Matches in SemOpenAlex for { <https://semopenalex.org/work/W2588893619> ?p ?o ?g. }
Showing items 1 to 84 of
84
with 100 items per page.
- W2588893619 endingPage "vi117" @default.
- W2588893619 startingPage "vi117" @default.
- W2588893619 abstract "Our aim is to target tumor cells specifically by directly suppressing their oncogenes with peptide nucleic acid (PNA) oligonucleotide analogues. These bind to DNA over 1000-fold more avidly than its native complement and when conjugated to delivery peptides can be made nuclear and cell membrane permeable. We have employed these PNA oligomers to target BRAF V600E in a sequence-specific complementary manner in order to disrupt transcription. For these studies, we have employed a novel delivery peptide conjugated to PNA modified to increase both cellular delivery and stability towards its target. We have assessed its ability to obstruct BRAF V600E transcription specifically in variety of cell lines by monitoring suppression of cell proliferation, BRAF V600E protein expression, and mRNA transcription. Tumor reduction was assessed through xenograft mouse models. Our results indicate that exposure of the melanoma cell lines to a modified PNA-peptide conjugate selective for BRAF V600E results in a concentration-dependent inhibition of cell growth that is specific for the BRAF V600E mutant melanoma cell lines with an IC50 range of 250 to 500 nM. Moreover, there is no inhibition of BRAF WT cell growth at these concentrations. This is associated with suppression of BRAF V600E protein over time. Furthermore, BRAF V600E protein expression was suppressed for up to 6 days following initial exposure proving its durability of inhibition. Exposure to this modified PNA-peptide down-regulates BRAF V600E mRNA transcription exclusively in the mutant cell lines. Live cell imaging of BRAF V600E mutant cells indicates localization of fluorescein-labeled PNA-delivery peptide conjugates to the nucleus within 3 hours of treatment. Xenograft mouse studies show reversal of tumor burden after four doses continuing for days following the last dose with a maximum tolerated dose to at least 50mg/kg. Our results indicate that these PNA-peptide derivatives could represent a novel and promising new therapy for patients with BRAF V600E mutant melanoma, and this technology could be applied to a multitude of other cancers either with specific translocations or mutations differing from wild-type cells even by only a single base pair." @default.
- W2588893619 created "2017-02-24" @default.
- W2588893619 creator A5006913373 @default.
- W2588893619 creator A5022744236 @default.
- W2588893619 creator A5026962347 @default.
- W2588893619 creator A5079178474 @default.
- W2588893619 creator A5081400151 @default.
- W2588893619 date "2016-10-01" @default.
- W2588893619 modified "2023-10-14" @default.
- W2588893619 title "Suppression of oncogene transcription - PNA as targeted cancer therapy for BRAF-V600E mutant melanoma" @default.
- W2588893619 doi "https://doi.org/10.1093/annonc/mdw368.11" @default.
- W2588893619 hasPublicationYear "2016" @default.
- W2588893619 type Work @default.
- W2588893619 sameAs 2588893619 @default.
- W2588893619 citedByCount "0" @default.
- W2588893619 crossrefType "journal-article" @default.
- W2588893619 hasAuthorship W2588893619A5006913373 @default.
- W2588893619 hasAuthorship W2588893619A5022744236 @default.
- W2588893619 hasAuthorship W2588893619A5026962347 @default.
- W2588893619 hasAuthorship W2588893619A5079178474 @default.
- W2588893619 hasAuthorship W2588893619A5081400151 @default.
- W2588893619 hasBestOaLocation W25888936191 @default.
- W2588893619 hasConcept C104317684 @default.
- W2588893619 hasConcept C129312508 @default.
- W2588893619 hasConcept C138885662 @default.
- W2588893619 hasConcept C143065580 @default.
- W2588893619 hasConcept C1491633281 @default.
- W2588893619 hasConcept C153911025 @default.
- W2588893619 hasConcept C179926584 @default.
- W2588893619 hasConcept C2776470698 @default.
- W2588893619 hasConcept C2777343594 @default.
- W2588893619 hasConcept C2777658100 @default.
- W2588893619 hasConcept C2779281246 @default.
- W2588893619 hasConcept C2781018059 @default.
- W2588893619 hasConcept C29537977 @default.
- W2588893619 hasConcept C41895202 @default.
- W2588893619 hasConcept C502942594 @default.
- W2588893619 hasConcept C54355233 @default.
- W2588893619 hasConcept C552990157 @default.
- W2588893619 hasConcept C55493867 @default.
- W2588893619 hasConcept C62112901 @default.
- W2588893619 hasConcept C81885089 @default.
- W2588893619 hasConcept C86803240 @default.
- W2588893619 hasConceptScore W2588893619C104317684 @default.
- W2588893619 hasConceptScore W2588893619C129312508 @default.
- W2588893619 hasConceptScore W2588893619C138885662 @default.
- W2588893619 hasConceptScore W2588893619C143065580 @default.
- W2588893619 hasConceptScore W2588893619C1491633281 @default.
- W2588893619 hasConceptScore W2588893619C153911025 @default.
- W2588893619 hasConceptScore W2588893619C179926584 @default.
- W2588893619 hasConceptScore W2588893619C2776470698 @default.
- W2588893619 hasConceptScore W2588893619C2777343594 @default.
- W2588893619 hasConceptScore W2588893619C2777658100 @default.
- W2588893619 hasConceptScore W2588893619C2779281246 @default.
- W2588893619 hasConceptScore W2588893619C2781018059 @default.
- W2588893619 hasConceptScore W2588893619C29537977 @default.
- W2588893619 hasConceptScore W2588893619C41895202 @default.
- W2588893619 hasConceptScore W2588893619C502942594 @default.
- W2588893619 hasConceptScore W2588893619C54355233 @default.
- W2588893619 hasConceptScore W2588893619C552990157 @default.
- W2588893619 hasConceptScore W2588893619C55493867 @default.
- W2588893619 hasConceptScore W2588893619C62112901 @default.
- W2588893619 hasConceptScore W2588893619C81885089 @default.
- W2588893619 hasConceptScore W2588893619C86803240 @default.
- W2588893619 hasLocation W25888936191 @default.
- W2588893619 hasOpenAccess W2588893619 @default.
- W2588893619 hasPrimaryLocation W25888936191 @default.
- W2588893619 hasRelatedWork W2003320760 @default.
- W2588893619 hasRelatedWork W2613842309 @default.
- W2588893619 hasRelatedWork W2765712504 @default.
- W2588893619 hasRelatedWork W2770351100 @default.
- W2588893619 hasRelatedWork W2808352915 @default.
- W2588893619 hasRelatedWork W2899361988 @default.
- W2588893619 hasRelatedWork W2901840572 @default.
- W2588893619 hasRelatedWork W2924445917 @default.
- W2588893619 hasRelatedWork W2977485281 @default.
- W2588893619 hasRelatedWork W3019229794 @default.
- W2588893619 hasVolume "27" @default.
- W2588893619 isParatext "false" @default.
- W2588893619 isRetracted "false" @default.
- W2588893619 magId "2588893619" @default.
- W2588893619 workType "article" @default.