悪性膵神経内分泌腫瘍の非侵襲的診断と治療標的の探索

2021 Fiscal Year Annual Research Report

• Project/Area Number: 19K09041
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: 工藤 篤 東京医科歯科大学, 東京医科歯科大学病院, 准教授 (20376734)
• Co-Investigator(Kenkyū-buntansha): 田中 真二 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (30253420) ; 田邉 稔 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50197513)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 転移能

Outline of Annual Research Achievements

我々は2016年に肉眼型分類を世界で初めて創設し、網羅的遺伝子解析で肝転移の指標を同定した.本研究はこれらについて新しい画像診断学的指標を開発し、分子生物学的特徴を調べることを目的とした。我々は2016年に病理学的、画像診断学的な肉眼型分類を世界で初めて創設し、非単純結節型の予後が極めて不良であることを示していた。
非単純結節型10例と単純結節型10例の網羅的遺伝子解析を行い、Gene set enrichment analysis ( GSEA )を行い、得られた標的遺伝子のタンパク発現は免疫染色を行っている。年齢、性別、遺伝疾患の有無、BMI、原発腫瘍の大きさ、個数、ホルモン症状、肉眼的周囲浸潤、リンパ節転移、分化度、Ki-67指数、血管侵襲、chromogranin A、synaptophysin、核分裂像、ホルモン産生、新しい標的遺伝子タンパク発現、PAX6免疫染色を行う。PAX6の抗体はsc-81649 anti-PAX6抗体を200倍希釈で用いた。SPSS version 23.0を用いて、無再発生存率および全生存率につき予後解析を行った。最終的な予後情報は2022年3月に収集を行った。
令和3年度は上記GSEAで得られた標的遺伝子のタンパク発現は免疫染色を行った。糖鎖マーカー発現の病態生理学的意義を検証した。PAX6の検査症例数を約200例まで増やした。CT, MRI, 術中超音波検査所見を利用した新しい非侵襲的指標のためのデータの蓄積を行った。
肉眼型分類のvalidation studyとして、全国規模の前向き研究でその予後予測因子としての意義を検討中である。全国から画像を収集中であり、TRI医療イノベーションセンターに蓄積された前向きデータとともに、肉眼型分類が及ぼす予後への影響を調査中である。
網羅的遺伝子解析のサンプル数は50例集まり、再解析中である

