Expression of Nrf2 and NF-κB transcription factors in breast cancer and breast fibroadenoma: Insights for a new therapeutic approach.

Background: Cancer and fibroadenoma are the most common breast tumors in women of reproductive age. Nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor kappaB (NF-κB) transcription factor play an important role in the inflammatory process and in cell proliferation. However, few studies have analyzed these markers in breast cancer and fibroadenoma in women of reproductive age. Results: Light microscopy showed a higher concentration of anti-Nrf2 and anti-NF-κB-stained nuclei in breast cancer than in fibroadenoma. The mean percentage of stained nuclei for Nrf2 was 7.12 ± 5.2 and 43.21 ± 19.83 in the control and study groups, respectively (p < 0.0001). The mean percentage of anti-NF-κB was 10.75 ± 7.09 and 56.14 ± 21.19 (mean ± standard deviation) in the control and study groups, respectively (p < 0.0001). Histological grade 3 tumors showed a significantly higher expression of Nrf2 and NF-κB than grade 1 tumors (p < 0.05). Material and methods: This study was approved by the Institutional Review Board of Federal University of Piaui and all patients assigned an inform consent term prior to the study initiation. Nrf2 and NF-κB expression was evaluated by immunohistochemistry in 66 patients, divided into two groups, control (fibroadenoma, n = 36) and study (cancer, n = 30). The data were analyzed using ANOVA test and the statistical significance was established at p < 0.05. Conclusion: Nrf2 and NF-κB expression was significantly higher in breast cancer than in fibroadenoma, in addition to having a greater association with more aggressive tumors.

Expression of matrix metalloproteinase 2 and 9 in breast cancer and breast fibroadenoma: a randomized, double-blind study.

BACKGROUND: Matrix metalloproteinases (MMPs) 2 and 9 may play an important role in cell proliferation and dissemination of cancer. However, few studies have compared the expression of these proteins between breast cancer and fibroadenoma. MATERIAL AND METHODS: A randomized, double-blind study was carried out in 66 premenopausal women, aged 20-49 years, who had been diagnosed with fibroadenoma or breast cancer. The patients were divided into two groups: Group A, control (fibroadenoma, n=36) and Group B, study (cancer, n=30). Immunohistochemical analysis was performed using tissue samples of fibroadenoma and breast cancer to assess MMP-2 and MMP-9 antigen expression. Cells were considered positive if exhibiting brown cytoplasmic staining. Fisher's exact test was used to compare the percentage of cases with cells expressing MMP-2 and MMP-9 in control and study groups (p < 0.05). RESULTS: Light microscopy showed a higher concentration of cells with positive cytoplasmic staining for MMP-2 and MMP-9 expression in breast cancer than in fibroadenoma. The percentage of cases with cells expressing MMP-2 in the control and study groups was 41.67% and 86.11%, respectively (p < 0.0009), whereas the percentage of cases with cells expressing MMP-9 in groups A and B was 66.67% and 93.33%, respectively (p<0.0138). MMP-2 and MMP-9 positive expression was significantly higher in moderately differentiated tumors compared to well and poorly differentiated tumors, p <0.005 and p<0.001, respectively. CONCLUSIONS: The current study shows that MMP-2 and MMP-9 protein expression was significantly higher in the breast cancer than in the fibroadenoma and also in moderately differentiated breast cancer.

A case-control study of Metallothionein-1 expression in breast cancer and breast fibroadenoma.

