Replication and cytolysis of an E1B-attenuated adenovirus in drug-resistant ovarian tumour cells is associated with reduced apoptosis

Gene Therapy
I GanlyR Brown

Abstract

Therapeutic approaches which are effective in tumour cells resistant to conventional chemotherapy would be of value. An E1B 55 kDa-deleted adenovirus (ONYX-015) induces lysis in cells with mutant p53, although the specificity of these observations for different cell types is unclear. We have used a matched set of drug-resistant human ovarian tumour cell lines to examine the potential of ONYX-015 for preferential replication and lysis of drug-resistant ovarian tumour cells with documented alterations in p53 function. Marked preferential replication of ONYX-015 is observed after infection of mutant p53 transfectant and cisplatin-resistant derivatives, compared to the wild-type p53 expressing parental A2780 line. Infection causes increased cytopathic effects in vitro and inhibition of tumour growth in vivo of the drug-resistant derivatives, but not the parental line. In apparent contrast, increased apoptosis and reduced clonogenic survival is induced by ONYX-015 infection of the chemosensitive parental cell line. ONYX-015 induces increased pro-apoptotic BAX and reduced anti-apoptotic BCLX(L) in parental cells, but not in the resistant derivative A2780/cp70. We propose that induction of apoptosis is one factor which prevents ONYX-0...Continue Reading

References

Jan 4, 1994·Proceedings of the National Academy of Sciences of the United States of America·J KollsB Beutler
Apr 1, 1993·Genes & Development·M Debbas, E White
Nov 14, 1997·Virology·P J RidgwayA W Braithwaite

❮ Previous
Next ❯

Citations

Mar 26, 2003·Seminars in Cancer Biology·Irina V LebedevaPaul B Fisher
Nov 22, 2005·Oncogene·J Michael MathisDavid T Curiel
Jun 15, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Marie C ChiaFei-Fei Liu
Sep 10, 2003·Hematology/oncology Clinics of North America·Tyler O KirbyRonald D Alvarez
Nov 22, 2005·Oncogene·Clodagh C O'Shea

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis