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Spatholobus suberectus column extract inhibit estrogen receptor positive breast cancer
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作者 SUN Jia-qi ZHANG Yi +5 位作者 NAN Nan SUN Xu ZHANG Gan-lin YU Ming-wei WANG Xiao-min LI Jin-ping 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2016年第10期1070-1070,共1页
OBJECTIVE To investigate the inhibitory effects of Spatholobus Suberectus Column Extract(SSCE)on estrogen receptor positive(ER+)breast cancer cel MCF-7and its possible molecular mechanism.METHODS MCF-7cells were cultu... OBJECTIVE To investigate the inhibitory effects of Spatholobus Suberectus Column Extract(SSCE)on estrogen receptor positive(ER+)breast cancer cel MCF-7and its possible molecular mechanism.METHODS MCF-7cells were cultured without estrogen and with 17-β-estrogen(10-8mol·L-1),respectively,then treated with SSCE(0,40,80,160,320μg·m L-1).MTT assay was employed to evaluate cell viability.Flow cytometry assays were performed to underlying apoptosis and detecting cel cycle of MCF-7 cells treated with SSCE(0,80,160,320μg·mL-1).Wound healing assays was conducted to detect the migration ability.Dual luciferase reporter system was used to detect the activity of p-ERα,p-ERβpresented in intra-nuclear estrogen response element(ERE).Western blotting assay was employed to identify the expression of protein such as Bax,Bcl-2,p-ERα,p-ERβ,ERK1/2,p-ERK1/2,AKT,p-AKT,m TOR,p-m TOR,PI3K,p-PI3K.RESULTS It showed that SSCE(80,160and 320μg·mL-1)significantly decreased the viability of MCF-7.SSCE also triggered apoptosis,arrested cell cycle at G0/G1phase,inhibited migration.Dual luciferase reporter system showed that SSCE suppressed intra-nuclear p-ER activity,Western blotting analysis confirmed that SSCE did repress the expression of phosphorylated-ER alpha(p-ERα),ERK1/2,p-ERK1/2,AKT,p-AKT,pmT OR,PI3K,p-PI3K,which indicate that SSCE suppress MAPK PI3K/AKT signal pathway.CONCLUSION Our result showed that SSCE cause ER+MCF-7 cells apoptosis,G0/G1phase arresting,migration decreasing,via hypo-active of ER,suppress MAPK PI3K/AKT pathway. 展开更多
关键词 Caulis Spatholobi breast neoplasms estrogen receptor PROLIFERATION
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The Relationship of CyclinD1 and Estrogen Receptor Expression in the Process of Proliferation and Metastasis in Breast Neoplasm 被引量:13
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作者 王欣 邹声泉 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2001年第3期231-232,共2页
The role of CyclinD1 and estrogen receptor (ER) in the process of proliferation and metastasis of breast neoplasm and their relationship were studied. The expression levels of CyclinD1 and ER in the tissue samples wer... The role of CyclinD1 and estrogen receptor (ER) in the process of proliferation and metastasis of breast neoplasm and their relationship were studied. The expression levels of CyclinD1 and ER in the tissue samples were detected by using flow cytometry and L SAB immunohistochemistry staining, respectively. The results showed that CyclinD1 and ER expression levels in breast cancer were significantly higher than in benign breast neoplasm (P<0.05). The CyclinD1 expression levels in stage I was much lower than in stages Ⅱ, Ⅲ, Ⅳ (P<0.05). The positive rate of ER was not related with tumor size, lymph node metastasis and TNM stage (P>0.05), but the CyclinD1 expression level in ER (+) group was significantly higher than in ER (-) group (P<0.05). It was concluded that CyclinD1 expression level might be obviously related with the proliferation and metastasis of breast neoplasm and ER. 展开更多
关键词 breast cancer CYCLIND1 flow cytometry estrogen receptor
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Current medical treatment of estrogen receptor-positive breast cancer 被引量:16
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作者 Franco Lumachi Davide A Santeufemia Stefano MM Basso 《World Journal of Biological Chemistry》 CAS 2015年第3期231-239,共9页
Approximately 80% of breast cancers(BC) are estrogen receptor(ER)-positive and thus endocrine therapy(ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adre... Approximately 80% of breast cancers(BC) are estrogen receptor(ER)-positive and thus endocrine therapy(ET) should be considered complementary to surgery in the majority of patients. The advantages of oophorectomy, adrenalectomy and hypophysectomy in women with advanced BC have been demonstrated many years ago, and currently ET consist of(1) ovarian function suppression(OFS), usually obtained using gonadotropinreleasing hormone agonists(Gn RHa);(2) selective estrogen receptor modulators or down-regulators(SERMs or SERDs); and(3) aromatase inhibitors(AIs), or a combination of two or more drugs. For patients aged less than 50 years and ER+ BC, there is no conclusive evidence that the combination of OFS and SERMs(i.e., tamoxifen) or chemotherapy is superior to OFS alone. Tamoxifen users exhibit a reduced risk of BC, both invasive and in situ, especially during the first 5 years of therapy, and extending the