Matches in SemOpenAlex for { <https://semopenalex.org/work/W2000859892> ?p ?o ?g. }
- W2000859892 endingPage "223" @default.
- W2000859892 startingPage "215" @default.
- W2000859892 abstract "The objective of the study was to evaluate the utility of NV1042, a replication competent, oncolytic herpes simplex virus (HSV) containing the interleukin-12 (IL-12) gene, as primary treatment for hepatic tumors and to further assess its ability to reduce tumor recurrence following resection. Resection is the most effective therapy for hepatic malignancies, but is not possible in the majority of the patients. Furthermore, recurrence is common after resection, most often in the remnant liver and likely because of microscopic residual disease in the setting of postoperative host cellular immune dysfunction. We hypothesize that, unlike other gene transfer approaches, direct injection of liver tumors with replication competent, oncolytic HSV expressing IL-12 will not only provide effective control of the parent tumor, but will also elicit an immune response directed at residual tumor cells, thus decreasing the risk of cancer recurrence after resection. Solitary Morris hepatomas, established in Buffalo rat livers, were injected directly with 10(7) particles of NV1042, NV1023, an oncolytic HSV identical to NV1042 but without the IL-12 gene, or with saline. Following tumor injection, the parent tumors were resected and measured and the animals were challenged with an intraportal injection of 10(5) tumor cells, recreating the clinical scenario of residual microscopic cancer. In vitro cytotoxicity against Morris hepatoma cells was similar for both viruses at a multiplicity of infection of 1 (MOI, ratio of viral particles to target cells), with >90% tumor cell kill by day 6. NV1042 induced high-level expression of IL-12 in vitro, peaking after 4 days in culture. Furthermore, a single intratumoral injection of NV1042, but not NV1023, induced marked IL-12 and interferon-gamma (IFN-gamma) expression. Both viruses induced a significant local immune response as evidenced by an increase in the number of intratumoral CD4(+) and CD8(+) lymphocytes, although the peak of CD8(+) infiltration was later with NV1042 compared with NV1023. NV1042 and NV1023 reduced parent tumor volume by 74% (P<.003) and 52% (P<.03), respectively, compared to control animals. Treatment of established tumors with NV1042, but not with NV1023, significantly reduced the number of hepatic tumors after resection of the parent tumor and rechallenge (16.8+/-11 (median=4) vs. 65.9+/-15 (median=66) in control animals, P<.025). In conclusion, oncolytic HSV therapy combined with local immune stimulation with IL-12 offers effective control of parent hepatic tumors and also protects against microscopic residual disease after resection. The ease of use of this combined modality approach, which appears to be superior to either approach alone, suggests that it may have clinical relevance, both as primary treatment for patients with unresectable tumors and also as a neoadjuvant strategy for reducing recurrence after resection." @default.
- W2000859892 created "2016-06-24" @default.
- W2000859892 creator A5003466529 @default.
- W2000859892 creator A5005824918 @default.
- W2000859892 creator A5012682133 @default.
- W2000859892 creator A5016615488 @default.
- W2000859892 creator A5021981756 @default.
- W2000859892 creator A5024750878 @default.
- W2000859892 creator A5026780606 @default.
- W2000859892 creator A5026961434 @default.
- W2000859892 creator A5040858834 @default.
- W2000859892 creator A5042440032 @default.
- W2000859892 creator A5056014313 @default.
- W2000859892 creator A5079376687 @default.
- W2000859892 date "2003-03-01" @default.
- W2000859892 modified "2023-10-10" @default.
- W2000859892 title "Neoadjuvant treatment of hepatic malignancy: an oncolytic herpes simplex virus expressing IL-12 effectively treats the parent tumor and protects against recurrence-after resection" @default.
- W2000859892 cites W1568231973 @default.
- W2000859892 cites W1773381788 @default.
- W2000859892 cites W1848603902 @default.
- W2000859892 cites W1970212185 @default.
- W2000859892 cites W1976158860 @default.
- W2000859892 cites W1979423262 @default.
- W2000859892 cites W1991148746 @default.
- W2000859892 cites W1993282202 @default.
