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World J Surg. 2004 Aug;28(8):826-33. Epub 2004 Aug 3.

Cell-specific cytotoxicity of human pancreatic adenocarcinoma cells using rat insulin promoter thymidine kinase-directed gene therapy.

Author information

1
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, 6550 Fannin, Suite 1661, 77030, Houston, Texas, USA.

Abstract

The formation of a normal pancreas and the activation of insulin production are, in part, dependent on the expression and activation of the pancreatic duodenal homeobox gene 1 (PDX-1). The expression of PDX-1 also has been detected in various human pancreatic ductal adenocarcinoma (PDA) cell lines. This has made it possible to generate a cancer cell-specific gene expression system to treat human pancreatic cancer. In this study, we have developed a cell-specific cytotoxic model of PDA cells using the expression of herpes simplex virus thymidine kinase (TK) under the control of the rat insulin promoter (RIP-TK). We have shown that the cell-specific cytotoxicity in human PDA cells depends on the presence of PDX-1. Our results also demonstrate that in vivo PDA-specific cytotoxicity can be achieved with RIP-TK using an intraperitoneal liposomal gene delivery method followed by a short period of ganciclovir treatment in severe combined immunodeficient (SCID) mice. Furthermore, PDX-1 protein was found in all six freshly isolated human pancreas cancer specimens and two liver metastasis samples that were group-tested, suggesting the feasibility of using RIP-TK gene therapy in humans. This study may provide an alternative strategy for the future treatment of pancreatic cancer.

PMID:
15457366
DOI:
10.1007/s00268-004-7291-x
[Indexed for MEDLINE]

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