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The term "gynecomastia" refers to the benign growth of glandular breast tissue in men. In older men, adolescents, and newborns, physiological gynecomastia is common. Although it is self-limited, it can be managed to reduce both physical and emotional discomfort. Chronic conditions (such as cirrhosis, hypogonadism, and renal insufficiency), drug use (including prescription, over-the-counter, and illicit drugs), and tumors are rare causes of nonphysiologic gynecomastia. Exogenous estrogens, antiandrogens, 5-alpha reductase inhibitors, spironolactone, and cimetidine are the active ingredients that are known to cause gynecomastia the most frequently. A patient's medical history is crucial in diagnosing drug-induced gynecomastia. Treating the underlying disease and stopping contributing medications are the cornerstones of treatment. In certain cases, gynecomastia can be treated with surgery and medications such as estrogen receptor modulators. Early intervention and patient-directed care are important aspects of treatment. We describe the pathogenetic mechanism of spironolactone-induced gynecomastia and provide a case report of a 52-year-old male patient.
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En la actualidad, más de la mitad de las pacientes con cáncer de mama receptor hormonal positivo recibe algún esquema de quimioterapia adyuvante. Sin embargo, sólo algunas de ellas obtendrían un beneficio real en términos de sobrevida. Las plataformas genómicas permiten un mejor entendimiento de la heterogeneidad tumoral entre carcinomas con receptores hormonales positivos, Her2 negativos, habiendo sido validadas como herramientas para identificar aquellas. pacientes que obtendrían un beneficio claro con el tratamiento quimioterápico. El objetivo de nuestro estudio es describir el uso de la plataforma genómica Oncotype Dx® y evaluar su impacto sobre la indicación del tratamiento adyuvante, evaluado principalmente a través del cambio de conducta en relación con la indicación final del tratamiento adyuvante. Material y método: Estudio multicéntrico observacional de cohorte llevado a cabo en distintas Unidades de Mastología de la República Argentina que utilizaran el Oncotype Dx* para esclarecer la indicación del tratamiento adyuvante en pacientes luminales Her2neu negativas en estadio inicial. Se registraron las decisiones relacionadas con el tratamiento antes y luego de realizar la prueba genómica. El objetivo secundario consistió en describir los eventos en aquellas pacientes en quiénes se solicitó dicho estudio. Resultados: Entre enero de 2013 y diciembre de 2018, 211 pacientes con carcinomas luminales A o B, Her2neu negativas realizaron el Oncotype Dx* y fueron incluidas en el estudio. Según nuestros registros, 40% de las pacientes experimentó un cambio en la indicación del tratamiento adyuvante luego de realizada la plataforma genómica. De aquellas pacientes que tenían indicación inicial de hormonoterapia según parámetros tradicionales clínico-patológicos, 24% recibió adicionalmente quimioterapia. En relación con las pacientes que tenían indicación inicial de quimio y hormonoterapia, 49% experimentó un cambio en la indicación de su adyuvancia pudiendo realizar únicamente hormonoterapia. En relación a los eventos descriptos en las pacientes participantes del trabajo, se registraron 4 muertes específicas por la enfermedad, una muerte por otra causa, 2 recaídas a distancia y un cáncer de mama contralateral. Conclusiones: En nuestra población de estudio el uso del Score de Recurrencia (RS) resultó clínicamente significativo en relación al cambio de conducta en la toma de decisión para adyuvancia. En consecuencia, para este grupo de investigadores, ha demostrado ser una herramienta de significativa importancia en la decisión del tratamiento adyuvante de pacientes con cáncer de mama temprano, luminal, Her2neu negativo(AU)
Objetive: Currently, over half of all patients diagnosed with hormone-receptor positive early stage breast cancer will receive some type of adjuvant chemotherapy (CHT), but only a few of them will actually benefit in terms of survival. Genomic platforms allow a better understanding of the heterogeneity among the different types of hormone receptor positive, her2 negative breast cancer, and have proven their validity as tools for identifying those patients who will obtain a clear benefit from CHT. The aim of our study was to analyze the use of the genomic platform Oncotype Dx® in our population and describe its impact on the decision of adjuvant treatment assessed through change in treatment decision. Material and method: this was a real world collaborative observational study, which was performed across several Breast Units in Argentina. Patients who underwent Oncotype Dx® testing to determine adjuvant treatment were included. Decisions regarding treatment were settled before and after the oncotype was performed by the tumor boards of each Breast Unit. Results: From January 2013 to December 2018, 211 patients with luminal A or B, her 2 negative breast cancer who underwent Oncotype Dx" testing were included. We found that treatment decisions were modified after Oncotype DX in approximately 40% of patients. In 24% percent of cases, chemotherapy was added to the initial treatment plan although endocrine therapy alone had initially been considered (potential subtreatment); and on the other hand, 49% of all patients were able to receive endocrine therapy only when, due to traditional prognostic factors, they would have received chemotherapy (potential overtreatment). Conclusions: In our population, we found that the use of the Recurrence Score was associated with a significant change in treatment recommendation We therefore consider it to be a very important tool and a decisive factor for the selection of adjuvant treatment in patients with hormone receptor positive, her2neu negative early breast cancer(AU)
