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排序方式: 共有205条查询结果,搜索用时 15 毫秒
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Palomba S Russo T Orio F Tauchmanovà L Zupi E Panici PL Nappi C Colao A Lombardi G Zullo F 《Human reproduction (Oxford, England)》2002,17(12):3213-3219
BACKGROUND: Raloxifene hydrochloride is a synthetic non-steroidal drug used for the prevention and treatment of post-menopausal osteoporosis. Pre-clinical and clinical data have shown that raloxifene may have a beneficial effect on leiomyomas. The aim of this prospective single-blind, randomized, placebo-controlled clinical trial was to evaluate the effectiveness of the addition of raloxifene to GnRH analogues on uterine, leiomyoma, and non-leiomyoma sizes, and on the occurrence of leiomyoma-related symptoms. METHODS: After randomization using a computer-generated list, 100 pre-menopausal women with symptomatic uterine leiomyomas received either leuprolide acetate depot plus raloxifene 60 mg daily (group A) or leuprolide plus placebo tablet (group B) for six cycles of 28 days. At baseline and after treatment, uterine, leiomyoma and non-leiomyoma sizes, and leiomyoma-related symptoms were evaluated for each woman. Analysis was by intention-to-treat method. RESULTS: After six cycles of treatment, a significant decrease in uterine, leiomyoma, and non-leiomyoma sizes was detected in both groups in comparison with baseline. At the same time, no significant difference in uterine and non-leiomyoma sizes was observed between the groups. Leiomyoma sizes were significantly (P < 0.05) lower in group A than in group B. No difference was observed in leiomyoma-related symptoms between groups throughout the study period. CONCLUSIONS: In women treated with GnRH analogue, the raloxifene administration induces a higher reduction of leiomyoma sizes. 相似文献
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4.
Sambrook P 《Best Practice & Research: Clinical Rheumatology》2005,19(6):975-981
Clinical trials have demonstrated that the selective estrogen receptor modulator raloxifene can reduce the risk of vertebral fracture, but have not unequivocally demonstrated an effect on non-vertebral fracture. Consequently it is recommended that raloxifene be used mainly in postmenopausal women with milder osteoporosis as a preventive measure or for treatment in those with predominantly spinal osteoporosis. Since the effects of raloxifene on bone mineral density and bone turnover may reverse soon after cessation, it is recommended that raloxifene be used as long-term therapy for 5-10 years. Because of its quicker offset, use of raloxifene may have advantages over potent bisphosphonates if use of anabolic agents are contemplated in an individual patient. 相似文献
5.
Chad Deal MD 《Clinical reviews in bone and mineral metabolism》2006,4(4):291-303
Combination therapy, the use of an anabolic agent with an antiresorptive agent in some sequence, has been evaluated in a number
of clinical trials. There is no fracture data on combination therapy except for a small trial using PTH and estrogen. It appears
that simultaneous use of a bisphosphonate (alendronate 10 mg per day) with PTH offers no advantage (and appears to blunt PTH's
effect) compared with the use of PTH alone based on bone density gains. Previous therapy with alendronate also blunts gains
in bone density with PTH therapy. Estrogen and raloxifene, whether given before or with PTH, do not blunt its anabolic effect.
Sequential therapy with PTH followed by an antiresorptive agent (alendronate) offers the greatest gains in bone mass. It is
possible that alendronate or other bisphosphonates given in a different dosing regimes may have different effects on PTH's
anabolic effect. More trial data on combination therapy is needed. 相似文献
6.
