FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2070351657> ?p ?o ?g. }

• W2070351657 endingPage "103" @default.
• W2070351657 startingPage "103" @default.
• W2070351657 abstract "Abstract Purpose: Exposure of human carcinoma and malignant glioma cells to ionizing radiation (IR)activates EGFR,which as a consequence mediates a cytoprotective response. We have demonstrated that expression of a dominant negative mutant, EGFR-CD533 disrupts this cytoprotective response, resulting in significant radiosensitization. During studies of in vivo radiosensitization with intratumoral delivery of the Adenovirus (Ad) vector, Ad-EGFR-CD533, it became apparent that xenografts from human carcinoma and malignant glioma cells invariably expressed the constitutively active EGFR mutant, EGFRvIII. This mutant EGFRvIII is frequently found in vivo in glioblastoma, breast, prostate, lung and ovarian carcinoma, but does not appear to be expressed in tumor cells under in vitro conditions. The functional consequences of EGFRvIII expression on tumor cell radiation responses are currently unknown. We have therefore investigated in a transient transfection cell system the responses of EGFRvIII and downstream signal transduction pathways to IR. In addition, the capacity of EGFR-CD533 to disrupt the function of EGFRvIII was tested. Materials and Methods: The MDA-MB-231, U-87 MG and U-373 MG cell lines were established as tumors and then intratumorally transduced with Ad-EGFR-CD533 or Ad-LacZ (control vector). The transduction efficiency was > 40% in MDA-MB-231 tumors and reached > 70% in the glioma xenografts. Radiosensitivity was measured by ex vivo colony formation and growth delay assays. The functional consequences of EGFRvIII expression on cellular IR responses were studied in transiently transfected Chinese hamster ovary (CHO) cells because tumor cells do not express EGFRvIII in vitro . Transfection with null vectors and vectors encoding either EGFRvIII or EGFR were performed and similar protein expression levels were verified by Western blot analyses. Results: The radiosensitivity of Ad-EGFR-CD533 transduced tumors was significantly increased compared with Ad-LacZ transduced tumors for MDA-MB-231 and U-87 MG tumors, with dose enhancement ratios of 1.9. U-373 MG tumors expressing EGFR-CD533 demonstrated a 4-fold increase in the tumor doubling time after IR (3 x 3 Gy) compared with LacZ transduced tumors. EGF treatment activated EGFR, as quantified by tyrosine phosphorylation (Tyr-P) and mediated activation of its downstream target mitogen activated protein kinase (MAPK), but had no effect on EGFRvIII. In contrast, IR stimulated a 4-fold increase in Tyr-P of EGFRvIII, resulting in a maximum 9-fold activation of MAPK and a 3-fold activation of the PI3K signal transduction pathway. A specific tyrphostin inhibitor of EGFR and EGFRvIII, AG1478, reduced the radiation-induced activation of MAPK and PI3K to a maximum of 2-fold, similar to the activation profile observed in CHO cells transfected with null vectors. Colony formation and cell growth assays verified that cells expressing EGFRvIII are markedly protected against the cytotoxic effects of IR. Finally, Ad-EGFR-CD533 transduction of U-373 MG cells expressing EGFRvIII significantly reduced basal Tyr-P and IR-induced activation of EGFRvIII. Conclusion: The effects of in vivo expression of constitutively active EGFRvIII on cellular radiosensitivity have not previously been considered. We demonstrate here that expression of EGFRvIII enhances the relative radioresistance of tumor cells in vitro and in vivo . This resistance is mediated by the significantly greater radiation-induced activation of EGFRvIII relative to EGFR and as a consequence a greater stimulation of both the MAPK and PI3K cytoprotective pathways. Importantly, the genetic disruption of EGFR function by expression of EGFR-CD533 is equally effective with either EGFR or EGFRvIII." @default.
• W2070351657 created "2016-06-24" @default.
• W2070351657 creator A5015195004 @default.
• W2070351657 creator A5017148671 @default.
• W2070351657 creator A5033284748 @default.
• W2070351657 creator A5041869023 @default.
• W2070351657 creator A5047550067 @default.
• W2070351657 creator A5051876224 @default.
• W2070351657 creator A5069980003 @default.
• W2070351657 creator A5076040219 @default.
• W2070351657 creator A5085768397 @default.
• W2070351657 date "2001-11-01" @default.
• W2070351657 modified "2023-09-23" @default.
• W2070351657 title "EGFR and its mutant EGFRvIII as modulators of tumor cell radiosensitivity" @default.
