Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers.

Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, has anticancer effects mediated, at least in part, by parasite-derived products which inhibit growth of tumor cells. We investigated whether immunity to T. cruzi antigens could induce antitumor activity, using two rat models which reproduce human carcinogenesis: colon cancer induced by 1,2-dimethylhydrazine (DMH), and mammary cancer induced by N-nitroso-N-methylurea (NMU). We found that vaccination with T. cruzi epimastigote lysates strongly inhibits tumor development in both animal models. Rats immunized with T. cruzi antigens induce activation of both CD4(+) and CD8(+) T cells and splenocytes from these animals showed higher cytotoxic responses against tumors as compared to rats receiving adjuvant alone. Tumor-associated immune responses included increasing number of CD11b/c(+) His48(-) MHC II(+) cells corresponding to macrophages and/or dendritic cells, which exhibited augmented NADPH-oxidase activity. We also found that T. cruzi lysate vaccination developed antibodies specific for colon and mammary rat cancer cells, which were capable of mediating antibody-dependent cellular cytotoxicity (ADCC) in vitro. Anti-T. cruzi antibodies cross-reacted with human colon and breast cancer cell lines and recognized 41/60 (68%) colon cancer and 38/63 (60%) breast cancer samples in a series of 123 human tumors. Our results suggest that T. cruzi antigens can evoke an integrated antitumor response involving both the cellular and humoral components of the immune response and provide novel insights into the understanding of the intricate relationship between parasite infection and tumor growth.

A novel clinically relevant animal model for studying galectin-3 and its ligands during colon carcinogenesis.

Galectin-3 (Gal-3) is a multifunctional protein that plays different roles in cancer biology. To better understand the role of Gal-3 and its ligands during colon carcinogenesis, we studied its expression in tumors induced in rats treated with 1,2-dimethylhydrazine (DMH) and in human tissues. Normal colon from untreated rats showed no staining using two specific monoclonal antibodies. In contrast, morphologically normal colon from DMH-treated rats and dysplastic aberrant crypt foci were strongly stained, indicating that increased Gal-3 expression is an early event during the neoplastic transformation in colon cells. Gal-3 was weakly expressed in adenocarcinomas. Overall, the Gal-3 expression pattern observed in the DMH rat model closely resembles that displayed by human colon stained with the same antibodies. We also found that Gal-3 phosphorylation diminishes in serines while increasing in tyrosines during rat colon carcinogenesis. Finally, we showed that Gal-3-ligands expression is strikingly similar in rat and human malignant colon and in non-malignant tissues. In conclusion, the DMH-induced rat colon cancer model displays expression patterns of Gal-3 and its ligands very similar to those observed in human samples. This animal model should contribute to clarifying the role of Gal-3 in colon carcinogenesis and also to finding effective preventive cancer agents based on Gal-3 targeting.

Screening for colorectal cancer in Uruguay with an immunochemical faecal occult blood test.

An observational prospective study was carried out in Uruguay to evaluate the feasibility of colorectal cancer screening using immunochemical faecal occult blood tests with no dietary restrictions in an average-risk population. An automated system was used for processing the samples with a cut-off haemoglobin level of 100 ng/ml. Of the 11,734 study participants who received an immunochemical test kit (OC-Hemodia), 10,573 (90.1%) returned samples for screening. The results of 1170 (11.1%) of the responders were positive. Subsequently, colonoscopy was performed on 879 (75.1%) of the participants with a positive test result and showed neoplasia in 330 participants. Fifty four had advanced cancer, 47 had early cancer, 131 had high-risk adenoma and 98 had low-risk adenoma. The detection rates and the positive predictive values were 0.95 and 8.6% for cancer, and 1.24 and 11.2% for high-risk adenoma, respectively. The high compliance and high detection rates for cancer and high-risk adenoma achieved in the colorectal cancer screening programme verifies the feasibility of an immunochemical faecal occult blood test in screening an average-risk population in Uruguay, a country with a small population, but with high morbidity and mortality rates for this disease.

Simple mucin-type cancer associated antigens are pre-cancerous biomarkers during 1,2-dimethylhydrazine-induced rat colon carcinogenesis.

The simple mucin-type truncated O-glycans Tn (GalNAc-O-Ser/Thr) and sialyl-Tn (STn) antigens are useful diagnostic markers for human colon cancer. We herein report the characterization of 1,2-dimethylhidrazine (DMH)-induced colon cancer in rats as a new model for the study of aberrant O-glycosylation products during carcinogenesis. Evaluated by immunohistochemistry, both anti-Tn and anti-STn MAbs revealed no staining of normal colonic mucosa. On the contrary, Tn and STn were expressed by the first lesions detected following carcinogen administration (aberrant crypt foci), observing the most intense and uniform pattern in crypts with severe dysplasia. Adenocarcinomas with non-secreting components showed moderately and strong stain, but mucin-secreting carcinomas were mildly stained. The biochemical characterization of soluble Tn glycoproteins from ascitic fluids of rats with colon cancer revealed that Tn is bearing high molecular weight glycoproteins (containing sialic acid and/or GlcNAc and GalNAc), which migrated as two major components (one of approximately 220 kDa and other>500 kDa). Evaluated by CsCl gradient ultracentrifugation and perchloric acid precipitation, it was shown that Tn is carried for mucins. These results indicate that Tn and STn are pre-cancerous biomarkers in colon of rats treated with DMH. This model of rat colon cancer could be useful to study in vivo the temporal sequence of molecular events responsible for the deregulation of O-glycosylation pathways during colon carcinogenesis, and could contribute to improve the evaluation of diagnostic and therapeutic strategies based on the utilization of Tn and STn antigens.

