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- ItemSomente MetadadadosAção Do Inibidor De Tripsina Isolado De Sementes De Enterolobium Contortisiliquum Sobre A Linhagem De Células De Câncer De Mama Mda-Mb-231(Universidade Federal de São Paulo (UNIFESP), 2017-08-31) Lobo, Yara Aparecida [UNIFESP]; Oliva, Maria Luiza Vilela [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Breast cancer is the most frequent type among women and one of the leading causes of death in the world. MOA-MB-231 is a hormone-independent human breast cancer cells and has least favorable prognosis. In tumor progression, the activity of proteinases is involved in the cellular processes of proliferation, invasion and metastasis, so inhibitors of these enzymes have emerged as potential therapeutic targets. EcTI is a Kunitz-type serine proteinases inhibitor isolated from Enterolobium contortisiliquum seeds with effective antitumor action on several cell lines. The objective of this study was to evaluate the action of EcTI on the breast cancer MOA-MB-231 cellline. The EcTI was tested on cell viability, proliferation, adhesion, migration and invasion and the understanding of its effect investigated by the expression of integrins, cytokines and proteolytic enzymes, as well as cell signaling. The inhibitor blocked adhesion of these cells to collagen I (reduction - 30%) as well as migration (60%) and invasion (70%), inhibited the expression of a6 and [34 integrin subunits decreasing the phosphorylation of FAK and ERK and Akt, pathways related to cell proliferation, survival, adhesion, migration, and invasion. In addition, IL-6 and consequently, NFKB, overexpressed in cancer, IL-8 'cytokine, involved in survival and metastasis processes, and proliferation-related cytokine TGF-a, were decreased. Regarding to proteinase expression, the EcTI decreases the TPSA and MCP-1, which participate in the degradation of the ECM. Finally, the EcTI increased the content of heparan and chondroitin sulfate. Although the mechanism involved in this process has not yet been elucidated, the effect suggests that the increase of this proteoglycan may have amplified the adhesive process of MOA - MB - 231 cells, decreasinq the metastatic potential. In this way, EcTI is able to interfere in the complex triple negative cell signaling system, being an important instrument for understanding the structural requirements involved in establishing the aggressiveness of this type of tumor, indicating that this protein may contribute to the understanding of the tumor etiology.
- ItemAcesso aberto (Open Access)Avaliação da satisfação e da qualidade de vida na paciente submetida ao tratamento cirúrgico de câncer de mama pelo questionário Breast-Q(Universidade Federal de São Paulo (UNIFESP), 2021) Okajima, Karina Helena [UNIFESP]; Nazario, Afonso Celso Pinto [UNIFESP]; Universidade Federal de São PauloIntroduction: The Breast-Q is an instrument for evaluating the opinion of the patient through the answers to the questionnaire of the module corresponding to the type of surgery applied for the treatment of breast cancer. Objective: To compare psychological well-being, satisfaction and sexual well-being between groups of patients who underwent mastectomy and breast-conserving surgery using the Breast-Q questionnaire. Methods: Participants in this prospective study were women (aged 18 to 81 years) diagnosed with invasive or in situ breast carcinoma. All selected patients underwent mastectomy (MT) or breast-conserving surgery (QDT) between January 2018 and January 2019 and were invited to complete the BREAST-Q questionnaire module before and up to one month after surgery. We compared the mean difference before and after surgery between the MT and QDT groups using the Wilcoxon test. Inclusion criteria were women over the age of 18 with no prior history of surgery or breast cancer. Results: Breast-Q was applied to 73 women (34 MT, 39 QDT). The mean age was 54 ± 15 years for the TM group and 60 ± 12 years for the QDT group (p=0.08). Patients undergoing QDT group reported better psychosocial well-being when compared to the MT group (8.6 ± 27 vs. – 15 ± 25, respectively, p=0.008). There was a trend towards greater satisfaction with the breasts in the QDT group when compared to the MT group (-6.7 ± 24 vs. – 25 ± 34, respectively, p=0.06). There was no difference between the groups in terms of physical well-being (p=0.6) and sexual well-being (p=0.4). Conclusion: The Breast-Q questionnaire is a valuable tool to qualify patient satisfaction in breast cancer surgery. Conservative surgery was superior to mastectomy for psychosocial well-being and with a tendency towards greater satisfaction with the breasts.
