Human papillomavirus type 18 E5 oncoprotein cooperates with E6 and E7 in promoting cell viability and invasion and in modulating the cellular redox state

BACKGROUND High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer. Among them, types 16 and 18 are the most prevalent worldwide. The HPV genome encodes three oncoproteins (E5, E6, and E7) that possess a high transformation potential in culture cells when transduced simultaneously. In the present study, we analysed how these oncoproteins cooperate to boost key cancer cell features such as uncontrolled cell proliferation, invasion potential, and cellular redox state imbalance. Oxidative stress is known to contribute to the carcinogenic process, as reactive oxygen species (ROS) constitute a potentially harmful by-product of many cellular reactions, and an efficient clearance mechanism is therefore required. Cells infected with HR-HPVs can adapt to oxidative stress conditions by upregulating the formation of endogenous antioxidants such as catalase, glutathione (GSH), and peroxiredoxin (PRX). OBJECTIVES The primary aim of this work was to study how these oncoproteins cooperate to promote the development of certain cancer cell features such as uncontrolled cell proliferation, invasion potential, and oxidative stress that are known to aid in the carcinogenic process. METHODS To perform this study, we generated three different HaCaT cell lines using retroviral transduction that stably expressed combinations of HPV-18 oncogenes that included HaCaT E5-18, HaCaT E6/E7-18, and HaCaT E5/E6/E7-18. FINDINGS Our results revealed a statistically significant increment in cell viability as measured by MTT assay, cell proliferation, and invasion assays in the cell line containing the three viral oncogenes. Additionally, we observed that cells expressing HPV-18 E5/E6/E7 exhibited a decrease in catalase activity and a significant augmentation of GSH and PRX1 levels relative to those of E5, E6/E7, and HaCaT cells. MAIN CONCLUSIONS This study demonstrates for the first time that HPV-18 E5, E6, and E7 oncoproteins can cooperate to enhance malignant transformation.

Evaluacion de la atencion al paciente diabetico en el nivel primario de salud. Municipio Playa, 1991 / Assessment of medical care for the diabetic patients at primary health

Se selecciono una muestra representativa de los diabeticos con 15 anos de edad o mas, residentes en el municipio Playa y dispenzarizados hasta el 31 de diciembre de 1990, en sus areas de salud, para conocer la calidady el nivel de satisfaccion de la poblacion por nuestros servicios. Se estudiaron584 pacientes, el 80 por ciento utilizaba los servicios de atencion primaria habitualmente. El 62,2 por ciento refirio no haber recibido cursos o instrucciones sobre la enfermedad. El 65 por ciento visito al medico por lo menos 3 veces al ano. El 77 por ciento considero adecuada la atencion recibida, mientras que 1 de cada 5 pacientes no compartio este criterio. Uno de cada 3 pacientes planteo dificultades para obtener cuidados para su diabetes y el 84,2 por ciento refirio satisfaccion con los servicios de salud. Respecto al examen minimo en cada consulta de seguimiento, el 76,5 por ciento refirio que nunca los examinaron con oftalmoscopio, al 44,4 por ciento nunca lo pesaron, al 40,3 nunca le revisaron los resultados de Benedict y al 55, 6 por ciento nunca le examinaron los pies, sin medias. La revision de las historias clinicas evidencio que el 24 por ciento no tenia ningun control reflejado en el ano analizado y en el resto, los porcentajes defondo de ojo, glicemia, examen de miembros inferiores y ECG, entre otros fueron muy bajos