Secuencia adenoma-carcinoma en el cáncer de apéndice cecal / Adenoma-carcinoma sequence in vermiform appendix

Los adenomas vellosos del apéndice cecal son de baja frecuencia (1 por ciento), y de hecho su hallazgo se vincula con la cirugía de la apendicitis aguda. Su alto potencial de malignización, la existencia de adenomas con grados variables de displasia y transformación carcinomatosa, así como la presencia de restos de adenoma en un cáncer invasor; permiten inferir que la secuencia adenoma - carcinoma en los tumores de apéndice, es similar a la propuesta por Morson para los cánceres colorectales. Las escasas comunicaciones en la literatura sobre el tema, no establecen esta secuencia etiológica. Se presentan tres pacientes operados de apendicitis aguda, que considerados en conjunto, permiten proponer que la secuencia carcinogénica adenoma - carcinoma en los tumores de apéndice es similar a la establecida por Morson para los cánceres colorectales.

Pericarditis supurada y estallido pericárdico: Doble complicación excepcional en un politraumatizado grave / Suppurative pericarditis and pericardial flare. Exceptional double complication in a severe multiple trauma patient

La pericarditis se define por la inflamación de la serosa pericárdica. En su forma aguda obedece a múltiples causas, entre las cuales el traumatismo es de muy baja incidencia. La pericarditis purulenta bacteriana es menos frecuente aun (0,26%) y se observa como complicación de un foco infeccioso extracardíaco. Es una enfermedad rápidamente fatal si no es tratada precozmente. El diagnóstico temprano suele ser dificultoso y librado a su evolución natural puede no ser evidente hasta que no ocurre cierto grado de taponamiento cardíaco. Se presenta el caso de un paciente gravemente traumatizado, con varios focos infecciosos, que en su segunda semana de internación desarrolló una pericarditis bacteriana con estallido del pericardio, seguido de empiema agudo y shock séptico, de la cual solamente se pudo realizar diagnóstico intraoperatorio. Esta observación permite concluir que -en el curso de un traumatismo grave de tórax- debe establecerse precozmente la existencia de líquido en la cavidad pericárdica y considerar la posibilidad de supuración ante la presencia de focos infecciosos sistémicos y hemocultivos positivos.

Summary Pericarditis is defined as the inflammation of the pericardial serous membrane. Acute pericarditis may be due to numerous causes. Among them, trauma is a very infrequent cause. Purulent bacterial pericarditis is even less frequent (0,26%); it is seen as a complication following an extra cardiac infectious focus and it can be fatal if it is not rapidly treated. Early diagnosis is usually difficult and it may not be evident and if it evolves naturally it may not be evident until certain degree of cardiac tamponade occurs. The case of a serious traumatized patient is reported. It presented numerous infectious foci and at the second week after hospitalization it developed a bacterial pericarditis with pericardiac burst followed by acute empyema and septic shock, and only intrasurgical diagnosis was possible. This finding allows us to conclude that during the course of serious thoracic trauma it is necessary to determine the presence of fluid in the pericardic cavity and to evaluate the occurrence of suppuration related to the presence of systemic infectious foci and positive haemocul-tures.

Résumé La péricardite est définie comme l'inflammation de la séreuse péricardique. Sous sa forme aigue, elle obéit à des causes multiples, parmi lesquelles le traumatisme a une très basse incidence. La péricardite purulente bactérienne est encore moins fréquente (0,26%) et on l'aborde comme un foyer infectieux extra-cardiaque. C'est une maladie fatale et rapide si elle n'est pas vite traitée. Le diagnostic précoce est difficile et dépend de son évolution naturelle; il arrive de passer inaperçu jusqu'à ce qu'il se produit un blocage cardiaque. On présente le cas d'un patient traumatisé, avec plusieurs foyers infectieux, qui pendant la deuxième semaine à l'hôpital a fait une péricardite bactérienne avec éclatement du péricarde, suivie d'empyème aigu et de shock septique, dont on n'a pu réaliser qu'un diagnostic intra-opératoire. Cette observation permet de conclure que- pendant un traumatisme grave de thorax- on doit établir auparavant la présence de liquide dans la cavité péricardique et considérer la possibilité de suppuration quand il y a des foyers d'infection systémiques et des hémocultures positives.