Username


Password

Forgot Password?

Preview

Sign-in free and Explore the Exciting World of BiomedExperts:
  • Over 1.500.000 Profiles
  • More than 1.800 Organizations worldwide
  • State of the Art Network Visualizations
  • Manage your own Profile
  • Locate Experts in your Country/Region
  • Locate Experts in your 1. and 2. Level Network
  • Connect to Experts Worldwide

find experts for

Sign-in to see more
2008: Liu Ta-Chiang; Castelo-Branco Pedro; Rabkin Samuel D; Martuza Robert L
Trichostatin A and oncolytic HSV combination therapy shows enhanced antitumoral and antiangiogenic effects.
Molecular therapy : the journal of the American Society of Gene Therapy 2008;16(6):1041-7.
Oncolytic herpes simplex viruses (HSVs) possess direct oncolytic and antiangiogenic activities and are promising anticancer agents, but their efficacy, when used as single agents, leaves room for improvement. We investigated whether combination therapy of HSV with histone deacetylase inhibitor trichostatin A (TSA), an agent that also targets cancer cells and tumor vasculature, would result in enhanced efficacy. In vitro, TSA and G47Delta showed strong synergy of action against proliferating endothelial cells, varying degrees of synergistic action against most cancer cell lines, but no effect in quiescent, normal endothelial and prostate epithelial cells. Synergy is dependent on viral replication; however, it is not dependent on the dosing sequence of TSA and G47Delta, viral genetic alterations, infectivity, or replication kinetics of G47Delta. Using an isogenic cell system, we found that a high level of cellular cyclin D1 is also critically important for the interaction. Normal cells with low cyclin D1 levels were not subjected to toxicity by either agent. In tumor cells and proliferating endothelial cells, the combination treatment enhanced the inhibition of cyclin D1 and vascular endothelial growth factor (VEGF). Concurrent systemic TSA and intratumoral G47Delta administration resulted in enhanced antiangiogenesis and enhanced antitumoral efficacy in animal models. Therefore, combination treatment with TSA and oncolytic HSV provides a novel approach to cancer therapy.

Post to CiteULike

Sign in free and see...

Visualized networks:
See your personal network in
sophisticated graphical views
GeoTargeted Searches:
Locate experts around the world
and connect with global collaborators
Research Profiles:
See the visualized research activity
of experts around the globe
Sign-in to see more