Liu J Matsuo H Xu Q Chen W Wang J Maruo T 《Human reproduction (Oxford, England)》2007,22(5):1253-1259
BACKGROUND: This study was conducted to elucidate the effects of raloxifeneon proliferation and apoptosis in cultured human uterine leiomyomacells. METHODS: The monolayer cultures were treated with graded concentrations(109, 108 and 107 M) of raloxifeneand 107 M 17-estradiol (E2). Cell viability, percentageof proliferating cell nuclear antigen (PCNA)-positive cells,percentage of terminal deoxynucleotidyl transferase-mediated2'-deoxyuridine 5'-triphosphate nick-end labelling (TUNEL)-positivecells and the expression of PCNA and Bcl-2 proteins were assessedby 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxylphenyl)-2-(4-sulphophenyl)-2H-tetrazolium assay, immunocytochemistry, TUNEL assay and western blotanalysis, respectively. RESULTS: Compared with untreated cultures, the number of viable culturedcells, percentage of PCNA-positive cells and PCNA protein expressionwere significantly decreased by treatment with 109 Mraloxifene, but increased by treatment with either 108 Mor 107 M raloxifene. In contrast, the percentageof TUNEL-positive cells was significantly increased and Bcl-2protein expression was significantly decreased by treatmentwith 109 M raloxifene, whereas they were not affectedby treatment with either 108 or 107 M raloxifene. CONCLUSIONS: In cultured leiomyoma cells, low concentration (109 M)of raloxifene may inhibit the growth of leiomyoma cells, whereashigh concentrations (108 M, 107 M) ofraloxifene may promote their growth. 相似文献
7.
The effect of raloxifene on markers of bone turnover in older women living in long-term care facilities 总被引:6,自引:0,他引:6
Hansdóttir H Franzson L Prestwood K Sigurdsson G 《Journal of the American Geriatrics Society》2004,52(5):779-783
OBJECTIVES: To examine the effect of raloxifene on bone turnover in elderly women. DESIGN: Clinical intervention. SETTING: Long-term care facilities. PARTICIPANTS: Nineteen women completed the study, mean age 85 (range 76-99). INTERVENTION: Raloxifene 60 mg was given daily for 12 weeks. MEASUREMENTS: Markers of bone turnover were plasma C-telopeptides of type I collagen (CTx), urine cross-linked N-telopeptides of type I collagen (NTx) and serum tartrate-resistant acid phosphatase (TRAP 5b), plasma osteocalcin, and serum bone alkaline phosphatase. Other markers were serum 25-OH vitamin D, parathyroid hormone, ionized calcium, and phosphate. Markers were measured at baseline, after calcium and vitamin D had been taken for 6 weeks, after raloxifene had been taken for 12 weeks, and 6 weeks after raloxifene had been stopped. Paired sample t test was used to examine changes in markers at each time point. RESULTS: Plasma CTx decreased on average by 31%, urinary NTx by 35%, plasma osteocalcin by 25%, serum bone alkaline phosphatase by 15% (P<.01), and serum TRAP 5b by 10% (P<.05) on treatment. CONCLUSION: Raloxifene reduces bone turnover in elderly women living in long-term care facilities. The effect of raloxifene on bone turnover is comparable with that seen in younger postmenopausal women. 相似文献
8.
The ability of estrogens to produce rapid changes in cellular function has been firmly established. The question remains whether
these changes are mediated by a modified form of the nuclear estrogen receptor (ER) that is associated with the plasma membrane
(mER) or by a completely novel membrane receptor. Therefore, we characterized the biochemical properties of the nuclear and
membrane-associated ERs expressed endogenously in a rat hypothalamic endothelial cell line (D12). Radioligand binding experiments
using D12 membrane fractions showed that these cells exhibit properties consistent with a binding site specific for estrogens
(mER). Equilibrium binding assays using [125I]16-α-iodo-3,17-β-estradiol revealed saturable binding to mER, an affinity value similar to nuclear ER, with differing receptor
expression levels. Competition assays revealed that 9 of 12 ER ligands tested had comparable affinities for mER and ER. For
example, 17-α-estradiol and estrone had similar binding characteristics for both receptors while differences were noted for
raloxifene, 17β-estradiol (E2), and genistein. Western blot and immunocytochemical analyses using antibodies specific for
ERα confirmed that D12 cells expressed a membrane-associated protein with a molecular mass (67 kDa) similar to that of ERα
that colocalized with caveolae-enriched membranes. A rapid increase in intracellar Ca2+ levels in the presence of E2 suggests that mER can mediate physiologic changes through calcium mobilization. These data support
the expression of mER in these brain-derived endothelial cells that is similar to, but biochemically distinguishable from,
nuclear ERα. 相似文献
9.
