Lack of association between delayed tooth emergence and single nucleotide polymorphisms in estrogen receptors

Abstract The purpose of the study was to investigate the association between single nucleotide polymorphisms (SNPs) in genes encoding estrogen receptors (ESR1 and ESR2, respectively) and delayed tooth emergence (DTE). This cross-sectional study was composed of biological unrelated children of both sexes, age ranging from 11 to 13 years old. DTE was defined when the successor primary tooth was still present in the oral cavity after its exfoliation time or the absence of the permanent tooth emergence into the oral cavity. Children were diagnosed with DTE when they had at least one delayed permanent tooth, according to age of exfoliation of each tooth proposed by The American Dental Association. Genomic DNA from saliva was used to evaluate the SNPs in ESR1 (rs9340799 and rs2234693) and ESR2 (rs1256049 and rs4986938) using Real-Time PCR. Chi-square or Fisher exact tests and Logistic Regression adjusted by age and gender were performed. SNP-SNP interaction was accessed by multifactor dimensionality reduction (MDR) analysis also adjusted by gender and age. The established alpha of this study was 5%. Among 537 included children, 296 (55%) were in the "DTE" group and the 241 (45%) were in the "Control" group. Age and gender were not statistically different among the groups (p>0.05). Genotype distribution of the SNPs rs9340799, rs2234693, rs1256049 and rs4986938 were not associated with DTE (p> 0.05). The models elected by MDR were not statistically significant either. Conclusions: The studied SNPs in ESR1 and ESR2 were not associated with permanent DTE.

RESUMO O objetivo do presente estudo foi investigar a associação entre polimorfismos de nucleotídeo único (SNPs) em genes que codificam receptores de estrógeno (ESR1 e ESR2, respectivamente) e o retardo na emergência dentária (DTE). Este estudo transversal foi composto por crianças biológicas não relacionadas de ambos os sexos, com idades entre 11 e 13 anos. O DTE foi definido pela presença do dente decíduo na cavidade bucal após seu tempo e também, quando as crianças apresentaram pelo menos um dente permanente com atraso. O DNA genômico foi usado para avaliar os SNPs em ESR1 (rs9340799 e rs2234693) e ESR2 (rs1256049 e rs4986938) usando PCR em tempo real. Foram realizados testes Qui-quadrado ou exato de Fisher e Regressão Logística ajustados por idade e sexo. A interação SNP-SNP foi acessada pela análise de redução de dimensionalidade multifatorial (MDR), também ajustada por sexo e idade. O alfa de 5% foi estabelecido. Entre 537 crianças incluídas, 296 (55%) estavam no grupo "DTE" e 241 (45%) estavam no grupo "Controle". A idade e o sexo não foram estatisticamente diferentes entre os grupos (p> 0,05). A distribuição de genótipos dos SNPs rs9340799, rs2234693, rs1256049 e rs4986938 não foi associada ao DTE (p> 0,05). Os modelos eleitos pelo MDR também não foram estatisticamente significativos. Conclusões: Os SNPs estudados na ESR1 e ESR2 não foram associados ao DTE na dentição permanente.

Estrogen receptor mRNA determined by Quantitative Real-Time PCR in the nasal mucosa of women taking oral contraceptives / Receptor ARNm de estrógeno determinado por PCR Cuantitativa en Tiempo Real en la mucosa nasal de mujeres tratadas con anticonceptivos orales

SUMMARY: Estrogen receptors (ER) have been identified in human nasal mucosa, but its physiologic and pathologic impacts are not totally established. ER have been demonstrated in nasal mucosa by several authors, mainly by immunohistochemical method in nasal mucosa samples surgically removed. The present study aimed to quantify ERα and ERβ mRNA concentration by using an absolute quantitative real-time PCR in cells from nasal mucosa smear of women under oral contraceptive therapy. Nasal epithelium smear samples were collected from 110 patients divided in two groups: 55 women who present regular menstrual cycle without using contraceptives and 55 women who present regular menstrual cycle and have been using oral contraceptives for more than 3 months. All the patients answered a rhinitis symptoms questionnaire. The current study showed the potential usefulness of nasal turbinate mucosa cell sourcing, collected through swab, for extracting useful RNA for gene expression. We have identified the predominant expression of ERα isoform in a ratio 10-15 times higher compared to ERβ isoform. There is a tendency for positive correlation between the ERb isoform and the rhinitis severity score.

