Dépistage organisé du cancer colorectal

Acta Endoscopica - C’est un test de sélection. C’est un outil important de communication et d’information, c’est dire si elle doit être connue, comprise et bien...     

Critical stages of tumor growth regulation in transgenic mice harboring a hepatocellular carcinoma revealed by distinct patterns of tumor necrosis factor-alpha and transforming growth factor-beta mRNA production

There is now good evidence that cytokines contribute to the regulation of tumor growth. The cytokine-driven modulation of tumor growth was investigated during the progression of a hepatocellular carcinoma (HCC) in SV40 large T tumor antigen transgenic mice. In vivo, an increased rate of liver growth correlated with increased transforming growth factor (TGF)-beta 1 mRNA expression, while the greatest amounts of tumor necrosis factor (TNF)-alpha mRNA were detected earlier during tumor development. Conversely, no particular alteration of IL-1 alpha, IL-1 beta, IL-6, IL-2, IL-4 and IFN-gamma mRNA production could be reported. In vitro, hepatocyte-like tumor cell lines established at two stages, either before or after HCC differentiation, were characterized. The early-stage-derived cell line produced TNF-alpha mRNA, but had barely detectable expression of TGF-beta 1 mRNA, while later-stage- derived cell lines showed the reciprocal pattern. All cell lines displayed a lack of sensitivity to TNF-alpha, although some degree of sensitivity to TNF-alpha could be observed in the presence of actinomycin-D or after treatment with IFN-gamma. The early-stage- derived cell line was sensitive to the growth inhibitory effects of TGF- beta 1, but late-stage-derived tumor cell lines displayed a loss of sensitivity to TGF-beta 1 which correlated with the increased expression of TGF-beta 1 mRNA. Altogether, this suggests that tumor cells contribute to the discrete TNF-alpha and TGF-beta 1 expression patterns during HCC progression. This model of HCC could be of valuable interest to assess the impact of various immunotherapeutic strategies on modulation of tumor growth.      

Xenogeneic recognition of soluble and cell surface HLA class II antigens by proliferative murine T cells

In order to characterize the murine anti-human xenogeneic mixed lymphocyte reactions (MLR), we studied T cell proliferative responses against various human lymphoid cells by immunization of mice either with cellular or purified HLA-DR antigens. Data presented here indicated that small amounts of soluble HLA-DR antigen were able to prime mice, and that the xenogeneic MLR depends on the expression of HLA class II antigens on the stimulating cells. Experiments using a mutant cell line clearly showed that HLA-DP molecules were also sufficient in eliciting a primary or a secondary xenogeneic MLR while no secondary proliferative response was obtained with cells expressing only HLA class I molecules. Using a large panel of human cells with various haplotypes, our results also showed that (a) nonpolymorphic determinants of HLA class II antigens trigger dominantly the murine T cells and (b) the xenogeneic response required I-E and L3T4 accessory molecules and was not inhibited with anti I-A and monomorphic anti-HLA class II antigen monoclonal antibodies. Altogether these results suggest that HLA class II antigens act as nominal antigens in triggering a murine anti-human proliferative response.     

Patterns of neuropsychological deficits in children with medulloblastoma according to craniospatial irradiation doses

This study aimed to analyse the relationship between supratentorial irradiation dose and the intellectual outcome in 36 children (aged between 5 and 15 years) treated for medulloblastoma. The supratentorial radiation dose was reduced to 25 Gy in 23 children and given at the standard dose, 35 Gy, in 13 other children. Neuropsychological evaluation was performed at a mean of 4.3 years (SD 4.7 years) after radiotherapy. The supratentorial radiation dose was the principal risk factor associated with impaired intellectual outcome. Verbal fluency, immediate word list recall, block design, and fine motricity of the dominant hand were significantly lower in children irradiated at the standard doses than in those irradiated at reduced doses. These findings suggest that the dose of radiotherapy applied to the brain strongly influences later verbal and non-verbal skills in children with medulloblastoma. This should be taken into account in treatment planning and in rehabilitation programs.     

High frequency of cholestasis in generalized pustular psoriasis: Evidence for neutrophilic involvement of the biliary tract

Generalized pustular psoriasis is a rare form of psoriasis that is sometimes associated with extracutaneous manifestations. Evidence for biliary involvement has been suggested in isolated cases. We investigated the prevalence and nature of liver abnormalities occurring in this disease. Twenty-two patients consecutively admitted for generalized pustular psoriasis who underwent liver biological tests at the time of the attack and during the following weeks were included. Twenty patients (90%) had at least one abnormal biological liver parameter. Eleven patients (50%) had pronounced abnormalities: jaundice (4/22), gammaglutamyl transferase higher than 5 times the normal value (10/22), alkaline phosphatase higher than twice the normal value (7/22), and/or aminotransferases higher than 3 times the normal value (7/22). These abnormalities returned to normal range at the time of remission of pustular psoriasis, suggesting that severe liver abnormalities could be associated with severe cutaneous disease. Neutrophilic cholangitis was observed on liver biopsy. Persistent magnetic resonance cholangiopancreatography features similar to those observed in sclerosing cholangitis were found in 3 of the 4 patients studied. No causal factor other than pustular psoriasis could be identified. In conclusion, our results demonstrate the high frequency of liver abnormalities in patients with generalized pustular psoriasis. Biliary involvement related to neutrophilic cholangitis should be added to the spectrum of extracutaneous manifestations of this disease, and physicians should be aware of such a complication.