Advances in medical prevention of breast cancer / 中国肿瘤临床

The development of optimal strategies for breast cancer prevention is necessary given the high incidence in China. Several prospective randomized clinical trials have investigated the effects of various pharmacologic agents on the incidence of invasive and noninvasive breast cancer. This review aimed to summarize the different approaches to reduce the incidence of breast cancer.

Effectiveness of Osteoporosis Drug in Postmenopausal Women with Spinal Compression Fracture: Combined Consecutive Therapy of Teriparatide and Raloxifene versus Bisphosphonate Single / 대한신경손상학회지

OBJECTIVE: Bisphosphonate, a typical bone resorption inhibitor, is an important first-line drug for treating osteoporosis. Recent studies show a novel paradigm in stimulating bone formation. Teriparatide, which is composed of recombinant human parathyroid hormone, stimulates osteoblasts and induces bone regeneration. Bone mineral density (BMD) that was used before and after the treatment with anti-osteoporosis drug was compared for the effectiveness in therapy between a combination of teriparatide and selective estrogen receptor modulator (SERM), and bisphosphonate. METHODS: We retrospectively reviewed the outcomes of 85 postmenopausal women who were concurrently diagnosed with osteoporosis and spinal compression fracture between November 2008 and January 2015. The targeted group were treated with teriparatide and SERM (TS group, n=26) and bisphosphonate (B group, n=59). RESULTS: In both groups, BMD of femur neck was not improved after the medication. In the TS group, on the other hand the BMD and T-score of lumbar spine has significantly improved. BMD ratio of lumbar spine was prominently higher than those of TS group. CONCLUSION: The combination therapy of teriparatide and SERM was very effective in treating the lumbar spine, compared to that of bisphosphonate. Although the period of teriparatide treatment has been relatively short, the preventive effects of compression fracture were considerable. Thus, combination therapy of teriparatide and SERM is highly recommended for patients who are concerned with spinal compression fracture from osteoporosis.

Selective Estrogen Receptor Modulators: A Review of Action Mechanism and Clinical Data / 대한골다공증학회지

Selective estrogen receptor modulators (SERMs) are a diverse group of synthetic non-steroidal compounds that have various levels of estrogen receptor (ER) agonist or antagonist activity depending on the target tissue. This feature of SERMs could be explained by the differential expression of two ER isoforms (ERalpha or ERbeta), the differential ER conformational change and the differential coregulatory proteins (coactivator or corepressor) in a selected tissue. Based on their efficacy and safety, SERMs have been used for the prevention and treatment of breast cancer (tamoxifene and toremifene), prevention and treatment of osteoporosis (relaoxifene and bazedoxifene), treatment for dyspareunia related to vulvovaginal atrophy (ospemifene) and treatment for vasomotor symptoms associated with menopause (tissue selective estrogen complex; TSEC). Many of the available SERMs are well-known for their anti-estrogenic effects in breast and for their estrogenic effects in bone. The effect on the endometrium have played a key role in differentiate SERMs in clinical practice. The effect of SERMs in the vagina also shows clear distinction among different SERMs. This review summarizes their action mechanism and describes their clinical findings in different target tissues. In the osteoporosis treatment, SERMs such as raloxifene and bazedoxifene is a safe and effective option for women who cannot tolerate or are unwilling to take bisphosphonates and may be appropriate for younger woman with the age of < or =70 years old who expect to remain on therapy for many years and are concerned about the long-term safety of bisphosphonates.

SERMs in the prevention and treatment of postmenopausal osteoporosis: an update / SERMs na prevenção e no tratamento da osteoporose pós-menopausa: uma atualização

Selective estrogen receptor modulators (SERMs) have the ability to bind the estrogen receptor (ER) and are known to confer ER agonist or antagonist effects depending on the target tissue. A number of newer SERMs, including bazedoxifene, lasofoxifene and ospemifene, are currently under clinical development for the prevention and treatment of postmenopausal osteoporosis and for other indications. Although the possibility of developing a single agent that has all of the desired characteristics of an ideal SERM seems to be unlikely, progress in the clinical development of SERMs targeted to the ER suggests that these newer compounds may have attributes that represent an improvement relative to existing SERMs. A new approach to menopausal therapy is the tissue selective estrogen complex or the pairing of a selective estrogen receptor modulator with estrogens. Further investigation will help to clarify relative benefits/risks of novel SERMs in development within specific indications.

