ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Hypoxia enhances the replication of oncolytic herpes simplex virus.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 69 citations in OpenAlex.
- Hypoxia increases the activity of oncolytic adenoviruses through HIF-2α-stimulated E1A expression.Signal transduction and targeted therapy · 2026Article
- Review
- The Potential of Oncolytic Virotherapy in the Treatment of Head and Neck Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Reduced vacuolar ATPase protects mice from Friend virus infection - an unintended but instructive effect in Hif-2afl mice.Journal of cell science · 2024Article
- Effects of HSV-G47Δ Oncolytic Virus on Telomerase and Telomere Length Alterations in Glioblastoma Multiforme Cancer Stem Cells Under Hypoxia and Normoxia Conditions.Current cancer drug targets · 2024Article
- Epstein-Barr virus-acquired immunodeficiency in myalgic encephalomyelitis-Is it present in long COVID?Journal of translational medicine · 2023Review
- Mesenchymal stem cell-released oncolytic virus: an innovative strategy for cancer treatment.Cell communication and signaling : CCS · 2023Review
- Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases.Frontiers in immunology · 2023Article
- Combining of Oncolytic Virotherapy and Other Immunotherapeutic Approaches in Cancer: A Powerful Functionalization Tactic.Global challenges (Hoboken, NJ) · 2023Review
- Hypoxia triggers the outbreak of infectious spleen and kidney necrosis virus disease through viral hypoxia response elements.Virulence · 2022Article
- Modifying oncolytic virotherapy to overcome the barrier of the hypoxic tumor microenvironment. Where do we stand?Cancer cell international · 2022Review
- Remodeling the tumor microenvironment by oncolytic viruses: beyond oncolysis of tumor cells for cancer treatment.Journal for immunotherapy of cancer · 2022Review
- Oncolytic Virotherapy in Peritoneal Metastasis Gastric Cancer: The Challenges and Achievements.Frontiers in molecular biosciences · 2022Review
- Impact of Hypoxia over Human Viral Infections and Key Cellular Processes.International journal of molecular sciences · 2021Review
- Review
- Article
- Oxygen: viral friend or foe?Virology journal · 2020Review
- Review
- Article
- Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.