Breakthrough in the mechanism of adenoviral gene delivery and new developments to apply the achievement in a clinical setting

• Project/Area Number: 21791298
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Kyushu University
• Principal Investigator: EGAMI Takuya Kyushu University, 医学研究院 (40507787)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 膵臓外科学 / 膵癌 / ウイルス治療

Research Abstract

We revealed that the efficacy of adenoviral therapy was enhanced with combination chemotherapy or radiation. We found that the efficiency of adenoviral therapy in radiation resistant cancer cells was lower than that in radiation sensitive cells, while the efficiency of adenoviral therapy in chemoresistant cancer cells was lower than that in chemosensitive cells. We also revealed that fibroblasts which constitute stroma weaken the efficacy of adenoviral therapy. Furthermore we figured out these mechanisms and identified the molecules responsible for the mechanisms. These data suggest that there are possibilities in adenoviral therapy for individual by evaluating the molecules responsible for adenoviral infection and uptake with respect to each case.

Research Products

• [Journal Article] Tumor-stroma interactions reduce the efficacy of adenoviral therapy through the HGF-MET pathway. (2011)
  • Author(s): Yasui T, Ohuchida K, Zhao M, Onimaru M, Egami T, Fujita H, Ohtsuka T, Mizumoto K, Tanaka M
  • Journal Title: Cancer Sci. 102 Pages: 484-491
  • NAID: 10029290639
• [Journal Article] Tumor-stroma interactions reduce the efficacy of adenoviral therapy through the HGF-MET pathway. (2011)
  • Author(s): Yasui T, Egami T, et al.
  • Journal Title: Cancer Science Volume: 102 Pages: 484-491
  • NAID: 10029290639
  • Peer Reviewed
• [Journal Article] Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer. (2010)
  • Author(s): Manabu Onimaru, Kenoki Ohuchida, Eishi Nagai, Kazuhiro Mizumoto, Takuya Egami, Lin Cui, Norihiro Sato, Junji Uchino, Koichi Takayama, Makoto Hashizume, Masao Tanaka
  • Journal Title: Cancer Lett 294 Pages: 178-186
• [Journal Article] Gemcitabine synergistically enhances the effect of adenovirus gene therapy through activation of the CMV promoter in pancreatic cancer cells. (2010)
  • Author(s): Onimaru M, Ohuchida K, Egami T, Mizumoto K, Nagai E, Cui L, Toma H, Matsumoto K, Hashizume M, Tanaka M,
  • Journal Title: Cancer Gene Ther. 17 Pages: 541-549
• [Journal Article] Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer. (2010)
  • Author(s): Onimaru M, Egami T, et.al.
  • Journal Title: Cancer gene therapy Volume: 17 Pages: 541-549
  • Peer Reviewed
• [Journal Article] Gemcitabine synergistically enhances the effect of adenovirus gene therapy through activation of the CMV promoter in pancreatic cancer cells. (2010)
  • Author(s): Onimaru M, Egami T, et at
  • Journal Title: Cancer Letter Volume: 294 Pages: 178-186
  • Peer Reviewed
• [Journal Article] Chemotherapeutic agents potentiate adenoviral gene therapy for pancreatic cancer. (2009)
  • Author(s): Takuya Egami, Kenoki Ohuchida, Kazuhiro Mizumoto, Manabu Onimaru, Hiroki Toma, Shoko Nishio, Eishi Nagai, Kunio Matsumoto, Toshikazu Nakamura, Masao Tanaka
  • Journal Title: Cancer Sci. 100 Pages: 722-729
  • NAID: 10025144686
• [Journal Article] Up-regulation of integrin beta3 in radioresistant pancreatic cancer impairs adenovirus-mediated gene therapy. (2009)
  • Author(s): Takuya Egami, Kenoki Ohuchida, Takaharu Yasui, Kazuhiro Mizumoto, Manabu Onimaru, Hiroki Toma, Norihiro Sato, Kunio Matsumoto, Masao Tanaka
  • Journal Title: Cancer Sci. 100 Pages: 1902-1907
• [Journal Article] hTERT-promoter-dependent oncolytic adenovirus enhances the transduction and therapeutic efficacy of replication-defective adenovirus vectors in pancreatic cancer cells. (2009)
  • Author(s): Onimaru Manabu, Ohuchida Kenoki, Mizumoto Kazuhiro, Nagai Eishi, Cui Lin, Toma Hiroki, Takayama Koichi, Matsumoto Kunio, Hashizume Makoto, Tanaka Masao
  • Journal Title: Cancer Sci 101 Pages: 735-742
• [Journal Article] Adenoviral Therapy Is More Effective in Gemcitabine-resistant Pancreatic Cancer than in Gemcitabine-sensitive Cells.
  • Author(s): Takaharu Yasui, Kenoki Ohuchida, Ming Zhao, Lin Cui, Manabu Onimaru, Takuya Egami, Hayato Fujita, Takao Ohtsuka, Kazuhiro Mizumoto, Kunio Matsumoto, Masao Tanaka.
  • Journal Title: Anticancer research. in press
• [Presentation] Adenoviral therapy is more effective for gemcitabine resistant pancreatic cancer cells than in gemcitabine sensitive cells. (2010)
  • Author(s): Yasui T, et al.
  • Organizer: International Association of Pancreatology
  • Place of Presentation: FUKUOKA
  • Year and Date: 2010-07-12
• [Presentation] Adenoviral therapy is more effective for gemcitabine resistant pancreatic cancer cells than in gemcitabine sensitive cells (2010)
  • Author(s): Yasui T, et al
  • Organizer: International Association of Pancreatology
  • Place of Presentation: FUKUOKA
  • Year and Date: 2010-07-12
• [Presentation] 膵癌の線維芽細胞によるアデノウイルス導入効率の阻害効果 (2010)
  • Author(s): 安井隆晴、他
  • Organizer: 日本外科学会総会
  • Place of Presentation: 名古屋
• [Presentation] 制限増殖型アデノウイルスによるアデノウイルスベクター導入効率の増強効果作用 (2009)
  • Author(s): 鬼丸学, 他
  • Organizer: 日本外科学会総会
  • Place of Presentation: 福岡
• [Presentation] 抗癌剤併用によるアデノウイルスベクターの遺伝子発現促進作用 (2009)
  • Author(s): 江上拓哉, 他
  • Organizer: 日本外科学会総会
  • Place of Presentation: 福岡
• [Presentation] 放射線耐性膵癌細胞株におけるアデノウイルス遺伝子導入効率の検討 (2009)
  • Author(s): 江上拓哉, 他
  • Organizer: 日本膵臓学会総会
  • Place of Presentation: 東京