Updated on 2024/12/02

写真a

 
HASE Tetsunari
 
Organization
Graduate School of Medicine Designated lecturer
Title
Designated lecturer

Degree 1

  1. 博士(医学) ( 2012.12   名古屋大学 ) 

Research Areas 1

  1. Life Science / Respiratory medicine

Education 2

  1. Nagoya University   Graduate School, Division of Medical Sciences

    2007.4 - 2011.3

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    Country: Japan

  2. Nagoya University   Faculty of Medicine

    1995.4 - 2001.3

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    Country: Japan

Professional Memberships 5

  1. 肺癌学会

  2. アレルギー学会

  3. 呼吸器内視鏡学会

  4. 呼吸器学会

  5. 臨床腫瘍学会

 

Papers 51

  1. Durvalumab plus carboplatin-etoposide treatment in a patient with small-cell lung cancer on hemodialysis: a case report and literature review

    Ushijima, F; Hase, T; Yamashita, Y; Kim, H; Shimokata, T; Kondo, C; Sato, T; Baba, T; Watanabe, S; Futamura, K; Ando, Y; Mizuno, M; Ishii, M

    INTERNATIONAL CANCER CONFERENCE JOURNAL   Vol. 13 ( 2 ) page: 88 - 92   2024.4

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  2. Circulating microRNA Panel for Prediction of Recurrence and Survival in Early-Stage Lung Adenocarcinoma

    Tai, MC; Bantis, LE; Parhy, G; Kato, T; Tanaka, I; Chow, CW; Fujimoto, J; Behrens, C; Hase, T; Kawaguchi, K; Fahrmann, JF; Ostrin, EJ; Yokoi, K; Chen-Yoshikawa, TF; Hasegawa, Y; Hanash, SM; Wistuba, II; Taguchi, A

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 25 ( 4 )   2024.2

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  3. Prospective observational study to explore genes and proteins predicting efficacy and safety of brigatinib for ALK-gene rearranged non-small-cell lung cancer: study protocol for ABRAID study (WJOG11919L)

    Ozawa, Y; Koh, Y; Hase, T; Chibana, K; Kaira, K; Okishio, K; Ichihara, E; Murakami, S; Shimokawa, M; Yamamoto, N

    THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY   Vol. 16   page: 17588359231225046   2024

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  4. Lethal ventricular arrhythmia due to entrectinib-induced Brugada syndrome: a case report and literature review

    Futamura Keisuke, Hase Tetsunari, Tanaka Akihito, Sakai Yoshinori, Okachi Shotaro, Shibata Hirofumi, Ushijima Futoshi, Hashimoto Takahiko, Nakashima Kuniya, Ito Katsuki, Yamamoto Takanori, Numaguchi Atsushi, Inden Yasuya, Ishii Makoto

    INTERNATIONAL CANCER CONFERENCE JOURNAL   Vol. 12 ( 4 ) page: 299 - 304   2023.10

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  5. Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer

    Hatta Takahiro, Hase Tetsunari, Hara Toru, Kimura Tomoki, Kojima Eiji, Abe Takashi, Horio Yoshitsugu, Goto Yasuhiro, Ozawa Naoya, Yogo Naoyuki, Shibata Hirofumi, Shimokata Tomoya, Oguri Tetsuya, Yamamoto Masashi, Yanagisawa Kiyoshi, Ando Masahiko, Ando Yuichi, Kondo Masashi, Ishii Makoto, Hasegawa Yoshinori

    CANCER MEDICINE   Vol. 12 ( 15 ) page: 15955 - 15969   2023.6

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  6. Abdominal pain accompanied by elevated serum inflammatory markers and biliary enzymes for diagnosing immune checkpoint inhibitor-induced sclerosing cholangitis

    Yamamoto Takafumi, Mizuno Kazuyuki, Ito Takanori, Yokoyama Shinya, Yamamoto Kenta, Imai Norihiro, Ishizu Yoji, Honda Takashi, Ishikawa Takuya, Kanamori Akira, Yasuda Satoshi, Toyoda Hidenori, Yokota Kenji, Hase Tetsunari, Nishio Naoki, Maeda Osamu, Ishii Makoto, Sone Michihiko, Ando Yuichi, Akiyama Masashi, Ishigami Masatoshi, Kawashima Hiroki

    INVESTIGATIONAL NEW DRUGS   Vol. 41 ( 3 ) page: 512 - 521   2023.6

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  7. Leukocyte Depletion and Size-Based Enrichment of Circulating Tumor Cells Using a Pressure-Sensing Microfiltration Device.

    Onoshima D, Hase T, Kihara N, Kuboyama D, Tanaka H, Ozawa N, Yukawa H, Sato M, Ishikawa K, Hasegawa Y, Ishii M, Hori M, Baba Y

    ACS measurement science au   Vol. 3 ( 2 ) page: 113 - 119   2023.4

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    Language:English  

    DOI: 10.1021/acsmeasuresciau.2c00057

    PubMed

  8. High-performance glass filters for capturing and culturing circulating tumor cells and cancer-associated fibroblasts.

    Tanaka H, Iwata D, Shibata Y, Hase T, Onoshima D, Yogo N, Shibata H, Sato M, Ishikawa K, Nagasawa I, Hasegawa Y, Ishii M, Baba Y, Hori M

    Scientific reports   Vol. 13 ( 1 ) page: 4130   2023.3

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    Language:English  

    DOI: 10.1038/s41598-023-31265-9

    PubMed

  9. Pharmacokinetic and dose-finding study of osimertinib in patients with impaired renal function and low body weight

    Fujiwara Yutaka, Makihara Reiko, Hase Tetsunari, Hashimoto Naozumi, Naito Tomoyuki, Tsubata Yukari, Okuno Takae, Takahashi Toshiaki, Kobayashi Haruki, Shinno Yuki, Zenke Yoshitaka, Ikeda Takaya, Hosomi Yukio, Watanabe Kageaki, Kitazono Satoru, Sakiyama Naomi, Makino Yoshinori, Yamamoto Noboru

    CANCER SCIENCE     2023.2

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  10. Clustering using unsupervised machine learning to stratify the risk of immune-related liver injury

    Yamamoto Takafumi, Morooka Hikaru, Ito Takanori, Ishigami Masatoshi, Mizuno Kazuyuki, Yokoyama Shinya, Yamamoto Kenta, Imai Norihiro, Ishizu Yoji, Honda Takashi, Yokota Kenji, Hase Tetsunari, Maeda Osamu, Hashimoto Naozumi, Ando Yuichi, Akiyama Masashi, Kawashima Hiroki

