The improvement of therapy-resistance with modified new virus and application to the treatment in pancreatic cancer

• Project/Area Number: 25462119
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: EGAMI Takuya 九州大学, 医学(系)研究科(研究院), 共同研究員 (40507787)
• Co-Investigator(Kenkyū-buntansha): MIZUMOTO Kazuhiro 九州大学, 大学病院, 准教授 (90253418) ; NAKATA Kohei 九州大学, 大学病院, 特別教員 (30419569)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膵癌 / 治療耐性 / ウイルス / レンチウイルス / calpeptin / ramininα4 / MAL2遺伝子 / Nodal / HDAC1 / Sainomycin / Pirfenidone / S100A4 / ポックスウイルス

Outline of Final Research Achievements

We investigated the factors which were involved in the radioresistance and anticancer drug resistance in pancreatic cancer in order to create a foundation for modifying the new viral vectors.
First, we found that S100A4 mRNA expression may predict radioresistance of pancreatic cancer cells and may play an important role in the poor response of pancreatic cancer cells to radiation therapy. Furthermore, we found that the antifibrotic agent, pirfenidone could be promising agents targeting desmoplasia by suppression of PSCs and production of growth factors and stromal components related to tumor-stromal interactions.

Research Products

• [Journal Article] CD146 attenuation in cancer-associated fibroblasts promotes pancreatic cancer progression. (2015)
  • Author(s): Zheng B, ohuchida K, Chijiiwa Y, Zhao M, Mizuuchi Y, Cui L, Horioka K, Ohtsuka T, Mizumoto K, Oda Y, Hashizume M, Nakamura M, Tanaka M
  • Journal Title: Mol Carcinog Volume: - Issue: 11 Pages: 1560-1572
  • DOI: 10.1002/mc.22409
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] MAL2 expression predicts distant metastasis and short survival in pancreatic cancer (2013)
  • Author(s): D．Eguchi, et,al
  • Journal Title: Surgery Volume: 154 Issue: 3 Pages: 573-582
  • DOI: 10.1016/j.surg.2013.03.010
  • Peer Reviewed
• [Journal Article] S100A4 mRNA expression level is a predictor of radioresistance of pancreatic cancer cells (2013)
  • Author(s): S. Kozono, et al
  • Journal Title: Oncol Rep Volume: 30 Issue: 4 Pages: 1601-1608
  • DOI: 10.3892/or.2013.2636
  • Peer Reviewed
• [Journal Article] Pirfenidone inhibits desmoplasia of pancreatic cancer by regulating stellate cells. (2013)
  • Author(s): Shingo Kozono, Kenoki Ohuchida, Daiki Eguchi, Naoki Ikenaga, Kenji Fujiwara, Ming Zhao, Lin Cui, Koji Shindo, Kazuhiro Mizumoto, and Masao Tanaka
  • Journal Title: Cancer Research Volume: 73 Issue: 7 Pages: 2345-2356
  • DOI: 10.1158/0008-5472.can-12-3180
  • Peer Reviewed
• [Presentation] 膵癌におけるNodal発現の特徴とその臨床的意義
  • Author(s): 小薗真吾、他
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡
• [Presentation] 膵癌細胞株におけるHiston deacetylase1の放射線耐性に関する評価
  • Author(s): 田中友晴、他
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡
• [Presentation] The effect of salinomycin on pancreatic cancer cell invasion and migration
  • Author(s): 趙茗、他
  • Organizer: 第113回日本外科学会定期学術集会
  • Place of Presentation: 福岡
• [Presentation] The development of pancreatic cancer therapy based on regulating pancreatic cancer desmoplasia by targeting pancreatic Stellate Cells
  • Author(s): S. Kozoo, et al
  • Organizer: International Pancreatic Research Forum 2013
  • Place of Presentation: 日本