膵癌間質のプロテオーム解析

• 研究課題/領域番号: 23592018
• 研究種目: 基盤研究(C)
• 配分区分: 基金
• 応募区分: 一般
• 研究分野: 消化器外科学
• 研究機関: 横浜市立大学
• 研究代表者: 遠藤 格 横浜市立大学, 医学(系)研究科(研究院), 教授 (60211091)
• 研究分担者: 平野 久 横浜市立大学, 生命ナノシステム科学研究科, 教授 (00275075) ; 森 隆太郎 横浜市立大学, 附属病院, 助教 (90596412) ; 廣島 幸彦 横浜市立大学, 医学研究科, 客員研究員 (60718021)
• 研究期間 (年度): 2011 – 2013
• 研究課題ステータス: 完了 (2013年度)
• 配分額: 5,330千円 (直接経費: 4,100千円、間接経費: 1,230千円); 2013年度: 1,430千円 (直接経費: 1,100千円、間接経費: 330千円); 2012年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円); 2011年度: 2,340千円 (直接経費: 1,800千円、間接経費: 540千円)
• キーワード: 膵癌 / 癌微小環境 / 転移 / 浸潤 / ノックアウトマウス / 膵炎 / リン酸化 / 間質 / イメージング

研究概要

膵癌は予後不良な疾患であり、新規治療薬の開発が期待されている。近年、膵癌間質が癌の進展を多面的に促進させ、抗癌剤耐性にも関与している事が実証された。本研究において、膵癌間質と正常膵間質で発現に差のある蛋白を網羅的に解析し、CRMP4という候補蛋白を選出した。膵癌においてCRMP4の発現は強力な予後、再発予測因子であり、静脈浸潤、肝転移とも相関を認めた。また、細胞実験系において、CRMP4の発現低下が増殖には変化を認めないが、浸潤能を低下させることを発見した。これらの結果から、CRMP4が膵癌細胞の浸潤を促進し、静脈浸潤、肝転移を増加させ、膵癌患者の予後を増悪させていることが示唆された。

