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Sensitization of chondrosarcoma cells with PARP inhibitor and high-LET radiation.

ABSTRACT: Chondrosarcoma is a malignant tumor that arises from cartilaginous tissue and is radioresistant and chemoresistant to conventional treatments. The preferred treatment consists of surgical resection, which might cause severe disabilities for the patient; in addition, this procedure might be impossible for inoperable locations, such as the skull base. Carbon ion irradiation (hadron therapy) has been proposed as an alternative treatment, primarily due to its greater biological effectiveness and improved ballistic properties compared with conventional radiotherapy with X-rays. The goal of this study was to characterize the genetic mutations of a grade III chondrosarcoma cell line (CH2879) and examine the cellular responses to conventional radiotherapy (X-rays) and hadron therapy (proton and carbon ions) in the presence of the PARP inhibitor Olaparib. To better understand PARP inhibition, we first analyzed the formation of poly-ADP ribose chains by western blot; we observed an increase in its signal after irradiation, which disappeared on addition of the PARP inhibitor. PARPi enhanced ratio of approximately 1.3, 1.8, and 1.5 following irradiation of cells with X-rays, protons, and C-ions, respectively, as detected by clonogenic assay. The decrease in cell survival was confirmed by proliferation assay. The radiosensitivity of CH2879 cells was associated with mutations in homologous recombination repair genes, such as RAD50, SMARCA2 and NBN. This study demonstrates the capacity of the PARP inhibitor Olaparib to radiosensitize mutated chondrosarcoma cells to conventional photon irradiation, proton and carbon ion irradiation.

SUBMITTER: Cesaire M

PROVIDER: S-EPMC6609837 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Sensitization of chondrosarcoma cells with PARP inhibitor and high-LET radiation.

Césaire Mathieu M Ghosh Utpal U Austry Jean-Baptiste JB Muller Etienne E Cammarata Francesco Paolo FP Guillamin Marilyne M Caruso Massimo M Castéra Laurent L Petringa Giada G Cirrone Giuseppe Antonio Pablo GAP Chevalier François F

Journal of bone oncology 20190620

Chondrosarcoma is a malignant tumor that arises from cartilaginous tissue and is radioresistant and chemoresistant to conventional treatments. The preferred treatment consists of surgical resection, which might cause severe disabilities for the patient; in addition, this procedure might be impossible for inoperable locations, such as the skull base. Carbon ion irradiation (hadron therapy) has been proposed as an alternative treatment, primarily due to its greater biological effectiveness and imp ...[more]

PMID: 31312595

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Dataset Information

Sensitization of chondrosarcoma cells with PARP inhibitor and high-LET radiation.

Publications

Sensitization of chondrosarcoma cells with PARP inhibitor and high-LET radiation.

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