Chronic degenerative mitral regurgitation is the most common valvular disease in the United States. The objective of this review article is to impart a balanced understanding of the basic concepts and new developments in assessment and management of patients with severe degenerative mitral regurgitation. Etiologic, epidemiologic, pathologic, and physiopathologic concepts are discussed, as well as the importance of surgical mitral valve repair as the current gold standard treatment. Research efforts in "decoding" the natural history and prognosis of patients with severe degenerative mitral regurgitation have produced important insights into the surgical timing of patients with asymptomatic mitral regurgitation, and the concept of early restorative surgery has emerged.
[Show abstract][Hide abstract] ABSTRACT: Even though commercialized anticancer drugs are now produced by pharmaceutical companies, most of them were originally obtained from natural sources, and more particularly from plants. Indeed, many structurally diverse compounds isolated from plants or marine flora have been purified and synthesized for their anticancer bioactivity. Among these, several molecules belong to the class of anticancer drugs which target the microtubule cytoskeleton, either by stabilizing it or destabilizing it. To characterize the activity of these drugs and to understand in which physiological context they are more likely to be used as therapeutic agents, it is necessary to fully determine their interaction with tubulin. Understanding the molecular basis of their effects on microtubule cytoskeleton is an important step in designing analogs with greater pharmacological activity and with fewer side effects. In addition, knowing the molecular mechanism of action of each drug that is already used in chemotherapy protocols will also help to find strategies to circumvent resistance. By taking examples of known anti-tubulin plant derived drugs, we show how identification of microtubule targeting agents and further characterization of their activity can be achieved combining biophysical and biochemical approaches. We also illustrate how continuing in depth study of molecules with already known primary mechanisms of action can lead to the discovery of new targets or biomarkers which can open new perspectives in anticancer strategies.
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