RESUMEN: Se han identificado receptores de estrógeno (RE) en la mucosa nasal humana, sin embargo sus impactos fisiológicos y patológicos aún no están totalmente establecidos. Varios autores han demostrado RE en la mucosa nasal, principalmente por método inmunohistoquímico en muestras obtenidas quirúrgicamente. El presente estudio tuvo como objetivo cuantificar la concentración de ARNm de REa y REb mediante el uso de una PCR cuantitativa absoluta en tiempo real en células de frotis de mucosa nasal de mujeres bajo terapia anticonceptiva oral. Se recolectaron muestras de frotis de epitelio nasal de 110 pacientes divididas en dos grupos: 55 mujeres que presentan ciclo menstrual regular sin uso de anticonceptivos y 55 mujeres que presentan ciclo menstrual regular con uso de anticonceptivos orales durante más de 3 meses. Todas las pacientes respondieron un cuestionario de síntomas de rinitis. El estudio actual mostró la utilidad de la obtención de células de la mucosa de la concha nasal, recolectadas a través de un hisopo, para extraer ARN para la expresión génica. Hemos identificado la expresión predominante de la isoforma REμ en una proporción de 10 a 15 veces mayor en comparación con la isoforma REß. Hemos identificado la expresión predominante de la isoforma REα en una proporción de 10 a 15 veces mayor en comparación con la isoforma REß. Existe una tendencia a una correlación positiva entre la isoforma REß y la puntuación de gravedad de la rinitis.

Clinico-pathological study of locally advanced breast cancer and their hormone receptor analysis

Background: Breast carcinoma is one of the most common malignant tumor of women. Determination of estrogen receptors (ER) and progesterone receptors (PR) status, prior to therapeutic intervention has become standard practice. Survival and response to hormone therapy are most favorable among women who are receptor positive. The aim of this study is to assess the hormone receptor status in locally advanced breast carcinomas and correlate this reactivity pattern with tumor stage, clinical stage and lymph node metastasis. Objective of the study was to co-relate the locally advanced breast cancer and their hormone receptor analysis.Methods: Patients who visited Department of General Surgery, Hamidia Hospital, Bhopal were assessed clinically, radiologically and histopathologically and then ER and PR study was done, for a total of 50 cases were done.Results: In our study majority of the cases were locally advanced breast cancer (50%) which may be due to the low socio economic status, late presentation, pain tolerance, illiteracy and availability of the resources. Majority of cases were in postmenopausal, clinical stage 3 and histological grade 2. ER positivity 50% and PR positivity 44% and it was found that hormone receptor positivity was high in locally advanced breast cancers 63.5%.Conclusions: Hormone receptor analysis should be an integral part of initial workup of carcinoma breast, as the percentage of hormone receptor positivity is increasing in our population in locally advanced breast cancer. So locally advanced breast cancer can be diagnosed at an early stage by screening and conducting breast awareness programs.

Fenugreek (Trigonella foenum-graceum) increases postmenopausal fibroblast-associated COL1A1 and COL3A1 production dominantly through its binding to estrogen receptor beta

In postmenopausal women, oral or topical administration of estradiol increases skin thickness and collagen synthesis,such as collagen type 1 alpha 1 (COL1A1) and collagen type 3 alpha 1 (COL3A1). Due to undesirable side effectsof estradiol, such as risks of breast and endometrium pathology, topical phytoestrogens are alternative treatments foraging-related skin changes. Phytoestrogen is a nonsteroidal substance derived from plants, like fenugreek (Trigonellafoenum-graceum L.), which has an estrogen like composition that appears to mimic estradiol. The mechanism ofaction remains unknown, especially in fibroblast-associated COL1A1 and COL3A1 production. In vitro experimentswere conducted using postmenopausal women's fibroblasts with estrogen receptor (ER) antagonists. Cell isolationused explant and enzymatic techniques with ELISA kit (MyBioSource, California) for COL1A1 and COL3A1. Pairedstudent t-tests compared results between control (no treatment), fenugreek extract 2 µg/ml alone, fenugreek extract 2µg/ml with receptor antagonists for ERα, ERβ, and both receptors. Greater suppresion of COL1A1 and COL3A1 wereshown by both antagonists ERα / ERβ group and antagonist ERβ group compared to antagonist ERα group. Theseresults indicate that the fenugreek increases secretion of COL1A1 and COL3A1 through ERα, ERβ, and is mainlymediated by ERβ in post menopausal women’s fibroblasts.

