Efecto del factor de crecimiento de hepatocitos en una línea celular de páncreas

Pancreatic diseases have been increased in Mexico and worldwide because changes in behaviors. The main risk factors for the development of pancreatitis are alcohol consumption and cholelithiasis, in addition to smoking and obesity that have been related to severe pancreatitis. The disease can proceed to stages more complicated such as fibrosis and cancer. The present work was focused to figure out the effect of HGF in the control of the damage induced by the alcohol and its metabolite acetaldehyde in a pancreatic cell line, the RINm5F. Data presented here show that HGF is capable to induce a survival response in cells treated with both toxics increasing antioxidants enzymes and abrogating the activity of the NADPH oxidase, the main ROS induced system, which eventually activates mechanisms of damage. An approach to address the signal transduction initiated by HGF showed that MAPK pathway, particularly ERK1/2 is the main mechanism of protection. This correlated with the increment of antioxidant enzymes and the abrogation of NADPH oxidase activity and expression. HGF can represent a possible therapeutic target for the control of some pancreatic diseasesEl daño al páncreas es cada vez más frecuente en México, siendo el consumo de alcohol y la colelitiasis las causas más frecuentes; sin embargo, se sabe también de tener efecto directo el tabaquismo, la obesidad, entre otras causas. La pancreatitis es la principal manifestación de la afectación del órgano, pudiéndose presentar tanto aguda como crónica. Esta última puede conducir al agravamiento presentándose como procesos fibrogénicos o carcinogénicos. El HGF representa una alternativa para el control del daño y su reparación. En el presente trabajo nos centramos en dar un primer paso en caracterizar el efecto del HGF en el daño inducido por el etanol y su metabolito el acetaldehído, en una línea celular de páncreas como las células RINm5F. Los resultados muestran que el HGF es capaz de mejorar la sobrevivencia afectada por ambos tóxicos, incrementando proteínas antioxidantes, así mismo indujo un efecto desregulador en la NADPH oxidasa, una de las principales entidades prooxidantes y que eventualmente se activan bajo esquemas de daño. Una primera exploración en el posible mecanismo molecular de dicho efecto protector mostró la activación de la ruta de sobrevivencia de las MAPK´s, particularmente la mediada por ERK1/2. Lo anterior correlacionó con un incremento en enzimas antioxidantes como producto de la estimulación con el HGF. Los resultados muestran que el HGF ejerce un efecto protector elevando enzimas antioxidantes y abrogando sistemas prooxidantes, efecto mediado por la ruta de señalización ERK1/2. El HGF puede representar un posible blanco terapéutico en el tratamiento de algunas patologías asociadas al páncreas

Clinical Strategies Targeting the Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma

Pancreatic cancer has a complex tumor microenvironment which engages in extensive crosstalk between cancer cells, cancer-associated fibroblasts, and immune cells. Many of these interactions contribute to tumor resistance to anti-cancer therapies. Here, new therapeutic strategies designed to modulate the cancer-associated fibroblast and immune compartments of pancreatic ductal adenocarcinomas are described and clinical trials of novel therapeutics are discussed. Continued advances in our understanding of the pancreatic cancer tumor microenvironment are generating stromal and immune-modulating therapeutics that may improve patient responses to anti-tumor treatment

Ginkgo biloba induces different gene expression signatures and oncogenic pathways in malignant and non-malignant cells of the liver.

Ginkgo biloba (EGb761) is a widely used botanical drug. Several reports indicate that EGb761 confers preventive as well as anti-tumorigenic properties in a variety of tumors, including hepatocellular carcinoma (HCC). We here evaluate functional effects and molecular alterations induced by EGb761 in hepatoma cells and non-malignant hepatocytes. Hepatoma cell lines, primary human HCC cells and immortalized human hepatocytes (IH) were exposed to various concentrations (0-1000 μg/ml) of EGb761. Apoptosis and proliferation were evaluated after 72h of EGb761 exposure. Response to oxidative stress, tumorigenic properties and molecular changes were further investigated. While anti-oxidant effects were detected in all cell lines, EGb761 promoted anti-proliferative and pro-apoptotic effects mainly in hepatoma cells. Consistently, EGb761 treatment caused a significant reduction in colony and sphere forming ability in hepatoma cells and no mentionable changes in IH. Transcriptomic changes involved oxidative stress response as well as key oncogenic pathways resembling Nrf2- and mTOR signaling pathway. Taken together, EGb761 induces differential effects in non-transformed and cancer cells. While treatment confers protective effects in non-malignant cells, EGb761 significantly impairs tumorigenic properties in cancer cells by affecting key oncogenic pathways. Results provide the rational for clinical testing of EGb761 in preventive and therapeutic strategies in human liver diseases