High concentration calcitriol induces endoplasmic reticulum stress related gene profile in breast cancer cells

WOS: 000399165600038PubMed ID: 28177777Calcitriol, the active form of vitamin D, is known for its anticancer properties including induction of apoptosis as well as the inhibition of angiogenesis and metastasis. Understanding the mechanisms of action for calcitriol will help with the development of novel treatment strategies. Since vitamin D exerts its cellular actions via binding to its receptor and by altering expressions of a set of genes, we aimed to evaluate the effect of calcitriol on transcriptomic profile of breast cancer cells. We previously demonstrated that calcitriol alters endoplasmic reticulum (ER) stress markers, therefore in this study we have focused on ER-stress-related genes to reveal calcitriols action on these genes in particular. We have treated breast cancer cell lines MCF-7 and MDA-MB-231 with previously determined IC50 concentrations of calcitriol and evaluated the transcriptomic alterations via microarray. During analysis, only genes altered by at least 2-fold with a P value < 0.05 were taken into consideration. Our findings revealed an ER-stress-associated transcriptomic profile induced by calcitriol. Induced genes include genes with a pro-survival function (NUPR1, DNAJB9, HMOX1, LCN2, and LAMP3) and with a pro-death function (CHOP (DDIT3), DDIT4, NDGR1, NOXA, and CLGN). These results suggest that calcitriol induces an ER-stress-like response inducing both pro-survival and pro-death transcripts in the process.Ege UniversityEge University [2011-TIP-038]This work is supported by Ege University Scientific Research Project 2011-TIP-038

Energetic and exergetic performance assessment of a turboprop engine at various loads

Karakoc, Tahir Hikmet Hikmet/0000-0001-8182-8667;WOS: 000328571400007It is necessary to understand the mechanisms that have enabled improvements of performance parameters such as thermodynamics efficiencies, thrust or power, specific fuel consumption and specific power in aero engines, thus reducing environmental impact. in this study, a thermodynamic analysis of a turboprop engine is performed at full and partial load conditions. the maximum overall and exergy efficiencies of the turboprop are found to be 30.7 and 29.2%, respectively. the minimum specific fuel consumption and maximum shaft power are found to be 0.2704 kg (kWh)(-1) and 1948 shp at maximum load, respectively. More important, the optimum functional load conditions of the engine are observed at higher loads. the results from this study are expected to assist propeller aero-engine design work, where the first and second laws provide a more comprehensive assessment of performance, allowing the turboprop engine concept to be better tailored to specific types of regional transport aircraft.Anadolu University, EskisehirAnadolu University; Recep Tayyip Erdogan University, Rize, TurkeyRecep Tayyip Erdogan UniversityThe authors are grateful for the support provided for the present work by Anadolu University, Eskisehir and Recep Tayyip Erdogan University, Rize, Turkey. They also would like to express their appreciation to TUSAS Engine Industries (TEI) and TUAF in Eskisehir city of Turkey for full support throughout the preparation of this study, while they would like to thank the reviewers for their valuable comments, which helped in increasing the quality of the paper

Exergetic Sustainability Indicators as a Tool in Commercial Aircraft: A Case Study for a Turbofan Engine

6th International Green Energy Conference (IGEC) -- JUN 05-09, 2011 -- Eskisehir, TURKEYKarakoc, Tahir Hikmet Hikmet/0000-0001-8182-8667WOS: 000348028600005This paper focuses on the exergetic sustainability indicators of a medium-range commercial aircraft engine for constant reference environment and ground running conditions. First, a detailed exergy analysis of turbofan engine have been performed based on engine test cell parameters. Starting from the sustainability considerations and the second law of the thermodynamics, the paper presents six exergy-based sustainability indicators. the indicators of the turbofan engine developed here in conjunction with exergetic analysis and sustainable development are exergy efficiency, waste exergy ratio, exergy destruction factor, recoverable exergy rate, environmental effect factor, and exergetic sustainability index. the investigated sustainable indicators have been calculated by using exergy analysis outputs for aircraft ground running condition. Results from this study show that values of exergy efficiency, waste exergy ratio, exergy destruction factor, recoverable exergy rate, environmental effect factor, and exergetic sustainability index of investigated turbofan engine are found to be 0.315, 0.685, 0.408, 0, 2.174, and 0.460, respectively. These parameters are expected to quantify how the turbofan engine and aircraft become more environmentally benign and sustainable.Turkish Engine Industries (TEI), Anadolu UniversityAnadolu University; Recep Tayyip Erdogan University in TurkeyRecep Tayyip Erdogan UniversityThe authors acknowledge the support provided by Turkish Engine Industries (TEI), Anadolu University and Recep Tayyip Erdogan University in Turkey