Moduladores seletivos do receptor do estrogênio (SERMs) têm a habilidade de se ligar ao receptor de estrogênio (ER) e são conhecidos por conferir um efeito agonista ou antagonista sobre o tecido-alvo. Um número de novos SERMs, incluindo bazedoxifeno, lasofoxifeno e ospemifeno, está atualmente em desenvolvimento clínico para prevenção e tratamento da osteoporose pós-menopausa e para outras indicações. Embora a possibilidade de desenvolver um simples agente que tenha todas as características desejadas de um SERM ideal parece ser pouco provável, esses novos SERMs apresentam propriedades que indicam uma melhora em relação aos SERMs existentes. Uma nova opção terapêutica é o uso do complexo estrogênico do tecido seletivo ou a associação do SERM com estrogênios. Novos estudos ajudarão a rastrear os riscos e benefícios dos novos SERMs em desenvolvimento dentro das suas indicações específicas.

Anti-osteoporotic effect of raloxifene on mice with osteoprotegerin gene deficiency / 中华内分泌代谢杂志

Objective To observe the effect of raloxifene, a selective estrogen receptor modulator, on osteoporosis in the osteoprotegerin (OPG) gene knock-out female and male mice. Methods Two groups of OPG gene deficient (OPG-/-) female and male mice, 20 mice in each group, were assigned to raloxifene-treated (3 mg The effect of raloxifene was evaluated by comparing the values of bone mineral density (BMD) , bone strength,histomorphometric measurement and osteoclast number between the raloxifene treated group and placebo group.Results As compared with placebo group osteoporotic manifestations were improved in OPG-/- female mice treated with raloxifene orally. BMD was increased both in lumbar vertebrae (P<0.05) and femurs (P<0.01).Bone strength was measured in femurs by three-point bending test and vertebrae by stress test. Results showed that ultimate load, ultimate stress and Young's modulus were increased both at lumbar and femur bone, suggesting decreased risk of fracture. Tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts, was detected, and the number of osteoclasts declined significantly after the treatment of raloxifene. At the same time, results of histomorphometric measurements indicated that bone trabecular volume was increased and bone formation rate decreased from(8.05±4.02)mm3·mm-2·year-1 to (5.48±1.89)mm3·mm-2· year-1(P＜0.05).These findings were found in the group of OPG-/- female mice treated with reloxifene but not in male mice. Conclusions Raloxifene is effective in treating osteoporosis in female OPG-/- mice, indicating that its action is at least in part independent of OPG gene. But it is ineffective in male OPG-/- mice.

The effect of selective estrogen receptor modulator,raloxifene on the gene expression of endothelin-1 in vascular endothelial cells and the relationship with estrogen receptor / 中华老年医学杂志

Objective To investigate the effect of raloxifene on the mRNA expression of endothelin-1 in vascular endothelial cells and assess the role of estrogen receptor. Methods Bovine carotid endothelial cells were pretreated with 10nM raloxifene for 24 hours, then total RNA was harvested and Northern blotting was performed to investigate the effect of raloxifene on the mRNA expression of endothelin-1. Furthermore, estrogen receptor inhibitor, 100nM ICI 182 780 was used to pretreat the cells together with raloxifene and the expression of endothelin-1 was observed too. Results The mRNA expression of endothelin-1 in bovine carotid endothelial cells was inhibited significantly by pretreatment with raloxifene and this effect could be blocked by ICI182 780 (0.16?0.05 vs 0.39?0.07, P

Effect of selective estrogen receptor modulator raloxifene on estrogen responsive element transcriptional activity in vascular endothelial cells / 中国病理生理杂志

AIM: To assess the effect of raloxifene, a selective estrogen modulator, on the transcriptional activity of estrogen responsive element (ERE) in vascular endothelial cells. METHODS: Vascular endothelial cells were transfected with ERE-TK-Luc reporter plasmid and PRL-SV40 control plasmid via FuGENE 6. The activities of firefly luciferase and renilla luciferase were measured with dual-luciferase reporter assay system. The transcriptional activity in transfected cells treated with raloxifene was compared with that in untreated cells. Furthermore, raloxifene was used to cotreat the cells with estradiol (E_2) and the influence of raloxifene to the effect of E_2 was assessed. RESULTS: Compared to untreated cells, the luciferase activity in cells treated with raloxifene decreased and showed significance at concentration of 10~(-7)mol/L (P