Matches in SemOpenAlex for { <https://semopenalex.org/work/W1529123847> ?p ?o ?g. }
Showing items 1 to 79 of
79
with 100 items per page.
- W1529123847 abstract "Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CAThe Wnt/beta-catenin pathway, which signals through the Frizzled (FZD) receptor family and several co-receptors, has long been implicated in cancer. We have previously demonstrated that inhibition of WNT/beta-catenin signaling by vantictumab (anti-FZD) or OMP-54F28 (FZD8-Fc) inhibits tumor growth, decreases tumorigenicity and induces differentiation in solid tumors. The anti-tumor effect of our Wnt antagonists is most evident in combination with chemotherapeutic agents. We sought to determine if the anti-tumor effect of Wnt pathway inhibitors varied with different chemotherapeutic agents. We compared the growth inhibitory effect of vantictumab and OMP-54F28 with either taxanes (paclitaxel and nab-paclitaxel) or with DNA synthesis inhibitors (gemcitabine and carboplatin) in patient-derived tumor xenografts. In a model for pancreatic ductal carcinoma, vantictumab with nab-paclitaxel was more efficacious than vantictumab with gemcitabine in inhibiting tumor growth and Wnt target gene expression (at doses of nab-paclitaxel and gemcitabine that were equivalent in their single-agent growth-inhibitory effects). Histologic analysis indicated that nab-paclitaxel increased mitotic cells and beta-catenin levels. Importantly, the addition of vantictumab to nab-paclitaxel reversed the nab-paclitaxel-induced increase in mitotic cells and beta-catenin expression. An independent experiment in a serous ovarian cancer xenograft model also showed enhanced anti-tumor activity when combining OMP-54F28 with either paclitaxel or nab-paclitaxel compared to the combination with carboplatin. A potential mechanism to account for these results involves on the observation that Wnt/beta-catenin signaling is under cell cycle control and peaks at the G2/M phase. Taxanes inhibit microtubule function and block the cell cycle at G2/M. In contrast, other chemotherapeutic agents, such as platinum compounds and nucleoside analogs, inhibit DNA synthesis and block cell proliferation at S phase. We hypothesize that combination of Wnt blockade with chemotherapeutic agents, such as taxanes, that induce G2/M arrest may result in optimal anti-tumor activity.Citation Format: Wan-Ching Yen, Marcus M. Fischer, John Lewicki, Austin Gurney, Timothy Hoey. Enhanced anti-tumor effect of WNT pathway antagonists in combination with taxanes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4547. doi:10.1158/1538-7445.AM2014-4547" @default.
- W1529123847 created "2016-06-24" @default.
- W1529123847 creator A5009721823 @default.
- W1529123847 creator A5010623992 @default.
- W1529123847 creator A5013439472 @default.
- W1529123847 creator A5014243027 @default.
- W1529123847 creator A5079033247 @default.
- W1529123847 date "2014-09-30" @default.
- W1529123847 modified "2023-09-26" @default.
- W1529123847 title "Abstract 4547: Enhanced anti-tumor effect of WNT pathway antagonists in combination with taxanes" @default.
- W1529123847 doi "https://doi.org/10.1158/1538-7445.am2014-4547" @default.
- W1529123847 hasPublicationYear "2014" @default.
- W1529123847 type Work @default.
- W1529123847 sameAs 1529123847 @default.
- W1529123847 citedByCount "1" @default.
- W1529123847 countsByYear W15291238472015 @default.
- W1529123847 crossrefType "proceedings-article" @default.
- W1529123847 hasAuthorship W1529123847A5009721823 @default.
- W1529123847 hasAuthorship W1529123847A5010623992 @default.
- W1529123847 hasAuthorship W1529123847A5013439472 @default.
- W1529123847 hasAuthorship W1529123847A5014243027 @default.
- W1529123847 hasAuthorship W1529123847A5079033247 @default.
- W1529123847 hasConcept C121608353 @default.
- W1529123847 hasConcept C126322002 @default.
- W1529123847 hasConcept C137620995 @default.
- W1529123847 hasConcept C2776694085 @default.
- W1529123847 hasConcept C2777292972 @default.
- W1529123847 hasConcept C2778239845 @default.
- W1529123847 hasConcept C2780258809 @default.
- W1529123847 hasConcept C2780427987 @default.
- W1529123847 hasConcept C2781451048 @default.
- W1529123847 hasConcept C502942594 @default.
- W1529123847 hasConcept C62478195 @default.
- W1529123847 hasConcept C71924100 @default.
- W1529123847 hasConcept C86803240 @default.
- W1529123847 hasConcept C95444343 @default.
- W1529123847 hasConcept C98274493 @default.
- W1529123847 hasConceptScore W1529123847C121608353 @default.
- W1529123847 hasConceptScore W1529123847C126322002 @default.
- W1529123847 hasConceptScore W1529123847C137620995 @default.
- W1529123847 hasConceptScore W1529123847C2776694085 @default.
- W1529123847 hasConceptScore W1529123847C2777292972 @default.
- W1529123847 hasConceptScore W1529123847C2778239845 @default.
- W1529123847 hasConceptScore W1529123847C2780258809 @default.
- W1529123847 hasConceptScore W1529123847C2780427987 @default.
- W1529123847 hasConceptScore W1529123847C2781451048 @default.
- W1529123847 hasConceptScore W1529123847C502942594 @default.
- W1529123847 hasConceptScore W1529123847C62478195 @default.
- W1529123847 hasConceptScore W1529123847C71924100 @default.
- W1529123847 hasConceptScore W1529123847C86803240 @default.
- W1529123847 hasConceptScore W1529123847C95444343 @default.
- W1529123847 hasConceptScore W1529123847C98274493 @default.
- W1529123847 hasLocation W15291238471 @default.
- W1529123847 hasOpenAccess W1529123847 @default.
- W1529123847 hasPrimaryLocation W15291238471 @default.
- W1529123847 hasRelatedWork W1509654317 @default.
- W1529123847 hasRelatedWork W1829323300 @default.
- W1529123847 hasRelatedWork W1867502355 @default.
- W1529123847 hasRelatedWork W2006871036 @default.
- W1529123847 hasRelatedWork W2015553036 @default.
- W1529123847 hasRelatedWork W2034787539 @default.
- W1529123847 hasRelatedWork W2035328939 @default.
- W1529123847 hasRelatedWork W2068852196 @default.
- W1529123847 hasRelatedWork W2124331403 @default.
- W1529123847 hasRelatedWork W2147188402 @default.
- W1529123847 hasRelatedWork W2152095899 @default.
- W1529123847 hasRelatedWork W2167749003 @default.
- W1529123847 hasRelatedWork W2180322951 @default.
- W1529123847 hasRelatedWork W2314353439 @default.
- W1529123847 hasRelatedWork W2332326112 @default.
- W1529123847 hasRelatedWork W2499778673 @default.
- W1529123847 hasRelatedWork W2502629403 @default.
- W1529123847 hasRelatedWork W2908863765 @default.
- W1529123847 hasRelatedWork W2971366905 @default.
- W1529123847 hasRelatedWork W3181700393 @default.
- W1529123847 isParatext "false" @default.
- W1529123847 isRetracted "false" @default.
- W1529123847 magId "1529123847" @default.
- W1529123847 workType "article" @default.