Citations

Abstract To better understand the molecular mechanisms behind esophageal adenocarcinoma (EAC) tumorigenesis, we used high-density single nucleotide polymorphism arrays to profile chromosomal aberrations at each of the four sequential progression stages, Barrett's metaplasia (BM), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC, in 101 patients. We observed a significant trend toward increasing loss of chromosomes with higher progression stage. For BM, LGD, HGD, and EAC, respectively, the average numbers of chromosome arms with loss per sample were 0.30, 3.21, 7.70, and 11.90 (P for trend = 4.82 × 10−7), and the mean percentages of single nucleotide polymorphisms with allele loss were 0.1%, 1.8%, 6.6%, and 17.2% (P for trend = 2.64 × 10−6). In LGD, loss of 3p14.2 (68.4%) and 16q23.1 (47.4%) was limited to narrow regions within the FHIT (3p14.2) and WWOX (16q23.1) genes, whereas loss of 9p21 (68.4%) occurred in larger regions. A significant increase in the loss of other chromosomal regions was seen in HGD and EAC. Loss of 17p (47.6%) was one of the most frequent events in EAC. Many recurrent small regions of chromosomal loss disrupted single genes, including FHIT, WWOX, RUNX1, KIF26B, MGC48628, PDE4D, C20orf133, GMDS, DMD, and PARK2, most of which are common fragile site regions in the human genome. However, RUNX1 at 21q22 seemed to be a potential tumor suppressor gene in EAC. Amplifications were less frequent than losses and mostly occurred in EAC. 8q24 (containing Myc) and 8p23.1 (containing CTSB) were the two most frequently amplified regions. In addition, a significant trend toward increasing amplification was associated with higher progression stage. Cancer Prev Res; 3(9); 1176–86. ©2010 AACR.

Abstract The mechanisms that render tau a toxic agent are still unclear, although increasing evidence supports the assertion that alterations of tau can directly cause neuronal degeneration. In addition, it is unclear whether neurodegeneration in various tauopathies occurs via a common mechanism or that specific differences exist. The aim of this review is to provide an overview of tauopathies from bench to bedside. The review begins with clinicopathological findings of familial and sporadic tauopathies. It includes a discussion of the similarities and differences between these two conditions. The second part concentrates on biochemical alterations of tau such as phosphorylation, truncation and acetylation. Although pathological phosphorylation of tau has been studied for many years, recently researchers have focused on the physiological role of tau during development. Finally, the review contains a summary of the significance of tauopathy model mice for research on neurofibrillary tangles, axonopathies, and synaptic alteration.

Abstract Diffuse large B-cell lymphoma (DLBCL) can be separated for prognostic purposes using gene expression profiling (GEP) into 2 subgroups: germinal center B-cell (GCB) and activated B-cell phenotypes. However, GEP is impractical for routine clinical use, and immunophenotyping is an imperfect surrogate. Therefore, we studied the relationship between expression of the purported germinal center marker LMO2 and the presence of IGH-BCL2 fusions, BCL6 translocations, and LMO2 translocations. In addition, we investigated the usefulness of LMO2 expression as a marker of GCB subtype in DLBCL. Immunohistochemical and fluorescence in situ hybridization studies were successfully performed on 101 cases of de novo DLBCL that had been incorporated into a tissue microarray. There was a statistically significant association between IGH-BCL2 fusion and LMO2 protein expression (P = .02) but not between BCL6 translocations and LMO2 expression. LMO2 translocations were not identified. Although uncommon, all cases that had both IGH-BCL2 fusion and BCL6 translocations expressed LMO2. The findings suggest LMO2 as a potential marker for the GCB phenotype.

Background— Whether mechanical dyssynchrony indices predict reverse remodeling (RR) or clinical response to cardiac resynchronization therapy (CRT) remains controversial. This prospective study evaluated whether echocardiographic dyssynchrony indices predict RR or clinical response after CRT. Methods and Results— Of 184 patients with heart failure with anticipated CRT who were prospectively enrolled, 131 with wide QRS and left ventricular ejection fraction <35% had 6-month follow-up after CRT implantation. Fourteen dyssynchrony indices (feasibility) by M-mode (94%), tissue velocity (96%), tissue Doppler strain (92%), 2D speckle strain (65% to 86%), 3D echocardiography (79%), and timing intervals (98%) were evaluated. RR (end-systolic volume reduction ≥15%) occurred in 55% and more frequently in patients without (71%) than in patients with (42%) ischemic cardiomyopathy ( P =0.002). Overall, only M-mode, tissue Doppler strain, and total isovolumic time had a receiver operating characteristic area under the curve (AUC) greater than the line of no information, but none of these were strongly predictive of RR (AUC, 0.63 to 0.71). In nonischemic cardiomyopathy, no dyssynchrony index predicted RR. In ischemic cardiomyopathy, M-mode (AUC, 0.67), tissue Doppler strain (AUC, 0.79), and isovolumic time (AUC, 0.76) -derived indices predicted RR ( P <0.05 for all), although the incremental value was modest. No indices predicted clinical response assessed by Minnesota Living with Heart Failure Questionnaire, 6-minute walk distance, and peak oxygen consumption. Conclusions— These findings are consistent with the Predictors of Response to CRT study and do not support use of these dyssynchrony indices to guide use of CRT.

Background— Contrast-induced nephropathy (CIN) is associated with significant morbidity and mortality. The objective of our meta-analysis was to assess the efficacy of iodixanol compared with low-osmolar contrast media (LOCM) for prevention of CIN. Methods and Results— We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and internet sources of cardiology trial results for individual and relevant reviews of randomized, controlled trials, for the terms contrast media, contrast nephropathy, renal failure, iodixanol, Visipaque, and low-osmolar contrast media. All studies reported an incidence rate of CIN for each study group; there was no restriction on the definition of CIN. There were no restrictions on journal type or patient population. Overall, 36 trials were identified for analysis of aggregated summary data on 7166 patients; 3672 patients received iodixanol and 3494 patients received LOCM. Overall, iodixanol showed no statistically significant reduction in CIN incidence below that observed with heterogeneous comparator agents ( P =0.11). Analysis of patient subgroups revealed that there was a significant benefit of iodixanol when compared with iohexol alone (odds ratio, 0.25; 95% confidence interval, 0.11 to 0.55; P <0.001) but not when compared with LOCM other than iohexol or with other ionic dimers or among patients receiving intra-arterial contrast injections or among patients undergoing coronary angiography with or without percutaneous intervention. Conclusions— Analysis of aggregated summary data from multiple randomized, controlled trials of iodixanol against diverse LOCMs for heterogeneous procedures and definitions of CIN show an iodixanol-associated reduction that is suggestive but statistically nonsignificant.