FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4297776382> ?p ?o ?g. }

• W4297776382 endingPage "S30" @default.
• W4297776382 startingPage "S30" @default.
• W4297776382 abstract "Objectives: Carcinosarcoma (CS) of the ovary and uterus are highly aggressive malignancies associated with poor survival. Poly (ADP-ribose)-polymerase (PARP) inhibitors are targeted agents impairing DNA repair via homologous-recombination-deficiency (HRD) mechanisms. We used whole-exome sequencing (WES) data from a large cohort of CS patients to investigate if ovarian carcinosarcoma (OCS) and uterine carcinosarcoma (UCS) possess the mutational signature of homologous recombination deficiency (HRD). The preclinical activity of olaparib in OCS and UCS cell lines and xenograft models were then evaluated. Methods: WES data from 73 CS samples (25 OCS and 48 UCS), including fresh frozen tissues and primary cell lines, were analyzed for HRD signatures as described by Alexandrov et al. (Nature;2020;578:94-101). Olaparib activity on cell cycle, apoptosis, and cytotoxicity was evaluated against ten fully WES primary CS cell lines. Olaparib antitumor activity was tested in vivo against HRD CS xenografts. Results: From a tot al of 73 CS patients, 60% (15 of 25) of OCS versus 17% (13 of 48) of UCS harbored an HRD-related signature (Signature-3), (p<0.002). Of the ten primary fully sequenced CS cell lines, four were HRD (3 OCS vs 1 UCS), and six were HR proficient (HRP) (5 UCS vs 1 OCS). HRD CS cell lines were significantly more sensitive to olaparib when compared to HRP cell lines [mean IC50 ± SEM: 2.94 μM ± 0.07 vs mean ± SEM: 23.3 μM ± 0.09, (p=0.02). In HRD cell lines, olaparib suppressed CS cell growth through cell cycle arrest in the G2/M phase and caused apoptosis (HRD vs HRP (p < 0.0001]). In vivo, olaparib significantly impaired HRD CS xenografts tumor growth (p= 0.001) and increased overall animal survival (p=0.002) (Figure). Objectives: Carcinosarcoma (CS) of the ovary and uterus are highly aggressive malignancies associated with poor survival. Poly (ADP-ribose)-polymerase (PARP) inhibitors are targeted agents impairing DNA repair via homologous-recombination-deficiency (HRD) mechanisms. We used whole-exome sequencing (WES) data from a large cohort of CS patients to investigate if ovarian carcinosarcoma (OCS) and uterine carcinosarcoma (UCS) possess the mutational signature of homologous recombination deficiency (HRD). The preclinical activity of olaparib in OCS and UCS cell lines and xenograft models were then evaluated. Methods: WES data from 73 CS samples (25 OCS and 48 UCS), including fresh frozen tissues and primary cell lines, were analyzed for HRD signatures as described by Alexandrov et al. (Nature;2020;578:94-101). Olaparib activity on cell cycle, apoptosis, and cytotoxicity was evaluated against ten fully WES primary CS cell lines. Olaparib antitumor activity was tested in vivo against HRD CS xenografts. Results: From a tot al of 73 CS patients, 60% (15 of 25) of OCS versus 17% (13 of 48) of UCS harbored an HRD-related signature (Signature-3), (p<0.002). Of the ten primary fully sequenced CS cell lines, four were HRD (3 OCS vs 1 UCS), and six were HR proficient (HRP) (5 UCS vs 1 OCS). HRD CS cell lines were significantly more sensitive to olaparib when compared to HRP cell lines [mean IC50 ± SEM: 2.94 μM ± 0.07 vs mean ± SEM: 23.3 μM ± 0.09, (p=0.02). In HRD cell lines, olaparib suppressed CS cell growth through cell cycle arrest in the G2/M phase and caused apoptosis (HRD vs HRP (p < 0.0001]). In vivo, olaparib significantly impaired HRD CS xenografts tumor growth (p= 0.001) and increased overall animal survival (p=0.002) (Figure)." @default.
• W4297776382 created "2022-10-01" @default.
• W4297776382 creator A5003477055 @default.
• W4297776382 creator A5006468298 @default.
• W4297776382 creator A5010339370 @default.
• W4297776382 creator A5014098371 @default.
• W4297776382 creator A5021257078 @default.
• W4297776382 creator A5026827320 @default.
• W4297776382 creator A5032849063 @default.
• W4297776382 creator A5034362857 @default.
• W4297776382 creator A5035219534 @default.
• W4297776382 creator A5042405282 @default.
• W4297776382 creator A5042993069 @default.
• W4297776382 creator A5046857977 @default.
• W4297776382 creator A5053887305 @default.
• W4297776382 creator A5060188962 @default.
• W4297776382 creator A5061191066 @default.
• W4297776382 creator A5062471254 @default.
