RESUMEN
Long noncoding RNAs (lncRNAs) have been reported to serve a key role in a variety of cardiovascular diseases, including in cardiac fibrosis. The present study aimed to investigate the biological role and underlying mechanisms of the induction of cardiac fibroblasts by the lncRNA, RNA component of mitochondrial RNA processing endoribonuclease (RMRP). The results demonstrated that RMRP expression was upregulated in the presence of cardiac fibrosis in an abdominal aortic bandingtreated rat model. Treatment with angiotensin II increased RMRP expression in cardiac fibroblasts, while the knockdown of RMRP by smallinterfering RNA inhibited cardiac fibroblast proliferation, differentiation and collagen accumulation. To further investigate the underlying mechanisms of this interaction, microRNA (miR)613 was predicted to be a target miR of RMRP and sequence alignment, luciferase activity and MS2 RNA immunoprecipitation were performed to detect the interaction between RMRP and miR613. The results suggested that RMRP negatively regulated miR613 in cardiac fibroblasts. Furthermore, miR613 was indicated to mediate the promoting effect of RMRP on cardiac fibroblast activation. The current study suggested that RMRP promoted cardiac fibroblast activation by acting as a competing endogenous RNA for miR613. Therefore, RMRP may be a novel target for the prevention or treatment of cardiac ï¬brosis.
Asunto(s)
Fibroblastos/metabolismo , MicroARNs/genética , Miocardio/metabolismo , ARN Largo no Codificante/genética , Regulación hacia Arriba , Animales , Células Cultivadas , Endorribonucleasas/genética , Fibroblastos/citología , Fibroblastos/patología , Fibrosis , Masculino , Miocardio/citología , Miocardio/patología , Ratas Sprague-DawleyRESUMEN
Gastrointestinal malignancies are a major health care challenge due to the high incidence and overall poor outcome. A biomarker is a molecular characteristic of a tumor that may be utilized in the initial risk assessment and the subsequent management of the patient. This review focuses on the most pertinent prognostic and predictive biomarkers used in the clinical management of gastric, pancreas, and colon cancer. The available assays, limitations and clinical use for each biomarker are reviewed. The clinical trials evaluating novel biomarkers in GI cancers are discussed.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias del Colon/diagnóstico , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Medicina de Precisión/métodos , Neoplasias del Colon/genética , Neoplasias Gastrointestinales/genética , Humanos , Neoplasias Pancreáticas/genética , Pronóstico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Immune therapy has traditionally had a limited role in the treatment of solid malignancies, outside of renal cancer and melanoma. However, early evidence of the ability to provoke an effective anti-tumor immune response in prostate cancer has led to interest in developing a variety of immune activating strategies in this disease. The first immune therapy to attain success in prolonging survival for metastatic prostate cancer patients is Sipuleucel-T. Rather than utilizing a typical vaccine approach in which antigens and immune activators are injected into the cancer host, sipuleucel-T was developed to stimulate autologous dendritic cells ex vivo, in order to evade the immune suppressive environment created by the cancer. We review the components of the immune system which may be harnessed in the development of immunotherapy in the setting of the recent success with sipuleucel-T.