Targeting proliferating tumor cells via the transcriptional control of therapeutic genes

ABSTRACT We have previously reported the construction of a cell cycle-regulated HSV-1 amplicon vector (denoted as pC8-36) that confers luciferase reporter gene activities dependent on

cellular divisions. However, luciferase reporter gene is well known for its relatively high sensitivity, thus, it is crucial to evaluate the therapeutic efficacy of a transcriptional

targeted vector. In this report, we have engineered the _FasL_ and FADD genes into pC8-36 and demonstrated their efficacy for the treatment of human gliomas _in vitro_ and _in vivo_. Using

trypan blue dye exclusion and TUNEL assay, _FasL_ expression mediated by pC8-36 was shown to induce a significantly higher percentage of cell death in proliferating cells than those observed

in the G1-arrested cells. The observed cell killing effect correlated well with the level of FasL protein expression when analyzed by ELISA assay. Furthermore, the incorporation of both

_FasL_ and FADD into pC8-36 resulted in the enhancement of apoptosis in the target glioma cells both _in vitro_ and _in vivo_. Targeting proliferating tumor cells via the transcriptional

control of therapeutic genes could potentially improve the safety and efficacy of cancer gene therapy, and thus would allow the development of strategies for more effective anticancer

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customer support SIMILAR CONTENT BEING VIEWED BY OTHERS CIRCKPNB1 MEDIATES A POSITIVE FEEDBACK LOOP AND PROMOTES THE MALIGNANT PHENOTYPES OF GSCS VIA TNF-Α/NF-ΚB SIGNALING Article Open

access 09 August 2022 A RUNX-TARGETED GENE SWITCH-OFF APPROACH MODULATES THE BIRC5/PIF1-P21 PATHWAY AND REDUCES GLIOBLASTOMA GROWTH IN MICE Article Open access 09 September 2022 HUMAN _SNF5_

ARMING OF DOUBLE-DELETED VACCINIA VIRUS SHOWS ONCOLYTIC AND CYTOSTATIC ACTIVITY AGAINST CENTRAL NERVOUS SYSTEM ATYPICAL TERATOID/RHABDOID TUMOR CELLS Article 17 July 2020 REFERENCES * Ho

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Biology and Tumor Research, Germany) for providing us with the plasmids GalcycA, Dr MV Clement (National University of Singapore) for providing us the FADD cDNA and Dr Nai-dy Wang (National

University of Singapore) for valuable discussions. This research was supported by grants from the Singapore National Medical Research Council (NMRC) and Singapore Biomedical Research Council

(BMRC). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Cellular and Molecular Research, Gene Vector Laboratory, National Cancer Centre, Singapore, Singapore I A W Ho, K M Hui 

& P Y P Lam Authors * I A W Ho View author publications You can also search for this author inPubMed Google Scholar * K M Hui View author publications You can also search for this author

inPubMed Google Scholar * P Y P Lam View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to P Y P Lam. RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ho, I., Hui, K. & Lam, P. Targeting proliferating tumor cells via the transcriptional control of therapeutic

genes. _Cancer Gene Ther_ 13, 44–52 (2006). https://doi.org/10.1038/sj.cgt.7700864 Download citation * Received: 31 January 2005 * Revised: 04 April 2005 * Accepted: 12 April 2005 *

Published: 22 July 2005 * Issue Date: 01 January 2006 * DOI: https://doi.org/10.1038/sj.cgt.7700864 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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KEYWORDS * HSV-1 amplicon viral vectors * cell cycle-regulatable * apoptosis * FasL * FADD