• W4297776382 creator A5080849182 @default.
• W4297776382 creator A5080997789 @default.
• W4297776382 creator A5081094174 @default.
• W4297776382 creator A5089407483 @default.
• W4297776382 date "2022-08-01" @default.
• W4297776382 modified "2023-10-16" @default.
• W4297776382 title "Homologous recombination deficiency (HRD) signature-3 in ovarian and uterine carcinosarcomas correlates with preclinical sensitivity to Olaparib, a Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor (043)" @default.
• W4297776382 doi "https://doi.org/10.1016/s0090-8258(22)01262-8" @default.
• W4297776382 hasPublicationYear "2022" @default.
• W4297776382 type Work @default.
• W4297776382 citedByCount "0" @default.
• W4297776382 crossrefType "journal-article" @default.
• W4297776382 hasAuthorship W4297776382A5003477055 @default.
• W4297776382 hasAuthorship W4297776382A5006468298 @default.
• W4297776382 hasAuthorship W4297776382A5010339370 @default.
• W4297776382 hasAuthorship W4297776382A5014098371 @default.
• W4297776382 hasAuthorship W4297776382A5021257078 @default.
• W4297776382 hasAuthorship W4297776382A5026827320 @default.
• W4297776382 hasAuthorship W4297776382A5032849063 @default.
• W4297776382 hasAuthorship W4297776382A5034362857 @default.
• W4297776382 hasAuthorship W4297776382A5035219534 @default.
• W4297776382 hasAuthorship W4297776382A5042405282 @default.
• W4297776382 hasAuthorship W4297776382A5042993069 @default.
• W4297776382 hasAuthorship W4297776382A5046857977 @default.
• W4297776382 hasAuthorship W4297776382A5053887305 @default.
• W4297776382 hasAuthorship W4297776382A5060188962 @default.
• W4297776382 hasAuthorship W4297776382A5061191066 @default.
• W4297776382 hasAuthorship W4297776382A5062471254 @default.
• W4297776382 hasAuthorship W4297776382A5080849182 @default.
• W4297776382 hasAuthorship W4297776382A5080997789 @default.
• W4297776382 hasAuthorship W4297776382A5081094174 @default.
• W4297776382 hasAuthorship W4297776382A5089407483 @default.
• W4297776382 hasConcept C102744134 @default.
• W4297776382 hasConcept C153911025 @default.
• W4297776382 hasConcept C181199279 @default.
• W4297776382 hasConcept C182979987 @default.
• W4297776382 hasConcept C2779138821 @default.
• W4297776382 hasConcept C2779962180 @default.
• W4297776382 hasConcept C502942594 @default.
• W4297776382 hasConcept C54355233 @default.
• W4297776382 hasConcept C552990157 @default.
• W4297776382 hasConcept C55493867 @default.
• W4297776382 hasConcept C71924100 @default.
• W4297776382 hasConcept C82381507 @default.
• W4297776382 hasConcept C86803240 @default.
• W4297776382 hasConceptScore W4297776382C102744134 @default.
• W4297776382 hasConceptScore W4297776382C153911025 @default.
• W4297776382 hasConceptScore W4297776382C181199279 @default.
• W4297776382 hasConceptScore W4297776382C182979987 @default.
• W4297776382 hasConceptScore W4297776382C2779138821 @default.
• W4297776382 hasConceptScore W4297776382C2779962180 @default.
• W4297776382 hasConceptScore W4297776382C502942594 @default.
• W4297776382 hasConceptScore W4297776382C54355233 @default.
• W4297776382 hasConceptScore W4297776382C552990157 @default.
• W4297776382 hasConceptScore W4297776382C55493867 @default.
• W4297776382 hasConceptScore W4297776382C71924100 @default.
• W4297776382 hasConceptScore W4297776382C82381507 @default.
• W4297776382 hasConceptScore W4297776382C86803240 @default.
• W4297776382 hasLocation W42977763821 @default.
• W4297776382 hasOpenAccess W4297776382 @default.
• W4297776382 hasPrimaryLocation W42977763821 @default.
• W4297776382 hasRelatedWork W3023457002 @default.
• W4297776382 hasRelatedWork W4224114820 @default.
• W4297776382 hasRelatedWork W4250426713 @default.
• W4297776382 hasRelatedWork W4304607276 @default.
• W4297776382 hasRelatedWork W4380590578 @default.
• W4297776382 hasRelatedWork W4380590638 @default.
• W4297776382 hasRelatedWork W4380590803 @default.
• W4297776382 hasRelatedWork W4385446042 @default.
• W4297776382 hasRelatedWork W4385457923 @default.
• W4297776382 hasRelatedWork W4385457983 @default.
• W4297776382 hasVolume "166" @default.
• W4297776382 isParatext "false" @default.
• W4297776382 isRetracted "false" @default.
• W4297776382 workType "article" @default.