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1.
Asian Journal of Andrology ; (6): 215-220, 2018.
Artigo em Inglês | WPRIM | ID: wpr-1009593

RESUMO

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.


Assuntos
Humanos , Masculino , Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/secundário , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Endotelinas/antagonistas & inibidores , Neoplasias da Próstata/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Rádio (Elemento)/uso terapêutico , Samário/uso terapêutico , Radioisótopos de Estrôncio/uso terapêutico
3.
Artigo em Inglês | IMSEAR | ID: sea-85830

RESUMO

Endothelins, endothelin-1 (ET1), endothelin-2 (ET2) and endothelin-3 (ET3), are the most potent vasoconstrictor peptides released by endothelial cells. ET production is stimulated by vasopressor hormones, platelet-derived factors, coagulation products and cytokines, whereas nitric oxide and prostacyclin reduce ET production. ET bind to ETA and ETB receptors and produce marked and sustained rise in blood pressure, intense vasoconstriction of coronary arteries and have positive inotropic and chronotropic effects on myocardium. Besides, they influence neuroendocrine, renal and smooth muscle functions. ET appears to function mostly as a paracrine or an autocrine hormone. ET may have a role in hypertension, atherosclerosis, heart failure, coronary artery disease, renal insufficiency, vascular hypertrophy, respiratory and cerebrovascular conditions. Several antagonists of ET acting at receptor level or influencing endothelin converting enzyme (ECE) are under investigation and have great potential as agents for use in the treatment of wide spectrum of disease entities and as biologic probes for understanding the actions of ET in human beings.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares , Endotelinas/antagonistas & inibidores , Hemodinâmica/fisiologia , Humanos
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