treatment to 10 years further reduced the risk of recurrences. SERDs(i.e., fulvestrant) are especially useful in the neoadjuvant treatment of advanced BC, alone or in combination with either cytotoxic agents or AIs. There are two types of AIs: type Ⅰ are permanent steroidal inhibitors of aromatase, while type Ⅱ are reversible nonsteroidal inhibitors. Several studies demonstrated the superiority of the third-generation AIs(i.e., anastrozole and letrozole) compared with tamoxifen, and adjuvant therapy with AIs reduces the recurrence risk especially in patients with advanced BC. Unfortunately, some cancers are or became ET-resistant, and thus other drugs have been suggested in combination with SERMs or AIs, including cyclin-dependent kinase 4/6 inhibitors(palbociclib) and mammalian target of rapamycin(m TOR) inhibitors, such as everolimus. Further studies are required to confirm their real usefulness. 展开更多
关键词 breast cancer ENDOCRINE therapy Gn RHagonists OVARIAN function suppression TAMOXIFEN Selective estrogen receptor MODULATOR AROMATASE inhibitors
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Polyubiquitination inhibition of estrogen receptor alpha and its implications in breast cancer 被引量:2
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作者 Angeles C Tecalco-Cruz Josué O Ramírez-Jarquín 《World Journal of Clinical Oncology》 CAS 2018年第4期60-70,共11页
Estrogen receptor alpha(ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear... Estrogen receptor alpha(ERα) is detected in more than 70% of the cases of breast cancer. Nuclear activity of ERα, a transcriptional regulator, is linked to the development of mammary tumors, whereas the extranuclear activity of ERα is related to endocrine therapy resistance. ERα polyubiquitination is induced by the estradiol hormone, and also by selective estrogen receptor degraders, resulting in ERα degradation via the ubiquitin proteasome system. Moreover, polyubiquitination is related to the ERα transcription cycle, and some E3-ubiquitin ligases also function as coactivators for ERα. Several studies have demonstrated that ERα polyubiquitination is inhibited by multiple mechanisms that include posttranslational modifica-tions, intera-ctions with coregula-tors, a-nd forma-tion of specific protein complexes with ERα. These events are responsible for an increase in ERα protein levels and deregulation of its signaling in breast cancers. Thus, ERα polyubiquitination inhibition may be a key factor in the progression of breast cancer and resistance to endocrine therapy. 展开更多
关键词 estrogen receptor ALPHA POLYUBIQUITINATION breast cancer estrogen receptor ALPHA
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Tumor biology in estrogen receptor-positive,human epidermal growth factor receptor type 2-negative breast cancer:Mind the menopausal status 被引量:1
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作者 Hiroko Yamashita 《World Journal of Clinical Oncology》 CAS 2015年第6期220-224,共5页
Breast cancer is not one disease,but can be categorized into four major molecular subtypes according to hormone receptor [estrogen receptor(ER) and progesterone receptor(Pg R)] and human epidermal growth factor recept... Breast cancer is not one disease,but can be categorized into four major molecular subtypes according to hormone receptor [estrogen receptor(ER) and progesterone receptor(Pg R)] and human epidermal growth factor receptor type 2(HER2) expression status. Ki67 labeling index and/or multigene assays are used to classify ERpositive,HER2-negative breast cancer into luminal A and luminal B(HER2-negative) subtypes. To date,most studies analyzing predictive or prognostic factors in ER-positive breast cancer have been performed in postmenopausal women,mainly using patients and samples in adjuvant aromatase inhibitor trials. In contrast,even the clinical roles of Pg R and Ki67 have been little analyzed so far in premenopausal women. Pg R is one of the estrogen-responsive genes,and it has been reported that plasma estradiol levels are related to expression levels of estrogen-responsive genes including PGR in ER-positive breast cancer. In this article,biological differences,especially differences in expression of Pg R and Ki67 in ER-positive breast cancer between pre- and postmenopausal women are discussed. Clinical roles of Pg R and Ki67 in ER-positive breast cancer differ between pre- and postmenopausal women. We suggest that the mechanisms of development and estrogen-dependent growth of ER-positive breast cancer might differ according to menopausal status. 展开更多
关键词 breast cancer PROGESTERONE receptor estrogen receptor KI67 MENOPAUSAL status
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The Prognostic Significance of a Combined Determination of Cathepsin D and Estrogen Receptors in Breast Carcinomas with Positive Axillary Lymph Nodes 被引量:2
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作者 Yun Niu Xue Yang Yu Fan Ajuan Lu Tieju Liu Xilin Fu 《Chinese Journal of Clinical Oncology》 CSCD 2006年第3期172-175,180,共5页
