Matches in SemOpenAlex for { <https://semopenalex.org/work/W1525691133> ?p ?o ?g. }
- W1525691133 endingPage "41" @default.
- W1525691133 startingPage "433" @default.
- W1525691133 abstract "Targeting activating mutations in the proto-oncogene B-Raf, in melanoma, has led to increases in progression free survival. Treatment with vemurafenib, which inhibits the most common activating-mutated form of B-Raf (B-Raf(V600E)), eventually results in resistance to therapy. VEGF-A is the principal driver of angiogenesis in primary and metastatic lesions. The bioactivity of VEGF-A is dependent upon alternative RNA splicing and pro-angiogenic isoforms of VEGF-A are upregulated in many disease states dependent upon angiogenesis, including cancers. Using techniques including RT-PCR, Western blotting, ELISA and luciferase reporter assays, the effect of vemurafenib on proliferation, ERK1/2 phosphorylation and the levels of pro- and anti-angiogenic VEGF-A isoforms was investigated in melanoma cell types expressing either wild-type B-Raf or B-Raf(V600E), including a primary melanoma culture derived from a highly vascularised and active nodule taken from a patient with a V600E mutant melanoma. The primary melanoma culture was characterised and found to have reverted to wild-type B-Raf. In B-Raf(V600E) A375 cells ERK1/2 phosphorylation, pro-angiogenic VEGF-A mRNA, total VEGF-A protein expression and VEGF-A 3'UTR activity were all decreased in a concentration-dependent manner by vemurafenib. Conversely vemurafenib treatment of wild-type B-Raf cells significantly increased ERK1/2 phosphorylation, pro-angiogenic VEGF-A mRNA and total VEGF-A expression in a concentration-dependent manner. A switch to pro-angiogenic VEGF-A isoforms, with a concomitant upregulation of expression by increasing VEGF-A mRNA stability, may be an additional oncogenic and pathological mechanism in B-Raf(V600E) melanomas, which promotes tumor-associated angiogenesis and melanoma-genesis. We have also identified the genetic reversal of B-Raf(V600E) to wild-type in an active melanoma nodule taken from a V600E-positive patient and continued vemurafenib treatment for this patient is likely to have had a detrimental effect by promoting B-Raf(WT) activity." @default.
- W1525691133 created "2016-06-24" @default.
- W1525691133 creator A5022667959 @default.
- W1525691133 creator A5025488742 @default.
- W1525691133 creator A5047261934 @default.
- W1525691133 creator A5057389049 @default.
- W1525691133 creator A5090535914 @default.
- W1525691133 date "2015-01-01" @default.
- W1525691133 modified "2023-09-23" @default.
- W1525691133 title "Novel mechanisms of resistance to vemurafenib in melanoma - V600E B-Raf reversion and switching VEGF-A splice isoform expression." @default.
- W1525691133 cites W1563171148 @default.
- W1525691133 cites W1624346216 @default.
- W1525691133 cites W1833106472 @default.
- W1525691133 cites W1898885736 @default.
- W1525691133 cites W1970578871 @default.
- W1525691133 cites W1995508663 @default.
- W1525691133 cites W1998981811 @default.
- W1525691133 cites W2007087942 @default.
- W1525691133 cites W2007964976 @default.
- W1525691133 cites W2026525219 @default.
- W1525691133 cites W2028871770 @default.
- W1525691133 cites W2036842663 @default.
- W1525691133 cites W2039857116 @default.
- W1525691133 cites W2080132341 @default.
- W1525691133 cites W2082639157 @default.
- W1525691133 cites W2096592500 @default.
- W1525691133 cites W2117058423 @default.
- W1525691133 cites W2128542677 @default.
- W1525691133 cites W2134812217 @default.
- W1525691133 cites W2143726472 @default.
- W1525691133 cites W2152394274 @default.
- W1525691133 cites W2155633497 @default.
- W1525691133 cites W2157769714 @default.