Progesterone and estradiol receptors and Ki-67 in the superficial and deep infiltrating endometriosis / Receptores de progesterona e estradiol e Ki-67 no estroma e no epitélio de endometriose superficial e profunda

ABSTRACT Introduction: Endometriosis is a hormone-dependent disease characterized by ectopic presence of endometrial tissue responsive to ovarian steroids. Estrogen and progesterone are the main regulators of endometrial tissue, and the expression of receptors of these hormones in the ectopic tissue seems to be related to the pathophysiology of the disease. Ki-67 is a marker of tissue proliferation and an important marker of epithelial kinetics. Endometriosis can be classified as superficial, in the peritoneum, and deep, when it extends into ligaments and other organs. Objective: Our objective was to analyze the expression of estrogen and progesterone receptors and Ki-67, through immunohistochemistry, in different sites of endometriosis tissues (superficial peritoneal/ovarian endometriosis and deep infiltrating endometriosis). Casuistic and methods: We studied nine patients; five with superficial and four with deep endometriosis. Statistical correlation was performed with the Shapiro-Wilk test (significance level of 5%) and linear correlation analysis using Spearman's non-parametric test (significance of 1%). There was a correlation of Spearman between the estrogen receptor variable and Ki-67 in patients with superficial endometriosis. There was also a correlation between the variables estrogen receptor and progesterone receptor in patients with deep endometriosis. Results: Contrary to what was found for superficial endometriosis, there is linear increase of the variables, with a strong and positive correlation coefficient. This demonstrates that the variation of estrogen receptors can be explained in 99.1% by the same variation of progesterone receptors in deep endometriosis. Conclusion: It is possible to infer that other factors are involved in the response to hormonal variations for superficial and deep endometriosis.

RESUMEN Introducción: Endometriosis es una enfermedad dependiente de hormonas que se caracteriza por la presencia ectópica de tejido endometrial sensible a los esteroides del ovario. El estrógeno y la progesterona son los principales reguladores del tejido endometrial, y la expresión de receptores de esas hormonas en el tejido ectópico parece tener conexión con la fisiopatología de la enfermedad. El Ki-67 es un marcador de proliferación tisular y de la cinética epitelial. La endometriosis puede ser clasificada en superficial y profunda, alcanzando ligamentos y otros órganos. Objetivo: El objetivo de este estudio fue analizar la expresión de los receptores de estrógeno y progesterona y Ki-67, mediante inmunohistoquímica en endometriosis superficial peritoneal/ ovárica y endometriosis infiltrativa profunda. Casuística y métodos: Estudiamos nueve casos: cinco de endometriosis superficial y cuatro de endometriosis profunda. La correlación estadística fue realizada con el test de Shapiro-Wilk (nivel de significación del 5%), y el análisis de correlación linear, por la prueba no paramétrica de Spearman (nivel de significación del 1%). Hubo correlación de Spearman entre la variable receptor de estrógeno (RE) y Ki-67 en pacientes con endometriosis superficial, y entre las variables RE y receptor de progesterona (RP) en pacientes con endometriosis profunda. Resultados: Al contrario de lo que se ha encontrado para endometriosis superficial, hay aumento lineal de las variables, con coeficiente de correlación fuerte e positivo. Eso demuestra que la variación de los receptores para estrógeno puede ser explicada en el 99,1% por la misma variación de los RP en la endometriosis profunda. Conclusión: Es posible deducir que otros factores estén involucrados en las diferentes respuestas hormonales para endometriosis superficial y profunda.

RESUMO Introdução: Endometriose é doença hormônio-dependente caracterizada pela presença ectópica de tecido endometrial responsivo aos esteroides ovarianos. O estrogênio e a progesterona são os principais reguladores do tecido endometrial, e a expressão de receptores desses hormônios no tecido ectópico parece ter relação com a fisiopatologia da doença. O Ki-67 é um marcador de proliferação tecidual e importante sinalizador da cinética epitelial. A endometriose pode ser classificada em superficial e profunda, atingindo ligamentos e outros órgãos. Objetivo: O objetivo deste estudo foi analisar a expressão dos receptores de estrógeno e progesterona e Ki-67, por meio de imuno-histoquímica em endometriose superficial peritoneal/ovariana e endometriose infiltrativa profunda. Casuística e métodos: Estudamos nove casos, cinco de endometriose superficial e quatro de endometriose profunda. A correlação estatística foi efetuada com os testes de Shapiro-Wilk (nível de significância 5%) e a análise de correlação linear, pelo teste não paramétrico de Spearman (1% de significância). Houve correlação de Spearman entre a variável receptor de estrogênio (RE) e Ki-67 em pacientes com endometriose superficial e entre as variáveis RE e receptor de progesterona (RP) em pacientes com endometriose profunda. Resultados: Ao contrário do que foi encontrado para endometriose superficial, há o aumento linear das variáveis, com coeficiente de correlação forte e positivo. Isso demonstra que a variação dos receptores para estrogênio pode ser explicada em 99,1% pela mesma variação dos RP na endometriose profunda. Conclusão: É possível inferir que estejam envolvidos outros fatores nas diferentes respostas hormonais para endometriose superficial e profunda.