OBJECTIVE The aim of this study was to investigate the correlation between cathepsin D (Cath-D) and estrogen receptor (ER)expression in breast cancer tissue and to explore the prognostic significance of their comb... OBJECTIVE The aim of this study was to investigate the correlation between cathepsin D (Cath-D) and estrogen receptor (ER)expression in breast cancer tissue and to explore the prognostic significance of their combined determination in breast carcinoma patients with positive axillary lymph nodes. METHODS One hundred and thirty-eight cases of breast carcinoma were examined by immunohistochemistry (IHC) and the results relating to patient follow-up analyzed. RESULTS The overall 5-year disease-free survival rate (DFS) was 60.9% (84/138) in the series. The positive rate of Cath-D expression in the tumor cells was 55.07% and the positive ER staining was 51.4%. A definite significant negative correlation was found between the positive rates for Cath-D and ER (r=-0.294, P=0.001) The Cath-D expression for the cases in clinical Stage Ⅱ, ≥10 positive-node and recurrence or distant metastasis, was higher than that those cases in clinical Stage II with fewer node-metastasis and with 5 year DFS (X^2=13.926, P=0.000; X^2=13.070, P=0.001; X^2=10.545, P=0.001). However, there was no significant difference of Cath-D expression between 2 groups of patients with different ages or among the different histopathologic types of the nonspecific invasive carcinoma. In the combined examination of Cath-D and ER, the cases that were ER (+) and Cath-D (-) had the highest 5-year DFS compared to other situations. In contrast, the cases that were reversed in expression, ie, ER(-) and Cath-D(+), had a lower 5-year DFS. There was a significant difference between the 2 conditions (X2=18.675, P=0.000). CONCLUSION A combined determination and analysis of Cath-D and ER expression may be more useful to establish a prognosis than the biological characteristics of carcinomas with positive lymph nodes. 展开更多
关键词 breast carcinoma CATHEPSIN-D estrogen receptor combined determination prognosis.
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Increased Cellular Invasion and Proliferation via Estrogen Receptor after 17-<i>β</i>-Estradiol Treatment in Breast Cancer Cells Using Stable Isotopic Labeling with Amino Acids in Cell Culture (SILAC) 被引量:1
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作者 Alimatou M. Tchafa Zhijiu Zhong +2 位作者 Rong Meng Judy N. Quong Andrew A. Quong 《Advances in Breast Cancer Research》 2013年第2期32-43,共12页
17-β-estradiol (estrogen) is a steroid hormone important to human development;however, high levels of this molecule are associated with increased risk of breast cancer primarily due to estrogen’s ability to bind and... 17-β-estradiol (estrogen) is a steroid hormone important to human development;however, high levels of this molecule are associated with increased risk of breast cancer primarily due to estrogen’s ability to bind and activate the estrogen receptor (ER) and initiate gene transcription. Currently, estrogen mechanisms of action are classified as genomic and non-genomic and occur in an ER-dependent and ER-independent manner. In this study, we examine estrogen signaling pathways, by measuring changes in protein expression as a function of time of exposure to estrogen in both ER-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. Using a robust experimental design utilizing isotopic labeling, two-dimensional LC-MS, and bioinformatics analysis, we report genomic and non-genomic ER regulated estrogen responsive proteins. We find a little over 200 proteins differentially expressed after estrogen treatment. Cell proliferation, transcription, actin filament capping and cell to cell signaling are significantly enriched in the MCF-7 cell line alone. Translational elongation and proteolysis are enriched in both cell lines. Subsets of the proteins presented in this study are for the first time directly associated with estrogen signaling in mammary carcinoma cells. We find that estrogen affected the expression of proteins involved in numerous processes that are related to tumorigenesis such as increased cellular division and invasion in an ER-dependent manner. Moreover, we identified negative regulation of apoptosis as a non-genomic process of estrogen. This study complements gene expression studies and highlights the need for both genomic and proteomic analyses in unraveling the complex mechanisms by which estrogen affects progression of breast cancer. 展开更多
关键词 17-Β-ESTRADIOL breast Cancer estrogen receptor Mass Spectrometry SILAC
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Correlation of Hormonal Receptors Estrogen Receptor, Progesterone Receptor and Her-2/Neu with Tumor Characteristics in Breast Carcinoma: Study of 100 Consecutive Cases
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作者 Priyadarshini Biswal Susmita Behera +4 位作者 Asaranti Kar Dilleswari Pradhan Pradeep Kumar Behera Subrat Burma Chandraprava Mishra 《International Journal of Clinical Medicine》 2015年第12期961-966,共6页