研究成果

• [雑誌論文] Hand-held high-resolution fluorescence imaging system for fluorescence-guided surgery of patient and cell-line pancreatic tumors growing orthotopically in nude mice. (2014)
  • 著者名/発表者名: Hiroshima Y, Maawy A, Sato S, Murakami T, Uehara F, Miwa S, Yano S, Momiyama M, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • 雑誌名: J Surg Res. 巻: 187(2) 号: 2 ページ: 510-7
  • DOI: 10.1016/j.jss.2013.11.1083
  • 査読あり
• [雑誌論文] Efficacy of Salmonella typhimurium A1-R Versus Chemotherapy on a Pancreatic Cancer Patient-Derived Orthotopic Xenograft (PDOX). (2014)
  • 著者名/発表者名: Hiroshima Y, Zhao M, Maawy A, Zhang Y, Katz MH, Fleming JB, Uehara F, Miwa S, Yano S, Momiyama M, Suetsugu A, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • 雑誌名: J Cell Biochem 巻: 115(7) 号: 7 ページ: 1254-61
  • DOI: 10.1002/jcb.24769
  • 査読あり
• [雑誌論文] Successful fluorescence-guided surgery on human colon cancer patient-derived orthotopic xenograft mouse models using a fluorophore-conjugated anti-CEA antibody and a portable imaging system. (2014)
  • 著者名/発表者名: Hiroshima Y, Maawy A, Metildi CA, Zhang Y, Uehara F, Miwa S, Yano S, Sato S, Murakami T, Momiyama M, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • 雑誌名: J Laparoendosc Adv Surg Tech A. 巻: 24(4) 号: 4 ページ: 241-7
  • DOI: 10.1089/lap.2013.0418
  • 査読あり
• [雑誌論文] Hand-Held High-Resolution Fluorescence Imaging System for Fluorescence-Guided Surgery of Patient and Cell-Line Pancreatic Tumors Growing Orthotopically in Nude Mice (2013)
  • 著者名/発表者名: Yukihiko Hiroshima, Ali Maawy, Sho Sato, Takashi Murakami, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo and Robert M. Hoffman
  • 雑誌名: J Surg Res. 巻: (in press)
  • 査読あり
• [雑誌論文] Successful fluorescence-guided surgery on human colon cancer patient-derived orthotopic xenograft (PDOX) mouse models using a fluorophore-conjugated anti-CEA antibody and a portable imaging system (2013)
  • 著者名/発表者名: Yukihiko Hiroshima, Ali Maawy, Cristina A. Metildi, Yong Zhang, Fuminari Uehara, Shinji Miwa, Shuya Yano, Sho Sato, Takashi Murakami, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo and Robert M. Hoffman
  • 雑誌名: J Laparoendosc Adv Surg Tech A. 巻: (Epub ahead of print)
  • 査読あり
• [雑誌論文] Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells. (2013)
  • 著者名/発表者名: Hiroshima Y, Zhao M, Zhang Y, Maawy A, Hassanein MK, Uehara F, Miwa S, Yano S, Momiyama M, Suetsugu A, Chishima T, Tanaka K, Bouvet M, Endo I, Hoffman RM.
  • 雑誌名: Cell Cycle 巻: 1;12(17) 号: 17 ページ: 2774-80
  • DOI: 10.4161/cc.25872
  • 査読あり
• [雑誌論文] Collapsin response mediator protein 4 expression is associated with liver metastasis and poor survival in pancreatic cancer (2013)
  • 著者名/発表者名: Hiroshima Y, Nagashima Y et al
  • 雑誌名: Ann Surg Oncol 巻: 20 (Suppl 3) 号: S3 ページ: 369-378
  • DOI: 10.1245/s10434-012-2491-3
  • 査読あり
• [雑誌論文] Collapsin Response Mediator Protein 4 Expression is Associated with Liver Metastasis and Poor Survival in Pancreatic Cancer. (2012)
  • 著者名/発表者名: Hiroshima Yukihiko
  • 雑誌名: Annals of Surgical Oncology 巻: -
  • 査読あり
• [学会発表] Establishment of a patient-derived orthotopic xenograft (PDOX) model of patient cervical cancer (2014)
  • 著者名/発表者名: Yukihiko Hiroshima1, Yong Zhang1, Ali Maawy2, Sho Sato3, Takashi Murakami3, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama3, Takashi Chishima3, Kuniya Tanaka3, Ali Maawy2, Itaru Endo3, Robert M. Hoffman1.
  • 学会等名: AACR
  • 発表場所: San Diego, USA
• [学会発表] The advantages of patient-derived orthotopic xenograft (PDOX) of metastatic cervical cancer for individualized therapy compared to the PDX model (2014)
  • 著者名/発表者名: Yukihiko Hiroshima1, Yong Zhang1, Ali Maawy2, Sho Sato3, Takashi Murakami3, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama3, Takashi Chishima3, Kuniya Tanaka3, Michael Bouvet2, Itaru Endo3, Robert M. Hoffman1.
  • 学会等名: AACR
  • 発表場所: San Diego, USA
• [学会発表] Efficacy of Salmonella typhimurium A1-R and anti-VEGF therapy on a patient-derived orthotopic xenograft (PDOX) pancreatic cancer model (2014)
  • 著者名/発表者名: Yukihiko Hiroshima1, Ming Zhao1, Matthew H.G. Katz2, Jason B. Fleming2, Sho Sato3, Takashi Murakami3, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama3, Yong Zhang1, Ali Maawy4, Takashi Chishima3, Kuniya Tanaka3, Michael Bouvet4, Itaru Endo3, Robert M. Hoffman1.
  • 学会等名: AACR
  • 発表場所: San Diego, USA
• [学会発表] Zoledronic acid inhibits proliferation and metastasis of human pancreatic cancer in the patient-derived orthotopic xenograft (PDOX) model by targeting tumor-educated macrophages (2014)