- ItemAcesso aberto (Open Access)Avaliação de marcadores cardíacos em pacientes com câncer de mama recebendo tratamento antineoplásico: uma revisão sistemática(Universidade Federal de São Paulo (UNIFESP), 2021) Soares, Tiago Nunes Da Silva [UNIFESP]; Pereira, Edimar Cristiano [UNIFESP]; Universidade Federal de São PauloCardiac markers are important biochemical indicators in the diagnosis of heart and coronary insufficiency, and it is through them that we can measure the damage to cardiac fibers resulting from these diseases. Recent research has shown that the levels of these biomarkers are altered in individuals who have neoplasms under chemotherapy treatment without these patients having any clinical manifestations. It is also known that one of the main adverse effects in treatment with antineoplastic agents is cardiotoxicity. The objective of this work was to carry out a systematic review of the main cardiac biomolecular markers in scientific publications bases and to verify how their levels present in individuals with breast cancer, as well as to analyze the influence of antineoplastic treatment in the circular levels of these markers as a resulting from the effects of cardiac damage on patient therapy and which are good predictors of cardiovascular diseases related to chemotherapy treatment. For this, three databases were used, namely: Medline, Lilacs and Cochrane. In these databases, systematic searches of publications were carried out between the years 2010 and 2020 using the descriptors "Mesh" or the equivalent in the chosen database. After searching the scientific publication in the databases, the duplicates were removed and the other publications were selected against the following eligibility criteria: studies only with breast cancer patients who received any type of chemotherapy treatment; studies that evaluated the following cardiac biomarkers: Troponin, pro-BNP / NT-pro-BNP, myoglobin, CK-MB, fibrinogen, and D-dimer; publications which the study design were clinical trials or observational studies; articles available in English, Spanish or Portuguese language. At the end, 31 published articles were obtained for analysis in which cardiac markers ultra-sensitive Troponin I and T, myoglobin, and NT-proBNP showed to be the best predictors of cardiotoxicity for breast cancer patient under chemotherapy.
- ItemAcesso aberto (Open Access)Avaliação do prognóstico em pacientes com carcinoma de mama invasivo e linfonodo sentinela axilar metastático tratadas com e sem linfonodectomia axilar(Universidade Federal de São Paulo (UNIFESP), 2020-11-17) Ferreira, Vanessa Monteiro Sanvido [UNIFESP]; Nazario, Afonso Celso Pinto [UNIFESP]; Universidade Federal de São PauloObjective: To evaluate the overall survival and locoregional recurrence in patients with sentinel lymph node (SLN) metastatic from breast cancer with or without complete axillary lymph node dissection (ALND). Methods: This is a case-control study evaluated patients with primary invasive breast cancer and clinically negative axilla who underwent lumpectomy and sentinel lymph node dissection (SLND), from February 2008 to December 2018. Patients with metastatic SLN were treated with SLND alone or ALND. Results: A total of 415 patients were included in this study, 23.3% (97 patients) were identified as metastatic SLN, 56 patients were treated with SLND only and 41 patients with ALND. The groups were homogeneous in relation to the variables: age group (50 years versus 51 years and over) (p = 0.279), race (p = 0.120), level of education (p = 0.142), pathological diagnosis (p = 0.210), histological grade (p = 0.983), hormonal receptors (p = 0.708), HER2 status (p = 0.695), pT (p = 0.334). Average age was 58.3 years (SLND) and 56.3 years (ALND), p = 0.456; and average tumor size was 1.8 cm (SLND) and 2.2 cm (ALND), p = 0.048. The ALND group had greater axillary involvement as evidenced by axillary pathological staging, with N1 (73.2%), N2 (19.5%), N3 (4.9%) and SLND group with N1 (62.5%) and no cases N2 or N3 (p <0.001). The 5-year survival was 80.1% in the SLND and 87.5% in the ALND (p = 0.376). The locoregional recurrence was a rare event, average time of 5 years was 1.8% SLND and 7.7% ALND (p = 0.196). Only 4 locoregional recurrences were described and all occurred within 18 months of follow-up. The intraoperative assessment before ACOSOG Z0011 was 90.2% and after ACOSOG Z0011 was 30.8%(p<0,00001). Additionally, the second surgical procedure for ACOSOG Z0011 exclusion criteria occurred only in 3.8% of cases. Conclusions: Overall survival and locoregional recurrence in patients with metastatic axillary sentinel lymph node treated with SLND alone did not differ from those who underwent ALND, corroborating ACOSOG Z0011 data. The omission of axillary lymph node dissection and the implementation of this practice in our service benefited the patients treated with less aggressive surgeries and, potentially, produces lower morbidity.
