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This study aimed to evaluate the effects of the estrogen depression during orthodontic tooth movement on alveolar bone microarchitecture and periodontal ligament. Female Wistar rats were divided into two groups, one consisting of non-ovariectomized animals subjected to orthodontic tooth movement, and one comprising ovariectomized animals subjected to orthodontic tooth movement. Micro-CT assessment of bone volume to total volume (BV/TV), total porosity, trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) in the alveolar bone of the orthodontically moved tooth was performed. Histomorphometric analyses were made in the periodontal ligament, and immunoexpression of RANK, RANKL, OPG, and TUNEL were quantified. Orthodontic tooth movement in the group of ovariectomized rats was faster than in non-ovariectomized animals. The alveolar bone area showed lower values of BV/TV and trabecular thickness, and higher bone porosity and trabeculae numbers in the ovariectomized rats. Histological analyses in the ovariectomized group revealed an increase in collagen fibers in the periodontal ligament. The apoptotic cell counts in the periodontal ligament were higher in the group of ovariectomized rats than in the sham-operated rats. Ovariectomy resulted in an increase in tooth movement and alteration of the alveolar bone microstructure in the first 7 day of orthodontic tooth movement, and in the presence of apoptotic cells in the periodontal ligament.
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A captive marmoset developed metastatic endometrioid carcinoma (EnC), a rare uterine tumor in non-human primates (NHPs). The neoplasm showed marked microscopical malignant and tubulopapillary aspects, immunopositivity for pan-cytokeratin, CK7, estrogen receptor, and a high mitotic index (Ki-67). These features may contribute to the diagnosis and therapeutics of EnC in NHPs.
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Callithrix , Carcinoma Endometrioide , Doenças dos Macacos , Animais , Feminino , Carcinoma Endometrioide/veterinária , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/diagnóstico , Doenças dos Macacos/patologia , Doenças dos Macacos/diagnóstico , Neoplasias Uterinas/veterinária , Neoplasias Uterinas/patologia , Neoplasias Uterinas/diagnósticoRESUMO
OBJECTIVE: To look into the effects of different anesthesia methods on the labor process and the expression of serum estrogen and progesterone in primiparas with painless labor. METHODS: 60 primiparas receiving painless labor were selected as the research objects, and they were divided into either a Spinal & Continuous epidural anesthesia group (n = 30) or a continuous epidural anesthesia group (n = 30), anesthesia is administered using the corresponding anesthesia method. The authors compared serum estrogen and progesterone, inflammatory index expression, pain degree and neonatal health status in different periods. RESULTS: At T2 and T3, serum P, LH, FSH and E2 levels in the Spinal & Continuous epidural anesthesia group were signally lower than those in the Spinal & Continuous epidural anesthesia group (p < 0.05). Spinal & Continuous epidural anesthesia group harbored faster onset and longer duration of sensory block and motor block than the Continuous epidural anesthesia group (p < 0.05). SAS and SDS scores of the Spinal & Continuous epidural anesthesia group were clearly lower than those of the Continuous epidural anesthesia group (p < 0.05). VAS score and serum TNF-α, IL-6 levels of pregnant women in the Spinal & Continuous epidural anesthesia group were memorably lower than those in the Continuous epidural anesthesia group at T2 and T3 (p < 0.05). The total incidence of postoperative complications in the Spinal & Continuous epidural anesthesia group was distinctively lower than that in the Continuous epidural anesthesia group (p < 0.05). CONCLUSION: Spinal anesthesia combined with continuous epidural anesthesia has a better anesthesia effect in the painless labor of primiparas, which can effectually ameliorate the labor process and the expression of serum estrogen and progesterone.
