Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361949658> ?p ?o ?g. }
Showing items 1 to 70 of
70
with 100 items per page.
- W4361949658 abstract "<div>Abstract<p><b>Purpose:</b> The “gate-keeper” mutations T674I platelet—derived growth factor receptor α (PDGFRα) in hypereosinophilic syndrome (HES) and T315I Bcr-Abl in chronic myeloid leukemia (CML) are resistant to imatinib and the second-generation small-molecule tyrosine kinase inhibitors (TKI). However, to combat acquired resistance to imatinib, an alternative approach is to decrease the expression of the addicted gene to efficiently kill resistant malignant hematologic cells. The purpose of this study was to evaluate the strategy of shutting down the transcription and expression of FIP1-like-1 (FIP1L1)–PDGFRα and Bcr-Abl with SNS-032, an inhibitor of cyclin-dependent kinase 7 (CDK7) and CDK9 in phase I clinical trials.</p><p><b>Experimental Design:</b> The effects of SNS-032 on PDGFRα and Bcr-Abl signaling pathways, apoptosis, and cell cycling were analyzed in TKI-resistant cells of HES and CML. The <i>in vivo</i> antitumor activity of SNS-032 was assessed with xenografted BaF3-T674I FIP1L1-PDGFRα and KBM5-T315I Bcr-Abl cells in nude mouse models.</p><p><b>Results:</b> SNS-032 inhibited the phosphorylation on Ser5 and Ser2 of RNA polymerase II. SNS-032 decreased both the mRNA and protein levels of FIP1L1-PDGFRα and Bcr-Abl and inhibited the proliferation of malignant cells expressing FIP1L1-PDGFRα or Bcr-Abl. It also decreased the phosphorylation of downstream molecules. It induced apoptosis by triggering both the mitochondrial pathway and the death receptor pathway.</p><p><b>Conclusions:</b> This CDK7/9 inhibitor potently inhibits FIP1L1-PDGFRα–positive HES cells and Bcr-Abl–positive CML cells regardless of their sensitivity to imatinib. SNS-032 may have potential in treating hematologic malignancy by abrogating oncogene addiction. <i>Clin Cancer Res; 18(7); 1966–78. ©2012 AACR</i>.</p></div>" @default.
- W4361949658 created "2023-04-05" @default.
- W4361949658 creator A5019496807 @default.
- W4361949658 creator A5021400904 @default.
- W4361949658 creator A5021426745 @default.
- W4361949658 creator A5034363096 @default.
- W4361949658 creator A5042363295 @default.
- W4361949658 creator A5043777663 @default.
- W4361949658 creator A5045314786 @default.
- W4361949658 creator A5071900138 @default.
- W4361949658 date "2023-03-31" @default.
- W4361949658 modified "2023-10-16" @default.
- W4361949658 title "Data from Cyclin-Dependent Kinase 7/9 Inhibitor SNS-032 Abrogates FIP1-like-1 Platelet-Derived Growth Factor Receptor α and Bcr-Abl Oncogene Addiction in Malignant Hematologic Cells" @default.
- W4361949658 doi "https://doi.org/10.1158/1078-0432.c.6519674.v1" @default.
- W4361949658 hasPublicationYear "2023" @default.
- W4361949658 type Work @default.
- W4361949658 citedByCount "0" @default.
- W4361949658 crossrefType "posted-content" @default.
- W4361949658 hasAuthorship W4361949658A5019496807 @default.
- W4361949658 hasAuthorship W4361949658A5021400904 @default.
- W4361949658 hasAuthorship W4361949658A5021426745 @default.
- W4361949658 hasAuthorship W4361949658A5034363096 @default.
- W4361949658 hasAuthorship W4361949658A5042363295 @default.
- W4361949658 hasAuthorship W4361949658A5043777663 @default.
- W4361949658 hasAuthorship W4361949658A5045314786 @default.
- W4361949658 hasAuthorship W4361949658A5071900138 @default.
- W4361949658 hasBestOaLocation W43619496582 @default.
- W4361949658 hasConcept C125418893 @default.
- W4361949658 hasConcept C185592680 @default.
- W4361949658 hasConcept C190283241 @default.
- W4361949658 hasConcept C2777583451 @default.
- W4361949658 hasConcept C2778729363 @default.
- W4361949658 hasConcept C2781018059 @default.
- W4361949658 hasConcept C29537977 @default.
- W4361949658 hasConcept C42362537 @default.
- W4361949658 hasConcept C502942594 @default.
- W4361949658 hasConcept C55493867 @default.
- W4361949658 hasConcept C62478195 @default.
- W4361949658 hasConcept C86803240 @default.
- W4361949658 hasConcept C95444343 @default.
- W4361949658 hasConceptScore W4361949658C125418893 @default.
- W4361949658 hasConceptScore W4361949658C185592680 @default.
- W4361949658 hasConceptScore W4361949658C190283241 @default.
- W4361949658 hasConceptScore W4361949658C2777583451 @default.
- W4361949658 hasConceptScore W4361949658C2778729363 @default.
- W4361949658 hasConceptScore W4361949658C2781018059 @default.
- W4361949658 hasConceptScore W4361949658C29537977 @default.
- W4361949658 hasConceptScore W4361949658C42362537 @default.
- W4361949658 hasConceptScore W4361949658C502942594 @default.
- W4361949658 hasConceptScore W4361949658C55493867 @default.
- W4361949658 hasConceptScore W4361949658C62478195 @default.
- W4361949658 hasConceptScore W4361949658C86803240 @default.
- W4361949658 hasConceptScore W4361949658C95444343 @default.
- W4361949658 hasLocation W43619496581 @default.
- W4361949658 hasLocation W43619496582 @default.
- W4361949658 hasOpenAccess W4361949658 @default.
- W4361949658 hasPrimaryLocation W43619496581 @default.
- W4361949658 hasRelatedWork W1984160018 @default.
- W4361949658 hasRelatedWork W1995217826 @default.
- W4361949658 hasRelatedWork W2072875377 @default.
- W4361949658 hasRelatedWork W2100041900 @default.
- W4361949658 hasRelatedWork W2137270304 @default.
- W4361949658 hasRelatedWork W2149357045 @default.
- W4361949658 hasRelatedWork W2385763410 @default.
- W4361949658 hasRelatedWork W2388585719 @default.
- W4361949658 hasRelatedWork W3112641790 @default.
- W4361949658 hasRelatedWork W4323519313 @default.
- W4361949658 isParatext "false" @default.
- W4361949658 isRetracted "false" @default.
- W4361949658 workType "article" @default.