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Novel Preclinical Testing Strategies for Treatment of Metastatic Pheochromocytoma

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Technical Report,15 Aug 2011,14 Aug 2015

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Tufts Medical Center Boston United States

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Pheochromocytomas PCC are catecholamine-producing neuroendocrine tumors. Up to 30 give rise to metastases, for which there is no effective treatment. A major deficiency in current treatment strategies is that they do not account for the fact that metastatic PCCs usually grow very slowly and most of the cells are quiescent at any given time. This project had two overall objectives to develop treatment paradigms targeting quiescent and replicating PCC cells and to develop new models for-pre-clinical testing. Because there are no human PCC cell lines, mouse pheochromocytoma cell lines developed in our laboratory were used as the principal model for testing of chemotherapeutic drugs and the findings were validated with primary cultures of human PCC. We identified two classes of drugs effective against non-dividing human PCC cells topoisomerase 1 inhibitors and the mitochondriotoxic agent gamitrinib. New approaches to propagating human PCC cells from primary tumors in cell cultures and xenografts were also tested. Attempts to establish cell lines were unsuccessful. Although there were no overt tumor takes in mice, histologic sections of the implantation sites in a new strain of immunodeficient mice called NSG show long-term cell survival. This provides a new model that can be used for future studies of tumor growth, drug responses and micro-imaging in vivo.

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