153 research outputs found
Simultaneous inhibition of PFKFB3 and GLS1 selectively kills KRAS-transformed pancreatic cells
No full textActivating mutations of the oncogenic KRAS in pancreatic ductal adenocarcinoma (PDAC) are associated with an aberrant metabolic phenotype that may be therapeutically exploited. Increased glutamine utilization via glutaminase-1 (GLS1) is one such feature of the activated KRAS signaling that is essential to cell survival and proliferation; however, metabolic plasticity of PDAC cells allow them to adapt to GLS1 inhibition via various mechanisms including activation of glycolysis, suggesting a requirement for combinatorial anti-metabolic approaches to combat PDAC. We investigated whether targeting the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) in combination with GLS1 can selectively prevent the growth of KRAS-transformed cells. We show that KRAS-transformation of pancreatic duct cells robustly sensitizes them to the dual targeting of GLS1 and PFKFB3. We also report that this sensitivity is preserved in the PDAC cell line PANC-1 which harbors an activating KRAS mutation. We then demonstrate that GLS1 inhibition reduced fructose-2,6-bisphosphate levels, the product of PFKFB3, whereas PFKFB3 inhibition increased glutamine consumption, and these effects were augmented by the co-inhibition of GLS1 and PFKFB3, suggesting a reciprocal regulation between PFKFB3 and GLS1. In conclusion, this study identifies a novel mutant KRAS-induced metabolic vulnerability that may be targeted via combinatorial inhibition of GLS1 and PFKFB3 to suppress PDAC cell growth.Fil: Ozcan, Selahattin C.. Koc University Research Center For Translational Medici; TurquíaFil: Mutlu, Aydan. Bursa Uludag University; TurquíaFil: Altunok, Tugba H.. Bursa Uludag University; TurquíaFil: Gurpinar, Yunus. Bursa Uludag University; TurquíaFil: Sarioglu, Aybike. Bursa Uludag University; TurquíaFil: Guler, Sabire. Bursa Uludag University; TurquíaFil: Muchut, Robertino José. Universidad Nacional del Litoral; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Iglesias, Alberto Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral; ArgentinaFil: Celikler, Serap. Bursa Uludag University; TurquíaFil: Campbell, Paul M.. The Marvin and Concetta Greenberg Pancreatic Cancer Institute; Estados UnidosFil: Yalcin, Abdullah. Bursa Uludag University; Turquí
PFKFB2 regulates glycolysis and proliferation in pancreatic cancer cells
No full textTumor cells increase glucose metabolism through glycolysis and pentose phosphate pathways to meet the bioenergetic and biosynthetic demands of rapid cell proliferation. The family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) are key regulators of glucose metabolism via their synthesis of fructose-2,6-bisphosphate (F2,6BP), a potent activator of glycolysis. Previous studies have reported the co-expression of PFKFB isozymes, as well as the mRNA splice variants of particular PFKFB isozymes, suggesting non-redundant functions. Majority of the evidence demonstrating a requirement for PFKFB activity in increased glycolysis and oncogenic properties in tumor cells comes from studies on PFKFB3 and PFKFB4 isozymes. In this study, we show that the PFKFB2 isozyme is expressed in tumor cell lines of various origin, overexpressed and localizes to the nucleus in pancreatic adenocarcinoma, relative to normal pancreatic tissue. We then demonstrate the differential intracellular localization of two PFKFB2 mRNA splice variants and that, when ectopically expressed, cytoplasmically localized mRNA splice variant causes a greater increase in F2,6BP which coincides with an increased glucose uptake, as compared with the mRNA splice variant localizing to the nucleus. We then show that PFKFB2 expression is required for steady-state F2,6BP levels, glycolytic activity, and proliferation of pancreatic adenocarcinoma cells. In conclusion, this study may provide a rationale for detailed investigation of PFKFB2’s requirement for the glycolytic and oncogenic phenotype of pancreatic adenocarcinoma cells.Fil: Ozcan, Selahattin C.. Koc University Research Center For Translational Medici; TurquíaFil: Sarioglu, Aybike. Bursa Uludag University; TurquíaFil: Altunok, Tugba H.. Bursa Uludag University; TurquíaFil: Akkoc, Ahmet. Bursa Uludag University; TurquíaFil: Guzel, Saime. Bursa Uludag University; TurquíaFil: Guler, Sabire. Bursa Uludag University; TurquíaFil: Imbert-Fernandez, Yoannis. University of Louisville; Estados UnidosFil: Muchut, Robertino José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Iglesias, Alberto Alvaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Agrobiotecnología del Litoral. Universidad Nacional del Litoral. Instituto de Agrobiotecnología del Litoral; ArgentinaFil: Gurpinar, Yunus. Bursa Uludag University; TurquíaFil: Clem, Amy L.. University of Louisville; Estados UnidosFil: Chesney, Jason A.. University of Louisville; Estados UnidosFil: Yalcin, Abdullah. Bursa Uludag University; Turquí
