Highlights from the 8th World Congress on Peritoneal Surface Malignancies

The 8th World Congress on Peritoneal Surface Malignancies was held in Berlin,Germany from October 31,2012 to November 2,2012,in which more than 571 delegates from 56 countries attended.This conference covered a variety of topics on peritoneal carcinomatosis(PC) from gastric, colorectal,and ovarian cancers,as well as pseudomyxoma peritonei,malignant peritoneal mesothelioma,and abdominal sarcoma.PC experts across the world presented the most upto -date results of their basic and translational studies as well as clinical trials.In particular,the following research interests were highlighted. Professor Paul H.Sugarbaker from the Washington Hospital Cancer Center,Washington DC,USA,systemically     

A Fatal Case of Thrombotic Microangiopathy Without Schistocytosis and Absent Biochemical Markers of Hemolysis

Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia with thrombocytopenia. In addition to the primary TMA syndromes, microangiopathic hemolytic anemia with thrombocytopenia can be seen in many systemic diseases. Transplant associated TMA (TA-TMA) affects patients following stem cell or solid organ transplant. A 48-year-old male who underwent autologous stem cell transplant for nonsecretory multiple myeloma was admitted to our hospital with worsening anemia, thrombocytopenia, renal dysfunction and hepatosplenomegaly. Initial blood work revealed rare schistocytes and normal lactate dehydrogenase and haptoglobin levels. He underwent an extensive workup looking for an infectious, inflammatory or malignant etiology but a definitive diagnosis could not be reached. Over his prolonged stay at the hospital, he suffered from multiorgan failure and eventually passed away. An autopsy revealed TMA involving all clinically affected organ systems and was deemed to be the cause of his demise. The absence of typical blood work suggestive of hemolysis does not rule out a diagnosis of TA-TMA. Knowledge of this rare disease entity will help physicians identify and treat this life-threatening condition early and effectively.     

Alu Methylation and Risk of Cancer: A Meta-analysis

BackgroundThe association between Alu methylation and risk of cancer remains uncertain. This meta-analysis was conducted to elucidate this issue.Materials and MethodsPubMed and Web of Science up to December 31, 2018, and the reference lists of studies, as well as those presented in relevant meta-analyses and reviews were systematically searched. Standardized mean difference (SMD) in Alu methylation level between cases and controls were pooled using random effects model and assessed heterogeneity between strata by stratified factors using meta-regression model. Sensitivity analysis and publication bias test were also conducted.ResultsTwenty-five articles, including 2719 cases and 3018 controls were included in the meta-analysis. The significant difference in Alu methylation level between cancer cases and controls was greater in tissue (SMD = −1.89, 95% CI: −2.72, −1.05) than blood (SMD = −0.46, 95% CI: −0.82, −0.09), and heterogeneity was found in materials (P = 0.038). In tissue samples, Alu hypomethylation was found in carcinoma (SMD = −2.50, 95% CI: −3.51, −1.48), while not in non-carcinoma. The inverse associations were consistently found in subgroups stratified by data sources and quality score in tissue samples, and publication year was considered to be the potential source of between-study heterogeneity. Moreover, reduced Alu methylation level was found in the European subgroup, detection method of SIRPH and COBRA, and original data source in blood samples.ConclusionsAlu hypomethylation was associated with increased risk of cancer, which could be a potential biomarker for cancer.     

Prognostic Utility of Monocyte to High-Density Lipoprotein Ratio in Patients With Acute Coronary Syndrome: A Meta-Analysis

