PMID- 19016769 OWN - NLM STAT- MEDLINE DCOM- 20081217 LR - 20121115 IS - 1349-7006 (Electronic) IS - 1347-9032 (Linking) VI - 99 IP - 10 DP - 2008 Oct TI - Optimal amount of monocyte chemoattractant protein-1 enhances antitumor effects of suicide gene therapy against hepatocellular carcinoma by M1 macrophage activation. PG - 2075-82 LID - 10.1111/j.1349-7006.2008.00951.x [doi] AB - Suicide gene therapy combined with chemokines provides significant antitumor efficacy. Coexpression of suicide gene and monocyte chemoattractant protein-1 (MCP-1) increases antitumor effects in murine models of hepatocellular carcinoma (HCC) and colon cancer. However, it is unclear whether the doses administered achieved the maximum antitumor effects. We evaluated antitumor effects of various amounts of recombinant adenovirus vector (rAd) expressing MCP-1 in the presence of a suicide gene in a murine model of HCC. HCC cells were transplanted subcutaneously into BALB/c nude mice, and transduced with a fixed amount of Ad-tk harboring the suicide gene, HSV-tk, and various doses of Ad-MCP1 harboring MCP-1 (ratios of 1:1, 0.1:1, and 0.01:1 relative to Ad-tk). Growth of primary tumors was suppressed when treated with Ad-tk plus Ad-MCP1 (1:1 and 1:0.1) as compared with Ad-tk alone. The antitumor effects against tumor rechallenge tended to be high in the Ad-tk plus Ad-MCP1 group (1:0.1). The effects were dependent on production of Th1 type-cytokines. Delivery of an optimal amount of rAd expressing MCP-1 enhanced the antitumor effects of suicide gene therapy against HCC by M1 macrophage activation, suggesting that this is a plausible form of cancer gene therapy to prevent HCC progression and recurrence. FAU - Tsuchiyama, Tomoya AU - Tsuchiyama T AD - Disease Control and Homeostasis, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. FAU - Nakamoto, Yasunari AU - Nakamoto Y FAU - Sakai, Yoshio AU - Sakai Y FAU - Mukaida, Naofumi AU - Mukaida N FAU - Kaneko, Shuichi AU - Kaneko S LA - eng PT - Journal Article PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Chemokine CCL2) SB - IM MH - Adenoviridae/genetics MH - Animals MH - Carcinoma, Hepatocellular/genetics/*therapy MH - Cell Line, Tumor MH - Chemokine CCL2/*genetics MH - Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Genes, Transgenic, Suicide/genetics MH - Genetic Therapy/*methods MH - Genetic Vectors MH - Humans MH - Immunohistochemistry MH - Liver Neoplasms, Experimental/genetics/*therapy MH - Macrophage Activation/*genetics MH - Macrophages, Peritoneal/immunology MH - Male MH - Mice MH - Mice, Nude MH - Xenograft Model Antitumor Assays EDAT- 2008/11/20 09:00 MHDA- 2008/12/18 09:00 CRDT- 2008/11/20 09:00 PHST- 2008/11/20 09:00 [pubmed] PHST- 2008/12/18 09:00 [medline] PHST- 2008/11/20 09:00 [entrez] AID - CAS951 [pii] AID - 10.1111/j.1349-7006.2008.00951.x [doi] PST - ppublish SO - Cancer Sci. 2008 Oct;99(10):2075-82. doi: 10.1111/j.1349-7006.2008.00951.x.