Value of p53 and estrogen receptors immunohistochemical staining in endometrial carcinoma

Background: Since there are many articles dealing with estimating prognostic and diagnostic value of ER and p53, using different, usually complex ICH interpretation methods, we wanted to evaluate significance of p53 and ER ICH positivity in endometrial carcinoma, using easily applicable criteria that would help pathologists and clinicians to be sure in ICH findings noted in the report.Methods: This paper deals with data of the patients treated for endometrial carcinoma in Public Hospitals in Travnik, gynecological department in the period from 1st January 2013 to 1st January 2019. The study included 97 women with endometrial carcinoma, with ages ranging from 42 to 90 years (mean of 64 years). Sample consisted of 72 cases (74.2%) of endometrioid and 25 cases (25.8%) of non-endometrioid carcinoma.Results: p53 expression was observed in 13.8% carcinomas of the endometrioid type and in 68% carcinomas of non-endometrioid type, while estrogen receptors were more frequently observed in tumors of the endometrioid type (61%) in contrast to non-endometrioid type (28%). Among 72 cases, those with grade I expressed estrogen receptors (26 out of 34 cases - 72%) more frequently than those with grades II and III. Frequency of p53 positivity was significantly higher at higher grades (grade I - 5.8%, grade II - 11.5%, grade III - 71.4%). Stage I carcinomas showed p53 staining less frequently (22.2%) that carcinomas diagnosed at later stages (31.5%).Conclusions: Using 80% nuclei stained as threshold for p53 positivity, we concluded that p53 is marker of high-grade endometrial carcinomas: high grade endometrioid and non-endometrioid carcinomas. Using 1% of cells as threshold for ER positivity, we confirmed that ER are common in endometrioid type carcinoma, in contrast to non-endometrioid type. Although observed, higher frequency of ER in tumors with lower grade and stage was not statistically confirmed in our study population.

Association of menopausal status, expression of progesterone receptor and ki67 to the clinical response to neoadjuvant chemotherapy in luminal breast cancer / Associação de status menopausal, expressão de receptor de progesterona e de Ki67 à resposta clínica à quimioterapia neoadjuvante no câncer luminal de mama

Abstract Objective To identify the biomarkers of response to neoadjuvant chemotherapy in early luminal breast cancer. Methods A cross-sectional study that included all patients with early or locallyadvanced luminal breast cancer submitted to neoadjuvant chemotherapy between 2013 and 2014. Demographic, clinic and pathologic data were retrieved from patient records. The expressions of the estrogen receptor (ER), the progesterone receptor (PR), and Ki67 were analyzed by immunohistochemistry (IHC). The status of the human epidermal growth factor receptor 2 (HER2) was evaluated by IHC and fluorescent in situ hybridization (FISH). Independent predictors of clinic and pathologic response were evaluated by stepwise logistic regression models and receiver operating characteristic (ROC) curve analysis. Results Out of 298 patients identified, 115 were included in the analysis. Clinical complete response (cCR) was observed in 43.4% of the patients (49/113), and pathologic complete response (pCR) was observed in 7.1% (8/115) of the patients. The independent predictors of cCR were premenopausal status (p < 0.001), low PR expression (≤ 50% versus > 50%; p = 0.048), and Ki67 expression ≥ 14% (versus < 14%; p = 0.01). Patients with cCR were more commonly submitted to breast conserving surgery (34.7% versus 7.8%; p < 0.001). Increasing cut-off points for Ki67 expression were associated with an increase in specificity and a decrease in sensitivity to identify patients with cCR. Conclusion Premenopausal status, lower PR expression and higher Ki67 expression were associated with a higher rate of cCR to neoadjuvant chemotherapy in luminal breast cancer.

Resumo Objetivo Identificar biomarcadores de resposta à quimioterapia neoadjuvante em câncer luminal de mama. Métodos Estudo transversal em que foram incluídas todas as pacientes com câncer luminal de mama em estádio inicial ou localmente avançado que foram submetidas a quimioterapia neoadjuvante nos anos de 2013 e 2014. Dados demográficos, clínicos e patológicos foram obtidos de prontuários médicos. As expressões de receptor de estrogênio (RE), de receptor de progesterona (RP), e de Ki67 foram avaliadas por imuno-histoquímica (IHQ). A expressão do receptor tipo 2 do fator de crescimento epidérmico humano (human epidermal growth factor receptor 2, HER2) foi avaliada por IHQ e hibridização in situ por imunofluorescência (HISI). Análises de regressão logística e de curva de característica de operação do receptor (COR) foram usadas para investigar fatores preditivos independentes de resposta clínica e patológica. Resultados De 298 pacientes identificadas, 115 foram incluídas na análise. Resposta clínica completa (RCc) foi observada em 43.4% das pacientes (49/113), e resposta patológica completa (RPc), em 7.1% (8/115). Os fatores preditivos independentes de RCc foram status menopausal (p < 0.001), baixa expressão de RP (≤ 50% versus > 50%; p = 0.048), e expressão de Ki67 ≥ 14% (versus < 14%; p = 0.01). Pacientes com RCc apresentaram maior probabilidade de serem submetidas a cirurgia conservadora da mama (34.7% versus 7.8%; p < 0.001). Aumento no ponto de corte para expressão de Ki67 foi associado a aumento da especificidade e redução da sensibilidade na identificação de pacientes com RCc. Conclusão Status premenopausal, baixa expressão de RP e maior expressão de Ki67 estiveram associados a maior taxa de RCc à quimioterapia neoadjuvante no câncer luminal de mama.

