Enhancer of zeste homolog 2 (EZH2) is the catalitic subunit of polycomb repressive complex 2 and mediates gene silencing. EZH2 is overexpressed in many cancers and correlates with poor prognosis. The ...role of the gene EZH2 in colorectal cancer survival is uncertainly, the aim of this study is clear this relationship. Relevant literaure was searched from electronic databases. A meta-analysis was performed with elegible studies which quantitatively evaluated the relationship between EZH2 overexpression and survival of patients with colorectal cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 8 studies (n = 1059 patients) that evaluated the correlation between EZH2 overexpression and survival in patients with colorectal cancer. Combined hazard ratios suggested that EZH2 overexpression was associated with better prognosis of overall survival (OS) HR(hazard ratio) = 0.61 95% CI (0.38-0.84) We performed bias analysis according Egger and Begg,s test and we did not find publication bias. EZH2 overexpression indicates a better prognosis for colorectal cancer.
Summary
Differences in the activity of monocytes/macrophages, important target cells of Mycobacterium tuberculosis, might influence tuberculosis progression. With the purpose of identifying candidate ...genes for tuberculosis susceptibility we infected monocytes from both healthy elderly individuals (a tuberculosis susceptibility group) and elderly tuberculosis patients with M. tuberculosis, and performed a microarray experiment. We detected 78 differentially expressed transcripts and confirmed these results by quantitative PCR of selected genes. We found that monocytes from tuberculosis patients showed similar expression patterns for these genes, regardless of whether they were obtained from younger or older patients. Only one of the detected genes corresponded to a cytokine: IL26, a member of the interleukin‐10 (IL‐10) cytokine family which we found to be down‐regulated in infected monocytes from tuberculosis patients. Non‐infected monocytes secreted IL‐26 constitutively but they reacted strongly to M. tuberculosis infection by decreasing IL‐26 production. Furthermore, IL‐26 serum concentrations appeared to be lower in the tuberculosis patients. When whole blood was infected, IL‐26 inhibited the observed pathogen‐killing capability. Although lymphocytes expressed IL26R, the receptor mRNA was not detected in either monocytes or neutrophils, suggesting that the inhibition of anti‐mycobacterial activity may be mediated by lymphocytes. Additionally, IL‐2 concentrations in infected blood were lower in the presence of IL‐26. The negative influence of IL‐26 on the anti‐mycobacterial activity and its constitutive presence in both serum and monocyte supernatants prompt us to propose IL26 as a candidate gene for tuberculosis susceptibility.
Bronchiectasis is considered a consequence of the neutrophilic inflammatory response to infection. Mycobacterial infections, mainly from the Mycobacterium avium complex and M. abscessus, have been ...inextricably linked to bronchiectasis development. The most important pathogen that infect patients with bronchiectasis is Pseudomonas aeruginosa, associated with an increased risk of death. Patients with bronchiectasis are often co-infected with P. aeruginosa and M. avium complex, and it was studied whether they interacted in immune cell cultures. Peripheral blood mononuclear cells from healthy volunteers were infected overnight with clinical isolates of mycobacteria, 18 h later co-infected with P. aeruginosa and Pseudomonas multiplication was quantified. Inoculated P. aeruginosa multiply faster when cells were previously infected in vitro with M. avium complex or M. tuberculosis, but not with M. kansasii or M. gordonae, mycobacteria not regularly isolated from patients with bronchiectasis. The interaction between mycobacteria and P. aeruginosa also takes place in the absence of cells, but to a lower degree. Growth of Staphylococcus aureus, less frequently co-isolated with mycobacteria, was not affected by previous infection with mycobacteria. Surprisingly, multiplication of P. aeruginosa in neutrophil cultures did not vary in the presence of mycobacteria. Nevertheless, co-infection of mycobacteria and P. aeruginosa induced the production of IL-1β, a mediator of neutrophilic inflammation. P. aeruginosa stimulation by mycobacteria provides evidence for explaining their common clinical association. Strategies to control mycobacteria may be useful to impair P. aeruginosa colonization.
•M. avium complex and M. tuberculosis co-infected cells promote P. aeruginosa growth.•Peripheral blood mononuclear cells, but not neutrophils, promote growth.•Less pathogenic mycobacteria (e.g. M. gordonae) do not promote growth.•Co-infected cells produce IL-1β, mediator of neutrophilic inflammation.•Observed mycobacteria - P. aeruginosa interaction may have clinical relevance.