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Anestesia Epidural , Estrogênios , Período Pós-Parto , Progesterona , Humanos , Feminino , Gravidez , Progesterona/sangue , Anestesia Epidural/métodos , Adulto , Estrogênios/sangue , Período Pós-Parto/sangue , Trabalho de Parto/sangue , Raquianestesia/métodos , Anestesia Obstétrica/métodos , Adulto Jovem , Fatores de Tempo , Medição da Dor , Paridade , Interleucina-6/sangue , Fator de Necrose Tumoral alfa/sangueRESUMO
Background: Breast cancer is the leading cause of cancer death among women worldwide. Studies about the genomic landscape of metastatic breast cancer (MBC) have predominantly originated from developed nations. There are still limited data on the molecular epidemiology of MBC in low- and middle-income countries. This study aims to evaluate the prevalence of mutations in the PI3K-AKT pathway and other actionable drivers in estrogen receptor (ER)+/HER2- MBC among Brazilian patients treated at a large institution representative of the nation's demographic diversity. Methods: We conducted a retrospective observational study using laboratory data (OC Precision Medicine). Our study included tumor samples from patients with ER+/HER2- MBC who underwent routine tumor testing from 2020 to 2023 and originated from several Brazilian centers within the Oncoclinicas network. Two distinct next-generation sequencing (NGS) assays were used: GS Focus (23 genes, covering PIK3CA, AKT1, ESR1, ERBB2, BRCA1, BRCA2, PALB2, TP53, but not PTEN) or GS 180 (180 genes, including PTEN, tumor mutation burden [TMB] and microsatellite instability [MSI]). Results: Evaluation of tumor samples from 328 patients was undertaken, mostly (75.6%) with GS Focus. Of these, 69% were primary tumors, while 31% were metastatic lesions. The prevalence of mutations in the PI3K-AKT pathway was 39.3% (95% confidence interval, 33% to 43%), distributed as 37.5% in PIK3CA and 1.8% in AKT1. Stratification by age revealed a higher incidence of mutations in this pathway among patients over 50 (44.5% vs 29.1%, p=0.01). Among the PIK3CA mutations, 78% were canonical (included in the alpelisib companion diagnostic non-NGS test), while the remaining 22% were characterized as non-canonical mutations (identifiable only by NGS test). ESR1 mutations were detected in 6.1%, exhibiting a higher frequency in metastatic samples (15.1% vs 1.3%, p=0.003). Additionally, mutations in BRCA1, BRCA2, or PALB2 were identified in 3.9% of cases, while mutations in ERBB2 were found in 2.1%. No PTEN mutations were detected, nor were TMB high or MSI cases. Conclusion: We describe the genomic landscape of Brazilian patients with ER+/HER2- MBC, in which the somatic mutation profile is comparable to what is described in the literature globally. These data are important for developing precision medicine strategies in this scenario, as well as for health systems management and research initiatives.
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This study had the aim of examining the relationships between variations in estrogen levels resulting from ovariectomy, and estrogen hormone replacement therapy (HRT) in rats subjected to an orofacial inflammatory pain model. Eighty adult female Wistar rats were initially divided into 2 groups: Sham or ovariectomy (OVX-D1). Seven days later (D7), the rats were subjected to an unilateral infiltration of Freund's Complete Adjuvant (CFA) or saline solution into the right temporomandibular joint (TMJ). Then, rats received 17ß-estradiol (28 µg/kg/day) or placebo for 21 days (D10-D31). Nociception was evaluated by the von Frey (VF) and the Hot Plate (HP) tests, and depressive-like behavior by the Forced Swimming (FS) test. On D32 all rats were euthanized and serum, hippocampus and brainstem were collected. The CFA groups presented a mechanical hyperalgesia until day 21 (p ≤ 0.05). No differences were observed among groups in the HP (p = 0.735), and in the immobility and swimming time of the FS (p = 0.800; p = 0.998, respectively). In the brainstem, there was a significant difference in the TNF-É levels (p = 0.043), and a marginal significant difference in BDNF levels (p = 0.054), without differences among groups in the hippocampal BDNF and TNF-É levels (p = 0.232; p = 0.081, respectively). In conclusion, the hormone replacement therapy did not alleviate orofacial pain in ovariectomized rats. However, there is a decrease in brainstem TNF-É levels in the animals submitted to both models, which was partially reverted by HRT.
