Shiba Hiroaki, Okamoto Tomoyoshi, Futagawa Yasuro, Misawa Takeyuki, Yanaga Katsuhiko, Ohashi Toya, Eto Yoshikatsu
Department of Surgery, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.
J Surg Res. 2006 Jun 15;133(2):193-6. doi: 10.1016/j.jss.2005.10.023.
When gene therapy is performed for malignant tumors, gene transfer efficiency and selectivity are extremely important. The delivery of anticancer agents and embolic agents through tumor feeding artery is known as transarterial embolization. We speculated that genes might be efficiently and selectively transferred to hepatocellular carcinomas (HCCs) by degradable starch microspheres (DSM) as the embolic agent, which could be trapped within the tumor and release a gene vector. Therefore, we studied the use of DSM for adenovirus vector-mediated gene transfer to HCC in vivo.
HCC was induced in rats with diethylnitrosamine and phenobarbital, after which either AxCALacZ and DSM or AxCALacZ alone was injected through the hepatic artery.
Histological examination revealed that beta-galactosidase expression was greater (P < 0.001), and more selective (P < 0.001) in tumors after injection of AxCALacZ and DSM, than after injection of the vector alone.
Injection of DSM together with an adenovirus vector through the hepatic artery can result in efficient and cancer-selective transfer of genes to HCC.
当对恶性肿瘤进行基因治疗时，基因转移效率和选择性极其重要。通过肿瘤供血动脉递送抗癌剂和栓塞剂被称为经动脉栓塞。我们推测，可降解淀粉微球（DSM）作为栓塞剂可能会将基因有效且选择性地转移至肝细胞癌（HCC），其可滞留在肿瘤内并释放基因载体。因此，我们研究了DSM在体内用于腺病毒载体介导的基因转移至HCC的情况。
用二乙基亚硝胺和苯巴比妥诱导大鼠发生HCC，之后通过肝动脉注射AxCALacZ和DSM或仅注射AxCALacZ。
组织学检查显示，注射AxCALacZ和DSM后，肿瘤中的β-半乳糖苷酶表达更高（P < 0.001）且更具选择性（P < 0.001），比仅注射载体后更高。
通过肝动脉将DSM与腺病毒载体一起注射可实现基因向HCC的高效且癌症选择性转移。
