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

受损腹膜易发生肿瘤种植和转移。易感性的原因之一是创伤组织中产生了HGF。创伤会导致炎症、血管生成和肉芽组织。1.建立肝细胞生长因子拮抗剂和生物凝胶膜对胆管癌细胞移植和转移的保护作用。2.创伤后5d，组织中HGF mRNA被激活，但不能确定产生HGF的细胞的性质。3.胆囊癌细胞株GB-d 1表达HGF受体，并对外源性HGF有反应，而其他恶性腹水来源的癌细胞则不表现出创伤部位特异性。4.覆盖癌细胞伤口保护转移的生物凝胶膜(透明质酸、氧化纤维素)。透明质酸盐膜在伤后近7天内消失，不影响伤口愈合过程。5.携带HGF拮抗剂(HGF/NK4)基因的腺病毒可抑制腹膜损伤部位的转移。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.免疫组织化学方法检测创面血管生成，但未检测到明显抑制肿瘤血管生成。

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.