Current drug targets
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Current drug targets · Dec 2011
ReviewSelective estrogen receptor modulators and aromatase inhibitors for breast cancer chemoprevention.
In premenopausal women, tamoxifen for 5 years reduces the risk of estrogen receptor (ER) - positive breast cancer for at least 10 years. Women < 50 years of age experience fewer serious side effects. Vascular and vasomotor events do not persist after treatment regardless of age. ⋯ No evidence exists establishing whether a reduction in breast cancer risk from either agent translates into reduced breast cancer mortality. Overall quality of life is similar with raloxifene or tamoxifen, but the incidence of dyspareunia, weight gain, and musculoskeletal complaints is higher with raloxifene use, whereas vasomotor symptoms, bladder incontinence, gynecologic symptoms, and leg cramps were higher with tamoxifen use. Ongoing randomized, placebo-controlled trials investigating the use of third-generation aromatase inhibitors in the chemoprevention of breast cancer in postmenopausal women include the NCIC Clinical Trials Group MAP3 (ExCel) Trial (Exemestane in Preventing Cancer in Postmenopausal Women at Increased Risk of Developing Breast Cancer), and the IBIS-II trial.71 The North American MAP3 study randomized patients to exemestane or placebo in patients who refuse treatment with a SERM, and the international IBIS-II trial compares anastrozole for 5 years versus placebo for chemoprevention in patients at increased risk.
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Current drug targets · Dec 2011
Role of advanced glycation end products (AGEs) in osteoporosis in diabetes.
Recent meta-analyses have revealed that the risk of bone fracture is increased in both type 1 and type 2 diabetic patients. Low bone mineral density (BMD) can not necessarily explain the link, because BMD is increased rather than decreased in type 2 diabetes, while it is consistently low in type 1 diabetes subjects. Although multiple factors could influence the quality of bone and increase the bone fragility in diabetes, there is accumulating evidence for the association between osteoporosis and vascular calcification, which is an independent predictor of cardiovascular disease morbidity and mortality. ⋯ Further, cross-linking in the organic bone matrix by AGEs could adversely affect the fracture resistance of bone. Therefore, in this paper, I review the pathophysiological role of the AGEs-RAGE-oxidative stress system in decreased BMD and increased bone fragility in diabetes. I also discuss here the potential therapeutic interventions of the AGEs-RAGE axis for preventing osteoporosis in diabetes.