Estrogen receptor(ER) is a vital biomarker in the development and development of breast cancer, and its status has great clinical value in clinical treatment strategy, endocrine therapy efficacy prediction, and breast...Estrogen receptor(ER) is a vital biomarker in the development and development of breast cancer, and its status has great clinical value in clinical treatment strategy, endocrine therapy efficacy prediction, and breast cancer prognosis. By specifically combining <sup>18</sup>F-FES with ER, <sup>18</sup>F-FES PET/CT imaging uses standard uptake value(SUV) to semi-quantitatively reflect the distribution of ER and its biological activity in patients, and assesses the expression of ER in breast cancer patients about primary and metastases before or after treatment, to provide a basis for personalized treatment of breast cancer. In this review, we will review the imaging principles of a new ER detection method <sup>18</sup>F-FES PET/CT, and the research progress in the clinical application of breast cancer, and compare its diagnostic and treatment value with non-specific tumor imaging <sup>18</sup>F-FDG PET/CT in breast cancer.展开更多
OBJECTIVE To investigate the expression of the nuclear transcription factor NF-κB, ER, HER2 and PCNA in breast cancers, and to study the relationship between activation of NF-κB and clinicopathologic parameters incl...OBJECTIVE To investigate the expression of the nuclear transcription factor NF-κB, ER, HER2 and PCNA in breast cancers, and to study the relationship between activation of NF-κB and clinicopathologic parameters including the level of PCNA, ER, HER2, lymph node involvement, tumor size and histological grade (differentiation). METHODS Sixty cases of human breast cancer tissues and adjacent non-neoplastic breast tissues were examined for NF-κB, HER2 and ER, as well as PCNA by immunohistochemical methodS. In addition the clinicopathologic parameters of the patients including lymph node involvement, tumor size and histological grade (differentiation) were collected. RESULTS The expression of NF-κB in the breast cancers and adjacent non-neoplastic breast tissue was 50.0% (30/60) and 40.0% (24/60) respectively, resulting in no significant difference (P〉0.05). NF-κB and HER2 expression was positively correlated whereas NF-κB and ER expression was negatively correlated. The NF-κB activation was 77.8% (14/18) in the breast cancers that were ER-/HER2^+, a level significantly higher (P〈0.001) in comparison to the other groups of patients. The expression of NF-κB in the low-differentiated group (grade Ⅲ) was 57.1%, and in the moderate-differentiated group (grade Ⅱ) was 50.3%, both of which were higher than the 35.7% found in the high-differentiated group (grade Ⅰ). NF-κB activation in the cancers was significantly correlated with the histological grade (P〈0.05), PCNA expression (P=0.003) and lymph node involvement and tumor size (P=0.03 and 0.002, respectively). CONCLUSION NF-κB was activated abnormally in a portion of the breast cancers. The finding that NF-κB activation was positively correlated with HER2 expression, the level of PCNA, tumor grade, size and lymph node involvement is in accord with the ability of NF-κB to promote cellular proliferation and migration, clearly identifies the protein as a hallmark for targeted dysregulation in oncogenesis. NF-κB may be a hopeful target for breast cancer therapy.展开更多
Objective:To determine the influence of the single nucleotide polymorphism(SNP)rs4245739 on the binding and expression of micro RNAs and subsequent MDM4 expression and the correlation of these factors with clinical de...Objective:To determine the influence of the single nucleotide polymorphism(SNP)rs4245739 on the binding and expression of micro RNAs and subsequent MDM4 expression and the correlation of these factors with clinical determinants of ER-negative breast cancers.Methods:Find Tar and miRanda were used to detect the manner in which potential micro RNAs are affected by the SNP rs4245739-flanking sequence.RNA sequencing data for ER-negative breast cancer from The Cancer Genome Atlas(TCGA)were used to compare the expression of miR-184,miR-191,miR-193a,miR-378,and MDM4 in different rs4245739 genotypes.Results:Comparison of ER-negative cancer patients with and without the expression of miR-191 as well as profile micro RNAs(miR-184,miR-191,miR-193a and miR-378 altogether)can differentiate the expression of MDM4 among different rs4245739 genotypes.Although simple genotyping alone did not reveal significant clinical relationships,the combination of genotyping and micro RNA profiles was able to significantly differentiate individuals with larger tumor size and lower number of involved lymph nodes(P<0.05)in the risk group(A allele).Conclusions:We present two novel methods to analyze SNPs within 3′UTRs that use:(i)a single miRNA marker expression and(ii)an expression profile of miRNAs predicted to bind to the SNP region.We demonstrate that the application of these two methods,in particular the miRNA profile approach,permits detection of new molecular and clinical features related to the rs4245739 variant in ER-negative breast cancer.展开更多
Objective: To study the relationship between theexpression of PS, protein and Estrogen (ER) andProgesterone Receptor (PR) status and their prognoticvalue in breast canceL Methods: Using theimmunohistochemical method, ...Objective: To study the relationship between theexpression of PS, protein and Estrogen (ER) andProgesterone Receptor (PR) status and their prognoticvalue in breast canceL Methods: Using theimmunohistochemical method, PS2 protein expressionswere detected in 105 cases with breast cancer. Results:The positive rate of PS2 protein was 50.48% (53/105) in105 cases. The positive rate of PS, in the patients whosurvived five years or more was 56.96% (45/79), whichwas higher than that of those who lived less than fiveyears (30.77%, 8/26). In the ER, PR (+) patients, thepositive rate of PS, was higher (76.74%, 33/34), thanthat of those with ER, PR (-) (22.5%, 9/40). Conclusions:Our results suggest that the expression of PS, proteinwas positively correlated with the 5-year-survival andthat of ER and PR in breast cancer. It is considered thatPS, may be as a prognostic predictor, and detection ofPS, protein expression was useful for a guidingtreatment of breast cancer.展开更多