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Objective@#To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.@*Methods@#The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells.@*Results@#A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner.@*Conclusion@#RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.
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Objective To find the correlation between phosphatidylinositol kinase-3 catalytic subunit A gene(PIK3CA)mutation and pathological features as well as clinical prognosis of breast cancer.Methods The patho-logical data of 181 patients diagnosed with invasive breast cancer from January 2018 to January 2020 were collected.The estrogen receptor(ER),progestogen receptor(PR),human epidermal growth factor receptor-2(HER2),Ki67 were examined by immuno-histochemistry(IHC).Mutation of exon 9 and exon 20 of PIK3CA were examined by quantitative real-time PCR(qPCR).Results Among 181 cases of invasive breast cancer,70 cases had PIK3CA mutation with 31 cases(44.28%)showed exon 9 mutations and 39 cases(55.71%)showed exon 20 mutations.The difference between PIK3CA mutation and their distribution in molecular typing of breast cancer was statistically significant(P<0.05).The expression of PIK3CA mutation in breast cancer with different Ki67 expression was sig-nificantly different(P<0.05).There were 34 cases(48.57%)showed PIK3CA mutations in the HR+/HER2 group and 36 cases(51.43%)of non HR+/HER2 group mutations.There was a statistically significant difference in the distribution of PIK3CA mutations between 2 groups(P<0.05).The death rate of PIK3CA mutation cases was higher than that of PIK3CA wild type cases(P<0.05).Conclusions PIK3CA mutation is associated with molecular typ-ing,Ki67 increment index and prognosis of breast cancer.Detection of PIK3CA mutation provides potential support to the development of precise treatment of breast cancer patients.
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BACKGROUND:The specific mechanism of Gushukang,as a Chinese traditional patent medicine for the treatment of postmenopausal osteoporosis of kidney deficiency and blood stasis,needs further studies. OBJECTIVE:To investigate the effect of Gushukang on serum sex hormones,bone microstructure and estrogen receptor in postmenopausal osteoporosis. METHODS:Firstly,network pharmacological analysis was performed.The active ingredients and action targets of Gushukang and the targets of postmenopausal osteoporosis were obtained respectively.Cytoscape was used to construct the active ingredient-target network.STRING database and Cytoscape were used for protein-protein interaction analysis and screening of core targets.DAVID database was used for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of intersection targets.Then the ovariectomized Sprague-Dawley rats were used in the animal experiment.Gushukang was administered by gavage for 3 months.The serum estrogen level was detected by ELISA,the bone microstructure was detected by microCT,and the protein expression of estrogen receptor α and estrogen receptor β in bone tiusse was detected by western blot. RESULTS AND CONCLUSION:The network pharmacological research results identified 132 active ingredients and 150 targets of Gushukang and 1155 targets of postmenopausal osteoporosis.After intersections with 1155 postmenopausal osteoporosis targets,87 targets of active ingredients of Gushukang against postmenopausal osteoporosis were obtained.By constructing the active ingredient-target network,it was found that the active ingredients at the core were quercetin,kaempferol,luteolin,naringin and isorhamnetin,and the targets at the core were NCOA2,ESR2,AR,F2,ESR1 and PTGS1.The final targets obtained after the protein-protein interaction analysis and screening included MAPK8,ESR1,JUN,R3C1,RELA and FOS,of which ESR1 was the common core target obtained from the two analyses.KEGG enrichment analysis showed estrogen,tumor necrosis factor,apoptosis and other signaling pathways.Therefore,animal experiments focused on the effect of Gushukang on different subtypes of estrogen receptors in the estrogen signaling pathway.The results showed that in the Gushukang group,bone microstructure was significantly improved,serum estrogen level had no significant change,but the protein expression of estrogen receptor α and β in bone tissue was significantly increased.All the findings indicate that the mechanism of Gushukang in the treatment of postmenopausal osteoporosis may be related to its hormone-like effect and the enhancement of estrogen receptor expression.
