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Publication : Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model.

First Author  Gao X Year  2015
Journal  Proc Natl Acad Sci U S A Volume  112
Issue  47 Pages  14676-81
PubMed ID  26554010 Mgi Jnum  J:228064
Mgi Id  MGI:5705172 Doi  10.1073/pnas.1512570112
Citation  Gao X, et al. (2015) Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model. Proc Natl Acad Sci U S A 112(47):14676-81
abstractText  Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect is not durable and its mechanism of action on nerve function is unknown. We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating tumor edema, which may further improve results by decreasing muscle atrophy and increasing nerve regeneration. Using a cranial window model, we showed that anti-VEGF treatment may achieve these effects via normalizing the tumor vasculature, improving vessel perfusion, and delivery of oxygenation. It is known that oxygen is a potent radiosensitizer; therefore, we further demonstrated that combining anti-VEGF with radiation therapy can achieve a better tumor control and help lower the radiation dose and, thus, minimize radiation-related neurological toxicity. Our results provide compelling rationale for testing combined therapy in human VS.
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