Terapia endocrina para la prevención primaria del cáncer de seno: Revisión sistemática y metaanálisis actualizado / Endocrine therapy for primary prevention of breast cancer: Systematic review and updated meta-analysis

Introducción. Debido a que el cáncer de seno es una enfermedad asociada a una significativa tasa de morbilidad y mortalidad cuando se diagnostica en el período sintomático, se han hecho enormes esfuerzos orientados hacia la prevención primaria de esta enfermedad. Métodos. Se realizó una búsqueda de todos los experimentos clínicos aleatorizados que evaluaran la eficacia de la terapia endocrina para la reducción del riesgo de desarrollar cáncer de seno. La calidad metodológica de los estudios seleccionados fue valorada utilizando la herramienta de la Colaboración Cochrane para medir el riesgo de sesgo en ensayos aleatorizados. Se evaluó la heterogeneidad de los estudios primarios elegibles utilizando los estadísticos T², I², H². El sesgo de publicación fue evaluado mediante el test de Harbord y mediante la gráfica de funnel plot. La medida de efecto utilizada en este metaanálisis fue el riesgo relativo (RR) con el cálculo de los intervalos de confianza (IC) del 95%. Resultados. Encontramos doce experimentos clínicos aleatorizados que reclutaron a 68.180 mujeres, las cuales fueron asignadas al azar para recibir algún tipo terapia endocrina para reducir el riesgo de desarrollar cáncer de seno o placebo. La terapia endocrina en conjunto redujo el riesgo proporcional de cáncer de seno (invasivo más in situ) en un 42 %, resultado estadísticamente significativo RR 0,58 (IC95% 0,50 ­ 0,69). Conclusiones. La terapia endocrina es el manejo estándar de prevención en mujeres sanas con riesgo de desarrollar cáncer de seno no hereditario.

Introduction. Because breast cancer is a disease associated with a significant morbidity and mortality rate when diagnosed in the symptomatic period, enormous efforts have been made towards the primary prevention of this disease. Methods. A search was conducted for all randomized clinical trials evaluating the efficacy of endocrine therapy in reducing the risk of developing breast cancer. The methodological quality of the selected studies was assessed using the Cochrane Collaboration tool to assess risk of bias in randomized trials. Heterogeneity of eligible primary studies was assessed using the T², I², H² statistics. Publication bias was evaluated using the Harbord test and the funnel plot. The effect measure used in this meta-analysis was the relative risk (RR) with the calculation of the 95% confidence intervals (CI).Results. We found twelve randomized clinical trials that recruited 68,180 women who were randomly assigned to receive some type of endocrine therapy to reduce the risk of developing breast cancer or placebo. Endocrine therapy as a whole reduced the proportional risk of breast cancer (invasive plus in situ) by 42%, a statistically significant result RR 0.58 (95% CI 0.50 - 0.69). Conclusions. Endocrine therapy is the standard preventive management in healthy women at risk of developing non-hereditary breast cancer.

The mechanism by which tamoxifen attenuates high glucose-induced epithelial-to-mesenchymal transition of rat peritoneal mesothelial cells / 中国基层医药