- ItemSomente MetadadadosComo Reduzir O Número De Bi-Rads" 3 Na Ultrassonografia De Mamas.(Universidade Federal de São Paulo (UNIFESP), 2018-02-22) Ramos, Igor Rodrigues [UNIFESP]; Mello, Giselle Guedes Netto De [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Breast Cancer Is The Leading Cause Of Cancer Death, Among Women. Imaging Methods Have Become Essential For Cancer Screening. Mammary Ultrasonography Has Its Use Diffused Mainly In The Complementation Of Inconclusive Mammograms And In Women With Risk Factors Important For Breast Cancer. The Bi-Rads 3 Category Rating "Probably Benign" Was Implemented To Reduce The Number Of Biopsies To Findings, Maintaining A High Rate Of Cancer Detection In Early Stage. Radiologists Commonly Find Lesions That Are Probably Benign During The Daily Ultrasound Examinations Of The Breast. Some Studies Have Shown That Incidence Of Probably Benign Lesions In Breast Ultrasound Screening Can Be As High As 36.9% And 33.6% In The General Population. For All Findings Evaluated As Likely To Be Benign On Ultrasound, The Follow-Up Protocol Must Be Identical To That Used For Mammographically Characterized Lesions, Involving Follow-Up Examinations At 6, 12 And 24 Months, Considering Lesions Of Bi-Rads Classification 3: Ovoid And Circumscribed
- ItemSomente MetadadadosEstudo Do P16Ink4A Em Carcinoma Espinocelular De Orofaringe E Cavidade Oral Para Pesquisa Do Hpv(Universidade Federal de São Paulo (UNIFESP), 2017-09-28) Greggio, Barbara [UNIFESP]; Abrahão, Marcio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objective: To describe the presence of HPV, in its active form, in squamous cell carcinoma of the oropharynx and oral cavity, by the study of the expression of the p16INK4a protein in immunohistochemical panel, and to relate it to smoking and alcoholism. Method: We selected 46 patients with oral cavity or oropharyngeal carcinoma, that were submitted to surgical treatment between 2014 and 2016. Of the 46 patients studied, 37 were male and 9 were female. Thirty-four patients had oral cavity carcinoma and 12 had oropharynx carcinoma. The 46 paraffin-embedded tumors tissues were analyzed in an immunhistochemistry panel for p16INK4a expression to study the presence of HPV infection in those samples. Results: HPV was present in 6 patients by the immunohistochemistry study of p16INK4a, representing 13.04% among the 46 patients. Among all the male patients, HPV was present in 10.81%. Among the female patients, it was present in 22.22%. Of the 34 patients with tumor in the oral cavity, HPV was present in 4. Of the 12 patients with oropharyngeal tumor, HPV was present in 2. Of all 11 non-smoking and non-alcoholic patients, HPV was present in 3. Among the 10 smoking patients , HPV was found in 1 and among the 25 alcoholic and smoking patients, HPV presented positivity in 2. Conclusion: The presence of HPV in squamous cell carcinoma of the oropharynx and oral cavity by the immunohistochemistry study of p16INK4a was 13.04% . Among the oral cavity tumors, this presence of HPV was 11.76% and in oropharyngeal tumors this presence was 16.66%. In the group of non-smokers and non-alcoholic patients, HPV was present in 27.27%. In smokers and alcohol users, it was present in 8% and in smokers, it was present in 10%.
