麻美, 鈴木綾, 田中伸幸, 寺崎浩司, 前門戸任, 貫和敏博

日本肺癌学会総会号　55th　388　2014/10/05

ISSN： 0386-9628
EGFR遺伝子変異陽性肺癌患者に対するSecond‐TKIの開始時期と治療効果の検討

福原達朗, 渡邉香奈, 鈴木綾, 盛田麻美, 突田容子, 前門戸任

日本臨床腫瘍学会学術集会(CD-ROM)　12th　ROMBUNNO.P2-18-5　2014
Crizotinibによる食道炎を繰り返し発症し,隔日投与で治療継続が可能であった肺腺癌の1例

小林真紀, 福原達朗, 突田容子, 盛田麻美, 鈴木綾, 渡邉香奈, 前門戸任, 野口哲也

肺癌(Web)　54　(6)　867(J-STAGE)　2014

ISSN： 1348-9992
A CASE OF SMALL CELL LUNG CANCER WITH CANCER-ASSOCIATED RETINOPATHY ( CAR) ACCOMPANIED BY CIRCULATING ANTI-CRMP5/CV2 ANTIBODIES

Mami Morita, Tatsuro Fukuhara, Yoko Tsukita, Zenta Watanuki, Aya Suzuki, Kana Watanabe, Nobuyuki Sato, Hidetoshi Takahashi, Shigemi Ito, Ikuro Sato, Makoto Maemondo

RESPIROLOGY　18　8-8　2013/11

ISSN： 1323-7799

eISSN： 1440-1843
EGFR遺伝子変異陽性患者に対するSecond‐TKIのタイミングとその治療成績

福原達朗, 渡邉香奈, 盛田麻美, 突田容子, 綿貫善太, 鈴木綾, 前門戸任

日本肺癌学会総会号　54th　601　2013/10/05

ISSN： 0386-9628
非小細胞肺癌脳転移マネージメント:MRI検査間隔による放射線治療方法の変化

渡辺香奈, 福原達朗, 突田容子, 盛田麻美, 綿貫善太, 鈴木綾, 松原信行, 前門戸任

日本臨床腫瘍学会学術集会(CD-ROM)　11th　ROMBUNNO.O3-077　2013

Show all ︎Show first 5

Research Projects 5

進行期非小細胞肺癌の免疫併用療法におけるNK細胞の役割の解明

突田容子

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 若手研究

Institution: 東北大学

2023/04/01 - 2026/03/31

More details Close

抗腫瘍免疫において、その直接的な細胞障害作用からCD8陽性T細胞が作用機序の主役として注目されている。しかし近年は獲得免疫系だけではなく、自然免疫系も抗腫瘍免疫において重要な役割を担うことがわかってきており、その中でもナチュラルキラー細胞（NK細胞）が注目されている。これまで免疫単剤療法の効果予測因子としての報告は少数なされているが、一定の見解は得られていない。さらに、現在の標準治療である免疫療法と細胞傷害性抗癌薬との併用療法において、NK細胞が効果予測因子になり得るかどうかは明らかになっていない。その役割から血液中のNK細胞の多寡、NK細胞の活性、ならびにサイトカイン分泌能などが予測因子として期待できると考える。免疫療法と細胞傷害性抗癌薬との併用療法を施行前の患者の血液検体を倫理審査に基づいて同意を得て採取した。血液検体から末梢血単核細胞（PBMC）を抽出した。フローサイトメトリーによりNK細胞分画の解析を実施した。NK細胞はCD45陽性CD11b陰性CD3e陰性CD56陽性の細胞集団として同定した。NK細胞のCD45陽性細胞に対する割合は、治療により抗腫瘍効果が得られた群（PR群）において抗腫瘍効果が得られなかった群（SD/PD群）よりも有意に上昇していた。NK細胞の割合は腫瘍のPD-L1の発現率、治療前の好中球・リンパ球比などよりもPR群とSD/PD群との判別能が優れていた。
免疫抵抗性克服のための非小細胞肺癌における放射線照射がもたらす免疫応答の解析