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BACKGROUND:Increasing studies have found that estrogen has a certain correlation with tendinopathy,but for a long time,there are few experiments and summaries of estrogen in tendinopathy,which makes it difficult for specialists and scholars in related fields to fully understand the research status. OBJECTIVE:To summarize the current clinical or preclinical original research,so as to summarize the role of estrogen in tendinosis,and make a certain prospect for the evaluation and management of estrogen in tendinosis in the future. METHODS:Relevant literature in PubMed,Web of Science,CNKI,WanFang,and VIP databases were searched by computer.Search time was from January 2008 to September 2023.The search terms were"oestrogen,estrogen,estrogen receptor,tendinopathy,tendonopathy,sinew,tendon,tendons,myotenositis"in English and"estrogen,estrogen receptor,tendinosis,tendon,tendinitis"in Chinese.According to the selection criteria,the search results were screened and excluded,and finally 60 documents were included for review and analysis. RESULTS AND CONCLUSION:In vivo studies have shown that estrogen can promote tendon anabolism.In vitro experiments have also proved that various estrogens can promote the proliferation of tendon cells and reduce inflammation and apoptosis,but most of the experiments are limited to animal models.Estrogen receptor β acts more in tendon injury and repair processes,but estrogen receptor α has not been found to have a major impact on tendon injury.The expression of estrogen receptor β can repair the tendon by affecting the formation of fat,the deposition of type I collagen and reducing the apoptosis of tendon cells,while its over-expression may promote inflammation and angiogenesis,thus promoting the inflammatory process and playing a role in tendon injury.Animal studies have shown that estrogen deficiency may reduce the synthesis efficiency of collagen in the tendon,decrease the elasticity of tendon,inhibit the synthesis and metabolism of the tendon,which is not conducive to the repair of tendon injury,while normal level of estrogen may stimulate the synthesis of type I collagen in tendon and promote the proliferation and metabolism of tendon cells.At present,the molecular mechanism of estrogen in tendon injury has not been fully explained.More experiments focus on tendon collagen synthesis,cell proliferation and apoptosis.Only a few documents have studied the molecular mechanisms of estrogen receptor β deficiency regulating interferon regulatory factor 5-chemokine ligand 3 axis,E2 regulating estrogen receptor α and PI-3K-Akt signaling pathways,and high levels of estradiol reducing the level of free-circulating insulin-like growth factor.Various estrogens,including endogenous estrogens and phytoestrogens,are beneficial to the repair of tendinopathy at normal levels,and estrogen receptor β mainly affects the formation of fat,the deposition of type I collagen and the reduction of apoptosis of tendon cells through,which lays a foundation for the future treatment of tendinopathy with different subtypes of estrogens in vivo and the influence of estrogen membrane receptors on tendinopathy.
