H-Ras and K-Ras Oncoproteins Induce Different Tumor Spectra When Driven by the Same Regulatory Sequences.

Genetic studies in mice have provided evidence that H-Ras and K-Ras proteins are bioequivalent. However, human tumors display marked differences in the association of RAS oncogenes with tumor type. Thus, to further assess the bioequivalence of oncogenic H-Ras and K-Ras, we replaced the coding region of the murine K-Ras locus with H-RasG12V oncogene sequences. Germline expression of H-RasG12V or K-RasG12V from the K-Ras locus resulted in embryonic lethality. However, expression of these genes in adult mice led to different tumor phenotypes. Whereas H-RasG12V elicited papillomas and hematopoietic tumors, K-RasG12V induced lung tumors and gastric lesions. Pulmonary expression of H-RasG12V created a senescence-like state caused by excessive MAPK signaling. Likewise, H-RasG12V but not K-RasG12V induced senescence in mouse embryonic fibroblasts. Label-free quantitative analysis revealed that minor differences in H-RasG12V expression levels led to drastically different biological outputs, suggesting that subtle differences in MAPK signaling confer nonequivalent functions that influence tumor spectra induced by RAS oncoproteins. Cancer Res; 77(3); 707-18. ©2016 AACR.

Registro Español de Trasplante Cardiaco. XXI Informe Oficial de la Sección de Insuficiencia Cardiaca y Trasplante Cardiaco de la Sociedad Española de Cardiología (1984-2009) / Spanish Heart Transplantation Registry. 21st Official Report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2009)

Introducción y objetivos. El propósito de este artículo es presentar los resultados del trasplante cardiaco desde que se inició esta modalidad terapéutica en España en mayo de 1984. Métodos. Se ha realizado un análisis descriptivo de todos los trasplantes cardiacos realizados hasta el 31 de diciembre de 2009. Resultados. El número total de trasplantes fue de 6.048. El perfil clínico medio del paciente que se trasplantó en España en 2009 fue el de un varón de 53 años, diagnosticado de cardiopatía isquémica no revascularizable con depresión grave de la función ventricular y situación funcional avanzada, al que se implantó un corazón procedente de un donante fallecido por hemorragia cerebral, con una media de edad de 37 años y un tiempo en lista de espera de 106 días. El tiempo medio de supervivencia se ha incrementado con los años. Así, mientras en el total de la serie la probabilidad de supervivencia tras 1, 5, 10 y 15 años es del 78, el 67, el 53 y el 40% respectivamente, en los últimos 5 años la probabilidad de supervivencia tras 1 y 5 años es del 85 y el 73% respectivamente. La causa más frecuente de fallecimiento es el fallo agudo del injerto (17%), seguido de infección (16%), un combinado de enfermedad vascular del injerto y muerte súbita (14%), tumores (12%) y rechazo agudo (8%). Conclusiones. La supervivencia obtenida en España con el trasplante cardiaco, sobre todo en los últimos años, lo sitúa como el tratamiento de elección para cardiopatías irreversibles en situación funcional avanzada y sin otras opciones médicas o quirúrgicas establecidas (AU)

Introduction and objectives. The purpose of this report is to present the results obtained with heart transplantation in Spain from the first use of this therapeutic modality in May 1984. Methods. A descriptive analysis of all heart transplantations performed up to December 31, 2009 is presented. Results. In total, 6048 transplants were carried out. The typical clinical profile of a Spanish heart transplant patient in 2009 was that of a 53-year-old male who had been diagnosed with nonrevascularizable ischemic heart disease and who had severely impaired ventricular function and a poor functional status. The implanted heart typically came from a donor who had died from a brain hemorrhage (mean age 37 years) and the average time on the waiting list was 106 days. Mean survival time has increased progressively over the years. Whereas for the whole time series, the probability of survival at 1, 5, 10 and 15 years was 78%, 67%, 53% and 40%, respectively, for the past 5 years, the probability of survival at 1 and 5 years was 85% and 73%, respectively. The most frequent cause of death was acute graft failure (17%), followed by infection (16%), the combination of graft vascular disease and sudden death (14%), tumor (12%) and acute rejection (8%). Conclusions. The survival rates obtained in Spain with heart transplantation, especially in recent years, make the procedure the treatment of choice for patients who have irreversible heart failure and a poor functional status and for whom there are few other established medical or surgical options (AU)