Importancia del Helicobacter pylori en la patogénesis del cáncer gástrico. Modelos experimentales en roedores / Importance of Helicobacter pylori in pathogenesis of gastric cancer: Experimental models in rodents

En el Instituto de Cáncer, la prevalencia de la infección de H. pylori en suero presentó un valor de significancia en el grupo con cáncer gástrico comparado con los controles estudiados por edad y sexo. Este estudio sugirió una relación epidemiológica entre la infección por H. pylori y cáncer gástrico. H. pylori muestra un complejo sistema de enzimas, las cuales le sirven para una amplia variedad de funciones. Los efectos tóxicos son producidos por ureasa (UR), fosfolipasa (PL) y alcoholdeshidrogenasa. En el Instituto nos abocamos a la tarea de efectuar una exploración métodica de las actividades enzimáticas en mucosa infectada con H. pylori utilizando el técnica de TLC-autorradioluminografía (cromatografía en papel fino-autorradioluminografía). Este método tiene un margen dinámico amplio y puede ofrecer una técnica analítica para estudiar un compuesto radioactivo y sus enzimas en la mucosa infectad con H. pylori. Fueron estudiadas muestras de biopsias provenientes de 21 pacientes con cáncer gástrico y 95 controles. Aunque una actividad aumentada de UR indica la presencia de lesión mediante H. pylori, las actividades de ADH y PL muestran la cronicidad del daño mucoso en cada grupo. Claramente, el perfil enzimático mostrado en el estudio refleja las "adaptaciones" fisiológicas secundarias a una mucosa lesionada en forma crónica, pero su relación con cáncer gástrico y H. pylori ameritan estudios más profundos. Existe la necesidad urgente de entender los procesos de carcinogénesis utilizando modelos animales. Se realizó un estudio preliminar para explorar el efecto de la infección por H. pylori sobre la inducción de cáncer en roedores C57BL/6 infectados con H. pylori y tratados en agua con N-Metil-N-nitrosourea(MNU). En términos de incidencia en el desarrollo de neoplasias mostró un imcremento en el grupo de MNU infectado previamente con H. pylori. Dichos hallazgos muestran que el modelo animal es adecuado para investigar el efecto de promoción en carcinogénesis gástrica

[Importance of Helicobacter pylori in the pathogenesis of gastric cancer. Experimental models in rodents]. / Importancia del Helicobacter pylori en la patogénesis del cáncer gástrico. Modelos experimentales en roedores.

UNLABELLED: We found that the seroprevalence in Cancer Institute of H. pylori infection was significantly more frequent in gastric cancer than in age- and gender-matched controls. This study suggested an epidemiological link between H. pylori infection and gastric cancer. H. pylori exhibits a complex system of enzymes which serve a range of functions. Toxic effects are produced by urease (UR), phospholipase (PL) and alcohol dehydrogenase (ADH). We embarked on an exploration of the enzyme activities of H. pylori infected patients using a TLC-autoradioluminography. This method has a wide dynamic range and could offer an analytical technique for studying a radioactive compound and its enzymes in H. pylori infected mucosa. Biopsies samples taken from 21 gastric cancer patients and 95 controls were studied. Although high activity of UR indicates well the presence of H. pylori impairment, activities of ADH and PL reflects more the chronicity of mucosal damage in both groups. Clearly, the enzyme profile showed in our study reflects the "physiological" adaptations behind chronic injured mucosal changes but its relation to gastric cancer and H. pylori needs further study. There is an urgent need to understand the carcinogenesis process using animal models. We performed previous study for to explore the effect of H. pylori infection on N- methyl-N-nitrosourea-induced (MNU) gastric carcinogenesis in mice C57BL/6 mice were administered broth culture of H. pylori and given MNU in drinking water. In terms of the incidence of neoplasms development was increase in the MNU group pre-infected with H. pylori. That findings showed that C57BL/6 mice-infected model is well suited for investigating the bacteria promoter effect in the gastric carcinogenesis. Finally another rodent model study (still in process) showed rapid development of hyperplastic gastritis with gastric erosions in H. pylori-infected MTH1 knockout mice. We sought to further evaluate MTH1 knockout mice as potential test animal for carcinogenesis. CONCLUSION: It is suggested that H. pylori infection is an important risk factor for the development of gastric cancer. The possibility that this organism acts etiologically, exerting its effect over long period of time, is biologically plausible. However, the role of H. pylori per se in that process is still a matter of discussion. The various enzymes of H. pylori discussed in this paper support colonization, and are perhaps important for epithelial damage, they could contribute to the stimulation and modulation of the chronic inflammatory response, but its relation to gastric cancer and H. pylori needs further study. Finally H. pylori in C57BL/6 and knockout mice showed excellent colonization at two months and six months after infection there was adenomatous, hyperplastic and ulcerative changes. Those findings showed that both mice-infected models are well suited for investigating the bacteria promoter effect in the gastric carcinogenesis.