Role of autophagy in the chemoresistance in pancreatic cancer

• Project/Area Number: 22591524
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: OHTSUKA Takao 九州大学, 大学病院, 助教 (20372766)
• Co-Investigator(Kenkyū-buntansha): MIYASAKA Yoshihiro 九州大学, 医学研究院, 共同研究員 (40507795) ; MIZUMOTO Kazuhiro 九州大学, 大学病院, 准教授 (90253418) ; TSUTSUMI Kohsuke 九州大学, 医学研究院, 共同研究員 (00467937)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 膵癌 / オートファジー / 薬剤耐性 / 遺伝子治療 / ASC

Research Abstract

Autophagy has been recently identified as a new mechanism to maintain protein degradation, and lots of efforts have been made to clarify this complicated mechanism. The mains of this study were to investigate the roles of autophagy in biological behavior and chemoresistance in pancreatic cancer, and to show the possibility of autophagy for the application of the treatment of pancreatic cancer. Salinomycin decrease cell viability in pancreatic cancer cell lines in dose- and time-dependent manner, and also induced autophagy. Salinomycin decreased expression levels of Akt and mTOR, regulators of tumor progression, and induced apoptosis. Taken together, autophagy would increase chemo-sensitivity and might be applicable for the treatment of pancreatic cancer.