V. Craig Jordan 《Breast cancer research and treatment》1995,36(3):267-285
Summary In 1973, McGuire and Chamness (In: O'Malley BW and Means AR (eds) Receptors for Reproductive Hormones, Plenum Press) summarized their work on the estrogen receptor in animal and human breast tumors, and in so doing described a target for therapeutic intervention. At that time there were no clinically useful antiestrogens, but the subsequent development of tamoxifen for breast cancer therapy has revolutionized the approach to treatment. Long-term adjuvant tamoxifen adjuvant therapy (i.e. greater than one year) has proven efficacy to enhance the survival of breast cancer patients. In addition, because there is an associated 40% decrease in contralateral breast cancer during adjuvant tamoxifen therapy and tamoxifen maintains bone density and reduces fatal myocardial infarction, clinical trials to test the worth of tamoxifen as a preventive for breast cancer in high risk women have started in the United States, United Kingdom, and Italy. Initial concerns that long-term tamoxifen causes endometrial cancer have been placed in perspective and analyzed by a review of the literature. Tamoxifen only doubles the normal risk of detecting endometrial cancer, (i.e. to 2 per 1,000 tamoxifen-treated women per year), and 80% of these cases are early stage, good prognosis disease. Annual gynecological examinations and education are essential to provide reassurance for patients.The success of tamoxifen has encouraged the development of new antiestrogens to exploit the estrogen receptor as a therapeutic target. Droloxifene and TAT-59 mimic the metabolite 4-hydroxytamoxifen in having a high affinity for the estrogen receptor (Jordan et al, J Endocrinol 75:305, 1977). These drugs appear to have a pharmacological profile similar to tamoxifen. In contrast, the new pure antiestrogens have a distinct mechanism of action and will be valuable either as a first line therapy for advanced breast cancer or as a second line endocrine therapy after the failure of long-term adjuvant tamoxifen therapy.Finally, a new strategy is being developed to exploit the target site specific action of antiestrogens. Raloxifene, an antiestrogen with high affinity for the estrogen receptor but only weak estrogenicity for the uterus, prevents rat mammary tumorigenesis and maintains bone density. The drug is to be evaluated as a treatment for osteoporosis, but may also prevent the development of breast and endometrial cancer in a broad group of treated subjects.The identification of the estrogen receptor as a target for therapeutic opportunities has proved to be extremely beneficial for the control of breast cancer and has the added potential to control osteoporosis and coronary heart disease in women.Presented at the 17th Annual San Antonio Breast Cancer Symposium. The William L. McGuire Memorial Lectures are sponsored by an educational grant from Wellcome Oncology. 相似文献
10.
Gutman M Couillard S Roy J Labrie F Candas B Labrie C 《International journal of cancer. Journal international du cancer》2002,99(2):273-278
EM-652 exerts pure antiestrogenic activity in the mammary gland and endometrium, while tamoxifen, the antiestrogen most widely used for the treatment of breast cancer, exerts mixed antiestrogenic-estrogenic activity in these tissues. Our objective was to compare the agonistic and antagonistic effects of EM-652 with tamoxifen and 5 other antiestrogens on the growth of ZR-75-1 human breast xenografts in ovariectomized nude mice. During the 23 weeks of treatment at a daily oral dose of 50 microg, EM-652 was the only compound that decreased tumor size relative to pretreatment values, whereas the 6 other antiestrogens only decreased to various extents the progression rate stimulated by estrone. Under estrone stimulation, all groups of animals had more than 60% of their tumors in the progression category except for the EM-652-treated group, where only 7% of the tumors progressed. In the absence of estrone stimulation, progression was seen in 60%, 33%, 21% and 12% of tumors in the tamoxifen-, idoxifene-, toremifene- and raloxifene-treated groups, respectively, while only 4% of tumors progressed in the EM-652-treated group. The agonistic and antagonistic actions of each antiestrogen were also measured on endometrial epithelial cell thickness. Our present findings indicate that EM-652, in addition to being the most potent antiestrogen on human breast tumor growth, has no agonistic effect in breast and endometrial tissues. Since previous data have shown benefits of EM-652 on bone density and lipid profile, this compound could be an ideal candidate for chemoprevention of breast and uterine cancers, while protecting against osteoporosis and cardiovascular disease. 相似文献