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Exosomes are tiny membrane-bound vesicles that are over produced by most proliferating cell types during normal and pathological states. Their levels are up-regulated during pregnancy and disease states such as cancer. Exosomes contain a wide variety of proteins, lipids, RNAs, non-transcribed RNAs, microRNAs and small RNAs that are representative to their cellular origin and shuttle from a donor cell to a recipient cell. From intercellular communication to tumor proliferation, exosomes carry out a diverse range of functions, both helpful and harmful. Useful as biomarkers, exosomes may be applicable in diagnostic assessments as well as cell-free anti-tumor vaccines. Exosomes of ovarian cancer contain different set of proteins and miRNAs compared to exosomes of normal, cancer-free individuals. These molecules may be used as multiple "barcode" for the development of a diagnostic tool for early detection of ovarian cancer. [ABSTRACT FROM AUTHOR]

Data on the duration of transgene expression in the liver, the presence of cytotoxic T lymphocytes (CTLs) against adenovirus, and serum cytokines from 18 strains of C57BL/6×DBA/2 (B×D) recombinant inbred mice were analyzed. Our aim was to detect quantitative trait loci (QTLs) that may have causal relationship with the duration of adenovirus-mediated transgene expression in the liver. Information from β-galactosidase (LacZ) expression; CTL production; and serum levels of gamma interferon, tumor necrosis factor-α, and interleukin-6 30 days after intravenous injection of liver LacZ were summarized by principal component analysis and analyzed using maximum likelihood interval mapping implemented in the QTL cartographer software. Two principal component (PC) scores explained 82.5% of the phenotypic variance in the original variables and identified QTLs not identified by analysis of individual traits. The distribution of original variables among PCs was such that variables in PC1 were predominantly cytokines with little CTL response whereas LacZ and CTL were the predominant contributors to PC2 with practically no contribution from cytokines. PC1 was significantly associated with two QTLs on chromosomes 7 and 9 located at 57.5 cM and 41.01 cM, respectively. Five QTLs were significantly associated with PC2 on chromosomes 12 (23.01 and 31.01 cM) and 15 (29.21, 36.01, and 56.31 cM). These results illustrate the use of principal component analysis in mapping QTLs using multiple correlated traits. [ABSTRACT FROM AUTHOR]

