ABSTRACT
Objective: To explore the key deubiquitinating enzymes that maintain the stemness of liver cancer stem cells and provide new ideas for targeted liver cancer therapy. Methods: The high-throughput CRISPR screening technology was used to screen the deubiquitinating enzymes that maintain the stemness of liver cancer stem cells. RT-qPCR and Western blot were used to analyze gene expression levels. Stemness of liver cancer cells was detected by spheroid-formation and soft agar colony formation assays. Tumor growth in nude mice was detected by subcutaneous tumor-bearing experiments. Bioinformatics and clinical samples were examined for the clinical significance of target genes. Results: MINDY1 was highly expressed in liver cancer stem cells. The expression of stem markers, the self-renewal ability of cells, and the growth of transplanted tumors were significantly reduced and inhibited after knocking out MINDY1, and its mechanism of action may be related to the regulation of the Wnt signaling pathway. The expression level of MINDY1 was higher in liver cancer tissues than that in adjacent tumors, which was closely related to tumor progression, and its high expression was an independent risk factor for a poor prognosis of liver cancer. Conclusion: The deubiquitinating enzyme MINDY1 promotes stemness in liver cancer cells and is one of the independent predictors of poor prognosis in liver cancer.
Subject(s)
Animals , Mice , Cell Line, Tumor , Mice, Nude , Liver Neoplasms/pathology , Prognosis , Deubiquitinating Enzymes/metabolism , Neoplastic Stem Cells/pathology , Gene Expression Regulation, NeoplasticABSTRACT
The aim of this study was to evaluate the predictive value of the polymorphism Glutathione S-transferase P1 (GSTP1) Ile(105)Val on oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. Patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. GSTP1 Ile(105)Val polymorphism was detected by TaqMan-MGB probe allelic discrimination method. Response to treatment was assessed by disease controlled rate. Time to progression, overall survival and toxicities were recorded. Final patient outcomes were as follows: the allele frequencies of GSTP1 were (105)Ile/(105)Ile 52%, (105)Ile/(105)Val 41% and (105)Val/(105)Val 7%. For patients with (105)Ile/(105)Ile and those with at least one (105)Val allele, disease control rate was 39% and 71% (P=0.026), respectively; median time to progression was 4.0 and 7.0 months (P=0.002); median overall survival time was 7.0 and 9.5 months (P=0.002). Neurological toxicity was more frequently occurred in patients with two (105)Ile alleles (P=0.005). In conclusion, patients with at least one (105)Val allele have better prognosis and response to oxaliplatin/5-FU-based regimen as first-line treatment for patients with advanced gastric cancer.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the T helper 1 and T helper 2 (Th1/Th2) balance and possible association to vascular endothelial cells injury in patients with acute coronary syndromes (ACS).</p><p><b>METHODS</b>Forty patients with ACS and 18 patients with stable angina pectoris (SAP) were included in this study. The concentrations of T helper 1/T helper 2 subsets related cytokines in plasma were evaluated by ELISA Kits. Cytotoxic activity of peripheral blood mononuclear cells (PBMCs) or PBMCs depleted CD(+) T cells against human umbilical vein endothelial cells (HUVECs) were evaluated by Cr51 cytotoxicity assay.</p><p><b>RESULTS</b>Concentrations of T helper 1 related cytokines IFN-gamma and IL-2 were significantly higher [IFN-gamma: (131.2 +/- 42.2) ng/L vs. (47.6 +/- 20.2) ng/L; IL-2: (83.7 +/- 21.3) ng/L vs. (46.2 +/- 16.7) ng/L, all P < 0.05] while T helper 2 related cytokine IL-10 concentration was significantly lower [(16.7 +/- 4.3) ng/L vs. (27.5 +/- 5.5) ng/L, P < 0.05] in patients with ACS compared to those in SAP patients. Cytotoxic activity of PBMCs against HUVECs in patients with ACS was also significantly higher than that in patients with SAP (28.84% +/- 4.20% vs. 20.28% +/- 2.71%, P < 0.05).</p><p><b>CONCLUSIONS</b>In patients with ACS, Th1 related cytokines were significantly upregulated while Th2 related cytokines were significantly downregulated. This imbalance of Th1/Th2 accelerated PBMCs mediated endothelium injury in patients with ACS.</p>