Tumor Specific Gene Therapy for Pancreatic Cancer

胰腺癌的肿瘤特异性基因治疗

• 批准号: 09557099
• 负责人: KATOH Hiroyuki
• 金额: $ 8.45万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557099/
• 关键词: Pancreatic Cancer; Cancer Gene Therapy; N116Y; Vector; 膵癌; 遺伝子治療; アデノウイルスペクター; RAS変異体; CEAプロモーター

The aim of this study is to assess whether N116Y can inhibit the proliferation of pancreatic cancer cell lines carrying K-ras mutations and cause reversion of the malignant phenotype. The growth inhibition activity of N116Y was evaluated by the colonyforming efficiency in selection medium. In order to examine the effect of N116Y on the neoplastic phenotype, we established N116Y-expressing clones and analyzed their growth ability in soft agar and tumorigenicity in nude mice. The growth of the eight pancreatic cancer cell lines was strongly inhibited by the transfection of pZIP-N116Y.Moreover, the N116Y-expressing clones became less spread and lost their anchorage-independent growth ability. Furthermore, they were nontumorigenic in vivo. N116Y significantly inhibits the growth of pancreatic cancer cell lines and causes reversion of the malignant phenotypes. These results suggest that N1I6Y may be a candidate gene for use in the gene therapy of pancreatic cancer.

本研究的目的是评估N116Y是否能抑制携带K-ras突变的胰腺癌细胞系的增殖，并导致恶性表型逆转。以菌落形成率为指标评价菌株N116Y的生长抑制活性。为了检测N116Y对肿瘤表型的影响，我们建立了表达N116Y的克隆，并对其在软琼脂中的生长能力和在裸鼠体内的成瘤性进行了分析。PZIP-N116Y对8株胰腺癌细胞株的生长有明显的抑制作用，并且表达N116Y的克隆细胞扩散较少，失去了非锚定生长能力。此外，它们在体内不会致癌。N116Y对胰腺癌细胞株的生长有明显的抑制作用，并使其恶性表型逆转。提示N1I6Y基因可能是胰腺癌基因治疗的候选基因。

项目成果

Toshiyuki Takahashi, et al.: "Predictive Factors for Long-term Survial in Patients with Pancreatic Carcinoma." Hepato-Gastroenterology. 44. 1463-1468 (1997)

Toshiyuki Takahashi 等人：“胰腺癌患者长期生存的预测因素”。

You Kawarada, and Hiroyuki Katoh, et al: "Inhibitory Effects of the Antiangiogenic Agent TNP-470 on Establishment and Growth of Hematogenous Metastasis of Human Pancreatic Carcinoma in SCID-Beige Mice In Vivo." Pancreas. 15. 251-257 (1997)

You Kawarada 和 Hiroyuki Katoh 等人：“抗血管生成剂 TNP-470 对 SCID 米色小鼠体内人胰腺癌血行转移的建立和生长的抑制作用”。

M.Takeuchi, N.Senmaru, T.Shichinohe, T.Takahashi, N.Kuzumaki, H.Katoh: "Growth in hibition of the pancreatic cancer cell lines induced by dominant negative H-ras mutant, N116Y using adenovirus vector" Cancer Gene Therapy. 4. 16 (1997)

M.Takeuchi、N.Senmaru、T.Shichinohe、T.Takahashi、N.Kuzumaki、H.Katoh：“使用腺病毒载体抑制显性失活 H-ras 突变体 N116Y 诱导的胰腺癌细胞系的生长”癌症基因

Toshiyuki Takahashi, and Hiroyuki Katoh, et al: "Predictive Factors for Long-term Survival in Patients with Pancreatic Carcinoma." Hepato-Gastroenterology. 44. 1463-1468 (1997)

Toshiyuki Takahashi 和 Hiroyuki Katoh 等人：“胰腺癌患者长期生存的预测因素”。

Toshiyuki Takahashi, Naoakira Niino, Hiroshi Ishikura, Shunichi Okushiba, Mitsuru Dohke, Hiroyuki Katoh: "Predictive Factors for Long-term Survival in Patients with Pancreatic Carcinoma" Hepato-Gastroenterology. 44. 1463-1468 (1997)

Toshiyuki Takahashi、Naoakira Niino、Hiroshi Ishikura、Shunichi Okushiba、Mitsuru Dohke、Hiroyuki Katoh：“胰腺癌患者长期生存的预测因素”肝胃肠病学。