Introduction-Breast cancer is the most common cancer and leading cause of death in women. In India, its incidence is rapidly rising over last few decades. Present study is aimed to study the pattern of expression of h... Introduction-Breast cancer is the most common cancer and leading cause of death in women. In India, its incidence is rapidly rising over last few decades. Present study is aimed to study the pattern of expression of hormonal receptors and Her-2/neu in invasive breast carcinoma and to correlate estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu expressions with various clinicopathological parameters. Material and methods: The present study was carried out in Department of Pathology, S.C.B. Medical College, Cuttack in the year 2013 taking consecutive 100 cases. Routine H&E staining for histological diagnosis and IHC analysis for ER, PR and Her 2/neu was carried out in all 100 cases of breast malignancies. Results: 99% of cases are invasive breast carcinoma, not otherwise specify (IDC-NOS). The age ranges from 23 years to 72 years. Majority of tumors are of grade 2 (70%) followed by grade 3 (30%). ER PR and Her-2/neu expression are seen in 45%, 35% and 30% respectively. Triple negative cases comprise 35%. Higher number of grade 2 tumor shows ER, PR positivity as compared to grade 3 tumors. Her-2/neu expression does not show any significant correlation with age or lymph node status of the patient. Conclusion: ER and PR expression in breast cancers in the current study are found to be comparable to the findings of other authors, but the frequency of HER-2/neu expression is slightly higher. Significant correlation is observed between hormonal receptor status and the grade of the tumor. Inverse relationship is found between Her-2/neu expression and ER, PR receptor status. Her-2/neu expression is increased with size and high grade of tumor. 展开更多
关键词 breast Carcinoma estrogen receptor (ER) PROGESTERONE receptor (PR) HER-2/NEU IMMUNOHISTOCHEMISTRY
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ESTROGEN RECEPTOR-NEGATIVE BREAST CANCER CELLS TRANSFECTED WITH ESTROGEN RECEPTOR EXHIBIT DECREASED TUMOUR PROGRESSION AND SENSITIVITY TO GROWTH INHIBITION BY ESTROGEN 被引量:4
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作者 邵志敏 江明 +2 位作者 余黎明 韩企夏 沈镇宙 《Chinese Medical Sciences Journal》 CAS CSCD 1997年第1期11-14,共4页
Breast cancer containing estrogen receptors (ER ) are responslve to antiestrogen treatment and have a better prognosis compared with ER-negative tumors. The loss of estrogen receptors appears to be associated with a p... Breast cancer containing estrogen receptors (ER ) are responslve to antiestrogen treatment and have a better prognosis compared with ER-negative tumors. The loss of estrogen receptors appears to be associated with a progression to less clifferentiated cells. We transfected the human ER into the ER-negative breast cancer cell line MDA MD 231 cells. We found that expresslon of adequate ER is strong associated with the ability of human breast cancer cell growth inhibition and progression. Compared with nontransfected or mock-trans fected cells, ER-transfected cells exhibited growth slower, forming smaller colonles in soft agar and growth inhibited by estrogen and tamoxifen. Therefore reactivation or transfection of the estrogen receptor gene can be considered as therapeutic approaches to hormone-independent breast cancer. 展开更多
关键词 estrogen receptor breast cancer stable transfection
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PRODUCTION AND APPLICATION OF MOUSE ANTISERUM TO HUMAN ESTROGEN RECEPTORS
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作者 张蕾 孙素莲 何洛文 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1995年第2期86-90,共5页
A polyclonal antibody to peptide containign 15 amino acids and corresponding to reion-D of human estrogen receptors(hERD)was obtained in mice by immunization with the coupler of peptide and KLH. Usuig this antiserum,t... A polyclonal antibody to peptide containign 15 amino acids and corresponding to reion-D of human estrogen receptors(hERD)was obtained in mice by immunization with the coupler of peptide and KLH. Usuig this antiserum,the ER stathe of paraffin-embeded sections of 95 human breast carcinomas were studied. The corresponding rate for determination of ER status between immunohistochemical staining(IHC)and dextran coated charcoal(DCC)assay was 89. 5%. The concordance for semiquantitative grades was 69.3%. In addition, in situ hybridization(ISH)of 15 frozen sections of same sample using digoxigenin labeled dUTP to identify the expreesion of ER mRNA for confirming the 1HC also be used. This technique revealed more specific,sensitive and convenient than DCC.The results of ISH were fully consistent with IHC(100%). Above results show that the mouse antsierum hERD obtained in this study is specific and sensitive for IHC assay of ER and IHC is a valuable adjunct and/or alternative to the biochemical method for determination of the ER status of breast cancer. 展开更多
关键词 breast cancer estrogen receptor Immunohistochemistry In situ hybridization.