Effect of cypermethrin on reproductive efficacy in zebrafish (Danio rerio): In-vivo and in- silico studies

Aim: The aim of the present study was to evaluate the reproductive efficacy of male and female zebrafish following cypermethrin exposure. Methodology: The adult zebrafish (Danio rerio) of both sexes were exposed to cypermethrin at three selected concentrations 0.1, 1.0 and 10 µgl-1 over a period of 21days. After completion of experimental period, the reproductive endpoints such as fecundity, hatchability, testis and ovarian histology and plasma vitellogenin levels were selected and determined in this study. Results: Cypermethrin exposure did not affect the cumulative fecundity rates in experimental fishes over controls. However, cypermethrin at 10 µgl-1 showed a significant reduction in the sperm number in male fishes over control. On the other hand, the same concentration of cypermethrin did not show significant changes in the plasma vitellogenin levels of both male and female fishes over their respective controls. Analysis of testicular and ovarian architectures of male and female zebrafish exposed to cypermethrin at 10 µgl-1 showed no marked differences over controls. In addition, molecular docking studies revealed that the binding energy between the cypermethrin and zebrafish estrogen receptor (zfER) β1 was almost similar to the binding energies exhibited by reference molecules, estradiol and ethinyl estradiol with zfERβ1. Further, binding energies between the ligands (cypermethrin and its metabolites phenoxybenzaldehyde and 3-phenoxybenzoic acid) with zfERα were low as compared to the binding energies between the reference molecules and zfERα. Interpretation: In-vivo studies indicated that cypermethrin at 10µg l-1 leads to spermatotoxicity in zebrafish and in silico analysis showed that the cypermethrin at least in part interfere with the signalling of zfERα.

Carcinoma ductal in situ de la mama con características apocrinas: reporte de un caso / Ductal carcinoma in situ of the breast with apocrine characteristics: case report

Resumen Se presenta el caso de una femenina de 69 años con un carcinoma ductal in situ de la mama, el cual presentaba diferenciación apocrina y alto grado nuclear. La forma de presentación clínica se hizo patente en forma de microcalcificaciones detectadas en la mamografía, y corroboradas histológicamente como comedonecrosis. La diferenciación apocrina se comprobó por medio de tinciones de inmunohistoquímica. El diagnóstico se realizó en una biopsia excisional, pero dado a que uno de los márgenes se encontraba comprometido, la paciente se sometió posteriormente a una mastectomía.

Abstract We present the case of a 69 year old female diagnosed with a ductal in situ carcinoma of the breast. The tumor had apocrine differentiation and a high nuclear grade. The clinical presentation corresponded to microcalcifications detected on mammography, which were histologically patent in the form of comedo type necrosis. The aforementioned apocrine differentiation was reassured using the aid of immunohistochemistry. The biopsy was an excisional biopsy, but due to positive quirurgical margins, the patient was later reintervened for total mastectomy.

Omitting Adjuvant Radiotherapy for Hormone Receptor‒Positive Early-Stage Breast Cancer in Old Age: A Propensity Score Matched SEER Analysis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to investigate the non-inferiority of omitting radiotherapy (RT) after breast-conserving surgery (BCS) for hormone receptor (HR)‒positive T1N0 breast cancer in elderly women. MATERIALS AND METHODS: From 2004 to 2014, HR-positive T1N0 breast cancer patients aged 50 years or older and receiving BCS were retrieved from the Surveillance, Epidemiology, and End RESULTS: 18 database. After propensity score matching between the no-RT and RT groups, univariate and multivariate analyses were performed. Identified prognostic factors were used to stratify the risk groups. In each risk group, 10-year cancer-specific survival (CSS) rates were compared between the no-RT and RT groups. RESULTS: After propensity score matching, the numbers of patients in the no-RT and RT groups were both 18,586. For patients who satisfied both a tumor size of 1-10 mm and a tumor grade of 1-2, omitting RT did not decrease the CSS rate at any age group, ranging from ≥ 50 to ≥ 85 years; for patients aged ≥ 50 years, the 10-year CSS rates in the no-RT and RT groups were 97.2% and 96.8%, respectively (adjusted hazard ratio, 0.862; p=0.312). However, for patients with a tumor size of 11-20 mm or tumor grade of 3-4, RT significantly increased the CSS rate irrespective of age. CONCLUSION: RT after BCS for HR-positive T1N0 breast cancer in elderly women might be omitted without causing a decrease in the CSS rate, but only in patients who satisfy both a small tumor size (≤ 10 mm) and low tumor grade (1-2).

