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.

miR-638 represses the stem cell characteristics of breast cancer cells by targeting E2F2.

OBJECTIVE: The miR-638 acted as a tumor suppressor and E2F transcription factor 2 (E2F2) was a critical regulator in some cancers, while the role of them on stemness of breast cancer stem cells (BCSCs) was rarely detailed. Hence, we focused on exploring the effects of miR-638 and E2F2 on BCSCs stemness. METHODS: The proportion of CD24 -/CD44 + cells of BCSCs was detected by flow cytometry. The target relationship of miR-638 and E2F2 was explored using luciferase assays. The ability of self-renewal, proliferation, and invasion of BCSCs were determined by Mammosphere forming, Cell Counting Kit-8 (CCK-8), colony formation, and transwell assays. Xenograft tumor was established to detect the influence of miR-638 on tumor growth. RESULTS: miR-638 was down-regulated, while E2F2 was elevated in breast cancer. The E2F2 level was negatively correlated with miR-638. The BCSCs represented higher proportion of CD24 -/CD44 + cells and levels of sex determining region Y-box 2 (SOX2) and octamer-binding transcription factor 4 (OCT4). The miR-638 was down-regulated and E2F2 was increased in BCSCs. MiR-638 could target to E2F2 and decreased the level of E2F2 in BCSCs cells. Overexpression of miR-638 decreased the proportion of CD24 -/CD44 + cells and the levels of SOX2 and OCT4 by inhibiting E2F2. The overexpression of miR-638 also inhibited the abilities of self-renewal, proliferation, and invasion of BCSCs by inhibiting E2F2. The miR-638 overexpression inhibited the breast tumor growth. CONCLUSION: MiR-638 represses the characteristics and behaviors of BCSCs by targeting E2F2. MiR-638 may be a potential target for breast cancer therapy.

Expression characteristics of KAI1 and vascular endothelial growth factor and their diagnostic value for hepatocellular carcinoma.

BACKGROUND/AIMS: We tried to investigate the expression characteristics of KAI1, a suppressor of wide-spectrum tumor metastasis, and vascular endothelial growth factor (VEGF), the most common angiogenesis factor, and then to analyze their diagnostic value for hepatocellular carcinoma (HCC). METHODS: The protein and mRNA expression levels of KAI1 or VEGF in HCC tissues and in self-controlled para-carcinoma tissues were analyzed by Western blot and real-time polymerase chain reaction, respectively. Serum levels of KAI1 and VEGF in the patients with HCC, benign liver disease or in healthy controls were quantitatively detected by enzyme-linked immunosorbent assay. RESULTS: The expression level of KAI1 was downregulated, while the expression level of VEGF was upregulated in the tissues or serum of the patients with HCC. The expression level of serum KAI1 in HCC patients was correlated with TNM staging, intrahepatic metastasis, lymph node or peritoneal metastasis, and portal vein thrombus. In addition to the factors that were correlated with KAI1 expression, VEGF expression was also closely related to the α-fetoprotein level of the patients. The area under the receiver operating characteristic curve for the diagnosis of HCC was 0.907 for KAI1 and 0.779 for VEGF. The sensitivity of serum KAI1 levels in the diagnosis of HCC was 86.96%; the accuracy was 83.06%, while the sensitivity, the accuracy and the negative predictive value were improved to 91.86%, 84.68%, and 78.79% according to the combined detection of KAI1 and VEGF, respectively. CONCLUSIONS: A combined detection of KAI1 and VEGF may greatly improve the efficiency of diagnosis and form a reliable panel of diagnostic markers for HCC.

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.