In order to investigate the estrogen and estrogen receptor β changes after mating behavior of male mandarin vole （Microtus mandarinus）, the radioimmunoassay （RIA） and immunohistochemistry methods were used to inv...In order to investigate the estrogen and estrogen receptor β changes after mating behavior of male mandarin vole （Microtus mandarinus）, the radioimmunoassay （RIA） and immunohistochemistry methods were used to investigate changes of the serum estrogen （E） concentrations, estrogen immunoreactive neurons （E-IRs） and estrogen receptor β immunoreactive neurons （ERβ-IRs） in the relevant brain regions following mating behavior. Fifteen sexually matured male voles were randomly divided into three groups and treated differently： （1） control group： voles were exposed to clean hard-wood shavings （n=5）, （2） exposure group： voles were exposed to the soiled bedding for more than 24h on which estrous females had been placed （n=5）, and （3） mating group： voles were placed with an estrous female for more than 24h （n=5）. The results showed circulating serum E concentrations were significantly higher in the mating group than in the exposure group and the control group, and there were no significant difference between the exposure group and the control group. E-IRs and ERβ-IRs were detected in the following brain regions related to mating behavior： the arcuate nucleus （ARC）, bed nucleus of the stria terminalis （BST）, lateral septal nucleus （LS）, medial amygdaloid nucleus （ME）, medial preoptic area （MPO） and ventromedial hypothalamic nucleus （VMH）. The results showed that there were significantly more E-IRs in the six brain regions in the mating group than in the control group and the exposure group, and there were no significant difference between the exposure group and the control group except for LS. There was no significant difference in ERβ-IRs in the six brain regions among the three groups, and there were some lighter -stained ERβ-IRs in these brain regions. The results suggested that estrogen affect mating activity of male mandarin voles, but ERβ might not play an important role in mating behavior of male mandarin voles. Instead, it might be through other receptors.展开更多
Postmenopausal osteoporosis （PMO） is considered a polygenic disease. The estrogen receptor β （ESR2） gene is a candidate mediating the genetic influence on bone mass and the risk of osteoporosis. The aim of this s...Postmenopausal osteoporosis （PMO） is considered a polygenic disease. The estrogen receptor β （ESR2） gene is a candidate mediating the genetic influence on bone mass and the risk of osteoporosis. The aim of this study is to investigate the association of a cytosine-adenine （CA） repeat polymorphism in the fifth intron of the ESR2 gene with PMO in Chinese Han population. The CA repeat polymorphism was genotyped in a case-control study, involving 78 femoral neck PMO patients vs. 122 controls and 108 lumbar spine （L2-4） PMO patients vs. 92 controls. The （CA）n〈22 and （CA）n≥22 alleles were designated short （S） and long （L）, respectively. ESR2 genotype was categorically defined as SS （2 S alleles）, SL （having the mixed S and L alleles）, and LL （2 L alleles）. At both the femoral neck and the L2-4 region, LL genotype and L allele frequencies of the PMO group were significantly higher than those of the control group （P〈0.01）. The subjects with the SL, the LL, and the combined SL and LL genotype had a significant increased risk of PMO when compared with those with the SS genotype （P〈0.05）. After adjustments for age, years since menopause, menopausal age, and body mass index, logistic regression analysis showed that the subjects with the combined SL and LL genotype had increased risk of PMO when compared with those with the SS genotype both at the femoral neck （adjusted OR 4.923, 95% CI 1.986-12.203 , P=0.001） and the L2-4 （adjusted OR 2.267, 95% CI 1.121-4.598, P=0.023）. This extensive association study has identified the ESR2 CA repeat polymorphism to be independently associated with PMO at the femoral neck and the L2-4 in Chinese Han population. The data also suggested that the presence of the L allele may dominantly increase the risk of PMO at the two regions.展开更多
AIM To investigate gender-specific liver estrogen receptor(ER) expression in normal subjects and patients with hepatitis C virus(HCV)-related cirrhosis and hepatocellular carcinoma(HCC).METHODS Liver tissues from norm...AIM To investigate gender-specific liver estrogen receptor(ER) expression in normal subjects and patients with hepatitis C virus(HCV)-related cirrhosis and hepatocellular carcinoma(HCC).METHODS Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERα and ERβ, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERα and ERβ was further determined in nuclear and cytoplasmic tissue lysates along with the expression ofinflammatory [activated NF-κB and IκB-kinase(IKK)] and oncogenic(cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERα and ERβ was correlated with the expression of activated NF-κB, activated IKK and cyclin D1 by Spearman's correlation. RESULTS Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERα than females(P < 0.05). We observed significantly higher m RNA expression of ERα in HCV-related HCC liver tissues as compared to normals(P < 0.05) and ERβ in livers of HCV-related cirrhosis and HCV-related HCC subjects(P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERα in livers of HCV-related HCC patients and nuclear ERβ in HCV-related cirrhosis patients as compared to normals(P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-κB and cyclin D1 in diseased livers(P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCVinfection may contribute to the progression of HCVrelated cirrhosis to HCV-related HCC.CONCLUSION Gender differences were observed in ERα expression in normal livers. Alterations in ER subtype expression observed in diseased livers may influence genderrelated disparity in HCV-related pathogenesis.展开更多
