Volume 42, Issue 5

Background The molecular mechanisms involved in tumorigenesis of lung cancer remain to be further elucidated. MicroRNA (miRNA) is a class of non-coding RNAs associated with carcinogenesis. The present study aims to investigate the role of miRNA-101 (miR-101) in lung cancer. Methods MiR-101 was measured in human non-small cell lung cancer (NSCLC) tissues compared with the matched adjacent tissues. MiR-101 was transfected into NSCLC A549 cells. Bioinformatics predictions revealed a potential binding site of miR-101 on the 3′UTR of C-Fos, which was further confirmed by the luciferase assay. Western blot analysis and knockdown method were used to detect the expression and function of C-Fos Results The expression of miR-101 was downregulated in NSCLC. Overexpression of miR-101 suppressed cell proliferation of NSCLC A549 cells, and induced cell apoptosis. C-Fos was downregulated by miR-101 at the protein level. In addition, knockdown of C-Fos induced similar effects as overexpression of miR-101 in NSCLC cells. Conclusion These findings indicate that miR-101 regulate NSCLC cells growth through targeting C-Fos. Thus, strategies on C-Fos and/or miR-101 may be a potential molecular therapy for NSCLC.

Objective The aim of this study was to investigate serum and tissue levels of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) and to evaluate correlations between serum and tissue parameters with respect to clinicopathological features in patients with lung cancer. Methods The study was conducted on 34 patients with stage I-IV primary lung cancer and 32 healthy controls. Preoperative serum, tumor and matched normal tissue VEGF, Ang-1 and Ang-2 levels were determined with ELISA. Results Serum Ang-2 levels were significantly increased in lung cancer patients (p<0.001). VEGF levels were significantly higher in tumor tissue than in matched normal tissue (p<0.001). Ang-1 and Ang-2 levels were significantly higher in normal tissue than in tumor tissue (p<0.001). A significant negative correlation was found between normal lung tissue Ang-2 and serum VEGF levels (r=−0.400, p=0.019). A significant correlation was observed between serum and lung tissue Ang-2 levels (r=0.397, p=0.020). Conclusion This study clearly demonstrated that VEGF, Ang-1 and Ang-2 are all involved in lung cancer process. This was the first study to show a correlation between serum and tissue levels of Ang-2 in lung cancer. This finding might be the basis for therapeutic strategies against lung cancer.

Objective(s) In this study, it was aimed to synthesize new chemotherapeutic agents based on known antiproliferative properties of benzothiazol-2-amine moiety. The antitumor activity of the newly synthesized compounds was determined against A549 lung cancer cell lines. Methods Eighteen compounds were obtained by two steps synthetic route. The anticancer potency of the compounds were detected using MTT assay and flow cytometric analysis on A549 cell line. Some physicochemical properties of the compounds were calculated, virtually. Results Compounds 15 and 18 showed the highest cytotoxic activity even than cisplatin. Also, it was determined that compound 18 caused 19.1% (early and late) apoptosis whereas cisplatin caused 21.6% (early and late). Conclusion Considering the calculated virtual data, eighteen new compounds were found within the boundaries of Lipinski rule of five to be an oral drug. Besides, the most potent compounds 15 and 18 were detected that both have 1-methylbenzimidazole structure, and also methoxy and ethoxy substituents on benzothiazole ring.

Background In recent years, studies on gastric cancer include changes in cancer associated immune system activation and the levels of immune system markers. It has been demonstrated that TNF-α (tumor necrosis factor-alpha) and IL-6 (interleukin-6) play a role in inflammatory associated carcinogenesis. Objective Our aim was to investigate serum soluble IL-1 decoy receptor (sIL- 1RII), TNF-α and IL-6 levels in gastric adenocarcinoma patients. Materials and methods Male gastric adenocarcinoma patients and dyspeptic participants, in total 55 cases were included. Serum sIL-1RII, TNF-α and IL-6 concentrations were measured. Results The median sIL-1RII levels of the patients were statistically significantly lower than the median of the control group (3111 ng/mL; 3601 ng/mL, respectively) (p=0.003). But the median TNF-α and IL-6 levels (58.17 ng/mL; 10.22 ng/mL, respectively) were both numerically higher than those of control group levels (16.62 ng/mL; 5.74 ng/mL, respectively). Also, patients’ median TNF-α levels were found statistically significantly higher (p=0.034). Conclusion This study showed the increase of TNF-α, IL-6 levels and for the first time the decrease of sIL-1RII in gastric cancer patients. We propose that negative regulation of gastric cancer using sIL-1RII could be a new anti-cancer strategy. General significance Our study provides target pathways for further studies in the pathophysiology of gastric cancer.