Research Products

• [Journal Article] Targeting the hedgehog signaling pathway with complementary peptides to Patched-1 (2012)
  • Author(s): Nakamura M, Ohtsuka T, et al
  • Journal Title: J Gastroenterol Volume: 47(4) Pages: 452-460
  • Peer Reviewed
• [Journal Article] MicroRNA-10a is overexpressed in human pancreatic cancer and involved in its invasiveness partially via suppression of the HOXA1 gene (2012)
  • Author(s): Ohuchida K, Ohtsuka T, et al
  • Journal Title: Ann Surg Oncol Volume: 19(7) Pages: 2394-2402
  • Peer Reviewed
• [Journal Article] Pancreatic cancer cells enhance the ability of collagen internalization via epithelial-mesenchymal transition (2012)
  • Author(s): Ikenaga N, Ohtsuka T, e al
  • Journal Title: Plos One Volume: 7(7)
  • Peer Reviewed
• [Journal Article] Claudin-4 expression predicts survival in pancreatic ductal adenocarcinoma (2012)
  • Author(s): Tsutsumi K, Ohtsuka T, e al
  • Journal Title: Ann Surg Oncol Volume: 19 Pages: 491-499
  • Peer Reviewed
• [Journal Article] CD271+ subpopulation of pancreatic stellate cells correlates with prognosis of ancreatic cancer and is regulated by interaction with cancer cells (2012)
  • Author(s): Fijiwara K, Ohtsuka T, e al
  • Journal Title: Plos One Volume: 7(12)
  • Peer Reviewed
• [Journal Article] Targeting the hedgehog signaling pathway with complementary (2012)
  • Author(s): Nakamura M
  • Journal Title: Journal of Gastroenterology Volume: 47 Issue: 4 Pages: 452-460
  • DOI: 10.1007/s00535-011-0507-6
• [Journal Article] MicroRNA-10a is Overexpressed in Human Pancreatic Cancer and Involved in Its Invasiveness Partially via Suppression of the HOXA1 Gene (2012)
  • Author(s): Ohuchida K, Mizumoto K, Lin C, Yamaguchi H, Ohtsuka T, Sato N, Toma H, Nakamura M, Nagai E, Hashizume M, Tanaka M.
  • Journal Title: Ann Surg Oncol Volume: 19(7) Issue: 7 Pages: 2394-2402
  • DOI: 10.1245/s10434-012-2252-3
  • Peer Reviewed
• [Journal Article] Pancreatic cancer cells enhance the ability of collagen internalization via epithelial-mesenchymal transition. (2012)
  • Author(s): Ikenaga N
  • Journal Title: Plos One Volume: 7 Issue: 7 Pages: 491-499
  • DOI: 10.1371/journal.pone.0040434
  • Peer Reviewed
• [Journal Article] CD271^+ subpopulation of pancreatic stellate cells correlates with prognosis of pancreatic cancer and is regulated by interaction with cancer cells (2012)
  • Author(s): Kenji Fujiwara
  • Journal Title: PLoS One Volume: 12 Issue: 12 Pages: e52682-e52682
  • DOI: 10.1371/journal.pone.0052682
  • Peer Reviewed
• [Journal Article] High EGFR expression is a prognostic factor for reduced survival in pancreatic cancer after gemcitabine-based adjuvant chemotherapy (2011)
  • Author(s): Fujita H, Ohtsuka T, et al
  • Journal Title: Int J Oncol Volume: 38 (3) Pages: 629-641
  • Peer Reviewed
• [Journal Article] Adenoviral therapy is more effective in gemcitabine- resistant pancreatic cancer than gemcitabine-sensitive cells (2011)
  • Author(s): Yasui T, Ohtsuka T, et al
  • Journal Title: Anticancer Res Volume: 31(4) Pages: 1279-1287
  • Peer Reviewed
• [Journal Article] Predicting the chemosensitivity of pancreatic cancer cells by quantifying the expression levels of genes associated with the metabolism of gemcitabine and 5-fluorouracil (2011)
  • Author(s): Kurata N, Ohtsuka T, et al
  • Journal Title: Int J Oncol Volume: 39 (2) Pages: 473-482
  • Peer Reviewed
• [Journal Article] MicroRNA expression as a predictive marker for gemcitabine response after surgical resection of pancreatic cancer (2011)
  • Author(s): Ohuchida K, Ohtsuka T et al
  • Journal Title: Ann Surg Oncol Volume: 18(8) Pages: 2381-2387
  • Peer Reviewed
• [Journal Article] Claudin-4 Expression Predicts Survival in Pancreatic Ductal Adenocarcinoma (2011)
  • Author(s): Tsutsumi K, et al
  • Journal Title: Ann Surg Oncol Volume: (in press)(未定) Issue: S3 Pages: 491-499
  • DOI: 10.1245/s10434-011-1970-2
  • Peer Reviewed
• [Journal Article] High EGFR expression is a prognostic factor for reduced survival in pancreatic cancer after gemcitabine-based adjuvant chemotherapy (2011)
  • Author(s): Fujita H, Ohtsuka T, et al
  • Journal Title: International Journal of Oncology Volume: 38(3) Pages: 629-641
  • Peer Reviewed
• [Journal Article] Adenoviral therapy is more effective in gemcitabine-resistant pancreatic cancer than in gemcitabine-sensitive cells (2011)
  • Author(s): Yasui T, Ohtsuka T, et al
  • Journal Title: Anticancer Reserch Volume: 31(4) Pages: 1279-1287
  • Peer Reviewed
• [Journal Article] Predicting the chemosensitivity of pancreatic cancer cells by quantifying the expression levels of genes associated with the metabolism of gemcitabine and 5-fluorouracil (2011)
  • Author(s): Kurata N, Ohtsuka T, et al
  • Journal Title: International Journal of Oncology Volume: 39(2) Pages: 473-482
  • Peer Reviewed
• [Journal Article] MicroRNA expression as a predictive marker for gemcitabine response after surgical resection of pancreatic cancer (2011)
  • Author(s): Ohuchida K, Ohtsuka T, et al
  • Journal Title: Annals of Surgical Oncology Volume: 18(8) Pages: 2381-2387
  • Peer Reviewed
• [Presentation] 膵癌に対する放射線治療とgemcitabine治療の交叉耐性についての検討 (2012)
  • Author(s): 赤川進、大内田研宙、大塚隆生
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 千葉
  • Year and Date: 2012-04-12
• [Presentation] ゲムシタビン耐性がアデノウイルスベクターを用いた治療に与える影響 (2011)
  • Author(s): 安井隆晴、大塚隆生
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 東京
• [Presentation] ゲムシタビン耐性がアデノウイルスベクターを用いた治療に与える影響 (2011)
  • Author(s): 安井隆晴、大塚隆生, ほか
  • Organizer: 第111回日本外科学会定期学術集会
  • Place of Presentation: 東京(招待講演)(紙上開催)
• [Presentation] 膵癌に対する放射線治療とgemcitabine治療の交叉耐性についての検討
  • Author(s): 赤川 進
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 千葉