Background There is no general agreement about whether patients who have already received neoadjuvant chemoradiotherapy need further postoperative chemotherapy based on 5-fluorouracil(5-FU) or 5-FU plus oxaliplatin. Methods Medicare beneficiaries from 1992 to 2008 with Union for International Cancer Control ypStages I to III primary carcinoma of the rectum who underwent 5-FU-based neoadjuvant chemoradiotherapy and surgery for curative intent were identified through the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. A Cox proportional hazards model and propensity score-matched techniques were used to evaluate the effect of treatment on survival. Results For patients with resected rectal cancer who have already received 5-FU-based neoadjuvant chemoradiotherapy, postoperative 5-FU-based chemotherapy did not prolong cancer-specific survival (CSS) in ypStage I (P = 0.960) and ypStage II (P = 0.134); however, it significantly improved the CSS in ypStage III (hazard ratio = 1.547, 95% CI = 1.101-2.173, P = 0.012). No significant differences in survival between the 5-FU group and oxaliplatin group were observed. Conclusions For patients with resected rectal cancer who have already received 5-FU-based neoadjuvant chemoradiotherapy, postoperative 5-FU-based chemotherapy prolongs the CSS of groups in ypStage III. Adding oxaliplatin to fluoropyrimidines in the postoperative chemotherapy did not improve the CSS for patients who received neoadjuvant chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: There is no general agreement about whether patients who have already received neoadjuvant chemoradiotherapy need further postoperative chemotherapy based on 5-fluorouracil(5-FU) or 5-FU plus oxaliplatin. Methods: Medicare beneficiaries from 1992 to 2008 with Union for International Cancer Control ypStages I to III primary carcinoma of the rectum who underwent 5-FU-based neoadjuvant chemoradiotherapy and surgery for curative intent were identified through the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. A Cox proportional hazards model and propensity score-matched techniques were used to evaluate the effect of treatment on survival. Results: For patients with resected rectal cancer who have already received 5-FU-based neoadjuvant chemoradiotherapy, postoperative 5-FU-based chemotherapy did not prolong cancer-specific survival (CSS) in ypStage I (P = 0.960) and ypStage II (P = 0.134); however, it significantly improved the CSS in ypStage III (hazard ratio = 1.547, 95% CI = 1.101-2.173, P = 0.012). No significant differences in survival between the 5-FU group and oxaliplatin group were observed. Conclusions: For patients with resected rectal cancer who have already received 5-FU-based neoadjuvant chemoradiotherapy, postoperative 5-FU-based chemotherapy prolongs the CSS of groups in ypStage III. Adding oxaliplatin to fluoropyrimidines in the postoperative chemotherapy did not improve the CSS for patients who received neoadjuvant chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background: Both laparoscopic and fast-track surgery (FTS) have shown some advantages in colorectal surgery. However, the effectiveness of using both methods together is unclear. We performed this meta-analysis to compare the effects of FTS with those of traditional perioperative care in laparoscopic colorectal cancer surgery. Methods: We searched the PubMed, EMBASE, Cochrane Library, and Ovid databases for eligible studies until April 2014. The main end points were the duration of the postoperative hospital stay, time to first flatus after surgery, time of first bowel movement, total postoperative complication rate, readmission rate, and mortality. Results: Five randomized controlled trials and 5 clinical controlled trials with 1,317 patients were eligible for analysis. The duration of the postoperative hospital stay (weighted mean difference [WMD], -1.64 days; 95% confidence interval [CI], -2.25 to -1.03; p < 0.001), time to first flatus (WMD, -0.40 day; 95% CI, -0.77 to -0.04; p = 0.03), time of first bowel movement (WMD, -0.98 day; 95% CI, -1.45 to -0.52; p < 0.001), and total postoperative complication rate (risk ratio [RR], 0.67; 95% CI, 0.56-0.80; p < 0.001) were significantly reduced in the FTS group. No significant differences were noted in the readmission rate (RR, 0.64; 95% CI, 0.41-1.01; p = 0.06) or mortality (RR, 1.55; 95% CI, 0.42-5.71; p = 0.51). Conclusion: Among patients undergoing laparoscopic colorectal cancer surgery, FTS is associated with a significantly shorter postoperative hospital stay, more rapid postoperative recovery, and, notably, greater safety than is expected from traditional care. [ABSTRACT FROM AUTHOR]

Background: Catalase (CAT) breaks down H2O2 into H2O and O2 to protects cells from oxidative damage. However, its translational potential is limited because exogenous CAT cannot enter living cells automatically. This study is aimed to investigate if PEP-1-CAT fusion protein can effectively protect cardiomyocytes from oxidative stress due to hypoxia/reoxygenation (H/R)-induced injury. Methods: H9c2 cardomyocytes were pretreated with catalase (CAT) or PEP-1-CAT fusion protein followed by culturing in a hypoxia and re-oxygenation condition. Cell apoptosis were measured by Annexin V and PI double staining and Flow cytometry. Intracellular superoxide anion level was determined, and mitochondrial membrane potential was measured. Expression of apoptosis-related proteins including Bcl-2, Bax, Caspase-3, PARP, p38 and phospho-p38 was analyzed by western blotting. Results: PEP-1-CAT protected H9c2 from H/R-induced morphological alteration and reduced the release of lactate dehydrogenase (LDH) and malondialdehyde content. Superoxide anion production was also decreased. In addition, PEP- 1-CAT inhibited H9c2 apoptosis and blocked the expression of apoptosis stimulator Bax while increased the expression of Bcl-2, leading to an increased mitochondrial membrane potential. Mechanistically, PEP-1-CAT inhibited p38 MAPK while activating PI3K/Akt and Erk1/2 signaling pathways, resulting in blockade of Bcl2/Bax/mitochondrial apoptotic pathway. Conclusion: Our study has revealed a novel mechanism by which PEP-1-CAT protects cardiomyocyte from H/R-induced injury. PEP-1-CAT blocks Bcl2/Bax/mitochondrial apoptotic pathway by inhibiting p38 MAPK while activating PI3K/Akt and Erk1/2 signaling pathways. [ABSTRACT FROM AUTHOR]