- W2000859892 cites W2002323372 @default.
- W2000859892 cites W2002845859 @default.
- W2000859892 cites W2005547640 @default.
- W2000859892 cites W2027178820 @default.
- W2000859892 cites W2036581805 @default.
- W2000859892 cites W2037832501 @default.
- W2000859892 cites W2039121456 @default.
- W2000859892 cites W2044295337 @default.
- W2000859892 cites W2053833504 @default.
- W2000859892 cites W2066696556 @default.
- W2000859892 cites W2071698515 @default.
- W2000859892 cites W2084470612 @default.
- W2000859892 cites W2084906660 @default.
- W2000859892 cites W2085778437 @default.
- W2000859892 cites W2090399539 @default.
- W2000859892 cites W2090841553 @default.
- W2000859892 cites W2091691801 @default.
- W2000859892 cites W2151707711 @default.
- W2000859892 cites W2156472127 @default.
- W2000859892 cites W2269945922 @default.
- W2000859892 cites W2314446169 @default.
- W2000859892 cites W2320971191 @default.
- W2000859892 cites W2327682512 @default.
- W2000859892 cites W87480255 @default.
- W2000859892 doi "https://doi.org/10.1038/sj.cgt.7700558" @default.
- W2000859892 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12637943" @default.
- W2000859892 hasPublicationYear "2003" @default.
- W2000859892 type Work @default.
- W2000859892 sameAs 2000859892 @default.
- W2000859892 citedByCount "41" @default.
- W2000859892 countsByYear W20008598922013 @default.
- W2000859892 countsByYear W20008598922014 @default.
- W2000859892 countsByYear W20008598922015 @default.
- W2000859892 countsByYear W20008598922016 @default.
- W2000859892 countsByYear W20008598922019 @default.
- W2000859892 countsByYear W20008598922020 @default.
- W2000859892 countsByYear W20008598922021 @default.
- W2000859892 countsByYear W20008598922022 @default.
- W2000859892 countsByYear W20008598922023 @default.
- W2000859892 crossrefType "journal-article" @default.
- W2000859892 hasAuthorship W2000859892A5003466529 @default.
- W2000859892 hasAuthorship W2000859892A5005824918 @default.
- W2000859892 hasAuthorship W2000859892A5012682133 @default.
- W2000859892 hasAuthorship W2000859892A5016615488 @default.
- W2000859892 hasAuthorship W2000859892A5021981756 @default.
- W2000859892 hasAuthorship W2000859892A5024750878 @default.
- W2000859892 hasAuthorship W2000859892A5026780606 @default.
- W2000859892 hasAuthorship W2000859892A5026961434 @default.
- W2000859892 hasAuthorship W2000859892A5040858834 @default.
- W2000859892 hasAuthorship W2000859892A5042440032 @default.
- W2000859892 hasAuthorship W2000859892A5056014313 @default.
- W2000859892 hasAuthorship W2000859892A5079376687 @default.
- W2000859892 hasBestOaLocation W20008598921 @default.
- W2000859892 hasConcept C104317684 @default.
- W2000859892 hasConcept C111599444 @default.
- W2000859892 hasConcept C121608353 @default.
- W2000859892 hasConcept C126322002 @default.
- W2000859892 hasConcept C142724271 @default.
- W2000859892 hasConcept C203014093 @default.
- W2000859892 hasConcept C203233990 @default.
- W2000859892 hasConcept C2522874641 @default.
- W2000859892 hasConcept C2779399171 @default.
- W2000859892 hasConcept C2781196997 @default.
- W2000859892 hasConcept C502942594 @default.
- W2000859892 hasConcept C55493867 @default.
- W2000859892 hasConcept C71924100 @default.
- W2000859892 hasConcept C82210918 @default.
- W2000859892 hasConcept C86803240 @default.
- W2000859892 hasConcept C8891405 @default.
- W2000859892 hasConcept C96232424 @default.
- W2000859892 hasConceptScore W2000859892C104317684 @default.
- W2000859892 hasConceptScore W2000859892C111599444 @default.
- W2000859892 hasConceptScore W2000859892C121608353 @default.