Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308137449> ?p ?o ?g. }
Showing items 1 to 72 of
72
with 100 items per page.
- W4308137449 endingPage "A479" @default.
- W4308137449 startingPage "A478" @default.
- W4308137449 abstract "Abstract Background A growing awareness regarding all molecular mechanisms involved in both tumor shrinkage and hormonal control might allow for medical treatment of pituitary neuroendocrine tumors (PitNETs), especially macroadenomas, rather than surgery. However, there are still no effectively therapeutic targets and corresponding drugs for all subtypes of PitNETs. Methods To identify druggable cell-intrinsic vulnerabilities and correspondingly promising therapeutic agents, we examined 3 PitNETs cell lines and 21 PitNETs patient-derived primary cell cultures in sequential quantitative high-throughput screens (HTS) of 2149 FDA-approved and bio-active targeted drugs. Furthermore, we verified the most effective drug which targeted the class of mechanistic vulnerabilities, histone deacetylase (HDAC) in vitro and in vivo PitNETs models. Further RNA sequencing was employed to reveal underlying molecular mechanisms following treatment with the most effective HDAC inhibitor, panobinostat. Results The HTS effort generated a total of 55296 single-agent dose responses which were enriched among multiple inhibitors for relevant PitNETs oncogenic targets, including HDAC, Akt/mTOR, proteasome, mitogenactivated protein kinase (MEK), and phosphoinositide-3-kinase (PI3K). Inhibitors from these mechanistic classes demonstrated a relatively wide potency-range, with HDAC inhibitors being, on average, the most potent drug class. Further in vitro and In vivo testing in PitNETs models validated HDACi, especially panobinostat as a promising therapeutic approach. Transcriptional surveys revealed substantial alterations to the oxidative redox mediated by the Akt/mTOR1/4EBP1/Nuclear factor-E2-related factor 2 (Nrf2) antioxidant signaling pathway following treatment with panobinostat. Conclusion The current study revealed a class of newfound anti-tumor drugs, HDACi based on the HTS technology, which may be potential drugs for the treatment of PitNETs. Presentation: No date and time listed" @default.
- W4308137449 created "2022-11-08" @default.
- W4308137449 creator A5023111958 @default.
- W4308137449 creator A5035643156 @default.
- W4308137449 creator A5049659189 @default.
- W4308137449 creator A5058415567 @default.
- W4308137449 creator A5064462119 @default.
- W4308137449 date "2022-11-01" @default.
- W4308137449 modified "2023-09-29" @default.
- W4308137449 title "LBODP077 The Therapeutic Potential Of Targeting Histone Deacetylase For Pituitary Neuroendocrine Tumors By High-throughout Drug Screening" @default.
- W4308137449 doi "https://doi.org/10.1210/jendso/bvac150.993" @default.
- W4308137449 hasPublicationYear "2022" @default.
- W4308137449 type Work @default.
- W4308137449 citedByCount "0" @default.
- W4308137449 crossrefType "journal-article" @default.
- W4308137449 hasAuthorship W4308137449A5023111958 @default.
- W4308137449 hasAuthorship W4308137449A5035643156 @default.
- W4308137449 hasAuthorship W4308137449A5049659189 @default.
- W4308137449 hasAuthorship W4308137449A5058415567 @default.
- W4308137449 hasAuthorship W4308137449A5064462119 @default.
- W4308137449 hasBestOaLocation W43081374491 @default.
- W4308137449 hasConcept C104317684 @default.
- W4308137449 hasConcept C10679952 @default.
- W4308137449 hasConcept C150903083 @default.
- W4308137449 hasConcept C207001950 @default.
- W4308137449 hasConcept C2778305200 @default.
- W4308137449 hasConcept C2780225316 @default.
- W4308137449 hasConcept C502942594 @default.
- W4308137449 hasConcept C55493867 @default.
- W4308137449 hasConcept C62478195 @default.
- W4308137449 hasConcept C64927066 @default.
- W4308137449 hasConcept C71924100 @default.
- W4308137449 hasConcept C75217442 @default.
- W4308137449 hasConcept C86554907 @default.
- W4308137449 hasConcept C86803240 @default.
- W4308137449 hasConcept C98274493 @default.
- W4308137449 hasConceptScore W4308137449C104317684 @default.
- W4308137449 hasConceptScore W4308137449C10679952 @default.
- W4308137449 hasConceptScore W4308137449C150903083 @default.
- W4308137449 hasConceptScore W4308137449C207001950 @default.
- W4308137449 hasConceptScore W4308137449C2778305200 @default.
- W4308137449 hasConceptScore W4308137449C2780225316 @default.
- W4308137449 hasConceptScore W4308137449C502942594 @default.
- W4308137449 hasConceptScore W4308137449C55493867 @default.
- W4308137449 hasConceptScore W4308137449C62478195 @default.
- W4308137449 hasConceptScore W4308137449C64927066 @default.
- W4308137449 hasConceptScore W4308137449C71924100 @default.
- W4308137449 hasConceptScore W4308137449C75217442 @default.
- W4308137449 hasConceptScore W4308137449C86554907 @default.
- W4308137449 hasConceptScore W4308137449C86803240 @default.
- W4308137449 hasConceptScore W4308137449C98274493 @default.
- W4308137449 hasIssue "Supplement_1" @default.
- W4308137449 hasLocation W43081374491 @default.
- W4308137449 hasLocation W43081374492 @default.
- W4308137449 hasOpenAccess W4308137449 @default.
- W4308137449 hasPrimaryLocation W43081374491 @default.
- W4308137449 hasRelatedWork W1988747615 @default.
- W4308137449 hasRelatedWork W2026140947 @default.
- W4308137449 hasRelatedWork W2406111920 @default.
- W4308137449 hasRelatedWork W2740548068 @default.
- W4308137449 hasRelatedWork W2912656088 @default.
- W4308137449 hasRelatedWork W2986129865 @default.
- W4308137449 hasRelatedWork W3006030203 @default.
- W4308137449 hasRelatedWork W3008678845 @default.
- W4308137449 hasRelatedWork W4309196680 @default.
- W4308137449 hasRelatedWork W4312127270 @default.
- W4308137449 hasVolume "6" @default.
- W4308137449 isParatext "false" @default.
- W4308137449 isRetracted "false" @default.
- W4308137449 workType "article" @default.