The overexpression of Metallothionein-1 (MT-1) may play an important role in breast cancer; however, few studies have compared MT-1 expression between breast cancer and fibroadenoma. A cross-sectional controlled study was performed in 66 premenopausal women, aged 20-49 years, who had been histologically diagnosed with breast fibroadenoma or breast cancer. The patients were divided into two groups: group A, control (fibroadenoma, n = 36) and group B, study (breast cancer, n = 30). Immunohistochemistry was performed on tissue samples of fibroadenoma and breast cancer patients to evaluate the expression of metallothionein using an anti-MT-1 polyclonal antibody (rabbit polyclonal anti-metallothionein-Catalog Number biorbyt-orb11042) at a dilution of 1:100. The data were analyzed using NOVA (p < 0.05). Microscopic analysis showed a higher concentration of anti-MT-1-stained nuclei in breast cancer tissues than in fibroadenoma tissues. The mean proportion of cells with anti-MT-1-stained nuclei was 26.93% and 9.10%, respectively, in the study and control groups (p < 0.001). Histological grade 3 tumors showed a significantly higher MT-1 expression than hitological grade 1 (p < 0.05), while breast tumors negative for estrogen-, progesterone- and HER2- receptors had a significantly higher MT-1 expression than positive breast tumors positive for these parameters (p < 0.05). MT-1 protein in women of reproductive age was significantly higher in breast cancer than in fibroadenoma in this study. Furthermore, there was higher MT-1 immunoreactivity in more aggressive tumors.

Review of Polymorphism of the Calcium-Sensing Receptor Gene and Breast Cancer Risk.

Polymorphism of the calcium-sensing receptor gene (CaSR or CaR) has been associated with an increased risk for breast cancer. This receptor plays an important role in calcium homeostasis, and has also been detected in several tissues that are unrelated to calcium metabolism, such as the skin, brain, and breast. The calcium-sensing receptor on cellular level, it regulates cell differentiation, proliferation, cell death, and gene expression. In breast cancer cells, CaSR seems to stimulate secretion of the parathyroid hormone-related protein (PTHrP), which stimulates cellular proliferation. Likewise, some studies have supported not only an association between calcium receptor gene polymorphism and breast cancer risk, but also a higher aggressiveness and unfavorable outcomes in breast cancer, which led us to make a survey in Pubmed on the subject in the last 10 years. Thus, in the literature there is a paucity of studies on the subject and the aim of this review was to show the role of calcium-sensing receptor and its association with breast cancer risk.

Bcl-2 antigen expression in luminal A and triple-negative breast cancer.

Biomarkers for the prognosis of breast cancer have been routinely used in clinical practice, including the expression of hormone receptors, Ki-67 and HER-2. More recently, Bcl-2 has been recognized as an important prognostic factor in breast cancer, although controversies persist with respect to the significance of its expression. The aim of the present study was to evaluate Bcl-2 antigen expression in luminal A and triple-negative breast cancer. Sixty women with invasive ductal carcinoma were included in the study and divided into two groups: Group A (luminal A) and Group B (triple-negative), with 30 cases in each group. Immunohistochemistry was performed on tissue sections to evaluate Bcl-2 antigen expression. Fisher's exact test was used to compare the proportions of cases with cells expressing Bcl-2 between the two subtype cancer groups, with statistical significance being established at p < 0.05. The number of cases with cells expressing Bcl-2 in Groups A and B was 26 (86.7%) and 12 (40.0%), respectively (p < 0.0003). In the present study, the expression of the anti-apoptotic protein Bcl-2 was greater in luminal A breast cancer tissue samples compared to triple-negative breast cancer.

Status do Zinco e sua Relação com Biomarcadores de Risco Cardiovascular / Zinc Status of and its Association to Cardiovascular Risk Biomarkers