- ItemSomente MetadadadosExpressão de epimerase de dermatam sulfato em linhagens de câncer de mama(Universidade Federal de São Paulo (UNIFESP), 2019-05-30) Xavier, Everton Galvao [UNIFESP]; Toma, Leny [UNIFESP]; Pinhal, Maria Aparecida Silva; http://lattes.cnpq.br/7511274763693292; http://lattes.cnpq.br/3669434753963813; http://lattes.cnpq.br/9368844129427591; Universidade Federal de São Paulo (UNIFESP)Breast cancer is one of the most incident cancers in the world population, especially in the female population. Estimates show that more than 1.7 million new cases are registered each year and 522,000 are killed. By the year 2050, more than 3.2 million new cases of this pathology are expected to be registered. Proteoglycans are macromolecules that contain a protein core, to which glycosaminoglycan chains (GAGs) are attached covalently. Dermatan sulfate (DS) is a GAG produced by the epimerization of glucuronic acid from chondroitin sulfate to iduronic acid (IduA) by the enzyme epimerase (epiDS). Several studies have shown that proteoglycans containing DS play an important role in tumorigenic processes. This is mainly due to the flexibility that the presence of IduA confers to the polysaccharide chain, allowing specific interactions with proteins, such as growth factors, among other molecule. Studies also show that EpiDS-1 is highly expressed in many tumors, especially esophageal squamous cell carcinoma. The aim of this study was to analyze the expression of epiDS in cell lines that characterize different types of breast cancer MCF-7 (Luminal A), MDA-MB-231 (Triple Negative) and SKBR-3 (HER2). The gene expression of the enzyme was performed by qPCR and the protein content was analyzed by flow cytometry and immunofluorescence. Cell viability was investigated by MTT assay and GAG profile analyzed by radioactive sulfate labeling and electrophoresis. Our results showed that the SKBR-3 cell line presented a pattern of increased cell viability compared to MCF-7 and MDA-MB231cells. Furthermore, SKBR-3 cells presented higher gene expression of the epiDS enzyme and higher 35S-DS content. Curiously, Immunofluorescence assays with specific epimerase (epiDS) antibodies demonstrated greater labeling in the MCF-7 cell line compared to the other cells. We observed that SKBR-3 cells presented epiDS preferably in the form of vesicles and in the perinuclear compartment, suggesting a location in the Golgi Complex, contrasting with the cytoplasm localization in MCF-7 and MDA-MB231 cells. In these cells, the cytoplasm location of the EpiDS enzyme probably compromised the formation of DS chains, but the core protein was able to be detected by the decorin antibody. Golgispecific labeling confirmed the localization of EpiDS in SKBR-3 cells at the Golgi Complex, evidencing that the location was determinant for the synthesis of dermatan sulfate in this lineage, and possibly the dermatan sulfate plays a decisive role in the cellular viability observed.
- ItemSomente MetadadadosRelação Entre Os Polimorfismos Pvuii E Xbai Do Gene Do Receptor De Estrogênio Alfa Com A Densidade Mamográfica Em Mulheres Após A Menopausa(Universidade Federal de São Paulo (UNIFESP), 2017-11-30) Baldisserotto, Fernanda Della Giustina [UNIFESP]; Nazario, Afonso Celso Pinto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Assess the relation between the presence of PVUII and XBAI polymorphisms in the estrogen receptor alpha gene and marrtmographic density in postmenopausal women. Methods For the present analysis, 189 postmenopausal women who had never used hormonal therapy and who did not have clinicai or mammographic features were selected. Based on the ACR-BIRAOS® 2003 classification, the mammographic density was determined by three independent readers (two subjective ratings and one computerized - Adobe Photoshop ® 7.0 software). Blood samples were available to extract DNA according to KIT GFX ® protocol. PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) was then used to identify the pc[ymorphisms. Results There was a high degree of agreement amoní; the trree readers to determine the mammographic density (Kappa>0.75). Sixty women (32%) had dense breasts and 129 (68%) had non-dense breasfci. The PVUII polymorphism was found in 132 (69.8%) of 189 women, while the XBAI was found in 135 (71.4%) of women. Parity (p=0.02) and body mass inaex (p<0.0001) were associated with mammographic density. It was observed that for the XBAI polymorphism, women with two mutated alleles were approximately 25 times more likely to be classified in dense breasts group (p=0.003) and the presence of both wild alleles was associated with fibroglandular tissue replacement by fat (p=0.02). Conclusions: There was no significant association of the PVLII polymorphism in the estrogen receptor alpha gene with mammograohic density (p=0.34). However, the XBAI polymorphism was observed at a higher mutated homozygous frequency in women with dense breasts and th are wau an increased frequency of wild-type homozygous and heterozygous vjomen with fat-replaced breasts (p=0.01).
