In addition to its role as a sex hormone, estrogen aff ects the struc ture and function of many other systems such as the bone, the cardiovascular and the nervous system. Here, we review the most recent supporting evidence for es trogen as an important player in ocular fundus diseases, focusing particularly o n the effects of estrogen on these diseases and the underlying mechanisms. Base d on this, we also discuss the clinical applicability of estrogen in treating va rious agerelated disorders including agerelated macular degeneration and ret in al neurodegeneration. Our growing understanding of estrogenmediated action at a molecular level will provide insight into the controversies surrounding hormon e replacement therapy.
This study aims to predict expression of estrogen receptor (ER) in breast cancer by radiomics. Firstly, breast cancer images are segmented automatically by phase-based active contour (PBAC) method. Secondly, high-throughput features of ultrasound images are extracted and quantized. A total of 404 high-throughput features are divided into three categories, such as morphology, texture and wavelet. Then, the features are selected by R language and genetic algorithm combining minimum-redundancy-maximum-relevance (mRMR) criterion. Finally, support vector machine (SVM) and AdaBoost are used as classifiers, achieving the goal of predicting ER by breast ultrasound image. One hundred and four cases of breast cancer patients were conducted in the experiment and optimal indicator was obtained using AdaBoost. The prediction accuracy of molecular marker ER could achieve 75.96% and the highest area under the receiver operating characteristic curve (AUC) was 79.39%. According to the results of experiment, the feasibility of predicting expression of ER in breast cancer using radiomics was verified.
Objective To explore therapeutic effect of endocrine therapy in breast cancer patients with negative hormone receptor (HR–) of primary lesion and positive HR (HR+) of metastatic axillary lymph node lesion. Methods Sixty-seven cases of breast cancer with HR– of primary lesion and HR+ of metastatic axillary lymph node lesion from January 2011 to January 2016 were selected. All the patients were randomly divided into endocrine therapy group (33 cases) and control group (34 cases). The patients were given the oral drug of tamoxifen on the basis of conventional chemotherapy in the endocrine therapy group after the surgery, 10 mg/time, twice daily, 5 years; while the patients in the control group were not given the oral drug of tamoxifen but the other therapy same as the endocrine therapy group. The survivals were compared in both groups. Results There were no significant differences in the age, menstrual condition, tumor diameter, preoperative TNM stage, and so on between the endocrine therapy group and the control group (P>0.05). All the patients were followed up for 12–60 months with a 48.5 months of median time. There were no significant differences in the rates of the local recurrence and metastasis, or death rate due to the recurrence and metastasis in both groups (P>0.05). The progression-free survival and overall survival in the endocrine therapy group were significantly higher than those in the control group (P<0.05). The 5-year cumulative progression-free survival and overall survival in the endocrine therapy group were significantly better than those in the control group (P<0.05). Conclusion Pay attention to molecular classification of primary lesion and metastatic axillary lymph node lesion in patients with breast cancer, and endocrine therapy might be able to improve survival rate of breast cancer patients with primary lesion HR– and metastatic axillary lymph node lesion HR+.
Objective To summarize the research progress of postmenopausal breast cancer and estrogen metabolites, which is aimed at providing the basis for early diagnosis and early treatment of postmenopausal breast cancer, at the same time, providing beneficial information for the future study. Methods In recent years, the literatures about postmenopausal breast cancer and estrogen metabolites were reviewed from the databases of WanFang, VIP, CNKI, PubMed, and so on, to make an review. Results Estrogen metabolites had a dual role for postmenopausal breast cancer, such as 2-hydroxyestrone (2-OHE1), 2-methoxyestrone1 (2-MeOE1), and 4-methoxyestrone1 (4-MeOE1) played a protective role for postmenopausal breast cancer, but 4-hydroxyestrone (4-OHE1) and 16α-hydroxyestrone (16α-OHE1) played a carcinogenic role for postmenopausal breast cancer, so it needed to be further studied. Conclusions Estrogen metabolites may be a reliable predictor for the risk of postmenopausal breast cancer, it is not only to provide clues for the mechanism of postmenopausal breast cancer, but also provide new train of thought for early diagnosis and treatment of postmenopausal breast cancer.
