Construction and validation of risk model of EMT-related prognostic genes for kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a prevalent type of urological malignancy. The present study aimed to predict biomarkers for KIRC. METHODS: We collected transcriptomic and clinical information for KIRC from The Cancer Genome Atlas and GSE22541 cohorts. RESULTS: Unsupervised clustering of 35 epithelial-mesenchymal transformation (EMT)-related differentially expressed gene profiles divided samples into two clusters with distinct immune characteristics. Six genes (IL20RB, DDC, ANKRD36BP2, F2RL1, TEK, and AMN) were found to construct a prognostic risk model using multivariate Cox regression analysis. Kaplan-Meier analysis suggested the better prognosis of the KIRC patients in the low-risk group than that in the high-risk group. Immune infiltration analyses was conducted using xCell and single-sample gene set enrichment analysis, indicating that the risk score was associated with the immune microenvironment of the KIRC. Prognostic marker gene-targeted medications with high drug sensitivity were predicted in KIRC patients. CONCLUSIONS: In summary, the present study identified IL20RB, DDC, ANKRD36BP2, F2RL1, TEK, and AMN as prognostic biomarkers, providing insight into immunotherapy and gene-targeted drugs of KIRC.

Three-dimensional conformal radiotherapy in combination with transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma.

PURPOSE: This study aimed to investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) in combination with three-dimensional conformal radiotherapy (3D-CRT) in the treatment for locally advanced unresectable hepatocellular carcinoma (HCC). METHODS: From March 2000 to March 2009 a total of 158 patients with unresectable HCC treated and followed at our hospital were divided into TACE group (N=80) and TACE combined with 3D-CRT group (N=78). The TACE group was treated 3-6 times. In the combination group, 2-3 TACE courses were administered and 3D-CRT was performed 2 weeks after the last TACE. Three months after the end of treatment, imaging and serum AFP were carried out to assess the treatment efficacy. RESULTS: The response rates of TACE and the combination groups were 53.7% (43/80) and 71.8% (58/78) (p<0.05). The 1, 2, and 3-year survival rates of patients in the TACE and combination groups were 58.75, 36.25, 16.25%, and 78.48, 55.12 and 25.64% (p<0.05), respectively. Treatment compliance was good, with at least 2 TACE administrations for each case and at least 52 Gy for radiotherapy. In the TACE and the combination group, there were 2 and 3 cases with grade III/IV toxicity, respectively, without treatment-related death. CONCLUSION: 3D-CRT in combination with TACE significantly improve the therapeutic outcome in patients with locally advanced unresectable HCC, without creating severe toxicity.

Phase II clinical study on the GEMOX regimen as second- line therapy for advanced ovarian cancer.

AIM: To investigate the effectiveness and adverse effects of gemcitabine by fixed-dose rate infusion plus oxaliplatin (GEMOX regimen) as second-line therapy for advanced ovarian cancer. METHODS: 64 patients with advanced ovarian cancer were divided into an experimental group (44 cases) and a control group (20 cases). The experimental group was treated with continuous intravenous infusion of gemcitabine at 1000 mg/m(2) with a fixed-dose rate of 10 mg/m(2)/min, on days 1 and 8 and oxaliplatin at 100 mg/m(2) on day 1, IVGTT, repeated every 3 weeks. The control group was treated with intravenous infusion of gemcitabine at 1000 mg/m(2) within 30 min on days 1 and and oxaliplatin at 100 mg/m(2) on day 1, IVGTT, again repeated every 3 weeks. CT scans or MRI were used for review every 1-2 cycles. RESULTS: The effective rate in the experimental group was significantly high than control group (43.2% vs 35.0%; P < 0.05), with no obvious difference of hematologic or non-hematologic toxicity between the two groups (P > 0.05). CONCLUSION: GEMOX regimen is very effective to treat advanced ovarian cancer, with low toxicity, good tolerance and improved life quality in patients.

Effects of monoclonal antibodies against human stathmin combined with paclitaxel on proliferation of the QG-56 human lung carcinoma cell line.

OBJECTIVE: To explore whether monoclonal antibodies against stathmin and the chemotherapuetic agent paclitaxel have synergenic effects in inhibiting growth and inducing apoptosis in human QG-56 cells. METHODS: QG-56 cells were treated with monoclonal antibodies against stathmin or paclitaxel alone or in combination, with untreated cells used as controls. After 24, 48, 72 and 96 hours the cell growth condition was observed under an inverted microscope and inhibition was studied by MTT assay; apoptosis was analyzed by flow cytometry. RESULTS: The populations decreased and cell shape and size changed after the various treatments. Monoclonal antibodies against stathmin and paclitaxel used alone or incombination inhibited the proliferation of QG-56 cells, especially in combination with synergism (P<0.05). Combined treatment also resulted in a significantly higher apoptosis rate than in the other groups (P<0.05). CONCLUSIONS: Monoclonal antibodies against stathmin and paclitaxel used alone or in combination can inhibit proliferation of QG-56 cells and induce apoptosis when applied together, The observed synergistic effects may have important implications for clinical application.

