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Prevention of intrahepatic metastasis of liver cancer by suicide gene therapy and chemokine ligand 2/monocyte chemoattractant protein-1 delivery in mice

フォーマット:
論文
責任表示:
Kakinoki, Kaheita ; Nakamoto, Yasunari ; Kagaya, Takashi ; Tsuchiyama, Tomoya ; Sakai, Yoshio ; Nakahama, Tohru ; Mukaida, Naofumi ; Kaneko, Shuichi
言語:
英語
出版情報:
Wiley-Blackwell, 2010-12-01
著者名:
Kakinoki, Kaheita
Nakamoto, Yasunari
Kagaya, Takashi
Tsuchiyama, Tomoya
Sakai, Yoshio
Nakahama, Tohru
Mukaida, Naofumi
Kaneko, Shuichi
続きを見る
掲載情報:
Journal of Gene Medicine
ISSN:
1099-498x  CiNii Articles  Webcat Plus  JAIRO
巻:
12
通号:
12
開始ページ:
1002
終了ページ:
1013
バージョン:
author
概要:
金沢大学医薬保健研究域医学系<br />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. 続きを見る
URL:
http://hdl.handle.net/2297/26395

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