FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2973127811> ?p ?o ?g. }

• W2973127811 endingPage "S222" @default.
• W2973127811 startingPage "S222" @default.
• W2973127811 abstract "Over 50% of cancer patients use radiation therapy (RT), but doses can be limited by normal tissue side effects. While RT can improve cancer-specific survival, cardiac morbidity can be increased in patients receiving RT to the heart. Mounting evidence suggests complex genetic modifiers contribute to the risk of RT-induced toxicity, but these genetic modifiers remain largely unknown and poorly understood. Thus, we have developed the first genetic mapping model of radiation-induced cardiotoxicity. Salt-sensitive (SS) and Brown Norway (BN) rats were selectively bred to produce SS.BN3 consomic rats genetically identical to SS rats, except chromosome 3 is inherited from the BN strain. SS and SS.BN3 rats were bred to produce 4 congenic rats that break up chromosome 3: CG1, CG2, CG3 and CG4. Adult female rats received image-guided whole-heart RT (24 Gy x1 or 9 Gy x5, AP:2 laterals). Echocardiograms with strain analysis, RNA-sequencing with pathway analysis, and IHC staining for immune infiltrates were performed. Student’s t-test and Fisher exact test were used for comparisons. SS rats exhibited enhanced cardiac toxicity vs. SS.BN3 rats. Increased cardiac mortality was observed after 24Gy (p<0.01). At 5 months, SS rats had increased pleural effusions (12.9 vs. 3.1 ml, p<0.01). Ejection fraction was lower in SS rats (81% vs. 94%, p<0.01), and other echocardiogram parameters indicated worse cardiac function in the SS rats. Similar results were seen with 9 Gy x5 and in male rats. IHC revealed increased mast cells in the SS.BN3 rat hearts (p<0.01), but decreased macrophages in SS.BN3 rat hearts at 10 weeks post-RT (p<0.05). RNA-seq demonstrated mitochondrial dysfunction pathways were differentially expressed in SS vs. SS.BN3 hearts. Only the CG4 congenic had heart damage similar to SS rats, with post-RT cardiac hypertrophy only seen in SS and CG.4, pleural effusions largest in SS and CG.4, and the lowest cardiac strain seen in SS and CG.4 (p<0.01). CG.4 contains a 25 MB unique region of SS chromosome 3 (0.9% of genome), containing 93 differentially expressed genes. SS rats are more sensitive to cardiac RT than SS.BN3 rats, demonstrating the role of heritable factors in determining cardiac radiosensitivity. Genetic mapping narrowed the region to a 25 MB region with <100 differentially expressed genes. RNA-seq identified potentially important pathways for cardiotoxicity. Immune cells differentially infiltrated the hearts post-RT, with increased mast cells in the more resistant SS.BN3 hearts, consistent with the protective role of mast cells post-cardiac RT in previous studies. Macrophage increases in the SS heart may be due to cardiac damage. Further genetic mapping and targeted studies of the genes/pathways and immune responses important in this model are ongoing. This project has the potential to enhance the effectiveness and toxicity profile of RT." @default.
• W2973127811 created "2019-09-19" @default.
• W2973127811 creator A5002387926 @default.
• W2973127811 creator A5015394743 @default.
• W2973127811 creator A5017129591 @default.
• W2973127811 creator A5019429399 @default.
• W2973127811 creator A5020694375 @default.
• W2973127811 creator A5021123766 @default.
• W2973127811 creator A5025093312 @default.
• W2973127811 creator A5045029073 @default.
• W2973127811 creator A5052008011 @default.
• W2973127811 creator A5065798455 @default.
• W2973127811 creator A5069690158 @default.
• W2973127811 creator A5078500350 @default.
• W2973127811 creator A5085007053 @default.
• W2973127811 date "2019-09-01" @default.
• W2973127811 modified "2023-09-23" @default.
• W2973127811 title "Identification of Pathways and Genetic Variants Important for Radiation-Induced Cardiotoxicity Using Genetic Mapping" @default.
• W2973127811 doi "https://doi.org/10.1016/j.ijrobp.2019.06.311" @default.
• W2973127811 hasPublicationYear "2019" @default.
• W2973127811 type Work @default.
• W2973127811 sameAs 2973127811 @default.
