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Selected AbstractsMolecular dissection of the chromosome band 7q21 amplicon in gastroesophageal junction adenocarcinomas identifies cyclin-dependent kinase 6 at both genomic and protein expression levelsGENES, CHROMOSOMES AND CANCER, Issue 8 2008H. van Dekken Amplification of chromosome band 7q21 has been frequently detected in various types of cancer including gastroesophageal junction (GEJ) adenocarcinomas. At present, no gene has been disclosed that can explain this frequent amplification of 7q21 in GEJ carcinomas. Therefore, a detailed genomic analysis of the 7q21 region was performed on a selected series of GEJ adenocarcinomas, i.e., 14 primary adenocarcinomas and 10 cell lines, by array comparative genomic hybridization (aCGH) with a 7q11.22-q31.2 contig array. A distinct peak of amplification was identified at 92.1 Mb in 7q21.2, precisely comprising cyclin-dependent kinase 6 (CDK6), a gene involved in cell cycle regulation. A smaller peak was seen at 116.2 Mb in 7q31.2, the locus of the MET proto-oncogene. No distinct peak was detected for the hepatocyte growth factor (HGF) at 81.3 Mb in 7q21.11. An immunoprofile of HGF, CDK6 and MET revealed a strong correlation between aCGH and immunohistochemical protein expression for CDK6 (P = 0.002). Furthermore, immunohistochemistry did not show expression of CDK6 in Barrett's dysplasia and carcinoma in situ, correlating expression of CDK6 with a malignant phenotype. We conclude that high-resolution genomic analysis and immunoprofiling identify CDK6 as the main candidate target for the recurrent amplification of 7q21 in GEJ adenocarcinomas. © 2008 Wiley-Liss, Inc. [source] Early and Late Results of Partial Left Ventriculectomy: Single Center Experience and Review of the LiteratureJOURNAL OF CARDIAC SURGERY, Issue 3 2003Raimondo Ascione M.D. Methods: From February 1996 to August 2001, 24 patients with dilated cardiomyopathy (DCM) (12 idiopathic, 12 ischemic) underwent PLV. Perioperative and follow-up data were prospectively entered into a database and analyzed. An observational analysis of the literature was carried out of all the published series of PLV reporting on ,15 patients. Results: In our series there were 22 males with amean age of 65 years (range 49 to73]). Of the 22, there were 3 (12.5%) in-hospital deaths. Mean duration of follow-up was 26 months (range 3 to 71) with 9 late deaths (38%), 6 in the idiopathic group. The five-year actuarial survival was 74% in the ischemic group and 33% in the idiopathic group. The observational analysis of literature included a total of 506 patients (425 males, age 50.2 ± 5.2 years)]. The etiology was idiopathic in 255 (50.4%), and ischemic in 89 (17.6%) patients. Baseline characteristics of the whole population include: ejection fraction 18.9 ± 3.9%, NYHA functional class 3.7 ± 0.2, and LVEDD of 7.7 ± 0.4 cm. Severe mitral regurgitation was present in 368 (72.7%) patients. There were 88 (17.4%) in-hospital deaths. Cause of death included 55 due to (62.5%) low cardiac output, 10 (11.3%) due to severe bleeding, 7 (7.95%) caused by malignant arrhythmias, 8 (9%) due to sepsis, and 5 (5.7%) as a result of stroke. Ten of the selected series (overall 386 patients) reported late outcome. There were 89 (22.9%) late deaths, 12 (13.5%) were not cardiac-related, 50 (56.2%) were due to recurrence of congestive heart failure (CHF), 20 (22.5%) caused by sudden arrhythmias, 5 (5.6%) due to infections, and 2 (2.2%) from strokes. Overall, there were 248 (64.2%) survivors, of whom 179 (72.17%) were reported to be in NYHA functional class I or II. All 10 papers reported one-year survival ranging from 50% to 85%. Seven reported a two-year survival of 45% to 72%, and 4 reported a three-year survival of 33% to 64%. Conclusions: Our results and the review of the literature seem to suggest a relatively high early mortality with satisfactory late results of PLV in patients with dilated cardiomyopathy.(J Card Surg 2003;18:190-196) [source] The importance of gel properties for mucoadhesion measurements: a multivariate data analysis approachJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2004Helene Hägerström ABSTRACT In this study we used tensile strength measurements and a recently developed interpretation procedure to evaluate the mucoadhesive properties of a large set of gel preparations with diverse rheological properties. Multivariate data analysis in the form of principal component analysis (PCA) and partial least square projection to latent structures (PLS) was applied to extract useful information from the rather large quantities of data obtained. PCA showed that the selected series of gels was heterogeneous. Some groupings could be detected but none of the gels was identified as an outlier. By using PLS we investigated the relations between the rheological properties of a gel and the parameters defining the cohesiveness, as