突田容子

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 若手研究

Institution: 東北大学

2020/04/01 - 2023/03/31

More details Close

進行期非小細胞肺がんに対して、薬物療法（免疫療法＋殺細胞性抗癌薬）に放射線照射（姑息照射）を追加していた13例、放射線照射を施行していない薬物療法のみの6例、の治療開始前後の血漿と末梢血単核細胞を解析した。フローサイトメトリーにより、末梢血単核細胞中のT細胞（CD4陽性T細胞、CD8陽性T細胞）、B細胞、骨髄由来抑制細、NK細胞、特にT細胞ではメモリーT細胞や疲弊T細胞、制御性T細胞、に分類して、免疫細胞の数と割合を解析した。収集した臨床情報と紐づけて解析を行った。放射線照射の有無による変化は現時点では明らかではないが、奏効例と非奏功例やPFSの比較において、奏功例や長期奏功例で治療前に有意に増加している細胞分画を同定した。これらの細胞分画は複合免疫療法における効果予測因子となりうるため、さらなる検証を行っていく。血漿のサイトカインやケモカインをLEGENDplexTM multiplex Assayにて13種類を測定した。奏功例では治療前の炎症性サイトカインであるTNFαなどが治療開始前の時点ですでに増加していることが分かった。先述した細胞分画と関連のあるサイトカインについても検証を進めている。放射線照射ではDAMPsが放出されるとの既報から、血漿中のDAMPs（HMGB1、カルレティキュリン）を測定したが、こちらは奏功例と非奏功例や放射線照射の有無における有意差を認めなかった。
The role of reactive sulfur species and cysteinyl-tRNA synthetase2 in lung cancer

Tsukita Yoko

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Research Activity Start-up

Institution: Tohoku University

2019/04/01 - 2020/03/31

More details Close

Cysteinyl-tRNA synthetase (CARS)2 is known as a novel cysteine hydropersulfide synthase. In our lung cancer tissue biobank, CARS2 mRNA expression decreased in cancer tissues compared to normal tissues. The protein expression of CARS2 in relapsed cancers tended to be lower than in non-relapsed cancers. CARS2 expression significantly correlated with expression of genes encoding other enzymes involved in sulfur metabolism. These data suggest that sulfur metabolis is associated with the carcinogenesis and cancers vary in their dependence on sulfur metabolism.
Intracellular analysis of M-CSF induced lymphangiogenesis stimulating factor VEGF-C,-D production

Kobayashi Makoto, Tsukita Youko, Komatsu Riyo

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Young Scientists (B)

Institution: Tohoku University

2015/04/01 - 2017/03/31

More details Close

The experimental plan was changed because the VEGF-C, -D production from the skeletal muscle cell line by the addition of MCSF which was the initial objective was not significantly observed. In our previous study, significant VEGF-C, -D production was also seen from the diaphragm by MCSF administration, experiments were conducted focusing on the lymphatic vessels of the diaphragm.The pleural blood vessels and lymphatic vessels are involved in pleural effusion. Therefore, we prepared a malignant pleurisy model and an inflammatory pleurisy model and analyzed lymphatic vessels. In both models, expansion of lymphatic vessel diameter was observed.And only in malignant pleurisy model,lymphatic vessel density was increased.We concluded that the increase in VEGF-C, -D production from the diaphragm by cancer and inflammation will bring about these changes.
Sunitinib improves tumor microenvironment and augments the T cell infiltration and the effect of immunotherapy by DR-5

Okazaki Tatsuma, Yagita Hideo, Kobayashi Makoto, Tamai Tokiwa, Nihei Mayumi, Tsukita Yoko, Komatsu Riyo

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2014/04/01 - 2017/03/31

More details Close

VEGFR-2 in angiogenesis and VEGFR-3 in lymphangiogenesis are the key players. An anti-DR-5 Ab, the apoptosis inducing antibody, has antitumor effects. Here, we combined anti-DR-5 Ab with VEGFR1-3 inhibitor sunitinib as anti-angiogenic and lymphangiogenic therapies. Mice were injected with 4T1 cells into the footpad and treated with sunitinib and/or anti-DR-5 Ab. The tumors and popliteal lymph nodes were isolated. The growth rate of 4T1 or CT26 tumors was measured. Sunitinib decreased the blood vessel and hypoxic area densities in the tumors, suggesting blood vessel normalization. Sunitinib decreased the amount of tumor injected evans blue and hyaluronic acid in tumors, suggesting better lymphatic flow. The combination increased the ratio of activated dendritic cells and CD8+ T cells in lymph nodes and the numbers of CD8+ and effector CD4+ T cells in tumors compared to controls. The combination decreased the tumor growth rate compared to each mono-therapy.