A light-activated NO donor attenuates anchorage independent growth of cancer cells: Important role of a cross talk between NO and other reactive oxygen species.

It is established that high concentrations of nitric oxide(1) (NO), as released from activated macrophages, induce apoptosis in breast cancer cells. In this study, we assessed the potential of a light-activated NO donor [(Me2bpb)Ru(NO)(Resf)], a recently reported apoptototic agent, in suppressing the anchorage independent growth potentials of an aggressive human breast cancer cell line. Our results demonstrated the down regulation of anchorage independent growth by light activated NO treatment in the aggressive human breast cancer cell line MDA-MB-231 and afforded insight into the associated mechanism(s). The investigation revealed an up-regulation of the bioactivity of catalase with an accompanied reduction in the endogenous levels of H2O2, a direct substrate of catalase and a recently identified endogenous growth modulator in breast cancer cells. An earlier publication reported that endogenous superoxide (O2(-)) in human breast cancer cells constitutively inhibits catalase bioactivity (at the level of its protein), resulting in increased H2O2 levels. Interestingly in this study, O2(-) was also found to be down- regulated following NO treatment providing a basis for the observed increase in catalase bioactivity. Cells silenced for the catalase gene exhibited compromised reduction in anchorage independent growth upon light activated NO treatment. Collectively this study detailed a mechanistic cross talk between exogenous NO and endogenous ROS in attenuating anchorage independent growth.

Dysthyroid optic neuropathy: update on pathogenesis, diagnosis, and management.

INTRODUCTION: Dysthyroid optic neuropathy (DON) is a severe manifestation of thyroid eye disease (TED) that can result in permanent vision loss. Management is complex, multidisciplinary, and involves medical and/or surgical therapies. This review describes current concepts in the epidemiology, pathophysiology, diagnosis, and treatment of DON. AREAS COVERED: An extensive review of the literature was performed to detail current concepts on the diagnosis and management of DON. This includes utilization of various medical and surgical modalities for disease management. EXPERT COMMENTARY: DON can result in permanent blindness and often requires the use of corticosteroids and surgical decompression. We favor the use of intravenous corticosteroids and a transcaruncular approach when surgical decompression is indicated. The use of orbital radiation for DON is often reserved for patients that are poor surgical candidates and/or patients with refractory disease.