Preview
Sign-in for full Details 
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
2009:
Aghi Manish K; Liu Ta-Chiang; Rabkin Samuel; Martuza Robert L
Hypoxia enhances the replication of oncolytic herpes simplex virus.
Molecular therapy : the journal of the American Society of Gene Therapy 2009;
17(
1):.
Hypoxia contributes to the resistance of tumors to conventional therapies. We hypothesized that their replication in hypoxic environments like brain or oral mucosa would make oncolytic herpes simplex viruses (HSVs) such as G207 (which has undergone clinical trials) replicate to a greater extent in hypoxic tumors like glioblastoma. Hypoxic cultured U87 cells yielded 4% more wild-type HSV (P = 0.04) and 3.6-fold more G207 (P = 0.001) after 48 hours of infection when compared with normoxic cells. Real-time RT-PCR confirmed a fivefold hypoxia-induced U87 upregulation of GADD34 mRNA, a factor complementing the gamma34.5 gene deletion in G207. The viral yield under conditions of hypoxia, as against normoxia, in GADD34 siRNA-treated U87 cells was 65% of that in control siRNA-treated cells. Treating subcutaneous U87 tumors in athymic mice with erythropoietin lowered the tumoral hypoxic fraction from 57.5 to 24.5%. Tumoral hypoxia dropped to 2.5% during 4 hours/day of hyperbaric chamber treatment. Each tumor-oxygenating maneuver reduced the G207 yield fourfold (P = 0.0001). Oncolytic HSV G207 exhibited enhanced replication in hypoxic environments, partly on account of increased GADD34 expression in hypoxic cells. The unique tropism of oncolytic HSVs for hypoxic environments contrasts with the hypoxia-mediated impairment of standard (radiation, chemotherapy) and other experimental therapies, and enhances HSV's appeal and efficacy in treating tumors like glioblastoma.
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