  • 著者名/発表者名: Yukihiko Hiroshima1, Mohamed K. Hassenein1, Rhiana Menen1, Matthew H.g. Katz2, Jason B. Fleming2, Sho Sato3, Takashi Murakami3, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama3, Ali Maawy4, Takashi Chishima3, Kuniya Tanaka3, Michael Bouvet4, Itaru Endo3, Robert M. Hoffman1.
  • 学会等名: AACR
  • 発表場所: San Diego, USA
• [学会発表] Efficacy of neoadjuvant chemotherapy in combination with fluorescence-guided surgery on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) (2014)
  • 著者名/発表者名: Yukihiko Hiroshima1, Ali Maawy1, Yong Zhang1, Sho Sato2, Takashi Murakami2, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama2, Takashi Chishima2, Kuniya Tanaka2, Michael Bouvet3, Itaru Endo2, Robert M. Hoffman1.
  • 学会等名: AACR
  • 発表場所: San Diego, USA
• [学会発表] UVC irradiation in combination with fluorescence-guided surgery cures metastatic human pancreatic cancer in orthotopic mouse models (2014)
  • 著者名/発表者名: Yukihiko Hiroshima1, Ali Maawy2, Sho Sato3, Takashi Murakami3, Mako Yamamoto1, Fuminari Uehara1, Shinji Miwa1, Shuya Yano1, Masashi Momiyama3, Takashi Chishima3, Kuniya Tanaka3, Michael Bouvet4, Itaru Endo3, Robert M. Hoffman1.
  • 学会等名: AACR
  • 発表場所: San Diego, USA
• [学会発表] Salmonella typhimurium A1-R effectively targets human-patient pancreatic tumorgrafts in nude mice (2013)
  • 著者名/発表者名: Ming Zhao, Matthew H. G. Katz, Jason B. Fleming, Atsushi Suetsugu, Yong Zhang, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman, Yukihiko Hiroshima
  • 学会等名: ASCO annual meeting
  • 発表場所: Chicago, IL
• [学会発表] Salmonella typhimurium A1-R targets chemoresistant stem-like human pancreatic cancer cells (2013)
  • 著者名/発表者名: Yukihiko Hiroshima, Ming Zhao, Yong Zhang, Ali Maawy, Mohamed K. Hassanein, Atsushi Suetsugu, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • 学会等名: ASCO annual meeting
  • 発表場所: Chicago, IL
• [学会発表] Efficacy of Salmonella typhimurium A1-R on chemoresistant stem-like human pancreatic cancer cells (2013)
  • 著者名/発表者名: Yukihiko Hiroshima, Ming Zhao, Yong Zhang, Ali Maawy, Mohamed Hassanein, Atsushi Suetsugu, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • 学会等名: AACR annual meeting
  • 発表場所: Washington, DC
• [学会発表] Fluorescence-guided surgery for human-patient colon cancer tumorgrafts using a fluorophore-conjugated anti-CEA antibody (2013)
  • 著者名/発表者名: Yukihiko Hiroshima, Ali Maawy, Yong Zhang, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • 学会等名: AACR annual meeting
  • 発表場所: Washington, DC
• [学会発表] Tumor-educated macrophages promote proliferation of human pancreatic cancer cells in vitro and in vivo (2013)
  • 著者名/発表者名: Yukihiko Hiroshima, Masashi Momiyama, Mohamed Hassanein, Ali Maawy, Rhiana Menen, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • 学会等名: AACR annual meeting
  • 発表場所: Washington, DC
• [学会発表] Efficacy of Salmonella typhimurium A1-R treatment on human patient pancreatic tumorgrafts (2013)
  • 著者名/発表者名: Yukihiko Hiroshima, Ming Zhao, Matthew H.G. Katz, Jason B. Fleming, Atsushi Suetsugu, Yong Zhang, Ali Maawy, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman
  • 学会等名: AACR annual meeting
  • 発表場所: Washington, DC
• [学会発表] Efficacy of Salmonella typhimurium A1-R on chemoresistant stem-like human pancreatic cancer cells (2013)
  • 著者名/発表者名: Hiroshima Yukihiko
  • 学会等名: AACR annual meeting
  • 発表場所: U.S.A., Washington, DC
• [学会発表] Fluorescence-guided surgery for human-patient colon cancer tumorgrafts using a fluorophore-conjugated anti-CEA antibody (2013)
  • 著者名/発表者名: Hiroshima Yukihiko
  • 学会等名: AACR annual meeting
  • 発表場所: U.S.A., Washington, DC
• [学会発表] Tumor-educated macrophages promote proliferation of human pancreatic cancer cells in vitro and in vivo (2013)
  • 著者名/発表者名: Hiroshima Yukihiko
  • 学会等名: AACR annual meeting
  • 発表場所: U.S.A., Washington, DC
• [学会発表] Efficacy of Salmonella typhimurium A1-R treatment on human patient pancreatic tumorgrafts (2013)
  • 著者名/発表者名: Hiroshima Yukihiko
  • 学会等名: AACR annual meeting
  • 発表場所: U.S.A., Washington, DC
• [学会発表] Collapsin response mediator protein 4 promotes tumor cell invasion and lethality of pancreatic cancer (2012)
  • 著者名/発表者名: Yukihiko Hiroshima, Fumio Nakamura, Hiroshi Miyamoto, Ryutaro Mori, Koichi Taniguchi, Ryusei Matsuyama, Kazuhisa Takeda, Hirotoshi Akiyama, Kuniya Tanaka, Yasushi Ichikawa, Yoji Nagashima, Yoshio Goshima, Itaru Endo
  • 学会等名: AACR annual meeting
  • 発表場所: Chicago, IL
• [学会発表] Collapsin Response Mediator Protein 4 Promotes Tumor Cell Invasion and Lethality of Pancreatic Cancer (2012)
  • 著者名/発表者名: 廣島 幸彦
  • 学会等名: AACR Annual Meeting 2012
  • 発表場所: アメリカ、シカゴ
• [備考]
  • URL: http://www.ycusurg2.jp/index.html