Chronic hepatitis B virus (HBV) infection is the most common cause of hepatic fibrosis and hepatocellular carcinoma (HCC),mainly as a result of chronic necroinflammatory liver disease. A characteristic feature of chro...Chronic hepatitis B virus (HBV) infection is the most common cause of hepatic fibrosis and hepatocellular carcinoma (HCC),mainly as a result of chronic necroinflammatory liver disease. A characteristic feature of chronic hepatitis B infection,alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD) is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes,which,in turn,activates hepatic stellate cells (HSCs). HSCs are the primary target cells for inflammatory and oxidative stimuli,and these cells produce extracellular matrix components. Chronic hepatitis B appears to progress more rapidly in males than in females,and NAFLD,cirrhosis and HCC are predominately diseases that tend to occur in men and postmenopausal women. Premenopausal women have lower hepatic iron stores and a decreased production of proinflammatory cytokines. Hepatic steatosis has been observed in aromatase-deficient mice,and has been shown to decrease in animals after estradiol treatment. Estradiol is a potent endogenous antioxidant which suppresses hepatic fibrosis in animal models,and attenuates induction of redox sensitive transcription factors,hepatocyte apoptosis and HSC activation by inhibiting a generation of reactive oxygen species in primary cultures. Variant estrogen receptors are expressed to a greater extent in male patients with chronic liver disease than in females. These lines of evidence suggest that the greater progression of hepatic fibrosis and HCC in men and postmenopausal women may be due,at least in part,to lower production of estradiol and a reduced response to the action of estradiol. A better understanding of the basic mechanisms underlying the sex-associated differences in hepatic fibrogenesis and carciogenesis may open up new avenues for the prevention and treatment of chronic liver disease.展开更多
Retinoids mediate their actions via retinoic acid receptors(RARs) and retinoid X receptors(RXRs).Each of class of these nuclear retinoid receptor is further subdivided into three species namelyα,βandγ.Recently stud...Retinoids mediate their actions via retinoic acid receptors(RARs) and retinoid X receptors(RXRs).Each of class of these nuclear retinoid receptor is further subdivided into three species namelyα,βandγ.Recently studies demonstrated that estrogen receptor(ER)-positive human breast cancer(HBC) cell lines are sensitive and ER-negative cell lines are resistant to growth inhibitory effects of retinoic acid(RA).In this study,we found that only RARαmRNA levels was strongly correlated with ER-status.To further investigate the major role of RARαin retinoid-mediated inhibition of growth,we transfected RARαcDNA into two RA-resistant ER-negative HBC cell lines.Analysis of different clonal populations of RARαtransfectants from each cell line revealed growth inhibition by retinoids.Our results demonstrated that RARαplays a major role in mediating retinoids inhibition of growth in HBC cells and adequate levels of RARαare required for such an effect.展开更多
Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significa...Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significance of Ki-67 index as a prognostic marker and predictor of recurrence in different molecular subtypes of breast cancer. The relationship of Ki-67 index with different clinicopathological factors was also analyzed.Methods: Ki-67 index was measured in 107 cases of primary breast cancer from 2010-2012. These patients were evaluated for estrogen receptor, progesterone receptor, and HER2. Ki-67 was divided according to percentage levels: < 15% and > 15%. Followup ranged from 32 months up to 6 years.Results: Approximately 44, 23, 15, and 25 cases were grouped as luminal A, luminal B, HER2 subtype, and triple-negative(TN),respectively. No luminal A patients showed Ki-67 level higher than 15%, and their recurrence was 20%. In luminal B group, Ki-67 level higher than 15% was observed in 69% of patients, and recurrence was 39%. In HER2 subtype, Ki-67 was higher than 15% in34% of cases, and recurrence was 40%. In triple-negative cases, Ki-67 was higher than 15% in 60% of cases, and recurrence was detected in 32% of patients. Patients with Ki-67 less than 15% displayed better overall survival than those with Ki-67 higher than15%(P = 0.01). Patients with Ki-67 higher than 15% exhibited higher incidence of metastasis and recurrence than those with Ki-67 less than 15%(P = 0.000).Conclusions: Ki-67 may be considered as a valuable biomarker in breast cancer patients.展开更多