Objective To analyze the relationship of the expression level of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor-2(HER-2,c-erbB-2)of breast invasive ductal carcinoma(IDC)with ...Objective To analyze the relationship of the expression level of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor-2(HER-2,c-erbB-2)of breast invasive ductal carcinoma(IDC)with ultrasonographic characteristics.Methods Totally 104 patients with IDCs confirmed pathologically were involved in this study.ER,PR and c-erbB-2 expression in the IDC specimens was determined by immunohistochemical staining technique.The correlation between the ultrasonographic features and the positive expression of ER,PR or c-erbB-2 was analyzed.Results The positive expression rate of ER and PR in the group with tumor spiculation sign and posterior acoustic attenuation was higher than that in the group without.The positive expression rate of ER differed significantly(P<0.05)while that of PR did not(P>0.05).The over-expression rate of c-erbB-2 in the group of microcalcification,sufficient blood flow and axillary lymph node metastasis was higher than that in the group of non-microcalcification,deficient blood flow or without axillary lymph node metastasis(P<0.05).The expression of ER,PR and c-erbB-2 was not related to the size of tumor(P>0.05).Conclusion The expression of ER and c-erbB-2 is closely related to the ultrasonographic characteristics of IDC,which may,to some extent,reflect the expression level of ER and c-erbB-2.展开更多
Objective: To investigate the correlations of expression of Bax inhibitor-1 (BI-1) gene and the receptors of estrogen and progestogen in breast cancer and its significance. Methods: Immunohistochemical methods had...Objective: To investigate the correlations of expression of Bax inhibitor-1 (BI-1) gene and the receptors of estrogen and progestogen in breast cancer and its significance. Methods: Immunohistochemical methods had been used to detect the expressions of BI-1 gene and receptors of estrogen and progestogen in breast cancer. Results: The positive rates of expressions of BI-1 gene, estrogen receptor (ER) and progestogen receptor (PR) in breast cancer were 77.08%, 60.42% and 54.17%, respectively. The positive rate of expression of BI-1 gene was higher in the group with negative expression of ER than the positive group, their positive rates were 76.92% and 52.27%, respectively; but there was no statistical difference between the two groups with positive and negative expressions of PR. The positive rate of expression of BI-1 gene was also higher in the group with positive lymph node metastasis than the non-lymph node metastasis group, and their positive rates were 64.58% and 36.36%, respectively. The difference was statistically significant (P 〈 0.05). Conclusion: BI-1 gene, in combination with ER, has guiding significance for patients with breast cancer to choose individual chemotherapy and radiotherapy after operation and can become an important indicator for judging the prognosis of breast cancer.展开更多
Objective: The purpose of the study was to investigate the relationship between the expression of estrogen receptor(ER), progestogen receptor(PR), human epidermal growth factor receptor(Her-2), Ki-67 and the effect of...Objective: The purpose of the study was to investigate the relationship between the expression of estrogen receptor(ER), progestogen receptor(PR), human epidermal growth factor receptor(Her-2), Ki-67 and the effect of neoadjuvant chemotherapy in breast cancer. Methods: The expression of ER, PR, Her-2 and Ki-67 in 45 breast cancers which received neoadjuvant chemotherapy was detected by immunohistochemistry. Results: The effective rates in ER negative and PR negative groups were higher than those in ER positive and PR positive groups(83.3% vs 59. 4%, 82.4% vs 60.6%). There was no significant difference of the effective rate between Her-2 overexpressed group and Her-2 non-overexpressed group(81.8% vs 64.1%), and the same thing happened between Ki-67 negative group and Ki-67 positive group(67.7% vs 63.2%). Conclusion: In the patients with breast cancer, ER, PR negative ones were more sensitive to neoadjuvant chemotherapy. These patients may get more benefits from chemotherapy. ER, PR could be feasible markers for predicting the effective rate of neoadjuvant chemotherapy.展开更多
Objective: We studied the alterations in the expression of estrogen receptor alpha (ER) in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinomas (IDC). Methods: The mastectomy specimens of...Objective: We studied the alterations in the expression of estrogen receptor alpha (ER) in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinomas (IDC). Methods: The mastectomy specimens of 120 cases containing both DCIS and IDC were examined. The expression of ER proteins were examined by immunohistochemistry. The difference of the expression of ER proteins between DCIS and IDC were compared. Results: There were 58.33% of the cases with DCIS expressing ER proteins, and 40.00% of the cases IDC expressing ER proteins. There was a significant decrease of ER expression in IDC compared to DCIS (χ2 = 4.034, P = 0.045). Conclusion: These findings substantiate the notion that breast cancer progression is often associated with alterations in expressions of ER. The underlying mechanisms of these alterations need further investigation.展开更多
