Estudo da correlação das características clínico-patológicas do câncer colorretal com a expressão imunohistoquímica de proteínas da progressão tumoral

Except the non-melanoma skin tumors, colorectal cancer is the second most common in the Southeastern Region of Brazil, the third most common in the Southern and Central Regions. It is also the forth most common in the Northern Region and it is the fifth one in the Northeastern. To assess pathological and clinical variables of colorectal Cancer is crucial to know the possible conclusions for the survival of patients and point out the characteristics in the progress of tumor, such as the profile of tumor invasion and its angiogenesis. This work focuses on analyzing clinically and pathologically some settings in colorectal cancer patients (CRC) in the city of Natal and its countryside through those variables as parameters of prognosis and determine the level of protein expression, for instance: E-cadherin (E-cad), beta- -catenin (β-cat), galectin-3 (gal-3), matrix metalloproteinases (MMP) 2 and 9 and vascular-endothelial growth factor alpha (α VEGF) in the tumor tissues. A retrospective study was done in colorectal cancer cases in the regions of Rio Grande do Norte state from 1995 to 2005, specifically in Natal city/RN/Brazil. The pathological and clinical variables, such as: age, gender, ethnicity, lifestyle, family history, the location of the primary tumor, level of differentiation, TDM staging, modified Dukes’, treatment and survival were analyzed. The pathological and clinical data were collected from medical records through a specific form and were filed on Excel. A total of 534 patients were selected from the Pathology Department file in this institution, however, 176 patients were excluded. 358 patients were included for Epidemiological analysis and its clinical and pathological correlations were selected. 180 patients were also selected for histological and immunohistochemical studies. The tumor progression of these selected proteins mentioned before were analyzed. The Paraffin blocks of these samples were treated by Microarray Tissue technique and its blades subjected to immunohistochemistry to test the intensity of these proteins in tumor tissues. The results of this analysis were correlated with clinicopathologic variables of patients. Statistical analysis using the chi-frame Pearson test and analysis of midlife by Kaplan-Meier curve was also utilized. P values < 0.05 were considered statistically significant. The average age of our sample was 58.8 years and 51.7 % were female. Alcohol consumption has increased by 1.71 time the risk of death by CCR (p = 0.034) and tobacco consumption increased 2.7 times the chance of developing tumors of high TNM stage (p = 0.001). Cancer patients had a family history of 3,833 times the chance of developing the CCR (p = 0.002). The expression of MMP-2 showed a significant association with tumors of high TNM stage (p <0.046) and mortality (p = 0.041). The α VEGF expression had statistically significant correlation with high TNM stage (p <0.009), degree of cell indifferentiation (p <0.025) and mortality (p <0.035). Expressions of E-cadherin and beta-catetina demonstrated tumor linked to high TNM stage (p = 0.0001) and Dukes› modified (p = 0.05), lesions in the rectum (p = 0.03 and p = 0.007, respectively), smoking (p = 0.05) and indifferentiation (p = 0.001). The expression of Gal-3 showed statistical significance with high TNM stage of patients (p = 0.01), smokers (p = 0.01), alcohol drinking (p = 0.03), indifferentiation (p = 0.0001) and mortality (p = 0.0001). Based on the results, therefore, we could realize that lifestyle and family history had correlation in the CCR prognosis, as well as MMP-2 expression, MMP-9, VEGF alpha, E-cadherin, Beta-catenin and Galectin-3 were important prognostic markers in tumor progression in colorectal cancer.

Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei

The occurrence of bioactive compounds in marine organisms comes awaking the interest of the pharmaceutical industry. Heparin, a sulfated polysaccharide which presence was already identified in several marine invertebrates, is very attractive due its remarkable functional versatility. Besides to intervene in blood coagulation, this molecule has a great anti-inflammatory potential. However, its strong anticoagulant activity difficult the clinical exploitation of its anti-inflammatory properties. Thus, the aims of this work were to evaluate the effect of a heparin-like compound (heparinoid), isolated from the cephalotorax of the Litopenaeus vannamei shrimp, on the inflammatory response, hemostasia and synthesis of antithrombotic heparan sulfate by endothelial cells, besides studying some aspects concerning its structure. The purified heparinoid was structurally characterized following an analytical boarding, involving electrophoresis and chromatography. The structural analysis have shown that this compound possess a high content of glucuronic acid residues and disulfated disaccharide units. In contrast to mammalian heparin, the heparinoid was incapable to stimulate the synthesis of heparan sulfate by endothelial cells in the tested concentrations, beyond to show reduced anticoagulant activity and hemorrhagic effect. In a model of acute inflammation, the compound isolated from the shrimp reduced more than 50% of the cellular infiltration. Besides reduce the activity of MMP-9 and proMMP-2 of the peritoneal lavage of inflamed animals, the heparinoid also reduced the activity of MMP-9 secreted by activated human leukocytes. These results demonstrate the potential of heparinoid from L. vannamei to intervene in the inflammatory response. For possessing reduced anticoagulant activity and hemorrhagic effect, this compound can serve as a structural model to direct the development of more specific therapeutical agents to the treatment of inflammatory diseases