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   Vol. 38 ( 2 ) page: 251 - 258   2023.2

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  11. Leukocyte Depletion and Size-Based Enrichment of Circulating Tumor Cells Using a Pressure-Sensing Microfiltration Device Reviewed

    Daisuke Onoshima* Daisuke Onoshima Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan *Email: onoshima-d@nanobio.nagoya-u.ac.jp More by Daisuke Onoshima Orcidhttps://orcid.org/0000-0002-3672-7514 , Tetsunari Hase*, Naoto Kihara, Daiki Kuboyama, Hiromasa Tanaka, Naoya Ozawa, Hiroshi Yukawa, Mitsuo Sato, Kenji Ishikawa, Yoshinori Hasegawa, Makoto Ishii, Masaru Hori, and Yoshinobu Baba

    ACS Meas. Sci. Au     2022.12

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    Authorship:Corresponding author   Language:English  

    DOI: https://doi.org/10.1021/acsmeasuresciau.2c00057

  12. Real-World Data Analysis of Pembrolizumab Monotherapy for NSCLC Using Japanese Postmarketing All-Case Surveillance Data.

    Terai H, Soejima K, Shimokawa A, Horinouchi H, Shimizu J, Hase T, Kanemaru R, Watanabe K, Ninomiya K, Aragane N, Yanagitani N, Sakata Y, Seike M, Fujimoto D, Kasajima M, Kubo A, Kusumoto S, Oyamada Y, Fujiwara K, Mori M, Hashimoto M, Shingyoji M, Kodani M, Sakamoto J, Agatsuma T, Kashiwabara K, Inomata M, Tachihara M, Tanaka K, Hayashihara K, Koyama N, Matsui K, Minato K, Jingu D, Sakashita H, Hara S, Naito T, Okada A, Tanahashi M, Sato Y, Asano K, Takeda T, Nakazawa K, Harada T, Shibata K, Kato T, Miyaoka E, Yoshino I, Gemma A, Mitsudomi T

    JTO clinical and research reports   Vol. 3 ( 11 ) page: 100404   2022.11

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    DOI: 10.1016/j.jtocrr.2022.100404

    PubMed

  13. Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade

    Kobayashi Tomoko, Iwama Shintaro, Yamagami Ayana, Yasuda Yoshinori, Okuji Takayuki, Ito Masaaki, Zhou Xin, Ando Masahiko, Onoue Takeshi, Miyata Takashi, Sugiyama Mariko, Hagiwara Daisuke, Suga Hidetaka, Banno Ryoichi, Hase Tetsunari, Morise Masahiro, Ito Takanori, Kikumori Toyone, Inoue Megumi, Ando Yuichi, Masuda Norikazu, Kawashima Hiroki, Hashimoto Naozumi, Arima Hiroshi

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM   Vol. 107 ( 10 ) page: E4115 - E4123   2022.9

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  14. Non-invasive early prediction of immune checkpoint inhibitor efficacy in non-small-cell lung cancer patients using on-treatment serum CRP and NLR

    Matsuzawa Reiko, Morise Masahiro, Kinoshita Fumie, Tanaka Ichidai, Koyama Junji, Kimura Tomoki, Kondoh Yasuhiro, Tanaka Taro, Shima Koichiro, Hase Tetsunari, Wakahara Keiko, Ishii Makoto, Hashimoto Naozumi

    JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY     2022.8

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  15. A case of antiprogrammed death-ligand 1 antibody-induced multisystem immune-related adverse events with pancreatitis and steroid-resistant sclerosing cholangitis

    Yamamoto Takafumi, Ito Takanori, Mizuno Kazuyuki, Shinya Yokoyama, Yamamoto Kenta, Imai Norihiro, Ishizu Yoji, Honda Takashi, Kawashima Hiroki, Matsui Toshinori, Hase Tetsunari, Hashimoto Naozumi, Ishigami Masatoshi

    JOURNAL OF DIGESTIVE DISEASES   Vol. 23 ( 7 ) page: 404 - 409   2022.7

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  16. Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

    Gen Soei, Tanaka Ichidai, Morise Masahiro, Koyama Junji, Kodama Yuta, Matsui Akira, Miyazawa Ayako, Hase Tetsunari, Hibino Yoshitaka, Yokoyama Toshihiko, Kimura Tomoki, Yoshida Norio, Sato Mitsuo, Hashimoto Naozumi

    BMC CANCER   Vol. 22 ( 1 ) page: 654   2022.6

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  17. Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline.

    Iwama S, Kobayashi T, Yasuda Y, Okuji T, Ito M, Ando M, Zhou X, Yamagami A, Onoue T, Kawaguchi Y, Miyata T, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Hase T, Morise M, Wakahara K, Yokota K, Kato M, Nishio N, Tanaka C, Miyata K, Ogura A, Ito T, Sawada T, Shimokata T, Niimi K, Ohka F, Ishigami M, Gotoh M, Hashimoto N, Saito R, Kiyoi H, Kajiyama H, Ando Y, Hibi H, Sone M, Akiyama M, Kodera Y, Arima H

    The Journal of clinical endocrinology and metabolism   Vol. 107 ( 4 ) page: e1620 - e1630   2022.3

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    Language:English  

    DOI: 10.1210/clinem/dgab829

    PubMed

  18. Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade

    Miyai Yuki, Sugiyama Daisuke, Hase Tetsunari, Asai Naoya, Taki Tetsuro, Nishida Kazuki, Fukui Takayuki, Chen-Yoshikawa Toyofumi Fengshi, Kobayashi Hiroki, Mii Shinji, Shiraki Yukihiro, Hasegawa Yoshinori, Nishikawa Hiroyoshi, Ando Yuichi, Takahashi Masahide, Enomoto Atsushi

    LIFE SCIENCE ALLIANCE   Vol. 5 ( 6 )   2022.3

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  19. (11)C-methionine- and (18)F-FDG-PET double-negative metastatic brain tumor from lung adenocarcinoma with paradoxical high (18)F-FDG uptake: A case report.