ObjectiveTo detect protein expression of androgen receptor (AR) in patients with estrogen receptor (ER)-positive primary breast cancer and investigate its significances on prognosis.MethodsThe clinicopathologic data of female patients with ER-positive primary breast cancer in the Affiliated Hospital of Southwest Medical University from January 2012 to December 2012 were retrospectively analyzed. The AR protein expression in the breast cancer tissue was detected by the immunohistochemistry. The relationship between the AR protein expression and the clinicopathologic characteristics such as the age, tumor diameter, invasive biological behavior, molecular typing or the survival after the operation was analyzed.ResultsThe positive rate of AR protein expression was 58.5% (76/130) in the patients with ER-positive primary breast cancer. The positive rates of AR protein expression in the patients with the low differentiation, clinical stage Ⅲ+Ⅳ, p53 positive, neurovascular invasion, and lymph node metastasis were significantly lower than those in the patients with the moderate and high differentiations, clinical stage Ⅰ +Ⅱ, p53 negative, without neurovascular invasion, and without lymph node metastasis (P<0.050). The positive rate of AR protein expression was not correlated with the age, menstrual status, tumor diameter, progesterone receptor and Her-2 statuses, Ki-67, or molecular typing (P>0.050). The 3-year and 5-year overall survival and tumor-free survival of the AR-positive patients were significantly higher than those of the AR-negative patients (P<0.050). The 5-year cumulative total survival and tumor-free survival of the AR-positive patients were significantly better than those of the AR-negative patients (χ2=8.134, P=0.004; χ2=9.150, P=0.002).ConclusionsPatient with AR protein positive expression in ER-positive breast cancer has a better differentiation, lower clinical stage, and weaker invasiveness. Long-term survival of patient with AR protein positive expression after standardized treatment is also better than that of patient with AR protein negative expression. It might provide an important additional information on prognosis and become a promising object for targeted therapy.
ObjectiveTo study the correlation of lymph node metastasis and recurrence with body mass index (BMI) and estrogen receptor (ER) in papillary thyroid carcinoma (PTC).MethodThe relevant literatures were retrieved in the past six years through the CNKI, VIP, Wanfang, CBM, PubMed, Medline, Embase, Cochrane Library, etc. databases for meta-analysis of relationship of lymph node metastasis and recurrence of PTC with BMI or ER and its subtypes.ResultsThe meta-analysis showed that the lymph node metastasis of PTC was associated with the BMI and ERα [OR=1.27, 95% CI (1.12, 1.42), P<0.000 1; OR=2.68, 95% CI (1.86, 3.86), P<0.000 01, respectively ], and which not associated with the ER and ERβ [OR=0.87, 95% CI (0.56, 1.35), P=0.53; OR=1.22, 95% CI (0.78,1.89), P=0.39, respectively ]. The ERα was associated with the PTC recurrence [OR=1.87, 95% CI (1.04, 3.35), P=0.04 ], but the BMI was not the risk factor for the recurrence of PTC [OR=1.187 1, 95% CI (0.930 0, 1.515 3), P=0.17 ].ConclusionsAlthough BMI was not found to be associated with PTC recurrence, high BMI promotes PTC metastasis, so lymph node dissection in obese patients should be more careful and comprehensive. Positive ERα increases risk of lymph node metastasis and recurrence of PTC, which can be used as a negative factor in evaluating prognosis of PTC and provide a new idea for endocrine therapy of PTC.
ObjectiveTo investigate the effect of circulating estrogen level on the outcome of free fat grafting in nude mice.MethodsEighteen female nude mice aged 6-8 weeks (weighing, 20-25 g) were randomly divided into 3 groups (n=6). The nude mice in the ovariectomized group were treated with ovariectomy. The nude mice in the high estrogen group and the normal estrogen group only made the same incision to enter the peritoneum without ovariectomy. The nude mice in the high estrogen group were given the estradiol (0.2 mg/g) every 3 days for 30 days. The other two groups were given the same amount of PBS every 3 days. At 30 days after operation, the tail vein blood of nude mice in 3 groups were detected by estradiol ELISA kit, and the free fat (0.3 mL) donated by the females was injected into the sub-scalp of nude mice. After 8 weeks of fat grafting, the samples were taken for gross observation and weighing, and the prepared slices were stained with HE staining, CD31-perilipin fluorescence staining, immunohistochemical staining of uncoupling protein 1 (UCP1), and immunofluorescence staining of estrogen receptor α. The diameter of adipocytes and vascular density of adipose tissue were measured. The mRNA expressions of UCP1 and estrogen receptor α were detected by realtime fluorescence quantitative PCR (qRT-PCR).ResultsAll nude mice survived during experiment. ELISA test showed that the concentration of estradiol significantly decreased in the ovariectomized group and increased in the high estrogen group compared with the normal estrogen group (P<0.05). At 8 weeks after fat grafting, the graft volume from large to small was ovariectomized group, normal estrogen group, and high estrogen group. There was significant difference in wet weight between the ovariectomized group and high estrogen group (P<0.05). Section staining showed that compared with the normal estrogen group, the adipocytes in the ovariectomized group were larger, the expression of peri-lipoprotein was weaker, the vascular density decreased, and the expressions of UCP1 was negative, and the estrogen receptor α positive cells reduced. The above observation results in the high estrogen group were contrary to those in the ovariectomized group. There were significant differences in the diameter of adipocytes, the vascular density of adipose tissue, the number of the estrogen receptor α positive cells between groups (P<0.05). The results of qRT-PCR showed that the mRNA expressions of UCP1 and estrogen receptor α significantly increased in the high estrogen group and decreased in the ovariectomized group compared with the normal estrogen group, and the differences were significant (P<0.05).ConclusionThe level of circulating estrogen has a significant effect on the outcome of free fat grafting in nude mice. Low estrogen level leads to hypertrophy of graft adipocytes, while high estrogen level leads to the production of a large amount of beige fat and high vascular density in fat grafts, which may be related to the activation of estrogen receptor α on adipocytes.
