Matches in SemOpenAlex for { <https://semopenalex.org/work/W2037761723> ?p ?o ?g. }
Showing items 1 to 90 of
90
with 100 items per page.
- W2037761723 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCPTBP1 (polypyrimidine tract-binding protein, PTB) is a 59.6-kD nuclear protein involved in pre-mRNA splicing. Its molecular functions include regulation of alternative splicing (AS) and internal ribosomal entry site (IRES)-mediated translation. Our previous work revealed that PTB was overexpressed in human ovarian tumors and that knockdown of PTB expression by shRNA impaired ovarian tumor cell growth and malignant properties in vitro (Oncogene 26:4961-68, 2007). We have also observed slower tumor growth in a xenograft mouse model of ovarian cancer when PTB was knocked down (unpublished). These data suggest that PTB is a novel therapeutic target. To attempt to identify small molecules that have potential to act as shRNA and inhibit PTB, we have designed a cell-based high-throughput screening (HTS) system that allows fast and reliable detection of small molecule inhibitors of PTB protein activity that have potential to alter mRNA splicing. Our approach is based on differential splicing of a PTB target gene (identified by microarray analysis) at different levels of PTB activity in the cell. We have subcloned exons 14 - 16 of one of these PTB targets, Gamma-aminobutyric acid type B receptor 1 (GABBR1, upstream of two different fluorescent markers; the resulting two minigenes were designated “Gred” [short form], and “Ggreen” [long form]). We further verified that the splicing of the minigenes is dependent on the PTB level in the cells. We are presently establishing stable reporter cell lines expressing both minigenes, and validating their compatibility for HTS assay by measuring the stability of fluorescence protein expression over time and response to known PTB inhibitory stimuli (e.g. PTBshRNA). Optimization for HTS includes testing cell seeding density, DMSO tolerance, pilot experiments with specific chemical libraries, data analyses, and verification of “hits” in vitro, followed by pilot HTS with small libraries of chemical diversity to determine if any of these agents will block the activity of PTB. Since overexpressed PTB plays an integral part in maintaining ovarian tumor cell growth and malignant properties, identification of small molecule PTB inhibitors by this approach may uncover novel drugs for the treatment of ovarian and possibly other cancers.(Support in part by grants RO1 CA40570 and RO1 CA138762 (to WTB), by OCRF (to XH), and by UIC.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3690." @default.
- W2037761723 created "2016-06-24" @default.
- W2037761723 creator A5014624359 @default.
- W2037761723 creator A5035824072 @default.
- W2037761723 creator A5059498891 @default.
- W2037761723 date "2010-04-15" @default.
- W2037761723 modified "2023-09-25" @default.
- W2037761723 title "Abstract 3690: Development of a cell based high-throughput assay for drug discovery to treat ovarian cancer" @default.
- W2037761723 doi "https://doi.org/10.1158/1538-7445.am10-3690" @default.
- W2037761723 hasPublicationYear "2010" @default.
- W2037761723 type Work @default.
- W2037761723 sameAs 2037761723 @default.
- W2037761723 citedByCount "0" @default.
- W2037761723 crossrefType "proceedings-article" @default.
- W2037761723 hasAuthorship W2037761723A5014624359 @default.
- W2037761723 hasAuthorship W2037761723A5035824072 @default.
- W2037761723 hasAuthorship W2037761723A5059498891 @default.
- W2037761723 hasConcept C104317684 @default.
- W2037761723 hasConcept C105580179 @default.
- W2037761723 hasConcept C121608353 @default.
- W2037761723 hasConcept C149364088 @default.
- W2037761723 hasConcept C153911025 @default.
- W2037761723 hasConcept C173396325 @default.
- W2037761723 hasConcept C182979987 @default.
- W2037761723 hasConcept C190232843 @default.
- W2037761723 hasConcept C194583182 @default.
- W2037761723 hasConcept C2777793812 @default.
- W2037761723 hasConcept C2779962180 @default.