Objective:To investigate the effects of tamoxifen on high glucose-induced epithelial-to-mesenchymal transition of rat peritoneal mesothelial cells and the underlying mechanism.Methods:The peritoneal mesothelial cells of normal male SD rats were selected between January 2015 and June 2016 and then cultured and divided into blank control, high-glucose stimulation and drug intervention groups. High-glucose stimulation group: primary cultured rat peritoneal mesothelial cells (RPMCs) were treated with 60 mmol/L high-concentration glucose to induce epithelial-to-mesenchymal transition. Drug intervention group: (1) RPMCs were treated with 60 mmol/L high-concentration glucose and different concentrations (0.5 μmol/L, 2 μmol/L) of tamoxifen. After 72 hours of stimulation, protein was extracted. (2) RPMCs were treated with 60 mmol/L high-concentration glucose and 2 μmol/L tamoxifen with or without 2 μmol/L ER-α antagonist for 1 hour to extract protein and for 6 hours to extract RNA. (3) RPMCs were treated with high-concentration glucose and 2 μmol/L tamoxifen with or without 1 μmol/L 1 μM proteasome inhibitor for 1 hour to extract protein. Western blot analysis was performed to analyze change in E-cadherin, α-SMA, Smad2, p-Smad2, Smad3, p-Smad3 and Smad4 protein. Real-time fluorescence quantitative PCR was performed to detect the change in mRNA expression of Smad2, Smad3, connective tissue growth factor and plasminogen activator inhibitor 1.Results:Tamoxifen attenuated epithelial-to-mesenchymal transition on RPMCs induced by high-level glucose, showing increased expression of epithelial cell marker E-cadherin and decreased expression of α-SMA in a concentration-dependent manner ( tE-cadherin = 2.31, tα-SMA =-2.53, both P < 0.05).TGF-β1/R-Smad signal pathway was activated by high-concentration glucose. Phosphorylation of Smad2/3 and mRNA expression of CTGF and PAI-1 were increased. Tamoxifen remarkably reduced protein and mRNA level of above mentioned protein and related target genes ( tp-Smad2 = -3.38, tCTGF = -3.81, P < 0.05), which could be blocked by ER-α antagonist. Finally, proteasome inhibitor could weaken the inhibitory effects of tamoxifen on p-Smad2/3 and increase p-Smad2/3 protein level ( tp-Smad2 = 3.94, P < 0.05). Conclusion:Tamoxifen activates ER-α on RPMCs, weakens the activation of TGF-β1/R-Smad signal pathway through decreasing p-Smad2 protein level, and effectively inhibits the progression of high-concentration glucose-induced epithelial-to-mesenchymal transition possibly through degrading p-Smad2 protein through proteasome. The role of tamoxifen in epithelial-to-mesenchymal transition may provide a possible guide for research, prevention and treatment of peritoneal fibrosis.

Ormeloxifene versus combined oral contraceptive pills to control blood loss in cases of dysfunctional uterine bleeding

Background: Dysfunctional uterine bleeding is one of the most often encountered gynecologic problems causing anemia, reduced quality of life and unnecessary hysterectomies. A prospective study was conducted on women with DUB to study the effect of ormeloxifene versus combined oral contraceptive pills in controlling blood loss in them.Methods: 100 Women with DUB were enrolled randomly in three groups. After baseline assessment each patient in group A was treated with iron tablets, containing 100 mg elemental iron and folic acid 1.5 mg, for three months and were termed as control group. Group B patients were treated with ormeloxifene in dose of 60 mg twice a week for twelve weeks. Group C patients were treated with combined oral contraceptive pills for twenty- one days starting from third day of their LMP. The treatment was continued for three consecutive cycles. The efficacy of the studied drugs was analyzed by comparing the baseline and post treatment PBAC score, haemoglobin level and endometrial thickness, using appropriate statistical tests.Results: Ormeloxifene was more effective than only iron or combined oral contraceptive therapy in controlling menstrual blood loss (79.11% versus 58.57%). There was a reduction in endometrial thickness in group receiving ormeloxifene as well as in the group receiving combined oral contraceptive pills (p=0.486), however this was statistically not significant.Conclusions: Ormeloxifene was significantly better than combined OCP in reduction of menstrual blood flow in cases of DUB. It has better compliance and marked improvement in subjective symptoms as compared to OCP.

Selective estrogen receptor modulator: efficacy in abnormal uterine bleeding in perimenopausal women

Background: Abnormal uterine bleeding affects 50% women of perimenopausal age group. The use of ormeloxifene (SERMS) in management of AUB is well known. The objective of the present study was aimed to see the effects of ormeloxifene on different types of endometrium.in the medical management of Abnormal Uterine Bleeding (AUB).Methods: It was Prospective, interventional study. A total of 90 women who attended Outpatient Gynaecology Department, Guwahati with complain of AUB in perimenopausal age group (37-48) were prescribed 60mg ormeloxifene twice weekly for 3 months followed by once weekly for next 3 months after preliminary D and C.Results: Ormeloxifene was found to be more effective in reducing PBAC score and ET in patients with proliferative and secretory endometrium The reduction in mean PBAC score with ormeloxifene (175.3 to 20.93)(p value 0.0001) and ET (9.6 to 2.9 mm) (p value 0.0001) in proliferative endometrium, (179.2 to 14.8 (p value 0.0001) ) and ET 11.1 to 1.9 mm (p value 0.0003)in secretory endometrium was observed after 6 months. However, it was found not to be effective in reducing PBAC score and ET in patients with atrophic endometrium. Change in PBAC SCORE from 176.4 to 150.8 (p value 0.08) and in ET from 2.8 to 2.1mm( p value 0.3) was observed. No major side effects were reported.Conclusions: Ormeloxifene is effective in AUB with proliferative and secretory endometrium.

