Early-onset colorectal cancer with stable microsatellite DNA and near-diploid chromosomes

Colorectal cancer has been described in terms of genetic instability selectively affecting either microsatellite sequences (MIN) or chromosome number and structure (CIN). A subgroup with apparently stable, near-diploid chromosomes and stable microsatellites (MACS) also exists. These distinctions are important, partly because of their value in highlighting different pathways of carcinogenesis, and partly because of their direct relevance to prognosis. Study of early-onset cancer has often proved a fruitful resource for the identification of the nature and function of cancer susceptibility genes. In a study of colorectal cancer with stable microsatellite DNA, we describe 22 early-onset tumours (mean age = 33), compared with 16 late-onset tumours (mean age = 68). Both groups contained carcinomas with the MACS phenotype, characterized by near diploid DNA content, as defined by flow cytometry, and minimal chromosome arm deletion or amplification (six or less events per genome), determined by comparative genomic hybridization (CGH). Minimal chromosome imbalance correlated strongly with diploid DNA content (P<0.001). The proportion of MACS cancers was significantly greater in early-onset as compared to late-onset tumours (64 vs 13%, P = 0.005). Of the chromosome arm imbalances commonly observed in late-onset tumours, only 18q - Was observed more than twice amongst the 14 early-onset MACS tumours. Seventy-nine per cent of these MACS tumours were located in the distal colon, and 69% were at advanced clinico-pathological stages (with lymph node or distant metastasis). A positive family history of colorectal or other cancers was elicited in seven patients in the MACS early-onset group, and one additional patient in this group had a metachronous ovarian cancer. The results suggest that MACS cancer may have a genetic basis different from either MIN or CIN, and further studies of these cancers may lead to discovery of new mechanisms of colorectal carcinogenesis and cancer susceptibility.link_to_subscribed_fulltex

Obesity, aspirin, and risk of colorectal cancer in carriers of hereditary colorectal cancer: a prospective investigation in the CAPP2 study

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Multi-material design: architecture and components simultaneous selection

The design of multi-materials requires the determination of several variables: morphology, components and geometric parameters. Previously developed methods help designer making these choices separately because they always lie on a reduction in the number of design variables, as some of them are fixed at the beginning of the study. This paper proposes a method to carry out the simultaneous definition of all these variables in a preliminary design step. The beginning of this work consists in the formalisation of the multi-scale decomposition of the architecture materials. This outline is a guide for the use of databases of materials and architectures, whose combination enables the generation of multi-materials. Within the huge solution space resulting from this approach, a genetic algorithm allows to find optimised materials to fulfil a set of requirements with a limited number of calculations. An analytic example illustrates the efficiency of this method and shows it can provide designers with several propositions of material