A GSDMB enhancer-driven HSV thymidine kinase-expressing vector for controlling occult peritoneal dissemination of gastric cancer cellsReport as inadecuate




A GSDMB enhancer-driven HSV thymidine kinase-expressing vector for controlling occult peritoneal dissemination of gastric cancer cells - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 15:439

Experimental therapeutics and drug development

Abstract

BackgroundGastric cancer GC is one of the major malignant diseases worldwide, especially in Asia, and Japan and Korea have the highest incidence in the world. Because most of the cases that are refractory to therapies die due to peritoneal dissemination PD of the cancer cells, controlling PD is important for patient survival. GSDMB is a member of the gasdermin gene family. Because GSDMB is expressed in many types of cancer, including GC, it is likely that the gene contains a regulatory region that is utilized for therapy of occult PD through cancer cell-specific expression of cytotoxic genes.

MethodsWe performed reporter assays to identify the regulatory region for the cancer cell-specific expression. We also constructed a lentiviral therapeutic vector that expresses herpes simplex virus thymidine kinase HSVtk in a GC cell-specific manner, and tested it in a mouse model of PD.

ResultsWe identified the regulatory region at +496 to +989 from the GSDMB transcription start site and designated it as a GSDMB enhancer. The lentiviral therapeutic vector suppressed proliferation of a GC cell line, 60As6, in vitro in the presence of ganciclovir, and intraperitoneal administration of the vector prolonged the survival term of mice that were intraperitoneally inoculated with 60As6 one week prior to the administration.

ConclusionsThe GSDMB-driven HSVtk expression vector had a therapeutic effect on the occult PD model mice. This strategy can potentially be used to treat GC patients with PD.

KeywordsStomach neoplasms Peritoneal cavity Genetic therapy HSV Thymidine kinase Electronic supplementary materialThe online version of this article doi:10.1186-s12885-015-1436-1 contains supplementary material, which is available to authorized users.

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Author: Norihisa Saeki - Rie Komatsuzaki - Fumiko Chiwaki - Kazuyoshi Yanagihara - Hiroki Sasaki

Source: https://link.springer.com/







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