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Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice

J. Synchrotron Rad. (2013). 20, 777-784 (http://doi.org/nst)

[Damage] (a) General model of PAT-Plat effects. Irradiation leads to cellular damages such as DNA breaks directly or indirectly via the creation of reactive oxygen species. These damages are less repaired thanks to the inhibition of repair pathways by cisplatin. The PAT-Plat reduces further the tumor blood perfusion. (b) Schematic representation of the regression (gray area) observed on a F98 glioma one month after the treatment and (c) a macrophotograph; white arrows point to the dark spots of blood vessel coagulations.

In the current study, we observed a synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas growing in nude mice. Beside direct tumor cell-killing effects after photoactivation of cisplatin present in tumor cells, we observed an unexpected reduction of the tumor blood perfusion. At the time of photoactivation, cisplatin may also be present in proliferating vascular endothelial cells, creating a drastic inhibition of the tumor blood perfusion during growth. This inhibition of blood perfusion was not observed after synchrotron irradiation or cisplatin treatment alone.

C. Ricard, M. Fernandez, H. Requardt, D. Wion, J.-C. Vial, C. Segebarth and B. van der Sanden
30 October 2013