Matches in SemOpenAlex for { <https://semopenalex.org/work/W3049390013> ?p ?o ?g. }
- W3049390013 endingPage "179" @default.
- W3049390013 startingPage "161" @default.
- W3049390013 abstract "Pancreatic ductal adenocarcinoma (PDAC) is resistant to most therapeutics owing to dense fibrotic stroma orchestrated by cancer-associated pancreatic stellate cells (CAPaSC). CAPaSC also support cancer cell growth, metastasis, and resistance to apoptosis. Currently, there is no effective therapy for PDAC that specifically targets CAPaSC. We previously reported a rationally designed protein, ProAgio, that targets integrin αvβ3 at a novel site and induces apoptosis in integrin αvβ3-expressing cells. Because both CAPaSC and angiogenic endothelial cells express high levels of integrin αvβ3, we aimed to analyze the effects of ProAgio in PDAC tumor.Expression of integrin αvβ3 was examined in both patient tissue and cultured cells. The effects of ProAgio on CAPaSC were analyzed using an apoptosis assay kit. The effects of ProAgio in PDAC tumor were studied in 3 murine tumor models: subcutaneous xenograft, genetic engineered (KrasG12D; p53R172H; Pdx1-Cre, GEM-KPC) mice, and an orthotopic KrasG12D; p53R172H; Pdx1-Cre (KPC) model.ProAgio induces apoptosis in CAPaSC. ProAgio treatment significantly prolonged survival of a genetically engineered mouse-KPC and orthotopic KPC mice alone or in combination with gemcitabine (Gem). ProAgio specifically induced apoptosis in CAPaSC, resorbed collagen, and opened collapsed tumor vessels without an increase in angiogenesis in PDAC tumor, enabling drug delivery into the tumor. ProAgio decreased intratumoral insulin-like growth factor 1 levels as a result of depletion of CAPaSC and consequently decreased cytidine deaminase, a Gem metabolism enzyme in cancer cells, and thereby reduced resistance to Gem-induced apoptosis.Our study suggests that ProAgio is an effective PDAC treatment agent because it specifically depletes CAPaSC and eliminates tumor angiogenesis, thereby enhancing drug delivery and Gem efficacy in PDAC tumors." @default.
- W3049390013 created "2020-08-21" @default.
- W3049390013 creator A5009885491 @default.
- W3049390013 creator A5015760127 @default.
- W3049390013 creator A5017221404 @default.
- W3049390013 creator A5020093525 @default.
- W3049390013 creator A5040557103 @default.
- W3049390013 creator A5051902236 @default.
- W3049390013 creator A5062706695 @default.
- W3049390013 creator A5063850857 @default.
- W3049390013 creator A5068823747 @default.
- W3049390013 creator A5069337756 @default.
- W3049390013 date "2021-01-01" @default.
- W3049390013 modified "2023-10-16" @default.
- W3049390013 title "Modulation of Cancer-Associated Fibrotic Stroma by An Integrin αvβ3 Targeting Protein for Pancreatic Cancer Treatment" @default.
- W3049390013 cites W1119620128 @default.
- W3049390013 cites W1979054814 @default.
- W3049390013 cites W1982854019 @default.
- W3049390013 cites W1988927889 @default.
- W3049390013 cites W1989308141 @default.
- W3049390013 cites W1992995822 @default.
- W3049390013 cites W1996912024 @default.
- W3049390013 cites W2010223161 @default.
- W3049390013 cites W2020425240 @default.
- W3049390013 cites W2023560058 @default.
- W3049390013 cites W2033878276 @default.
- W3049390013 cites W2041246767 @default.
- W3049390013 cites W2052617606 @default.
- W3049390013 cites W2055091294 @default.
- W3049390013 cites W2061797905 @default.
- W3049390013 cites W2066521983 @default.
- W3049390013 cites W2075582906 @default.
- W3049390013 cites W2076201009 @default.
- W3049390013 cites W2088110734 @default.
- W3049390013 cites W2098158472 @default.
- W3049390013 cites W2100035095 @default.
- W3049390013 cites W2100363932 @default.
- W3049390013 cites W2100614336 @default.
- W3049390013 cites W2107441200 @default.
- W3049390013 cites W2115820646 @default.
- W3049390013 cites W2117692326 @default.
- W3049390013 cites W2131052485 @default.
- W3049390013 cites W2132696375 @default.
- W3049390013 cites W2137357003 @default.
- W3049390013 cites W2144869905 @default.
- W3049390013 cites W2164193797 @default.
- W3049390013 cites W2167664390 @default.
- W3049390013 cites W2225173575 @default.
- W3049390013 cites W2347175105 @default.
- W3049390013 cites W2461667278 @default.
- W3049390013 cites W2481871524 @default.
- W3049390013 cites W2530909341 @default.
- W3049390013 cites W2579131879 @default.
- W3049390013 cites W2618524597 @default.
- W3049390013 cites W2808293799 @default.
- W3049390013 cites W2947548345 @default.
- W3049390013 doi "https://doi.org/10.1016/j.jcmgh.2020.08.004" @default.
- W3049390013 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7674520" @default.
- W3049390013 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32810598" @default.
- W3049390013 hasPublicationYear "2021" @default.
- W3049390013 type Work @default.
- W3049390013 sameAs 3049390013 @default.
- W3049390013 citedByCount "20" @default.
- W3049390013 countsByYear W30493900132021 @default.
- W3049390013 countsByYear W30493900132022 @default.
- W3049390013 countsByYear W30493900132023 @default.
- W3049390013 crossrefType "journal-article" @default.
- W3049390013 hasAuthorship W3049390013A5009885491 @default.
- W3049390013 hasAuthorship W3049390013A5015760127 @default.
- W3049390013 hasAuthorship W3049390013A5017221404 @default.
- W3049390013 hasAuthorship W3049390013A5020093525 @default.
- W3049390013 hasAuthorship W3049390013A5040557103 @default.
- W3049390013 hasAuthorship W3049390013A5051902236 @default.
- W3049390013 hasAuthorship W3049390013A5062706695 @default.
- W3049390013 hasAuthorship W3049390013A5063850857 @default.
- W3049390013 hasAuthorship W3049390013A5068823747 @default.
- W3049390013 hasAuthorship W3049390013A5069337756 @default.
- W3049390013 hasBestOaLocation W30493900131 @default.
- W3049390013 hasConcept C121608353 @default.
- W3049390013 hasConcept C126322002 @default.
- W3049390013 hasConcept C142724271 @default.
- W3049390013 hasConcept C170493617 @default.
- W3049390013 hasConcept C190283241 @default.
- W3049390013 hasConcept C195687474 @default.
- W3049390013 hasConcept C204232928 @default.
- W3049390013 hasConcept C2779013556 @default.
- W3049390013 hasConcept C2780210213 @default.
- W3049390013 hasConcept C2780258809 @default.
- W3049390013 hasConcept C2780394083 @default.
- W3049390013 hasConcept C502942594 @default.
- W3049390013 hasConcept C52124034 @default.
- W3049390013 hasConcept C55493867 @default.
- W3049390013 hasConcept C71924100 @default.
- W3049390013 hasConcept C86803240 @default.
- W3049390013 hasConcept C96232424 @default.
- W3049390013 hasConceptScore W3049390013C121608353 @default.
- W3049390013 hasConceptScore W3049390013C126322002 @default.
- W3049390013 hasConceptScore W3049390013C142724271 @default.