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Objective:To explore the effects of estrogen receptor α (ERα) encoded by protein encoding gene ESR1 on the radiation resistance of breast cancer cells and their molecular mechanisms.Methods:The ESR1 overexpression plasmid was transfected into estrogen receptor (ER)-negative breast cancer cells. Then, the shRNA-ESR1 vector was introduced into ER-positive cell to establish models with different phenotype. The ATG5 mRNA level and protein expression levels of LC3B-I, LC3B-II, P62, FIP200, ATG5, ATG7, ATG12, Beclin1, ULK1 were detected using qPCR and Western blot techniques. Cell death was measured using flow cytometry. The radiation sensitivity was determined through the colony formation assay. The mortality of breast cancer cells under the autophagy gene knockdown and overexpression or treated with estrogen receptor inhibitor (TAM) combined with ionizing radiation were detected by trypan blue staining.Results:Under the condition of 8 Gy X-ray irradiation, the knockdown of ESR1 in ER-positive ZR75 breast cancer cells promoted cell death ( t = 3.49, 3.13, P < 0.05), while the overexpression of ESR1 in ER-negative MDA-MB-231 breast cancer cells inhibited cell death ( t = 4.16, 7.48, P < 0.05). Compared to the control group, the treatment with chloroquine increased the number of formed colonies of ESR1 knockdown ZR75 cells ( t = 8.49, P < 0.05), and inhibiting autophagy could reduce the death of ZR75 cells caused by ESR1 silencing. Under the treatment with ionizing radiation, the overexpression of ESR1 in MDA-MB-231 cells promoted protective autophagy, which, however, was reduced after ESR1 knockdown in ZR75 cells. Furthermore, it was observed that the knockdown of ATG5 in ZR75 cells was associated with reduced autophagy and an increase in cell death ( t = 4.19, 6.39, P < 0.05). In contrast, the overexpression of ATG5 in ZR75 cells reversed the increase in cell death caused by ESR1 knockdown ( t = 1.70, 4.65, P < 0.05). After the treatment of ER-positive ZR75 breast cancer cells with TAM, the expressions of ATG5 and ATG12 decreased, suggesting inhibited autophagy and an increase in cell death ( t = 18.70, P < 0.05). Furthermore, these processes were promoted by ionizing radiation ( t = 16.82, P < 0.05). Conclusions:The estrogen receptor encoded by ESR1 promotes protective autophagy of ER-positive breast cancer cells by increasing ATG5, further leading to radiation resistance in ER-positive breast cancer cells. Treatment with tamoxifen combined with ionizing radiation can increase the radiation sensitivity of ER-positive breast cancer cells.
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Objective To investigate the causal association between 91 kinds of circulating inflammatory proteins and different subtypes of breast cancer (estrogen receptor-positive and -negative breast cancer) using a two-sample Mendelian randomization (MR) method. Methods Corresponding exposure and outcome data were extracted from the genome-wide association study database. The data were analyzed by two-sample MR with inverse-variance weighting (IVW) as the primary study method, and MR-Egger, weighted median, simple mode, and weighted mode were used to complement the results. The results were complemented by sensitivity analysis to verify the reliability of the data. Results The IVW results showed that SULT1A1 (P=0.0007) was associated with an increased risk of total BC, whereas IL-5 (P=0.0011) was associated with a decreased risk of total BC. SULT1A1 (P=0.0011) and CX3CL1 (P=0.0005) were associated with an increased risk of ER+BC, whereas beta-NGF (P=0.0001) was associated with an increased risk of ER−BC. Supplementary analysis methods validated that the findings were consistent in direction and magnitude. The results of the sensitivity analysis showed that the data were reliable and unbiased. Conclusion Using the MR method, this study confirms that SULT1A1 is a risk factor for overall breast cancer, whereas IL-5 is a protective factor for overall breast cancer. SULT1A1 and CX3CL1 are risk factors for estrogen receptor-positive breast cancer, and beta-NGF is a risk factor for estrogen receptor-negative breast cancer.
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Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.