Young Patients with Hormone Receptor-Positive Breast Cancer Have a Higher Long-Term Risk of Breast Cancer Specific Death / 한국유방암학회지

PURPOSE: Although it is widely accepted that hormone receptor (HR) status is associated with later post-diagnostic periods, a debate exists as to whether the association is independent of age. The aim of our study was to confirm the impact of HR status on later period breast cancer-specific death (LP-BCSD) and later period non-breast cancer-specific death (LP-non-BCSD) in different age subgroups. METHODS: Surveillance, Epidemiology, and End Results databases were utilized to identify 181,108 breast cancer patients with > 5 years survival. The cumulative incidence of LP-BCSD and LP-non-BCSD was calculated using the Gray method. The subdistribution hazard ratio (SHR) of variables was estimated via the Fine and Gray proportional hazard regression model. Subgroup analyses for LP-BCSD and LP-non-BCSD were performed according to the HR status. RESULTS: The risk of LP-BCSD was exceeded by that of LP-non-BCSD at > 5 years since the diagnosis, particularly in old women. The competing risk regression model indicated that hormone receptor-positive (HR+) was an independent factor for more LP-BCSD (hazard ratio, 1.54; 95% confidence interval, 1.44–1.54; p < 0.001). However, stratified analysis indicated that HR+ was only associated with more LP-BCSD in the young women subgroup. Although HR+ was associated with more LP-non-BCSD, the predictive value of HR+ for LP-non-BCSD was eliminated after adjusting for age. CONCLUSIONS: HR+ was related to LP-BCSD in the premenopausal population. LP-BCSD should be an optimal endpoint in future trials designed to evaluate the role of extended adjuvant endocrine therapy.

Treatment Outcomes of Weakly Positive Hormone Receptor Breast Cancer and Triple-Negative Breast Cancer

PURPOSE: In breast cancer, response to endocrine therapy depends on estrogen receptor and progesterone receptor status. However, poor prognosis is conferred on patients with hormone receptor (HR)-positive breast cancer. We aimed to examine weakly positive HR breast cancer by comparing weakly positive HR to strongly positive HR and negative HR breast cancer. METHODS: We examined the clinical and biological features of 1,496 women with breast cancer, and these patients were categorized according to HR status as weakly positive, strongly positive, and negative HR breast cancer. RESULTS: In this study, among 1,496 patients with breast cancer, negative HR breast cancer was found in 374, weakly positive HR breast cancer in 90 and strongly positive HR breast cancer in 1,032 patients. Our multivariate analysis showed that there were differences in T stage, tumor-node-metastasis stage, vascular invasion, histologic grade and type, and Ki-67 index. Patients with weakly positive HR breast cancer had an increased risk of death and recurrence compared with those with strongly positive HR breast cancer and had similar prognosis as patients with negative HR breast cancer. CONCLUSION: Patients with weakly positive HR breast cancer received endocrine therapy because they were regarded as having positive HR breast cancer. However, their prognosis of overall survival and relapse-free survival was similar to that in patients with negative HR breast cancer. Therefore, we need to closely observe and consider active treatment for patients with weakly positive breast cancer.

Clinical Differences in Triple-Positive Operable Breast Cancer Subtypes in Korean Patients: An Analysis of Korean Breast Cancer Registry Data / 한국유방암학회지