Influence of Supplementary Vitamin D on Bone Mineral Density When Used in Combination with Selective Estrogen Receptor Modulators

OBJECTIVES: Vitamin D is regarded as one of the major nutrients that significantly influence bone metabolism. This study aims to look at the effect of supplementary vitamin D on bone mineral density (BMD) in female osteoporosis patients. METHODS: The retrospective hospital record review was performed on 282 patients who were diagnosed with osteoporosis and treated with selective estrogen receptor modulators (SERMs) between January 2015 and December 2016. Of these patients, 151 were treated with SERMs only while 131 were treated using both SERMs and vitamin D supplements. The BMD and any occurrence of osteoporotic fracture episode were investigated after one year. The result of two groups was compared to find the significance of vitamin D. RESULTS: Overall, improvement in BMD score was observed in 76% of the patients. The BMD of the SERMs only group improved by 3% in spine and 1% in the hip while that of the SERMs with vitamin D group improved by 6% and 1% respectively. Statistical significance was noticed in the spine only. One distal radius fracture and one single level vertebral fracture occurred in patients of SERMs group while two distal radius fractures occurred in SERMs with vitamin D group. There was no occurrence of around hip fracture in both groups. CONCLUSION: The result of the current study suggests that additional vitamin D may have some additive effect on improving BMD of the spine. Further study with the larger study population and the extended study period is recommended.

Uterine Malignant Mixed Müllerian Tumors Following Treatment with Selective Estrogen Receptor Modulators in Patients with Breast Cancer: A Report of 13 Cases and Their Clinicopathologic Characteristics

BACKGROUND: Breast cancer treatment with selective estrogen receptor modulators (SERMs) increases the incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologic characteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discuss possible pathogenetic mechanisms. METHODS: Among 28,104 patients with breast cancer, clinicopathologic features and incidence of uMMMT were compared between patients who underwent SERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period, incidence, dose, and duration of SERM treatment, as well as overall survival rate, were compared for patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMT vs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathological findings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ, progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT. RESULTS: The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold). All patients with SERM were postmenopausal and received daily 20–40 mg SERM. Cumulative SERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologic features, such as International Federation of Gynecology and Obstetrics stage and overall survival, were not significantly different between patients with S-uMMMT and NS-uMMMT or between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available for immunostaining exhibited strong overexpression/null expression of p53 protein and significantly increased ERβ expression in carcinomatous and sarcomatous components. CONCLUSIONS: SERM therapy seemingly increases risk of S-uMMMT development; however, clinicopathologic features were similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expression might be involved in the etiology of S-uMMMT.

Antiplatelet Therapy in Breast Cancer Patients Using Hormonal Therapy: Myths, Evidence and Potentialities - Systematic Review / Terapia Antiplaquetária em Pacientes com Câncer de Mama em Uso de Terapia Hormonal: Mitos, Evidências e Potencialidades - Revisão Sistemática

Abstract Breast cancer is the most frequently diagnosed tumor in women worldwide, with a significant impact on morbidity and mortality. Chemotherapy and hormone therapy have significantly reduced mortality; however, the adverse effects are significant. Aspirin has been incorporated into clinical practice for over 100 years at a low cost, making it particularly attractive as a potential agent in breast cancer prevention and as an adjunct treatment to endocrine therapy in the prophylaxis of cardiovascular complications. The objective of this study was to evaluate the role of aspirin in reducing the incidence of breast cancer and to evaluate the impact of its use on morbidity and mortality and reduction of cardiovascular events as adjuvant therapy during breast cancer treatment with selective estrogen receptor modulators. A systematic review was performed using the PRISMA methodology and PICO criteria, based on the MEDLINE, EMBASE and LILACS databases. The original articles of clinical trials, cohort, case-control studies and meta-analyses published from January 1998 to June 2017, were considered. Most studies showed an association between the use of selective estrogen receptor modulators and the increase in thromboembolic events. The studies suggest a protective effect of aspirin for cardiovascular events during its concomitant use with selective estrogen receptor modulators and in the prevention of breast cancer. This systematic review suggests that aspirin therapy combines the benefit of protection against cardiovascular events with the potential reduction in breast cancer risk, and that the evaluation of the benefits of the interaction of endocrine therapy with aspirin should be further investigated.

