FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2605047085> ?p ?o ?g. }

• W2605047085 endingPage "1099" @default.
• W2605047085 startingPage "1099" @default.
• W2605047085 abstract "4755 Phosphorylation of the retinoblastoma protein (Rb) by cyclin dependent kinases 4 and 6 (CDK4/6) is typically required for human cancer cell proliferation. PD0332991 is a potent, selective, and orally bioavailable inhibitor of CDK4/6. In human tumor xenografts, PD0332991 caused significant reductions in tumor mass and/or growth delay in several xenograft models but had less effect in others despite effectively blocking Rb phosphorylation in all models. To investigate differences in sensitivity to PD0332991, we characterized gene expression in human tumor cell cultures and xenografts treated with PD0332991 using Affymetrix GeneChip (HU133A) technology. Three human xenograft tumors were chosen that varied in response to PD0332991: Colo205 (tumor regression), MDAMB435 (tumor stasis), and SW620 (slight tumor growth delay). There was an apparent association between the extent of gene modulation (both in number of genes and in magnitude of response for individual genes) and the sensitivity to tumor growth delay of the xenograft model. Indeed, the capacity of PD0332991 to modulate gene expression as determined by number of gene changes (≥2-fold, p ≤0.05) was correlated with objective measures of tumor growth delay across the 3 xenograft models and 3 dose levels, suggesting that efficacy is mechanistically linked to the ability of PD0332991 to alter gene expression. The physiological roles of genes regulated by PD0332991 were characterized using Gene Ontology annotation. In both MDAMB435 cell cultures and the 3 xenograft models, PD0332991 primarily downregulated genes associated with DNA replication and repair, cell cycle, signal transduction, and mitosis. Many genes modulated by PD0332991 have been previously characterized as being transcriptionally activated by E2F transcription factors. Gene changes shared between models were identified. This gene cohort was similar to the previously described proliferation gene signature noted in several cancer types and may be an appropriate efficacy related clinical biomarker for PD0332991. Changes in gene expression were confirmed for selected markers using RT-PCR, ELISA, and western blotting. The results suggest that PD0332991, by selectively blocking Rb phosphorylation, causes transcriptional down-regulation of genes required for cancer cell proliferation. Differences in sensitivity to PD0332991 may be due to factors that associate with hypophosphorylated Rb to regulate transcription." @default.
• W2605047085 created "2017-04-14" @default.
• W2605047085 creator A5010999026 @default.
• W2605047085 creator A5016938641 @default.
• W2605047085 creator A5027633490 @default.
• W2605047085 creator A5029175020 @default.
• W2605047085 creator A5033059231 @default.
• W2605047085 creator A5036416730 @default.
• W2605047085 creator A5041780198 @default.
• W2605047085 creator A5048873469 @default.
• W2605047085 creator A5059505683 @default.
• W2605047085 creator A5069735960 @default.
• W2605047085 creator A5084743212 @default.
• W2605047085 creator A5087583913 @default.
• W2605047085 creator A5088653445 @default.
• W2605047085 date "2004-04-01" @default.
• W2605047085 modified "2023-10-17" @default.
• W2605047085 title "Gene expression changes linked to efficacy in human tumor xenografts treated with the CDK4/6 inhibitor PD0332991" @default.
• W2605047085 hasPublicationYear "2004" @default.
• W2605047085 type Work @default.
• W2605047085 sameAs 2605047085 @default.
• W2605047085 citedByCount "0" @default.
• W2605047085 crossrefType "journal-article" @default.
• W2605047085 hasAuthorship W2605047085A5010999026 @default.
• W2605047085 hasAuthorship W2605047085A5016938641 @default.
• W2605047085 hasAuthorship W2605047085A5027633490 @default.
• W2605047085 hasAuthorship W2605047085A5029175020 @default.
• W2605047085 hasAuthorship W2605047085A5033059231 @default.
• W2605047085 hasAuthorship W2605047085A5036416730 @default.
• W2605047085 hasAuthorship W2605047085A5041780198 @default.
• W2605047085 hasAuthorship W2605047085A5048873469 @default.
• W2605047085 hasAuthorship W2605047085A5059505683 @default.
• W2605047085 hasAuthorship W2605047085A5069735960 @default.
• W2605047085 hasAuthorship W2605047085A5084743212 @default.
• W2605047085 hasAuthorship W2605047085A5087583913 @default.
• W2605047085 hasAuthorship W2605047085A5088653445 @default.
• W2605047085 hasConcept C121608353 @default.
• W2605047085 hasConcept C124320809 @default.
• W2605047085 hasConcept C199649820 @default.
• W2605047085 hasConcept C2775930923 @default.
• W2605047085 hasConcept C2779744173 @default.
• W2605047085 hasConcept C29537977 @default.
• W2605047085 hasConcept C502942594 @default.
• W2605047085 hasConcept C530470458 @default.
• W2605047085 hasConcept C54355233 @default.
• W2605047085 hasConcept C62112901 @default.
• W2605047085 hasConcept C86803240 @default.
• W2605047085 hasConceptScore W2605047085C121608353 @default.
• W2605047085 hasConceptScore W2605047085C124320809 @default.
• W2605047085 hasConceptScore W2605047085C199649820 @default.
• W2605047085 hasConceptScore W2605047085C2775930923 @default.
• W2605047085 hasConceptScore W2605047085C2779744173 @default.
• W2605047085 hasConceptScore W2605047085C29537977 @default.
• W2605047085 hasConceptScore W2605047085C502942594 @default.
• W2605047085 hasConceptScore W2605047085C530470458 @default.
• W2605047085 hasConceptScore W2605047085C54355233 @default.
• W2605047085 hasConceptScore W2605047085C62112901 @default.
• W2605047085 hasConceptScore W2605047085C86803240 @default.
• W2605047085 hasLocation W26050470851 @default.
• W2605047085 hasOpenAccess W2605047085 @default.
• W2605047085 hasPrimaryLocation W26050470851 @default.
• W2605047085 hasRelatedWork W1657226110 @default.
• W2605047085 hasRelatedWork W1974534085 @default.
• W2605047085 hasRelatedWork W2039663699 @default.
• W2605047085 hasRelatedWork W2049966539 @default.
• W2605047085 hasRelatedWork W2077108721 @default.
• W2605047085 hasRelatedWork W2107641193 @default.
• W2605047085 hasRelatedWork W2153468936 @default.
• W2605047085 hasRelatedWork W2329031450 @default.
• W2605047085 hasRelatedWork W2330794259 @default.
• W2605047085 hasRelatedWork W2365056729 @default.
• W2605047085 hasRelatedWork W2499065405 @default.
• W2605047085 hasRelatedWork W2571801221 @default.
• W2605047085 hasRelatedWork W2584411905 @default.
• W2605047085 hasRelatedWork W2730233714 @default.
• W2605047085 hasRelatedWork W2735236663 @default.
• W2605047085 hasRelatedWork W2787774382 @default.
• W2605047085 hasRelatedWork W2891835310 @default.
• W2605047085 hasRelatedWork W2972715430 @default.
• W2605047085 hasRelatedWork W3042934550 @default.
• W2605047085 hasRelatedWork W3127511895 @default.
• W2605047085 hasVolume "64" @default.
• W2605047085 isParatext "false" @default.
• W2605047085 isRetracted "false" @default.
• W2605047085 magId "2605047085" @default.
• W2605047085 workType "article" @default.