Effects of royal jelly on ovary cancer cells proliferation and apoptosis
No full textThe aim of the present study is to investigate the proliferative or apoptotic effects of different doses and durations of Royal jelly (RJ) on serous type epithelial ovarian cancer, which is the most common epithelial ovarian cancer. For this purpose, cells of the Skov-3 human ovarian adenocarcinoma cell line were grown in McCoy medium and seeded in 6-well plates. RJ was prepared as a stock solution (1000 mg RJ/10 ml dH2O) and 1, 5, 10, 20, and 50 mg/ml RJ doses from the prepared stock solution were added to the medium for 24, 48, and 72 h incubated. After the treatment of RJ, the cell viability test (Tripan Blue), Ki-67 to determine the proliferative effect, cleaved-Caspase-3 and cleaved PARP expressions to determine its apoptotic effect were examined by immunocytochemical and immunofluorescence methods. In addition, findings were supported by the TUNEL method. As a result of the experiments, it was determined that 1 mg/ml and 24 h treatment of RJ did not affect cell proliferation and apoptosis, but generally, 50 mg/ml of RJ for 72 h inhibited proliferation in cancer cells and induced apoptosis. The use of royal jelly both monotherapeutically and in combination as an alternative treatment for ovarian cancer may provide the basis for new experimental protocols
Unveiling the actual progress of Digital Building Permit: Getting awareness through a critical state of the art review
No full textGrowing interest is awarded to the digitalization of the building permitting use case and many works are developed about the topic. However, the subject is very complex and many aspects are usually tackled separately, making it very hard for traditional literature reviews to grasp the actual progress in the overall topic. This paper unveils the detailed state of the art in Digital Building Permitting (DBP) by critically analysing the literature by means of a set of coding tags (research progress, implementation, affected DBP workflow steps, ambitions addressed) assigned by a multidisciplinary team. The executed research shows that the mainly addressed aspects of the digitalization of building permit process are the technologies to check the compliance of design proposals against regulations, followed by the digitalization of regulations. Improvable aspects identified in the entire building permit system are instead e.g. the involvement of officers, scalability of solutions and interoperability of data, intended both as data validation and as integration of geospatial data with building models.Urban Data Scienc
Obliteração pulpar em incisivo decíduo traumatizado
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. Programa de Pós-Graduação em Odontologia.Este estudo descritivo retrospectivo em incisivos centrais superiores decíduos traumatizados teve por objetivo, verificar a ocorrência de obliteração pulpar, o tempo decorrido entre o trauma e o desenvolvimento desta seqüela, a presença de alteração de cor da coroa bem como a freqüência de necrose pulpar secundária nos dentes obliterados, além de avaliar a existência de associação entre a obliteração e o sexo, a idade do paciente no momento do trauma dental, o tipo e a reincidência de trauma. Para isto, realizou-se uma pesquisa desenvolvida a partir dos dados clínicos e radiográficos dos prontuários de pacientes participantes do Programa de Atendimento ao Paciente Traumatizado da Universidade Federal de Santa Catarina, entre agosto de 1998 e agosto de 2007. Seguindo os critérios de elegibilidade, foram incluídos 112 dentes de 82 crianças. Destes, 60 (53,6%) apresentavam obliteração pulpar, sendo que em 58,3% dos casos esta foi diagnosticada em até 12 meses após o trauma. A associação entre alteração de cor da coroa e obliteração pulpar foi confirmada (p<0,001), e não houve casos de necrose pulpar secundária. Não se observou associação estatística entre as variáveis sexo e idade dos pacientes, bem como tipo e recorrência de trauma em relação a obliteração pulpar. Os resultados deste estudo permitem concluir que a ocorrência de obliteração pulpar em dentes decíduos traumatizados é alta e a proservação clínica e radiográfica periódica é a melhor conduta para esta seqüela
How to exploit BIM/IFC for 3D registration of ownership rights in multi-storey buildings: an evidence from Turkey
