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71.
Gemma Binefa Francisco Rodríguez-Moranta àlex Teule Manuel Medina-Hayas 《World journal of gastroenterology : WJG》2014,20(22):6786-6808
Colorectal cancer(CRC)is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors.CRC develops through a gradual accumulation of genetic and epigenetic changes,leading to the transformation of normal colonic mucosa into invasive cancer.CRC is one of the most prevalent and incident cancers worldwide,as well as one of the most deadly.Approximately 1235108 people are diagnosed annually with CRC,and 609051 die from CRC annually.The World Health Organization estimates an increase of77%in the number of newly diagnosed cases of CRCand an increase of 80%in deaths from CRC by 2030.The incidence of CRC can benefit from different strategies depending on its stage:health promotion through health education campaigns(when the disease is not yet present),the implementation of screening programs(for detection of the disease in its early stages),and the development of nearly personalized treatments according to both patient characteristics(age,sex)and the cancer itself(gene expression).Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application,not all strategies meet the criteria required for screening tests in population programs;the three most accepted tests are the fecal occult blood test(FOBT),colonoscopy and sigmoidoscopy.FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe.Due to its non-invasive nature and low cost,it is one of the most accepted techniques by population.CRC is a very heterogeneous disease,and with a few exceptions(APC,p53,KRAS),most of the genes involved in CRC are observed in a small percentage of cases.The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy.In recent years,the use of DNA,RNA and protein markers in different biological samples has been explored as strategies for CRC diagnosis.Although there is not yet sufficient evidence to recommend the analysis of biomarkers such as DNA,RNA or proteins in the blood or stool,it is likely that given the quick progression of technology tools in molecular biology,increasingly sensitive and less expensive,these tools will gradually be employed in clinical practice and will likely be developed in mass. 相似文献
72.
Mario Strazzabosco Paolo A. Cortesi Sara Conti Stefano Okolicsanyi Matteo Rota Antonio Ciaccio Paolo Cozzolino Carla Fornari Marta Gemma Luciana Scalone Giancarlo Cesana Luca Fabris Michele Colledan Stefano Fagiuoli Gaetano Ideo Claudio Zavaglia Giovanni Perricone Luca M. Munari Lorenzo G. Mantovani Luca S. Belli 《Liver international》2020,40(1):60-73
73.
Giuseppe Limongelli Teo Roselli Giuseppe Pacileo Paolo Calabró Valeria Maddaloni Daniele Masarone Lucia Riegler Rita Gravino Raffaella Scarafile Gemma Salerno Tiziana Miele Antonello D’Andrea Lucio Santangelo Massimo Romano Giovanni Di Salvo Maria Giovanna Russo Raffaele Calabró 《Internal and emergency medicine》2014,9(1):43-50
Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines. Plasma CT-1 levels correlate with the left ventricle mass index in patients with dilatated cardiomyopathy and congestive heart failure (CHF). The aim of this paper was to evaluate CT-1 plasma levels, before and after cardiac resynchronization therapy CRT, and to characterizeits prognostic role in patients with CHF. Fifty-two consecutive patients (M/F = 39/13; 56 ± 11 years old) underwent clinical and echocardiographic evaluation, and blood sample collection at baseline. The same evaluation was repeated 6.4 ± 0.79 months after CRT. Patients with a decreased LV end-systolic volume by at least 15% (reverse remodeling) were considered echo responders to CRT. Twenty-nine patients (56%) were responders to CRT. After CRT, only 15 patients (29%) showed increased CT-1 after CRT. They were all non responders to CRT. A multivariate, logistic modelshowed CT-1 as an independent predictor of CRT echo response (p = 0.005; OR 0.97). During follow-up (18 ± 7 months), 21 cardiac events in 18 patients occurred. A Cox multivariable model showed plasma BNP pre-CRT (p = 0.02; CI 1.2–5.6; OR 3.1) and CT1 post-CRT (p = 0.01; CI 1.4–4.3; OR 2.7) as independent predictors of cardiac events. Analysis of CT-1 plasma levels deserves future consideration for larger, longitudinal studies in patients with CHF. 相似文献
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75.