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Phytoestrogens refer to a class of compounds in plants that can bind to and activate estrogen receptors in mammalian organisms,exerting varying degrees of protective and improvement effects on the body.Modern pharmacological studies have found that phytoestrogens have therapeutic effects on the cardiovascular system,nervous system,endocrine system,immune system,and so on.It is worth noting that the binding of phytoestrogens to estrogen receptors in the brain can produce central neuroprotective effects and improve learning and cognitive impairment in Alzheimer's pectients through multiple targeted pathways.This paper describes the research progress and related mechanisms of phytoestrogen-like monomers,Chinese herbal medicine,and compound formulations in Alzheimer's disease.The aim is to provide new drug design ideas and solutions for the effective treatment of senile dementia with traditional Chinese medicine.
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Background: Dysfunctional uterine bleeding (DUB) is one of the most common menstrual disorder of women in any age group and is a diagnosis of exclusion. Medical management of menorrhagia is a difficult task as there are wide variations in the available drugs and a lot of different regimes are available. Present study evaluates efficacy and safety of ormeloxifene a selective estrogen receptor modulator (SERMs) in treatment of dysfunctional uterine bleeding in perimenopausal women.Methods: The study was conducted on 120 patients in the age group of 40-55 years who were treated with 60 mg ormeloxifene twice a week for first 12 weeks and once weekly for next 12 weeks. The primary outcome measures were menstrual blood loss (assessed by pictorial blood assessment chart score), hemoglobin concentration and endometrial thickness. The secondary outcome measures were aceptability and side effects of ormeloxifene.Results: 86.66% of women showed marked improvement in symptoms. Mean endometrial thickness decreased significantly from 9.825 mm to 6.25 mm after 6 months of treatment (p value <0.001). A significant decrease in median PBAC score (p value <0.001) was observed. Also, the mean haemoglobin level increased significantly from 8.03 g/dl to 9.60 g/dl (p value <0.001). Most common side effect reported was amenorrhoea (16%). 4% patient not relieved underwent hysterectomy.Conclusions: Ormeloxifene could be the drug of choice in patients with DUB. It is safe, cost-effective with manageable side effects. The therapy has facilitated compliance, tolerability and reduction of symptoms resulting in adherence towards the treatment.
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SUMMARY: Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is highly expressed in various types of cancers including breast cancer. However, the role of AhR with its endogenous ligand 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) on the progression of breast cancer remains poorly understood. We aimed to investigate cell proliferation and migration states in breast cancer after activating AhR with the endogenous ligand ITE. Breast cancer tissue was evaluated by cell lines, immunohistochemistry, reverse transcription-polymerase chain reaction, cell proliferation, flow cytometry, migration assays and western blot techniques. We found that AhR was widely expressed in breast cancer tissues and metastasis lymph node tissues, but not in normal tissues. The expression AhR was independent between the age, grades and TNM classifications for breast cancer tissues. ITE treatment significantly induced the activation of AhR in a time-dependent manner in both MCF-7 and T47D breast cancer cell lines. Meanwhile, ITE did not affect the cell migration but significantly suppressed the cell proliferation in estrogen receptor positive (ER+) MCF-7 andT47D cells, which probably attribute to the induction of cell cycle arrest in G1 phase and shortened S phase. Further mechanism study showed that ERK1/2 and AKT signaling were required for the activation of AhR in MCF-7 cells. These data suggest that AhR is a potential new target for treating patients with breast cancer. ITE may be more potentially used for therapeutic intervention for breast cancer with the kind of ER(+).
