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Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma.
Gene Ther. 2006 Sep; 13(17):1263-71.GT

Abstract

MIG (monokine induced by interferon-gamma) is a CXC chemokine ligand (CXCL9) that can potently inhibit angiogenesis, and displays thymus-dependent antitumor effects. The effectiveness of a treatment combining gene therapy with plasmid-borne MIG (pORF-MIG) and low-dose cisplatin chemotherapy was determined using colon carcinoma (CT26) and Lewis lung carcinoma (LL/2c) murine models. The program was carried out via intramuscular delivery of pORF-MIG at 100 mug/mouse twice a week for 4 weeks, and/or intraperitoneal delivery of cisplatin at 0.6 mg/kg/mouse every 3 days for 48 days. Tumor volume and survival time were evaluated after treatment. CD31 immunohistochemical staining in tumor tissues and alginate capsule models in vivo was used to evaluate angiogenesis. Induction of apoptosis and cytotoxic T-lymphocyte (CTL) activity were also assessed. The combination of pORF-MIG and low-dose cisplatin produced significant antitumor activity, with complete tumor regression in 4/10 of CT26 colon carcinomas and 3/10 of LL/2c lung carcinomas, low vascularity, in alginate capsules, apparently degraded tumor microvessel density, and increased induction of apoptotic and CTL activities compared with either treatment alone. This study suggests that the combination of pORF-MIG plus cisplatin augments the inhibition of angiogenesis and the induction of apoptosis or CTL activity, all of which enhance antitumor activity. These findings may prove useful in further explorations of the application of combinatorial approaches to the treatment of solid tumors.

Authors+Show Affiliations

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16672984

Citation

Zhang, R, et al. "Combination of MIG (CXCL9) Chemokine Gene Therapy With Low-dose Cisplatin Improves Therapeutic Efficacy Against Murine Carcinoma." Gene Therapy, vol. 13, no. 17, 2006, pp. 1263-71.
Zhang R, Tian L, Chen LJ, et al. Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma. Gene Ther. 2006;13(17):1263-71.
Zhang, R., Tian, L., Chen, L. J., Xiao, F., Hou, J. M., Zhao, X., Li, G., Yao, B., Wen, Y. J., Li, J., Zhang, L., Chen, X. C., Luo, F., Peng, F., Jiang, Y., & Wei, Y. Q. (2006). Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma. Gene Therapy, 13(17), 1263-71.
Zhang R, et al. Combination of MIG (CXCL9) Chemokine Gene Therapy With Low-dose Cisplatin Improves Therapeutic Efficacy Against Murine Carcinoma. Gene Ther. 2006;13(17):1263-71. PubMed PMID: 16672984.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combination of MIG (CXCL9) chemokine gene therapy with low-dose cisplatin improves therapeutic efficacy against murine carcinoma. AU - Zhang,R, AU - Tian,L, AU - Chen,L-J, AU - Xiao,F, AU - Hou,J-M, AU - Zhao,X, AU - Li,G, AU - Yao,B, AU - Wen,Y-J, AU - Li,J, AU - Zhang,L, AU - Chen,X-C, AU - Luo,F, AU - Peng,F, AU - Jiang,Y, AU - Wei,Y-Q, Y1 - 2006/05/04/ PY - 2006/5/5/pubmed PY - 2007/1/19/medline PY - 2006/5/5/entrez SP - 1263 EP - 71 JF - Gene therapy JO - Gene Ther VL - 13 IS - 17 N2 - MIG (monokine induced by interferon-gamma) is a CXC chemokine ligand (CXCL9) that can potently inhibit angiogenesis, and displays thymus-dependent antitumor effects. The effectiveness of a treatment combining gene therapy with plasmid-borne MIG (pORF-MIG) and low-dose cisplatin chemotherapy was determined using colon carcinoma (CT26) and Lewis lung carcinoma (LL/2c) murine models. The program was carried out via intramuscular delivery of pORF-MIG at 100 mug/mouse twice a week for 4 weeks, and/or intraperitoneal delivery of cisplatin at 0.6 mg/kg/mouse every 3 days for 48 days. Tumor volume and survival time were evaluated after treatment. CD31 immunohistochemical staining in tumor tissues and alginate capsule models in vivo was used to evaluate angiogenesis. Induction of apoptosis and cytotoxic T-lymphocyte (CTL) activity were also assessed. The combination of pORF-MIG and low-dose cisplatin produced significant antitumor activity, with complete tumor regression in 4/10 of CT26 colon carcinomas and 3/10 of LL/2c lung carcinomas, low vascularity, in alginate capsules, apparently degraded tumor microvessel density, and increased induction of apoptotic and CTL activities compared with either treatment alone. This study suggests that the combination of pORF-MIG plus cisplatin augments the inhibition of angiogenesis and the induction of apoptosis or CTL activity, all of which enhance antitumor activity. These findings may prove useful in further explorations of the application of combinatorial approaches to the treatment of solid tumors. SN - 0969-7128 UR - https://www.unboundmedicine.com/medline/citation/16672984/Combination_of_MIG__CXCL9__chemokine_gene_therapy_with_low_dose_cisplatin_improves_therapeutic_efficacy_against_murine_carcinoma_ L2 - https://doi.org/10.1038/sj.gt.3302756 DB - PRIME DP - Unbound Medicine ER -