    Tanahashi K, Hirano M, Chalise L, Tsugawa T, Okumura Y, Hase T, Ohka F, Motomura K, Takeuchi K, Nagata Y, Nakahara N, Hashimoto N, Saito R

    Surgical neurology international   Vol. 13   page: 372   2022

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    DOI: 10.25259/SNI_264_2022

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  20. Clinical characteristics of gastrointestinal immune-related adverse events of immune checkpoint inhibitors and their association with survival

    Yamada Kentaro, Sawada Tsunaki, Nakamura Masanao, Yamamura Takeshi, Maeda Keiko, Ishikawa Eri, Iida Tadashi, Mizutani Yasuyuki, Kakushima Naomi, Ishikawa Takuya, Furukawa Kazuhiro, Ohno Eizaburo, Honda Takashi, Kawashima Hiroki, Ishigami Masatoshi, Furune Satoshi, Hase Tetsunari, Yokota Kenji, Maeda Osamu, Hashimoto Naozumi, Akiyama Masashi, Ando Yuichi, Fujishiro Mitsuhiro

    WORLD JOURNAL OF GASTROENTEROLOGY   Vol. 27 ( 41 ) page: 7190 - 7206   2021.11

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  21. Immune-related liver injury is a poor prognostic factor in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.

    Yamamoto T, Ito T, Hase T, Ishigami M, Mizuno K, Yamamoto K, Imai N, Ishizu Y, Honda T, Shibata H, Hatta T, Yogo N, Yasuda S, Toyoda H, Abe T, Kawashima H, Hashimoto N, Fujishiro M

    Cancer investigation     page: 1 - 31   2021.10

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    DOI: 10.1080/07357907.2021.1994586

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  22. SRGN-Triggered Aggressive and Immunosuppressive Phenotype in a Subset of TTF-1-Negative Lung Adenocarcinomas.

    Tanaka I, Dayde D, Tai MC, Mori H, Solis LM, Tripathi SC, Fahrmann JF, Unver N, Parhy G, Jain R, Parra ER, Murakami Y, Aguilar-Bonavides C, Mino B, Celiktas M, Dhillon D, Casabar JP, Nakatochi M, Stingo F, Baladandayuthapani V, Wang H, Katayama H, Dennison JB, Lorenzi PL, Do KA, Fujimoto J, Behrens C, Ostrin EJ, Rodriguez-Canales J, Hase T, Fukui T, Kajino T, Kato S, Yatabe Y, Hosoda W, Kawaguchi K, Yokoi K, Chen-Yoshikawa TF, Hasegawa Y, Gazdar AF, Wistuba II, Hanash S, Taguchi A

    Journal of the National Cancer Institute     2021.9

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    DOI: 10.1093/jnci/djab183

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  23. Amelanotic Malignant Melanoma with a BRAF V600E Mutation Mimicking Primary Lung Cancer.

    Matsuzawa R, Morise M, Tanaka I, Hayai S, Tamiya Y, Koyama J, Hase T, Wakahara K, Deoksu K, Shimoyama Y, Hashimoto N

    Internal medicine (Tokyo, Japan)     2021.8

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    DOI: 10.2169/internalmedicine.6657-20

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  24. Clinical course of liver injury induced by immune checkpoint inhibitors in patients with advanced malignancies

    Ito Takanori, Ishigami Masatoshi, Yamamoto Takafumi, Mizuno Kazuyuki, Yamamoto Kenta, Imai Norihiro, Ishizu Yoji, Honda Takashi, Kawashima Hiroki, Yasuda Satoshi, Toyoda Hidenori, Yokota Kenji, Hase Tetsunari, Nishio Naoki, Maeda Osamu, Kato Masashi, Hashimoto Naozumi, Hibi Hideharu, Kodera Yasuhiro, Sone Michihiko, Ando Yuichi, Akiyama Masashi, Shimoyama Yoshie, Fujishiro Mitsuhiro

    HEPATOLOGY INTERNATIONAL   Vol. 15 ( 5 ) page: 1278 - 1287   2021.8

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  25. CEBP gamma facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation

    Shi Hanxiao, Niimi Atsuko, Takeuchi Toshiyuki, Shiogama Kazuya, Mizutani Yasuyoshi, Kajino Taisuke, Inada Kenichi, Hase Tetsunari, Hatta Takahiro, Shibata Hirofumi, Fukui Takayuki, Chen-Yoshikawa Toyofumi Fengshi, Nagano Kazuki, Murate Takashi, Kawamoto Yoshiyuki, Tomida Shuta, Takahashi Takashi, Suzuki Motoshi

    CANCER SCIENCE   Vol. 112 ( 7 ) page: 2770 - 2780   2021.7

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  26. Efficacies of programmed cell death 1 ligand 1 blockade in non-small cell lung cancer patients with acquired resistance to prior programmed cell death 1 inhibitor and development of diabetic ketoacidosis caused by two different etiologies: a retrospective case series.

    Ishi A, Tanaka I, Iwama S, Sakakibara T, Mastui T, Kobayashi T, Hase T, Morise M, Sato M, Arima H, Hashimoto N

    Endocrine journal     2021.4

  27. CEBP gamma and YBX1 regulate lung cancer metastasis via CERS6 expression and lamellipodia formation.

    Shi Hanxiao, Niimi Atsuko, Takeuchi Toshiyuki, Mizutani Yasuyoshi, Shiogama Kazuya, Inada Kenichi, Hase Tetsunari, Hasegawa Yoshinori, Takahashi Takashi, Suzuki Motoshi

    CANCER SCIENCE   Vol. 112   page: 700 - 700   2021.2

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    Language:Japanese  

    Web of Science

  28. Development of an immuno-wall device for the rapid and sensitive detection of EGFR mutations in tumor tissues resected from lung cancer patients

    Yogo Naoyuki, Hase Tetsunari, Kasama Toshihiro, Nishiyama Keine, Ozawa Naoya, Hatta Takahiro, Shibata Hirofumi, Sato Mitsuo, Komeda Kazuki, Kawabe Nozomi, Matsuoka Kohei, Chen-Yoshikawa Toyofumi Fengshi, Kaji Noritada, Tokeshi Manabu, Baba Yoshinobu, Hasegawa Yoshinori

    PLOS ONE   Vol. 15 ( 11 )   2020.11

  29. Short hydration with 20 mEq of magnesium supplementation for lung cancer patients receiving cisplatin-based chemotherapy: a prospective study

    Hase Tetsunari, Miyazaki Masayuki, Ichikawa Kazuya, Yogo Naoyuki, Ozawa Naoya, Hatta Takahiro, Ando Masahiko, Sato Mitsuo, Kondo Masashi, Yamada Kiyofumi, Hasegawa Yoshinori

    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY   Vol. 25 ( 11 ) page: 1928 - 1935   2020.11

  30. Comparing incidences of infusion site reactions between brand-name and generic vinorelbine in patients with non-small cell lung cancer