Aim Breast cancer is one of the lethal gynecological malignancy in the world. Tamoxifen (TAM) and fulvestrant (FUL) are the major drugs for patients with estrogen receptor-positive (ER + ) breast cancers. Howev...Aim Breast cancer is one of the lethal gynecological malignancy in the world. Tamoxifen (TAM) and fulvestrant (FUL) are the major drugs for patients with estrogen receptor-positive (ER + ) breast cancers. Howev- er, the development of endocrine resistance is the impediment for successful treatment. In this study, we explored the mechanisms of endocrine resistance and therapeutic strategy for overcoming resistance against TAM and FUL. Methods The experiments were performed in Ell + and estrogen/TAM-sensitive MCF7 cells and antiestrogen-re- sistant MCF7/LCC9 cells. Western blot and confocal microscopy were used to determine cell autophagy. Cell trans- fection and luciferase activity assay were performed to identify the target gene of miR-214. Results It showed that 4-OHT/FUL treatment induced apoptosis as well as autophagy in breast cancer cells. The increase of autophagy might be the major cause of endocrine resistance to 4-OHT or FUL. Mill-214 increased the sensitivity of breast cancer cells to the 4-OHT/FUL-induced apoptosis through inhibition of autophagy. Importantly, a negative correla- tion was established between miR-214 and UCP2 in human breast cancer tissue specimens by RT-qPCR assay. UCP2 was identified to be a direct target of mill-214. Further study in MCF7/LCC9 cells indicated that endocrine resistance might arise from activation of the PI3 K-Akt-mTOll pathway, thereby inducing autophagy by overexpres- sion of UCP2. Conclusions MiR-214 increased the sensitivity of breast cancer cells to TAM and FUL through in- hibition of autophagy by targeting UCP2. Mill-214 shows potential as a novel therapeutic strategy for overcoming endocrine resistance in ER + breast cancers.展开更多
Objective: To investigate whether dietary daidzein interact with endogenous 17β-Estradiol (E2) to give rise to additive or inhibitory effects on proliferation and apoptosis in breast cancer cells. Methods: Cell ...Objective: To investigate whether dietary daidzein interact with endogenous 17β-Estradiol (E2) to give rise to additive or inhibitory effects on proliferation and apoptosis in breast cancer cells. Methods: Cell cycle distribution and apoptosis induction were analyzed by using flow cytometry when breast cancer cell lines MCF-7 were cotreated with daidzein (1, 5 μmol/L) and E2 (0.1-10 nmol/L) for 5 days. Whether daidzein could alter E2-modulated mRNA expression of estrogen receptor alpha (ERα), estrogen receptor beta (ERI3) and ERβ-estrogen response element (ERE) dependent transcription was investigated by RT-PCR and luciferase induction assays. The effects of daidzein on E2-modulated expression of proapoptotic p53, bax and antiapoptotic bcl-2 at both mRNA and protein levels were also investigated by RT-PCR and Western blot. Results: Daidzein enhanced the antiapoptotic effect in an Ea dose-dependent manner, but had no effect on E2-induced proliferation. Daidzein antagonized E2-induced ERβ mRNA expression and ERβ-ERE dependent transcription. In addition, daidzein only antagonized E2-upregulated expression of p53 and bax, but had no effect on E2-upregulated expression of bcl-2. Conclusion: Daidzein enhances the antiapoptotic effect of E2 on breast cancer cells by inhibiting E2-mediated p53-bax proapoptotic pathway. These results suggest that dietary daidzein may enhance deleterious effect of endogenous E2 in hormone-dependent breast cancer.展开更多
Objective: hER-α36 is a variant of estrogen receptor-a, identified and cloned by a team of American. This research is to determine whether hER-α36 can enhance or weaken chemosensitivity to docetaxel in breast cance...Objective: hER-α36 is a variant of estrogen receptor-a, identified and cloned by a team of American. This research is to determine whether hER-α36 can enhance or weaken chemosensitivity to docetaxel in breast cancer cell line MCF-7(ERα66 positive). Methods: RT-PCR was used to detect the expressions of ERα66 and ERa36 in the two human breast cancer cell lines MCF-7(MCF-7/ERα66) and MCF-7 transfected with ERa36(MCF-7/ERα36). The two cell lines were treated with docetaxel(0-100umol/L), and cell growth and apoptosis were evaluated using MTT (3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide) assay (using adriamycin (0-50umol/L) as the control) and flowcytometry. Western blot analysis was used to measure the effect of docetaxel on phosphor-ERKl/2 expression in the two cell lines. Results: The expressions of ERct36 and ERα66 were detectable in both MCF-7/ERα66 and MCF-7/ERα36 cell lines, while the expression of ERα36 in MCF-7/ER36 cells was higher. Both docetaxel and adriamycin inhibited the proliferation of both cells lines in a dose and time dependent manner. In comparison with MCF-7/ERα36 cell line, the MCF-7/ERα66 cells produced greater growth inhibition and apoptosis after treatment with docetaxel, but there was no significant difference in growth inhibition between the two cell lines treated with adriamycin; The MCF-7/ERα36 cell line resulted in a significant activation (phosphorylation) of ERK1/2 after treatment with docetaxel in a dose-dependent manner, but in the MCF-7/ERα66 cell line , a decrease in the level of phosphor- ERK1/2 expression was observed as the dose of docetaxel increased. Conclusion: ERa36 may be an agent that weakens chemosensitivity to docetaxel in breast cancer, probably by activating the expression of ERKI/2.展开更多
