FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3168584911> ?p ?o ?g. }

• W3168584911 endingPage "2251" @default.
• W3168584911 startingPage "2240" @default.
• W3168584911 abstract "Leflunomide (Lef) is an agent used in autoimmune disorders that interferes with DNA synthesis. De Novo pyrimidine synthesis is a mechanism of Gemcitabine (Gem) resistance in pancreatic cancer. This study aims to assess the efficacy and changes in the tumor microenvironment of Lef monotherapy and in combination with Gem, in a syngeneic mouse model of pancreatic cancer. Methods: MTS proliferation assays were conducted to assess growth inhibition by Gem (0-20 nM), Lef (0-40 uM) and Gem+Lef in KPC (KrasLSL.G12D/+;p53R172H/+; PdxCretg/+) cells in vitro. An in vivo heterotopic KPC model was used and cohorts were treated with: PBS (control), Gem (75 mg/kg/q3d), Lef (40 mg/kg/d), or Gem+Lef. At d28 post-treatment, tumor burden, proliferation index (Ki67), and vascularity (CD31) were measured. Changes in the frequency of peripheral and intratumoral immune cell subsets were evaluated via FACS. Liquid chromatography-mass spectrometry was used for metabolomics profiling. Results: Lef inhibits KPC cell growth and synergizes with Gem in vitro (P<0.05; Combination Index 0.44 (<1 indicates synergy). In vivo, Lef alone and in combination with Gem delays KPC tumor progression (P<0.001). CTLA-4+T cells are also significantly decreased in tumors treated with Lef, Gem or in combination (Gem+Lef) compared to controls (P<0.05). Combination therapy also decreased the Ki67 and vascularity (P<0.01). Leflunomide inhibits de novo pyrimidine synthesis both in vitro (p<0.0001) and in vivo (p<0.05). Conclusions: In this study, we demonstrated that Gem+Lef inhibits pancreatic cancer growth, decrease T cell exhaustion, vascularity and as proof of principle inhibits de novo pyrimidine synthesis. Further characterization of changes in adaptive immunity are necessary to characterize the mechanism of tumor growth inhibition and facilitate translation to a clinical trial." @default.
• W3168584911 created "2021-06-22" @default.
• W3168584911 creator A5019127443 @default.
• W3168584911 creator A5022693796 @default.
• W3168584911 creator A5025468423 @default.
• W3168584911 creator A5025588089 @default.
• W3168584911 creator A5053467552 @default.
• W3168584911 creator A5070651494 @default.
• W3168584911 creator A5079132331 @default.
• W3168584911 creator A5079532813 @default.
• W3168584911 creator A5081810781 @default.
• W3168584911 creator A5082530695 @default.
• W3168584911 creator A5084580082 @default.
• W3168584911 creator A5089096974 @default.
• W3168584911 creator A5089440321 @default.
• W3168584911 date "2021-01-01" @default.
• W3168584911 modified "2023-10-07" @default.
• W3168584911 title "Inhibition of <i>de novo</i> pyrimidine synthesis augments Gemcitabine induced growth inhibition in an immunocompetent model of pancreatic cancer" @default.
• W3168584911 cites W1965037168 @default.
• W3168584911 cites W2045246542 @default.
• W3168584911 cites W2071349823 @default.
• W3168584911 cites W2096439168 @default.
• W3168584911 cites W2127459073 @default.
• W3168584911 cites W2133708837 @default.
• W3168584911 cites W2192943385 @default.
• W3168584911 cites W2461774736 @default.
• W3168584911 cites W2530363394 @default.
• W3168584911 cites W2560233728 @default.
• W3168584911 cites W2592487518 @default.
• W3168584911 cites W2622943546 @default.
• W3168584911 cites W2624816244 @default.
• W3168584911 cites W2729738977 @default.
• W3168584911 cites W2735063286 @default.
• W3168584911 cites W2752122202 @default.
• W3168584911 cites W2763221792 @default.
• W3168584911 cites W2767073776 @default.
• W3168584911 cites W2769094265 @default.
• W3168584911 cites W2783642736 @default.
• W3168584911 cites W2793393227 @default.
• W3168584911 cites W2896506245 @default.
• W3168584911 cites W2905589125 @default.
• W3168584911 cites W2929868087 @default.
• W3168584911 cites W2946547542 @default.
• W3168584911 cites W2963642174 @default.
• W3168584911 cites W2970828652 @default.
• W3168584911 cites W2985148590 @default.
• W3168584911 cites W3028579353 @default.
• W3168584911 cites W3092057003 @default.
• W3168584911 cites W3119005666 @default.
• W3168584911 cites W3127189019 @default.
• W3168584911 cites W3129957552 @default.
• W3168584911 cites W3134721707 @default.
• W3168584911 cites W4251725022 @default.
• W3168584911 doi "https://doi.org/10.7150/ijbs.60473" @default.
• W3168584911 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8241727" @default.
• W3168584911 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34239352" @default.
• W3168584911 hasPublicationYear "2021" @default.
• W3168584911 type Work @default.
• W3168584911 sameAs 3168584911 @default.
• W3168584911 citedByCount "6" @default.
• W3168584911 countsByYear W31685849112021 @default.
• W3168584911 countsByYear W31685849112022 @default.
• W3168584911 countsByYear W31685849112023 @default.
• W3168584911 crossrefType "journal-article" @default.
• W3168584911 hasAuthorship W3168584911A5019127443 @default.
• W3168584911 hasAuthorship W3168584911A5022693796 @default.
• W3168584911 hasAuthorship W3168584911A5025468423 @default.
• W3168584911 hasAuthorship W3168584911A5025588089 @default.
• W3168584911 hasAuthorship W3168584911A5053467552 @default.
• W3168584911 hasAuthorship W3168584911A5070651494 @default.
• W3168584911 hasAuthorship W3168584911A5079132331 @default.
• W3168584911 hasAuthorship W3168584911A5079532813 @default.
• W3168584911 hasAuthorship W3168584911A5081810781 @default.
• W3168584911 hasAuthorship W3168584911A5082530695 @default.
• W3168584911 hasAuthorship W3168584911A5084580082 @default.
• W3168584911 hasAuthorship W3168584911A5089096974 @default.
• W3168584911 hasAuthorship W3168584911A5089440321 @default.
• W3168584911 hasBestOaLocation W31685849111 @default.
• W3168584911 hasConcept C121608353 @default.
• W3168584911 hasConcept C126322002 @default.
• W3168584911 hasConcept C13576564 @default.
• W3168584911 hasConcept C150903083 @default.
• W3168584911 hasConcept C181199279 @default.
• W3168584911 hasConcept C185592680 @default.
• W3168584911 hasConcept C200159599 @default.
• W3168584911 hasConcept C202751555 @default.
• W3168584911 hasConcept C203014093 @default.
• W3168584911 hasConcept C207001950 @default.
• W3168584911 hasConcept C2775905006 @default.
• W3168584911 hasConcept C2776107976 @default.
• W3168584911 hasConcept C2776476023 @default.
• W3168584911 hasConcept C2779321679 @default.
• W3168584911 hasConcept C2780210213 @default.
• W3168584911 hasConcept C2780258809 @default.
• W3168584911 hasConcept C2781059491 @default.
• W3168584911 hasConcept C3020616263 @default.
• W3168584911 hasConcept C502942594 @default.
• W3168584911 hasConcept C55493867 @default.

• next