    Ozawa Naoya, Hase Tetsunari, Hatta Takahiro, Sagara Atsunobu, Ichikawa Kazuya, Miyazaki Masayuki, Yogo Naoyuki, Ando Masahiko, Hashimoto Naozumi, Yamada Kiyofumi, Hasegawa Yoshinori

    BRITISH JOURNAL OF CLINICAL PHARMACOLOGY     2020.8

  31. Primary Prophylaxis Indication for Docetaxel Induced Febrile Neutropenia in Elderly Patients with Non-Small Cell Lung Cancer

    Matsui Akira, Morise Masahiro, Tanaka Ichidai, Ozone Sachiko, Matsuzawa Reiko, Koyama Junji, Hase Tetsunari, Hashimoto Naozumi, Sato Mitsuo, Hasegawa Yoshinori

    CANCER INVESTIGATION   Vol. 38 ( 7 ) page: 424 - 430   2020.8

  32. Clinical value of serum bone resorption markers for predicting clinical outcomes after use of bone modifying agents in metastatic bone tumors: A prospective cohort study

    Urakawa Hiroshi, Ando Yuichi, Hase Tetsunari, Kikumori Toyone, Arai Eisuke, Maeda Osamu, Mitsuma Ayako, Sugishita Mihoko, Shimokata Tomoya, Ikuta Kunihiro, Ishiguro Naoki, Nishida Yoshihiro

    INTERNATIONAL JOURNAL OF CANCER   Vol. 146 ( 12 ) page: 3504 - 3515   2020.6

  33. Real world data of liver injury induced by immune checkpoint inhibitors in Japanese patients with advanced malignancies

    Mizuno Kazuyuki, Ito Takanori, Ishigami Masatoshi, Ishizu Yoji, Kuzuya Teiji, Honda Takashi, Kawashima Hiroki, Inukai Yosuke, Toyoda Hidenori, Yokota Kenji, Hase Tetsunari, Maeda Osamu, Kiyoi Hitoshi, Nagino Masato, Hibi Hideharu, Kodera Yasuhiro, Fujimoto Yasushi, Sone Michihiko, Gotoh Momokazu, Ando Yuichi, Akiyama Masashi, Hasegawa Yoshinori, Fujishiro Mitsuhiro

    JOURNAL OF GASTROENTEROLOGY   Vol. 55 ( 6 ) page: 653 - 661   2020.6

  34. Potential Benefits of Bevacizumab Combined With Platinum-Based Chemotherapy in Advanced Non-Small-Cell Lung Cancer Patients With EGFR Mutation

    Tanaka Ichidai, Morise Masahiro, Miyazawa Ayako, Kodama Yuta, Tamiya Yutaro, Gen Soei, Matsui Akira, Hase Tetsunari, Hashimoto Naozumi, Sato Mitsuo, Hasegawa Yoshinori

    CLINICAL LUNG CANCER   Vol. 21 ( 3 ) page: 273 - +   2020.5

  35. UHRF1, a Regulator of Methylation, as a Diagnostic and Prognostic Marker for Lung Cancer

    Goto Daiki, Komeda Kazuki, Uwatoko Natsuki, Nakashima Moeka, Koike Mayu, Kawai Kaho, Kodama Yuta, Miyazawa Ayako, Tanaka Ichidai, Hase Tetsunari, Morise Masahiro, Hasegawa Yoshinori, Kawabe Tsutomu, Sato Mitsuo

    CANCER INVESTIGATION   Vol. 38 ( 4 ) page: 240 - 249   2020.4

  36. Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study

    Okada Norio, Iwama Shintaro, Okuji Takayuki, Kobayashi Tomoko, Yasuda Yoshinori, Wada Eri, Onoue Takeshi, Goto Motomitsu, Sugiyama Mariko, Tsunekawa Taku, Takagi Hiroshi, Hagiwara Daisuke, Ito Yoshihiro, Suga Hidetaka, Banno Ryoichi, Hase Tetsunari, Morise Masahiro, Kanda Mitsuro, Yokota Kenji, Hashimoto Naozumi, Ando Masahiko, Fujimoto Yasushi, Nagino Masato, Kodera Yasuhiro, Fujishiro Mitsuhiro, Hibi Hideharu, Sone Michihiko, Kiyoi Hitoshi, Gotoh Momokazu, Ando Yuichi, Akiyama Masashi, Hasegawa Yoshinori, Arima Hiroshi

    BRITISH JOURNAL OF CANCER   Vol. 122 ( 6 ) page: 771 - 777   2020.3

  37. Risk factors for pulmonary infection after diagnostic bronchoscopy in patients with lung cancer

    Shimizu Takahiro, Okachi Shotaro, Imai Naoyuki, Hase Tetsunari, Morise Masahiro, Hashimoto Naozumi, Sato Mitsuo, Hasegawa Yoshinori

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 82 ( 1 ) page: 69 - 77   2020.2

  38. Phase I study of vorinostat with gefitinib in BIM deletion polymorphism/epidermal growth factor receptor mutation double-pnositive lung cancer

    Takeuchi Shinji, Hase Tetsunari, Shimizu Shinobu, Ando Masahiko, Hata Akito, Murakami Haruyasu, Kawakami Takahiro, Nagase Katsuhiko, Yoshimura Kenichi, Fujiwara Tadami, Tanimoto Azusa, Nishiyama Akihiro, Arai Sachiko, Fukuda Koji, Katakami Nobuyuki, Takahashi Toshiaki, Hasegawa Yoshinori, Ko Tun Kiat, Ong S. Tiong, Yano Seiji

    CANCER SCIENCE   Vol. 111 ( 2 ) page: 561 - 570   2020.2

  39. Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: a prospective study

    Kobayashi Tomoko, Iwama Shintaro, Yasuda Yoshinori, Okada Norio, Okuji Takayuki, Ito Masaaki, Onoue Takeshi, Goto Motomitsu, Sugiyama Mariko, Tsunekawa Taku, Takagi Hiroshi, Hagiwara Daisuke, Ito Yoshihiro, Suga Hidetaka, Banno Ryoichi, Yokota Kenji, Hase Tetsunari, Morise Masahiro, Hashimoto Naozumi, Ando Masahiko, Fujimoto Yasushi, Hibi Hideharu, Sone Michihiko, Ando Yuichi, Akiyama Masashi, Hasegawa Yoshinori, Arima Hiroshi

    JOURNAL FOR IMMUNOTHERAPY OF CANCER   Vol. 8 ( 2 )   2020

  40. BK virus-associated viruria and viremia in a patient with lymphangioleiomyomatosis after lung re-transplantation: A case report and review of the literature on BK virus infection post-lung transplantation