• W2973127811 citedByCount "0" @default.
• W2973127811 crossrefType "journal-article" @default.
• W2973127811 hasAuthorship W2973127811A5002387926 @default.
• W2973127811 hasAuthorship W2973127811A5015394743 @default.
• W2973127811 hasAuthorship W2973127811A5017129591 @default.
• W2973127811 hasAuthorship W2973127811A5019429399 @default.
• W2973127811 hasAuthorship W2973127811A5020694375 @default.
• W2973127811 hasAuthorship W2973127811A5021123766 @default.
• W2973127811 hasAuthorship W2973127811A5025093312 @default.
• W2973127811 hasAuthorship W2973127811A5045029073 @default.
• W2973127811 hasAuthorship W2973127811A5052008011 @default.
• W2973127811 hasAuthorship W2973127811A5065798455 @default.
• W2973127811 hasAuthorship W2973127811A5069690158 @default.
• W2973127811 hasAuthorship W2973127811A5078500350 @default.
• W2973127811 hasAuthorship W2973127811A5085007053 @default.
• W2973127811 hasBestOaLocation W29731278111 @default.
• W2973127811 hasConcept C104317684 @default.
• W2973127811 hasConcept C111566952 @default.
• W2973127811 hasConcept C126322002 @default.
• W2973127811 hasConcept C127716648 @default.
• W2973127811 hasConcept C142724271 @default.
• W2973127811 hasConcept C204232928 @default.
• W2973127811 hasConcept C2778022156 @default.
• W2973127811 hasConcept C2778198053 @default.
• W2973127811 hasConcept C2778233292 @default.
• W2973127811 hasConcept C29730261 @default.
• W2973127811 hasConcept C30481170 @default.
• W2973127811 hasConcept C54355233 @default.
• W2973127811 hasConcept C71924100 @default.
• W2973127811 hasConcept C78085059 @default.
• W2973127811 hasConcept C84951073 @default.
• W2973127811 hasConcept C86803240 @default.
• W2973127811 hasConceptScore W2973127811C104317684 @default.
• W2973127811 hasConceptScore W2973127811C111566952 @default.
• W2973127811 hasConceptScore W2973127811C126322002 @default.
• W2973127811 hasConceptScore W2973127811C127716648 @default.
• W2973127811 hasConceptScore W2973127811C142724271 @default.
• W2973127811 hasConceptScore W2973127811C204232928 @default.
• W2973127811 hasConceptScore W2973127811C2778022156 @default.
• W2973127811 hasConceptScore W2973127811C2778198053 @default.
• W2973127811 hasConceptScore W2973127811C2778233292 @default.
• W2973127811 hasConceptScore W2973127811C29730261 @default.
• W2973127811 hasConceptScore W2973127811C30481170 @default.
• W2973127811 hasConceptScore W2973127811C54355233 @default.
• W2973127811 hasConceptScore W2973127811C71924100 @default.
• W2973127811 hasConceptScore W2973127811C78085059 @default.
• W2973127811 hasConceptScore W2973127811C84951073 @default.
• W2973127811 hasConceptScore W2973127811C86803240 @default.
• W2973127811 hasIssue "1" @default.
• W2973127811 hasLocation W29731278111 @default.
• W2973127811 hasOpenAccess W2973127811 @default.
• W2973127811 hasPrimaryLocation W29731278111 @default.
• W2973127811 hasRelatedWork W2010795729 @default.
• W2973127811 hasRelatedWork W2073911958 @default.
• W2973127811 hasRelatedWork W2101382021 @default.
• W2973127811 hasRelatedWork W2356471183 @default.
• W2973127811 hasRelatedWork W2501648659 @default.
• W2973127811 hasRelatedWork W2579944075 @default.
• W2973127811 hasRelatedWork W2890579914 @default.
• W2973127811 hasRelatedWork W3004931599 @default.
• W2973127811 hasRelatedWork W3092986513 @default.
• W2973127811 hasRelatedWork W4312619599 @default.
• W2973127811 hasVolume "105" @default.
• W2973127811 isParatext "false" @default.
• W2973127811 isRetracted "false" @default.
• W2973127811 magId "2973127811" @default.
• W2973127811 workType "article" @default.