| Concurrent chemotherapy inhibits herpes simplex virus-1 replication and oncolysis. | |
| | |
MedLine Citation:
|
PMID: 23348635 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Herpes simplex virus-1 (HSV-1) replication in cancer cells leads to their destruction (viral oncolysis) and has been under investigation as an experimental cancer therapy in clinical trials as single agents, and as combinations with chemotherapy. Cellular responses to chemotherapy modulate viral replication, but these interactions are poorly understood. To investigate the effect of chemotherapy on HSV-1 oncolysis, viral replication in cells exposed to 5-fluorouracil (5-FU), irinotecan (CPT-11), methotrexate (MTX) or a cytokine (tumor necrosis factor-α (TNF-α)) was examined. Exposure of colon and pancreatic cancer cells to 5-FU, CPT-11 or MTX in vitro significantly antagonizes both HSV-1 replication and lytic oncolysis. Nuclear factor-κB (NF-κB) activation is required for efficient viral replication, and experimental inhibition of this response with an IκBα dominant-negative repressor significantly antagonizes HSV-1 replication. Nonetheless, cells exposed to 5-FU, CPT-11, TNF-α or HSV-1 activate NF-κB. Cells exposed to MTX do not activate NF-κB, suggesting a possible role for NF-κB inhibition in the decreased viral replication observed following exposure to MTX. The role of eukaryotic initiation factor 2α (eIF-2α) dephosphorylation was examined; HSV-1-mediated eIF-2α dephosphorylation proceeds normally in HT29 cells exposed to 5-FU, CPT-11 or MTX. This report demonstrates that cellular responses to chemotherapeutic agents provide an unfavorable environment for HSV-1-mediated oncolysis, and these observations are relevant to the design of both preclinical and clinical studies of HSV-1 oncolysis.Cancer Gene Therapy advance online publication, 25 January 2013; doi:10.1038/cgt.2012.97. |
| | |
Authors:
|
Y Kulu; H Kawasaki; J M Donahue; H Kasuya; J C Cusack; E W Choi; D K Kuruppu; B C Fuchs; K K Tanabe |
Related Documents
:
|
23395675 - Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interl... 23363775 - Activation of microglial cells triggers a release of brain-derived neurotrophic factor ... 23635775 - Plasmacytoid dendritic cells promote rotavirus-induced human and murine b cell responses. 23277025 - Thymoquinone induces apoptosis in malignant t-cells via generation of ros . 15279785 - The switch from survival responses to apoptosis after chromosomal breaks. 8549875 - Molecular mechanisms of liver fibrogenesis--a homage to the role of activated fat-stori... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2013-1-25 |
Journal Detail:
|
Title: Cancer gene therapy Volume: - ISSN: 1476-5500 ISO Abbreviation: Cancer Gene Ther. Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2013-1-25 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9432230 Medline TA: Cancer Gene Ther Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Division of Surgical Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: CD16<formula>^{+}</formula> monocyte subsets are increased in large abdominal aortic aneurysms and a...
Next Document: PROPEL: A randomized trial of mericitabine plus peginterferon alfa-2a/ribavirin therapy in treatment...