    Okumura Junya, Nakahara Yoshio, Nakaguro Masato, Shindo Yuichiro, Hase Tetsunari, Wakahara Keiko, Hashimoto Naozumi, Hasegawa Yoshinori

    JOURNAL OF INFECTION AND CHEMOTHERAPY   Vol. 25 ( 10 ) page: 820 - 824   2019.10

  41. A 65-nm CMOS Fully Integrated Analysis Platform Using an On-Chip Vector Network Analyzer and a Transmission-Line-Based Detection Window for Analyzing Circulating Tumor Cell and Exosome

    Niitsu Kiichi, Nakanishi Taiki, Murakami Shunya, Matsunaga Maya, Kobayashi Atsuki, Karim Nissar Mohammad, Ito Jun, Ozawa Naoya, Hase Tetsunari, Tanaka Hiromasa, Sato Mitsuo, Kondo Hiroki, Ishikawa Kenji, Odaka Hidefumi, Hasegawa Yoshinori, Hori Masaru, Nakazato Kazuo

    IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS   Vol. 13 ( 2 ) page: 470 - 479   2019.4

  42. Potential for afatinib as an optimal treatment for advanced non-small cell lung carcinoma in patients with uncommon EGFR mutations

    Tanaka Ichidai, Morise Masahiro, Kodama Yuta, Matsui Akira, Ozawa Naoya, Ozone Sachiko, Goto Daiki, Miyazawa Ayako, Hase Tetsunari, Hashimoto Naozumi, Sato Mitsuo, Hasegawa Yoshinori

    LUNG CANCER   Vol. 127   page: 169 - 171   2019.1

  43. The Subunit eIF2 ss of Translation- Initiation Factor EIF2 Is a Potential Therapeutic Target for Non-Small Cell Lung Cancer

    Sato Mitsuo, Tanaka Ichidai, Goto Daiki, Kato Toshio, Kakumu Tomohiko, Miyazawa Ayako, Yogo Naoyuki, Hase Tetsunari, Morise Masahiro, Sekido Yoshitaka, Kondo Masashi, Hasegawa Yoshinori

    CANCER SCIENCE   Vol. 109   page: 1181 - 1181   2018.12

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  44. eIF2 beta, a subunit of translation-initiation factor EIF2, is a potential therapeutic target for non-small cell lung cancer

    Tanaka Ichidai, Sato Mitsuo, Kato Toshio, Goto Daiki, Kakumu Tomohiko, Miyazawa Ayako, Yogo Naoyuki, Hase Tetsunari, Morise Masahiro, Sekido Yoshitaka, Girard Luc, Minna John D., Byers Lauren A., Heymach John V., Coombes Kevin R., Kondo Masashi, Hasegawa Yoshinori

    CANCER SCIENCE   Vol. 109 ( 6 ) page: 1843 - 1852   2018.6

  45. Low-autofluorescence fluoropolymer membrane filters for cell filtration

    Kihara Naoto, Kuboyama Daiki, Onoshima Daisuke, Ishikawa Kenji, Tanaka Hiromasa, Ozawa Naoya, Hase Tetsunari, Koguchi Ryohei, Yukawa Hiroshi, Odaka Hidefumi, Hasegawa Yoshinori, Baba Yoshinobu, Hori Masaru

    JAPANESE JOURNAL OF APPLIED PHYSICS   Vol. 57 ( 6 )   2018.6

  46. Safety and efficacy of diagnostic flexible bronchoscopy in very old patients with lung cancer

    Okachi Shotaro, Imaizumi Kazuyoshi, Imai Naoyuki, Shimizu Takahiro, Hase Tetsunari, Morise Masahiro, Hashimoto Naozumi, Sato Mitsuo, Hasegawa Yoshinori

    EUROPEAN GERIATRIC MEDICINE   Vol. 9 ( 2 ) page: 255 - 262   2018.4

  47. Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study

    Kobayashi Tomoko, Iwama Shintaro, Yasuda Yoshinori, Okada Norio, Tsunekawa Taku, Onoue Takeshi, Takagi Hiroshi, Hagiwara Daisuke, Ito Yoshihiro, Morishita Yoshiaki, Goto Motomitsu, Suga Hidetaka, Banno Ryoichi, Yokota Kenji, Hase Tetsunari, Morise Masahiro, Hashimoto Naozumi, Ando Masahiko, Kiyoi Hitoshi, Gotoh Momokazu, Ando Yuichi, Akiyama Masashi, Hasegawa Yoshinori, Arima Hiroshi

    JOURNAL OF THE ENDOCRINE SOCIETY   Vol. 2 ( 3 ) page: 241 - 251   2018.3

  48. A phase II trial of Ifosfamide combination with recommended supportive therapy for recurrent SCLC in second-line and heavily treated setting

    Tanaka Ichidai, Kawada Kenji, Morise Masahiro, Hase Tetsunari, Hayashi Hiroaki, Sokai Akihiko, Fukatsu Asuki, Kondo Masashi, Nomura Fumio, Hasegawa Yoshinori

    CANCER CHEMOTHERAPY AND PHARMACOLOGY   Vol. 81 ( 2 ) page: 339 - 345   2018.2

  49. Lung Metastases from Bile Duct Adenocarcinoma Mimicking Chronic Airway Infection and Causing Diagnostic Difficulty

    Sato Mitsuo, Okachi Shotaro, Fukihara Jun, Shimoyama Yoshie, Wakahara Keiko, Sakakibara Toshihiro, Hase Tetsunari, Onishi Yasuharu, Ogura Yasuhiro, Maeda Osamu, Hasegawa Yoshinori

    INTERNAL MEDICINE   Vol. 57 ( 10 ) page: 1429 - 1432   2018

  50. An EGFR-mutated Lung Adenocarcinoma Undergoing Squamous Cell Carcinoma Transformation Exhibited a Durable Response to Afatinib

    Sato Mitsuo, Matsui Akira, Shimoyama Yoshie, Omote Norihito, Morise Masahiro, Hase Tetsunari, Tanaka Ichidai, Suzuki Kojiro, Hasegawa Yoshinori

    INTERNAL MEDICINE   Vol. 57 ( 23 ) page: 3429 - 3432   2018

  51. Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer

    Kakumu Tomohiko, Sato Mitsuo, Goto Daiki, Kato Toshio, Yogo Naoyuki, Hase Tetsunari, Morise Masahiro, Fukui Takayuki, Yokoi Kohei, Sekido Yoshitaka, Girard Luc, Minna John D., Byers Lauren A., Heymach John V., Coombes Kevin R., Kondo Masashi, Hasegawa Yoshinori

    CANCER SCIENCE   Vol. 108 ( 4 ) page: 732 - 743   2017.4

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MISC 17

  1. The Prognostic Impact of Postoperative EGFR Mutation Status in Lung Cancer Patients with Stage II - III

    Nakamura, S; Hase, T; Takada, Y; Iwashimizu, H; Imamura, Y; Okado, S; Nomata, Y; Watanabe, H; Noritake, O; Nakanishi, K; Kadomatsu, Y; Ueno, H; Kato, T; Mizuno, T; Ishii, M; Chen-Yoshikawa, TF

    JOURNAL OF THORACIC ONCOLOGY   Vol. 18 ( 11 ) page: S489 - S490   2023.11

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  2. CEBP gamma and YBX1 regulate lung cancer metastasis via CERS6 expression and lamellipodia formation.