measured with the texture analyser used for the mucoadhesion measurements. The rheological properties proved to be important for the results of both the mucoadhesion and the cohesiveness measurements. Furthermore, by using PLS two different measurement configurations were evaluated and it was concluded that the combination of a relatively small volume of gel and two pieces of mucosa seems to be more appropriate than a large volume of gel in combination with one piece of mucosa. [source] Comparison of atopic and nonatopic children with chronic cough: Bronchoalveolar lavage cell profile,PEDIATRIC PULMONOLOGY, Issue 10 2007Flavia de A Ferreira MD Abstract Chronic cough is a common complaint in children and its relationship with asthma is controversial. The aim of the present study was to determine the pattern of airway inflammation in atopic and nonatopic children with chronic cough, and to investigate whether atopy is a predictive factor for eosinophilic inflammation in cough. Bronchoalveolar lavage (BAL; three aliquots of 1 ml/kg saline) was performed in the right middle lobe of 24 (11 atopic and 13 nonatopic) children with persistent cough (8 females, 16 males), mean age 4.7 years (range: 1,11). Atopy was defined as an elevated total serum IgE or a positive RAST test. Both atopic and nonatopic children with persistent cough had an increase in total cells/ml in BAL (atopic: median 39,×,104, range: 20,123; nonatopic: median 22,×,104, range: 17,132) compared to nonatopic controls (median 11,×,104, range 9,30). The increases were mainly in neutrophils (atopic: median 17%, range 2.5,88.5%; nonatopic: median 6%, range 1.0,55.0%) compared to controls (median 1.55%, range 0.5,7.0%; atopics vs. controls, P,<,0.005). There were no significant increases in eosinophils, lymphocytes, epithelial cells, or mast cells. Eosinophils were elevated in only 5/11 atopic and none of the nonatopic children. The increased percentage of neutrophils in the BAL fluid of atopic and nonatopic children with persistent cough could be due to an underlying inflammatory process driving the cough, or even conceivably, due to the effect of coughing itself. In this highly selected series, the absence of eosinophilic inflammation in the majority suggests that most would be predicted not to respond to inhaled corticosteroid therapy. This study underscores the need to be cautious about treating coughing children with inhaled corticosteroids, even in the context of a tertiary referral practice. Pediatr Pulmonol. 2007;42:857,863. © 2007 Wiley-Liss, Inc. [source] Fas ligand and tumour counter-attack in colorectal cancer stratified according to microsatellite instability statusTHE JOURNAL OF PATHOLOGY, Issue 1 2003Julie M Michael-Robinson Abstract Expression of membrane-bound Fas ligand (FasL) by colorectal cancer cells may allow the development of an immune-privileged site by eliminating incoming tumour-infiltrating lymphocytes (TILs) in a Fas-mediated counter-attack. Sporadic colorectal cancer can be subdivided into three groups based on the level of DNA microsatellite instability (MSI). High-level MSI (MSI-High) is characterized by the presence of TILs and a favourable prognosis, while microsatellite-stable (MSS) cancers are TIL-deficient and low-level MSI (MSI-Low) is associated with an intermediate TIL density. The purpose of this study was to establish the relationship between MSI status and FasL expression in primary colorectal adenocarcinoma. Using immunohistochemistry and a selected series of 101 cancers previously classified as 31 MSI-High, 30 MSI-Low, and 40 MSS, the present study sought to confirm the hypothesis that increased TIL density in MSI-High cancers is associated with low or absent membrane-bound FasL expression, while increased FasL in MSS cancers allows the killing of host TILs. TUNEL/CD3 double staining was also used to determine whether MSS cancers contain higher numbers of apoptotic TILs in vivo than MSI-High or MSI-Low cancers. Contrary to the initial hypothesis, it was found that MSI-High cancers were associated with higher FasL expression (p = 0.04) and a stronger intensity of FasL staining (p = 0.007). In addition, mucinous carcinomas were independently characterized by increased FasL expression (p = 0.03) and staining intensity (p = 0.0005). Higher FasL expression and staining intensity did not correlate with reduced TIL density or increased numbers of apoptotic TILs. However, consistent with the hypothesis that curtailment of the host anti-tumour immune response contributes to the poor prognosis in MSS cancers, it was found that apoptotic TILs were most abundant in MSS carcinomas and metastatic Dukes' stage C or D tumours (p = 0.004; p = 0.046 respectively). This study therefore suggests that MSS colorectal cancers are killing incoming TILs in an effective tumour counter-attack, but apparently not via membrane-bound FasL. Copyright © 2003 John Wiley & Sons, Ltd. [source] |