Estrogen receptor alpha(ERα/ESR1)is overexpressed in over half of all breast cancers and is considered a valuable therapeutic target in ERαpositive breast cancer.Here,we designed a membrane-permeant Chaperonemediate...Estrogen receptor alpha(ERα/ESR1)is overexpressed in over half of all breast cancers and is considered a valuable therapeutic target in ERαpositive breast cancer.Here,we designed a membrane-permeant Chaperonemediated Autophagy Targeting Chimeras(CMATAC)peptide to knockdown endogenous ERαprotein through chaperone-mediated autophagy.The peptide contains a cell membrane-penetrating peptide(TAT)that allows the peptide to by-pass the plasma membrane,anαI peptide as a protein-binding peptide(PBD)that binds specifically to ERα,and CMA-targeting peptide(CTM)that targeting chaperone-mediated autophagy.We validated that ERαtargeting peptide was able to target and degrade ERαto reduce the viability of ERαpositive breast cancer cells.Taken together,our studies provided a new method to reduce the level of intracellular ERαprotein via CMATAC,and thus may provide a new strategy for the treatment of ERαpositive breast cancer.展开更多
Background: Several molecular markers have been detected that are important in clinical aspect of malignancies especially in breast cancer. More recently, the expression of vascular endothelial growth factor (VEGF), t...Background: Several molecular markers have been detected that are important in clinical aspect of malignancies especially in breast cancer. More recently, the expression of vascular endothelial growth factor (VEGF), the most potent endothelial cell mitogen and also a regulator of vascular permeability, is emerging as a prognostic marker in patients with several types of cancer including breast cancer. This study assessed the expression of VEGF in a series of breast cancers in correlation with HER-2/neu and steroid receptors (ER and PR) in standard clinicopathological parameters in an attempt to clarify its potential clinical importance in Iraqi females of Middle Euphrates area. Findings: The present investigation was performed over a period starting from September 2011 through September 2012. Formalin-fixed, paraffin-embedded blocks from 52 patients with breast cancer (44 ductal and 8 lobular carcinoma) were included in this study. A group of 20 patients with fibroadenoma was included as a comparative group, and 20 samples of normal breast tissue sections were used as controls. Labeled streptavidin-biotin (LSAB+) complex method was employed for immunohistochemical detection of VEGF, HER-2/neu, ER and PR. The detection rate of VEGF, HER-2/neu, ER and PR was 59.62%, 36.96%, 34.62% and 36.54% respectively. There was a significant difference in immunoexpression between ductal and lobular carcinoma, but not significantly different among tumor sizes, tumor grades, axillary lymph node involvement and age of the patients. However, VEGF was positively correlated with tumor grade, tumor size, nodal involvement and HER-2/neu, but negatively correlated with ER and PR, which show the most unfavorable biopathological profile. Conclusion: VEGF overexpression play an important role in pathogenesis of breast carcinoma evolution, as its positivity associated with biologically aggressive tumors, so incorporation of this biomarker with other parameters into a prognostic index will more accurately predict clinical outcome and determine the effects of anti cancer therapy.展开更多
Results of comparative study of Human Leu-cocytic Antigen (HLA-A), -B typing in 73 breast cancer (BC) patients having different estrogen receptor (ER) status and 50 healthy individuals in the northern part of China ar...Results of comparative study of Human Leu-cocytic Antigen (HLA-A), -B typing in 73 breast cancer (BC) patients having different estrogen receptor (ER) status and 50 healthy individuals in the northern part of China are reported. In 58 of the 73 patients, HLA-C, -DR typing were also studied in addition. The results of this study showed that HLA-Bw61 (40) were negatively associated with BC, while -Cw7 and -DRw6 were positively associated with BC. Moreover, -DR was more closely associated with ER(+) status with a RR value of 8.621. In the ER(-) group, there were no specific related antigens. In the light of the differences in pathology, prognosis and effect of endocrine therapy between ER(+) and ER(-) status, the authors are inclined to the view that the two kinds of breast cancer may be a heterogeneous disease.展开更多
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
Aim Recent evidence has revealed that Eukaryotic elongation factor-2 kinase (eEF2K) activity may confer cancer cell adaptation to metabolic stress, and high expression of eEF2K is found in several types of cancer. T...Aim Recent evidence has revealed that Eukaryotic elongation factor-2 kinase (eEF2K) activity may confer cancer cell adaptation to metabolic stress, and high expression of eEF2K is found in several types of cancer. Therefore, eEF2K may contribute to carcinogenesis and represent a promising therapeutic target; however, inhibi- tion of eEF2K for cancer drug discovery still remains in its infancy. This study aimed at developing a series of eEF2K inhibitor as candidate anti-tumor drugs in breast cancer and illustrating the possible mechanisms of its anti- tumor activity in vitro and in vivo. Methods In silico screening, structure modifications, MTT assay and molecular dynamics (MD) simulations were applied for the discovery of the novel eEF2K inhibitor (BL-EKI03). Observa- tions of cell morphology were executed through several methods including ER-traeker, MDC and Hoeehst 33258 staining and GFP-LC3 transfeetion. Flow eytometrie analyses of MDC and Annexin V/PI were used for quantifica- tion of autophagy and apoptosis ratio. Western blot and ITRAQ analysis were used to explore the detailed mecha- nisms of BL-EKI03-induced ER stress, autophagie death and apoptosis in breast cancer cells. Furthermore, an in vivo xenograft mouse model was established for validating the anti-tumor efficacy of BL-EKI03. Results Firstly, a novel eEF2K inhibitor (BL-EKI03) with a good affinity for eEF2K was eventually discovered after computational screening