ObjectiveTo investigate the relationship between female estrogen metabolism and breast cancer.MethodBy searching the contents of Chinese Knowledge Network, Wanfang Database, PubMed and other databases, the relationship between breast cancer hormone receptor status, menstrual status and estrogen metabolism and breast cancer, estrogen metabolism pathway and signal in vivo a review of the transduction aspects.ResultsEstrogen and its metabolites was closely related to the occurrence and development of breast cancer. Among the main metabolic pathways of estrogen, 2-methoxyestradiol in the 2-hydroxy metabolic pathway had a potential protective effect on breast cancer; 4-hydroxyestradiol, 16α-hydroxyestrone might induce breast cancer; the ratio of 4-hydroxyestradiol to 2-hydroxyestradiol might be used as a biomarker for predicting malignant breast tumors. However, the estrogen metabolism patterns before and after menopause were different, and the effects on hormone receptor status were also different. Different hormone receptor status might affect the treatment and prognosis of breast cancer.ConclusionsThe relationship between estrogen and its metabolites and breast cancer in different receptor states is not completely clear. More large-scale prospective studies are needed to help us find out the rules to promote early diagnosis and early prevention of breast cancer.
The purpose of this study was to investigate the effect of low-magnitude vibration on osteogenesis of osteoblasts in ovariectomized rats with osteoporosis via estrogen receptor α(ERα). The mRNA expression of osteogenic markers were examined with qRT-PCR, based on which the optimal vibration parameter for promoting osteogenesis was determined (45 Hz × 0.9 g, g = 9.8 m/s2). Then we loaded the optimal vibration parameter on the osteoblasts of ovariectomized rats with osteoporosis. The protein expression of osteogenic markers and ERα were detected with Western blot; the distribution of ERα was examined with immunofluorescence technique. Finally, through inhibiting the expression of ERα with estrogen receptor inhibitor ICI182780, the protein and mRNA expression of osteogenic markers were examined. First, the results showed that low-magnitude vibration could promote the expression of osteogenic markers and ERα in osteoblasts of ovariectomized rats with osteoporosis (P < 0.05), and make ERα transfer to the nucleus. On the other hand, the results also showed that after inhibiting the expression of ERα in osteoblasts of ovariectomized rats with osteoporosis, the protein and mRNA expression of osteogenic marker were decreased (P < 0.05). In our study, low-magnitude vibration played an important role in the osteogenesis of osteoblasts in ovariectomized rats with osteoporosis through increasing the expression and causing translocation of ERα. Furthermore, it provides a theoretical basis for the application of low-magnitude vibration in the prevention and treatment of postmenopausal osteoporosis.
ObjectiveTo investigate whether Osteoglycin (OGN) gene inhibits the proliferation of Luminal breast cancer cells by up-regulating the expression of estrogen receptor (ER). Methods① Ualcan online database was used to analyze the expression of OGN in the breast cancer, and Kaplan-Meier Plotter was used to analyze the effect of OGN on the prognosis of patients with breast cancer. The median OGN mRNA expression level was taken as the cut-off point for high or low OGN expression. ② The expression of OGN mRNA in the Luminal breast cancer tissue of clinical case was examined using real time quantitative PCR (qRT-PCR). ③ Up-regulation of OGN expression in the Luminal breast cancer cell lines MCF-7 and T47D cells by transfection of overexpressing OGN plasmid, the expressions of OGN and ER were detected by qRT-PCR and Western blot, respectively. CCK8 assay and colony formation assay were applied to detect the cell proliferation and colony formation of Luminal breast cancer cells. ④ siRNA transfection was used to interfere with the expression of ER (ESR1) of breast cancer cells in the overexpressing OGN of breast cancer cells, then the CCK8 assay was used to detect the proliferation ability of the breast cancer cell lines after down-regulating the expression of ER in the overexpressing OGN patients. Results① The results of Ualcan online database showed that the expression of OGN mRNA in the breast cancer tissues of different types of breast cancer was lower than that in the normal breast tissues (P<0.001), and which was highest in the Luminal breast cancer tissues (P<0.001). The Kaplan-Meier Plotter prognosis analysis showed that in all breast cancer or Luminal breast cancer patients, the prognosis of patients with high OGN expression was better than those with low OGN expression (P=0.000 14, P=0.001 80). ② The OGN mRNA expression was decreased in the 30 Luminal breast cancer samples as compared with the corresponding adjacent normal breast tissues (t=4.774, P=0.000 019). ③ The expressions of OGN and ER in the MCF-7 and T47D cells were up-regulated after transfection of overexpressing OGN plasmid (P=0.000 002, P=0.000 001). The cell proliferation was inhibited (P<0.05) and the number of cell clones was decreased significantly (P<0.05). ④ After transient transfection of siRNA interfered with breast cancer cell lines of overexpressing OGN, ER mRNA level decreased (P<0.05), and cell proliferation ability increased significantly (P<0.05). Conclusion OGN could exert a tumor suppressor effect in Luminal breast cancer by mediating expression of ER.