@article{oai:kanazawa-u.repo.nii.ac.jp:00013383,
 author = {Kakinoki, Kaheita and Nakamoto, Yasunari and Kagaya, Takashi and Tsuchiyama, Tomoya and Sakai, Yoshio and Nakahama, Tohru and Mukaida, Naofumi and Kaneko, Shuichi},
 issue = {12},
 journal = {Journal of Gene Medicine},
 month = {Dec},
 note = {The prognosis of patients with hepatocellular carcinoma (HCC) remains poor, largely as a result of intrahepatic metastasis. Using a mouse model of intrahepatic metastasis, we investigated whether chemokine ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) could potentiate the antitumor effects of the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system.Methods: Mouse hepatoma cells infected with recombinant adenovirus vectors expressing HSV-tk, CCL2/MCP-1 and LacZ at multiplicities of infection of Ad-tk/Ad-MCP1 = 3/0.03 (T/MLow), 3/3 (T/MHigh) and Ad-tk/Ad-LacZ = 3/3 (T/L) were injected into BALB/c mice.Results: Intrahepatic tumor growth was significantly lower in T/MLow mice. By contrast, no tumor suppression was observed in T/MHigh mice. The tumor-specific cytolytic activities of splenocytes from T/MLow and T/MHigh mice were comparable. Immunohistochemical analysis of liver tissues showed similar infiltration by Mac-1+ and T cells in these animals, whereas the proportions of classical activated (M1) monocytes/macrophages were significantly higher in T/MLow mice. In addition, interleukin-12 production was elevated in these tissues. Vascular endothelial growth factor-A expression and CD31+ microvessels were increased in T/MHigh mice.Conclusions: Collectively, these results demonstrate that an adequate amount of CCL2/MCP-1, together with the HSV-tk/GCV system, may induce T helper 1-polarized antitumor effects without inducing tumor angiogenesis in the microenvironment of intrahepatic HCC progression. © 2010 John Wiley & Sons, Ltd., 金沢大学医薬保健研究域医学系},
 pages = {1002--1013},
 title = {Prevention of intrahepatic metastasis of liver cancer by suicide gene therapy and chemokine ligand 2/monocyte chemoattractant protein-1 delivery in mice},
 volume = {12},
 year = {2010}
}