PURPOSE: Triple-positive breast cancer is defined by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) positivity. Several systemic breast cancer therapies target hormonal and HER2 responsiveness. We compared clinical outcomes of triple-positive disease with those of HER2-enriched and luminal HER2-negative disease and investigated the clinical efficacy of anti-HER2 therapy for triple-positive disease. METHODS: We retrospectively compared overall and recurrence-free survival among cases included in the Korean Breast Cancer Society (KBCS) and Seoul St. Mary's Hospital breast cancer registries and the therapeutic efficacy of trastuzumab for triple-positive and HER2-enriched cases. RESULTS: KBCS registry data (2006–2010; median follow-up, 76 months) indicated that patients with triple-positive breast cancer had intermediate survival between those with luminal A and HER2-enriched subtypes (p < 0.001). Trastuzumab did not improve overall survival among patients with triple-positive breast cancer (p=0.899) in contrast to the HER2-enriched subtype (p=0.018). Seoul St. Mary's Hospital registry data indicated similar recurrence-free survival outcomes (p < 0.001) and a lack of improvement with trastuzumab among patients with triple-positive breast cancer (median follow-up, 33 months; p=0.800). Multivariate analysis revealed that patients with triple-positive breast cancer had better overall survival than those with HER2-enriched disease and similar survival as those with the luminal A subtype (triple-positive: hazard ratio, 1.258, p=0.118; HER2-enriched: hazard ratio, 2.377, p < 0.001). CONCLUSION: Our findings showed that anti-HER2 therapy was less beneficial for treatment of triple-positive breast cancer than for HER2-enriched subtypes of breast cancer, and the triple-positive subtype had a distinct prognosis.

Correlation of Liver Depression Grading with Estrogen Receptor Alpha and Beta,G Protein-coupled Receptor 30 of Perimenopausal Women with Non-organic Insomnia / 广州中医药大学学报

Objective To explore the correlation of liver depression grading with estrogen receptor alpha and beta(ERα,ERβ)and G protein-couple receptor 30(GPR30)of the perimenopausal women suffering from non-organic insomnia. Methods A total of 127 perimenopausal women suffering from non-organic insomnia were enrolled into the study. The data collected by four diagnostic methods and the scores of Pittsburgh Sleep Quality Index(PSQI)were used for the scoring and grading of liver depression according to Syndrome Element Differentiation. The mRNA and protein expression levels of ERα,ERβand GPR30 in the mononuclear cells of peripheral blood from the patients were detected with real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB)method respectively. Results (1)The differences of mRNA levels of ERα,ERβ and GPR30 were insignificant among the patients with different degrees of liver depression (P > 0.05). ERα mRNA/ERβ mRNA ratio was decreased with the increase of liver depression grading,the differences being significant (F = 6.710, P < 0.001). (2) The differences of protein levels of ERα, ERβ and GPR30 were insignificant among the patients with different degrees of liver depression (P > 0.05);ERα/ERβ protein gray value ratio was decreased with the increase of liver depression grading, and the differences were significant (P < 0.05) . Conclusion The decline of ERα/ERβ is probably contributed to the pathological basis of liver depression in perimenopausal non-organic insomnia women.

High Estradiol Differentially Affects the Expression of the Glucose Transporter Type 4 in Pelvic Floor Muscles of Rats / 대한배뇨장애요실금학회지

PURPOSE: To characterize the relationship between serum estradiol levels and the expression of glucose transporter type 4 (Glut4) in the pubococcygeus and iliococcygeus muscles in female rats. METHODS: The muscles were excised from virgin rats during the metestrus and proestrus stages of the estrous cycle, and from sham and ovariectomized rats implanted with empty or estradiol benzoate–filled capsules. The expression of estrogen receptors (ERs) was inspected in the muscles at metestrus and proestrus. Relative Glut4 expression, glycogen content, and serum glucose levels were measured. Appropriate statistical tests were done to identify significant differences (P≤0.05). RESULTS: The pubococcygeus and iliococcygeus muscles expressed ERα and ERβ. Glut4 expression and glycogen content in the pubococcygeus muscle were higher at proestrus than at metestrus. No significant changes were observed in the iliococcygeus muscle. In ovariectomized rats, the administration of estradiol benzoate increased Glut4 expression and glycogen content in the pubococcygeus muscle alone. CONCLUSIONS: High serum estradiol levels increased Glut4 expression and glycogen content in the pubococcygeus muscle, but not in the iliococcygeus muscle.

Research progress on the changes of subchondral bone in osteoarthritis and its molecular mechanisms / 复旦学报（医学版）

Osteoarthritis (OA) is one of the most common chronic osteoarthritic diseases,which can involve the whole joint.Subchondral bone is an important part of the joint and has a close relationship to the development of OA.The changes and mechanisms of subchondral bone in OA are complex and remain disputes.In this review,we will discuss the advances of the molecular mechanisms of subchondral bone in OA,which include the pathological changes and the roles of the OPG/RANKL/RANK system,transforming growth factor β (TGFβ),estrogen-estrogen receptors and lipid metabolism in OA.

Research progress of tamoxifen resistance mechanism in breast cancer / 实用肿瘤学杂志

Tamoxifen(TAM)is an important therapeutic strategy for the treatment of estrogen receptor(ER)-positive breast cancer.However,tamoxifen resistance is a major cause of endocrine therapy failure.The potential mechanism of TAM resistance is multifactorial and most of them are still unknown.This review presents recent advances in the mechanism of TAM resistance in breast cancer,providing valuable information and ideas for elucidating the mechanism of tamoxifen resistance and overcoming drug resistance.