    Shi Hanxiao, Niimi Atsuko, Takeuchi Toshiyuki, Mizutani Yasuyoshi, Shiogama Kazuya, Inada Kenichi, Hase Tetsunari, Hasegawa Yoshinori, Takahashi Takashi, Suzuki Motoshi

    CANCER SCIENCE   Vol. 112   page: 700 - 700   2021.2

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  3. Pharmacokinetic and dose finding study of osimertinib in patients with impaired renal function and low body weight

    Hase T., Fujiwara Y., Makihara R. A., Hashimoto N., Tsubata Y., Okuno T., Naito T., Takahashi T., Kobayashi H., Shinno Y., Ikeda T., Goto K., Hosomi Y., Watanabe K., Kitazono S., Sakiyama N., Makino Y., Yamamoto N.

    ANNALS OF ONCOLOGY   Vol. 32   page: S982 - S983   2021

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  4. PREDICT1: An observational study for identifying blood biomarkers associated with clinical benefit from carboplatin and pemetrexed (CbP) treatment in patients with non-squamous (NS) non-small cell lung cancer (NSCLC) (CJLSG1201).

    Hase Tetsunari, Yanagisawa Kiyoshi, Fukatsu Asuki, Kimura Tomoki, Kojima Eiji, Abe Takashi, Imaizumi Kazuyoshi, Horio Yoshitsugu, Oguri Tetsuya, Yamamoto Masashi, Ogasawara Tomohiko, Sugino Yasuteru, Morise Masahiro, Nakatochi Masahiro, Ando Masahiko, Kondo Masashi, Saka Hideo, Saito Hiroshi, Hasegawa Yoshinori, Takahashi Takashi

    JOURNAL OF CLINICAL ONCOLOGY   Vol. 38 ( 15 )   2020.5

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    Language:Japanese  

    Web of Science

  5. Prognostic Factors in Myositis-Related Interstitial Lung Disease: A Retrospective Multicenter Study

    Waseda Y., Shiraki A., Saeki K., Watanabe S., Shoda T., Ishida T., Makino S., Tomii K., Hase T., Hasegawa Y., Okamoto M., Izumi S., Miyamoto A., Kishi K., Kishaba T., Nara M., Komatsuda A., Arita M., Kawamura K., Ichikado K., Koreeda Y., Mitsuma T., Hamaguchi Y., Muro Y., Egashira R., Sumikawa H., Ishizuka T., Johkoh T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 201   2020

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    Language:Japanese  

    Web of Science

  6. Exosomal Analysis of ALK Rearrangements by Spin Column with Porous Glass Filter

    Hatta T., Hase T., Ozawa N., Yogo N., Yukawa H., Tanaka H., Onoshima D., Sato M., Hori M., Baba Y., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 14 ( 10 ) page: S676 - S676   2019.10

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    Language:Japanese  

    Web of Science

  7. UHRF1 as a Potential Therapeutic Target for KRAS Mutated Non-Small Cell Lung Cancer

    Goto D., Kizuki M., Uwatoko N., Kawai K., Koike M., Nakashima M., Miyazawa A., Tanaka I., Hase T., Morise M., Hasegawa Y., Minna J., Sato M.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 14 ( 10 ) page: S692 - S692   2019.10

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    Language:Japanese  

    Web of Science

  8. Serum CRP Decrease Has Predictive Value for LongTerm Disease Control by PD-1/ PD-L1 Inhibitors in Patients with NSCLC

    Matsuzawa R., Morise M., Tanaka I., Koyama J., Kimura T., Kondoh Y., Hase T., Sakamoto K., Hashimoto N., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 14 ( 10 ) page: S716 - S716   2019.10

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    Language:Japanese  

    Web of Science

  9. Impact of Combined Evaluation Using Tumor Volume and Metastatic Nodal Extent in Stage III NSCLC Treated with CRT

    Tamiya Y., Morise M., Matsuzawa R., Tanaka I., Okada T., Iwano S., Hase T., Hashimoto N., Sato M., Itoh Y., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 14 ( 10 ) page: S909 - S910   2019.10

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    Language:Japanese  

    Web of Science

  10. Analysis of Clinical Features by Both Diagnosis and Types of Antibodies in Patients with Myositis Related Interstitial Lung Disease: A Retrospective Multicenter Study

    Waseda Y., Shiraki A., Saeki K., Watanabe S., Shoda T., Ishida T., Makino S., Tomii K., Hase T., Hasegawa Y., Okamoto M., Izumi S., Miyamoto A., Kishi K., Kishaba T., Nara M., Komatsuda A., Arita M., Kawamura K., Ichikado K., Koreeda Y., Mitsuma T., Hamaguchi Y., Muro Y., Egashira R., Sumikawa H., Ishizuka T., Johkoh T.

    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE   Vol. 199   2019

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    Language:Japanese  

    Web of Science

  11. Development of the immuno-wall device for rapid detection of ALK and ROS1 fusions in lung cancer

    Yogo N., Hase T., Kasama T., Hatta T., Ozawa N., Sato M., Kaji N., Tokeshi M., Baba Y., Hasegawa Y.

    ANNALS OF ONCOLOGY   Vol. 29   2018.11

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  12. Retrospective analysis of risk factor of injection site reaction induced by infusion of cisplatin plus vinorelbine

    Ozawa N., Hase T., Hatta T., Sagara A., Ichikawa K., Miyazaki M., Ando M., Yamada K., Hasegawa Y.

