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

HGF 拮抗剂 (HGF/NK4) 基因治疗胰胆癌。

• 批准号: 14571248
• 负责人: SHIMURA Hideo
• 金额: $ 2.11万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571248/
• 关键词: gallbladder cancer; hepatocyte growth factor; antagonist; adenovirus; metastasis; wound healing; hyaluronate film; gene therapy; 膵胆道癌; HGFアンタゴニスト; 創傷冶癒; 高分子ゲル

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.

损伤的腹膜易发生癌的种植和转移。易感性的一个原因是受伤组织中HGF的产生。伤口引起炎症、血管生成和肉芽组织。1.建立胆管癌细胞创伤转移模型，观察HGF拮抗剂和明胶膜对胆管癌细胞种植和转移的保护作用。2.伤后5天，组织中的HGF mRNA被刺激，但不能确定产生HGF的细胞的性质。3.胆囊癌细胞系GB-d1表达HGF受体，并对外源性HGF有反应，但其他来源于恶性腹水的癌细胞不显示伤口部位特异性。4.生物凝胶膜（透明质酸，氧化纤维素）覆盖伤口保护癌细胞的转移。透明质酸盐膜在创伤后几乎7天内消失，并且不干扰伤口愈合过程。5.携带HGF拮抗剂（HGF/NK 4）基因的腺病毒可抑制腹膜损伤部位的转移。在体外培养的癌细胞和腹膜间皮细胞中均检测到大量的拮抗剂。6.通过免疫组织化学方法检测了创伤部位的血管生成，但未检测到肿瘤血管生成的明显抑制。

项目成果

Sasaki T, Sasahira T, Shimura H, Ikeda S, Kuniyasu H: "Effect of Nma on growth inhibition by TGF-beta in human gastric carcinoma cell lines"Oncology Report. (In press). (2004)

Sasaki T、Sasahira T、Shimura H、Ikeda S、Kuniyasu H：“Nma 对人胃癌细胞系中 TGF-β 生长抑制的影响”肿瘤学报告。

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 pri

Tanaka T.、Shimura H、Sasaki T、Narumi K、Maemondo M、Nukiwa T、Matsumoto K、Nakamura T、Ikeda S.：“在腹膜植入模型中使用表达 HGF/NK4 基因的腺病毒治疗胆囊癌。”癌症基因

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 Model."Surgical Endosc. (in p

T Sasaki、H Shimura、T Tanaka、K Nakashima、K Matsuo、S Ikeda：“在小鼠模型中使用基于透明质酸钠羧甲基纤维素的生物可吸收膜（Seprafilm）保护套管针部位免受胆囊癌植入。”外科内镜。

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

T Sasaki、H Shimura、T Tanaka、K Nakashima、K Matsuo、S Ikeda：“小鼠 Madel 中基于透明质酸钠羧甲基纤维素的生物可吸收膜 (Seprafilm) 保护套管针部位免受胆囊癌植入。”外科内窥镜检查。

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)

Tanaka T.、Shimura H、Sasaki T、Narumi K、Maemondo M、Nukiwa T、Matsumoto K、Nakamura T、Ikeda S：“在腹膜植入模型中使用表达 HGF/NK4 基因的腺病毒治疗胆囊癌。”癌症基因治疗