• W2070351657 doi "https://doi.org/10.1016/s0360-3016(01)02012-0" @default.
• W2070351657 hasPublicationYear "2001" @default.
• W2070351657 type Work @default.
• W2070351657 sameAs 2070351657 @default.
• W2070351657 citedByCount "1" @default.
• W2070351657 crossrefType "journal-article" @default.
• W2070351657 hasAuthorship W2070351657A5015195004 @default.
• W2070351657 hasAuthorship W2070351657A5017148671 @default.
• W2070351657 hasAuthorship W2070351657A5033284748 @default.
• W2070351657 hasAuthorship W2070351657A5041869023 @default.
• W2070351657 hasAuthorship W2070351657A5047550067 @default.
• W2070351657 hasAuthorship W2070351657A5051876224 @default.
• W2070351657 hasAuthorship W2070351657A5069980003 @default.
• W2070351657 hasAuthorship W2070351657A5076040219 @default.
• W2070351657 hasAuthorship W2070351657A5085768397 @default.
• W2070351657 hasBestOaLocation W20703516571 @default.
• W2070351657 hasConcept C126322002 @default.
• W2070351657 hasConcept C150903083 @default.
• W2070351657 hasConcept C206684579 @default.
• W2070351657 hasConcept C207001950 @default.
• W2070351657 hasConcept C2778227246 @default.
• W2070351657 hasConcept C502942594 @default.
• W2070351657 hasConcept C509974204 @default.
• W2070351657 hasConcept C54009773 @default.
• W2070351657 hasConcept C54355233 @default.
• W2070351657 hasConcept C62478195 @default.
• W2070351657 hasConcept C71924100 @default.
• W2070351657 hasConcept C81885089 @default.
• W2070351657 hasConcept C86803240 @default.
• W2070351657 hasConcept C95444343 @default.
• W2070351657 hasConceptScore W2070351657C126322002 @default.
• W2070351657 hasConceptScore W2070351657C150903083 @default.
• W2070351657 hasConceptScore W2070351657C206684579 @default.
• W2070351657 hasConceptScore W2070351657C207001950 @default.
• W2070351657 hasConceptScore W2070351657C2778227246 @default.
• W2070351657 hasConceptScore W2070351657C502942594 @default.
• W2070351657 hasConceptScore W2070351657C509974204 @default.
• W2070351657 hasConceptScore W2070351657C54009773 @default.
• W2070351657 hasConceptScore W2070351657C54355233 @default.
• W2070351657 hasConceptScore W2070351657C62478195 @default.
• W2070351657 hasConceptScore W2070351657C71924100 @default.
• W2070351657 hasConceptScore W2070351657C81885089 @default.
• W2070351657 hasConceptScore W2070351657C86803240 @default.
• W2070351657 hasConceptScore W2070351657C95444343 @default.
• W2070351657 hasIssue "3" @default.
• W2070351657 hasLocation W20703516571 @default.
• W2070351657 hasOpenAccess W2070351657 @default.
• W2070351657 hasPrimaryLocation W20703516571 @default.
• W2070351657 hasRelatedWork W1567015123 @default.
• W2070351657 hasRelatedWork W1604653849 @default.
• W2070351657 hasRelatedWork W1973608355 @default.
• W2070351657 hasRelatedWork W1980995086 @default.
• W2070351657 hasRelatedWork W1992454248 @default.
• W2070351657 hasRelatedWork W1995895703 @default.
• W2070351657 hasRelatedWork W2013878898 @default.
• W2070351657 hasRelatedWork W2027557150 @default.
• W2070351657 hasRelatedWork W2082454341 @default.
• W2070351657 hasRelatedWork W2111848398 @default.
• W2070351657 hasRelatedWork W2114734809 @default.
• W2070351657 hasRelatedWork W2117776838 @default.
• W2070351657 hasRelatedWork W2124129653 @default.
• W2070351657 hasRelatedWork W2156991532 @default.
• W2070351657 hasRelatedWork W2168557205 @default.
• W2070351657 hasRelatedWork W2372648634 @default.
• W2070351657 hasRelatedWork W2378588995 @default.
• W2070351657 hasRelatedWork W2968936915 @default.
• W2070351657 hasRelatedWork W358436998 @default.
• W2070351657 hasRelatedWork W2476006886 @default.
• W2070351657 hasVolume "51" @default.
• W2070351657 isParatext "false" @default.
• W2070351657 isRetracted "false" @default.
• W2070351657 magId "2070351657" @default.
• W2070351657 workType "article" @default.