Research Products

• [Journal Article] Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors (2022)
  • Author(s): Watanabe Hirofumi、Fujishima Fumiyoshi、Komoto Izumi、Imamura Masayuki、Hijioka Susumu、Hara Kazuo、Yatabe Yasushi、Kudo Atsushi、Masui Toshihiko、Tsuchikawa Takahiro、Sakamoto Kazuhiro、Shiga Hisashi、Nakamura Tomohiro、Nakaya Naoki、Motoi Fuyuhiko、Unno Michiaki、Sasano Hironobu
  • Journal Title: Cancers Volume: 14 Pages: 775～775
  • DOI: 10.1002/ags3.12458
  • Peer Reviewed
• [Journal Article] Surgery after sunitinib administration to improve survival of patients with advanced pancreatic neuroendocrine neoplasms (2021)
  • Author(s): Murase Yoshiki、Kudo Atsushi、Akahoshi Keiichi、Maekawa Aya、Ishikawa Yoshiya、Ueda Hiroki、Ogawa Kosuke、Ono Hiroaki、Tanaka Shinji、Tanabe Minoru
  • Journal Title: Annals of Gastroenterological Surgery Volume: 5 Pages: 692～700
  • DOI: 10.1111/cas.15134
  • Peer Reviewed
• [Journal Article] Inhibitor library screening identifies ispinesib as a new potential chemotherapeutic agent for pancreatic cancers (2021)
  • Author(s): Murase Yoshiki、Ono Hiroaki、Ogawa Kosuke、Yoshioka Risa、Ishikawa Yoshiya、Ueda Hiroki、Akahoshi Keiichi、Ban Daisuke、Kudo Atsushi、Tanaka Shinji、Tanabe Minoru
  • Journal Title: Cancer Science Volume: 112 Pages: 4641～4654
  • DOI: 10.1371/journal.pone.0252917
  • Peer Reviewed
• [Journal Article] Cytoplasmic RRM1 activation as an acute response to gemcitabine treatment is involved in drug resistance of pancreatic cancer cells (2021)
  • Author(s): Kato Tomotaka、Ono Hiroaki、Fujii Mikiya、Akahoshi Keiichi、Ogura Toshiro、Ogawa Kosuke、Ban Daisuke、Kudo Atsushi、Tanaka Shinji、Tanabe Minoru
  • Journal Title: PLOS ONE Volume: 16 Pages: 0252917～0252917
  • DOI: 10.1007/s00432-021-03660-0
  • Peer Reviewed
• [Journal Article] A novel classification of portal venous tumor invasion to predict residual tumor status after surgery in patients with pancreatic neuroendocrine neoplasms (2021)
  • Author(s): Kato Tomotaka、Kudo Atsushi、Kinowaki Yuko、Ishikawa Yoshiya、Watanabe Shuichi、Akahoshi Keiichi、Ogawa Kosuke、Ono Hiroaki、Ban Daisuke、Tanaka Shinji、Tanabe Minoru
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: 148 Pages: 931～941
  • DOI: 10.1007/s00432-021-03650-2
  • Peer Reviewed
• [Journal Article] Hormonal tumor mapping for liver metastases of gastroenteropancreatic neuroendocrine neoplasms: a novel therapeutic strategy (2021)
  • Author(s): Maekawa Aya、Kudo Atsushi、Kishino Mitsuhiro、Murase Yoshiki、Watanabe Shuichi、Ishikawa Yoshiya、Ueda Hiroki、Akahoshi Keiichi、Ogawa Kosuke、Ono Hiroaki、Tanaka Shinji、Kinowaki Yuko、Tanabe Minoru
  • Journal Title: Journal of Cancer Research and Clinical Oncology Volume: 148 Pages: 697～706
  • DOI: 10.1245/s10434-021-09856-5
  • Peer Reviewed
• [Journal Article] A Pilot Study Analyzing the Clinical Utility of Comprehensive Genomic Profiling Using Plasma Cell-Free DNA for Solid Tumor Patients in Japan (PROFILE Study) (2021)
  • Author(s): Matsudera Shotaro、Kano Yoshihito、Aoyagi Yasuko、Kudo Atsushi et al
  • Journal Title: Annals of Surgical Oncology Volume: 28 Pages: 8497～8505
  • DOI: 10.2337/dc20-0864
  • Peer Reviewed
• [Journal Article] Importance of Intestinal Environment and Cellular Plasticity of Islets in the Development of Postpancreatectomy Diabetes (2021)
  • Author(s): Fukuda Tatsuya、Bouchi Ryotaro、Takeuchi Takato、Amo-Shiinoki Kikuko、Kudo Atsushi、Tanaka Shinji、Tanabe Minoru、Akashi Takumi、Hirayama Kazuhiro、Odamaki Toshitaka、Igarashi Miki、Kimura Ikuo、Tanabe Katsuya、Tanizawa Yukio、Yamada Tetsuya、Ogawa Yoshihiro
  • Journal Title: Diabetes Care Volume: 44 Pages: 1002～1011
  • DOI: 10.1186/s12885-020-07579-6
  • Peer Reviewed
• [Presentation] Cross-sectional study of genomic sequencing in HBP malignancies (2021)
  • Author(s): Hiroaki Ono,Sadakatsu Ikeda,Yoshiya Ishikawa,Shuichi Watanabe,Keiichi Akahoshi,Kosuke Ogawa,Daisuke Ban,Atsushi Kudo,Satoshi Miyake,Minoru Tanabe
  • Organizer: 第75回日本消化器外科学会総会
  • Int'l Joint Research
• [Presentation] Evaluation of laparoscopic distal pancreatectomy for pancreatic neuroecdocrine tumors (2021)
  • Author(s): Kohei Yagi,Atsushi Kudo, Aya Maekawa, Yoshiki Murase, Takeshi Ishii, Tomotaka Kato, Masafumi Sugawara, Yoshiya Ishikawa, Shuichi Watanabe, Keiichi Akahoshi, Kosuke Ogawa, Hiroaki Ono, Daisuke Ban, Shinji Tanaka, Minoru Tanabe
  • Organizer: The 32nd Meeting of Japanese Society of Hepato-Biliary-Pancreatic Surgery
  • Int'l Joint Research
• [Presentation] Iver resection after systemic chemotherapy improved overallsuvival of metastatic neuroendocrine neoplasms (2021)
  • Author(s): Keiichi Akahoshi, Yoshiya Ishikawa, Hiroki Ueda, Kosuke Ogawa, Hiroaki Ono, Atsushi Kudo, Shinji Tanaka, Minoru Tanabe
  • Organizer: The 32nd Meeting of Japanese Society of Hepato-Biliary-Pancreatic Surgery
  • Int'l Joint Research
• [Presentation] Combination of Weekly Streptozocin and Oral S-1 Treatment is e ective treatment for unresectable or metastatic pancreatic NET-G1 and NET-G2 patients (2021)
  • Author(s): Hiroaki Ono, Atsushi Kudo, Yoshiya Ishikawa, Hiroki Ueda, Keiichi Akahoshi, Kosuke Ogawa, Shinji Tanaka, Minoru Tanabe
  • Organizer: The 33rd Meeting of Japanese Society of Hepato-Biliary-Pancreatic Surgery
  • Int'l Joint Research
• [Presentation] The management of GEP-NET with MEN type 1 in our department (2021)
  • Author(s): Takeshi Ishii, Atsushi Kudo, Yoshiki Murase, Aya Maekawa, Toshitaka Sugawara, Yoshiya Ishikawa, Shuichi Watanabe, Hiroki Ueda, Keiichi Akahoshi, Kousuke Ogawa, Hiroaki Ono, Shinji Tanaka, Minoru Tanabe
  • Organizer: The 33rd Meeting of Japanese Society of Hepato-Biliary-Pancreatic Surgery
  • Int'l Joint Research