Antidiabetic exendin-4 activates apoptotic pathway and inhibits growth of breast cancer cells

Exendin-4 is a GLP-1 analog used for the treatment of type 2 diabetes mellitus in its synthetic form. As women with diabetes have higher breast cancer incidence and mortality, we examined the effect of the incretin drug exendin-4 on breast cancer cells. The aim of the study is to investigate anticancer mechanism of exendin-4 in MCF-7 breast cancer cells. Cytotoxic effects of exendin-4 were determined by XTT assay. IC50 dose in MCF-7 cells were detected as 5 μM at 48th hour. Gene messenger RNA (mRNA) expressions were evaluated by real-time PCR. According to results, caspase-9, Akt, and MMP2 expression was reduced in dose group cells, compared with the control group cells. p53, caspase-3, caspase-8, caspase-10, BID, DR4, DR5, FADD, TRADD, PARP, PTEN, PUMA, NOXA, APAF, TIMP1, and TIMP2 expression was increased in dose group cells, compared with the control group cells. Effects of exendin-4 on cell invasion, colony formation, and cell migration were detected by Matrigel chamber, colony formation assay, and wound-healing assay, respectively. To conclude, it is thought that exendin-4 demonstrates anticarcinogenesis activity by effecting apoptosis, invasion, migration, and colony formation in MCF-7 cells. Exendin-4 may be a therapeutic agent for treatment of breast cancer as single or in combination with other agents. More detailed researches are required to define the pathways of GLP-1 effect on breast cancer cells because of the molecular biology of breast cancer that involves a complex network of interconnected signaling pathways that have role in cell growth, survival, and cell invasion. © 2015, International Society of Oncology and BioMarkers (ISOBM)

Social media adoption and export intensity: The moderating role of firm size

Purpose: Social media (SM) networks offer a golden opportunity for firms that particularly engage in international activities to set up sustainable customer relationships and improve competitiveness. The purpose of this study is to examine the influence of SM adoption on the export intensity (EI) of firms listed on Borsa Istanbul (BIST) for the years 2010–2020. The authors use social media index (SMI) to measure SM adoption and firm size (FSize) as a moderator on exploring the interaction of SM and EI. Design/methodology/approach: Using a sample of 150 firms listed on the BIST Industrials Index, this study explores how the adoption of SM affects EI by using panel data analysis over the period of 2010–2020. Findings: The results indicate that the SMI has a positive and significant effect on the EI. FSize positively moderates the interaction of SMI and EI, indicating that large firms benefit more from the SM in increasing export performance. The findings reflect high potential of EI improvement through adopting right SM policies in emerging markets. Research limitations/implications: The sample covers only public companies listed on the BIST Industrials Index. Future studies may extend the coverage and include multiple emerging markets to draw generalized results for the export-oriented firms. This research also analyzes solely four SM networks, i.e. Facebook, Instagram, Twitter and YouTube. However, there are many other SM networks that firms use in online marketing in foreign markets. Finally, this research did not discuss the potential factors that could influence the use of SM in emerging market firms. Practical implications: This study denotes the significant role of SM adoption on the EI of firms in an emerging market setting from the perspective of resource-based view. It presents an insightful approach in understanding the mission played by SM networks in enhancing the EI of Turkish firms. Policymakers may use the findings to develop public support programs to promote the adoption and implementation of the SM among exporting firms in emerging markets. Originality/value: The study provides evidence on the effects of SM adoption on the EI from the perspective of emerging countries. It also helps to gain a deeper understanding of how different SM platforms contribute to the internationalization of firms