AIM:To investigate the relationship between the mast cell density(MCD)and the context of clinicopathological parameters and expression of p185,estrogen receptor(ER), and proliferating cell nuclear antigen(PCNA)in gast...AIM:To investigate the relationship between the mast cell density(MCD)and the context of clinicopathological parameters and expression of p185,estrogen receptor(ER), and proliferating cell nuclear antigen(PCNA)in gastric carcinoma. METHODS:Mast cell,p185,ER,and PCNA were detected using immunohistochemical S-P labeling method.Mast cell was counted in tissue of gastric carcinoma and regional lymph nodes respectively,and involved lymph nodes(ILN)were examined as usual. RESULTS:MCD was significantly related to both age and depth of penetration(x^2=4.688,P<0.05 for age and x^2=9.350, P<0.01 for depth of penetration)between MCD>21/0.03 mm^2 and MCD≤21/0.03 mm^2 in 100 patients;MCD in 1-6 ILN group patients was significantly higher than that in 7-15 ILN or>15 ILN group patients(u=6.881,8.055,P<0.01); There were significant differences intergroup in positive expression rate of p185,ER and PCNA between MCD>21/ 0.03 mm^2 and MCD≤21/0.03 mm^2 in 100 patients. CONCLUSION:Mast cell may have effect on inhibiting invasive growth of tumor,especially in the aged patients; The number of mast cells,in certain degree,may predicate the number of involved lymph nodes,which is valuable for assessment of prognosis;MCD was related to the expression of p185,ER,and PCNA in gastric carcinoma.It suggests that mast cell accumulation may inhibit the proliferation and the dissemination of the gastric carcinoma. INTRODUCTION Recently,many studies have reported on the association of mast cell with various tumorst.In several malignancies,mast cell has been found to correlate with growth,penetration and prognosis of tumor.Therefore,our study was undertaken to investigate the relationship between the mast cell density (MCD)and the context of clinicopathological parameters and expression of p 185,estrogen receptor(ER),and proliferating cell nuclear antigen(PCNA)in gastric carcinoma.展开更多
A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and wa...A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and was resistant to conventional chemotherapy regimens. Computed tomography and the circulating tumor cell test indicated that the patient's tumor burden increased rapidly even after several chemotherapy sessions. Multiple genetic aberrances in the phosphatidylinositol3-kinases(PI3 K) signaling pathway were detected via next-generation sequencing(NGS)-based liquid biopsy, including a p. G1007 R missense mutation in exon 21 of PIK3 CA(33.61%), a p.L70 fs frameshift mutation in exon 3 of phosphatase and tension homolog deleted on chromosome ten(PTEN)(49.14%), and a p. D1542 Y missense mutation in exon 32 of mammalian target of rapamycin(m TOR)(1.66%). Therefore, only the m TOR inhibitor everolimus was administered to the patient. Partial remission(PR) was observed after 2 months, and sustained stable disease(SD) was observed after a year and a half. Subsequent sequencing showed that the mutation ratio of PIK3 CA decreased to 4.17%, and that the PTEN and m TOR mutations disappeared, which revealed the significant curative effect of everolimus. We report the first case of successful monotherapy treatment using everolimus in a patient with advanced breast cancer bearing mutations in genes involved in the PI3 K/ARK/m TOR signaling pathway. The success of this case highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it successfully provided an optimal therapeutic target for the patient with advanced breast cancer.展开更多
Esophageal adenocarcinoma is a cancer with poor prognosis, and its incidence has risen sharply over recent decades. Obesity is a major risk factor for developing this cancer and there is a clear male gender bias in th...Esophageal adenocarcinoma is a cancer with poor prognosis, and its incidence has risen sharply over recent decades. Obesity is a major risk factor for developing this cancer and there is a clear male gender bias in the incidence that cannot be fully explained by known risk factors. It is possible that a difference in the expression of estrogen, or its signaling axes, may contribute to this gender bias. We undertook a com- prehensive literature search and analyzed the available data regarding estrogen and estrogen receptor expres- sion, and the possible sex-specific links with esopha- geal adenocarcinoma development. Potentially relevant associations between visceral vs subcutaneous fat deposition and estrogen expression, and the effect of crosstalk between estrogen and leptin signaling were identified. We also found limited studies suggesting a role for estrogen receptor 13 expression in esophageal adenocarcinoma development. The current literature supports speculation on an etiological role for estrogen in the male gender bias in esophageal adenocarcino- ma, but further studies are required.展开更多
In the present study expression of estrogen receptor subtype -alpha (ERalpha) and -beta (ERbeta) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1 to approximatel...In the present study expression of estrogen receptor subtype -alpha (ERalpha) and -beta (ERbeta) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1 to approximately 3-days-old) and adult (250 to approximately 350 g) rats, using reverse transcription-polymerase chain reaction (RT-PCR). No ERalpha transcripts were detectable in the adult cerebellum and olfactory bulb, whereas very weak expression of ERalpha was present in the adult cerebral cortex. No significant difference in ERbeta transcripts was detectable between the neonatal and adult rats. While transcripts for both ER subtypes were co-expressed in these brain areas of neonatal rats, although ERalpha expression was significantly weaker than ERbeta. Even in the cerebral cortex known to contain both ER subtypes in adult rats, ERalpha transcripts in neonatal rats were much higher than in adult. These observations provide evidence for the existence of different expression patterns of ERalpha/ERbeta transcripts in these three brain areas between the neonatal and adult rats, suggesting that each ER subtype may play a distinct role in the regulation of differentiation, development, and functions of the brain by estrogen.展开更多
