Inhibitors of HIF-1α and CXCR4 Mitigate the Development of Radiation Necrosis in Mouse Brain.

International Journal of Radiation Oncology, Biology, Physics
Ruimeng YangJoel R Garbow

Abstract

There is mounting evidence that, in addition to angiogenesis, hypoxia-induced inflammation via the hypoxia-inducible factor 1α (HIF-1α)-CXC chemokine receptor 4 (CXCR4) pathway may contribute to the pathogenesis of late-onset, irradiation-induced necrosis. This study investigates the mitigative efficacy of an HIF-1α inhibitor, topotecan, and a CXCR4 antagonist, AMD3100, on the development of radiation necrosis (RN) in an intracranial mouse model. Mice received a single-fraction, 50-Gy dose of hemispheric irradiation from the Leksell Gamma Knife Perfexion and were then treated with either topotecan, an HIF-1α inhibitor, from 1 to 12 weeks after irradiation, or AMD3100, a CXCR4 antagonist, from 4 to 12 weeks after irradiation. The onset and progression of RN were monitored longitudinally via noninvasive, in vivo magnetic resonance imaging (MRI) from 4 to 12 weeks after irradiation. Conventional hematoxylin-eosin staining and immunohistochemistry staining were performed to evaluate the treatment response. The progression of brain RN was significantly mitigated for mice treated with either topotecan or AMD3100 compared with control animals. MRI-derived lesion volumes were significantly smaller for both of the treated groups, and hi...Continue Reading

Citations

Jun 21, 2019·Current Oncology Reports·Faisal S AliYoshua Esquenazi
Dec 14, 2018·Frontiers in Neurology·David M RoutmanDaniel M Trifiletti
Jul 1, 2018·International Journal of Particle Therapy·David R GrosshansGabriel Sawakuchi
May 2, 2020·Signal Transduction and Targeted Therapy·Rui-Xue Huang, Ping-Kun Zhou
Jan 10, 2019·Frontiers in Immunology·Franziska EckertStephan M Huber
Sep 19, 2020·International Journal of Radiation Biology·Eloise ParisetSylvain V Costes
May 1, 2018·Journal of Magnetic Resonance·Joel R GarbowScott C Beeman
Jun 17, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jingzhe WangHuabiao Chen
Dec 10, 2019·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·J Martin BrownLawrence Recht

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