RESUMEN
Both cardiotrophin-1 (CT-1) and B-type or brain natriuretic peptide (BNP) are activated by cardiomyocyte stretch, and gene expression of CT-1 and BNP are augmented in the heart in experimental and human congestive heart failure (CHF). The goal of this study was to define cardiac gene expression of CT-1 and BNP by Northern blot analysis in normal (n=5), early left ventricular dysfunction (ELVD, n=5) and overt CHF dogs (n=5), in which ventricular function is progressively decreased. CT-1 mRNA was detected in both atria and ventricles in normal dogs. Ventricular CT-1 mRNA production increased in ELVD, and it further increased in overt CHF. Ventricular BNP mRNA remained below or at the limit of detection in normal and ELVD models, and it markedly increased in overt CHF. This study reports differential regulation of gene expression of CT-1 and BNP in the heart during the progression of CHF, and demonstrates that ventricular CT-1 gene activation precedes ventricular BNP gene activation.
Asunto(s)
Citocinas/genética , Insuficiencia Cardíaca/genética , Ventrículos Cardíacos/metabolismo , Péptido Natriurético Encefálico/genética , Animales , Presión Sanguínea/genética , Modelos Animales de Enfermedad , Perros , Activación Enzimática , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Masculino , ARN Mensajero/análisis , ARN Mensajero/genéticaRESUMEN
OBJECTIVES: Intraductal papillary mucinous tumor (IPMT) is frequently associated with pancreatic cancer. We hypothesized that IPMT progresses to invasive cancer with K-ras mutations as an early event, and that invasive cancer affects survival. We compared survival after resection and determined whether K-ras mutations predicted survival in IPMT patients without or with invasive cancer. METHODS: Records of 47 patients with IPMT who were seen between 1983 and 1998 were reviewed retrospectively in 15 cases and prospectively in 32. All histological material was reviewed to confirm the diagnosis of IPMT and to assess invasion. Kaplan-Meier survival curves were analyzed by the log-rank test. The chi2 test was used for differences in K-ras between groups. RESULTS: There were 30 men and 17 women, with a mean age of 65 yr (range 36-90 yr). Of the patients, 26 had IPMT without invasive cancer and 19 had IPMT with invasion. Tissue diagnosis was available in 45 patients. K-ras was analyzed in 40 patients. Mutations were present in 15 of 23 patients (65%) without invasive cancer and in 14 of 17 patients (82%) with invasive cancer (p = ns). At 2.5 yr, the overall cumulative survival of IPMT patients without invasive cancer was 94% compared to 24% of patients with invasive cancer (p < 0.001). The 5-yr survival of IPMT patients without invasive cancer was 94%. K-ras mutations did not correlate with survival. CONCLUSIONS: Invasive cancer in IPMT reduces the 2.5-yr survival after surgery from 93% to 24%. K-ras mutations occur before invasive cancer, and do not predict postoperative survival.