Telomere profiling : toward glioblastoma personalized medicine
| Autor: | Ferrandon, S., Saultier, P., Carras, J., Battiston-Montagne, P., Hau-Debat, N., Beuve, M., Alphonse, G., Rodriguez-Lafrasse, C., Delphine Poncet |
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| Přispěvatelé: | Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Transfer and molecular Oncology Unit, Hospices Civils de Lyon (HCL), Institut de Physique Nucléaire de Lyon (IPNL), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Faculté de Médecine |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Zdroj: | 39th European Radiation Research (ERR2012) 39th European Radiation Research (ERR2012), Oct 2012, Vietri sul Mare, Italy HAL |
| Popis: | International audience; Despite a standard of care combining surgery, radio therapy (RT) and Temozolomide chemotherapy, average Glioblastoma patient survival is still less than one year. Telomere length (TL) and telomerase activity (TA) are prognosis factor in patients treated by surgery and radiotherapy alone. Increased TL and presence of TA are also known to increase resistance to conventional radiot herapy. These parameters could thus be efficient predictive biomarker of patient radio-resistance. What's more telomere protection, function and length also depend on the Shelterin protein complex (TRF1, TRF2, TPP1, POT1, TIN2, hRAP1). We have thus evaluated an enlarged telomeric status (TL, telomerase catalytic subunit (hTERT) and the shelterin component expression level) on a panel of 11 glioblastoma-derived cell lines, before and after photon irradiation. We report a significant correlation between TL, basal POT1 expression level and photon radioresistance and a significant variation in TERT, TERF1 and POT1 expression after photon irradiation. We thus propose (i) to assess POT1 expression level or TL on tumor biopsy to identify radioresistant patients. These patients could benefit from alternative irradiation technics such as carbon ion hadrontherapy boost, or be treated by anti- telomerase agent prior to RT to decrease TL and potentiate RT effect. In view of these results, we have also evaluated the telomeric status after carbon ion hadrontherapy, and strickingly cell response to carbon ion was totally independent of the telomeric parameters. This mean that (ii) patients with a poor telomeric status keep all their chance to be good carbon ion hadrontherapy responders. We go further in identification of telomeric damages induced by both type of irradiation and (iii) propose a model of telomeric damage implications in cell response to photon and carbon ion irradiation. In parallel, we led a preclinical evaluation of anti-telomerase induction treatment combined with RT on a murin orthotopic model of glioblastoma. Preliminary results will be reported. |
| Databáze: | OpenAIRE |
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