Methylation of CpG dinucleotides and/or CCWGG motifs at the promoter of TP53 correlates with decreased gene expression in a subset of acute lymphoblastic leukemia patients

It has been shown that methylation of CpG dinucleotides located in the promoter region of TP53 is associated with low expression levels of this gene. We have analysed the methylation status of one CpG dinucleotide and of three CCWGG motifs, also located in the promoter region of the gene, in bone marrow samples obtained from patients with acute lymphoblastic leukemia (ALL). Eight out of 25 samples analysed showed methylation of either the CpG dinucleotide, the CCWGG motifs or both. Relative to nonmethylated leukemia samples, TP53 expression levels were decreased in all methylated samples in which TP53 expression could be measured. Methylation of CpG and CCWGG motifs in the promoter of TP53 could represent a novel mechanism leading to functional impairment of this tumor suppressor gene in ALL.     

Lack of CpG island methylator phenotype defines a clinical subtype of T-cell acute lymphoblastic leukemia associated with good prognosis.

PURPOSE: To examine cancer genes undergoing epigenetic inactivation in a set of T-cell acute lymphoblastic leukemias (T-ALLs) to obtain the CpG island methylator phenotype (CIMP) in the disease and its possible correlation with clinical features and outcome of the patients. PATIENTS AND METHODS: Methylation-specific polymerase chain reaction was used to analyze methylation of the ADAMTS-1, ADAMTS-5, APAF-1, ASPP-1, CDH1, CDH13, DAPK, DIABLO, DKK-3, LATS-1, LATS-2, NES-1, p14, p15, p16, p57, p73, PARK-2, PTEN, sFRP1/2/4/5, SHP-1, SYK, TMS-1, and WIF-1 genes in samples from 50 consecutive T-ALL patients (19 children and 31 adults). Results were compared with results obtained in 286 B-cell acute lymphoblastic leukemias (B-ALLs). RESULTS: A total of 88% of the T-ALL samples had at least one gene methylated. According to the number of methylated genes observed in each individual sample, 12 patients (24%) were included in the CIMP- group (zero to two methylated genes), and 38 patients (76%) were included in the CIMP+ group (> two methylated genes). Clinical features and remission rate did not differ significantly among both groups of patients. Estimated disease-free survival (DFS) rate at 12 years and overall survival (OS) rate at 13 years were 100% and 91% for the CIMP- group and 20% and 17% for the CIMP+ group, respectively (P = .0006 and P = .003, respectively). Multivariate analysis demonstrated that methylation profile was an independent prognostic factor in predicting DFS (P = .05) and OS (P = .02). A group of five genes (SYK-1, ASPP-1, sFRP-2, sFRP-5, and WIF-1) showed specificity for T-ALL compared with B-ALL. CONCLUSION: Our results suggest that the methylation profile may be a potential new biomarker of risk prediction in T-ALL.     

Recent advances and new insights in the management of early-stage epidermal growth factor receptor-mutated non-small-cell lung cancer

Patients with early-stage non-small-cell lung cancer (NSCLC) are candidates for curative surgery; however, despite multiple advances in lung cancer management, recurrence rates remain high. Adjuvant chemotherapy has been demonstrated to significantly prolong overall survival (OS), but this benefit is modest and there is an urgent need for effective new therapies to provide a cure for more patients. The high efficacy of tyrosine kinase inhibitors (TKIs) against epidermal growth factor receptor-mutated (EGFR) in patients with advanced EGFR-mutated NSCLC has led to the evaluation of these agents in early stages of the disease. Multiple clinical trials have evaluated the safety and efficacy of EGFR TKIs as an adjuvant treatment, in patients with resected EGFR-mutated NSCLC, and shown that they significantly prolong disease-free survival (DFS), but this benefit does not translate to OS. Recently, an interim analysis of the ADAURA trial demonstrated that, surprisingly, osimertinib improved DFS. This led to the study being stopped early, leaving many unanswered questions about its potential effect on OS and its incorporation as a standard adjuvant treatment in this patient subgroup. These targeted agents are also being evaluated in locally-advanced disease, with promising results, although prospective studies with larger sample sizes are needed to confirm these results. In this article, we review the most relevant studies on the role of EGFR TKIs in the management of early-stage EGFR-mutated NSCLC.     

Effect of influenza vaccine status on winter mortality in Spanish community-dwelling elderly people during 2002-2005 influenza periods

This study assessed the relationship between the reception of conventional inactivated influenza vaccine and winter mortality in a prospective cohort that included 11,240 Spanish community-dwelling elderly individuals followed from January 2002 to April 2005. Annual influenza vaccine status was a time-varying condition and primary outcome was all-cause death during study period. Multivariable Cox proportional-hazard models adjusted by age, sex and co-morbidity were used to evaluate vaccine effectiveness. Influenza vaccination was associated with a significant reduction of 23% in winter mortality risk during overall influenza periods. The attributable mortality risk in non-vaccinated people was 24 deaths per 100,000 persons-week within influenza periods, the prevented fraction for the population was 14%, and one death was prevented for every 239 annual vaccinations (ranging from 144 in Winter 2005 to 1748 in Winter 2002).     

Trends in smoking and alcohol consumption among nursing students

ObjectiveTo determine trends in smoking and alcohol consumption, as well as risk behaviors associated with alcohol and driving, among nursing students throughout the diploma in nursing.MethodA longitudinal epidemiological study was performed in a cohort of 81 nursing students of the San Sebastian School of Nursing. Data were collected using a self-administrated, bilingual (Spanish-Basque) questionnaire completed voluntarily and anonymously. The questionnaire was distributed in one of the most highly attended lectures.ResultsNinety-one percent of the cohort (71 students) were women. The percentage of current smokers (25%, 26.7% and 26.9%) and current drinkers (70.4%, 69.7% and 69.6%) showed no change during the 3-year diploma. The percentage of students at risk of an alcohol-related traffic accident was very high and increased during the course (from 32.3% in the first year to 45% in the third).ConclusionsThe present study identifies unhealthy habits and behaviors that do not improve during the diploma in nursing, suggesting that nursing studies do not always help to encourage healthy habits. Therefore, health education programs should be developed to promote healthy habits and life styles.