Objective: To investigate estrogen receptor β (ERβ) gene Rsa1 polymorphism and concentration of estrogen, FSH and LH in serum in peri-menopausal and menopausal women with depressive disorder. Methods: Seventy-four p...Objective: To investigate estrogen receptor β (ERβ) gene Rsa1 polymorphism and concentration of estrogen, FSH and LH in serum in peri-menopausal and menopausal women with depressive disorder. Methods: Seventy-four peri-menopausal and menopausal women with depressive disorder met ICD-10 and CCMD-3 assessment criteria for depressive disorder were recruited. ERβ gene Rsa1 polymorphism was analyzed with PCR-RFLP. Serum levels of estrogen, FSH and LH were measured by magnetism-ELISA. Results: The respective frequency of ERβ gene Rsa1 polymorphism was no significant difference between women with depressive disorder and the healthy women (χ 2=1.106,P>0.05). The serum level of estrogen was lower in women with depressive disorder than in the healthy women (P<0.05). No difference was found for FSH and LH between two groups. Conclusion: ERβ gene Rsa1 polymorphism may be not associated with depressive disorder in the peri-menopausal and menopausal women. The serum level of estrogen is associated with depressive disorder in the peri-menopausal and menopausal women.展开更多
Triple-negative breast cancers (TNBCs) neither express estrogen receptor and progesterone receptor nor over- express human epidermal growth factor receptor-2. Because of the special molecular features, triple-negative...Triple-negative breast cancers (TNBCs) neither express estrogen receptor and progesterone receptor nor over- express human epidermal growth factor receptor-2. Because of the special molecular features, triple-negative breast cancer is not either sensitive to endocrine therapy or targeted therapy of trastuzumab. There has not been standard treatment regimen for triple-negative breast cancer yet and chemotherapy has still been the chief therapy currently. However, with the great progress of oncology and molecular biology, the understanding of the natural history, pathophysiology and molecular features of this disease has been greatly improved, and a growing number of novel and effective therapies and discoveries of new biological targets for this phenotype of breast cancers have been reported, which provide new insights into therapeutic strategies for the women suffering from it.展开更多
Objective: To investigate the relationship between estrogen receptor(ER) gene and the clinical indexes associated with coronary heart disease (CHD). Methods: By means of polymerase chain reaction-restriction fragment ...Objective: To investigate the relationship between estrogen receptor(ER) gene and the clinical indexes associated with coronary heart disease (CHD). Methods: By means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), we analyzed ER gene polymorphism in 84 CHD patients and 61 healthy subjects and non-CHD inpatients. The clinical indexes associated with CHD were analyzed in relation to the three ER genotypes. Results: There were significant differences in the incidence of hypertension (58.62%), fibrinogen (Fib) concentration (3.5±0.8 g/L), body mass index (BMI, 25.1±3.2), HDL-C concentration (1.0±0.2 mmol/L) between PP genotype group and other genotype groups (P<0.05). Conclusion: ER gene polymorphism may affect ER-mediated cardiovascular protective effect by modulating the expression of ER.展开更多
Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's dis...Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung' s disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modif ier genes.展开更多
Objective To investigate the effects of different fractions from Fuke Qianjin Formula(妇科千金方,FKQJF)on uterine leiomyoma(UL)to determine the best fraction.Methods FKQJF was extracted and isolated to obtain polysacc...Objective To investigate the effects of different fractions from Fuke Qianjin Formula(妇科千金方,FKQJF)on uterine leiomyoma(UL)to determine the best fraction.Methods FKQJF was extracted and isolated to obtain polysaccharides(FKP),flavonoids(FKF),and grease(FKG).140 female SPF SD rats were divided into 14 groups[model(MOD),normal control(NC),Gouliuqing(GLQ),Mifepristone(MFST),FKQJF,low,medium,and high dose of polysaccharides(l-FKP,m-FKP,and h-FKP),low,medium,and high dose of flavonoids(l-FKF,m-FKF,and h-FKF),low,medium,and high dose of grease(l-FKG,m-FKG,and h-FKG)],and uterine fibroids model rats were treated with drugs for four weeks.Serum levels of estrogen and progesterone were measured using enzyme-linked immunoassay assay(ELISA)kits.The expression of estrogen receptor(ER-α,ER-β)and progesterone receptor(PR)in the uterus was observed using immunohistochemistry(IHC).Serum metabolite profiles and FKG were analyzed using gas chromatography-mass spectrometry(GC-MS).Results FKQJF,h-FKF,m-FKG,and h-FKG significantly downregulated the estrogen level in the uterine fibroid model rats(P<0.01).FKQJF,h-FKF,and h-FKG significantly reduced the level of progesterone in the uterine fibroid model rats(P<0.01).The levels of ER-α,ER-β,and PR in uterine fibroid model rats were significantly decreased by FKQJF and h-FKG(P<0.01).The levels of ER-α,ER-β,and PR in the fibroid model rats were decreased by m-FKG(P<0.05).Additionally,serum metabolism results revealed that h-FKG and FKQJF could regulate related endogenous metabolites and make the pathological indices of uterine fibroids in rats close to the normal group.Forty-six components were identified in the oil,accounting for 91.97%of the total oil components.Conclusion FKQJF and h-FKG showed a significant anti-myoma activity and significantly improved the pathological state of the uterus in rats with hysteromyoma.The mechanism of action may be related to the regulation of estrogen progesterone and its receptor in uterine fibroid model animals.These findings proved the effect of FKQJF on uterine leiomyoma and provided an experimental basis for its clinical research and application.展开更多