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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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BACKGROUND: Breast cancer (BC) is the world's largest tumor species in which hormone receptor-positive patients have relatively good prognosis. However, majority of patients will develop late resistance, one of the important factors is due to the loss of the original estrogen receptor (ER) expression. METHODS: We conducted this study in 115 patients with BC who experienced second biopsy at Jiangsu Province Hospital (JSPH) and divided patients into two subgroups ER + to - and ER + to + . First, clinicopathological characteristics between two groups were evaluated. Second, we explored candidate genes related to BC ER intratumor heterogeneity by applying next-generation sequencing (NGS) in 42 patients. Multi-omics integrative analysis of tumor transcriptomic, cancer-related pathway, diagnostic and prognostic value and immune profile were conducted. Besides, preliminary assay were also used to evaluate the correlation between KMT2C and ERα (ESR1) expression. The CCK-8, 5-Ethynyl-2'-deoxyuridine (EdU) assays, Transwell assays and the wound scratch tests were applied to explore the cellular interactions between KMT2C and BC. RESULTS: We find the histological type (p = 0.008) and disease-free survival (DFS) (p = 0.004) were significantly different in two subgroups. In Cox survival analysis, metastasis (Hazard ratio (HR) > 1, p = 0.007) and neo-adjuvant (HR < 1, p < 0.001) are independent prognostic factors of DFS. Besides, by analyzing NGS results, we found four genes KMT2C, FGFR19, FGF1 and FGF4 were highly mutated genes in ER + to - subgroup. Furthermore, the gene KMT2C displayed significant diagnostic value and prognostic value in BC and pan-cancer. In addition, a positive correlation between KMT2C expression and immune infiltrating levels of T cell CD4 + , macrophage and neutrophil was found. In the end, Western blot and RT-qPCR assay were used and found KMT2C and ERα (ESR1) expressions are strongly positive correlated in mRNA and protein level. Inhibition of KMT2C significantly reduced proliferation, invasion, and migration of MCF7 cells. CONCLUSION: People in two cohorts from JSPH presented different clinical characteristics and prognosis. The gene KMT2C may affect the progression of BC by regulating the molecular, epigenetic activity and immune infiltration. It may also serve as a novel prognostic biomarker for BC patients who underwent ER status converted from positive to negative.
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Objectives: This study aimed to evaluate the vagina clinically, cytologically, and histologically before and after treating genitourinary syndrome of menopause (GSM) with fractional microablative carbon dioxide LASER (CO2L), radiofrequency (RF), and estrogen vaginal cream (CT). Methods: Women with moderate-to-severe symptoms of GSM, denoted by a GSM Visual analog scale (VAS) score of >4, were eligible for this study. The patients were randomized into treatment groups. In the energy groups, three vulvovaginal applications were administered monthly. The CT group used 0.5 mg vaginal estriol cream for 14 consecutive days, followed by twice a week for 4 months. The follow-up visits occurred 120 days after the beginning of the treatments. The same parameters obtained at the first visit were re-evaluated: GSM VAS score, Incontinence Quality of Life Questionnaire (I-QOL), gynecological examination determining Vaginal Health Index (VHI), vaginal smear for Vaginal Maturation Value (VMV), and vaginal biopsy. Results: Seventy-one women were included, 48 completed the study and provided adequate samples for analysis (CO2L [21 patients], RF [15 patients], and CT [12 patients]). GSM symptoms, I-QOL, and VHI significantly improved after all proposed treatments, with no significant differences between them. VMV did not change after any treatment; however, only 22.9% of the patients presented with cytological atrophy before treatment. Histological vaginal atrophy was identified in 6 (12.5%) pretreated vaginal samples. After the intervention, all histological parameters were normalized, no tissue damage was observed, and no major clinical complications were observed. Conclusion: CO2L and RF seem to be good alternatives to CT for GSM treatment, with no tissue damage.