    ANNALS OF ONCOLOGY   Vol. 29   2018.11

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  13. eIF2 beta, A Subunit of Translation-Initiation Factor EIF2, as a Potential Therapeutic Target for Non-Small Cell Lung Cancer

    Goto D., Tanaka I., Sato M., Kato T., Miyazawa A., Hase T., Morise M., Sekido Y., Girard L., Minna J., Byers L., Heymach J., Coombes K., Kondo M., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 13 ( 10 ) page: S516 - S517   2018.10

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  14. Short Hydration Regimen with a Modified Dose of Magnesium Supplementation for Lung Cancer Patients Receiving Cisplatin-Based Chemotherapy

    Hase T., Miyazaki M., Ichikawa K., Yogo N., Ozawa N., Ando M., Morise M., Sato M., Kondo M., Yamada K., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 13 ( 10 ) page: S880 - S880   2018.10

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  15. Development of the immuno-wall device for rapid, low-cost detection of EGFR mutations in tumor samples from patients with lung cancer

    Yogo N., Hase T., Kasama T., Ozawa N., Sato M., Kaji N., Tokeshi M., Baba Y., Hasegawa Y.

    ANNALS OF ONCOLOGY   Vol. 28   2017.11

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  16. Phase I study of combined therapy with vorinostat and gefitinib to treat BIM deletion polymorphism-associated resistance in EGFR-mutant lung cancer (VICTROY-J)

    Hase T., Takeuchi S., Ando M., Hata A., Kenmotsu H., Fujiwara T., Shimizu S., Nagase K., Yoshimura K., Katakami N., Takahashi T., Hasegawa Y., Yano S.

    ANNALS OF ONCOLOGY   Vol. 28   2017.11

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  17. Identification of Proteosomal Catalytic Subunit PSMA6 as a Therapeutic Target for Lung Cancer through a Pooled shRNA Screen

    Sato M., Kakumu T., Goto D., Kato T., Yogo N., Hase T., Morise M., Fukui T., Yokoi K., Sekido Y., Girard L., Minna J., Byers L., Heymach J., Coombes K., Kondo M., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 12 ( 11 ) page: S2277 - S2278   2017.11

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Research Project for Joint Research, Competitive Funding, etc. 3

  1. 気管支鏡検査時の飛沫感染防止シールドの開発

    2020.7 - 2021.6

    新型コロナウイルス感染症対策助成プログラム 

  2. 肺癌体細胞遺伝子変異の免疫学的診断システムの開発

    2017.7 - 2018.3

    橋渡し研究戦略的推進プログラムシーズB 

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    Grant type:Competitive

  3. 肺癌体細胞遺伝子変異の免疫学的診断システムの開発

    2016.4 - 2017.3

    橋渡し研究加速ネットワークプログラム事業  

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    Grant type:Competitive

KAKENHI (Grants-in-Aid for Scientific Research) 7

  1. ドライバー癌遺伝子誘導性の細胞老化を作用機序とする変異KRAS肺癌の創薬研究

    Grant number:21H02924  2021.4 - 2024.3

    科学研究費助成事業  基盤研究(B)

    佐藤 光夫, 芳川 豊史, 長谷 哲成, 湯川 博, 田中 一大, 松井 佑介

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    変異KRAS癌の創薬を目的とする。代表者は自身開発の正常気管支上皮細胞モデルHBECにおいて、変異KRASの導入が細胞の悪性度を増強する一方で、細胞の増殖を停止させる癌遺伝子誘導細胞老化(oncogene-induced senescence; OIS)という現象に着目した。HBECモデルを用いたOIS回避機能に基づくプールshRNAライブラリースクリーニングを実施し、遺伝子Xを有望な治療標的候補として特定した。本課題では世界初のOIS誘導機序による肺癌治療薬の開発を目標とする。

  2. 肺癌免疫チェックポイント阻害薬併用療法のバイオマーカー研究

    Grant number:21K08177  2021.4 - 2024.3

    長谷 哲成

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    Authorship:Principal investigator 

    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

  3. 部分的上皮間葉細胞転換(ハイブリッドEMT)の安定化因子を標的とする肺癌治療

    Grant number:19K22617  2019.6 - 2021.3

    挑戦的研究(萌芽)

    佐藤 光夫

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    上皮間葉細胞転換(EMT)は癌細胞が上皮系から間葉系へ転換し悪性度を増強する現象である。これまではEMTを完了した細胞の悪性度が最も高いとされてきた。しかし、応募者の準備データは部分的なEMT細胞の方が完全なEMT細胞に比べ悪性形質が高いことを示唆する。また、部分的EMTを安定化する未知の因子の存在が推測され、これは癌の悪性形質を決定する有望な治療標的の可能性がある。以上より、本研究は肺癌治療標的として期待される部分的EMTの“安定化因子”の発見およびそれらを標的とする創薬を目的とする。方法として、応募者開発の正常気管支上皮細胞モデル(HBEC)を用いた機能的なスクリーニングなどを実施する。
    上皮間葉細胞転換(epithelial to mesenchymal transition, EMT)は癌細胞が上皮系から間葉系へ転換し悪性度を増強する現象である。これまでは、完全にEMTを完了した細胞の悪性度が最も高いと信じられてきた。しかし、最近の報告と応募者の準備データは予想に反し、部分的なEMT細胞、すなわちハイブリッドEMTの方が完全なEMT細胞に比べ癌幹細胞性質などの悪性形質が高いと示唆する。また、ハイブリッドEMTを安定化する未知の因子の存在が推測され、これは癌の悪性形質を決定している有望な治療標的の可能性がある。本研究は肺癌治療標的として期待されるハイブリッドEMTの“安定化因子”の発見を目的とする。2019年度はEMT安定化因子候補である遺伝子A(論文未発表にてAとする)の肺癌細胞における機能を評価した。複数の肺癌細胞株を使用し、RNA干渉によって遺伝子Aノックダウンを実施した。遺伝子ノックダウンの効率をウエスタンブロットで評価した。癌細胞の増殖を足場依存性および足場非依存性条件の両者において評価した。足場非依存性増殖能は軟寒天中のコロニー形成にて評価した。我々はある肺癌細胞株において、遺伝子Aノックダウン足場依存性増殖にはほとんど影響がなく、足場非依存性増殖能を強く抑制する結果を得た。足場非依存性増殖は細胞が細胞外のマトリックス等への接着を失った状態での増殖である。正常細胞は足場非依存性の状態では通常、細胞死に至る。対照的に癌細胞は足場非依存性増殖能を獲得していることが多く、その能力は浸潤能や転移能と深く関係しており、癌細胞の重要な悪性形質の一つである。したがって、我々の結果は遺伝子Aが肺癌の有望な治療標的となりうることを示唆した。今後は、足場非依存性増殖能を別のアッセイ系で評価し結果の確認を実施する。確認された場合は、遺伝子Aノックダウンによる足場非依存性増殖の抑制機序を明らかとする。
    2019年度はEMT安定化因子候補である遺伝子A(論文未発表にてAとする)の肺癌細胞における機能を評価した。複数の肺癌細胞株を使用し、RNA干渉によって遺伝子Aノックダウンを実施した。遺伝子ノックダウンの効率をウエスタンブロットで評価した。癌細胞の増殖を足場依存性および足場非依存性条件の両者において評価した。足場非依存性増殖能は軟寒天中のコロニー形成にて評価した。我々はある肺癌細胞株において、遺伝子Aノックダウン足場依存性増殖にはほとんど影響がなく、足場非依存性増殖能を強く抑制する結果を得た。今後は、足場非依存性増殖能を別のアッセイ系で評価し結果の確認を実施する。確認された場合は、遺伝子Aノックダウンによる足場非依存性増殖の抑制機序を明らかとする。また、遺伝子Aを含む候補遺伝子ならびにEMT関連遺伝子のタンパク発現をウエスタンブロットによって肺癌細胞パネルを使用して実施予定である。そのために、肺癌細胞パネルからのタンパク、RNA、DNAの抽出をほぼ完了した。2020年度も継続して実施する。
    肺癌の治療標的としての可能性を持つ遺伝子Aの機能評価を軸に研究を推進する。具体的には、複数のEMT状態の異なる肺癌細胞における遺伝子Aのがん促進作用を評価する。これによって、遺伝子Aの機能がEMT状態依存性であるかどうかを明らかとする。また、遺伝子Aノックダウンによる足場非依存性増殖能の抑制作用の機序を明らかとしていく。さらに、in vivo実験を追加し、遺伝子A標的治療の臨床応用への可能性も評価する。

