title: Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice.
abstract: Among brain tumors, glioblastoma multiforme appears as one of the most aggressive forms of cancer with poor prognosis and no curative treatment available. Recently, a new kind of radio-chemotherapy has been developed using synchrotron irradiation for the photoactivation of molecules with high-Z elements such as cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98 glioma but the efficiency of the treatment was only measured in terms of overall survival. Here, characterization of the effects of the PAT-Plat on tumor volume and tumor blood perfusion are proposed. Changes in these parameters may predict the overall survival. Firstly, changes in tumor growth of the F98 glioma implanted in the hindlimb of nude mice after the PAT-Plat treatment and its different modalities have been characterized. Secondly, the effects of the treatment on tumor blood perfusion have been observed by intravital two-photon microscopy. Cisplatin alone had no detectable effect on the tumor volume. A reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in tumor growth, indicating a synergistic effect of both synchrotron irradiation and cisplatin treatment. A high number of unperfused vessels (52%) were observed in the peritumoral area in comparison with untreated controls. In the PAT-Plat protocol the transient tumor growth reduction may be due to synergistic interactions of tumor-cell-killing effects and reduction of the tumor blood perfusion.
authors: INSERM U836, Grenoble Institut des Neurosciences, Grenoble, France.
authors: Clement
authors: C
authors: Ricard
authors: Manuel
authors: M
authors: Fernandez
authors: Herwig
authors: H
authors: Requardt
authors: Didier
authors: D
authors: Wion
authors: Jean Claude
authors: JC
authors: Vial
authors: Christoph
authors: C
authors: Segebarth
authors: Boudewijn
authors: B
authors: van der Sanden
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D017619:Hemibody Irradiation; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017356:Synchrotrons; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: cisplatin; glioma; synchrotron photoactivation therapy; synergistic effects; two-photon microscopy
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