HGF antagonist (HGF/NK4) gene therapy for pancreatobiliary cancer.

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14571248
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Fukuoka University
• Principal Investigator: SHIMURA Hideo Fukuoka University, School of Medicine, Associate Professor, 医学部, 助教授 (80178996)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Hiroshi Fukuoka University, School of Medicine, Assistant, 医学部, 助手 (60309911) ; MATSUO Katsuichi Fukuoka University, School of Medicine, Assistant, 医学部, 助手 (60341442) ; IKEDA Seiyo Fukuoka University, School of Medicine, Professor, 医学部, 教授 (40038758)
• Project Period (FY): 2002 – 2003
• Keywords: gallbladder cancer / hepatocyte growth factor / antagonist / adenovirus / metastasis / wound healing / hyaluronate film / gene therapy

Research Abstract

Injured peritoneum is susceptible for cancer implantation and metastasis. One reason of the susceptibility is HGF production in the wounded tissue. The wounding causes inflammation, angiogenesis and granulation tissue. 1. We established a model of the metastasis in the wounded site, and examined the protection of implantation and metastasis of the biliary cancer cells by HGF antagonist and the biogel film. 2. HGF mRNA was stimulated in the tissue for 5 days after wounding, but the nature of cells producing HGF could not be determined. 3. A gallbladder cancer cell line, GB-d 1, expressed HGF receptor and responded to extrinsic HGF, but other cancer cells derived from malignant ascites did not show the wound-site specificity. 4. Biogel membranes (hyaluronic acid, oxidated cellulose) covering the wound protected metastasis of the cancer cells. The hyaluronate membrane disappeared within almost 7 days after the wounding and did not disturb wound healing processes. 5. Adenovirus carrying HGF antagonist (HGF/NK4) gene suppressed metastasis in the wounded site of the peritoneum. Substantial amount of antagonist was detected both in cancer cells and peritoneal mesothelial cells in vitro. 6. Angiogenesis in the wounded sites was examined by immunohistochemical methods, but the apparent suppression of tumor angiogenesis was not detected.

Research Products

• [Publications] T Sasaki, H Shimura, T Tanaka, K Nakashima, K Matsuo, S Ikeda: "Protection of Trocar Sites from Gallbladder Cancer Implantation by Sodium Hyaluronate Carboxymethylcellulose-Based Bioresorbable Membrane (Seprafilm) in a Murine Madel."Surgical Endoscopy. 18・2. 246-251 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] T Sasaki, H Shimura, T Tanaka, K Nakashima, K Matsuo, S Ikeda: "Protection of Trocar Sites from Gallbladder Cancer Implantation by physically covering the sites in a Murine Model."International Surgery. (in press). (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Tanaka T., Shimura H, Sasaki T, Narumi K, Maemondo M, Nukiwa T, Matsumoto K, Nakamura T, Ikeda S: "Gollbladder cancer treatment using adenovirus expressing the HGF/NK4 gene in a peritoneal implantation model."Cancer Gene Therapy. April 30. (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sasaki T, Sasahira T, Shimura H, Ikeda S, Kuniyasu H: "Effect of Nma on growth inhibition by TGF-beta in haman gastric carcinoma cell lines"Oncology Report. 11. 1219-1223 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Sasaki T, Sasahira, T, Shimura H, Ikeda S, Kuniyasu: "Effect of human Noxa on irinotecan-induced apoptosis in human gastric carcinoma cell lines"Hepato-gastroenterology. 51. 912-915 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takehara, N., Shimura, H., Miyazaki, R., Sasaki, T., Maeshiro, K., Ikeda, S.: "Relationship between the shape and patency of accessory pancreatic Santorini's duct revealed by a balloon endoscopic retrograde pancreatography compression study."Digestive Endoscopy. 16・2. 129-133 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takamitsu Sasaki, Hideo Shimura, Toshihiro Tanaka, Keisuke Nakashima, Katsuichi Matsuo, Seiyo Ikeda.: "Protection of Trocar Sites from Gallbladder Cancer Implantation by Sodium Hyaluronate Carboxymethylcellulose-Based Bioresorbable Membrane (Seprafilm^【○!R】) in a Murine Model."Surgical Endosc.. 18(2). 246-251 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takamitsu Sasaki, Hideo Shimura, Toshihiro Tanaka, Keisuke Nakashima, Katsuichi Matsuo, Seiyo Ikeda.: "Protection of Trocar Sites from Gallbladder Cancer Implantation by physically covering the sites in a Murine Model."International Surgery. (in press). (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Tanaka T., Shimura H, Sasaki T, Narumi K, Maemondo M, Nukiwa T, Matsumoto K, Nakamura T, Ikeda S.: "Gallbladder cancer treatment using adenovirus expressing the HGF/NK4 gene in a peritoneal implantation model."Cancer Gene Therapy. Apr 30(Epub ahead of print). (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sasaki T, Sasahira T, Shimura H, Ikeda 5, Kuniyasu H.: "Effect of Nma on growth inhibition by TGF-β in human gastric carcinoma cell lines."Oncology reports. 11. 1219-1223 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Sasaki T, Sasahira, T, Shimura H, Ikeda S, Kuniyasu H.: "Effect of human Noxa on irinotecan-induced apoptosis in human gastric carcinoma cell lines"Hepato-gastroenterology. 51. 912-915 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takehara, N., Shimura, H., Miyazaki, R., Sasaki, T., Maeshiro, K., Ikeda, S.: "Relationship between the shape and patency of accessory pancreatic Santorini's duct revealed by a balloon endoscopic retrograde pancreatography compression study."Digestive Endoscopy. 16(2). 129-133 (2004)
  • Description: 「研究成果報告書概要(欧文)」より