Antitumor effects of co-treatment of resveratrol with antitumor drugs in ER- and HER2-positive breast cancer cells are due to induction of apoptosis and modulation of estrogen receptor expression.

BACKGROUND: Resveratrol, a natural compound, may be an alternative to improving conventional breast cancer therapy. Thus, we assessed the capability of resveratrol at a low dose to enhance the in vitro effect of conventional theray in estrogen receptor (ER) and human epidermal growth factor receptor type 2 (HER2)-positive breast cancer cells. METHODS: Cell viability of breast cancer cells was measured with neutral red uptake assay. Apoptosis, autophagy, cell cycle progression and cell proliferation were detected through hypotonic fluorescent solution assay, formation of acidic vesicular organelles, flow cytometry, and bromodeoxyuridine assay, respectively. Western blotting was performed to study the expression of pro-apoptotic, anti-apoptotic and autophagic proteins, and estrogen receptors. RESULTS: Resveratrol combined with tamoxifen metabolites or trastuzumab reduced cell viability of ER- and HER2-positive breast cancer cells, respectively. This effect was mainly associated with induction of apoptosis due to a greater formation of hypodiploid nuclei, reduced protein expression of procaspase-7, Bcl-2, Bcl-xL, and PARP; and increased expression of cleaved PARP. Resveratrol decreased the expression of ERα and increased that of ERß, contributing to the reduced viability on breast cancer cells. Combined treatments induced autophagy, evidenced by increased levels of acidic vesicular organelles and degradation of p62/SQSTM1 protein. Nevertheless, on inhibiting autophagy with 3-methyladenine, cell viability was further reduced and apoptosis was induced, suggesting a pro-survival role of autophagy, impairing apoptosis. CONCLUSIONS: Resveratrol increasead the in vitro cytotoxic effect of conventional therapy in breast cancer cells. However, it was necessary to block resveratrol-induced autophagy to improve the therapeutic response.

BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation.

BACKGROUND: Breast cancer is the neoplasm with both the highest incidence and mortality rate among women worldwide. Given the known snake venom cytotoxicity towards several tumor types, we evaluated the effects of BthTX-I from Bothrops jararacussu on MCF7, SKBR3, and MDAMB231 breast cancer cell lines. METHODS: BthTX-I cytotoxicity was determined via MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide assay. Cell death was measured by a hypotonic fluorescent solution method, annexin-V-FITC/propidium iodide staining and by apoptotic/autophagic protein expression. Cancer stem cells (CSCs) were quantified by flow cytometry using anti-CD24-FITC and anti-CD44-APC antibodies and propidium iodide. RESULTS: BthTX-I at 102 µg/mL induced cell death in all cell lines. The toxin induced apoptosis in MCF7, SKBR3, and MDAMB231 in a dose-dependent manner, as confirmed by the increasing number of hypodiploid nuclei. Expression of pro-caspase 3, pro-caspase 8 and Beclin-1 proteins were increased, while the level of the antiapoptotic protein Bcl-2 was diminished in MCF7 cells. BthTX-I changed the staining pattern of CSCs in MDAMB231 cells by increasing expression of CD24 receptors, which mediated cell death. CONCLUSIONS: BthTX-I induces apoptosis and autophagy in all breast cancer cell lines tested and also reduces CSCs subpopulation, which makes it a promising therapeutic alternative for breast cancer.

BthTX-I from Bothrops jararacussu induces apoptosis in human breast cancer cell lines and decreases cancer stem cell subpopulation

Breast cancer is the neoplasm with both the highest incidence and mortality rate among women worldwide. Given the known snake venom cytotoxicity towards several tumor types, we evaluated the effects of BthTX-I from Bothrops jararacussu on MCF7, SKBR3, and MDAMB231 breast cancer cell lines. Methods: BthTX-I cytotoxicity was determined via MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide assay. Cell death was measured by a hypotonic fluorescent solution method, annexin-V-FITC/propidium iodide staining and by apoptotic/autophagic protein expression. Cancer stem cells (CSCs) were quantified by flow cytometry using anti-CD24-FITC and anti-CD44-APC antibodies and propidium iodide. Results: BthTX-I at 102 µg/mL induced cell death in all cell lines. The toxin induced apoptosis in MCF7, SKBR3, and MDAMB231 in a dose-dependent manner, as confirmed by the increasing number of hypodiploid nuclei. Expression of pro-caspase 3, pro-caspase 8 and Beclin-1 proteins were increased, while the level of the antiapoptotic protein Bcl-2 was diminished in MCF7 cells. BthTX-I changed the staining pattern of CSCs in MDAMB231 cells by increasing expression of CD24 receptors, which mediated cell death. Conclusions: BthTX-I induces apoptosis and autophagy in all breast cancer cell lines tested and also reduces CSCs subpopulation, which makes it a promising therapeutic alternative for breast cancer.(AU)

Levantamento de dados de exames de urina rotina, com possível hematúria, realizados no laboratório de Fluidos Orgânicos do Laboratório Central de Patologia Clínica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto- Universidade de São Paulo

Os sistemas biológicos são um conjunto de órgãos funcionais que se relacionam. A integração entre os componentes desses sistemas possibilita a manutenção da homeostase. Neste contexto, tem destaque o sistema renal, que tem como finalidade controlar a quantidade de água e produtos do catabolismo. A função primária do rim é a formação da urina e qualquer anormalidade que ocorrer ao longo do trato urinário e órgãos anexos, pode produzir alterações quantitativas ou qualitativas dos constituintes urinários ou resultar na excreção de elementos anormais, alterando a composição final da urina. Dentre as síndromes nefrológicas, tem destaque a síndrome de anormalidade urinária, também denominada hematúria. Dessa forma, foi realizado um levantamento de dados dos laudos químicos (hemoglobina-automatizado) e sedimentoscópicos (hematúria – manual) do primeiro trimestre de 2014 de todas as urinas recebidas no Setor de Fluidos Orgânicos do Laboratório Central de Patologia Clínica do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Dos 7.297 exames realizados nesse período, verificou-se que 65,5% dos resultados são negativos (não tem Hb), 23,2% são traços, 6,1% são uma cruz, 2,5% são duas cruzes e 2,7% são três cruzes, dando um total de 34,5% positivos na tira reativa. Dos resultados negativos na tira reativa, 86,7% estão dentro do intervalo de referência determinado para a sedimentoscopia, que é de zero a três hemácias por campo. Notou-se que existe uma grande variedade de intervalos para hematúria na sedimentoscopia e que muitas vezes esses resultados se sobrepõem. Intervalos de 1 a 2; 1 a 3 ou 2 a 3 hemácias por campo, não mudam a interpretação do resultado. Sugerimos que estudos futuros sejam feitos para padronizar intervalos adequados. .