BackgroundThe monocyte to high-density lipoprotein ratio (MHR) has been used to predict adverse clinical outcomes in patients with acute coronary syndrome (ACS). This meta-analysis aimed to evaluate the prognostic utility of MHR in patients with ACS.Materials and MethodsWe comprehensively searched for relevant studies in Pubmed, Embase, CNKI, WanFang and VIP databases until March 12, 2019. Epidemiologic studies investigating the association between MHR and major adverse cardiovascular events (MACE) or all-cause mortality in patients with ACS were included. Pooled effect was expressed as risk ratios (RR) with 95% confidence intervals (CI) for the highest versus the reference lower MHR group.ResultsEight studies involving 6,480 patients with ACS were included and analyzed. Meta-analysis indicated that the highest MHR was significantly associated with higher risk of MACE (RR 1.65; 95%CI 1.36-2.02) and all-cause mortality (RR 2.61; 95%CI 1.29-4.89) after adjusting for the conventional confounders. The prognostic values of MACE with the highest MHR caused no significant changes in the in-hospital follow-up (RR 1.76; 95%CI 1.34-2.32) and >6 months follow-up (RR 1.68; 95%CI 1.08-2.62) subgroups. Furthermore, ST elevation myocardial infarction patients with the highest MHR had a 2.07-fold higher risk of in-hospital MACE (RR 2.07; 95%CI 1.52-2.80).ConclusionsElevated MHR is independently associated with an increased risk of MACE and all-cause mortality in patients with ACS. MHR may serve as a potential prognostic indicator for ACS prognosis.     

硒结合蛋白1通过抑制超氧化物歧化酶增强奥沙利铂的细胞毒作用

目的:探讨人硒结合蛋白1(SBP1)在结直肠癌DLD-1细胞中的表达水平对超氧化物歧化酶(SOD)的影响及其引起的DLD-1细胞对奥沙利铂的敏感性变化,揭示SBP1的部分抗肿瘤作用机制。方法:MTS法检测不同浓度奥沙利铂处理SBP1siRNA或SOD1siRNA转染细胞后的细胞存活率,CuZn/Mn-SOD活性检测试剂盒检测SBP1siRNA转染对DLD-1细胞SOD酶活性的影响;实时荧光定量PCR检测下调SBP1后,SOD1和SOD2mRNA水平的变化;Western blot法检测下调SBP1或SOD1后DLD-1细胞内SBP1、SOD1及SOD2蛋白水平的变化;超氧化物阴离子荧光探针DHE染色法检测抗肿瘤药物引起的细胞内超氧化物阴离子的水平。结果:下调SBP1后,奥沙利铂对DLD-1细胞的毒性作用[半数毒性浓度IC50为(36.7±1.6)μmol/L]相比对照组[IC50为(17.5±0.8)μmol/L]明显减小(P<0.05);同时下调SBP1和SOD1后,奥沙利铂对DLD-1细胞的毒性作用[IC50为(16.8±1.0)μmol/L]相比对照组[IC50为(17.3±1.2)μmol/L]无明显变化(P>0.05);下调SBP1分别在转录水平、蛋白水平及酶活性水平上调了SOD,并减少了由奥沙利铂引起的DLD-1细胞内产生的超氧阴离子。结论:下调SBP1能上调SOD的水平,进而减小了奥沙利铂对DLD-1细胞的毒性作用,故SBP1能通过抑制SOD增强奥沙利铂对DLD-1细胞的毒性作用。     

CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma

1. Download : Download high-res image (164KB)
2. Download : Download full-size image

     

Myosteatosis and myofibrosis: Relationship with aging,inflammation and insulin resistance

The mechanisms impairing muscle quality and leading to myofibrosis (MF) and myosteatosis (MS) are incompletely known. In biopsies of paraspinous muscle (PM) of 16 elderly men undergoing elective vertebral surgery, we histologically determined the area of MF and MS expressed as muscle quality index (MQI), in order to investigate the relation between them, as well as the main predictors of muscle quality. Total PM area and intermuscular adipose tissue (IMAT) were evaluated by MRI and body composition by DXA. Circulating fasting glucose, insulin, hs-CRP, leptin, adiponectin and IL-6 were measured and HOMA index calculated. Quantification of gene expression in PM and in subcutaneous adipose tissue (SAT) overlying the muscle was performed by rt-PCR. The degree of MS and MF was significantly and positively related to each other and positively associated with BMI, waist, FM and FM% as well as with IMAT. The area of PM was negatively related with MF even after adjustment for weight. Leptin was positively associated with MF and MS, whereas hs-CRP to MF. In backward regression analyses, larger waist and smaller PM area explained 90% of MF variance, whereas leptin about 80% of MS variance. IL-6 expression in SAT was significantly higher in participants with higher MQI values. In PM biopsies we found significantly higher expression of SOCS-3 and a trend toward higher expression of myostatin with greater degrees of MQI. MS and MF are related phenomena that concur to alter muscle quality and both should be considered in further studies on the evolution of sarcopenia.