CD133 expression in circulating tumor cells from breast cancer patients: potential role in resistance to chemotherapy.

CD133 has been associated with cell properties such as self renewal, migration and vasculogenic mimicry, potentially involved in generation of circulating tumor cells (CTCs). We characterized CD133 expression in CTCs of 98 nometastatic breast cancer (BC) patients. CTCs were isolated by immunomagnetic techniques using magnetic beads labeled with a multicytokeratin(CK)-specific antibody (CK3-11D5) and CTCs and CD133 detection through immunocytochemical methods. CK(+) /CD133(+) CTCs were identified in 65% of patients at baseline and 47.8% after systemic therapy (p = 0.53). Correlation of CD133 status in CTCs with classical clinicopathological characteristics and response to therapy was performed. Her2 not amplified and low Ki-67 index were positively correlated with presence of CK(+) /CD133(+) CTCs. Before any treatment, CK(+) /CD133(+) CTCs were more frequently isolated in patients with luminal BC subtype. No statistically significant differences were found between proportion of CK(+) /CD133(+) CTCs and BC subtypes after systemic therapy, implying a relative enrichment of CK(+) /CD133(+) CTCs in triple negative and HER2-amplified tumors. While CK(+) /CTCs decreases after chemotherapy when analyzing the whole population, CK(+) /CD133(+) CTCs were enriched in post-treatment samples in nonluminal BC subtypes. These findings suggest the potential role of CD133 as a promising marker of chemoresistance in nonluminal BC patients. Further prospective studies and extensive preclinical modeling will be needed to confirm whether CD133 is a marker of resistance to chemotherapy, and its role as a target for novel anticancer therapies targeting cancer stem cells and tumor vasculature.

Biomarkers characterization of circulating tumour cells in breast cancer patients.

INTRODUCTION: Increasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcomes of nonmetastatic breast cancer patients. CTCs differ genetically from the primary tumor and may contribute to variations in prognosis and response to therapy. As we start to understand more about the biology of CTCs, we can begin to address how best to treat this form of disease. METHODS: Ninety-eight nonmetastatic breast cancer patients were included in this study. CTCs were isolated by immunomagnetic techniques using magnetic beads labelled with a multi-CK-specific antibody (CK3-11D5) and CTC detection through immunocytochemical methods. Estrogen receptor, progesterone receptor and epidermal growth factor receptor (EGFR) were evaluated by immunofluorescence experiments and HER2 and TOP2A by fluorescence in situ hybridization. We aimed to characterize this set of biomarkers in CTCs and correlate it with clinical-pathological characteristics. RESULTS: Baseline detection rate was 46.9% ≥ 1 CTC/30 ml threshold. CTC-positive cells were more frequent in HER2-negative tumors (p = 0.046). In patients younger than 50 years old, HER2-amplified and G1-G2 tumors had a higher possibility of being nondetectable CTCs. Heterogeneous expression of hormonal receptors (HRs) in samples from the same patients was found. Discordances between HR expression, HER2 and TOP2A status in CTCs and their primary tumor were found in the sequential blood samples. Less that 35% of patients switched their CTC status after receiving chemotherapy. EGFR-positive CTCs were associated with Luminal tumors (p = 0.03). CONCLUSIONS: This is the largest exploratory CTC biomarker analysis in nonmetastatic BC patients. Our study suggests that CTC biomarkers profiles might be useful as a surrogate marker for therapeutic selection and monitoring since heterogeneity of the biomarker distribution in CTCs and the lack of correlation with the primary tumor biomarker status were found. Further exploration of the association between EGFR-positive CTCs and Luminal tumors is warranted.

Women’s Risk Perception and Responses to Intimate Partner Sexual Coercion: The Role of Type of Tactic, Previous Experience, and Myths Acceptance

Sexual coercion is among the subtlest forms of sexual violence in an intimate relationship and sometimes goes unnoticed by victims. The present study analyzed factors that potentially mitigate women’s negative perceptions of intimate partner sexual coercion (IPSC). A total of 427 women completed an online survey, in which they were shown vignettes illustrating a growing risk of sexual coercion according to the perpetrators’ use of different coercive tactics. Participants replied to questions that reflected their risk perception, their perceptions of perpetrator behavior, and the probability of their leaving the relationship. The survey also queried their previous IPSC experience, and their degree of acceptance of sexual aggression myths. According to the results, women exposed to positive (vs. negative) verbal sexual coercion (VSC) condition decided to leave the abusive situation later (risk response), presented a longer time lag between the moment they recognized the risk and the moment they responded to it, perceived the perpetrator’s behavior as more acceptable and excusable, and were less likely to leave the relationship. Finally, greater myth acceptance and previous IPSC experience predicted a lower probability of leaving the relationship, due to delayed risk responses and to perceiving the perpetrator’s behavior as more acceptable and excusable. This was true regardless of the type of coercive tactic used by the perpetrator. The results highlight the need to consider the type of coercive tactic, previous experience, and myths acceptance as risk factors that may impede a woman to adequately perceive and respond to an intimate partner’s sexual violence. (AU)

Modelos probabilísticos de mortalidad para pacientes hospitalizados en unidades convencionales / Probabilistic models of mortality for patients admitted in conventional hospital units

FUNDAMENTO: Se ha desarrollado un instrumento de medida de la gravedad para pacientes hospitalizados en unidades convencionales, adecuado para evaluar y comparar la efectividad y la calidad de la asistencia sanitaria en nuestro entorno. PACIENTES Y MÉTODO: Se ha incluido a 2.274 pacientes adultos ingresados consecutivamente en unidades de hospitalización de los Servicios de Medicina, Cirugía y Cirugía Ortopédica y Traumatológica de la Corporació Sanitària Parc Taulí de Sabadell entre el 1 de noviembre de 1997 y el 30 de septiembre de 1998. Se han recogido variables demográficas, estado de salud previo, hábitos tóxicos, comorbilidades previas al ingreso, características del ingreso, variables clínicas de las primeras 24 h del ingreso, resultados de laboratorio y datos del Conjunto Mínimo Básico de Datos de alta hospitalaria. Se utilizó el análisis de regresión logística múltiple para desarrollar modelos probabilísticos de mortalidad durante la estancia hospitalaria. RESULTADOS: El modelo probabilístico de mortalidad en el momento del ingreso (MPMHOS-0) contiene 7 variables asociadas a la mortalidad durante la estancia hospitalaria: edad, ingreso urgente, insuficiencia cardíaca crónica, insuficiencia respiratoria crónica, hepatopatía crónica, presencia de neoplasia y síndrome demencial. El modelo probabilístico de mortalidad a las 24-48 h del ingreso (MPMHOS-24) contiene 9 variables: las incluidas en el modelo MPMHOS-0 más dos variables de laboratorio que resultaron estadísticamente significativas: hemoglobina y creatinina. CONCLUSIONES: Las medidas de gravedad, en particular las que se presentan en este estudio, pueden ayudar a interpretar las tasas de mortalidad hospitalarias y orientar a los comités de mortalidad o de calidad en la detección de problemas asistenciales (AU)