Effects of monensin on caspase-10 mediated apoptosis in glioblastoma multiforme

Glioblastoma multiforme (GBM), en kötü huylu primer merkezi sinir sistemi tümörüdür. Şu anda, GBM için iyileştirici tedavi seçenekleri yoktur ve 5 yıllık hayatta kalma oranı %5’den daha azdır. Monensin, ‘’Streptomyces cinnamonensis’’ den elde edilen antibakteriyal ve antiparazitik etkileri bilinen iyonofor bir antibiyotiktir. Literatürde monensinin GBM hücrelerinin apoptoz mekanizması üzerine etki göster- diği bir çalışmaya rastlanmadığından yapılan bu çalışmanın amacı monensinin U373 GBM hücrelerinde apoptoz aracılı hücre proliferasyonu üzerine etkilerini araştırmaktır. Monensinin U373 hücre canlılığı üzerine etkileri XTT ile apoptoz üzerine etkileri ise RT-PCR ve Annexin V ile araştırılmıştır. Monensinin U373 GBM hücrelerinde IC 50 değeri 48’inci saatte 4 μM olarak bulunmuştur. Monensin U373 GBM hücrele- rinde apoptoz oranında 6 katlık bir artışa neden olmuştur. Bununla birlikte monensin kaspaz-10 gen ekspresyonunu arttırarak apoptozu anlamlı olarak aktive etmiştir. Sunulan çalışma monensinin GBM hücrelerinin kaspaz-10 aracılı apoptoz mekanizması üzerine etkilerini gösteren ilk çalışmadır. Bizim sonuçlarımız monensinin GBM kanserinde güçlü apoptotik etkileri olan terapötik bir antikanser ilaç bileşiği olabileceğini önermektedir.Glioblastoma multiforme (GBM) is the most malignant primary central nervous system tumor. Currently, there are no curative treatment options for GBM and the 5-year survival rate is less than 5%. Therefore, further studies are needed to identify effective markers and thera- peutic targets for GBM treatment. Monensin is an ionophore antibiotic obtained from Streptomyces cinnamonensis with known antibacterial and antiparasitic effects. In the literature, no study has been found that shows an effect of monensin on the apoptosis mechanism of GBM cells. The aim of the present study was to investigate the effects of monensin on apoptosis-mediated cell proliferation in U373 GBM cells. The effects of monensin on U373 cell viability were investigated by XTT and its effects on apoptosis were investigated by RT-PCR and Annexin V. The IC50 value of monensin in U373 GBM cells was 4 μM at 48 hours. Monensin caused a 6-fold increase in the rate of apoptosis in U373 GBM cells. Monensin also significantly triggered apoptosis by increasing caspase-10 gene expression. The present study is the first to demonstrate the effects of monensin on the caspase-10-mediated apoptosis mechanism of GBM cells. Our results suggest that monensin may be a therapeutic anticancer drug compound with potent apoptotic effects in GBM cancer

Extract of Calvatia gigantea inhibits proliferation of A549 human lung cancer cells

In this study, in order to investigate the anticancer mechanism of Calvatia gigantea extract, edible mushroom species, which belong to Lycoperdaceae family, changes of CCND1, CCND2, CDK4, p21, Akt, Bax, Bcl-2, p53, caspase-3 and caspase-9 were evaluated in A549 lung cancer cells. Cytotoxic effect of C.gigantea extract was evaluated by using XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5 carboxanilide). The C. gigantea extract was treated in a time and dose dependent manner within the range 25 μg/ml–2 mg/ml to determine the IC50 dose. IC50 dose for C. gigantea extract was detected as 500 μg/ml for 72 h. According to expression results, while CCND1, CCND2, CDK4, Akt and Bcl-2 expression clearly decreased, Bax, p53, caspase-3 and caspase-9 expression clearly increased in the dose group cells (A549 cells treated with 500 μg/ml dose of C. gigantea extract for 72 h). However, there was no change in p21 expression. C. gigantea extract induced cell cycle arrest and apoptosis by decreasing the CCND1, CCND2, CDK4, Akt and Bcl-2 expression and by increasing Bax, p53, caspase-3 and caspase-9 expression in A549 cells. Mushrooms are eukaryotic organisms heavily used because of their supposedly anticancer effect. Many mushroom species have been used for medical purposes, as a result of also having many effects such as antibiotic, antiviral and anticancer effects. It is thought that the C. gigantea extract may be a significant agent for treatment of lung cancer as a single agent or in combination with other drugs. © 2016, Springer Science+Business Media Dordrecht

Investigation of the effects of erianin on proliferation and colony formation of HT29 colorectal cancer cells