基金Natural Science Foundation of China (30670273)Natural Science Foundation of Shaanxi (2008C269)+1 种基金Science and Technology Plan Project of Xi'an Bureau of Science and Technology (YF07194)Special Science Research Fund for Xi'an University of Arts and Science (KY200520)~~
文摘In order to investigate the estrogen and estrogen receptor β changes after mating behavior of male mandarin vole （Microtus mandarinus）, the radioimmunoassay （RIA） and immunohistochemistry methods were used to investigate changes of the serum estrogen （E） concentrations, estrogen immunoreactive neurons （E-IRs） and estrogen receptor β immunoreactive neurons （ERβ-IRs） in the relevant brain regions following mating behavior. Fifteen sexually matured male voles were randomly divided into three groups and treated differently： （1） control group： voles were exposed to clean hard-wood shavings （n=5）, （2） exposure group： voles were exposed to the soiled bedding for more than 24h on which estrous females had been placed （n=5）, and （3） mating group： voles were placed with an estrous female for more than 24h （n=5）. The results showed circulating serum E concentrations were significantly higher in the mating group than in the exposure group and the control group, and there were no significant difference between the exposure group and the control group. E-IRs and ERβ-IRs were detected in the following brain regions related to mating behavior： the arcuate nucleus （ARC）, bed nucleus of the stria terminalis （BST）, lateral septal nucleus （LS）, medial amygdaloid nucleus （ME）, medial preoptic area （MPO） and ventromedial hypothalamic nucleus （VMH）. The results showed that there were significantly more E-IRs in the six brain regions in the mating group than in the control group and the exposure group, and there were no significant difference between the exposure group and the control group except for LS. There was no significant difference in ERβ-IRs in the six brain regions among the three groups, and there were some lighter -stained ERβ-IRs in these brain regions. The results suggested that estrogen affect mating activity of male mandarin voles, but ERβ might not play an important role in mating behavior of male mandarin voles. Instead, it might be through other receptors.
文摘Postmenopausal osteoporosis （PMO） is considered a polygenic disease. The estrogen receptor β （ESR2） gene is a candidate mediating the genetic influence on bone mass and the risk of osteoporosis. The aim of this study is to investigate the association of a cytosine-adenine （CA） repeat polymorphism in the fifth intron of the ESR2 gene with PMO in Chinese Han population. The CA repeat polymorphism was genotyped in a case-control study, involving 78 femoral neck PMO patients vs. 122 controls and 108 lumbar spine （L2-4） PMO patients vs. 92 controls. The （CA）n〈22 and （CA）n≥22 alleles were designated short （S） and long （L）, respectively. ESR2 genotype was categorically defined as SS （2 S alleles）, SL （having the mixed S and L alleles）, and LL （2 L alleles）. At both the femoral neck and the L2-4 region, LL genotype and L allele frequencies of the PMO group were significantly higher than those of the control group （P〈0.01）. The subjects with the SL, the LL, and the combined SL and LL genotype had a significant increased risk of PMO when compared with those with the SS genotype （P〈0.05）. After adjustments for age, years since menopause, menopausal age, and body mass index, logistic regression analysis showed that the subjects with the combined SL and LL genotype had increased risk of PMO when compared with those with the SS genotype both at the femoral neck （adjusted OR 4.923, 95% CI 1.986-12.203 , P=0.001） and the L2-4 （adjusted OR 2.267, 95% CI 1.121-4.598, P=0.023）. This extensive association study has identified the ESR2 CA repeat polymorphism to be independently associated with PMO at the femoral neck and the L2-4 in Chinese Han population. The data also suggested that the presence of the L allele may dominantly increase the risk of PMO at the two regions.
基金Supported by Cancer Sucks,Bixby,Oklahoma Research grantto Kaul R
文摘AIM To investigate gender-specific liver estrogen receptor(ER) expression in normal subjects and patients with hepatitis C virus(HCV)-related cirrhosis and hepatocellular carcinoma(HCC).METHODS Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERα and ERβ, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERα and ERβ was further determined in nuclear and cytoplasmic tissue lysates along with the expression ofinflammatory [activated NF-κB and IκB-kinase(IKK)] and oncogenic(cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERα and ERβ was correlated with the expression of activated NF-κB, activated IKK and cyclin D1 by Spearman's correlation. RESULTS Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERα than females(P < 0.05). We observed significantly higher m RNA expression of ERα in HCV-related HCC liver tissues as compared to normals(P < 0.05) and ERβ in livers of HCV-related cirrhosis and HCV-related HCC subjects(P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERα in livers of HCV-related HCC patients and nuclear ERβ in HCV-related cirrhosis patients as compared to normals(P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-κB and cyclin D1 in diseased livers(P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCVinfection may contribute to the progression of HCVrelated cirrhosis to HCV-related HCC.CONCLUSION Gender differences were observed in ERα expression in normal livers. Alterations in ER subtype expression observed in diseased livers may influence genderrelated disparity in HCV-related pathogenesis.