Fundamento: A ação antioxidante de alguns nutrientes é importante na proteção vascular. O zinco, em particular, tem sido associado a um risco reduzido de aterosclerose, acidente vascular cerebral e trombose.Objetivo: O estudo avaliou o status do zinco e sua relação com biomarcadores de risco cardiovascular em adultos saudáveis. Métodos: Estudo transversal com 186 estudantes universitários de ambos os sexos, com idades entre 20 e 30 anos, selecionados através de amostra por conveniência. As medições dos biomarcadores de risco cardiovascular incluíram o perfil lipídico, o índice de Castelli I e II e circunferência da cintura. O zinco dietético foi avaliado por registro alimentar de três dias utilizando o programa NutWin versão 1.6.0.7. As concentrações plasmáticas e de eritrócitos do mineral foram determinadas por espectrofotometria de absorção atômica com chama. O perfil lipídico foi determinado pelo método enzimático colorimétrico. Resultados: Os valores médios do consumo de zinco estavam superiores à NME (Necessidade Média Estimada) em ambos os sexos. Os participantes apresentaram concentrações médias de zinco no plasma e eritrócitos inferiores aos pontos de corte. Os valores médios do perfil lipídico, índice de Castelli I e II, e circunferência da cintura estavam adequados. Houve correlação negativa entre o zinco dietético e colesterol total e triglicérides. Conclusões: Os participantes têm uma ingestão elevada de zinco e apresentam concentrações plasmáticas e eritrocitárias reduzidas do mineral. Além disso, esse estudo revelou uma associação negativa entre a ingestão de zinco dietético e o colesterol total e triglicérides, biomarcadores do risco cardiovascular, sugerindo a importância do zinco na proteção contra doenças cardiovasculares

Background: The antioxidant action of some nutrients is important in vascular protection. Zinc, particularly, has been associated with reduced risk of atherosclerosis, stroke and thrombosis. Objective: The study evaluated zinc status and its association to cardiovascular risk biomarkers in healthy adults. Methods: Cross-sectional study with 186 university students of both genders, aged between 20 and 30 years, selected using the convenience sampling method. The cardiovascular risk biomarker measurements included the lipid profile, Castelli index I and II, and waist circumference. Zinc analysis was performed by a three-days food record using NutWin program version 1.6.0.7. Plasma and erythrocyte mineral concentrations were determined by flame atomic absorption spectrophotometry. The lipid profile was determined by enzymatic colorimetric methods. Results: The mean values of zinc intake were higher than the EAR in both genders. Participants had mean plasma and erythrocyte zinc concentrations lower than the cutoff points. The mean values of the lipid profile, Castelli index I and II, and waist circumference were adequate. There was a negative correlation between dietary zinc and total cholesterol and triglycerides. Conclusions: The participants have a high dietary zinc intake and reduced plasma and erythrocyte concentrations of this mineral. Additionally, this study showed a negative association between zinc dietary intake and total cholesterol and triglycerides, biomarkers of cardiovascular risk, suggesting the importance of zinc in protecting against cardiovascular disease

Polimorfismo arg213gly na sod3 e aterogênese / Polymorphism arg213gly in sod3 and atherogenesis

A aterosclerose é uma doença inflamatória crônica de origem multifatorial que ocorre em resposta à agressão endotelial e sua progressão está associada com o aumento das espécies reativas de oxigênio na parede vascular. Interações entre fatores ambientais e genéticos resultam em aumento do risco para essa desordem metabólica. Nesse sentido, estudos clínicos e observacionais têm evidenciado o papel de enzimas antioxidantes na proteção vascular, em particular, a superóxido dismutase 3, uma importante enzima altamente expressa na matriz extracelular dos vasos sanguíneos. A presença do polimorfismo Arg213Gly no gene da SOD3 resulta em prejuízo na ligação dessa enzima com a heparina refletindo em um nível antioxidante reduzido no tecido endotelial, e consequentemente, em um aumento do estresse oxidativo e da oxidação de lipoproteínas nas paredes arteriais. Dessa forma, o estudo tem como objetivo trazer informações atualizadas sobre o papel da SOD3 na proteção vascular e as recentes considerações sobre a presença do polimorfismo Arg213Gly no gene dessa enzima como fator contribuinte para a aterogênese. Realizou-se um levantamento bibliográfico, mediante consulta à base de dados PubMed, Scielo e Lilacs. Diversos estudos têm demonstrado associação entre o polimorfismo Arg213Gly na SOD3 com o aumento do risco cardiovascular, incluindo hipertensão, infarto do miocárdio e acidente vascular cerebral isquêmico, devido à redução da ligação da enzima às células endoteliais com diminuição da sua proteção antioxidante. Nesse sentido, faz-se necessária a realização de novos estudos na perspectiva de esclarecer o papel desse polimorfismo na progressão da aterogênese e no desenvolvimento de doenças cardiovasculares.