PMID: 11933215Apr 5, 2002Paper

Intratumoral activation of cyclophosphamide by retroviral transfer of the cytochrome P450 2B1 in a pancreatic tumor model. Combination with the HSVtk/GCV system

The Journal of Gene Medicine
M CarrióC Fillat

Abstract

Pancreatic cancer is one of the most aggressive human tumors and the development of new therapeutic approaches is particularly urgent since current therapies are not effective. The use of pro-drug-activating genes is a possible approach for cancer gene therapy. The present study evaluated the efficiency of the cytochrome P4502B1 (CYP2B1) suicide gene that encodes the enzyme responsible for activating the pro-drug cyclophosphamide (CPA), in pancreatic tumor cells invitro and in vivo. The effects on tumor growth of the combination of two suicide systems, CYP2B1/CPA and herpes simplex virus thymidine kinase gene/ganciclovir (HSVtk/GCV), were also studied. Retroviral CYP2B1 transfer followed by CPA treatment highly sensitized pancreatic tumor cells NP-9, NP-18, and NP-31, and led to stabilization of tumor growth in a pancreatic tumor model. Differences in tumor volume at the end of the treatment were statistically significant when compared with animals injected with CPA alone. The combination of both suicide systems CYP2B1/CPA and HSVtk/GCV in vitro resulted in a potentiation of the killing effect. However, no potentiation was achieved in vivo, although retardation in tumor growth was evident. The results show that in situ transduc...Continue Reading

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Citations

Jan 5, 2006·Human Gene Therapy·Anna CascanteCristina Fillat
Sep 13, 2005·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Jing ZhangShufeng Zhou
Jun 9, 2017·International Journal of Molecular Sciences·Marie RouanetLouis Buscail
Jan 1, 2011·Cancers·Cristina FillatLuciano Sobrevals
Sep 30, 2004·International Journal of Cancer. Journal International Du Cancer·Eduard RyschichMatthias Löhr
Oct 14, 2014·World Journal of Gastroenterology : WJG·Si-Xue LiuYing-Qiang Zhong
Feb 5, 2004·World Journal of Gastroenterology : WJG·Jing WangLi-Shan Zhang
Nov 6, 2009·Molecular Cancer Therapeutics·Jordi Martinez-QuintanillaRamon Alemany

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