Abstract. The mechanisms underlying drug resistance in colorectal cancer (CRC) treatment remain to be fully elucidated. Therefore, the present study aimed to investigate the underlying mechanism resistance to a widely used anticancer drug, 5-Fluorouracil (5-FU). Nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important transcription factor involved in cellular protection. In the present study, it was hypothesized that the epigenetic modification of Nrf2 may be a potential target for 5-FU resistance in CRC treatment. Protein and messenger RNA levels of Nrf2, heme oxygenase-1 (HO-1), DNA methylases and DNA methyltransferases were determined and DNA methylation analysis for the Nrf2 promoter was performed in a human CRC control (SNU-C5) and resistant (SNU-C5R) cell line. The results demonstrated that Nrf2 expression levels, nuclear translocation and promoter binding were significantly increased in SNU-C5R cells compared with SNU-C5 cells. Elevated levels of activated Nrf2 in SNU-C5R cells resulted in the increased protein expression and activity of HO-1. In addition, increased production of reactive oxygen species (ROS) and upregulation of ten-eleven translocation (TET)1 were observed in SNU-C5R cells compared with SNU-C5 cells. Furthermore, methylation analysis revealed Nrf2 promoter cytosine-phosphate-guanine island hypomethylation in 5-FU-treated cells. In conclusion, the results indicated that 5-FU-induced ROS production resulted in the upregulation of TET1 expression and function. In addition, these results indicated that TET-dependent demethylation of the Nrf2 promoter upregulated Nrf2 and HO-1 expression, which induced cellular protection mechanisms, ultimately leading to drug resistance.

Background. Colorectal cancer is the third frequent tumor in the whole world. MiR-483, located at the 11p15.5 locus, acts as an oncogene in multiple tumors. The purpose of this study is to explore the important roles of miR-483 in colorectal cancer. Materials and Methods. RT-qPCR and western blot were applied to calculate the mRNA levels of miR-483 and genes. The Kaplan–Meier method was conducted to calculate the survival of patients with colorectal cancer. The proliferation and invasive abilities were measured by Methyl Thiazolyl Tetrazolium (MTT) and transwell assays. Results. MiR-483 was upregulated in colorectal cancer tissues, and the upregulation of miR-483 predicted poor prognosis of colorectal cancer patients. NDRG2 was a target gene of miR-483 in colorectal cancer. Furthermore, miR-483 has been reported to promote colorectal cancer cell proliferation and invasion through targeting NDRG2 by the PI3K/AKT pathway and epithelial-to-mesenchymal transition (EMT). In addition, the overexpression of miR-483 promoted xenograft growth of LOVO cells. Conclusion. MiR-483 promoted cell proliferation through the NDRG2/PI3K/AKT pathway and invasion-mediated EMT in colorectal cancer. In view of the multiple mechanisms of molecular immunotherapy, it is necessary to further study the relationship between miR-483 and colorectal cancer, so as to find a more direct and effective treatment method to prevent colorectal cancer.

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Objective. To investigate the clinical value of lentinan combined with (125)I brachytherapy in the treatment of recurrent ovarian cancer. Methods. A total of 160 patients with recurrent ovarian cancer admitted at Jiaozhou Central Hospital from June 2009 to October 2015 were enrolled in this study and randomly divided into observation group (80 cases) and control group (80 cases). The control group received chemotherapy. Observation group (80 cases) was treated with lentinan combined with (125)I brachytherapy on the basis of control group, and the efficacy, adverse reactions, and Karnofsky Performance Scale (KPS) and quality of life scale (QOL) scores of the two groups were analyzed and compared. Results. After treatment, the levels of CA125, CA199, and CA724 in the 2 groups were markedly lower than those before treatment, and the observation group was lower than the control group ( P < 0.05 ). After treatment, the proportion of CD4+/CD8+ cells and helper T cells and NK cells in the control group remarkably depleted, while the proportion of CD4+/CD8+ cells, NK cells, and B cells in the observation group increased significantly compared to that before treatment, and the level of IgA, IgG, and IgM in the control group decreased, while that in the observation group showed no conspicuous difference compared with that before chemotherapy ( P > 0.05 ). The effective rate of observation group (85%) was higher than that of control group (75%) ( P < 0.05 ). The overall survival of patients in the control group was (16.2 ± 2.04) months and that of the observation group was (24.8 ± 1.8) months. KPS and QOL scores in both groups were enormously higher than those before treatment, and the observation group was higher than the control group ( P < 0.05 ). The incidence of hemoglobin reduction, leukopenia, aglobulia, granulocytopenia, nausea and vomiting, hepatorenal toxicity, and neurovirulence in the observation group was significantly lower than that in the control group. Conclusion. Lentinan combined with (125)I brachytherapy is effective in treating recurrent ovarian cancer, with mild adverse reactions and good tolerance.

Background: The efficacy of color Doppler ultrasound, multislice spiral CT combined with serum alpha-fetoprotein (AFP) and alpha-fetoprotein heterogeneity (AFP-L3) in the diagnosis of primary hepatic carcinoma was evaluated. Methods: Seventy-nine patients with primary hepatic carcinoma (PHC group) and 50 patients with benign liver lesions (benign control group) admitted in Yantaishan Hospital (Yantai, China) from January 2016 to December 2018 were selected. The liver was scanned by color Doppler ultrasound and multiple multislice spiral CT. The serum AFP and AFP-L3 levels were detected by electrochemiluminescence. The value of color Doppler ultrasound, multislice spiral CT combined with serum AFP and AFP-L3 in diagnosis of primary liver cancer was retrospectively analyzed. Results: The color Doppler flow imaging (CDFI) showed a high-speed and high-resistance spectrum. The serum AFP and AFP-L3 levels of patients with primary hepatic carcinoma were significantly higher than those of the benign control group were (U=138.000 and 155.500, P=0.000 and 0.000), P<0.01. The sensitivity, accuracy and negative predictive value of color Doppler ultrasound, multislice spiral CT combined with serum AFP and AFP-L3 examinations for diagnosis of primary hepatic carcinoma were 96.20, 90.70 and 93.18%, which was significantly improved compared with each single examination (X2=27.888, 17.511 and 16.202, P=0.000, 0.002 and 0.003), P<0.01. Conclusion: Color Doppler ultrasound, multislice spiral CT combined with AFP and AFP-L3 examination could significantly improve the diagnosis efficiency of primary hepatic carcinoma, which was beneficial to early clinical diagnosis and early treatment.