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Background: Cancers can survive the oxidative conditions by upregulating nucleoside diphosphate linked moiety X-type motif 1 (NUDT1). However, the mechanisms underlying gastric carcinogenesis and the dys-regulation of NUDT1 in gastric cancer (GC) remain unknown. Our study aimed to explore the role of NUDT1 and its regulatory pathway by miR-485-5p in GC. Methods: Gastric cancer tissues and paired noncancerous tissue samples were collected, and the expression level of NUDT1 and miR-485-5p were detected. Two cohorts from The Cancer Genome Atlas (TCGA) database and another cohort from the Tianjin Medical University Cancer Institute and Hospital were further analyzed. Luciferase assays were performed, and the efects of the miR-485-5p/NUDT1 axis on GC cells and normal gastric cells were determined by subsequent experiments. Results: We found that the expression of miR-485-5p was clearly repressed in GC tissues, while NUDT1 expression level was dramatically increased. The overexpression of NUDT1 correlated closely with an increase in invasive depth and a decrease in survival in GC patients. MiR-485-5p could directly bind to the 3'UTR of NUDT1 mRNA and induce its degradation, thus down-regulate its expression. The miR-485-5p/NUDT1 axis could lead to the changes of 8-oxo-dG in GC cells. And the increased expression of NUDT1 resulting from the downregulation of miR-485-5p could accelerate cell proliferation and metastasis in GC. However, the growth and migration of normal gastric cells did not depend on the protection of NUDT1, while the overexpression of NUDT1 could promote malignant transition in normal gastric cells. Conclusions: MiR-485-5p acts as a tumor suppressor by targeting NUDT1 in GC. The miR-485-5p/NUDT1 axis is [ABSTRACT FROM AUTHOR]

Background: The effect of chemotherapy combined with monoclonal antibodies (mAbs) on the immune state of the tumor environment remains unclear and controversial. The aim of this study is to examine the effect of chemotherapy combined with cetuximab (C225, an anti-EGFR mAb) on the immune state of tumor environment, and the correlation of that effect and the clinical efficacy. Methods: Twelve patients with colorectal cancer, who received the treatment of chemotherapy combined with C225, were enrolled in this study. The tumor specimen of the primary colorectal cancer before and after treatment was obtained. The expression of a series of immune factors (TGF-β1, CD8, IL-2, TNF-α, and VEGF) was measured by immunochemistry. The expression of these immune factors before and after treatment was compared by the Wilcoxon signed-rank test. The correlation of the change of immune parameter expression after treatment and clinical efficacy was examined by chi-square tests. The correlation of the expression of immune factors, clinical efficacy, and treatment number was examined by the Spearman's correlation analysis. Results: There was no significant difference between the expression of TGF-β1 before and after the treatment (P >0.05). The change of TGF-β1 expression after treatment significantly correlated negatively with clinical efficacy (P = 0.05). As for CD8, IL-2, VEGF, and TNF-α, there were no significant differences between the expression before and after the treatment (P >0.05), and the change of expression after treatment also did not correlate significantly with clinical efficacy (P >0.05). The change of IL-2 expression after treatment significantly correlated negatively with treatment number (correlation coefficient = -0.585, P = 0.046). The change of TGF-β1 expression after treatment significantly correlated negatively with clinical efficacy (correlation coefficient = -0.684, P = 0.014). Before treatment, the expression of TNF-α significantly correlated positively with the expression of IL-2 (correlation coefficient = 0.629, P = 0.028). After treatment, the expression of TGF-β1 significantly correlated negatively with the expression of CD8 (correlation coefficient = -0.664, P = 0.019). Conclusions: These results suggested that, in the tumor environment, the change of immune factors after treatment of cetuximab combined with chemotherapy may be associated with clinical efficacy [ABSTRACT FROM AUTHOR]

Background: Oxaliplatin, an effective antineoplastic agent againstgastrointestinal tumors, can cause severe peripheral neurotoxicity, which seriously limits its clinical application. To date, there are no effective treatments for this complication. Ganglioside-monosialic acid (GM1) has been shown to protect neurons against injuries and degeneration. The aim of this study was to evaluate the effects of GM1 on preventing oxaliplatin-induced neurotoxicity in patients with gastrointestinal tumors. Methods: In this study, 120 patients with gastrointestinal tumors were enrolled, and they received the treatment of XELOX (oxaliplatin and capecitabine) and FOLFOX4 (oxaliplatin, leukovolin and 5-fluorouracil). The patients were randomly divided into two groups, the experimental group and control group, with 60 patients in each. On the day chemotherapy was initiated, the experimental group received GM1 intravenously (100 mg once daily) for 3 days, while no neuroprotective agents were applied in the control group. The incidence rates and classification of neurotoxicity in the two groups were evaluated and the differences between the two groups were examined. Furthermore, whether GM1 affected the therapeutic effects of chemotherapy was also examined. Results: The grade of neurotoxicity in the experimental group was significantly lower than in the control group (P<0.05, Mann-Whitney U test). The probability of occurrence of low-grade neurotoxicity (grade 0 and 1) in the experimental group was higher than that in the control group (logistic ordinal regression); whereas the probability of occurrence of high-grade neurotoxicity (grade 2 and 3) in the experimental group was lower than in the control group (logistic ordinal regression). Conclusion: The data suggested that GM1 could reduce the grade of oxaliplatin-induced neurotoxicity and was an effective neuroprotective agent against oxaliplatin-induced high-grade neurotoxicity in patients with gastrointestinal tumors. [ABSTRACT FROM AUTHOR]