Morganchoi5339

biocuckoo.cn. OBJECTIVE To explore contextual factors associated with high or low risk of bias judgement in case of incomplete or unclear information in study reports. STUDY DESIGN AND SETTING Research-on-research study, using matched case-control design, with a sample of 304 RCTs included in two Cochrane reviews for which there was disagreement on the risk of bias judgement related to incomplete or unclear information in the study report. A case was defined as an RCT judged at high or low risk of bias; a control was the same RCT judged at unclear risk. We used a conditional logistic regression model for analysis. RESULTS Review authors being also authors of the RCT were more likely to assess an item at low risk of bias than unclear (OR 11.71 (95% CI 1.39-98.76). Earlier trials in a review were more often assigned a low risk (OR 0.37 [0.15-0.96]). Review groups and authors that had completed a lower number of reviews slightly more often assigned a low risk whereas others reported "unclear" (OR 0.97 (95% CI 0.95-0.99) for groups) and 0.97 (95% CI 0.95-0.998) for authors). CONCLUSIONS Risk-of-bias assessment of RCTs in case of incomplete or unclear information may be affected by contextual factors. Myeloid-derived suppressor cells (MDSCs) are one of the key players that contribute to immune evasion. The purpose of the present study was to investigate whether MDSCs could be a novel target for the treatment of cisplatin-resistant bladder cancer. We established cisplatin-resistant bladder cancer cell lines (MB49R, MBT-2R, and T24R) and evaluated chemokine expression and MDSC expansion. We also assessed the antitumor effect by depleting MDSCs with or without a α-PD-L1 antibody using MB49R xenograft models. The chemokine expression of CXCL1, CXCL2, and CCL2 increased in cisplatin-resistant cells compared to those in their parent strains. Monocytic MDSCs (Mo-MDSCs) were observed more frequently compared to polymorphonuclear MDSCs (PMN-MDSCs) in MB49R tumors. The immunosuppressive genes arginase 1 and iNOS were comparably expressed in each MDSC subtype. In vivo, combination therapy targeting both PMN- and Mo-MDSCs using α-Gr1 and α-Ly6C antibodies significantly reduced tumor volume with increased infiltration of CD8 T cells in the tumor. Finally, co-targeting pan-MDSCs and PD-L1 remarkably reduced the tumor growth. These findings suggest that targeting MDSCs might enhance the therapeutic effect of immune checkpoint inhibitors in cisplatin-resistant bladder cancers. V.Triple-negative breast cancer (TNBC) has special characteristics of significant aggressiveness, and strong potential for metastasis and recurrence; currently there are no targeted drugs for TNBC. Abnormal activation of epithelial-mesenchymal transition (EMT) plays an important role in these malignant behaviors of TNBC. In the crosstalk among the multiple EMT-associated signaling pathways, many miRNAs participate in regulating pathway activity, where they act as "traffic lights" at the intersection of these pathways. In this study, we used miRNA microarray technology to detect differentially expressed miRNAs related to EMT in TNBC, and we identified and verified 9 highly expressed oncogenic miRNAs (OncomiRs). High expression of these OncomiRs in clinical breast cancer tissues affected the prognosis of patients, and inhibition of their expression blocked EMT in TNBC cell lines and suppressed cancer cell proliferation and migration. We constructed an oncolytic adenovirus (AdSVP-lncRNAi9) armed with an artificially-designed interfering lncRNA (lncRNAi9), which exhibited an activity to block EMT in TNBC cells by disrupting the functions of multiple OncomiRs; the efficacy of such a treatment for TNBC was demonstrated in cytology and animal experiments. This research provides a new candidate oncolytic virotherapy for treating highly malignant refractory TNBC. Gemcitabine (GEM) chemotherapy, as the first-line regimen for pancreatic cancer, tends to induce drug resistance, which ultimately worsens the prognosis of patients with pancreatic cancer. Our previous study indicated a close correlation between pancreatic cancer progression and glucose metabolism, especially at the chemoresistant stage, highlighting the importance of the application of 18F-FDG PET dual-phase imaging in the early detection of pancreatic cancer. K-Ras(G12C) inhibitor 12 cost We speculate that glycolysis, participates in the development of chemoresistance in pancreatic cancer. In this article, we wanted to determine whether manipulating hENT1 expression in pancreatic cancer cells can reverse GEM chemoresistance and whether glucose transport and glycolysis are involved during this process. We found that hENT1 reversed GEM-induced drug resistance by inhibiting glycolysis and altering glucose transport mediated by HIF-1α in pancreatic cancer. Our findings also suggest that 18F-FDG PET dual-phase imaging after the 4th chemotherapy treatment can accurately identify drug-resistant pancreatic tumors and improve hENT1 reversal therapy. Our findings highlight that the dynamic observation of (retention index) RI changes from the beginning of treatment can also be helpful for evaluating the therapeutic effect. The antitumour effects of OTX015, a first-in-class BET inhibitor (BETi), were investigated as a single agent or in combination with ionizing radiation (IR) in preclinical in vitro models of rhabdomyosarcoma (RMS), the most common childhood soft tissue sarcoma. Herein, we demonstrated the upregulation of BET Bromodomain gene expression in RMS tumour biopsies and cell lines compared to normal skeletal muscle. In vitro experiments showed that OTX015 significantly reduced RMS cell proliferation by altering cell cycle modulators and apoptotic related proteins due to the accumulation of DNA breaks that cells are unable to repair. Interestingly, OTX015 also impaired migration capacity and tumour-sphere architecture by downregulating pro-stemness genes and was able to potentiate ionizing radiation effects by reducing the expression of different drivers of tumour dissemination and resistance mechanisms, including the GNL3 gene, that we correlated for the first time with the RMS phenotype. In conclusion, our research sheds further light on the molecular events of OTX015 action against RMS cells and indicates this novel BETi as an effective option to improve therapeutic strategies and overcome the development of resistant cancer cells in patients with RMS.