17β-Estradiol and fulvestrant inhibit glomerular mesangial cell fibrogenesis downstream of protein kinase C activation / 中国药科大学学报

To investigate the effect of estrogen receptor (ER) agonist 17β-estradiol and G protein-coupled estrogen receptor 1 (GPER) agonist fulvestrant on masangial cell fibrogenesis under protein kinase C (PKC),we quantified type Ⅳ collagen (COL4A1),fibronectin (FN1),connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGFβ1) gene transcription and semi-quantified phosphorylation of Akt signal upon Phorbol 12-myristate 13-acetate stimulation (which increased COL4A1,FN1,CTGF and TGFβ1 gene transcription to 2.5-0.5,1.4 ±0.2,26 ± 11 and 1.9 ±0.3 times compared with baseline,P ＜0.05) when incubated with the two drugs.It was found that 17β-estradiol and fulvestrant down-regulated COL4A1,FN1,CTGF and TGFβ1 genes transcription (P ＜0.05) and Akt signaling under PKC activation via ER and GPER.ER and GPER agonists are beneficial in protecting the mesangial cells from fibrogenic stimuli by inhibiting PKC signaling and excessive extracellular matrix production.

Prognostic Value of Estrogen and Progesterone Receptor Expression in Low Proliferative Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer

PURPOSE: Approximately two-thirds of breast cancer are estrogen-dependent cancers, which express estrogen receptor (ER)/progesterone receptor (PR). We investigated the prognostic value of ER/PR expression in human epidermal growth factor receptor 2 (HER2)-negative and low proliferative (Ki-67 ≤20%) breast cancer. METHODS: A retrospective review was performed of 252 breast cancer data records, identified as ER/PR-positive, low Ki-67 proliferation index (≤20%) and HER2-negative. The data were divided into two subgroups: a strong luminal subgroup and a weak luminal subgroup, according to hormonal receptor expression status. Outcome measures included age at diagnosis, tumor size, tumor-node-metastasis (TNM) stage, ER, PR, Bcl-2, recurrent or metastatic characteristics, disease-free survival and overall survival, of each subgroup. RESULTS: There were no statistical differences in TNM stage or tumor numbers between the two subgroups. The strong luminal subgroup was associated with a higher Bcl-2 expression (p<0.001). The weak luminal subgroup was associated with more frequent neural invasion (p=0.051) and lung (p=0.031), liver (p=0.031) and brain (p=0.033) metastases, than the strong luminal subgroup. Disease-free survival was significantly longer in the strong luminal subgroup than weak luminal subgroup (p=0.015). Overall survival was also significantly improved in the strong luminal subgroup relative to the weak luminal subgroup (p=0.014). CONCLUSION: The weak luminal subgroup showed worse prognosis than the strong luminal subgroup, among ER/PR-positive HER2-negative low proliferative breast cancer patients. Weak ER or PR expression, can be considered a poor prognostic factor in ER/PR-positive HER2-negative low proliferative breast cancer.

Wnt7a Deficiency Could Predict Worse Disease-Free and Overall Survival in Estrogen Receptor-Positive Breast Cancer / 한국유방암학회지

PURPOSE: Wnt7a is a glycoprotein involved in embryonic development and the progression of different types of malignant tumors. This study aimed to detect the level of Wnt7a expression in breast cancer and explore its role in the disease progression and prognosis. METHODS: A total of 258 patients diagnosed with invasive ductal carcinoma of the breast were included in this study. Using tissue microarray and immunohistochemical staining, we evaluated the association between Wnt7a expression and clinicopathological parameters, and the prognostic value of Wnt7a. RESULTS: Wnt7a expression was significantly correlated with estrogen receptor (ER) expression (odds ratio, 3.95; 95% confidence interval [CI], 1.99–7.80; p < 0.001). On univariate and multivariate analyses, loss of Wnt7a expression was associated with poor disease-free survival (DFS) (multivariate hazard ratio [HR], 9.12; 95% CI, 1.80–46.09; p=0.008), but not with poor overall survival (OS). In the ER-positive group (n=114), loss of Wnt7a expression was an independent prognostic factor for shorter DFS (multivariate HR, 13.54; 95% CI, 1.11–165.73; p=0.042) and OS (multivariate HR, 4.76; 95% CI, 1.29–17.61; p=0.019) on univariate and multivariate analyses. However, in the ER-negative group, there was no significant difference in DFS and OS according to Wnt7a expression. CONCLUSION: The loss of Wnt7a expression might be a meaningful factor in assessing DFS and OS, especially in ER-positive breast cancer.