37 research outputs found

    An overview of cancer/testis antigens expression in classical Hodgkin's lymphoma (cHL) identifies MAGE-A family and MAGE-C1 as the most frequently expressed antigens in a set of Brazilian cHL patients

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    <p>Abstract</p> <p>Background</p> <p>Cancer/testis antigens are considered potential targets for immunotherapy due to their tumor-associated expression pattern. Although recent studies have demonstrated high expression of CT45 in classical Hodgkin's lymphomas (cHL), less is known about the expression pattern of other families of CTAs in cHL. We aim to evaluate the expression of MAGE-A family, MAGE-C1/CT7, MAGE-C2/CT10, NY-ESO1 and GAGE family in cHL and to correlate their expression with clinical and prognostic factors in cHL.</p> <p>Methods</p> <p>Tissue microarray was generated from 38 cHL archival cases from Pathology Department of Universidade Federal de Sao Paulo. Immunohistochemistry (IHC) was done using the following panel of antibodies: MAGE-A family (MA454, M3H67, 57B and 6C1), GAGE (#26), NY-ESO-1 (E978), MAGE-C1/CT7 (CT7-33) and MAGE-C2/CT10 (CT10#5).</p> <p>Results</p> <p>We found CTA expression in 21.1% of our cHL series. Among the tested CTAs, only MAGE-A family 7/38 (18.4%) and MAGE-C1/CT7 5/38 (13.2%) were positive in our cHL samples. We found higher CTA positivity in advanced stage (28.6%) compared to early stage (11.8%) disease, but this difference was not statistically significant. Analysis of other clinicopathological subgroups of cHL including histological subtypes, EBV status and response to treatment also did not demonstrate statistical significant differences in CTA expression.</p> <p>Conclusion</p> <p>We found CTA expression in 21.1% of cHL samples using our panel. Our preliminary findings suggest that from all CTAs included in this study, MAGE-A family and MAGE-C1/CT7 are the most interesting ones to be explored in further studies.</p

    Outcome of cardiac surgery in patients with low preoperative ejection fraction

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    Background: In patients undergoing cardiac surgery, a reduced preoperative left ventricular ejection fraction (LVEF) is common and is associated with a worse outcome. Available outcome data for these patients address specific surgical procedures, mainly coronary artery bypass graft (CABG). Aim of our study was to investigate perioperative outcome of surgery on patients with low pre-operative LVEF undergoing a broad range of cardiac surgical procedures. Methods: Data from patients with pre-operative LVEF ≤40 % undergoing cardiac surgery at a university hospital were reviewed and analyzed. A subgroup analysis on patients with pre-operative LVEF ≤30 % was also performed. Results: A total of 7313 patients underwent cardiac surgery during the study period. Out of these, 781 patients (11 %) had a pre-operative LVEF ≤40 % and were included in the analysis. Mean pre-operative LVEF was 33.9 ± 6.1 % and in 290 patients (37 %) LVEF was ≤30 %. The most frequently performed operation was CABG (31 % of procedures), followed by mitral valve surgery (22 %) and aortic valve surgery (19 %). Overall perioperative mortality was 5.6 %. Mitral valve surgery was more frequent among patients who did not survive, while survivors underwent more frequently CABG. Post-operative myocardial infarction occurred in 19 (2.4 %) of patients, low cardiac output syndrome in 271 (35 %). Acute kidney injury occurred in 195 (25 %) of patients. Duration of mechanical ventilation was 18 (12-48) hours. Incidence of complications was higher in patients with LVEF ≤30 %. Stepwise multivariate analysis identified chronic obstructive pulmonary disease, pre-operative insertion of intra-aortic balloon pump, and pre-operative need for inotropes as independent predictors of mortality among patients with LVEF ≤40 %. Conclusions: We confirmed that patients with low pre-operative LVEF undergoing cardiac surgery are at higher risk of post-operative complications. Cardiac surgery can be performed with acceptable mortality rates; however, mitral valve surgery, was found to be associated with higher mortality rates in this population. Accurate selection of patients, risk/benefit evaluation, and planning of surgical and anesthesiological management are mandatory to improve outcome

    Unbiased Quantitation of Alveolar Type II to Alveolar Type I Cell Transdifferentiation during Repair after Lung Injury in Mice

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    The alveolar epithelium consists of squamous alveolar type (AT) I and cuboidal ATII cells. ATI cells cover 95-98% of the alveolar surface, thereby playing a critical role in barrier integrity, and are extremely thin, thus permitting efficient gas exchange. During lung injury, ATI cells die, resulting in increased epithelial permeability. ATII cells re-epithelialize the alveolar surface via proliferation and transdifferentiation into ATI cells. Transdifferentiation is characterized by down-regulation of ATII cell markers, up-regulation of ATI cell markers, and cell spreading, resulting in a change in morphology from cuboidal to squamous, thus restoring normal alveolar architecture and function. The mechanisms underlying ATII to ATI cell transdifferentiation have not been well studied in vivo. A prerequisite for mechanistic investigation is a rigorous, unbiased method to quantitate this process. Here, we used SPCCreERT2;mTmG mice, in which ATII cells and their progeny express green fluorescent protein (GFP), and applied stereologic techniques to measure transdifferentiation during repair after injury induced by LPS. Transdifferentiation was quantitated as the percent of alveolar surface area covered by ATII-derived (GFP+) cells expressing ATI, but not ATII, cell markers. Using this methodology, the time course and magnitude of transdifferentiation during repair was determined. We found that ATI cell loss and epithelial permeability occurred by Day 4, and ATII to ATI cell transdifferentiation began by Day 7 and continued until Day 16. Notably, transdifferentiation and barrier restoration are temporally correlated. This methodology can be applied to investigate the molecular mechanisms underlying transdifferentiation, ultimately revealing novel therapeutic targets to accelerate repair after lung injury
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