The effect of calcitriol on endoplasmic reticulum stress response

WOS: 000355225900013PubMed ID: 25916601Calcitriol, the active form of vitamin D, is known for its anticancer properties including induction of apoptosis, inhibition of angiogenesis, and metastasis. Calcitriol also increases intracellular calcium triggering apoptosis in a calpain-dependent manner. Since the main storage unit for cellular calcium is endoplasmic reticulum (ER) and a decrease in ER calcium levels might induce ER stress associated cell death, we hypothesized that the cellular actions of calcitriol occur via ER stress. We have evaluated induction of ER stress by assessing BIP expression and XBP-1 splicing in breast cancer cell lines (MCF-7 and MDA-MB-231) and mammary epithelial cell line MCF10A. Our results suggest that cytotoxic concentrations of calcitriol induce an ER stress related response indicated as increased BIP levels and XBP-1 splicing not only in breast cancer cells but also in mammary epithelial cell line. However, vehicle treatment also induced a similar response de-emphasizing the importance of such effect. Calcitriol also failed to activate calpains, further weakening the idea of ER stress as the main mechanism for apoptotic effects of calcitriol. Taken together our results suggest an association between ER stress and vitamin D signaling. However present data indicates that ER stress by itself is not sufficient to explain anticancer properties of calcitriol.Ege UniversityEge University [2012-TIP-072]This project is supported by Ege University Scientific Research Project Grant No. 2012-TIP-072

Polymorphisms in the activin A receptor type 2A gene affect the onset time and severity of preeclampsia in the Turkish population

WOS: 000321288000007PubMed ID: 23633461Aim: To investigate the possible roles of selected single nucleotide gene polymorphisms (SNPs) of the activin A receptor type 2A (ACVR2A) gene in the pathogenesis of preeclampsia. Methods: Ninety-four patients with preeclampsia and 166 healthy pregnant women were included in this study. Genomic DNA was extracted from venous blood and were stored at -80 degrees C before the analysis. Selected ACVR2A SNPs (rs10497025, rs1128919, rs13430086) were determined in an ABI 7900 HT Real-Time PCR instrument. Results: For all three SNPs, no statistically significant difference was found between preeclampsia and control groups in terms of genotype and allele frequencies. In the late preeclampsia group, with regard to the rs1128919 SNP, the frequency of GG genotype was found to be significantly lower (P = 0.02). Although the frequency of "A" allele was found to be higher (P = 0.05; OR = 1.54), and the "G" allele was found to be lower (P = 0.05; OR = 0.65), the results did not reach statistical significance in late preeclamptic patients. For the rs1128919 SNP, the frequency of the AA genotype was found to be significantly higher in both mild (P = 0.004) and severe (P = 0.0001) preeclampsia groups, whereas the frequency of GG genotype was found to be significantly lower (P = 0.008, and P = 0.0001, respectively). For the rs13430086 SNP, while the frequency of the AA genotype was found to be significantly lower in both mild (P = 0.02) and severe (P = 0.0001) preeclamptic patients, the frequency of TT genotype was found to be significantly higher in only severe preeclampsia group (P = 0.0001). Conclusion: ACVR2A gene polymorphisms may play a role in the development of preeclampsia

Synergistic Interactions between GW8510 and Gemcitabine in an In Vitro Model of Pancreatic Cancer

Background: One of the main reasons for the poor survival rates of pancreatic cancer patients is the development of gemcitabine resistance, indicating that novel treatment strategies that have the ability to improve gemcitabine sensitivity are in need to combat this devastating disease. Methods: TCGA PAAD data was used to determine the clinicopathological significance of high RRM2 (Ribonucleotide reductase subunit M2) expression for Pancreatic Ductal Adenocarcinoma (PDAC). The effects of GW8510 and gemcitabine on PANC-1 cell viability were determined using WST-8 assay. The potential synergistic interaction between GW8510 and gemcitabine was evaluated by the Combination Index (CI) analysis. The effects of GW8510 treatment on apoptosis, cell cycle, and cell migration, either in combination with gemcitabine or alone, were investigated. The effect of GW8510 on RRM2 protein levels was evaluated using ELISA assay. Results: RRM2 is significantly over-expressed in PDAC compared to healthy pancreatic tissues (p 0.0001). RRM2 mRNA expression was found to be significantly correlated with the overall survival rate of patients (HR=2.17 [1.44-3.27], p=0.00016) and the pathological stages of the disease (p=0.0054). GW8510 significantly decreased the RRM2 protein levels compared to the control. Cell viability analysis showed that GW8510 has a similar effect to gemcitabine in inhibiting PANC-1 cell viability. GW8510 was found to synergize with gemcitabine to inhibit PANC-1 cell viability and migration. However, the effects of GW8510 on PANC-1 cells could not be explained by induction of apoptosis or cell cycle arrest. Conclusion: Targeting RRM2 using GW8510 may have the potential to increase gemcitabine sensitivity in pancreatic cancer.This research was funded by the Technological Research Council of Turkey (TUBITAK) within the framework of the national project as 1002 Short Term R;D Funding Program (Project no: 318S052) .Technological Research Council of Turkey (TUBITAK) [318S052