  4. ドライバー癌遺伝子により誘導される細胞老化 (OIS) を利用した肺癌治療の開発

    Grant number:18H02819  2018.4 - 2021.3

    佐藤 光夫

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    【本課題の目的】肺癌のドライバー癌遺伝子の一つ変異KRASは腺癌の20%程度に認められるが、その標的治療の開発は未成功である。これは変異KRASの癌化シグナルの薬物的な遮断が困難なためである。応募者は正常気管支モデルであるHBEC実験系を確立し(Sato, Cancer Res 2006)、さらに、変異KRASをHBECに導入すると悪性度の増強にもかかわらず細胞分裂を停止する現象を発見した(Sato, Mol Cancer Res 2013)。これは正常細胞が癌化を防御する機構の一つ癌遺伝子誘導細胞老化(oncogene-induced senescence; OIS)である。以上より、応募者は変異KRAS肺癌の新たな治療として変異KRASシグナルの遮断ではなく、OISを活用する治療を着想した。その実現のために、まず、HBECを用いて、OIS抑制作用を表現型とする機能的なプールshRNAスクリーニングを実施し、複数の標的候補を特定した。特に、肺癌細胞株が高発現する遺伝子Xは小分子化合物による治療標的となる可能性があるため、学内創薬産学協同研究センター(ラクオリア創薬株式会社)化合物スクリーニングを予定した(機密保持契約締結済み)。本研究はこれらの研究を発展させ、変異KRASならびに変異EGFRやALK遺伝子によるOIS誘導治療の開発を目的とする。
    <BR>
    【2019年度の成果】
    これまでに、複数の化合物ライブラリーを使用したハイスループットスクリーニング(HTS)を実施した。初期に同定したヒット化合物の活性が再現できなかったため、化合物選択基準の見直しを行い、ヒット化合物を選び直した。ヒット化合物の再現性、選択性、構造活性相関(Structure-Activity Relationship: SAR)解析の結果に基づき、数個のシーズ化合物に絞り込んだ。
    これまでに、複数の化合物ライブラリーを使用したハイスループットスクリーニング(HTS)を実施した。初期に同定したヒット化合物の活性が再現できなかったため、化合物選択基準の見直しを行い、ヒット化合物を選び直した。ヒット化合物の再現性、選択性、構造活性相関(Structure-Activity Relationship: SAR)解析の結果に基づき、数個のシーズ化合物に絞り込んだ。ヒット化合物の再現性ができなかったことなどにより当初の計画よりやや遅れている。
    これまでの研究成果に基づいて2020年度は以下を計画する。①SARの結果に基づいて新規化合物(リード化合物)を合成する。②リード化合物および遺伝子X産物との結晶構造解析を外部委託に実施する。③新規化合物に対して評価・解析およびデザイン・合成のステップを繰り返し実施し、さらに薬効の優れるリード化合物を合成する。④前記と併行して、遺伝子Xノックアウト肺癌細胞クローンを用いて、遺伝子X阻害の癌細胞の増殖抑制機序の解明を継続して実施する。⑤2020年度までに合成されるリード化合物に対して、各種非臨床試験(薬理、毒性、薬物動態試験など)に必要な予備的試験を実施する。具体的には、複数の化合物の薬効(XenograftやPDXモデル)、薬物動態(経口吸収率、血中半減期、代謝・排出経路、代謝物)、短期毒性(心血管作用、中枢作用、病理)、物性(溶解性、固体安定性)を評価する。以上の結果に基づいて、2020年度末までにリード化合物の基本特許申請を目標とする。

  5. Analysis of resistance against molecular targeted therapy with circulating tumor cells with stemness properties

    Grant number:17K09651  2017.4 - 2020.3

    Hase Tetsunari

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    In this study, we isolated circulating tumor cells from lung cancer patients, and investigated mechanisms underlying resistance to molecular targeted therapy. First, we conducted isolation of lung cancer cell-lines as a model of circulating tumor cells, which were spiked into the blood from healthy donor, and gene analyses were successfully performed. Then, circulating tumor cells were isolated from the blood of lung cancer patients whose tumors exhibited resistance to the molecular target therapy, and gene analyses revealed additional gene alteration related to the resistance of the molecular target drug.

  6. 癌幹細胞性を有する循環腫瘍細胞を標的とした個別化医療の開発

    2015.4 - 2017.3

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

  7. 治療標的としての肺癌新規幹細胞候補遺伝子の機能解析

    2012.4 - 2014.3

    科学研究費補助金  若手研究(B)

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    Authorship:Principal investigator 

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Teaching Experience (On-campus) 3

  1. 修士課程医科学専攻必修科目

    2021

  2. 呼吸器疾患の診断と胸膜・縦隔疾患

    2021

  3. 呼吸器疾患の診断と胸膜・縦隔疾患

    2020