El receptor de hidrocarburo de arilo (AhR) es un factor de transcripción activado por ligando que se expresa en gran medida en varios tipos de cáncer, incluido el cáncer de mama. Sin embargo, el papel de AhR con su ligando endógeno 2- (1'H-indol-3'-carbonil)-tiazol-4-ácido carboxílico metil éster (ITE) en la progresión del cáncer de mama sigue siendo poco conocido. Nuestro objetivo fue investigar la proliferación celular y los estados de migración en el cáncer de mama después de activar AhR con el ligando endógeno ITE. El tejido de cáncer de mama se evaluó mediante líneas celulares, inmunohistoquímica, reacción en cadena de la polimerasa con transcriptasa inversa, proliferación celular, citometría de flujo, ensayos de migración y técnicas de transferencia Western. Descubrimos que AhR se expresó ampliamente en tejidos de cáncer de mama y en linfonodos con metástasis, pero no en tejidos normales. La expresión AhR fue independiente entre la edad, grados y clasificaciones TNM para tejidos de cáncer de mama. El tratamiento con ITE indujo significativamente la activación de AhR de manera dependiente del tiempo en las líneas celulares de cancer de mama MCF-7 y T47D. Mientras tanto, ITE no afectó la migración celular, pero suprimió significativamente la proliferación celular en células MCF-7 y T47D con receptor de estrógeno positivo (ER+), lo que probablemente se atribuye a la inducción de la detención del ciclo celular en la fase G1 y la fase S acortada. Un estudio adicional del mecanismo mostró que las señales de ERK1/2 y AKT eran necesarias para la activación de AhR en las células MCF-7. Estos datos sugieren que AhR es un nuevo objetivo potencial para el tratamiento de pacientes con cáncer de mama. ITE puede ser utilizado más potencialmente en la intervención terapéutica para el cáncer de mama con el tipo de ER (+).
Subject(s)
Humans , Female , Thiazoles/administration & dosage , Breast Neoplasms/pathology , Receptors, Aryl Hydrocarbon/drug effects , Indoles/administration & dosage , Thiazoles/pharmacology , Immunohistochemistry , Receptors, Estrogen , Blotting, Western , Cytochrome P-450 CYP1A1/genetics , Cell Line, Tumor/drug effects , Cell Proliferation/drug effects , Cell Migration Assays , Cytochrome P-450 CYP1B1/genetics , Flow Cytometry , Indoles/pharmacologyABSTRACT
Background: Abnormal uterine bleeding is symptom, not disease. Bleeding per vaginum is labelled to be pathological when there is constant irregularity in pattern and flow of bleeding, altered duration or increased amount of menstrual blood. Histopathological examination of endometrium biopsies remains a gold standard diagnostic tool. Methods: A prospective study was done on 150 patients presenting with AUB over the period January 2022 to December 2022 in the department of pathology, Hind institute of medical sciences, Sitapur, Uttar Pradesh, India. The sections were stained with hematoxylin and eosin and special stain estrogen receptor was used. Results: Majority of the patients were seen in the perimenopausal age group and most common complaint was menorrhagia in 73 patients (48%). The commonest pathology observed in our study was proliferative phase endometrium in 48 patients (32%). Most of the endometrial carcinoma (4%) were presented after the age of 50 years. The association between histopathological patterns and estrogen receptor category were found to be statistically significant as the p<0.05. Conclusions: Disease burden on a global scale is witnessed by women affected by AUB thus having a detrimental impact. Accurate diagnosis of AUB in women over the age of 35yrs is important to rule out preneoplastic lesions and malignancies so that surgical interventions can be avoided by initiating proper medical management. Comparing the hyperplastic and neoplastic endometrium to that of the proliferative phase, ER expression was lower. Endometrial carcinoma with advanced stage often lacks the expression of the receptors.
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Background: Abnormal uterine bleeding is symptom, not disease. Bleeding per vaginum is labelled to be pathological when there is constant irregularity in pattern and flow of bleeding, altered duration or increased amount of menstrual blood. Histopathological examination of endometrium biopsies remains a gold standard diagnostic tool. Methods: A prospective study was done on 150 patients presenting with AUB over the period January 2022 to December 2022 in the department of pathology, Hind institute of medical sciences, Sitapur, Uttar Pradesh, India. The sections were stained with hematoxylin and eosin and special stain estrogen receptor was used. Results: Majority of the patients were seen in the perimenopausal age group and most common complaint was menorrhagia in 73 patients (48%). The commonest pathology observed in our study was proliferative phase endometrium in 48 patients (32%). Most of the endometrial carcinoma (4%) were presented after the age of 50 years. The association between histopathological patterns and estrogen receptor category were found to be statistically significant as the p<0.05. Conclusions: Disease burden on a global scale is witnessed by women affected by AUB thus having a detrimental impact. Accurate diagnosis of AUB in women over the age of 35yrs is important to rule out preneoplastic lesions and malignancies so that surgical interventions can be avoided by initiating proper medical management. Comparing the hyperplastic and neoplastic endometrium to that of the proliferative phase, ER expression was lower. Endometrial carcinoma with advanced stage often lacks the expression of the receptors.