- W1525691133 cites W2166559064 @default.
- W1525691133 cites W2172009773 @default.
- W1525691133 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4300704" @default.
- W1525691133 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25628951" @default.
- W1525691133 hasPublicationYear "2015" @default.
- W1525691133 type Work @default.
- W1525691133 sameAs 1525691133 @default.
- W1525691133 citedByCount "6" @default.
- W1525691133 countsByYear W15256911332016 @default.
- W1525691133 countsByYear W15256911332017 @default.
- W1525691133 countsByYear W15256911332020 @default.
- W1525691133 countsByYear W15256911332021 @default.
- W1525691133 crossrefType "journal-article" @default.
- W1525691133 hasAuthorship W1525691133A5022667959 @default.
- W1525691133 hasAuthorship W1525691133A5025488742 @default.
- W1525691133 hasAuthorship W1525691133A5047261934 @default.
- W1525691133 hasAuthorship W1525691133A5057389049 @default.
- W1525691133 hasAuthorship W1525691133A5090535914 @default.
- W1525691133 hasConcept C104317684 @default.
- W1525691133 hasConcept C11960822 @default.
- W1525691133 hasConcept C121608353 @default.
- W1525691133 hasConcept C126322002 @default.
- W1525691133 hasConcept C127561419 @default.
- W1525691133 hasConcept C153911025 @default.
- W1525691133 hasConcept C2776131300 @default.
- W1525691133 hasConcept C2776470698 @default.
- W1525691133 hasConcept C2777658100 @default.
- W1525691133 hasConcept C2779013556 @default.
- W1525691133 hasConcept C2780394083 @default.
- W1525691133 hasConcept C2994587330 @default.
- W1525691133 hasConcept C501734568 @default.
- W1525691133 hasConcept C502942594 @default.
- W1525691133 hasConcept C55493867 @default.
- W1525691133 hasConcept C71924100 @default.
- W1525691133 hasConcept C86803240 @default.
- W1525691133 hasConcept C95444343 @default.
- W1525691133 hasConceptScore W1525691133C104317684 @default.
- W1525691133 hasConceptScore W1525691133C11960822 @default.
- W1525691133 hasConceptScore W1525691133C121608353 @default.
- W1525691133 hasConceptScore W1525691133C126322002 @default.
- W1525691133 hasConceptScore W1525691133C127561419 @default.
- W1525691133 hasConceptScore W1525691133C153911025 @default.
- W1525691133 hasConceptScore W1525691133C2776131300 @default.
- W1525691133 hasConceptScore W1525691133C2776470698 @default.
- W1525691133 hasConceptScore W1525691133C2777658100 @default.
- W1525691133 hasConceptScore W1525691133C2779013556 @default.
- W1525691133 hasConceptScore W1525691133C2780394083 @default.
- W1525691133 hasConceptScore W1525691133C2994587330 @default.
- W1525691133 hasConceptScore W1525691133C501734568 @default.
- W1525691133 hasConceptScore W1525691133C502942594 @default.
- W1525691133 hasConceptScore W1525691133C55493867 @default.
- W1525691133 hasConceptScore W1525691133C71924100 @default.
- W1525691133 hasConceptScore W1525691133C86803240 @default.
- W1525691133 hasConceptScore W1525691133C95444343 @default.
- W1525691133 hasIssue "1" @default.
- W1525691133 hasLocation W15256911331 @default.
- W1525691133 hasOpenAccess W1525691133 @default.
- W1525691133 hasPrimaryLocation W15256911331 @default.
- W1525691133 hasRelatedWork W1801698032 @default.
- W1525691133 hasRelatedWork W1875726064 @default.
- W1525691133 hasRelatedWork W1895874031 @default.
- W1525691133 hasRelatedWork W1999890621 @default.
- W1525691133 hasRelatedWork W2003800038 @default.
- W1525691133 hasRelatedWork W2016139330 @default.
- W1525691133 hasRelatedWork W2081774718 @default.