文摘Chronic hepatitis B virus (HBV) infection is the most common cause of hepatic fibrosis and hepatocellular carcinoma (HCC),mainly as a result of chronic necroinflammatory liver disease. A characteristic feature of chronic hepatitis B infection,alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD) is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes,which,in turn,activates hepatic stellate cells (HSCs). HSCs are the primary target cells for inflammatory and oxidative stimuli,and these cells produce extracellular matrix components. Chronic hepatitis B appears to progress more rapidly in males than in females,and NAFLD,cirrhosis and HCC are predominately diseases that tend to occur in men and postmenopausal women. Premenopausal women have lower hepatic iron stores and a decreased production of proinflammatory cytokines. Hepatic steatosis has been observed in aromatase-deficient mice,and has been shown to decrease in animals after estradiol treatment. Estradiol is a potent endogenous antioxidant which suppresses hepatic fibrosis in animal models,and attenuates induction of redox sensitive transcription factors,hepatocyte apoptosis and HSC activation by inhibiting a generation of reactive oxygen species in primary cultures. Variant estrogen receptors are expressed to a greater extent in male patients with chronic liver disease than in females. These lines of evidence suggest that the greater progression of hepatic fibrosis and HCC in men and postmenopausal women may be due,at least in part,to lower production of estradiol and a reduced response to the action of estradiol. A better understanding of the basic mechanisms underlying the sex-associated differences in hepatic fibrogenesis and carciogenesis may open up new avenues for the prevention and treatment of chronic liver disease.
文摘Retinoids mediate their actions via retinoic acid receptors(RARs) and retinoid X receptors(RXRs).Each of class of these nuclear retinoid receptor is further subdivided into three species namelyα,βandγ.Recently studies demonstrated that estrogen receptor(ER)-positive human breast cancer(HBC) cell lines are sensitive and ER-negative cell lines are resistant to growth inhibitory effects of retinoic acid(RA).In this study,we found that only RARαmRNA levels was strongly correlated with ER-status.To further investigate the major role of RARαin retinoid-mediated inhibition of growth,we transfected RARαcDNA into two RA-resistant ER-negative HBC cell lines.Analysis of different clonal populations of RARαtransfectants from each cell line revealed growth inhibition by retinoids.Our results demonstrated that RARαplays a major role in mediating retinoids inhibition of growth in HBC cells and adequate levels of RARαare required for such an effect.
文摘Objective: Ki-67 plays an important function in cell division, but its exact role is still unknown. Moreover, few works regarding its overall function were published. The present study evaluated the clinical significance of Ki-67 index as a prognostic marker and predictor of recurrence in different molecular subtypes of breast cancer. The relationship of Ki-67 index with different clinicopathological factors was also analyzed.Methods: Ki-67 index was measured in 107 cases of primary breast cancer from 2010-2012. These patients were evaluated for estrogen receptor, progesterone receptor, and HER2. Ki-67 was divided according to percentage levels: < 15% and > 15%. Followup ranged from 32 months up to 6 years.Results: Approximately 44, 23, 15, and 25 cases were grouped as luminal A, luminal B, HER2 subtype, and triple-negative(TN),respectively. No luminal A patients showed Ki-67 level higher than 15%, and their recurrence was 20%. In luminal B group, Ki-67 level higher than 15% was observed in 69% of patients, and recurrence was 39%. In HER2 subtype, Ki-67 was higher than 15% in34% of cases, and recurrence was 40%. In triple-negative cases, Ki-67 was higher than 15% in 60% of cases, and recurrence was detected in 32% of patients. Patients with Ki-67 less than 15% displayed better overall survival than those with Ki-67 higher than15%(P = 0.01). Patients with Ki-67 higher than 15% exhibited higher incidence of metastasis and recurrence than those with Ki-67 less than 15%(P = 0.000).Conclusions: Ki-67 may be considered as a valuable biomarker in breast cancer patients.
文摘AIM:To investigate the relationship between the mast cell density(MCD)and the context of clinicopathological parameters and expression of p185,estrogen receptor(ER), and proliferating cell nuclear antigen(PCNA)in gastric carcinoma. METHODS:Mast cell,p185,ER,and PCNA were detected using immunohistochemical S-P labeling method.Mast cell was counted in tissue of gastric carcinoma and regional lymph nodes respectively,and involved lymph nodes(ILN)were examined as usual. RESULTS:MCD was significantly related to both age and depth of penetration(x^2=4.688,P<0.05 for age and x^2=9.350, P<0.01 for depth of penetration)between MCD>21/0.03 mm^2 and MCD≤21/0.03 mm^2 in 100 patients;MCD in 1-6 ILN group patients was significantly higher than that in 7-15 ILN or>15 ILN group patients(u=6.881,8.055,P<0.01); There were significant differences intergroup in positive expression rate of p185,ER and PCNA between MCD>21/ 0.03 mm^2 and MCD≤21/0.03 mm^2 in 100 patients. CONCLUSION:Mast cell may have effect on inhibiting invasive growth of tumor,especially in the aged patients; The number of mast cells,in certain degree,may predicate the number of involved lymph nodes,which is valuable for assessment of prognosis;MCD was related to the expression of p185,ER,and PCNA in gastric carcinoma.It suggests that mast cell accumulation may inhibit the proliferation and the dissemination of the gastric carcinoma. INTRODUCTION Recently,many studies have reported on the association of mast cell with various tumorst.In several malignancies,mast cell has been found to correlate with growth,penetration and prognosis of tumor.Therefore,our study was undertaken to investigate the relationship between the mast cell density (MCD)and the context of clinicopathological parameters and expression of p 185,estrogen receptor(ER),and proliferating cell nuclear antigen(PCNA)in gastric carcinoma.