and synthesis of a series of candidate compounds targeting eEF2K. Subsequently, our results demonstra- ted that BL-EKI03 has remarkable anti-proliferative activities and induces endoplasmie retieulum (ER) stress, au- tophagy and apoptosis in MCF-7 and MDA-MB-436 cells. More importantly, the mechanism for BL-EKI03-indueed autophagie death involves eEF2K-mediated AMPK-mTOR-ULK complex pathways. The proteomies analyses and ex-perimental validation revealed that the BL-EKI03-induced mechanism was also involved BIRC6, BNIP1, SNAP29 and Bif-1, which might be regulated by eEF2K. Moreover, BL-EKI03 exerted its anti-tumor activities without re- markable toxicity, and it also induced autophagy and apoptosis by targeting eEF2K in fifo. Conclusion In this study, a novel eEF2K inhibitor (BL-EKI03) was discovered with remarkable anti-proliferative activities and in- duced endoplasmic reticulum (ER) stress, autophagy and apoptosis of breast cancer in vitro and in fifo. These findings highlight a new small-molecule eEF2K inhibitor (BL-EKI03) that has the potential to impact future breast cancer therapy.展开更多
文摘Estrogen receptor(ER) is a vital biomarker in the development and development of breast cancer, and its status has great clinical value in clinical treatment strategy, endocrine therapy efficacy prediction, and breast cancer prognosis. By specifically combining <sup>18</sup>F-FES with ER, <sup>18</sup>F-FES PET/CT imaging uses standard uptake value(SUV) to semi-quantitatively reflect the distribution of ER and its biological activity in patients, and assesses the expression of ER in breast cancer patients about primary and metastases before or after treatment, to provide a basis for personalized treatment of breast cancer. In this review, we will review the imaging principles of a new ER detection method <sup>18</sup>F-FES PET/CT, and the research progress in the clinical application of breast cancer, and compare its diagnostic and treatment value with non-specific tumor imaging <sup>18</sup>F-FDG PET/CT in breast cancer.
基金This work was supported by the National Natural Science Foundation of China (No. 30471962).
文摘OBJECTIVE To investigate the expression of the nuclear transcription factor NF-κB, ER, HER2 and PCNA in breast cancers, and to study the relationship between activation of NF-κB and clinicopathologic parameters including the level of PCNA, ER, HER2, lymph node involvement, tumor size and histological grade (differentiation). METHODS Sixty cases of human breast cancer tissues and adjacent non-neoplastic breast tissues were examined for NF-κB, HER2 and ER, as well as PCNA by immunohistochemical methodS. In addition the clinicopathologic parameters of the patients including lymph node involvement, tumor size and histological grade (differentiation) were collected. RESULTS The expression of NF-κB in the breast cancers and adjacent non-neoplastic breast tissue was 50.0% (30/60) and 40.0% (24/60) respectively, resulting in no significant difference (P〉0.05). NF-κB and HER2 expression was positively correlated whereas NF-κB and ER expression was negatively correlated. The NF-κB activation was 77.8% (14/18) in the breast cancers that were ER-/HER2^+, a level significantly higher (P〈0.001) in comparison to the other groups of patients. The expression of NF-κB in the low-differentiated group (grade Ⅲ) was 57.1%, and in the moderate-differentiated group (grade Ⅱ) was 50.3%, both of which were higher than the 35.7% found in the high-differentiated group (grade Ⅰ). NF-κB activation in the cancers was significantly correlated with the histological grade (P〈0.05), PCNA expression (P=0.003) and lymph node involvement and tumor size (P=0.03 and 0.002, respectively). CONCLUSION NF-κB was activated abnormally in a portion of the breast cancers. The finding that NF-κB activation was positively correlated with HER2 expression, the level of PCNA, tumor grade, size and lymph node involvement is in accord with the ability of NF-κB to promote cellular proliferation and migration, clearly identifies the protein as a hallmark for targeted dysregulation in oncogenesis. NF-κB may be a hopeful target for breast cancer therapy.
基金supported by grants from UK Medical Research Councils(Grant No.MC_UU_12019/2 and MC_UU_12019/4)Sumadi Lukman Anwar received a grant from PTUPT(Grant No.Ristekdikti 09_18)
文摘Objective:To determine the influence of the single nucleotide polymorphism(SNP)rs4245739 on the binding and expression of micro RNAs and subsequent MDM4 expression and the correlation of these factors with clinical determinants of ER-negative breast cancers.Methods:Find Tar and miRanda were used to detect the manner in which potential micro RNAs are affected by the SNP rs4245739-flanking sequence.RNA sequencing data for ER-negative breast cancer from The Cancer Genome Atlas(TCGA)were used to compare the expression of miR-184,miR-191,miR-193a,miR-378,and MDM4 in different rs4245739 genotypes.Results:Comparison of ER-negative cancer patients with and without the expression of miR-191 as well as profile micro RNAs(miR-184,miR-191,miR-193a and miR-378 altogether)can differentiate the expression of MDM4 among different rs4245739 genotypes.Although simple genotyping alone did not reveal significant clinical relationships,the combination of genotyping and micro RNA profiles was able to significantly differentiate individuals with larger tumor size and lower number of involved lymph nodes(P<0.05)in the risk group(A allele).Conclusions:We present two novel methods to analyze SNPs within 3′UTRs that use:(i)a single miRNA marker expression and(ii)an expression profile of miRNAs predicted to bind to the SNP region.We demonstrate that the application of these two methods,in particular the miRNA profile approach,permits detection of new molecular and clinical features related to the rs4245739 variant in ER-negative breast cancer.
