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- W2091762004 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCWe have previously established the important role of FGF-2 pathways in tumor cell radioresistance. Although radiotherapy is commonly used in the treatment of pancreatic carcinomas which are known to express FGF and FRGFR, the role of FGFR pathways in radioresistance of pancreatic tumor has not yet been studied. We established a new syngenic mouse model of orthotopic pancreatic xenograft of Panc02 cells transfected with hFGFR1-receptor (Panc02-FGFR1). Whereas the in vitro radioresistance of the parental cell line (Panc02) was not affected by the addition of the specific FGF-receptor antagonist SSR128129, Panc02-FGFR1 radioresistance was significantly decreased by treating cells with SSR128129 (1 µM) 4 hours before irradiation (mean inactivation dose [MID] was 6.1±0.2 Gy in control PancO2-FGFR1 versus 4.2±0.2 Gy in SSR128129 treated cells, P<0.001). Orthotopic injection of Panc02-FGFR1 cells in syngeneic C57B6 mice led to rapid growth of pancreatic tumors. While SSR128129 (30 mg/kg/d) was ineffective on the tumor growth, this compound significantly decreased microvessel density in Panc02-FGFR1 tumors (104.7±14.6 vs 136.6±10.3 vessels/field, P<0.001). Local irradiation (2×2.5 Gy) of tumor-bearing animals previously treated for 1 week with SSR128129, led to a strong decrease of tumor size (40% decrease, P<0.05) one week after radiotherapy, whereas the tumor size of untreated animals was not affected by irradiation. The effect of SSR128129 on microvessel density was not affected by radiotherapy. Together, these data show that inhibiting FGFR pathways leads to a major radiosensitization of pancreatic tumors in vitro and in vivo.Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.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 1396." @default.
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- W2091762004 date "2010-04-15" @default.
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- W2091762004 title "Abstract 1396: FGFR1-induced radioresistance of Panc02 pancreatic tumor cells is decreased by SSR128129 treatmentin vitroandin vivo" @default.
- W2091762004 doi "https://doi.org/10.1158/1538-7445.am10-1396" @default.
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