Introduction: Spontaneous osteonecrosis of the navicular bone in adults is a rare entity, known as Müller-Weiss syndrome. We report here on our experience with six patients with Müller-Weiss syndrome accompanied by flatfoot deformity, but on a literature search found no reports on this phenomenon. Because the natural history and treatment are controversial, an understanding of how to manage this deformity may be helpful for surgeons when choosing the most appropriate operative procedure. Case presentation: Six patients (five women, one man; average age, 54 years) with flatfoot caused by osteonecrosis of the navicular bone were followed up between January 2005 and December 2008 (mean follow-up period, 23.2 months). Conservative treatment, such as physical therapy, and non-steroidal anti-inflammatory drugs were used, but failed. Physical examinations revealed flattening of the medial arch of the involved foot and mild tenderness at the mid-tarsal joint. Weight-bearing X-rays (anterior-posterior and lateral views), computed tomography, and MRI scans were performed for each case. Talonavicular joint arthrodesis was performed in cases of single talonavicular joint arthritis. Triple arthrodesis was performed in cases of triple joint arthritis to reconstruct the medial arch. Clinical outcomes were assessed using the American Orthopaedic Foot and Ankle Society ankle-hindfoot scale; the scores were 63.0 pre-operatively and 89.8 post-operatively. All patients developed bony fusion. Conclusions: The reason for the development of flatfoot in patients with Müller-Weiss syndrome is unknown. Surgical treatment may achieve favorable outcomes in terms of deformity correction, pain relief, and functional restoration. The choice of operative procedure may differ in patients with both flatfoot and posterior tibial tendon dysfunction. [ABSTRACT FROM AUTHOR]

Background: Our previous studies indicate that either PEP-1-superoxide dismutase 1 (SOD1) or PEP-1-catalase (CAT) fusion proteins protects myocardium from ischemia-reperfusion-induced injury in rats. The aim of this study is to explore whether combined use of PEP-1-SOD1 and PEP-1-CAT enhances their protective effects.Methods: SOD1, PEP-1-SOD1, CAT or PEP-1-CAT fusion proteins were prepared and purified by genetic engineering. In vitro and in vivo effects of these proteins on cell apoptosis and the protection of myocardium after ischemia-reperfusion injury were measured. Embryo cardiac myocyte H9c2 cells were used for the in vitro studies. In vitro cellular injury was determined by the expression of lactate dehydrogenase (LDH). Cell apoptosis was quantitatively assessed with Annexin V and PI double staining by Flow cytometry. In vivo, rat left anterior descending coronary artery (LAD) was ligated for one hour followed by two hours of reperfusion. Hemodynamics was then measured. Myocardial infarct size was evaluated by TTC staining. Serum levels of myocardial markers, creatine kinase-MB (CK-MB) and cTnT were quantified by ELISA. Bcl-2 and Bax expression in left ventricle myocardium were analyzed by western blot.Results: In vitro, PEP-1-SOD1 or PEP-1-CAT inhibited LDH release and apoptosis rate of H9c2 cells. Combined transduction of PEP-1-SOD1 and PEP-1-CAT, however, further reduced the LDH level and apoptosis rate. In vivo, combined usage of PEP-1-SOD1 and PEP-1-CAT produced a greater effect than individual proteins on the reduction of CK-MB, cTnT, apoptosis rate, lipoxidation end product malondialdehyde, and the infarct size of myocardium. Functionally, the combination of these two proteins further increased left ventricle systolic pressure, but decreased left ventricle end-diastolic pressure.Conclusion: This study provided a basis for the treatment or prevention of myocardial ischemia-reperfusion injury with the combined usage of PEP-1-SOD1 and PEP-1-CAT fusion proteins. [ABSTRACT FROM AUTHOR]