文摘Objective: To study the relationship between theexpression of PS, protein and Estrogen (ER) andProgesterone Receptor (PR) status and their prognoticvalue in breast canceL Methods: Using theimmunohistochemical method, PS2 protein expressionswere detected in 105 cases with breast cancer. Results:The positive rate of PS2 protein was 50.48% (53/105) in105 cases. The positive rate of PS, in the patients whosurvived five years or more was 56.96% (45/79), whichwas higher than that of those who lived less than fiveyears (30.77%, 8/26). In the ER, PR (+) patients, thepositive rate of PS, was higher (76.74%, 33/34), thanthat of those with ER, PR (-) (22.5%, 9/40). Conclusions:Our results suggest that the expression of PS, proteinwas positively correlated with the 5-year-survival andthat of ER and PR in breast cancer. It is considered thatPS, may be as a prognostic predictor, and detection ofPS, protein expression was useful for a guidingtreatment of breast cancer.
文摘Objective To analyze the relationship of the expression level of estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor receptor-2(HER-2,c-erbB-2)of breast invasive ductal carcinoma(IDC)with ultrasonographic characteristics.Methods Totally 104 patients with IDCs confirmed pathologically were involved in this study.ER,PR and c-erbB-2 expression in the IDC specimens was determined by immunohistochemical staining technique.The correlation between the ultrasonographic features and the positive expression of ER,PR or c-erbB-2 was analyzed.Results The positive expression rate of ER and PR in the group with tumor spiculation sign and posterior acoustic attenuation was higher than that in the group without.The positive expression rate of ER differed significantly(P<0.05)while that of PR did not(P>0.05).The over-expression rate of c-erbB-2 in the group of microcalcification,sufficient blood flow and axillary lymph node metastasis was higher than that in the group of non-microcalcification,deficient blood flow or without axillary lymph node metastasis(P<0.05).The expression of ER,PR and c-erbB-2 was not related to the size of tumor(P>0.05).Conclusion The expression of ER and c-erbB-2 is closely related to the ultrasonographic characteristics of IDC,which may,to some extent,reflect the expression level of ER and c-erbB-2.
文摘Objective: To investigate the correlations of expression of Bax inhibitor-1 (BI-1) gene and the receptors of estrogen and progestogen in breast cancer and its significance. Methods: Immunohistochemical methods had been used to detect the expressions of BI-1 gene and receptors of estrogen and progestogen in breast cancer. Results: The positive rates of expressions of BI-1 gene, estrogen receptor (ER) and progestogen receptor (PR) in breast cancer were 77.08%, 60.42% and 54.17%, respectively. The positive rate of expression of BI-1 gene was higher in the group with negative expression of ER than the positive group, their positive rates were 76.92% and 52.27%, respectively; but there was no statistical difference between the two groups with positive and negative expressions of PR. The positive rate of expression of BI-1 gene was also higher in the group with positive lymph node metastasis than the non-lymph node metastasis group, and their positive rates were 64.58% and 36.36%, respectively. The difference was statistically significant (P 〈 0.05). Conclusion: BI-1 gene, in combination with ER, has guiding significance for patients with breast cancer to choose individual chemotherapy and radiotherapy after operation and can become an important indicator for judging the prognosis of breast cancer.
文摘Objective: The purpose of the study was to investigate the relationship between the expression of estrogen receptor(ER), progestogen receptor(PR), human epidermal growth factor receptor(Her-2), Ki-67 and the effect of neoadjuvant chemotherapy in breast cancer. Methods: The expression of ER, PR, Her-2 and Ki-67 in 45 breast cancers which received neoadjuvant chemotherapy was detected by immunohistochemistry. Results: The effective rates in ER negative and PR negative groups were higher than those in ER positive and PR positive groups(83.3% vs 59. 4%, 82.4% vs 60.6%). There was no significant difference of the effective rate between Her-2 overexpressed group and Her-2 non-overexpressed group(81.8% vs 64.1%), and the same thing happened between Ki-67 negative group and Ki-67 positive group(67.7% vs 63.2%). Conclusion: In the patients with breast cancer, ER, PR negative ones were more sensitive to neoadjuvant chemotherapy. These patients may get more benefits from chemotherapy. ER, PR could be feasible markers for predicting the effective rate of neoadjuvant chemotherapy.
基金Supported by a grant from the National Science Foundation of China (No. 30772100)
文摘Objective: We studied the alterations in the expression of estrogen receptor alpha (ER) in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinomas (IDC). Methods: The mastectomy specimens of 120 cases containing both DCIS and IDC were examined. The expression of ER proteins were examined by immunohistochemistry. The difference of the expression of ER proteins between DCIS and IDC were compared. Results: There were 58.33% of the cases with DCIS expressing ER proteins, and 40.00% of the cases IDC expressing ER proteins. There was a significant decrease of ER expression in IDC compared to DCIS (χ2 = 4.034, P = 0.045). Conclusion: These findings substantiate the notion that breast cancer progression is often associated with alterations in expressions of ER. The underlying mechanisms of these alterations need further investigation.
