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Nerve Degeneration and Regeneration Associated with NF1 Tumors

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Annual rept. 15 May 2011-14 May 2012

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Infiltrating peripheral nerve sheath tumors PNST are associated with significant neurological deficits and nerve damage. An initial aim of this project is to determine how tumor progression leads to loss of nerve function. A second aim is to determine if nerve damage caused by PNST is reversible and the potential for nerve regeneration after PNST eradication. Additional aims will test photodynamic therapy as modality for eradication of PNST without incurring substantial collateral damage to functioning nerve. To date we have mainly accomplished the first and second aims. Our work tested that hypothesis that tumor-induced nerve damage and loss of neurological function is reversible. Findings indicate that this is true only in the formative stages of tumor growth associated with low-level functional deficits. Tumor progression leads to increasing and permanent loss of nerve function. Function deficits persist even after tumor eradication. Results indicate that the tumor destroys the nerve, ablates supporting cells and replaces nerve structure with an impenetrable fibrotic mass. Even though afflicted neurons remain viable they fail to regrow axons into the fibrotic mass even when devoid of tumor cells. The main conclusion of our findings is that tumor eradication does not induce or support nerve regeneration. Instead, a fibrotic mass remains that must be resolved for axonal regrowth to occur. This suggests that conventional therapies e.g., radiation may not provide for nerve regeneration and recovery of function. Our next objectives will provide a better understanding of the way PNST and therapies damage nerve. We will look much more closely at ways to resolve these obstacles and hopefully discover ways to allow for nerve regeneration when treating PNST.

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  • Medicine and Medical Research

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