Objective Gastric cancer is one of the most common malignancies worldwide. The risk factors for gastric cancer include environmental and genetic factors. Inflammation and the immune system are known to contribute to the development of the gastric cancer. We examined the influence of critical polymorphisms of CTLA-4 and CD28 genes and circulating protein levels on the etiology of gastric cancer. Methods Genotyping of SNPs was performed in 55 gastric cancer patients and 105 healthy individuals using the PCR-RFLP method, and circulating levels of sCTLA-4 and sCD28 were measured. Results There were no significant differences in the genotype and allele distributions of the evaluated SNPs [CTLA-4-318 C>T (rs5742909), CTLA-4+49 A>G (rs231775), CD28 C>T (rs3116496)] between gastric cancer patients and controls (p=0.36, p=0.78, and p=0.80, respectively). The circulating levels of sCTLA-4 and sCD28 were significantly different between the gastric cancer group and the control group (p<0.001 and p<0.001, respectively). Conclusion The present results suggest that the CTLA-4 and CD28 gene polymorphisms that were evaluated do not play an important role in Turkish patients with gastric cancer. However, sCTLA4 and sCD28 levels were higher in cancer patients and may be useful as an auxiliary parameter in the diagnosis and monitoring of gastric cancer.

Background The neutrophil-lymphocyte ratio (NLR) is a good marker of malignant diseases. The aim of this study was to investigate NLR as a diagnostic marker of thyroid cancer in patients with malignant thyroid diseases compared to those with benign thyroid diseases. Methods Two hundred and fifty three patients were divided into two groups: benign and malignant thyroid disease patients. Malignant thyroid disease group was not sub-grouped further into differentiated and undifferentiated. The preoperative complete blood count and biochemical parameters, including NLR, were evaluated. Results The mean neutrophil count was found to be significantly higher, whereas the mean lymphocyte count was found to be significantly lower in the malignant group which includes 40 of the patients. As a result, NLR was significantly higher in the malignant group than in the benign group (p<0.001). Conclusion This is the first study to show the value of NLR as a marker for malignant thyroid diseases including all subtypes.

Objective A pattern recognition model was developed for aptamers against SMMC-7721 by applying the support vector machine (SVM) algorithm. Subsequently, according to computer-aided aptamer design, eight DNA aptamer sequences were synthesized and tested. Methods Candidate aptamer sequences selected for SMMC-7721 liver carcinoma cells were obtained with whole cell-SELEX. Their reverse-complement sequences were used for descriptor calculation to develop structure-activity relationships (SAR) model. SVM was adopted for the pattern recognition for candidate aptamer sequences with high or low affinity against SMMC-7721 liver carcinoma cells. By the model predictions, we designed, synthesized and tested eight DNA aptamer sequences against SMMC-7721. Results Five molecular descriptors from reverse-complement sequences were obtained to develop the SAR model of pattern recognition. The predicted fractions of winner aptamers with high affinity for the 3rd, 5th, 7th, 9th, 11th, and 13th rounds of SELEX selection are 0.09, 0.17, 0.69, 0.84, 0.90 and 0.98, respectively. Their fitting curve and the corresponding exponential equation conform to the aptamer evolutionary principles of SELEX based screening. These new designed sequences belonging to the class of sequences with high binding affinity have experimental dissociation constants K d in the nanomolar range. Conclusion The feasibility of applying computer-aided aptamer design has been demonstrated.

Background Altered signalling of human epidermal growth factor receptor-2 (HER-2/neu), insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF) have been shown to play important role in tumor development and progression in various cancers. Their serum levels may be reliable indicator for diagnosis and progression of cancer. Objective To examine the serum levels of soluble HER-2/neu (sHER-2/neu), IGF1 and EGF in patients with urinary bladder cancer (UBC). Material and methods Serum levels of sHER-2/neu, IGF1 and EGF were measured by enzyme-linked immune assay in newly diagnosed, untreated patients with UBC. Results In the patient group, sHER-2/neu level was found to be increased, IGF1 level was found to be decreased in comparison to those in the control group. Although serum level of sHER-2/neu was lower in the patients with Ta stage than that in the patients with T1 and T2 stages, this difference was not at a statistically significant level. Conclusion Serum level of sHER-2/neu is increased in patients with UBC. Despite the lack of a significant association between sHER-2/neu level and pathological pT stage, sHER-2/neu may be a promising marker for UBC but IGF-1 and EGF have not such a potential.

Aim Impaired mitochondrial function is a consequence of HIF1-induced overexpression of pyruvate dehydrogenase kinase (PDK) which phosphorylates and inactivates pyruvate dehydrogenase multi-enzyme complex (PDC), which converts pyruvate to acetyl-CoA for entry into the TCA cycle. Shifting cancer cells from glycolysis to oxidative phosphorylation induces apoptosis, which is a new therapeutic strategy by utilizing PDK inhibitors. In this work, the effect of PDK inhibitor, dichloroacetate (DCA) has been investigated in Human renal carcinoma cell line. Methods Adherent epithelium renal cell adenocarcinoma (ACHN) cells were treated with different concentrations of DCA at different time periods. Cell viability was measured by WST assay, cell-cycle profile and apoptosis were assessed by using flow cytometry. Metabolites of the cell extracts were analyzed by LC-MS/MS. Results DCA reduced cell viability in a concentration- and time-dependent manner. Treatment with DCA induced G1 arrest and apoptosis in ACHN cells. Additionally, metabolite changes of ACHN cell line upon DCA treatments showed that lactate, citrate, N-acetylaspartate and 5-oxoproline levels, which were high in untreated cells, significantly reduced upon DCA treatment. Conclusion Potential anti-carcinogenic effects of DCA, including inhibition of cell proliferation and growth, and induction of apoptosis, as well as the ability of markedly reducing lactate levels make this agent a promising drug candidate in renal adenocarcinomas.