Adenoviral-mediated herpes simplex virus thymidine kinase gene transfer: Regression of hepatic metastasis of pancreatic tumors
Adenoviral-mediated herpes simplex virus thymidine kinase gene transfer: Regression of hepatic metastasis of pancreatic tumors
复制标题
DOI：
10.1097/00006676-199707000-00004
复制
发表时间：
1997-07-01
期刊：
影响因子：
2.9
通讯作者：
Woo, SLC
中科院分区：
文献类型：
--
作者：
Block, A;Chen, SH;Woo, SLC
胰腺癌是美国癌症死亡的第五大原因。大多数患者在就诊时有明显的转移或局部晚期疾病。手术切除不会显著改变临床结果。联合化疗诱导部分反应，但总生存率仍然很低。本研究的目的是评估腺病毒介导的自杀基因转导作为胰腺癌治疗方法的可行性。从鼠胰腺导管腺癌建立细胞系，并通过将胰腺癌细胞接种到左外侧肝叶中产生肝内肿瘤。在体外和体内表征转导效率。瘤内腺病毒注射联合腹腔注射更昔洛韦治疗肝内肿瘤。腺病毒介导的单纯疱疹病毒（HSV）-胸苷激酶（tk）基因表达后，更昔洛韦治疗是非常有效的抑制胰腺癌细胞的增殖在体外。在表达HSV-tk的细胞存在下，未转导细胞的增殖显著降低。胰腺癌细胞的肝内接种导致同基因受体中实体腺癌的成功形成。腺病毒RSV-tk注射的肿瘤，随后腹腔内更昔洛韦应用引起高度显着的肿瘤体积缩小和坏死。这些结果表明，转导HSV-tk基因后再用更昔洛韦对胰腺癌肝转移的生长抑制是高效的。
Pancreatic cancer is the fifth leading cause of cancer death in the United States. Most patients have obvious metastases or locally advanced disease at the time of presentation. Surgical resection does not significantly change the clinical outcome. Combination chemotherapy induces a partial response but overall survival remains low. The aim of this study was to evaluate the feasibility of adenovirus-mediated suicide gene transduction as a therapeutic approach for pancreatic cancer. A cell line was established from a murine pancreatic ductal adenocarcinoma and intrahepatic tumors were generated by inoculation of pancreatic cancer cells into the left lateral liver lobe. Transduction efficiency was characterized in vitro and in vivo. Intrahepatic tumors were treated by intratumoral adenovirus injection in combination with intraperitoneal administration of ganciclovir. Adenovirus-mediated herpes simplex virus (HSV)-thymidine kinase (tk) gene expression followed by ganciclovir treatment was highly efficient in inhibiting pancreatic cancer cell proliferation in vitro. The proliferation of nontransduced cells was significantly reduced in the presence of HSV-tk expressing cells. Intrahepatic inoculation of pancreatic cancer cells leads to successful formation of solid adenocarcinomas in syngeneic recipients. Ad.RSV-tk injection of the tumor followed by intraperitoneal ganciclovir application caused highly significant tumor volume reduction and necrosis. These results indicate that transduction of the HSV-tk gene followed by ganciclovir is highly efficient for growth inhibition of hepatic metastases of pancreatic carcinoma.