Document Detail


Oncolytic herpes simplex virus vectors and taxanes synergize to promote killing of prostate cancer cells.
MedLine Citation:
PMID:  19197321     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Genetically engineered oncolytic herpes simplex virus-1 (HSV-1) vectors selectively replicate in tumor cells causing direct killing whereas sparing normal cells. One clinical limitation of using oncolytic HSV vectors is their attenuated growth. We hypothesized that the appropriately chosen chemotherapeutic agent combined with an oncolytic HSV could be an effective means to promote augmented prostate cancer cell killing both in vitro and in vivo. Here we have identified that G47Delta synergizes with the microtubule-stabilizing taxane agents docetaxel and paclitaxel to enhance the in vitro killing of prostate cancer cells. In vivo efficacy studies show that when combined with docetaxel, G47Delta could be reduced at least 10-fold. Immunoblot analysis revealed that docetaxel-induced accumulation of the phospho-specific mitotic markers op18/stathmin or histone-H3 was markedly reduced by G47Delta, which correlated with enhanced apoptosis and required active viral replication. Furthermore, cell-cycle analysis demonstrated that in the presence of G47Delta, the majority of 4N cells arrested in mitosis were MPM-2-negative, indicative of cells exiting mitosis prematurely. These findings suggest that G47Delta may act in part, on mitotically blocked cells to enhance cell death, which may account for the enhanced antitumor efficacy observed in vivo.
Authors:
B J Passer; P Castelo-Branco; J S Buhrman; S Varghese; S D Rabkin; R L Martuza
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-02-06
Journal Detail:
Title:  Cancer gene therapy     Volume:  16     ISSN:  1476-5500     ISO Abbreviation:  Cancer Gene Ther.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-06-16     Completed Date:  2009-08-25     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  9432230     Medline TA:  Cancer Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  551-60     Citation Subset:  IM    
Affiliation:
Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. bpasser@partners.org
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / therapeutic use*
Cell Line, Tumor
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Genetic Vectors / genetics,  physiology*
Herpesvirus 1, Human / genetics,  physiology*
Humans
Male
Oncolytic Virotherapy / methods*
Prostatic Neoplasms / drug therapy,  therapy*
Simplexvirus / genetics,  physiology
Taxoids / therapeutic use*
Virus Replication
Grant Support
ID/Acronym/Agency:
DK43351/DK/NIDDK NIH HHS; DK57521/DK/NIDDK NIH HHS; R01 CA102139/CA/NCI NIH HHS; R01 CA102139-06A1/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Taxoids
Comments/Corrections

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