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Dialogue between estrogen receptor and E2F signaling pathways: The transcriptional coregulator RIP140 at the crossroads
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作者 Marion Lapierre Aurélie Docquier +4 位作者 Audrey Castet-Nicolas Stéphan Jalaguier Catherine Teyssier Patrick Augereau Vincent Cavaillès 《Advances in Bioscience and Biotechnology》 2013年第10期45-54,共10页
Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between t... Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between these two pathways have been deciphered and deregulation of the E2F pathway has been shown to impact the response of breast cancer cells to endocrine therapies. The present review focuses on the transcriptional coregulator RIP140/NRIP1 which is involved in several regulatory feed-back loops and inhibitory cross-talks between different nuclear signaling pathways. RIP140 regulates the transactivation potential of estrogen receptors and E2Fs and is also a direct transcriptional target of these transcription factors. Published data highlight the complex regulation of RIP140 expression at the transcriptional level and its potential role in transcription cross-talks. Indeed, a subtle regulation of RIP140 expression levels has important consequences on other transcription networks targeted by this coregulator. Another level of regulation implies titration mechanisms by which activation of a pathway leads to sequestration of the RIP140 protein and thus impinges other gene regulatory circuitries. Altogether, RIP140 occupies a place of choice in the dialogue between nuclear receptors and E2Fs, which could be highly relevant in various human pathologies such as cancer or metabolic diseases. 展开更多
关键词 RIP140 E2F Transcription Factors estrogen receptors Gene Expression Cell Proliferation breast Cancer ENDOCRINE THERAPIES
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Effect of Artemisia species on cellular proliferation and apoptosis in human breast cancer cells via estrogen receptor-related pathway 被引量:5
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作者 Eunjeong Choi Gunhee Kim 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2013年第5期658-663,共6页
OBJECTIVE:To investigate the mechanism underlying the anticancer effect of Artemisia species through the inhibition of cell growth and induction of apoptosis in breast carcinoma cells.METHODS:To evaluate the anticance... OBJECTIVE:To investigate the mechanism underlying the anticancer effect of Artemisia species through the inhibition of cell growth and induction of apoptosis in breast carcinoma cells.METHODS:To evaluate the anticancer activity of methanol extracts of eight Artemisia species(Artemisia stolonifera,Artemisia selengensis,Artemisia japonica,Artemisia Montana,Artemisia capillaris,Artemisia sylvatica,Artemisia keiskeana,and Artemisia scoparia),we first investigated the proliferation of estrogen receptor(ER)-positive MCF-7breast carcinoma cells exposed to 5 or 200 g/mL for72 h.Apoptosis induction was assessed by an Annexin V binding assay in cells exposed to extracts at a high concentration(200 g/mL).To verify the mechanism of apoptosis,ER expression and its related signaling was investigated using an immunoblot assay under the same conditions.RESULTS:MCF-7 cells showed the strongest antiproliferative response to the tested extracts.Howev-er,a biphasic effect was observed:the extracts inhibited proliferation at high concentrations whereas they stimulated it at low ones.ER expression was similarly modulated by the extracts.However,all of the extracts induced apoptosis at a high concentration(200 g/mL).Compared to the control level,exposure to the extracts resulted in a remarkable increase in the shift of cell populations.CONCLUSION:The present study suggests that the tested Artemisia species exerted their anticancer effects through the induction of apoptosis via an ER-related pathway. 展开更多
关键词 Artemisia breast neoplasms Bcl-2gene Cyclin D1 estrogen receptor
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Effect of neoadjuvant chemotherapy on expressions of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67 in breast cancer 被引量:13
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作者 Qin Qinghong Gao Fangfang +3 位作者 Jiang Wei Tan Qixing Mo Qinguo Wei Changyuan 《Chinese Medical Journal》 SCIE CAS CSCD 2014年第18期3272-3277,共6页