Kolorektal kanser, dünyada kanser ilişkili ölümlerin en yaygın dördüncü sebebidir. Erianin antioksidan ve anti-tümör etkilere sahip Dendrobium ekstraktından elde edilen yeni bir dibenzil bileşiğidir. Bu çalışmada, erianinin HT29 kolorektal kanser hücreleri üzerine olan terapötik etkileri araştırılmıştır. Erianinin HT29 hücre canlılığı üzerine etkileri XTT test ile koloni oluşumu üzerine etkileri ise koloni formasyonu ile değerlendirilmiştir. Erianinin HT29 hücrelerinde IC50 değeri 48. saatte 59.05 µM olarak belirlenmiştir. HT29 hücre dizisinde erianin uygulanan grupta koloni sayısı 67±33 iken kontrol grubunda 350±89 olarak hesaplanmıştır. Erianin, HT29 kolorektal kanser hücrelerinde koloni oluşumunu ise anlamlı derecede azaltmıştır. Yapılan çalışmaların sonuçları, erianinin kolorektal kanser tedavisinde doğal elde edilen bir bileşik olarak güvenli, kolay ulaşılabilir ve umut veren terapötik bir ilaç olabileceğini destekler niteliktedir. Gelecekte erianinin kolorektal kanser hücreleri üzerindeki etki mekanizmasını aydınlatacak daha kapsamlı ve çok merkezli desteklenecek ileri düzeyde klinik çalışmalara ihtiyaç vardır.Colorectal cancer (CRC) is the 4th most common cause of cancer-related death in the global world. Erianin, a novel dibenzyl compound in Dendrobium extract, has antioxidative and antitumor activities. In this study, the therapeutic effects of erianin on HT29 colorectal cancer cells were investigated. Effects of erianin on cell viability were evaluated by XTT test. Effects of erianin on colony formation were evaluated by colony formation analysis. IC50 values of Erianin on HT29 cells were determined as 59.05 µM at 48th hour. While the number of colonies in the HT29 cell line was 67±33 in the erianin treated group, it was calculated as 350±89 in the control group. Erianin significantly reduced colony formation in HT29 colorectal cancer cells. The results of the presented studies support that erianin as a natural product in the treatment of colorectal cancer can be a safe, easily accessible and promising therapeutic drug. In the future, more comprehensive and multi-center supported clinical studies are needed to elucidate the mechanism of action of erianin on colorectal cancer cells

Anti-proliferative and anti-invasive effects of ferulic acid in TT medullary thyroid cancer cells interacting with URG4/URGCP

Ferulic acid (4-hydroxy-3-methoxycinnamic acid; FA), a common dietary plant phenolic compound, is abundant in fruits and vegetables. The aim of present study is to investigate the effects of FA on cell cycle, apoptosis, invasion, migration, and colony formation in the TT medullary thyroid cancer cell line. The effect of FA on cell viability was determined by using CellTiter-Glo assay. IC50 dose in the TT cells was detected as 150 μM. URG4/URGCP (upregulated gene-4/upregulator of cell proliferation) is a novel gene in full-length mRNA of 3.607 kb located on 7p13. It was determined that FA caused a decrease in the expression of novel gene URG4/URGCP, CCND1, CDK4, CDK6, BCL2, MMP2, and MMP9, a significant increase in the expression of p53, PARP, PUMA, NOXA, BAX, BID, CASP3, CASP9, and TIMP1 genes in TT human thyroid cancer cell line by using real-time PCR. It was found that FA in TT cells suppressed invasion, migration, and colony formation by using matrigel invasion chamber, wound healing, and colony formation assay, respectively. In conclusion, it is thought that FA indicates anticarcinogenesis activity by affecting cell cycle arrest, apoptosis, invasion, migration, and colony formation on TT cells. © 2015, International Society of Oncology and BioMarkers (ISOBM)

Development, test and comparison of two Multiple Criteria Decision Analysis(MCDA) models: A case of healthcare infrastructure location

