1,721,181 research outputs found
Novel prognostic biomarkers in colorectal cancer
No full textThe main predictor of outcome of patients with colorectal cancer (CRC) remains the TNM staging system. Biomarkers, i.e. biological indicators of disease progression or of responsiveness to a pharmacological intervention, are expected to be of help in the management of CRC. Despite high expectations, biomarkers have not entered into clinical practice due to contradictory results of large-scale studies and to some complexity in data interpretation. Here we briefly review the main genetic and immunological changes that have been considered potential CRC biomarkers and that might be considered for further testing aimed at clinical use, at least in specific disease settings. Copyright © 2012 S. Karger AG, Basel
Gender difference for promoter methylation pattern of hMLH1 and p16 in sporadic MSI colorectal cancer
No full textNew insights into inflammatory bowel disease pathophysiology: Paving the way for novel therapeutic targets
No full textThe etiopathogenesis of Crohn's disease (CD) and ulcerative Colitis (UC), the two major forms of inflammatory bowel disease (IBD), is still unknown. Although the exact cause and mechanisms of both IBD have yet to be completely understood, it is widely accepted that both CD and UC result from an inappropriate immune response that occurs in genetically susceptible individuals as the result of a complex interaction among environmental factors, microbial factors, and the intestinal immune system. In the last few years a tremendous advance in knowledge of the mechanisms underling intestinal inflammation in IBD has been achieved, leading to new therapeutic targets and novel drugs. These new therapeutic weapons have been specifically designed to selective shut down intestinal inflammation at different levels. Aim of this review is to summarize the recent advances in IBD pathophysiology and the new therapeutic targets and drugs that are changing the IBD clinical management.The etiopathogenesis of Crohn's disease (CD) and ulcerative Colitis (UC), the two major forms of inflammatory bowel disease (IBD), is still unknown. Although the exact cause and mechanisms of both IBD have yet to be completely understood, it is widely accepted that both CD and UC result from an inappropriate immune response that occurs in genetically susceptible individuals as the result of a complex interaction among environmental factors, microbial factors, and the intestinal immune system. In the last few years a tremendous advance in knowledge of the mechanisms underlying intestinal inflammation in IBD has been achieved, leading to new therapeutic targets and novel drugs. These new therapeutic weapons have been specifically designed to selective shut down intestinal inflammation at different levels. Aim of this review is to summarize the recent advances in IBD pathophysiology and the new therapeutic targets and drugs that are changing the IBD clinical managemen
Reduced metastatic potential of microsatellite unstable colorectal cancers with hMLH1 defect, hMSH3 frameshift mutations and ensuing MutS beta defects
No full textDifferent spectrum of target gene mutations in hereditary non polyposis colorectal cancers according to hMLH1 and Hmsh2 defects
No full textCalcium supplementation for the prevention of colorectal adenomas: a systematic review and meta-analysis of randomized controlled trials
No full textAIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. " METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials. gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or ""high-risk"" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95% CI) were calculated using fixed-and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE." RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95% CI: 0.82-0.96 random-effects, RR = 0.87, 95% CI: 0.77-0.98 high quality of evidence). The NNT was 20 (95% CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95% CI: 0.75-1.13 random-effects, RR = 0.92, 95% CI: 0.71-1.18 moderate quality of evidence). CONCLUSION: Our results suggest a modest chemo-preventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's riskof- bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; randomeffects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted
Iron metabolism in cancer progression
No full textIron is indispensable for cell metabolism of both normal and cancer cells. In the latter, several disruptions of its metabolism occur at the steps of tumor initiation, progression and metastasis. Noticeably, cancer cells require a large amount of iron, and exhibit a strong dependence on it for their proliferation. Numerous iron metabolism-related proteins and signaling pathways are altered by iron in malignancies, displaying the pivotal role of iron in cancer. Iron homeostasis is regulated at several levels, from absorption by enterocytes to recycling by macrophages and storage in hepatocytes. Mutations in HFE gene alter iron homeostasis leading to hereditary hemochromatosis and to an increased cancer risk because the accumulation of iron induces oxidative DNA damage and free radical activity. Additionally, the iron capability to modulate immune responses is pivotal in cancer progression. Macrophages show an iron release phenotype and potentially deliver iron to cancer cells, resulting in tumor promotion. Overall, alterations in iron metabolism are among the metabolic and immunological hallmarks of cancer, and further studies are required to dissect how perturbations of this element relate to tumor development and progression
Prognostic value of innate and adaptive immunity in colorectal cancer
No full textColorectal cancer (CRC) remains one of the major public health problems throughout the world. Originally depicted as a multi-step dynamical disease, CRC develops slowly over several years and progresses through cytologically distinct benign and malignant states, from single crypt lesions through adenoma, to malignant carcinoma with the potential for invasion and metastasis. Moving from histological observations since a long time, it has been recognized that inflammation and immunity actively participate in the pathogenesis, surveillance and progression of CRC. The advent of immunohistochemical techniques and of animal models has improved our understanding of the immune dynamical system in CRC. It is well known that immune cells have variable behavior controlled by complex interactions in the tumor microenvironment. Advances in immunology and molecular biology have shown that CRC is immunogenic and that host immune responses influence survival. Several lines of evidence support the concept that tumor stromal cells, are not merely a scaffold, but rather they influence growth, survival, and invasiveness of cancer cells, dynamically contributing to the tumor microenvironment, together with immune cells. Different types of immune cells infiltrate CRC, comprising cells of both the innate and adaptive immune system. A relevant issue is to unravel the discrepancy between the inhibitory effects on cancer growth exerted by the local immune response and the promoting effects on cancer proliferation, invasion, and dissemination induced by some types of inflammatory cells. Here, we sought to discuss the role played by innate and adaptive immune system in the local progression and metastasis of CRC, and the prognostic information that we can currently understand and exploit. © 2013 Baishideng. All rights reserved
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