Bakker GJ Eich C Torreno-Pina JA Diez-Ahedo R Perez-Samper G van Zanten TS Figdor CG Cambi A Garcia-Parajo MF 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(13):4869-4874
Integrins are cell membrane adhesion receptors involved in morphogenesis, immunity, tissue healing, and metastasis. A central, yet unresolved question regarding the function of integrins is how these receptors regulate both their conformation and dynamic nanoscale organization on the membrane to generate adhesion-competent microclusters upon ligand binding. Here we exploit the high spatial (nanometer) accuracy and temporal resolution of single-dye tracking to dissect the relationship between conformational state, lateral mobility, and microclustering of the integrin receptor lymphocyte function-associated antigen 1 (LFA-1) expressed on immune cells. We recently showed that in quiescent monocytes, LFA-1 preorganizes in nanoclusters proximal to nanoscale raft components. We now show that these nanoclusters are primarily mobile on the cell surface with a small (ca. 5%) subset of conformational-active LFA-1 nanoclusters preanchored to the cytoskeleton. Lateral mobility resulted crucial for the formation of microclusters upon ligand binding and for stable adhesion under shear flow. Activation of high-affinity LFA-1 by extracellular Ca(2+) resulted in an eightfold increase on the percentage of immobile nanoclusters and cytoskeleton anchorage. Although having the ability to bind to their ligands, these active nanoclusters failed to support firm adhesion in static and low shear-flow conditions because mobility and clustering capacity were highly compromised. Altogether, our work demonstrates an intricate coupling between conformation and lateral diffusion of LFA-1 and further underscores the crucial role of mobility for the onset of LFA-1 mediated leukocyte adhesion. 相似文献
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79.
Martínez-Avilés L Alvarez-Larrán A Besses C Navarro G Torres E Longarón R Angona A Pedro C Florensa L Serrano S Bellosillo B 《Annals of hematology》2012,91(10):1555-1562
JAK2V617F-negative essential thrombocythemia (ET) is a heterogeneous disease including clonal cases and others without evidence of clonality. However, it is unknown if the detection of myeloid clonality in JAK2V617F-negative ET patients confers a different clinical outcome than those in whom clonal hematopoiesis cannot be demonstrated. The objective of the present study was to evaluate the clinical significance of clonality assessment in patients with JAK2V617F-negative ET. Clonality investigation including mutational status of MPL, TET2, and ASXL1 genes and human androgen receptor (HUMARA) assay was performed in 73 JAK2V617F-negative cases out of 186 subjects consecutively diagnosed with ET in a single institution, at diagnosis or during follow-up. Mutations in MPL, TET2, and ASXL1 were observed in 7, 4, and 2 cases, respectively, whereas clonality by HUMARA assay was demonstrated in 21 out of 46 (46?%) female patients. With a median follow-up of 8?years, death, thrombosis, bleeding, and disease transformation were registered in 7, 10, 8, and 6 patients, respectively. No differences in thrombosis, bleeding or survival were observed according to clonality assessment. The probability of disease transformation at 10?years was higher in patients showing clonal hematopoiesis by presenting mutations in either MPL, TET2, or ASXL1 (64 versus 2?% in patients without mutations, p?0.001) and in those with HUMARA clonality (35 versus 0?% in patients with polyclonal hematopoiesis, p?0.004). In conclusion, disease transformation is associated with evidence of clonality in JAK2V617F-negative ET. 相似文献
80.
Odena G Miquel M Serafín A Galan A Morillas R Planas R Bartolí R 《World journal of gastroenterology : WJG》2012,18(17):2084-2091
AIM: To compare rifaximin and insulin-like growth factor (IGF)-1 treatment of hyperammonemia and brain edema in cirrhotic rats with portal occlusion.METHODS: Rats with CCl4-induced cirrhosis with ascites plus portal vein occlusion and controls were randomized into six groups: Cirrhosis; Cirrhosis + IGF-1; Cirrhosis + rifaximin; Controls; Controls + IGF-1; and Controls + rifaximin. An oral glutamine-challenge test was performed, and plasma and cerebral ammonia, glucose, bilirubin, transaminases, endotoxemia, brain water content and ileocecal cultures were measured and liver histology was assessed.RESULTS: Rifaximin treatment significantly reduced bacterial overgrowth and endotoxemia compared with cirrhosis groups, and improved some liver function parameters (bilirubin, alanine aminotransferase and aspartate aminotransferase). These effects were associated with a significant reduction in cerebral water content. Blood and cerebral ammonia levels, and area-under-the-curve values for oral glutamine-challenge tests were similar in rifaximin-treated cirrhotic rats and control group animals. By contrast, IGF-1 administration failed to improve most alterations observed in cirrhosis.CONCLUSION: By reducing gut bacterial overgrowth, only rifaximin was capable of normalizing plasma and brain ammonia and thereby abolishing low-grade brain edema, alterations associated with hepatic encephalopathy. 相似文献