When planning a new development, location decisions have always been a major issue. This paper examines and compares two modelling methods used to inform a healthcare infrastructure location decision. Two Multiple Criteria Decision Analysis (MCDA) models were developed to support the optimisation of this decision-making process, within a National Health Service (NHS) organisation, in the UK. The proposed model structure is based on seven criteria (environment and safety, size, total cost, accessibility, design, risks and population profile) and 28 sub-criteria. First, Evidential Reasoning (ER) was used to solve the model, then, the processes and results were compared with the Analytical Hierarchy Process (AHP). It was established that using ER or AHP led to the same solutions. However, the scores between the alternatives were significantly different; which impacted the stakeholders‟ decision-making. As the processes differ according to the model selected, ER or AHP, it is relevant to establish the practical and managerial implications for selecting one model or the other and providing evidence of which models best fit this specific environment. To achieve an optimum operational decision it is argued, in this study, that the most transparent and robust framework is achieved by merging ER process with the pair-wise comparison, an element of AHP. This paper makes a defined contribution by developing and examining the use of MCDA models, to rationalise new healthcare infrastructure location, with the proposed model to be used for future decision. Moreover, very few studies comparing different MCDA techniques were found, this study results enable practitioners to consider even further the modelling characteristics to ensure the development of a reliable framework, even if this means applying a hybrid approach

Explant Culture of Ovarian Tissue

INTRODUCTION: In this study, it was aimed to isolate, reproduce and characterize stromal cells migrating from tissues by creating ovarian tissue explant culture. It is also aimed to create a mixed cell culture (ovarian stromal stem cells and ovarian surface epithelium) with the tissues obtained from different parts of the ovary and to examine the interactions of the cells with each other. METHODS: Explant cultures were formed from ovarian tissues of 4 week old (prepubertal) two female Wistar Albino type rats. Then, the expression of CD29, CD54, CD90 (mesenchymal stem cell surface antigen) and CD45 (hematopoietic stem cell surface antigen) was investigated by performing flow cytometry analysis on proliferating ovarian stromal cells in the 2nd passage (P2). RESULTS: The proliferation abilities and morphological characteristics of the cells in the culture medium were examined by serial passaging. In flow cytometry analysis of isolated ovarian stromal cells, it was determined that they expressed CD54, CD90 and CD45 surface antigens, but did not express CD29 surface antigens. DISCUSSION AND CONCLUSION: In the analysis, we determined that the ovarian stromal cells we isolated and produced in the culture medium expressed hematopoietic and some mesenchymal stem cell markers

Barriers to smart waste management for a circular economy in China

Waste management requires a new vision and drastic improvements for a transition to a zero-waste circular economy. In reality, however, many economies are producing more and more waste, which poses a serious challenge to environmental sustainability. The problem is enormously complex as it involves a variety of stakeholders, demands behavioral changes, and requires a complete rethinking of the current waste management systems and the dominant linear economic model. Smart enabling technologies can aid in a transformation of waste management toward a circular economy, but many barriers persist. This study first shortlists twelve important barriers to smart waste management in China based on interviews with experienced practitioners. It then prioritizes these barriers through a scientific prioritization technique, fuzzy Decision-Making Trial and Evaluation Laboratory (DEMATEL), based on the survey data from three representative stakeholders. It identified three key causal barriers: the lack of regulatory pressures, the lack of environmental education and culture of environmental protection, and the lack of market pressures and demands. Practical and theoretical implications were discussed based on the research results and findings

A review of application of multi-criteria decision making methods in construction

Construction is an area of study wherein making decisions adequately can mean the difference between success and failure. Moreover, most of the activities belonging to this sector involve taking into account a large number of conflicting aspects, which hinders their management as a whole. Multi-criteria decision making analysis arose to model complex problems like these. This paper reviews the application of 22 different methods belonging to this discipline in various areas of the construction industry clustered in 11 categories. The most significant methods are briefly discussed, pointing out their principal strengths and limitations. Furthermore, the data gathered while performing the paper are statistically analysed to identify different trends concerning the use of these techniques. The review shows their usefulness in characterizing very different decision making environments, highlighting the reliability acquired by the most pragmatic and widespread methods and the emergent tendency to use some of them in combination