Cuadernos para el docente

Horizontes representa una propuesta pedagógica que incluye programas de televisión para las áreas de Lengua, Matemática, Ciencias Sociales y Ciencias Naturales. Su intención es acompañar las actividades de la Escuela Secundaria Rural y difundir contenidos audiovisuales articulados con las unidades didácticas desarrolladas a lo largo de los CUADERNOS DE ESTUDIO de las áreas disciplinares mencionadas

Capecitabine plus gemcitabine in thymic epithelial tumors: final analysis of a Phase II trial

Background: A multi-institutional Phase II trial was initiated in 2005 to test the combination gemcitabine and capecitabine in patients with thymic epithelial malignancies (TETs). Patients & methods: Patients with histologic confirmation of TET diagnosis by central review who had received >1 systemic chemotherapy treatment were included. Patients received oral capecitabine (650 mg/mq twice daily on days 1-14) and intravenous gemcitabine (1000 mg/mq on days 1 and 8 every 3 weeks). Results: Of the 30 patients included (18 men, 12 women; median age: 57 years, range: 48-61 years), the majority (73%) had thymoma, and the remaining thymic carcinoma. Eight patients developed grade 3-4 neutropenia. A total of 12 patients had a response. Median progression-free survival was 11 months (range: 6.5-16.5). Conclusion: Capecitabine and gemcitabine is highly active in TETs

Genomic basis for RNA alterations in cancer.

Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer

High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations.

The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the promoter is often increased with nearby SV breakpoint, which may involve inactivation of repressor elements

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Continuous circular cycling in bipolar disorder as a predictor of poor outcome

OBJECTIVE: This prospective study aims to determine if patients with bipolar disorder with a continuous circular course (CCC) are significantly different on clinical characteristics and response to long-term treatment from those with a non-continuous circular course (N-CCC). CCC was defined as the alternation of depression and (hypo)mania without a completely free interval, and N-CCC as the presence of free intervals after the sequence mania-depression or depression-mania. METHOD: The study sample includes 140 consecutive patients with bipolar I or II disorder according to DSM-IV criteria, aged 18-65 years and receiving prophylactic treatment for. Treatment was based upon international guidelines and clinical experience at the time of patient's enrollment (from January 1998 to January 2006). Primary outcome was the absence of new episodes during the follow-up. Significance level was set at p<0.05. RESULTS: Twenty-eight percent of the sample has CCC. Compared with N-CCC, CCC patients were older, had a later onset, a higher number of total, depressive and (hypo)manic episodes, and of switches, and spent a higher percentage of time ill in the year before entering the study. Polarity at onset and subsequent recurrences were more frequently mixed in N-CCC than in CCC patients. The proportion of patients in the CCC group who had no recurrences during the follow-up was significantly lower than in the N-CCC group. CONCLUSION: The presence or absence of a free intervals over the course of illness identifies two subtypes of bipolar disorder that differ in clinical presentation, outcome, and response to long-term treatment

Liver cell apoptosis in chronic hepatitis C and its relation to necroinflammatory activity, clinic and virologic parameters.

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