Resumo O câncer de mama é o tumor mais frequentemente diagnosticado em mulheres de todo o mundo, com impacto importante na morbimortalidade. A quimioterapia e a terapia hormonal reduziram significativamente a mortalidade, mas os efeitos adversos são consideráveis. A aspirina está incorporada à prática clínica há mais de 100 anos, com baixo custo, tornando-a particularmente atraente como potencial agente na prevenção do câncer de mama e auxiliar durante o tratamento endócrino, na profilaxia de complicações cardiovasculares. Objetivou-se avaliar o papel da aspirina na redução da incidência do câncer de mama e avaliar o impacto de seu uso na morbimortalidade e na redução de eventos cardiovasculares como terapia adjuvante durante o tratamento do câncer de mama com moduladores seletivos do receptor do estrogênio. Procedeu-se à revisão sistemática utilizando-se a metodologia PRISMA e os critérios PICO, nas bases MEDLINE, EMBASE e LILACS. Foram considerados os artigos originais do tipo ensaio clínico, coorte, caso-controle e metanálises, publicados no período de janeiro de 1998 até junho de 2017. Na maioria dos estudos, houve relação entre o uso dos moduladores seletivos do receptor do estrogênio e o aumento de eventos tromboembólicos. Os estudos sugerem efeito protetor da aspirina para eventos cardiovasculares em uso concomitante aos moduladores seletivos do receptor do estrogênio e na prevenção do câncer de mama. Esta revisão sistemática sugere que o tratamento com aspirina combina o benefício da proteção contra eventos cardiovasculares com a potencial redução do risco de câncer de mama, e que a avaliação dos benefícios da interação da terapia endócrina com a aspirina deve ser melhor investigada.

Neuroprotective effects of selective estrogen receptor modulators in cerebral ischemia / 国际脑血管病杂志

Selective estrogen receptor modulators tamoxifen,raloxifene,and bazedoxifene reduce neuronal death through the mechanisms of anti-inflammation,antioxidant stress,and inhibition of glutamate excitotoxicity.They play a neuroprotective role in cerebral ischemia and may become a new neuroprotective agent for the treatment of ischemic stroke.

Research progress on the selective estrogen receptor modulators / 药学实践杂志

Breast cancer has become the main malignant tumors which pose a serious threat to women's health .Selective estrogen receptor modulators ,which served as the effective drug treatment ,have been attracting more attention .Present re‐search progress on the selective estrogen receptor modulators was summarized in this paper .

Selective Estrogen Receptor Modulators

Selective estrogen receptor modulators (SERMs) are now being used as a treatment for breast cancer, osteoporosis and postmenopausal symptoms, as these drugs have features that can act as an estrogen agonist and an antagonist, depending on the target tissue. After tamoxifen, raloxifene, lasofoxifene and bazedoxifene SERMs have been developed and used for treatment. The clinically decisive difference among these drugs (i.e., the key difference) is their endometrial safety. Compared to bisphosphonate drug formulations for osteoporosis, SERMs are to be used primarily in postmenopausal women of younger age and are particularly recommended if there is a family history of invasive breast cancer, as their use greatly reduces the incidence of this type of cancer in women. Among the above mentioned SERMs, raloxifene has been widely used in prevention and treatment of postmenopausal osteoporosis and vertebral compression fractures, and clinical studies are now underway to test the comparative advantages of raloxifene with those of bazedoxifene, a more recently developed SERM. Research on a number of adverse side effects of SERM agents is being performed to determine the long-term safety of this class of compouds for treatment of osteoporosis.

Effect of bazedoxifene on endometriosis in a rat model / 中华妇产科杂志

Objective To investigate the therapeutic mechanism of bazedoxifene, the third-generation selective ER modulator (SERM), on endometriosis lesions in a rat model. Methods Endometriosis was induced by transplanting pieces of endometrium from other syngeneic rats that were as donors onto the subcutaneous of other unmated female rats. The rats with successful ectopic implants were divided into two groups:control group (n=10) and bazedoxifene group (n=10). The macroscopic morphology, volume, histopathology of ectopic implant and rats uterine wet weight were determined before and after the treatment. Expression of proliferation cell nuclear antigen (PCNA), ER and PR in the eutopic endometrium and endometriosis lesions detected by immunohistochemistry in the two groups. Results (1) The gross morphology and histological changes of endometriosis lesions in rats after treatment: compared with the control group, it was obviously depauperated and had more less glands and blood vessels in the stroma. (2) The change of rats′weight, the volume of endometriosis lesion before and after treatment and rats uterine wet weigh after treatment respectively in the control group and the bazedoxifene group:rats′ weight were respectively before treatment: (201±17) g, (202±18) g, that were respectively after treatment: (266±16) g, (261±16) g, which showed no significant difference between two groups before and after treatment (P>0.05). The volume of ectopic implant before treatment were respectively (85±17) mm3, (85±12) mm3, and showed no significant difference between two groups;that were respectively (48±11) mm3, (24±9) mm3 afte rtreatment, which was significantly decreased compared with the control group (P0.05). Conclusion Bazedoxifene could obviously reduce the size of endometriosis lesions, the mechanism may be related with suppressing estrogen-induced proliferation, the expression of ER and direct ER antagonism by this SERM.