文摘A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and was resistant to conventional chemotherapy regimens. Computed tomography and the circulating tumor cell test indicated that the patient's tumor burden increased rapidly even after several chemotherapy sessions. Multiple genetic aberrances in the phosphatidylinositol3-kinases(PI3 K) signaling pathway were detected via next-generation sequencing(NGS)-based liquid biopsy, including a p. G1007 R missense mutation in exon 21 of PIK3 CA(33.61%), a p.L70 fs frameshift mutation in exon 3 of phosphatase and tension homolog deleted on chromosome ten(PTEN)(49.14%), and a p. D1542 Y missense mutation in exon 32 of mammalian target of rapamycin(m TOR)(1.66%). Therefore, only the m TOR inhibitor everolimus was administered to the patient. Partial remission(PR) was observed after 2 months, and sustained stable disease(SD) was observed after a year and a half. Subsequent sequencing showed that the mutation ratio of PIK3 CA decreased to 4.17%, and that the PTEN and m TOR mutations disappeared, which revealed the significant curative effect of everolimus. We report the first case of successful monotherapy treatment using everolimus in a patient with advanced breast cancer bearing mutations in genes involved in the PI3 K/ARK/m TOR signaling pathway. The success of this case highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it successfully provided an optimal therapeutic target for the patient with advanced breast cancer.
文摘Esophageal adenocarcinoma is a cancer with poor prognosis, and its incidence has risen sharply over recent decades. Obesity is a major risk factor for developing this cancer and there is a clear male gender bias in the incidence that cannot be fully explained by known risk factors. It is possible that a difference in the expression of estrogen, or its signaling axes, may contribute to this gender bias. We undertook a com- prehensive literature search and analyzed the available data regarding estrogen and estrogen receptor expres- sion, and the possible sex-specific links with esopha- geal adenocarcinoma development. Potentially relevant associations between visceral vs subcutaneous fat deposition and estrogen expression, and the effect of crosstalk between estrogen and leptin signaling were identified. We also found limited studies suggesting a role for estrogen receptor 13 expression in esophageal adenocarcinoma development. The current literature supports speculation on an etiological role for estrogen in the male gender bias in esophageal adenocarcino- ma, but further studies are required.
文摘In the present study expression of estrogen receptor subtype -alpha (ERalpha) and -beta (ERbeta) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1 to approximately 3-days-old) and adult (250 to approximately 350 g) rats, using reverse transcription-polymerase chain reaction (RT-PCR). No ERalpha transcripts were detectable in the adult cerebellum and olfactory bulb, whereas very weak expression of ERalpha was present in the adult cerebral cortex. No significant difference in ERbeta transcripts was detectable between the neonatal and adult rats. While transcripts for both ER subtypes were co-expressed in these brain areas of neonatal rats, although ERalpha expression was significantly weaker than ERbeta. Even in the cerebral cortex known to contain both ER subtypes in adult rats, ERalpha transcripts in neonatal rats were much higher than in adult. These observations provide evidence for the existence of different expression patterns of ERalpha/ERbeta transcripts in these three brain areas between the neonatal and adult rats, suggesting that each ER subtype may play a distinct role in the regulation of differentiation, development, and functions of the brain by estrogen.
文摘Objective: To investigate estrogen receptor β (ERβ) gene Rsa1 polymorphism and concentration of estrogen, FSH and LH in serum in peri-menopausal and menopausal women with depressive disorder. Methods: Seventy-four peri-menopausal and menopausal women with depressive disorder met ICD-10 and CCMD-3 assessment criteria for depressive disorder were recruited. ERβ gene Rsa1 polymorphism was analyzed with PCR-RFLP. Serum levels of estrogen, FSH and LH were measured by magnetism-ELISA. Results: The respective frequency of ERβ gene Rsa1 polymorphism was no significant difference between women with depressive disorder and the healthy women (χ 2=1.106,P>0.05). The serum level of estrogen was lower in women with depressive disorder than in the healthy women (P<0.05). No difference was found for FSH and LH between two groups. Conclusion: ERβ gene Rsa1 polymorphism may be not associated with depressive disorder in the peri-menopausal and menopausal women. The serum level of estrogen is associated with depressive disorder in the peri-menopausal and menopausal women.