- W2037761723 hasConcept C2780427987 @default.
- W2037761723 hasConcept C2781018059 @default.
- W2037761723 hasConcept C29537977 @default.
- W2037761723 hasConcept C36823959 @default.
- W2037761723 hasConcept C502942594 @default.
- W2037761723 hasConcept C54355233 @default.
- W2037761723 hasConcept C54458228 @default.
- W2037761723 hasConcept C67705224 @default.
- W2037761723 hasConcept C77430603 @default.
- W2037761723 hasConcept C81885089 @default.
- W2037761723 hasConcept C82381507 @default.
- W2037761723 hasConcept C86803240 @default.
- W2037761723 hasConceptScore W2037761723C104317684 @default.
- W2037761723 hasConceptScore W2037761723C105580179 @default.
- W2037761723 hasConceptScore W2037761723C121608353 @default.
- W2037761723 hasConceptScore W2037761723C149364088 @default.
- W2037761723 hasConceptScore W2037761723C153911025 @default.
- W2037761723 hasConceptScore W2037761723C173396325 @default.
- W2037761723 hasConceptScore W2037761723C182979987 @default.
- W2037761723 hasConceptScore W2037761723C190232843 @default.
- W2037761723 hasConceptScore W2037761723C194583182 @default.
- W2037761723 hasConceptScore W2037761723C2777793812 @default.
- W2037761723 hasConceptScore W2037761723C2779962180 @default.
- W2037761723 hasConceptScore W2037761723C2780427987 @default.
- W2037761723 hasConceptScore W2037761723C2781018059 @default.
- W2037761723 hasConceptScore W2037761723C29537977 @default.
- W2037761723 hasConceptScore W2037761723C36823959 @default.
- W2037761723 hasConceptScore W2037761723C502942594 @default.
- W2037761723 hasConceptScore W2037761723C54355233 @default.
- W2037761723 hasConceptScore W2037761723C54458228 @default.
- W2037761723 hasConceptScore W2037761723C67705224 @default.
- W2037761723 hasConceptScore W2037761723C77430603 @default.
- W2037761723 hasConceptScore W2037761723C81885089 @default.
- W2037761723 hasConceptScore W2037761723C82381507 @default.
- W2037761723 hasConceptScore W2037761723C86803240 @default.
- W2037761723 hasLocation W20377617231 @default.
- W2037761723 hasOpenAccess W2037761723 @default.
- W2037761723 hasPrimaryLocation W20377617231 @default.
- W2037761723 hasRelatedWork W103152546 @default.
- W2037761723 hasRelatedWork W1505264346 @default.
- W2037761723 hasRelatedWork W1568167490 @default.
- W2037761723 hasRelatedWork W1967982639 @default.
- W2037761723 hasRelatedWork W1982673000 @default.
- W2037761723 hasRelatedWork W2020884631 @default.
- W2037761723 hasRelatedWork W2075869504 @default.
- W2037761723 hasRelatedWork W2106531363 @default.
- W2037761723 hasRelatedWork W2397650557 @default.
- W2037761723 hasRelatedWork W2467177869 @default.
- W2037761723 hasRelatedWork W2492982804 @default.
- W2037761723 hasRelatedWork W2567099197 @default.
- W2037761723 hasRelatedWork W2585385206 @default.
- W2037761723 hasRelatedWork W2596052773 @default.
- W2037761723 hasRelatedWork W2612699151 @default.
- W2037761723 hasRelatedWork W2740513312 @default.
- W2037761723 hasRelatedWork W2803686670 @default.
- W2037761723 hasRelatedWork W2886644267 @default.
- W2037761723 hasRelatedWork W2913565581 @default.
- W2037761723 hasRelatedWork W2955241856 @default.
- W2037761723 isParatext "false" @default.
- W2037761723 isRetracted "false" @default.
- W2037761723 magId "2037761723" @default.
- W2037761723 workType "article" @default.