Specific Gene Therapy for Pancreatic Cancer

胰腺癌特异性基因治疗

• 批准号: 10470236
• 负责人: KATOH Hiroyuki
• 金额: $ 8.06万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470236/
• 关键词: CEA promoter; Pancreatic Cancer; Cancer Gene Therapy; N116Y; Vector

In pancreatic cancer, the mutation of c-K-ras is a critical event of tumor growth and meastasis. We have previously demonstrated a dominant negative effect of N116Y on the growth of pancreatic cancer cells. To evaluate the potential of N116Y for suppressing the metastatic growth of pancreatic tumor cells, we made a replication-deficient recombinant N116Y adenovirus driven by the carcinoembryonic antigen (CEA) promoter (Ad CEA-N116Y). We demonstrated that the expression of N116Y, growth inhibition, and apoptotic death induction were all specific to pancreatic cancer cell lines (PCI-35 and PCI-43) that were promoter positive, whereas no growth retardation was observed in human embrynic pancreas-derived cell line 1C3D3 after Ad CEA-N116Y infection. We examined the effect of Ad CEA-N116Y on the metastatic growth of PCI-43 colonies in liver, which were generated by tumor injection into the spleen of nude mice. The results showed that Ad CEA-N116Y effectively reduced the number of metastatic colonies without any complication by injecting intrasplenically five days after tumor cell inoculation. Thus N116Y can selectively suppress the metastatic growth of pancreatic tumor cell by using the CEA promoter driven adenovirus vector indicating the N116Y gene therapy may be potentially useful for the treatment of pancreatic cancer patients with liver micrometastasis.

在胰腺癌中，C-K-RAS的突变是肿瘤生长和MEASTASIS的关键事件。以前，我们已经证明了N116Y对胰腺癌细胞生长的主要负面影响。为了评估N116Y在抑制胰腺肿瘤细胞转移性生长的潜力，我们制造了由致癌症抗原抗原（CEA）启动子（AD CEA-N116Y）驱动的缺乏复制的重组N116Y腺病毒。我们证明，N116Y，生长抑制和凋亡死亡诱导的表达均针对胰腺癌细胞系（PCI-35和PCI-43），它们呈启动子呈阳性，而在Ad Cea-n116y感染后，在人类胚胎胰腺中1C3D3中未观察到生长延迟。我们检查了AD CEA-N116Y对肝脏PCI-43菌落转移的影响，这些菌落是由肿瘤注射到裸鼠脾脏中产生的。结果表明，AD CEA-N116Y有效地减少了转移菌落的数量，而不会在肿瘤细胞接种后五天内注射脑内部，而没有任何并发​​症。因此，N116Y可以使用CEA启动子驱动的腺病毒载体有选择地抑制胰腺肿瘤细胞的转移性生长，表明N116Y基因治疗可能对治疗胰腺癌患者的治疗可能有用。

项目成果

Tomoyuki Yano, et al.: "Hepatoid adenocarcinoma of the pancreas"Histopathology. 35. 90-92 (1999)

Tomoyuki Yano 等：“胰腺肝样腺癌”组织病理学。

Yomoyuki Yano et al.: "Hepatoid adenocarcinoma of the pancreas"Histopathology. 35. 90-02 (1999)

Yomoyuki Yano 等：“胰腺肝样腺癌”组织病理学。

Katsunori Saito,et al.: "INTERLEUKIN-6 PRODUCED BY PANCREATIC CARCINOMA CELLS ENHANCES HUMORAL IMMUNE RESPONSES AGAINST TUMOR CELLS:A POSSIBLE EVENT IN TUMOR REGRESSION." International Journal of Cancer. 75. 284-289 (1998)

Katsunori Saito 等人：“胰腺癌细胞产生的 INTERLEUKIN-6 增强了针对肿瘤细胞的体液免疫反应：肿瘤消退中的一个可能事件。”

Hiroyuki Katoh.: "Analysis of metastasis of pancreatic cancer."Medical Journal. 351 (1998)

Hiroyuki Katoh.：“胰腺癌转移分析。”医学杂志。

Hida Y, Morita T, Fujita M, Miyasaka Y, Horita S, Fujioka Y, Nagashima K, Katoh H.: "Clinical significance of hepatocyte growth factor and c-Met expression in extrahepatic biliary tract cancers."Oncology Report. 6. 1051-1056 (1999)

Hida Y、Morita T、Fujita M、Miyasaka Y、Horita S、Fujioka Y、Nagashima K、Katoh H.：“肝外胆道癌中肝细胞生长因子和 c-Met 表达的临床意义。”肿瘤学报告。