[Serum-and-glucocorticoid-inducible-kinase-2 is overexpressed and mediates glycogen synthase kinase-3ß/ ß-catenin signal transduction in hepatocellular carcinoma].

Objective: To investigate the differential expression of serum-and-glucocorticoid-inducible-kinase-2 (SGK2) in hepatocellular carcinoma (HCC) and normal liver tissues and the related mechanism mediating signal transduction of GSK-3 ß / ß catenin in HCC cells. Methods: Twenty pairs of matched HCC and normal tissues were collected and the situation of expression of SGK2 mRNA was detected by real-time fluorescence quantitative PCR. Western blot was used to detect the levels of SGK2 protein in human HCC cell lines (Huh-7, SMMC-7721) and normal human liver cell line (L02). SGK2 siRNA was used to transfect human HCC cell lines (SMMC-7721 and Huh-7), and then the protein expression levels of GSK-3 ß/ ß - catenin was successfully detected with the above-mentioned transfected cell line by western blot. Measurement data were expressed as mean ± standard deviation (x±s), and the Student t -test was used as the statistical method. Results: SGK2 mRNA expression was up-regulated in all 20 HCC samples than that of the expression of matched normal liver tissues. SGK2 protein levels were significantly higher in Huh-7 and SMMC-7721 than normal human liver cell lines (P < 0.01). The downregulation of SGK2 expression in human HCC cell lines (SMMC-7721 and Huh-7) had inhibited the expression of unphosphorylated GSK-3 ß. In addition, the downregulation of SGK2 expression in HCC cell lines had decreased the dephosphorylation of ß - catenin to prevent degradation of the ß - catenin proteasome. Conclusion: SGK2 is overexpressed in HCC and mediates GSK-3ß/ß- catenin signaling in HCC cells.

Effects of curcumin on the role of MMP-2 in endometrial cancer cell proliferation and invasion.

OBJECTIVE: This study aims to investigate the effect of curcumin concentrations on the proliferation and invasion of endometrial cancer cells. MATERIALS AND METHODS: Endometrial cancer cells were cultured with 0, 15, and 30 µmol/l curcumin, and were divided into control group, low concentration group, and high concentration group. The treatment included the silencing and overexpression of MMP-2. The expression of MMP-2 and E-cadherin were detected by Western blot and the expression level changes were recorded after MMP-2 was silenced and overexpressed. Pearson's analysis was used to determine the relationship of curcumin concentration between MMP-2 mRNA. CCK-8 was used to detect the optical density of cancer cells in three groups. Transwell invasion assay was performed to analyze the invasion inhibition rate in the three groups. RESULTS: Western blot and qPCR results: MMP-2 expression levels were lower and E-cadherin was higher in high concentration group than that in the low concentration group (p<0.01). MMP-2 protein and mRNA decreased after ShRNA and increased after overexpression (p<0.01). Pearson analysis revealed that the curcumin concentration was negatively correlated with the MMP-2 mRNA (r=-0.497, p=0.036). Cell optical density was lower with curcumin and the lowest was in high concentration group (p<0.01). After MMP-2 silencing, optical cell density decreased and this value increased after overexpression (p=0.000). Cell invasion results: Curcumin improves the rate of cell invasion (p<0.01). After silencing of MMP-2, cell invasion inhibition rate increased, while the invasion inhibition rate decreased after overexpression (p<0.01). CONCLUSIONS: Curcumin can downregulate MMP-2, inhibit the proliferation and invasion of cancer cells.

The research on the influences of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis.