文摘Aim Breast cancer is one of the lethal gynecological malignancy in the world. Tamoxifen (TAM) and fulvestrant (FUL) are the major drugs for patients with estrogen receptor-positive (ER + ) breast cancers. Howev- er, the development of endocrine resistance is the impediment for successful treatment. In this study, we explored the mechanisms of endocrine resistance and therapeutic strategy for overcoming resistance against TAM and FUL. Methods The experiments were performed in Ell + and estrogen/TAM-sensitive MCF7 cells and antiestrogen-re- sistant MCF7/LCC9 cells. Western blot and confocal microscopy were used to determine cell autophagy. Cell trans- fection and luciferase activity assay were performed to identify the target gene of miR-214. Results It showed that 4-OHT/FUL treatment induced apoptosis as well as autophagy in breast cancer cells. The increase of autophagy might be the major cause of endocrine resistance to 4-OHT or FUL. Mill-214 increased the sensitivity of breast cancer cells to the 4-OHT/FUL-induced apoptosis through inhibition of autophagy. Importantly, a negative correla- tion was established between miR-214 and UCP2 in human breast cancer tissue specimens by RT-qPCR assay. UCP2 was identified to be a direct target of mill-214. Further study in MCF7/LCC9 cells indicated that endocrine resistance might arise from activation of the PI3 K-Akt-mTOll pathway, thereby inducing autophagy by overexpres- sion of UCP2. Conclusions MiR-214 increased the sensitivity of breast cancer cells to TAM and FUL through in- hibition of autophagy by targeting UCP2. Mill-214 shows potential as a novel therapeutic strategy for overcoming endocrine resistance in ER + breast cancers.
基金supported by the National Natural Science Foundation of China (No.30671508)by State Key Laboratory for Agrobiotechnology of China (No.2009SKLAB07-5)
文摘Objective: To investigate whether dietary daidzein interact with endogenous 17β-Estradiol (E2) to give rise to additive or inhibitory effects on proliferation and apoptosis in breast cancer cells. Methods: Cell cycle distribution and apoptosis induction were analyzed by using flow cytometry when breast cancer cell lines MCF-7 were cotreated with daidzein (1, 5 μmol/L) and E2 (0.1-10 nmol/L) for 5 days. Whether daidzein could alter E2-modulated mRNA expression of estrogen receptor alpha (ERα), estrogen receptor beta (ERI3) and ERβ-estrogen response element (ERE) dependent transcription was investigated by RT-PCR and luciferase induction assays. The effects of daidzein on E2-modulated expression of proapoptotic p53, bax and antiapoptotic bcl-2 at both mRNA and protein levels were also investigated by RT-PCR and Western blot. Results: Daidzein enhanced the antiapoptotic effect in an Ea dose-dependent manner, but had no effect on E2-induced proliferation. Daidzein antagonized E2-induced ERβ mRNA expression and ERβ-ERE dependent transcription. In addition, daidzein only antagonized E2-upregulated expression of p53 and bax, but had no effect on E2-upregulated expression of bcl-2. Conclusion: Daidzein enhances the antiapoptotic effect of E2 on breast cancer cells by inhibiting E2-mediated p53-bax proapoptotic pathway. These results suggest that dietary daidzein may enhance deleterious effect of endogenous E2 in hormone-dependent breast cancer.
文摘Objective: hER-α36 is a variant of estrogen receptor-a, identified and cloned by a team of American. This research is to determine whether hER-α36 can enhance or weaken chemosensitivity to docetaxel in breast cancer cell line MCF-7(ERα66 positive). Methods: RT-PCR was used to detect the expressions of ERα66 and ERa36 in the two human breast cancer cell lines MCF-7(MCF-7/ERα66) and MCF-7 transfected with ERa36(MCF-7/ERα36). The two cell lines were treated with docetaxel(0-100umol/L), and cell growth and apoptosis were evaluated using MTT (3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide) assay (using adriamycin (0-50umol/L) as the control) and flowcytometry. Western blot analysis was used to measure the effect of docetaxel on phosphor-ERKl/2 expression in the two cell lines. Results: The expressions of ERct36 and ERα66 were detectable in both MCF-7/ERα66 and MCF-7/ERα36 cell lines, while the expression of ERα36 in MCF-7/ER36 cells was higher. Both docetaxel and adriamycin inhibited the proliferation of both cells lines in a dose and time dependent manner. In comparison with MCF-7/ERα36 cell line, the MCF-7/ERα66 cells produced greater growth inhibition and apoptosis after treatment with docetaxel, but there was no significant difference in growth inhibition between the two cell lines treated with adriamycin; The MCF-7/ERα36 cell line resulted in a significant activation (phosphorylation) of ERK1/2 after treatment with docetaxel in a dose-dependent manner, but in the MCF-7/ERα66 cell line , a decrease in the level of phosphor- ERK1/2 expression was observed as the dose of docetaxel increased. Conclusion: ERa36 may be an agent that weakens chemosensitivity to docetaxel in breast cancer, probably by activating the expression of ERKI/2.
基金the National Natural Science Foundation of China(Grant Nos:81272260&81572712 to L.Chen)Natural Science Fund for Distinguished Young Scholars of Jiangsu Province(SBK2020010058)the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘Estrogen receptor alpha(ERα/ESR1)is overexpressed in over half of all breast cancers and is considered a valuable therapeutic target in ERαpositive breast cancer.Here,we designed a membrane-permeant Chaperonemediated Autophagy Targeting Chimeras(CMATAC)peptide to knockdown endogenous ERαprotein through chaperone-mediated autophagy.The peptide contains a cell membrane-penetrating peptide(TAT)that allows the peptide to by-pass the plasma membrane,anαI peptide as a protein-binding peptide(PBD)that binds specifically to ERα,and CMA-targeting peptide(CTM)that targeting chaperone-mediated autophagy.We validated that ERαtargeting peptide was able to target and degrade ERαto reduce the viability of ERαpositive breast cancer cells.Taken together,our studies provided a new method to reduce the level of intracellular ERαprotein via CMATAC,and thus may provide a new strategy for the treatment of ERαpositive breast cancer.