Research advances of the antioxidative activities of selective estrogen receptor modulators / 医学研究生学报

Selective estrogen receptor modulators (SERMs) is a class of estrogen-like non-steroid compounds that are able to bind to steroid hormone receptors .They can act as estrogen receptor agonist or antagonist depending on the target tissue and hormonal environment .Additionally , SERMs play an antioxidant role by scavenging oxygen free redicals , inhibiting lipid peroxidation , adjusting the level of NO and NOS , inhibiting mitochondrial permeability transition , improving the metabolism of free fatty acids in the mitochon-drial and regulating non-genomic transcription pathway .

Pattern Alopecia during Hormonal Anticancer Therapy in Patients with Breast Cancer

We report five cases of pattern alopecia in female patients who are undergoing hormonal anticancer therapy for the prevention of recurrence of breast cancer after surgery. Three patients demonstrated male pattern alopecia with receding frontal hairlines, and two patients demonstrated female pattern alopecia without receding hairlines. The detailed clinical history showed that the pattern alopecia of the patients developed after the full recovery of global hair loss of the entire scalp due to previous cytotoxic chemotherapy. All of the adjuvant hormonal anticancer drugs that were used in the patients are antiestrogenic agents, either aromatase inhibitors or selective estrogen receptor modulators. Considering androgen effect on the hair follicles of the fronto-parietal scalp, the androgen-estrogen imbalance caused by the drugs was thought to be the reason for the onset of pattern alopecia in the patients. In general, alopecia that develops during cytotoxic chemotherapy is well known to both physicians and patients; however, the diagnosis of pattern alopecia during hormonal anticancer therapy in breast cancer patients seems to be overlooked.

Moduladores seletivos do receptor estrogênico: novas moléculas e aplicações práticas / Selective estrogen receptor modulators: new molecules and practical uses

Os moduladores seletivos do receptor de estrogênio são moléculas que se ligam ao receptor estrogênico com ações agonistas e antagonistas, em tecidos específicos. Eles apresentam efeitos estrogênicos e antiestrogênicos em vários órgãos, o que lhes permite diferentes atuações clínicas específicas. As diferenças nas estruturas moleculares conferem propriedades diferentes de ligação ao receptor-alvo, resultando em diferenças nos efeitos terapêuticos e adversos. Desde a descoberta dos primeiros compostos, há 50 anos, vários outros têm sido estudados e são usados frequentemente por ginecologistas, oncologistas e mastologistas. O raloxifeno é aprovado para a prevenção e o tratamento de osteoporose na pós-menopausa e para o câncer de mama receptor de estrogênio positivo; o tamoxifeno, para prevenção e tratamento do câncer de mama receptor de estrogênio positivo na pós-menopausa; e o clomifeno, primeiro modulador seletivo com receptor de estrogênio a ser estudado e empregado clinicamente, para infertilidade. Outras moléculas como bazedoxifeno, lasofoxifeno e arzoxifeno vêm sendo estudadas e vêm se mostrando como alternativas eficazes, algumas com menos efeitos colaterais

Selective estrogen receptor modulators are molecules that bind to estrogen receptor with agonistic and antagonistic actions in specific tissues. They exert estrogenic and anti-estrogenic effects in several organs, allowing them to perform differently in specific clinical situations. The differences in molecular structures provide different binding properties to the target receptor, resulting in differences in therapeutic and adverse effects. Since the discovery of the first compounds 50 years ago, several others have been studied and are often used by gynecologists and oncologists, and mastologists. Raloxifene is approved for preventing and treating osteoporosis in postmenopausal women and for treating estrogen receptor-positive breast cancer; tamoxifen is used for preventing and treating estrogen receptor-positive postmenopausal breast cancer; and clomiphene, the first selective estrogen receptor modulator to be studied and clinically employed, is used for infertility treatment. Other molecules such as bazedoxifene, lasofoxifene and arzoxifene have been studied and shown to be effective alternatives, some with fewer side effects