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Background: Gallbladder carcinoma (GBC) although rare is most frequent malignant neoplasm of biliary tract system and sixth most common malignancy of digestive tract. GBC is more common in females and there are studies which show expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 neu (HER2/neu) in GBC suggesting possible molecules for targeted therapy, but results are inconsistent. Aims and Objectives: The aim of this study was to find out expression of ER, PR, and HER2/neu in GBC in North Indian population and their possible association with clinicopathological features. Materials and Methods: A total 59 resected cases of GBC diagnosed by histopathological examination were included in the study. Expression of ER, PR, and HER2/neu was accessed by immunohistochemistry method and correlated with various clinicopathological features. Results: ER expression was absent in all GBC cases. PR expression was present in only one case. Positive expression of HER2/neu was present in 13 (22%) cases, in which 12 cases were of conventional adenocarcinoma and one case was of papillary adenocarcinoma. Well and moderately differentiated tumor had significantly higher HER2/neu expression as compared to poorly differentiated tumors (P = 0.001). Pre-obese patients had significantly higher HER2/neu expression as compared to non-obese patients (P = 0.008). Conclusion: In our study, there was no expression of estrogen and PR in GBC in North Indian population. Although small in number, there is a subset of patients who overexpress HER2/neu receptor that may benefit from targeted therapy.
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OBJECTIVE To analyze the main components of Chelidonii Herba-Corydalis Rhizoma (CHCR), and to predict pharmacodynamic substances against estrogen receptor (ER) -positive breast cancer and their potential targets and signaling pathways, followed by verifying experiments. METHODS The ethanol extract of CHCR was analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS). The network pharmacology analysis was performed for the screened components. The network diagram of CHCR “active components-target-pathway” was constructed, and the enrichment pathway in vitro was validated. RESULTS A total of 58 chemical components were identified, including 57 alkaloids and 1 organic acid. A total of 38 active ingredients were screened from the network pharmacology, and 38 core targets were found in the protein-protein interaction network of “component-disease” intersection targets; 258 gene ontology entries and 137 Kyoto encyclopedia of genes and genomics pathways were obtained, mainly including estrogen signal pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signal pathway, etc. The results of validation test showed that the median inhibitory concentration of CHCR to MCF-7 cells was 693 μg/mL; 150, 300, 600 μg/mL CHCR could significantly reduce the expressions of phosphorylated PI3K, phosphorylated Akt, ERα protein and ESR1 mRNA (P<0.01). CONCLUSIONS The anti-ER-positive breast cancer effect of CHCR may be related to the regulation of ER and PI3K/Akt pathways, which has the characteristics of multi-component and multi-target effects.
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To investigate the cardioprotective effect of formononetin (FMN) on no-reflow (NR) after myocardial ischemia-reperfusion and its molecular mechanism based on integrated pharmacology and experimental verification, firstly, human breast cancer MCF-7 cells and myocardial NR rats were used to confirm the estrogenic activity and the effect of alleviating NR of FMN, respectively. Male SD rats were divided into Sham, NR, FMN (20 mg·kg-1) and sodium nitroprusside (SNP, 5.0 mg·kg-1) groups, which were administered once a day for one week, the experiment was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (TCM-LAEC2019095). The pharmacological analysis and in vivo study of NR rats were integrated to reveal the mechanism of FMN improving NR. The results showed that FMN had estrogenic effect and reduced NR by improving cardiac structure and function, reducing NR, ischemic myocardial area and pathological injury of cardiomyocytes. Integrated pharmacology predicts that the mechanism of FMN improving NR is mainly related to phosphatidyinositol-3-kinase-protein kinase B (PI3K-Akt) signal pathway. Phytoestrogens play a role in cardiovascular protection mainly by activating G protein-coupled estrogen receptor (GPER). GPER is also an important regulator in the upstream of PI3K-Akt signaling pathway. This study found that FMN can significantly activate GPER, p-PI3K, p-Akt and phospho-endothelial nitric oxide synthase (p-eNOS). It has good binding ability with GPER and eNOS protein. In this study, through the integration of pharmacology and experimental evaluation, it is revealed that FMN activates PI3K/Akt/eNOS signal pathway by activating GPER, thus significantly improving NR.