文摘Background: Several molecular markers have been detected that are important in clinical aspect of malignancies especially in breast cancer. More recently, the expression of vascular endothelial growth factor (VEGF), the most potent endothelial cell mitogen and also a regulator of vascular permeability, is emerging as a prognostic marker in patients with several types of cancer including breast cancer. This study assessed the expression of VEGF in a series of breast cancers in correlation with HER-2/neu and steroid receptors (ER and PR) in standard clinicopathological parameters in an attempt to clarify its potential clinical importance in Iraqi females of Middle Euphrates area. Findings: The present investigation was performed over a period starting from September 2011 through September 2012. Formalin-fixed, paraffin-embedded blocks from 52 patients with breast cancer (44 ductal and 8 lobular carcinoma) were included in this study. A group of 20 patients with fibroadenoma was included as a comparative group, and 20 samples of normal breast tissue sections were used as controls. Labeled streptavidin-biotin (LSAB+) complex method was employed for immunohistochemical detection of VEGF, HER-2/neu, ER and PR. The detection rate of VEGF, HER-2/neu, ER and PR was 59.62%, 36.96%, 34.62% and 36.54% respectively. There was a significant difference in immunoexpression between ductal and lobular carcinoma, but not significantly different among tumor sizes, tumor grades, axillary lymph node involvement and age of the patients. However, VEGF was positively correlated with tumor grade, tumor size, nodal involvement and HER-2/neu, but negatively correlated with ER and PR, which show the most unfavorable biopathological profile. Conclusion: VEGF overexpression play an important role in pathogenesis of breast carcinoma evolution, as its positivity associated with biologically aggressive tumors, so incorporation of this biomarker with other parameters into a prognostic index will more accurately predict clinical outcome and determine the effects of anti cancer therapy.
文摘Results of comparative study of Human Leu-cocytic Antigen (HLA-A), -B typing in 73 breast cancer (BC) patients having different estrogen receptor (ER) status and 50 healthy individuals in the northern part of China are reported. In 58 of the 73 patients, HLA-C, -DR typing were also studied in addition. The results of this study showed that HLA-Bw61 (40) were negatively associated with BC, while -Cw7 and -DRw6 were positively associated with BC. Moreover, -DR was more closely associated with ER(+) status with a RR value of 8.621. In the ER(-) group, there were no specific related antigens. In the light of the differences in pathology, prognosis and effect of endocrine therapy between ER(+) and ER(-) status, the authors are inclined to the view that the two kinds of breast cancer may be a heterogeneous disease.
文摘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.
文摘Aim Recent evidence has revealed that Eukaryotic elongation factor-2 kinase (eEF2K) activity may confer cancer cell adaptation to metabolic stress, and high expression of eEF2K is found in several types of cancer. Therefore, eEF2K may contribute to carcinogenesis and represent a promising therapeutic target; however, inhibi- tion of eEF2K for cancer drug discovery still remains in its infancy. This study aimed at developing a series of eEF2K inhibitor as candidate anti-tumor drugs in breast cancer and illustrating the possible mechanisms of its anti- tumor activity in vitro and in vivo. Methods In silico screening, structure modifications, MTT assay and molecular dynamics (MD) simulations were applied for the discovery of the novel eEF2K inhibitor (BL-EKI03). Observa- tions of cell morphology were executed through several methods including ER-traeker, MDC and Hoeehst 33258 staining and GFP-LC3 transfeetion. Flow eytometrie analyses of MDC and Annexin V/PI were used for quantifica- tion of autophagy and apoptosis ratio. Western blot and ITRAQ analysis were used to explore the detailed mecha- nisms of BL-EKI03-induced ER stress, autophagie death and apoptosis in breast cancer cells. Furthermore, an in vivo xenograft mouse model was established for validating the anti-tumor efficacy of BL-EKI03. Results Firstly, a novel eEF2K inhibitor (BL-EKI03) with a good affinity for eEF2K was eventually discovered after computational screening and synthesis of a series of candidate compounds targeting eEF2K. Subsequently, our results demonstra- ted that BL-EKI03 has remarkable anti-proliferative activities and induces endoplasmie retieulum (ER) stress, au- tophagy and apoptosis in MCF-7 and MDA-MB-436 cells. More importantly, the mechanism for BL-EKI03-indueed autophagie death involves eEF2K-mediated AMPK-mTOR-ULK complex pathways. The proteomies analyses and ex-perimental validation revealed that the BL-EKI03-induced mechanism was also involved BIRC6, BNIP1, SNAP29 and Bif-1, which might be regulated by eEF2K. Moreover, BL-EKI03 exerted its anti-tumor activities without re- markable toxicity, and it also induced autophagy and apoptosis by targeting eEF2K in fifo. Conclusion In this study, a novel eEF2K inhibitor (BL-EKI03) was discovered with remarkable anti-proliferative activities and in- duced endoplasmic reticulum (ER) stress, autophagy and apoptosis of breast cancer in vitro and in fifo. These findings highlight a new small-molecule eEF2K inhibitor (BL-EKI03) that has the potential to impact future breast cancer therapy.