Murine Models and Cell Lines for the Investigation of Pheochromocytoma: Applications for Future Therapies?

Pheochromocytomas (PCCs) are slow-growing neuroendocrine tumors arising from adrenal chromaffin cells. Tumors arising from extra-adrenal chromaffin cells are called paragangliomas. Metastases can occur up to approximately 60% or even more in specific subgroups of patients. There are still no well-established and clinically accepted “metastatic” markers available to determine whether a primary tumor is or will become malignant. Surgical resection is the most common treatment for non-metastatic PCCs, but no standard treatment/regimen is available for metastatic PCC. To investigate what kind of therapies are suitable for the treatment of metastatic PCC, animal models or cell lines are very useful. Over the last two decades, various mouse and rat models have been created presenting with PCC, which include models presenting tumors that are to a certain degree biochemically and/or molecularly similar to human PCC, and develop metastases. To be able to investigate which chemotherapeutic options could be useful for the treatment of metastatic PCC, cell lines such as mouse pheochromocytoma (MPC) and mouse tumor tissue (MTT) cells have been recently introduced and they both showed metastatic behavior. It appears these MPC and MTT cells are biochemically and molecularly similar to some human PCCs, are easily visualized by different imaging techniques, and respond to different therapies. These studies also indicate that some mouse models and both mouse PCC cell lines are suitable for testing new therapies for metastatic PCC

Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myeloid leukaemia

The association of interferon (IFN) therapy with haemolytic uraemic syndrome in patients with chronic myeloid leukaemia (CML) has been reported infrequently. The pathogenesis of the renal lesion in such cases remains unclear. We report the case of a patient with chronic myeloid leukaemia who developed nephrotic syndrome and renal failure while being treated with hydroxyurea and IFN-α. Renal biopsy showed features of chronic thrombotic microangiopathy. The discontinuation of IFN-α, and a prompt institution of plasmapheresis and steroids resulted in improvement of the nephrotic syndrome and renal function. These findings suggest that long-term IFN-α therapy can induce thrombotic microangiopathy and haemolytic uraemic syndrome in patients with chronic myeloid leukaemia