Background This study was designed in an attempt to determine the influence of neoadjuvant chemotherapy on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2), an... Background This study was designed in an attempt to determine the influence of neoadjuvant chemotherapy on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2), and Ki-67 expressions in patients with breast cancer. Methods Pre- and post-neoadjuvant chemotherapy, paired-tumor specimens from 103 patients with breast cancer administrated with anthracycline or anthracycline combined taxane regimen were collected. Immunohistochemical staining for ER, PR, Her-2, and Ki-67 was performed by the DAKO EnVision method. Results Among the 103 cases, five patients (4.9%) had a complete response (CR), 82 (79.6%) partial response (PR), 15 (14.6%) stable disease (SD), and one (0.9%) progressive disease (PD), yielding an overall response rate (CR + PR) of 84.5%. Nine patients achieved pathological CR. There was a significant decrease in the average index of Ki-67 post- neoadjuvant chemotherapy, compared with that before chemotherapy (24.1% vs. 39.7%, P 〈0.001). After neoadjuvant chemotherapy, the changes of Ki-67 in different subtypes of breast cancer were different (P 〈0.001), and these changes correlated with response to neoadjuvant chemotherapy (P 〈0.001). No significant changes in immunohistochemical expression were observed for ER, PR and Her-2. Conclusions Neoadjuvant chemotherapy apparently reduced Ki-67 index in primary breast carcinomas, but profiles for ER, PR and Her-2 were not significantly different before and after neoadjuvant chemotherapy. The change of Ki- 67 correlated with molecular subtypes and response to neoadjuvant chemotherapy, suggesting that Ki-67 index was a surrogate marker to predict the treatment response of neoadjuvant chemotherapy. 展开更多
关键词 breast cancer neoadjuvant chemotherapy growth factor receptor 2 Ki-67 estrogen receptor progesterone receptor human epidermal
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Stable transfection of estrogen receptor-alpha suppresses expression of cyclooxygenase-2 and vascular endothelial growth factor-C in MDA-MB-231 breast cancer cells 被引量:4
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作者 ZHANG Hui LIN Ying XIAO Ying WANG San-ming LIU Xiang-xia WANG Shen-ming 《Chinese Medical Journal》 SCIE CAS CSCD 2010年第15期1989-1994,共6页
Background Estrogen receptor (ER)-negative breast cancer cells are more aggressive than ER-positive cells. Elevated levels of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor-C (VEGF-C) expression... Background Estrogen receptor (ER)-negative breast cancer cells are more aggressive than ER-positive cells. Elevated levels of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor-C (VEGF-C) expression have been detected in cultured human breast cancer cells and are associated with negative hormone receptor status. In this study, we created ERα stable transfectants in MDA-MB-231 cells to explore the effect of ERα on cell growth and COX-2 and VEGF-C expression.Methods The green fluorescent protein (GFP)-ERα plasmids were stably transfected into ER-negative MDA-MB-231 cells. The proliferation and migration of untransfected MDA-MB-231 cells, ERα-transfected MDA-MB-231 cells and ER-positive MCF-7 cells were determined. The expression of COX-2, and the levels of VEGF-C mRNA and the VEGF-C secretion concentration were assayed in these cell lines.Results The proliferation and migration capacities of ERα-tranfected MDA-MB-231 cells were significantly decreased (P 〈0.05). The expression of COX-2 was significantly lower in ERa-tranfected MDA-MB-231 cells than in untranfected MDA-MB-231 cells. The mRNA and protein levels of VEGF-C were lower in ERa-tranfected MDA-MB-231 cells than in untransfected MDA-MB-231 cells (P〈0.05).Conclusions ERα stable transfection inhibits proliferation and migration capacities of MDA-MB-231 cells and decreases expression of COX-2 and VEGF-C. The decreases of proliferation and migration capacities may be related to suppression of COX-2 and VEGF-C expression. 展开更多
关键词 breast neoplasms estrogen receptor-alpha CYCLOOXYGENASE-2 vascular endothelial growth factor-C
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Role of interleukin-8 in the progression of estrogen receptor-negative breast cancer 被引量:8
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作者 YAO Chen LIN Ying YE Cai-sheng BI Jiong ZHU Yi-fan WANG Shen-ming 《Chinese Medical Journal》 SCIE CAS CSCD 2007年第20期1766-1772,共7页
Background Estrogen receptor (ER) is a very important biomarker of breast cancer. ER deletion has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis, but the biological me... Background Estrogen receptor (ER) is a very important biomarker of breast cancer. ER deletion has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis, but the biological mechanism is still unclear. ER negative breast cancer expresses high levels of interleukin-8 (IL-8). ER expression can downregulate IL-8 promotor activity. As a multifunctional cytokine, IL-8 has many important biological activities in tumor genesis and development. With the goal of investigating the role of IL-8 in ER-negative breast cancer progression, we applied RNA interference technology to specifically