OBJECTIVE: To investigated the influence of hyperthermal perfusion chemotherapy combined with immunologic therapy on the immunologic function and levels of circulating tumor cells of the advanced colorectal cancer patients with liver metastasis. PATIENTS AND METHODS: We enrolled 98 advanced colorectal cancer patients with liver metastasis that were admitted to this hospital for treatment and were randomly divided into two groups, the observation group (n = 49) and the control group (n = 49). We administered systemic vein chemotherapy for patients in the control group, and hyperthermal perfusion chemotherapy for the patients in the observation group in order to compare the subgroup levels of T lymphocytes, NK cells and immunoglobulin (IgG, IgA, and IgM) in the immune system of patients in both groups. We also assayed the circulating tumor cells (CTC) in the peripheral blood of patients in both groups using the cell search method, and compared the efficacy using response evaluation criteria in solid tumors and the survival rates of patients in both groups using the Kaplan-Meier method. RESULTS: After two treatment courses, the levels of CD3+, CD4+ and CD4+/CD8+ of the patients in the observation group were significantly higher than those of the control group, but the levels of CD8+ of patients in the observation group was lower than that in the control group (p< 0.05). The levels of immunoglobulins (IgG, IgA, and IgM) in the observation group were higher than the control group (p < 0.05). The levels of NK cell cells were significantly lower than the control group (p < 0.05). The objective response rate, as well as the disease control rate of the observation group, were remarkably higher than those of the control group (p < 0.05). Compared to the control group, the observation group enjoyed a prolonged survival time, higher survival rate and significantly lower positive rate of CTC (p < 0.05). CONCLUSIONS: Better efficacy and tolerance, fewer toxic and side effects, improvement in the immunologic functions of patients for the indirect anti-tumor effect, a significant decrease in CTC of patients, and a higher long-term survival rate have been achieved in the treatment with hyperthermal perfusion chemotherapy combined with immunologic therapy for the advanced colorectal cancer patients with liver metastasis. Thus, it can serve as the preferable drug for the treatment of advanced colorectal cancer with liver metastasis.

Radiation-enhancing effect of sodium glycididazole in patients suffering from non-small cell lung cancer with multiple brain metastases: A randomized, placebo-controlled study.

PURPOSE: Median survival of patients with brain metastases from non-small cell lung cancer is poor. This study was to investigate the radiation-enhancing effect of sodium glycididazole combined with whole-brain radiotherapy of multiple brain metastases from non-small cell lung cancer. PATIENTS AND METHODS: Sixty-four patients with multiple brain metastases from non-small cell lung cancer were included: the study group (n=32) received whole-brain radiotherapy combined with sodium glycididazole at a dose of 700mg/m(2) intravenous infusion 30minutes before radiotherapy, three times a week; the control group (n=32) only received whole-brain radiotherapy. The primary end point was central nervous system (CNS) progression-free survival and overall survival. The treatment-related toxicity was also recorded. RESULTS: The CNS disease control rate was better (90.6% vs 65.6%, P=0.016) in the study group than in the control group at 3 month of follow-up. The median CNS progression-free survival time was longer in the study group than in the control group (7.0 months vs 4.0 months, P=0.038). There was no significant difference of the median overall survival time between the study group and the control group (11.0 months vs 9.0 months, P=0.418). On the other hand, the treatment-related toxicity showed no statistically significant difference between these two groups (P>0.05). CONCLUSIONS: The study indicated that sodium glycididazole was an effective, promising radiation-enhancing agent that improved CNS disease control rate, extended the median CNS progression-free survival time and was well tolerated in patients suffering from non-small cell lung cancer with multiple brain metastases.

Serum levels of selenium in patients with brain metastases from non-small cell lung cancer before and after radiotherapy.

