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MicroRNA-137 objectives EZH2 to be able to exert suppressive characteristics within uveal melanoma via regulation of Wnt/β-catenin signaling and also epithelial-to-mesenchymal changeover.
Obesogenic conditions induced altered tissue fatty acid (FA) compositions, which reduced doxorubicin's treatment efficacy. In mammary adipose tissue breast cancer cells suppressed the storage of FAs, thereby increasing the availability of free FAs and favored inflammation under obesogenic conditions. Copyright © 2020 Mentoor, Nell, Emjedi, van Jaarsveld, de Jager and Engelbrecht.Background Although clinical practice guidelines for the management of Immune Checkpoint Inhibitor (ICI)-related adverse events have recently been published, precise and nuanced toxicity data for combination ICI therapy are lacking. LDN-212854 molecular weight Therefore, herein we have conducted a systematic review and meta-analysis of published clinical trials on combination ICI to synthesize the treatment-related adverse event (TRAE) profile of combination ICI therapy. Methods PUBMED, EMBASE, and the Cochrane Database/EBM were searched for eligible studies. Clinical trials evaluating combination immune checkpoint inhibitor therapy in advanced unresectable cancer were included in the analysis based on prespecified criteria. Risk of bias across studies was evaluated using Begg's funnel plot and Egger's regression test. The summary outcomes were pooled risk ratios (RR) and the logit-transformed proportion for incidence data. Results A total of 18 studies comprising 2,767 patients across 10 cancer types were included in the final analysis. Combination ICI was associated with a slightly higher risk of all-grade adverse events (RR 1.07 [95% CI 1.03-1.11]) and markedly greater risk of grade 3 or higher adverse events (RR 2.21 [95% CI 1.57-3.10]) compared to monotherapy ICI. Subgroup analyses showed significant differences in risk of grade 3 or higher adverse events between treatment types (PD-1 + CTLA-4 and PD-L1 + CTLA-4), among cancer types, and among dosing regimens (N1I3, N3I1, and D20T1). The incidence of all-grade adverse events was 0.905 [95% CI 0.842-0.945], and the ratio of grade 3 or higher events to all-grade adverse events was 0.396 [95% CI 0.315-0.483]. The most common all-grade TRAEs were diarrhea/colitis, fatigue/asthenia, nausea/vomiting, rash, and pruritis. Conclusion Combination ICI therapy has a significantly different treatment-related adverse event profile compared to monotherapy. Copyright © 2020 Park, Lopes, Cristancho, Riano and Saeed.Gliomas are the most prevalent malignant primary brain tumors with poor outcome, and four different molecular subtypes (Mesenchymal, Proneural, Neural, and Classical) are popularly applied in scientific researches and clinics of gliomas. Public databases contain an abundant genome-wide resource to explore the potential biomarker and molecular mechanisms using the informatics analysis. The aim of this study was to discover the potential biomarker and investigate its effect in gliomas. Weighted gene co-expression network analysis (WGCNA) was used to construct the co-expression modules and explore the biomarker among the dataset CGGA mRNAseq_693 carrying 693 glioma samples. Functional annotations, ROC, correlation, survival, univariate, and multivariate Cox regression analyses were implemented to investigate the functional effect in gliomas, and molecular experiments in vitro were performed to study the biological effect on glioma pathogenesis. The brown module was found to be strongly related to WHO grade of gliomas, and KEGG pathway analysis demonstrated that TNFRSF1A was enriched in MAPK signaling pathway and TNF signaling pathway. Overexpressed TNFRSF1A was strongly related to clinical features such as WHO grade, and functioned as an independent poor prognostic predictor of glioma patients. Notably, TNFRSF1A was preferentially upregulated in the Mesenchymal subtype gliomas (Mesenchymal-associated). Knockdown of TNFRSF1A inhibited proliferation and migration of glioma cell lines in vitro. Our findings provide a further understanding of the progression of gliomas, and Mesenchymal-associated TNFRSF1A might be a promising target of diagnosis, therapy, and prognosis of gliomas. Copyright © 2020 Yang, Pan, Ma and Chu.To sustain their high proliferation rates, most cancer cells rely on glycolytic metabolism, with production of lactic acid. For many years, lactate was seen as a metabolic waste of glycolytic metabolism; however, recent evidence has revealed new roles of lactate in the tumor microenvironment, either as metabolic fuel or as a signaling molecule. Lactate plays a key role in the different models of metabolic crosstalk proposed in malignant tumors among cancer cells displaying complementary metabolic phenotypes and between cancer cells and other tumor microenvironment associated cells, including endothelial cells, fibroblasts, and diverse immune cells. This cell metabolic symbiosis/slavery supports several cancer aggressiveness features, including increased angiogenesis, immunological escape, invasion, metastasis, and resistance to therapy. Lactate transport is mediated by the monocarboxylate transporter (MCT) family, while another large family of G protein-coupled receptors (GPCRs), not yet fully characterized in the cancer context, is involved in lactate/acidosis signaling. In this mini-review, we will focus on the role of lactate in the tumor microenvironment, from metabolic affairs to signaling, including the function of lactate in the cancer-cancer and cancer-stromal shuttles, as well as a signaling oncometabolite. We will also review the prognostic value of lactate metabolism and therapeutic approaches designed to target lactate production and transport. Copyright © 2020 Baltazar, Afonso, Costa and Granja.Background The optimal strategy for the management of high-grade glioma in the elderly (≥60.0 years) remains controversial, especially regarding the effects of surgical extent on survival outcomes. The purpose of this study was to compare gross total resection (GTR) with subtotal resection (STR) for treatment effects in elderly patients with high-grade glioma. Methods Three electronic databases were systematically searched, including PubMed, EmBase, and the Cochrane library, from inception to August 2018. Hazard ratios (HRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to express summary effect estimates using the random-effects model. Nineteen retrospective observational studies involving a total of 10,815 elderly patients with high-grade glioma were included in this meta-analysis. Results The summary results indicated that GTR was associated with a significant improvement in overall survival (OS) compared with STR (HR = 0.70, 95% CI = 0.64-0.77). In addition, elderly patients administered GTR showed lower risk of 3-month mortality (OR = 0.
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