FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4307860306> ?p ?o ?g. }

• W4307860306 endingPage "A900" @default.
• W4307860306 startingPage "A899" @default.
• W4307860306 abstract "Abstract Pancreatic ductal adenocarcinoma (PDAC) comprises more than 90% of pancreatic cancer cases and commonly harbors mutations in KRAS and TP53. PDAC is the third leading cause of cancer-related deaths in the US with approximately 10% 5-year relative survival rate. The poor survival rate largely pertains to aggressive growth following metastasis and limited understanding of prognostic factors. Accumulated evidence indicates that PDAC survival rates are inversely correlated with the pancreatic gene expression of INHBA, which encodes inhibin βA, and circulating levels of activin A (a dimer of inhibin βA), which is overexpressed in pancreatic cancer cells. However, potential mechanisms supporting the correlations have remained unclear. PDAC is etiologically related to sustained metaplasia of acinar cells to ductal-like cells (ADM). Therefore, in this study, we tested the hypothesis that activin A plays a tumor-promoting role via ADM. We implanted mouse PDAC KPC (KrasG12D and Tp53R172H) cells into the pancreata of C57BL/6 male mice and divided them into four groups; sham and three groups of orthotopic mice intraperitoneally (IP) injected with either no (TO), scramble (sc) or inhba siRNA (inhba) packaged with CPX nanoparticles, which previously exhibited tumor-targeted delivery, starting on postoperative day 4. On day 16, blood and tissues were harvested for analyses of tumor-related prognostic blood markers and tumor histology. Implanted KPC cells significantly elevated serum activin A levels and induced tumors as demonstrated by the accumulation of SOX9-positive ADM and a-SMA-positive fibroblasts when compared to sham group. Also, metastases occurred to the liver, spleen, kidney, and intestine. No differences were observed between TO and sc groups. However, when compared to sc group, inhba group had significantly suppressed serum activin A levels and reduced tumor size. Statistically, inhba group had fewer metastases and longer survival rates. Histologically, inhba group exhibited more amylase-positive acini conserved and less accumulation of a-SMA-positive cells in the pancreas. Further, the expression of activin A receptor type 2B (ACVR2B) was greatly induced on the acinar cells undergoing ADM transition in sc group, whereas such expression was subdued in inhba group. Collectively, our data indicate that inhba suppression impedes ADM mediated by KPC cells in mice and suggests activin A as one of tumor-initiating factors. It warrants further investigations in human PDAC models and clinical settings to test the potential therapeutic roles of targeting tumor INHBA in early PDAC development. Presentation: Sunday, June 12, 2022 12:30 p.m. - 12:35 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m." @default.
• W4307860306 created "2022-11-06" @default.
• W4307860306 creator A5005641350 @default.
• W4307860306 creator A5009136371 @default.
• W4307860306 creator A5016187749 @default.
• W4307860306 creator A5020245341 @default.
• W4307860306 creator A5050380300 @default.
• W4307860306 creator A5085045290 @default.
• W4307860306 date "2022-11-01" @default.
• W4307860306 modified "2023-10-18" @default.
• W4307860306 title "RF19 | PSUN383 Potential Role of Activin A During Pancreatic Acinar-to-Ductal Metaplasia of Orthotopic Pancreatic Tumor Mice" @default.
• W4307860306 doi "https://doi.org/10.1210/jendso/bvac150.1863" @default.
• W4307860306 hasPublicationYear "2022" @default.
• W4307860306 type Work @default.
• W4307860306 citedByCount "0" @default.
• W4307860306 crossrefType "journal-article" @default.
• W4307860306 hasAuthorship W4307860306A5005641350 @default.
• W4307860306 hasAuthorship W4307860306A5009136371 @default.
• W4307860306 hasAuthorship W4307860306A5016187749 @default.
• W4307860306 hasAuthorship W4307860306A5020245341 @default.
• W4307860306 hasAuthorship W4307860306A5050380300 @default.
• W4307860306 hasAuthorship W4307860306A5085045290 @default.
• W4307860306 hasBestOaLocation W43078603061 @default.
• W4307860306 hasConcept C121608353 @default.
• W4307860306 hasConcept C126322002 @default.
• W4307860306 hasConcept C134018914 @default.
• W4307860306 hasConcept C142724271 @default.
• W4307860306 hasConcept C2777996000 @default.
• W4307860306 hasConcept C2778764654 @default.
• W4307860306 hasConcept C2779013556 @default.
• W4307860306 hasConcept C2780210213 @default.
• W4307860306 hasConcept C2781187634 @default.
• W4307860306 hasConcept C502942594 @default.
• W4307860306 hasConcept C526805850 @default.
• W4307860306 hasConcept C71924100 @default.
• W4307860306 hasConcept C86803240 @default.
• W4307860306 hasConceptScore W4307860306C121608353 @default.
• W4307860306 hasConceptScore W4307860306C126322002 @default.
• W4307860306 hasConceptScore W4307860306C134018914 @default.
• W4307860306 hasConceptScore W4307860306C142724271 @default.
• W4307860306 hasConceptScore W4307860306C2777996000 @default.
• W4307860306 hasConceptScore W4307860306C2778764654 @default.
• W4307860306 hasConceptScore W4307860306C2779013556 @default.
• W4307860306 hasConceptScore W4307860306C2780210213 @default.
• W4307860306 hasConceptScore W4307860306C2781187634 @default.
• W4307860306 hasConceptScore W4307860306C502942594 @default.
• W4307860306 hasConceptScore W4307860306C526805850 @default.
• W4307860306 hasConceptScore W4307860306C71924100 @default.
• W4307860306 hasConceptScore W4307860306C86803240 @default.
• W4307860306 hasIssue "Supplement_1" @default.
• W4307860306 hasLocation W43078603061 @default.
• W4307860306 hasLocation W43078603062 @default.
• W4307860306 hasOpenAccess W4307860306 @default.
• W4307860306 hasPrimaryLocation W43078603061 @default.
• W4307860306 hasRelatedWork W1983942428 @default.
• W4307860306 hasRelatedWork W1986829345 @default.
• W4307860306 hasRelatedWork W2131760969 @default.
• W4307860306 hasRelatedWork W2171603493 @default.
• W4307860306 hasRelatedWork W2480039331 @default.
• W4307860306 hasRelatedWork W2943331335 @default.
• W4307860306 hasRelatedWork W2996406734 @default.
• W4307860306 hasRelatedWork W3013358603 @default.
• W4307860306 hasRelatedWork W3083688322 @default.
• W4307860306 hasRelatedWork W4200520781 @default.
• W4307860306 hasVolume "6" @default.
• W4307860306 isParatext "false" @default.
• W4307860306 isRetracted "false" @default.
• W4307860306 workType "article" @default.