Chalcone JAI-51 improves efficacy of synchrotron microbeam radiation therapy of brain tumors

Bouchet, Audrey; Boumendjel, Ahcene; Khalil, Enam; Serduc, Raphael; Bräuer, Elke; Siegbahn, Erik Albert; Laissue, Jean A; Boutonnat, Jean (2012). Chalcone JAI-51 improves efficacy of synchrotron microbeam radiation therapy of brain tumors. Journal of synchrotron radiation, 19(Pt 4), pp. 478-82. Oxford: Blackwell Publishing 10.1107/S0909049512015105

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Microbeam radiation therapy (MRT), a preclinical form of radiosurgery, uses spatially fractionated micrometre-wide synchrotron-generated X-ray beams. As MRT alone is predominantly palliative for animal tumors, the effects of the combination of MRT and a newly synthesized chemotherapeutic agent JAI-51 on 9L gliosarcomas have been evaluated. Fourteen days (D14) after implantation (D0), intracerebral 9LGS-bearing rats received either MRT, JAI-51 or both treatments. JAI-51, alone or immediately after MRT, was administered three times per week. Animals were kept up to ∼20 weeks after irradiation or sacrificed at D16 or D28 after treatment for cell cycle analysis. MRT plus JAI-51 increased significantly the lifespan compared with MRT alone (p = 0.0367). JAI-51 treatment alone had no effect on rat survival. MRT alone or associated with JAI-51 induced a cell cycle blockade in G2/M (p < 0.01) while the combined treatment also reduced the proportion of G0/G1 cells. At D28 after irradiation, MRT and MRT/JAI-51 had a smaller cell blockade effect in the G2/M phase owing to a significant increase in tumor cell death rate (<2c) and a proportional increase of endoreplicative cells (>8c). The combination of MRT and JAI-51 increases the survival of 9LGS-bearing rats by inducing endoreduplication of DNA and tumor cell death; further, it slowed the onset of tumor growth resumption two weeks after treatment.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Laissue, Jean

ISSN:

0909-0495

Publisher:

Blackwell Publishing

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:34

Last Modified:

05 Dec 2022 14:10

Publisher DOI:

10.1107/S0909049512015105

PubMed ID:

22713877

Web of Science ID:

000305529100002

URI:

https://boris.unibe.ch/id/eprint/13286 (FactScience: 219801)

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