PURPOSE: This study was to evaluate the influence of radiotherapy on the selenium serum levels of non-small cell cancer patients with brain metastases. PATIENTS AND METHODS: This prospective study included 95 non-small cell cancer patients with brain metastases treated by radiotherapy from December 2007 until November 2010. Plasma selenium levels were determined before and at the end of the radiotherapy. Age, body mass index (BMI), prior chemotherapy, pathological type and personal habits (smoking and alcoholism) were recorded for each patient. RESULTS: The mean age was 63 years; the mean BMI was 27.6. Seventy-six patients (80%) were non-smokers. Sixty-two patients (65.3%) showed no drinking habits and 8 (8.4%) have no prior chemotherapy. Thirty-nine patients (41.1%) were adenocarcinoma, 51 (53.7%) were squamous cell carcinoma and five (5.3%) were large cell carcinoma. At the beginning of radiotherapy, the mean selenium level for all patients was 90.4 µg/l and after radiation this value dropped to 56.3 µg/l. Multivariate analysis showed statistically significant difference in the plasma selenium concentration before and after radiotherapy for age (P<0.001), BMI (P<0.001), smoking (P<0.001), alcoholism (P<0.001), prior chemotherapy (P<0.001) and pathological type (P<0.001). CONCLUSION: Significant reduction in plasma levels of selenium was recorded in patients undergoing radiotherapy, suggesting attention to the nutritional status of this micronutrient and other antioxidant agents.

Safety and radiation-enhancing effect of sodium glycididazole in locoregionally advanced laryngeal cancers previously treated with platinum-containing chemotherapy regimens: A preliminary report.

PURPOSE: To determine the safety and radiation-enhancing effect of sodium glycididazole in laryngeal squamous cell carcinoma (stage T3-4,N0-3,M0) with conventional radiotherapy. PATIENTS AND METHODS: Patients with locoregional advanced laryngeal cancer (stage T3-4,N0-3,M0) were included: group 1(control, n=30)were not administered of sodium glycididazole; group 2 (test, n=30) received sodium glycididazole at a dose of 700 mg/m(2) intravenous infusion 30 minutes before radiotherapy three times a week. Surrogate end-points of efficacy were tumor and nodal size. Safety parameters were vomiting, nausea, mucositis, laryngeal edema, esophagus and skin reaction, dysphagia, dyspnea, neurological deficit. Patients were evaluated weekly during treatment for 7 weeks and thereafter monthly for 3 months. RESULTS: In the test, the overall response rate was 88.89% (95%CI, 71.00-97.00%) at 7 weeks and 92.59% (95%CI, 76.00 to 99.00%) at 1 month of follow-up. In the control, the overall response rate was 62.5% (95%CI, 41.00 to 81.00%) at 7 weeks and 58.33% (95%CI, 37.00 to 78.00%) at 1 month of follow-up. The short-term locoregional response rate was better in the test group at 7 weeks (p=0.027) and at 1 month (p=0.005) of follow-up. The test group had significantly more nausea and vomiting in weeks 1 (p=0.047), 2 (p=0.007), and 3 (p=0.01) of treatment. CONCLUSIONS: The study indicates sodium glycididazole is an effective radiation-enhancing agent that improves short-term locoregional control and is well tolerated in patients with locoregionally advanced laryngeal cancer.

[Preliminary study on the purification of IL-2].

Interleukin-2 (IL-2) which is produced by T-lymphocytes is a protein molecule with the molecular weight of 15,420-Daltons. It has good functions in curing a lot of diseases such as cancer and AIDS even with a small quantity. A new method for purification of IL-2 by preparative high performance liquid chromatography is described. It was the first time to use hydroxyapatite as the packing to separate IL-2. IL-2 has one disulphide bridge (between 58th Cys and 105th Cys) and one free cysteine. In order to prevent aggregation and formation of wrong disulphide bond, 50 mumol/L Cu2+ and 1.5 mol/L guanidine hydrochloride was used for autoxidation and denaturing. Then we used mainly two chromatographic steps: First, Sephadex G-25 Gel permeation chromatography was used to separate guanidine hydrochloride and small molecules. Second, large scale preparative HPLC was used to separate impure protein from IL-2. Gradient elution was performed with phosphate buffer (pH 6.8). Its purity was examined by SDS-PAGE. Its activity reached 1 x 10(6) U/mg by CTLL-2 cell MTT method. The results showed that it is a suitable method for the large-scale purification of IL-2.