FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1991676144> ?p ?o ?g. }

• W1991676144 abstract "Bladder cancer, which consists mainly of Transitional Cell Carcinoma (TCC), is the fifth most common cancer in the United States with over 70,000 cases and 15,000 deaths expected in 2013. Despite the successful development of molecularly targeted therapeutics for many cancers, there has been little change in the standard of care for TCC patients over the last few decades. New studies have revealed that aberrant epigenetic events, such as DNA hypermethylation and altered histone modifications, are common in TCC and are thought to promote tumorigenesis. Epigenetic therapies targeting these dysregulated pathways may reverse these effects and can have a profound influence on tumor growth.One such epigenetic modifier, EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), is overexpressed in a variety of cancers and was found to enhance tumor progression by silencing several tumor suppressor genes. Recently, we have verified that EZH2 is upregulated in human TCC through an FGF2-NDY1/KDM2B-dependent suppression of miR-101. These data suggest that FGF2-NDY1/KDM2B-EZH2 pathway may be important in transitional cell carcinogenesis and may provide relevant epigenetic targets for the treatment of TCC. Spontaneous canine TCC also exhibits activation of FGF2 signaling and has been suggested as a model for bladder cancer. Therefore, we hypothesized that the development of aberrant epigenetic mechanisms downstream of FGF2 would be conserved between humans and dogs and that canine TCC could serve as a relevant large animal model for the clinical targeting of the FGF2-NDY1-EZH2 axis.To test our hypothesis, we employed canine TCC cell lines that we developed from dogs of various breeds and found that both EZH2 and NDY1/KDM2B are upregulated in canine TCC when compared to normal tissue. In order to target the pathway, we inhibited EZH2 both pharmacologically, using the commercially available inhibitor DZNep (3-deazaneplanocin), and through targeted knockdown. We determined that both DZNep and shRNA knockdown of EZH2 inhibited proliferation and induced apoptosis in canine TCC cells in anchorage-dependent (2D) and anchorage-independent (3D) cultures. By conducting these experiments in parallel with human TCC cell lines, we showed that sensitivity to DZNep is comparable between human and canine TCC cell lines. Western blot analysis and qRT-PCR demonstrated that, upon DZNep treatment, there is reduction of EZH2 at the protein level and inhibition of its activity, as evidenced by decreased global trimethylation of Histone H3 at lysine 27 (H3K27me3). Furthermore, inhibition of EZH2 was associated with upregulation of a set of genes that are commonly silenced by H3K27me3.Human and canine bladder cancer share histopathologic characteristics and clinical behavior. With this study, we confirm that the molecular underpinnings of spontaneous TCC are also shared between dogs and humans. Therefore canine TCC provides a means to understand epigenetic dysregulation in the urothelium as well as to investigate its clinical targeting.Citation Format: Parthena Foltopoulou, Monica Betancur-Boissel, Philip N. Tsichlis, Elizabeth A. McNiel. Targeting epigenetic dysregulation in a canine model of bladder cancer. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr B52." @default.
• W1991676144 created "2016-06-24" @default.
• W1991676144 creator A5056527296 @default.
• W1991676144 creator A5078223851 @default.
• W1991676144 creator A5081838988 @default.
• W1991676144 creator A5090059379 @default.
• W1991676144 date "2013-07-01" @default.
• W1991676144 modified "2023-09-26" @default.
• W1991676144 title "Abstract B52: Targeting epigenetic dysregulation in a canine model of bladder cancer" @default.
• W1991676144 doi "https://doi.org/10.1158/1538-7445.cec13-b52" @default.
• W1991676144 hasPublicationYear "2013" @default.
• W1991676144 type Work @default.
• W1991676144 sameAs 1991676144 @default.
• W1991676144 citedByCount "0" @default.
• W1991676144 crossrefType "proceedings-article" @default.
• W1991676144 hasAuthorship W1991676144A5056527296 @default.
• W1991676144 hasAuthorship W1991676144A5078223851 @default.
• W1991676144 hasAuthorship W1991676144A5081838988 @default.
• W1991676144 hasAuthorship W1991676144A5090059379 @default.
• W1991676144 hasConcept C104317684 @default.
• W1991676144 hasConcept C114691636 @default.
• W1991676144 hasConcept C121608353 @default.
• W1991676144 hasConcept C150425827 @default.
• W1991676144 hasConcept C2776915012 @default.
• W1991676144 hasConcept C2778065480 @default.
• W1991676144 hasConcept C2780352672 @default.
• W1991676144 hasConcept C41091548 @default.
• W1991676144 hasConcept C50171091 @default.
• W1991676144 hasConcept C502942594 @default.
• W1991676144 hasConcept C54355233 @default.
• W1991676144 hasConcept C555283112 @default.
• W1991676144 hasConcept C64927066 @default.
• W1991676144 hasConcept C71924100 @default.
• W1991676144 hasConcept C86803240 @default.
• W1991676144 hasConceptScore W1991676144C104317684 @default.
• W1991676144 hasConceptScore W1991676144C114691636 @default.
• W1991676144 hasConceptScore W1991676144C121608353 @default.
• W1991676144 hasConceptScore W1991676144C150425827 @default.
• W1991676144 hasConceptScore W1991676144C2776915012 @default.
• W1991676144 hasConceptScore W1991676144C2778065480 @default.
• W1991676144 hasConceptScore W1991676144C2780352672 @default.
• W1991676144 hasConceptScore W1991676144C41091548 @default.
• W1991676144 hasConceptScore W1991676144C50171091 @default.
• W1991676144 hasConceptScore W1991676144C502942594 @default.
• W1991676144 hasConceptScore W1991676144C54355233 @default.
• W1991676144 hasConceptScore W1991676144C555283112 @default.
• W1991676144 hasConceptScore W1991676144C64927066 @default.
• W1991676144 hasConceptScore W1991676144C71924100 @default.
• W1991676144 hasConceptScore W1991676144C86803240 @default.
• W1991676144 hasLocation W19916761441 @default.
• W1991676144 hasOpenAccess W1991676144 @default.
• W1991676144 hasPrimaryLocation W19916761441 @default.
• W1991676144 hasRelatedWork W1604570239 @default.
• W1991676144 hasRelatedWork W1989733556 @default.
• W1991676144 hasRelatedWork W1994595742 @default.
• W1991676144 hasRelatedWork W2021640126 @default.
• W1991676144 hasRelatedWork W2042237007 @default.
• W1991676144 hasRelatedWork W2066719894 @default.
• W1991676144 hasRelatedWork W2067155951 @default.
• W1991676144 hasRelatedWork W2129356506 @default.
• W1991676144 hasRelatedWork W2327422888 @default.
• W1991676144 hasRelatedWork W2396829420 @default.
• W1991676144 hasRelatedWork W2427007523 @default.
• W1991676144 hasRelatedWork W2513850591 @default.
• W1991676144 hasRelatedWork W2770615157 @default.
• W1991676144 hasRelatedWork W2885585336 @default.
• W1991676144 hasRelatedWork W2921421046 @default.
• W1991676144 hasRelatedWork W2936128661 @default.
• W1991676144 hasRelatedWork W2968075657 @default.
• W1991676144 hasRelatedWork W3049101641 @default.
• W1991676144 hasRelatedWork W3124459087 @default.
• W1991676144 hasRelatedWork W3088192947 @default.
• W1991676144 isParatext "false" @default.
• W1991676144 isRetracted "false" @default.
• W1991676144 magId "1991676144" @default.
• W1991676144 workType "article" @default.