- ItemSomente MetadadadosRessonância Magnética Com Contraste Dinâmico Como Ferramenta Complementar Para A Avaliação De Calcificações Bi-Rads 4(Universidade Federal de São Paulo (UNIFESP), 2017-11-30) Zacarias, Marina Silva [UNIFESP]; Lederman, Henrique Manoel [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Breast cancer is the second most common neoplasm in the world among women, with an average estimate of 22% of new cases each year. According to the National Institute of Cancer José Alencar Gomes da Silva (INCA), the estimate for 2014 is 57120 new cases with 13345 deaths, 13225 women and 120 men (1). Due to the limitations in the primary prevention of breast cancer applicable to the population in general, the technological advances have been directed to its early diagnosis, once that in the early stages or in the noninvasive form, this disease has a good chance of cure, with a 5-year survival rate of 98% (2). As a result, tracking programs have emerged, the main role of which is to reduction of breast cancer mortality through the detection of early-stage cancer in asymptomatic women, ie without clinical signs that can be detected in self-examination or clinical examination. As a secondary result, there is an increase in survival due to the disease and reduction of surgical treatment extension, allowing less mutilating surgeries, as well as as reducing the need for chemotherapy (3). Despite the significant increase in the number of new cases both in developed countries, mortality rates are in decline in populations under regular programs of screening (4,5). These programs chose to adopt mammography as the method of which is considered the most sensitive method to detect breast cancer in the pre-clinical phase (6). The most important mammographic finding for screening is calcification. She may represent the only sign of malignancy, the first finding being in about 70% of ductal carcinomas in situ (DCIS) detected in screening tests (7). Histologically, these represent intraductal calcifications in areas of necrotic tumor or calcifications mucin secreting tumors, such as the cribriform or micropapillary subtype of intraductal cancer (8-10). The radiological appearance of suspected calcifications includes amorphous, coarse and heterogenous and fine pleomorphic with or without a linear branching pattern (2,7,8). Branched linear calcifications have a higher predictive value for malignancy than nonlinear calcifications, especially for high grade DCIS. Unfortunately, cancer of the breast, including CDIS, most often presents as granular, overlapping 6 with benign findings, which reduces the specificity of mammography (10% to 60%) and results in in the detection of a large number of calcifications that require a complementary examination (7,10). The mammographic aspect just can not differentiate between breast cancers invasive ductal carcinomas, because there is no invasion of the basement membrane. In addition, the method may be limited in the assessment of the extension of the disease, due to areas of the tumor without calcification in the interior (11,12). Due to the fact that some areas of these tumors are not calcified, several studies report changes in therapeutic planning in 11% to 15% of cases when mammography to another imaging method, evidencing additional foci of malignancy not detectable mammographically in about 27% to 34% of the cases (4,11,13). In this scenario, magnetic resonance imaging (MRI) complement the mammographic evaluation (11,13,14). Recent studies have shown that the magnetic resonance imaging of the breast with intravenous contrast injection has sensitivity exceptional for the diagnosis of invasive carcinoma (88% - 100%) (13,15,16). For another To date, there has been no agreement on the sensitivity and specificity of magnetic resonance imaging for the detection of CDIS; although cases of DCIS detected only in MRI have been reported, the role of magnetic resonance imaging in the characterization of suspect calcifications remains a controversial subject (13,17).