knockdown the IL-8 expression in ER-negative breast cancer cell line MDA-MB-231.Methods Interfering pRNA-IL-8 and the control was transfected into ER(-) MDA-MB-231. The proliferation, cell apotosis, and invasive ability were recorded in transfected, untransfected and negative transfected cells. These cells were injected into nude mice to assess tumorigenicity, proliferation, metastasis and microvessel density (MVD).Results In vitro, decreased expression of IL-8 was associated with reduced cell invasion (P〈0.001), but had no effect on cell proliferation (P〉0.05). In vivo, neutrophils infiltration was significantly inhibited in pRNA-IL-8 transfected cells compared with untransfected and negatively transfected cells (P=0.001, P〈0.001). Less metastasis was found in transfected cells compared with negatively transfected cells (0% vs 80%, P=0.048). Nevertheless, we observed less MVD in transfected cells compared with control in nude mice (P〈0.001).Conclusions IL-8 inhibits ER-negative breast cancer cell growth and promotes its metastasis in vivo, which may be correlated with neutrophils infiltration induced by IL-8. 展开更多
关键词 breast cancer INTERLEUKIN-8 estrogen receptor RNA interference
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Estrogen receptor alpha gene amplification in breast cancer:25 years of debate 被引量:2
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作者 Frederik Holst 《World Journal of Clinical Oncology》 CAS 2016年第2期160-173,共14页
Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical sign... Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration,which affects one of the most important genes in breast cancer.Since then,a multitude of studies on this topic has been published,covering a wide range of divergent results and arguments.The reported prevalence of this alteration in breast cancer ranges from 0% to 75%,suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues.To date,two major issues related to ESR1 amplification remain to be conclusively addressed:(1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1,and(2) the clinical relevance of ESR1 amplification:Such relevance is strongly disputed,with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies,or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1.This review provides a comprehensive summary of the various views on ESR1 amplification,and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research. 展开更多
关键词 estrogen receptor alpha GENE breast cancer TAMOXIFEN GENE AMPLIFICATION Methodology
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Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer:A Single-Institution Study
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作者 KONG Zi Qing LIU Li Qun +11 位作者 HUANG De Qin WANG Yu Tong LI Jing Jie ZHANG Zheng WANG Xi Xi LIU Chuan Ling ZHANG Ya Di SHAO Jia Kang ZHU Yi Min CHEN Yi Meng LIU Mei ZHAO Wei Hong 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2024年第5期457-470,共14页
Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and H... Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC.Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups.Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszelχ^(2)test,P<0.001,Pearson’s R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%.Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles. 展开更多
关键词 HER2 HER2-low breast cancer estrogen receptor Trastuzumab deruxtecan
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Discovery of novel covalent selective estrogen receptor degraders against endocrine-resistant breast cancer 被引量:2
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作者 Yubo Wang Jian Min +10 位作者 Xiangping Deng Tian Feng Hebing Hu Xinyi Guo Yan Cheng Baohua Xie Yu Yang Chun-Chi Chen Rey-Ting Guo Chune Dong Hai-Bing Zhou 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2023年第12期4963-4982,共20页
Endocrine-resistance remains a major challenge in estrogen receptorαpositive(ERα^(+))breast cancer(BC)treatment and constitutively active somatic mutations in ERαare a common mechanism.There is an urgent need to de... Endocrine-resistance remains a major challenge in estrogen receptorαpositive(ERα^(+))breast cancer(BC)treatment and constitutively active somatic mutations in ERαare a common mechanism.There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrineresistance.Given aberrant ERαactivity,we herein report the identification of novel covalent selective estrogen receptor degraders(cSERDs)possessing the advantages of both covalent and degradation strategies.A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERa+breast cancer cell lines including mutant ERα.Crystal structure of ERα-29c complex alongside intact mass spectrometry revealed that 29c disrupted ERa protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11,thus enforcing a unique antagonist conformation and driving the ERαdegradation.These significant effects of the cSERD on ERαhomeostasis,unlike typical ERαdegraders that occur directly via long side chains perturbing the morphology of H12,demonstrating a distinct mechanism of action(MoA).In vivo,29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity.This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC. 展开更多