ABSTRACT
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have led transformative breakthrough of clinical therapy for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER-2)-negative breast cancer patients. CDK4/6 inhibitors that have been marketed in China include Ribociclib, Palbociclib, Abemaciclib and Dalpiciclib. For HR-positive HER-2-negative locally advanced and metastatic breast cancer, CDK4/6 inhibitors combined with endocrine therapy have become standard regimen, which can prolong the survival of patients. In the adjuvant treatment stage of early breast cancer, CDK4/6 inhibitors have also achieved positive results and been approved for indications. At present, CDK4/6 inhibitors have been widely used in clinical practice in China. In order to further improve the standardized application of CDK4/6 inhibitors in China, the Breast Cancer Expert Committee of the National Center for Cancer Quality Control and the Professional Committee of Clinical Research of Cancer Drugs of the Chinese Anti-Cancer Association organized the related expert to update the consensus based on the "CDK4/6 inhibitor consensus on clinical application of in the treatment of hormone receptor positive human epidermal growth factor receptor 2 negative advanced breast cancer (2021 edition)" . The updated consensus systematically introduces the pharmacological characteristics, drug monitoring and adverse event management, etc., of CDK4/6 inhibitors to promote the accuracy of clinical decision-making with the ultimate goal to prolong the overall survival of patients and improve the quality of life.
Subject(s)
Humans , Female , Breast Neoplasms/pathology , Quality of Life , Consensus , Triple Negative Breast Neoplasms/drug therapy , Receptor, ErbB-2/metabolism , Protein Kinase Inhibitors , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclin-Dependent Kinase 4/metabolismABSTRACT
Objective:To investigate the relationship between Golgi membrane protein 1 (GOLM1) expression and the sensitivity of estrogen receptor (ER) positive breast cancer to endocrine therapy.Methods:Tamoxifen (TAM) -resistant ER-positive breast cancer cells were established, and the expression of GOLM1 in these cells was detected. The expression level of GOLM1 in the cells was regulated, and the effects of GOLM1 expression on cell proliferation and colony formation were detected by MTT and colony formation assay, respectively. Western blot was used to detect the effect of GOLM1 expression on the expression of drug resistance proteins P-gp and MRP1. Breast cancer patients recruited for endocrine therapy and patients without endocrine therapy were divided into high GOLM1 expression group and low GOLM1 expression group, and the effect of GOLM1 expression level on the survival rate of the two groups of patients was observed.Results:Colony formation assay showed that after TAM treatment, the colony formation ability of TAM-resistant MCF-7 cells was significantly higher than that of TAM-sensitive McF-7 cells (all P<0.05). The expression level of GOLM1 in MCF-7R cells (2.31±0.18) was higher than that in MCF-7 cells (1±0.10) ( t=11.02, P<0.001). Knockdown of GOLM1 in MCF-7R cells decreased the cell proliferation and colony formation ability, and the expression of drug resistance proteins P-gp and MRP1 also decreased (all P<0.05). The survival rate of patients with high GOLM1 expression was lower than that of patients with low GOLM1 expression after endocrine therapy ( χ2=5.45, P=0.020). In patients without endocrine therapy, there was no significant difference in survival between patients with high and low GOLM1 expression ( χ2=1.49, P=0.223) . Conclusion:High expression of GOLM1 is significantly associated with decreased sensitivity to endocrine therapy in ER-positive breast cancer patients.