[Colorectal oncogenesis]. / Oncogenèse colorectale.

Recent progress in the field of molecular biology has allowed us to identify at least two different molecular mechanisms implicated in colorectal carcinogenesis (CRC): chromosomal instability (CIN) and genetic instability. Even though the two molecular mechanisms differ, their signalling pathways, implicated in malignant transformation of colonic epithelial cells, appear to be similar. The most frequent group of CRC, which represents 80% of sporadic CRC, is characterized by allelic losses on the short arm of chromosome 17 and 8 and on the long arm of chromosome 5, 18 and 22. These allelic losses are associated with mutations in TP53, APC, SMAD2 and SMAD4 genes. All of these alterations are grouped under the phenotype CIN. A genetic instability termed MSI (microsatellite instability), which results from a mismatch repair (MMR) deficiency, appears in 12-15% of CRC cases. The presence of MMR deficiency leads to the accumulation of mutations in genes controlling cell cycle and apoptosis (TGFBRII, BAX or CASPASE5). More recently, the existence of a third phenotype was suggested. The main alteration associated with this group of tumors is the hypermethylation of the promoter region of numerous genes, leading to their inactivation. An activating mutation of BRAF is frequently associated with this phenotype. As described above, CRC shows genetic heterogeneity, however the consequences in terms of signalling pathway alterations are similar. For example, the activation of Wnt signalling pathways can result from the inactivation of the APC gene in the CIN phenotype or from an activating mutation in the ß-catenin gene in MSI tumors. The inactivation of TGFß pathways is also present in both tumor types and is driven by SMAD4, and more rarely by a SMAD2 inactivating mutation in CIN tumors, or by the existence of a frame-shift mutation occurring in a polyG coding track of the TGFß (transforming growth factor) receptor type II in MSI tumors. The RAS-MAP kinase pathway is activated by KRAS mutations in CIN tumors or by BRAF mutations in MSI tumors. The p53 pathway is inactivated by TP53 inactivation in CIN tumors or by BAX inactivating mutations in MSI tumors.

Executive function and cognitive remediation.

Through the use of multiple case study design, this project examined the variations in executive function exhibited by two subjects who sustained frontal lobe damage. The study then investigated the relationship between executive functional deficit and activity preference. Subjects were trained in computerized cognitive retraining and conventional cognitive retraining. Subjects were then asked to select either modality. Each subject was tested for initiation and overall executive function, cognitive status and disability level. Findings revealed that executive functional deficits present in varied and unique ways and that activity preferrence is related to the unique constellation of sequelae rather than location of injury. Further implications point to the value of combining informal and formal inquiry techniques to patient assessment as well as research on closed head injury intervention.

The effects of teacher intrusion on social play interactions between children with autism and their nonhandicapped peers.

This study investigated the effects of two levels of teacher intrusion upon the behavior of elementary age children with autism and nonhandicapped peers during dyadic play interactions occurring in two special education classrooms. High versus low levels of teacher intrusion were contrasted in a mixed between- and within-subjects design counterbalanced for order across the two conditions. There were few differences in behavior across the two conditions, though the low-intrusion condition was associated with higher levels of toy contact, appropriate and inappropriate play, and lower levels of spontaneous verbalizations by the students with autism. There was no difference in the occurrence of excess behavior by condition. Results are discussed with respect to future investigations of effective teacher mediation to prepare children for positive peer interactions.