关键词 Covalent strategy estrogen receptor degraders Endocrine-resistant breast cancer X-ray crystallography
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Shugan Liangxue Decoction(舒肝凉血方)Down-Regulates Estrogen ReceptorαExpression in Breast Cancer Cells 被引量:1
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作者 ZHOU Ning HAN Shu-yan +3 位作者 CHEN Yan-zhi ZHOU Fei ZHENG Wen-xian LI Ping-ping 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2018年第7期518-524,共7页
Objective: To observe the effect of Shugan Liangxue Decoction(舒肝凉血方, SGLXD) on estrogen receptor α(ERα) in human breast cancer cells. Methods: The effect of SGLXD(0.85–5.10 mg/m L) on the proliferation... Objective: To observe the effect of Shugan Liangxue Decoction(舒肝凉血方, SGLXD) on estrogen receptor α(ERα) in human breast cancer cells. Methods: The effect of SGLXD(0.85–5.10 mg/m L) on the proliferation of breast cancer cells were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT) assay. The nuclear ERα protein levels in MCF-7, T47 D and ZR-75-1 cells which treated by SGLXD for 24 h were examined by western blot and immunofluorescence assay. MCF-7 and MDA-MB-231 cells were treated by 17β-estradiol(E2) with or without SGLXD, for 24 h, and the E2 targeted genes c-myc and bcl-2 protein product was evaluated by western blot. Results: SGLXD showed dose-dependent inhibition on the proliferation of MCF-7, T47 D and ZR-75-1 cells, but did not inhibit the proliferation of MDA-MB-231 cells. Furthermore, the promotive effect on cell growth induced by E2 was also significantly inhibited by SGLXD treatment. With the treatment of 1.70, 3.40, 5.10 mg/m L SGLXD, the nuclear ERα protein level was reduced to 88.1%, 70.4% and 60.9% in MCF-7 cells, and was decreased to 43.0%, 38.4% and 5.9% in ZR-75-1 cells as compared with the control group. In T47 D cells, the nuclear ERα protein was down-regulated to 51.3% and 4.3% by 3.40 and 5.10 mg/m L SGLXD treatment. The down-regulative effect of SGLXD on nuclear ERα was confirmed by immunofluorescence assay. SGLXD decreased the protein product of c-myc and bcl-2. Conclusions: SGLXD may exhibit selective inhibition effect on the proliferation of ER positive breast cancer cells. SGLXD reduced the nuclear ERα expression and the protein product of E2 target gene c-myc and bcl-2. 展开更多
关键词 breast cancer estrogen receptor Shugan Liangxue Decoction estrogen receptor inhibitor
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PI3K/mTOR mediate mitogen-dependent HDAC1 phosphorylation in breast cancer:a novel regulation of estrogen receptor expression 被引量:1
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作者 Simona Citro Claudia Miccolo +1 位作者 Laura Meloni Susanna Chiocca 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2015年第2期132-142,共11页
Histone deacetylase 1(HDAC1)is an important epigenetic controller involvedin transcriptional regulation throughmodification of chromatin structure.Genetic and epigenetic changes and deregulation of signal transduction... Histone deacetylase 1(HDAC1)is an important epigenetic controller involvedin transcriptional regulation throughmodification of chromatin structure.Genetic and epigenetic changes and deregulation of signal transduction pathways have been implicated in the development of breast cancer.Downregulation of estrogen receptor a(ERa)expression is one of the mechanisms behind the acquisition of endocrine resistance.Sustained and increased hormone and growth factor receptor signaling in breast cancer cells contribute to resistance to endocrine therapy.Both HDACs and the PI3K/mTOR signaling pathway are becoming promising targets in breast cancer,reversing also acquired hormone resistance.Here we show how mitogens,activating the PI3K/mTOR pathway,trigger the phosphorylation of HDAC1 in breast cancer cells,which is completely dependent on the activity of the p70 S6 kinase(S6K1).Our findings show that S6K1,overexpressed in many breast cancers,controls HDAC1-dependent transcriptional regulation of ERa levels upon mitogenic stimuli,controlling HDAC1 recruitment to the ERa promoter.Furthermore,cell treatment with both mTOR and HDACs inhibitors shows an additive effect in inhibiting breast cancer proliferation.This confirms the novel cross-talk between the HDAC1 and PI3K pathways with clinical implications towards the treatment of this malignant disease. 展开更多
关键词 breast cancer estrogen receptor HDAC1/mTOR/PI3K/S6K1
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