MicroRNAs (miRNAs), which are small single-stranded RNA molecules composed of 18-23 nucleotides, act as oncogenes or tumor suppressor genes playing important roles in tumor formation, infiltration and metastasis. Subsequently, miRNAs expression contributes to cancer diagnosis and prognosis. Gastric cancer currently has high morbidity and mortality among all malignant tumors, yet it lacks early specific diagnostic markers and effective treatments. In gastric cancer, many studies have detected abnormal expression forms of miRNAs and confirmed their involvement in its tumorigenesis, progression, invasion and metastasis. They may become valuable diagnostic markers and therapeutic targets for gastric cancer. Studying the role of miRNAs in gastric cancer and its relationship with diagnostic and prognostic parameters might help to improve the sensitivity of diagnosis as well as the efficacy of gastric cancer treatment. This review aims to highlight the advancements which might provide new methods for early clinical diagnosis and effective therapeutic options, along with predict response to treatment for gastric cancer.
This study aimed to explore the pattern of accumulation of some of main heavy metals in blood and various organs of rats after exposed to the atmospheric fine particulate matter (PM2.5). Rats were randomly divided into control and three treatment groups (tracheal perfusion with 10 mg/kg, 20 mg/kg and 40 mg/kg of PM2.5 suspension liquid, respectively). Whole blood and the lung, liver, kidney, and cerebral cortex were harvested after rats were treated and sacrificed. The used heavy metals were detected using inductively coupled plasma-mass spectrometry (ICP-MS) instrument. As results, Lead was increased in the liver, lung and cerebral cortex and the level of manganese was significantly elevated in the liver and cerebral cortex in PM2.5 treated rats. Besides, arsenic was prominently enriched both in cerebral cortex and in blood, and so did the aluminum in the cerebral cortex and the copper in the liver. However, cadmium, chromium and nickel have shown no difference between the control group and the three PM2.5 treated groups. Following the exposure of PM2.5, different heavy metals are preferentially accumulated in different body tissues.
BackgroundRobust ERK1/2 activity, which frequently results from KRAS mutation, invariably occurs in pancreatic ductal adenocarcinoma (PDAC). However, direct interference of KRAS signaling has not led to clinically successful drugs. Correct localization of RAF is regulated by the scaffold protein prohibitin (PHB) that ensures the spatial organization between RAS and RAF in plasma membranes, thus leading to activation of downstream effectors.MethodsPHB expression was analyzed in human pancreatic cancer cell lines, normal pancreas, and PDAC tissue. Furthermore, genetic ablation or pharmacological inhibition of PHB was performed to determine its role in growth, migration, and signaling of pancreatic cancer cells in vitro and in vivo.ResultsThe level of PHB expression was crucial for maintenance of oncogenic ERK-driven pancreatic tumorigenesis. Additionally, rocaglamide (RocA), a small molecular inhibitor, selectively bound to PHB with nanomolar affinity to disrupt the PHB-CRAF interaction by altering its localization to the plasma membrane. Consequently, there was an impairment of oncogenic RAS-ERK signaling, thereby blocking in vitro and in vivo growth and metastasis of pancreatic cancer cells that were addicted to RAS-ERK signaling. More importantly, RocA treatment resulted in a significant increase of the lifespan of tumor-bearing mice without any detectable toxicity.ConclusionsBlockade of the PHB scaffold-CRAF kinase interaction, which is distinct from direct kinase inhibition, may be a new therapeutic strategy to target oncogenic ERK-driven pancreatic cancer.
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