Abordagens atuais para a recuperação da perda óssea em portadoras de osteoporose / Current approaches to recovery from bone loss in patients with osteoporosis

Fraturas osteoporóticas constituem um grave problema de saúde pública, e sua prevenção é fundamental. As medidas preventivas incluemmodificações no estilo de vida, nos hábitos nutricionais e na prática de exercícios. A terapia estrogênica ainda é muito usada no tratamento da osteoporose após a menopausa. Porém, seus efeitos adversos limitam o seu uso. Os moduladores seletivos do receptor estrogênico (SERMs) são uma nova classe de medicamentos que foram desenvolvidos com o objetivo de manter os efeitos benéficos da terapia hormonal, porém sem seus efeitos adversos, sendo o raloxifeno, o mais usado contra a perda. Para mulheres na pós-menopausa ou àqueles pacientes muito idosos que não podem fazer exercícios físicos, muitos trabalhos têm demonstrado que a vibração mecânica de baixa intensidade tem sido considerada uma alternativa não-medicamentosa e não-invasiva no tratamento e/ou prevenção da osteoporose. Os mecanismos de ação da vibração mecânica debaixa intensidade ainda são pouco conhecidos.

Osteoporotic fractures are a public health problem and their prevention is an important issue. Prevention of osteoporosis requires changes in life style, in healthy eating habits, as well as in physical exercises. Estrogen therapy is still very used in the treatment of osteoporosis after menopause. However, its adverse effects limit its use. Selective estrogen receptor modulators are a new class of drugs developed to maintain the beneficial effects of the hormone replacement therapy, but without its adverse effects, and raloxifen is the most used selective estrogen receptor modulator to prevent and treat postmenopausal osteoporosis. Thus, the demand for alternatives for the treatment postmenopausal bone loss has increased. Lowmagnitude mechanical vibration has been proposed as noninvasive and nonpharmacological alternative for prevention of osteoporosis of elderly people who are unable to practice regular physical exercises. However, the action mechanisms of low-magnitude mechanical vibration are not fully understood.

Anti-inflammatory mechanism of selective estrogen receptor modulator in mice with experimental autoimmune encephalomyelitis / 第二军医大学学报

Objective: To explore the anti-inflammatory mechanisms of selective estrogen receptor modulator (SERM) on experimental autoimmune encephalomyelitis(EAE). Methods: EAE models were induced with MOG35-55 peptide in 60 mice and all animals were ovarectomized. The model animals were then divided into treatment group and control group (n = 30). Treatment group was treated with SERM. The clinical symptom scores were compared between the two groups. The pathologic changes of the brain and spinal cord were studied by H-E staining and luxol fast blue(LFB)-HE staining. The expressions of MMP-9, TNF-α, IFN-γ, and IL-4 mRNA and protein were examined by quantitative real-time PCR and ELISA. Western blotting analysis was used to analyze the expression of myelin basic protein (MBP) so as to analyze the demyelination status. Results: Clinical symptom scores and incidence of EAE in the treatment group were improved compared with those in the control group (P<0.01, P<0.05). H-E staining showed that infiltration of inflammatory cells was decreased in the treatment group (P<0.05). LFB-H-E staining and Western blotting analysis showed that the demyelination was improved in the treatment group (P<0.05). The results of quantitative real-time PCR and ELISA showed that the expression of MMP-9,TNF-α, and IFN-γ were decreased and the expression of IL-4 was increased (P<0.05, P<0. 01). Conclusion: SERM can alleviate the inflammation symptom in EAE mice through decreasing MMP-9, TNF-α, and IFN-γ and increasing IL-4 expression.

Studies on antiestrogen compounds and their structure-activity relationships / 国际药学研究杂志

Antiestrogens have been proven to be highly effective in the treatment of estrogen receptor-dependent breast cancer. According to the mechanism, antiestrogen compounds were mainly categorized as selective estrogen receptor modulators (SERM) and pure antiestrogens, which structurally include estradiol derivatives, triphenylethylenes, benzo heterocyclic and polyphenol of natural compounds. The research advances on the antiestrogen compounds and their structure-activity relationships are reviewed.

Mechanisms of estrogen action / 中国病理生理杂志

Estrogen has widespread biological actions. Besides sexual organs, estrogen plays an important role in cardiovascular system, central nervous sy s tem and bone tissue. However, the mechanisms of estrogen action are very complex and not fully understood. The actions of estrogen are not identical and even co mpletely different in some organs system. In this review, we will focus on the n ew development of molecular mechanisms of estrogen action.