Introduction
10–16% of non-small cell lung cancer (NSCLC) cases have the epidermal growth factor receptor (EGFR) amplified and/or mutated. Studies show that EGFR tyrosine kinase inhibitors (TKIs) ...significantly prolong progression-free survival (PFS) in patients with advanced NSCLC compared to those treated with platinum-based chemotherapy (CT) doublets. Our aim is to perform a real-world survival analysis of patients treated with TKI as first-line therapy at the Hospital of Leon (CAULE) in Spain. The impact on global survival rates and responses to clinical and histopathological factors were also analyzed.
Material and methods
We retrospectively reviewed patients diagnosed with EGFR-mutated NSCLC who received treatment with EGFR-TKI in the Department of Oncology at the University of Leon Health Center complex between March 2011 and June 2018. Data was analyzed with Kaplan-Meier and Cox regression models to show overall survival (OS), progression-free survival (PFS), and the associated variables.
Results
53 patients were included in the study, 50% (n = 27) were treated with gefitinib, 32% (n = 18) with erlotinib and 10% (n = 6) with afatinib. The median OS and PFS were 27.7 months (95% CI: 21–33.8 months) and 18 months (95% CI 14.25–21.89 months), respectively. The variables associated with OS and with PFS were exon19 deletion as a protective factor and presence of extrathoracic metastasis as a risk factor. The most frequent adverse effects were rash, diarrhea, asthenia, and conjunctivitis.
Conclusions
Real-world analysis of this data confirms that treatment with TKI is beneficial for patients diagnosed with EGFR-mutated NSCLC. Our OS outcomes were similar to those reported in clinical trials.
Highlights • Blood antimycobacterial activity is normal in individuals with type 2 diabetes. • Phagocytosis is inhibited in neutrophils from individuals with diabetes. • Higher production of TNFα in ...blood from diabetes patients infected with M. tuberculosis.
The increasing worldwide incidence of mycobacteriosis and the need to achieve improved clinical management makes nontuberculous mycobacteria (NTM) genotyping a useful tool. However, because of ...technical difficulties, medium size microbiology laboratories do not attempt to compare the genetic patterns that each of their isolates present. We have aimed to optimize a genotyping method with a reduced hands-on experimental time and that requires few technical resources. A strategy based on the Amplified Fragment Length Polymorphism (AFLP) methodology was developed using two rare-cutters enzymes (
Sac
I and
Bgl
II). One out of seven primers was sequentially used in each amplification reaction that was analyzed by agarose gel electrophoresis. This approach makes it possible the timely genotyping of a moderate number of strains and its characterization without the need of image analysis software. We have genotyped 28
Mycobacterium intracellulare
and 4 M
. abscessus
. Clinical researchers are encouraged to routinely genotype their NTM isolates.
1 AgResearch, Molecular Biology Unit, Department of Biochemistry, University of Otago, Dunedin
2 AgResearch, Invermay Agricultural Centre, Mosgiel
3 AgResearch, Lincoln, New Zealand
Gastrointestinal ...nematodes infect sheep grazing contaminated pastures. Traditionally, these have been controlled with anthelmintic drenching. The selection of animals resistant to nematodes is an alternative to complete reliance on drugs, but the genetic basis of host resistance is poorly understood. Using a 10,204 bovine cDNA microarray, we have examined differences in gene expression between genetically resistant and susceptible lambs previously field challenged with larval nematodes. Northern blot analysis for a selection of genes validated the data obtained from the microarrays. The results identified over one hundred genes that were differentially expressed based on conservative criteria. The microarray results were further analyzed to identify promoter motifs common to the differentially expressed genes. Motifs identified in upregulated gene promoters were primarily restricted to those promoters; however, motifs identified in downregulated gene promoters were also found in the promoters of upregulated genes but not in the promoters of genes whose expression was unaltered. Protein Annotators Assistant was used for lexical analysis of the differentially expressed genes, and Gene Ontology was used to look for metabolic and cell signaling pathways associated with parasite resistance. Two pathways represented by genes differentially expressed in resistant animals were those involved with the development of an acquired immune response and those related to the structure of the intestine smooth muscle. Genes involved in these processes appear from our analysis to be key genetic determinants of parasite resistance.
gastrointestinal nematodes; major histocompatibility complex class II; transgelin; actin
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