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Lasers de Gás , Menopausa , Vagina , Humanos , Feminino , Lasers de Gás/uso terapêutico , Pessoa de Meia-Idade , Vagina/efeitos da radiação , Síndrome , Doenças Urogenitais Femininas/terapia , Qualidade de Vida , Cremes, Espumas e Géis Vaginais/uso terapêutico , IdosoRESUMO
LncRNA is a group of transcripts with a length exceeding 200 nucleotides that contribute to tumour development. Our research group found that LINC00052 expression was repressed during the formation of breast cancer (BC) multicellular spheroids. Intriguingly, LINC00052 precise role in BC remains uncertain. We explored LINC00052 expression in BC patients` RNA samples (TCGA) in silico, as well as in an in-house patient cohort, and inferred its cellular and molecular mechanisms. In vitro studies evaluated LINC00052 relevance in BC cells viability, cell cycle and DNA damage. Results. Bioinformatic RNAseq analysis of BC patients showed that LINC00052 is overexpressed in samples from all BC molecular subtypes. A similar LINC00052 expression pattern was observed in an in-house patient cohort. In addition, higher LINC00052 levels are related to better BC patient´s overall survival. Remarkably, MCF-7 and ZR-75-1 cells treated with estradiol showed increased LINC00052 expression compared to control, while these changes were not observed in MDA-MB-231 cells. In parallel, bioinformatic analyses indicated that LINC00052 influences DNA damage and cell cycle. MCF-7 cells with low LINC00052 levels exhibited increased cellular protection against DNA damage and diminished growth capacity. Furthermore, in cisplatin-resistant MCF-7 cells, LINC00052 expression was downregulated. Conclusion. This work shows that LINC00052 expression is associated with better BC patient survival. Remarkably, LINC00052 expression can be regulated by Estradiol. Additionally, assays suggest that LINC00052 could modulate MCF-7 cells growth and DNA damage repair. Overall, this study highlights the need for further research to unravel LINC00052 molecular mechanisms and potential clinical applications in BC.
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Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante , Feminino , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/genética , Biologia Computacional/métodos , Dano ao DNA , Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica , Células MCF-7 , Prognóstico , RNA Longo não Codificante/genéticaRESUMO
Endothelial cells express multiple receptors mediating estrogen responses; including the G protein-coupled estrogen receptor (GPER). Past studies on nitric oxide (NO) production elicited by estrogens raised the question whether 17-ß-estradiol (E2) and natural phytoestrogens activate equivalent mechanisms. We hypothesized that E2 and phytoestrogens elicit NO production via coupling to distinct intracellular pathways signalling. To this aim, perfusion of E2 and phytoestrogens to the precontracted rat mesentery bed examined vasorelaxation, while fluorescence microscopy on primary endothelial cells cultures quantified single cell NO production determined following 4-amino-5-methylamino-2',7'-difluoroescein diacetate (DAF) incubation. Daidzein (DAI) and genistein (GEN) induced rapid vasodilatation associated to NO production. Multiple estrogen receptor activity was inferred based on the reduction of DAF-NO signals; G-36 (GPER antagonist) reduced 75 % of all estrogen responses, while fulvestrant (selective nuclear receptor antagonist) reduced significantly more the phytoestrogens responses than E2. The joint application of both antagonists abolished the E2 response but not the phytoestrogen-induced DAF-NO signals. Wortmannin or LY-294002 (PI3K inhibitors), reduced by 90% the E2-evoked signal while altering significantly less the DAI-induced response. In contrast, H-89 (PKA inhibitor), elicited a 23% reduction of the E2-induced signal while blocking 80% of the DAI-induced response. Desmethylxestospongin-B (IP3 receptor antagonist), decreased to equal extent the E2 or the DAI-induced signal. Epidermal growth factor (EGF) induced NO production, cell treatment with AG-1478, an EGF receptor kinase inhibitor reduced 90% DAI-induced response while only 53% the E2-induced signals; highlighting GPER induced EGF receptor trans-modulation. Receptor functional selectivity may explain distinct signalling pathways mediated by E2 and phytoestrogens.