Overexpression of ßIII-tubulin and survivin associated with drug resistance to docetaxel-based chemotherapy in advanced gastric cancer.

PURPOSE: To study the roles of ßIII-tubulin and survivin in the development of gastric cancer, and see for any relationship between the expression levels of these two genes and docetaxel chemoresistance in advanced gastric cancer. METHODS: Patients with advanced gastric cancer treated with docetaxel-based chemotherapy were enrolled and their tumor samples were collected retrospectively for analysis (study group). The control group consisted of patients with benign gastric mucosa lesions. Expression levels of ßIII-tubulin and survivin were evaluated with immunohistochemistry. RESULTS: The expression levels of ßIII-tubulin and survivin in the study group were significantly higher compared with those in the control group (p<0.01). Spearman's correlation analysis suggested that the expression of ßIII-tubulin was also correlated with that of survivin (p<0.05), but no correlation existed between the expression levels of ßIII-tubulin and survivin with age, gender and pathological tumor type. The complete response (CR) + partial response (PR) rates were 54.10%. Patients with ßIII-tubulin and/or survivin overexpression were less responsive to docetaxel-based therapy (p<0.05) and also had shorter median time to progression and 1- and 2-year survival rates (p<0.05). CONCLUSION: Overexpression of ßIII-tubulin and survivin in gastric cancer cells was associated with resistance to docetaxel-based chemotherapy in patients with advanced gastric cancer.

Expression of ß-tubulin III and survivin in advance stage breast cancer correlates with chemotherapeutic effects of docetaxel.

AIMS: To investigate the relationship between the expression of ß-tubulin III and survivin in advanced breast cancers and chemotherapeutic effects of docetaxel. METHODS: Clinical pathological data of 74 patients with advanced breast cancer were retrospectively analyzed after docetaxel chemotherapy. Expression of ß-tubulin III and survivin was assessed by immunohistochemistry and analyzed with reference to therapeutical and adverse effects of docetaxel. RESULTS: The positive expression rate of ß-tubulin III was 38.1% (32/84), while that of survivin was 76.2% (64/84). The effective rate (complete response + partial response) was 52.4%. That for patients with the positive expression of ß-tubulin III or/and survivin was significantly lower than for those with negative expression (P<0.05). There were significant differences in the non-progression of median diseases, 1-year and 2-year survival rates of between the patients with positive and negative expression (P<0.05). The main side effects were myelosuppression, alimentary canal response and alopecia, no differences being observed between groups. CONCLUSIONS: The combined detection of ß-tubulin III and survivin is a predictive index for chemotherapy effects of docetaxel in metastatic breast cancer.

Intrapleural chemo- and hyperthermotherapies for malignant pleural effusion: a randomized prospective study.

OBJECTIVE: The current prospective randomized study was designed to evaluate the safety and efficacy of combined intrapleural cisplatin and OK-432 (picibanil) plus hyperthermotherapy in patients with malignant pleural effusion (MPE). METHODS: A total of 358 patients with MPE due to end-stage malignancies were enrolled and randomly divided into two groups, A and B: the intrapleural combination of cisplatin and OK-432 with hyperthermotherapy (n = 179) or without hyperthermotherapy (n = 179), respectively. Mild toxicities such as nausea, vomiting or anorexia, bone marrow depression, and pyrexia were similar in both groups. RESULT: Patients in Group A (with hyperthermotherapy) showed a significantly higher overall response (93.4%) compared to those in Group B (79.8%, χ(2) = 43.11, p < .05). The median survival time for patients in Group A and Group B were 8.9 and 6.2 months, respectively (p > .05). After treatment, the quality of life scores were significantly increased in both groups as compared to prior treatment (p < .05). CONCLUSION: In conclusion, our study suggests that combined intrapleural cisplatin and OK-432 followed by hyperthermotherapy are more effective in the control of MPE and improve patients' quality of life.

[Effect of monoclonal antibodies against LI-cadherin on the proliferation of human hepatocellular carcinoma cells].

OBJECTIVE: To obtain monoclonal antibodies (mAb) against LI-cadherin and investigate their effects on the proliferation of human hepatocellular carcinoma cells. METHODS: Balb/c mice were immunized with recombinant LI-cadherin, and hybridoma cell lines secreting monoclonal antibodies against LI-cadherin were established with routine cell fusion and subcloning approach. The specificity of these mAbs was determined by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effect of the mAbs obtained on the growth of HepG2 cells was assessed using inverted microscope and MTT assay. RESULTS: Two hybridoma cell lines (F001 and F002) stably secreting specific mAbs were obtained. Western blot analysis showed that the two antibodies specifically recognized LI-cadherin antigen derived from human eucaryotic cells or tissue. Treatment of the HepG2 cells with the mAbs resulted in reduced viable cell number and changes in the cell morphologies, and the two mAbs inhibited the proliferation of HepG2 cells in a concentration-dependent manner (P<0.05). CONCLUSION: The two specific mAbs obtained can inhibit the proliferation of HepG2 cells in vitro, which facilitates further study of the relationship between LI-cadherin and tumors.