Electrochemical aptasensor for the detection of HER2 in human serum to assist in the diagnosis of early stage breast cancer.

Human epidermal growth factor receptor-2 (HER2) is an important biomarker in the diagnosis and prognosis of breast cancer. This work aimed to develop an aptasensor to detect HER2 in human serum. HER2 aptamer was immobilized by electrostatic adsorption on the surface of a homemade screen-printed electrode modified with poly-L-lysine. Measurements were made by differential pulse voltammetry using methylene blue as a redox indicator. A calibration curve was constructed (R2 = 0.997) using different concentrations of HER2 protein (10-60 ng/mL) in PBS buffer (pH 7.4), with a detection limit of 3.0 ng/mL. The aptasensor showed good reproducibility with relative standard deviations (RSDs) of 3% and remained stable for 3 days with an RSD around 2%. When the tests were performed with serum from a healthy woman, a peak of 6.72 µA was found without the addition of the protein. When we tested the serum of a woman with HER2+ breast cancer, we obtained a signal of 2.65 µA; the same pattern was found when adding to protein in serum control, i.e., the higher the concentration of protein, the lower the signal. The aptasensor was characterized by scanning electron microscopy and isothermal titration calorimetry (ITC), showing excellent interaction between aptamer and target protein. The results revealed a promising and sensitive tool capable of detecting HER2 protein in human serum with albumin depletion, aiding in the molecular diagnosis of breast cancer. Graphical abstract.

The challenge of determining the impact of FUT3 tumor-associated polymorphism rs2306969 (-6951 C> T) in invasive breast cancer cells.

FUT3 gene is responsible for encode an homonymous α1,3/4-fucosyltransferase involved in the synthesis of sialyl-Lewis antigens. FUT3-fucosylated glycoconjugates play key roles in pathways involved in tumor biology and metastasis, such as cellular ligation to E-selectins, TGF-ß-induced epithelial-mesenchymal transition, NK cell-mediated tumor cytotoxicity and apoptosis. Tumor-associated FUT3 promoter polymorphism rs2306969 (-6951 C> T, position related to the gene's translation start site) has been linked to breast, ovarian and intestinal gastric cancer. Although non-coding polymorphisms accounts for the majority of variations founded in breast cancer, their functional roles are still poorly understood. This study aimed to investigate the impact of different alleles for this variation in FUT3 expression of invasive breast tumors. A luciferase reporter assay was performed using two breast tumor cell lines to evaluate respectively the impact of FUT3 rs2306969 (-6951 CC) and (-6951 TT) on protein expression. Gene and protein expressions were also measured in twenty-nine fresh biopsies of invasive breast tumors. Rs2306969 did not significantly influence FUT3 expression in both used systems. However, this study is defiant since the biological role of this polymorphism in breast cancer and other tumor types could be linked to cis/trans modulation of other genes, respond to different environmental stimuli or impact gene expression only in association with other variations. Rs2306969 did not modulate FUT3 expression in breast tumors under non-stimulated conditions. Nevertheless, our study contributes to the notably challenging task that is to understand how non-coding polymorphisms can drive the overall risk in cancer development.

Avaliação da citotoxicidade da microemulsão contendo o fotossensibilizador ZNPCSO4, sobre cultura de célula de linhagem de câncer de mama / Evaluación de la citotoxicidad de la microemulsión que contiene el fotosensibilizador ZNPCSO4, en la cultura celular del cáncer de mama / Cytotoxicity evaluation of microemulsion containing the photosensibilizer ZNPCSO4, on breast cancer cell culture line

Introdução: O câncer de mama tem alta incidência e mortalidade dentre todos os tipos de câncer e, apesar de todos os avanços tecnológicos recentes,mantém-se ainda como um problema mundial de saúde pública. Novas estratégias terapêuticas, como a Terapia Fotodinâmica, têm sido usadas para tratarvários tipos de tumores de tecidos moles e hiperplasia. Objetivo: Caracterizar o efeito citotóxico da microemulsão contendo zinco ftalocianina tetrasulfonada(ZnPcSO4). Material e Método: A microemulsão (ME) foi preparada por adição da fase aquosa (15%) composta de propilenoglicol e água (3:1), em umamistura de fase oleosa composta pelos surfactantes monooleato de sorbitanol e polissorbato 80 (47%) e óleo de canola (38%). Para o teste de citotoxicidadefoi realizado o ensaio de MTT com as células MCF-7 de adenocarcinoma de mama humana. Resultados: Os baixos valores de condutividade obtidos (0,63e 0,53 para ME com e sem ZnPcSO4, respectivamente) indicaram que a ME era de tipo água/óleo. O diâmetro interno das partículas foi na ordem de 60nmna presença e ausência do ZnPcSO4 sugerindo que a presença do fotossensibilizante não alterou as propriedades do sistema nanoestruturado. O índicede polidispersividade foi menor do que 0,10, enquanto que a carga superfi cial da nanopartícula foi negativa, em concordância com as característicasdos compostos utilizados para o preparo da ME. A atividade metabólica das células não sofreu interferências com as MEs não demonstrando toxicidade...

Introduction: Breast cancer has a high incidence and mortality among all types of cancer and, despite all the recent technological advances, still remains aworldwide public health problem. New therapeutic strategies, such as Photodynamic Therapy, have been used to treat various types of soft tissue tumorsand hyperplasia. Objective: To characterize the cytotoxic effect of the zinc-containing microemulsion containing tetrasulf...

Introducción: El cáncer de mama tiene alta incidencia y mortalidad entre todos los tipos de cáncer y, a pesar de todos los avances tecnológicos recientes,sigue siendo un problema mundial de salud pública. Nuevas estrategias terapéuticas, como la Terapia Fotodinámica, se han utilizado para tratar varios tiposde tumores de tejidos blandos e hiperplasia. Objetivo: Caracterizar el efecto citotóxico de la microemulsión que contiene el cinc ftalocianina tetrasulfonada(ZnPcSO4). Material y método: La microemulsión (ME) fue preparada por adición de la fase acuosa (15%) compuesta de propilenglicol y agua (3: 1), enuna mezcla de fase oleosa compuesta por los surfactantes monooleato de sorbitanol y polisorbato 80 (47%), Y el aceite de canola (38%). Para la pruebade citotoxicidad se realizó el ensayo de MTT con las células MCF-7 de adenocarcinoma de mama humana. Resultados: Los bajos valores de conductividadobtenidos (0,63 y 0,53 para ME con y sin ZnPcSO4, respectivamente)...