文摘Triple-negative breast cancers (TNBCs) neither express estrogen receptor and progesterone receptor nor over- express human epidermal growth factor receptor-2. Because of the special molecular features, triple-negative breast cancer is not either sensitive to endocrine therapy or targeted therapy of trastuzumab. There has not been standard treatment regimen for triple-negative breast cancer yet and chemotherapy has still been the chief therapy currently. However, with the great progress of oncology and molecular biology, the understanding of the natural history, pathophysiology and molecular features of this disease has been greatly improved, and a growing number of novel and effective therapies and discoveries of new biological targets for this phenotype of breast cancers have been reported, which provide new insights into therapeutic strategies for the women suffering from it.
基金Supported by the Key Basic Research and Development Project of National "973" Program of China (G200057008) the Foundation for University Leading Teachers Sponsored by the Ministry of Education of China, and by Funds for Key Natural Science Research of
文摘Objective: To investigate the relationship between estrogen receptor(ER) gene and the clinical indexes associated with coronary heart disease (CHD). Methods: By means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), we analyzed ER gene polymorphism in 84 CHD patients and 61 healthy subjects and non-CHD inpatients. The clinical indexes associated with CHD were analyzed in relation to the three ER genotypes. Results: There were significant differences in the incidence of hypertension (58.62%), fibrinogen (Fib) concentration (3.5±0.8 g/L), body mass index (BMI, 25.1±3.2), HDL-C concentration (1.0±0.2 mmol/L) between PP genotype group and other genotype groups (P<0.05). Conclusion: ER gene polymorphism may affect ER-mediated cardiovascular protective effect by modulating the expression of ER.
基金Supported by The National Health and Medical Research Council of Australia to Anderson RB: Project grant, No. 509219a CDA Fellowship, No. 454773
文摘Hirschsprung's disease is a congenital disorder that occurs in 1:5000 live births. It is characterised by an absence of enteric neurons along a variable region of the gastrointestinal tract. Hirschsprung's disease is classified as a multigenic disorder, because the same phenotype is associated with mutations in multiple distinct genes. Furthermore, the genetics of Hirschsprung's disease are highly complex and not strictly Mendelian. The phenotypic variability and incomplete penetrance observed in Hirschsprung' s disease also suggests the involvement of modifier genes. Here, we summarise the current knowledge of the genetics underlying Hirschsprung's disease based on human and animal studies, focusing on the principal causative genes, their interactions, and the role of modif ier genes.
基金funding support from the Major Science and Technology Projects in Hunan Province(No.2015SK1001)Special Funds from the Central Government to Guide Local Science and Technology Development(No.2019XF5076)+1 种基金Natural Science Foundation of Hunan Province(No.2017JJ1023 and No.2019JJ50443)the Research project of Hunan Education Department(No.17B198 and No.19C1398)。
文摘Objective To investigate the effects of different fractions from Fuke Qianjin Formula(妇科千金方,FKQJF)on uterine leiomyoma(UL)to determine the best fraction.Methods FKQJF was extracted and isolated to obtain polysaccharides(FKP),flavonoids(FKF),and grease(FKG).140 female SPF SD rats were divided into 14 groups[model(MOD),normal control(NC),Gouliuqing(GLQ),Mifepristone(MFST),FKQJF,low,medium,and high dose of polysaccharides(l-FKP,m-FKP,and h-FKP),low,medium,and high dose of flavonoids(l-FKF,m-FKF,and h-FKF),low,medium,and high dose of grease(l-FKG,m-FKG,and h-FKG)],and uterine fibroids model rats were treated with drugs for four weeks.Serum levels of estrogen and progesterone were measured using enzyme-linked immunoassay assay(ELISA)kits.The expression of estrogen receptor(ER-α,ER-β)and progesterone receptor(PR)in the uterus was observed using immunohistochemistry(IHC).Serum metabolite profiles and FKG were analyzed using gas chromatography-mass spectrometry(GC-MS).Results FKQJF,h-FKF,m-FKG,and h-FKG significantly downregulated the estrogen level in the uterine fibroid model rats(P<0.01).FKQJF,h-FKF,and h-FKG significantly reduced the level of progesterone in the uterine fibroid model rats(P<0.01).The levels of ER-α,ER-β,and PR in uterine fibroid model rats were significantly decreased by FKQJF and h-FKG(P<0.01).The levels of ER-α,ER-β,and PR in the fibroid model rats were decreased by m-FKG(P<0.05).Additionally,serum metabolism results revealed that h-FKG and FKQJF could regulate related endogenous metabolites and make the pathological indices of uterine fibroids in rats close to the normal group.Forty-six components were identified in the oil,accounting for 91.97%of the total oil components.Conclusion FKQJF and h-FKG showed a significant anti-myoma activity and significantly improved the pathological state of the uterus in rats with hysteromyoma.The mechanism of action may be related to the regulation of estrogen progesterone and its receptor in uterine fibroid model animals.These findings proved the effect of FKQJF on uterine leiomyoma and provided an experimental basis for its clinical research and application.