No full textThe condominium rights, which is a special ownership type that can only exist in the buildings that have an occupancy permit, are needed to be examined and depicted as three-dimensional (3D) in order to prevent misinterpretations and disputes regarding Rights, Restrictions, and Responsibilities (RRRs). This paper, therefore, aims to provide the model that extends the Industry Foundation Classes (IFC) schema by referencing Land Administration Domain Model (LADM) in the sense of reusing the Building Information Modeling (BIM)/IFC model of the building for 3D registration of condominium rights in Turkey. The results of the study show that there is a solid potential to benefit from BIM/IFC model in order for both 3D representation of the ownership rights in the multi-storey buildings and obtaining the semantics of the condominiums in terms of wide ranges of attributes such as area, volume, land share, and RRRs.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.GIS Technologi
Effect of high-fat diet on the various morphological parameters of the ovary
No full textIncreased food consumption rich in fat and carbohydrate and sedentary lifestyle have seriously increased the rates of obesity and obesity-associated diseases in developed countries. Female mice with diet-induced obesity exhibit infertility and thus can serve as a model for human polycystic ovary syndrome. The aim of the present study was to examine how ovary is affected by diet-induced obesity. The effects of high-fat diet (HFD) on ovary morphology in mice fed with HFD were investigated using unbiased stereological methods. The ovary of mice fed with HFD (n=8, C1090-60, Altromine) for 9 weeks, were compared with that of mice fed with standard chow diet (n=8, C1090-10, Altromine). Stereological parameters were obtained in diestrus cycle. The samples were processed through routine and standard paraffin embedding and were serially sectioned in 5-mu m thickness then, every 10th section was saved, stained with Crossman's triple stain for counting and measuring. In all sampled sections mean follicle numbers, diameters, total ovarian volume cortex to medulla ratio (Vv), ovum to cell ratio in secondary follicle were examined in all sampled sections. The present results showed that weight of ovarian and amount of intraperitoneal adipose tissue and the body weight markedly increased in obese mice when compared with control groups. Moreover, follicle numbers (except primordial follicles) and diameters were significantly increased in obese mice. Cortex to medulla ratio (Vv) and ovum to cell ratio in secondary follicle were also considerably different between experimental and the control groups. The present findings indicate that obesity adversely affects overall ovarian morphology.Eskisehir Osmangazi University Research Projects Center [2014-586]The present study was also financially supported by Eskisehir Osmangazi University Research Projects Center with the project code 2014-586
ORGANIZATION OF SELLING PRODUCTS IN CENTRAL ASIAN COUNTRIES: CASE OF TURKUAZ GROUP OF COMPANIES
No full textThe term organization of selling products acquires a major importance in success of business environment. World has withessed huge economic development in last century. Industrial revolution of two centuries back has resulted into all round economic growth and prosperity across the nations. So, the world's successful business environment is the main driver of stable workplaces and high GDP for the economy. But under successful sales organization there are so many details, like satisfaction of customers, training and educating or sales reps, researching of marketplaces, designing of sales territory and sales people. All these details are engine for successful business environment. In this research author tried to find the efficient organization of selling products in Kazakhstan and Central Asian countries. So, author has found that in Kazakhstan there are so many challenges in organization of selling products especially in logistics as well as privileges in legal system of the Republic of Kazakhstan
Spread of retailer food quality standards: an international perspective
No full textPrivately initiated food quality standards are currently important elements in the marketing of food and agricultural products. At the same time, they stand in the centre of a discussion about potential negative effects on small farmers and farmers in developing countries. This study aims at analysing the adoption of two private food standards, BRC Technical Food Standard and GlobalGAP, at an aggregated crosscountry level. The results of the econometric analysis reveal some (potential) barriers for developing countries to access this type of organisational innovation. Certificates seem to be issued more probably in larger and wealthier countries, countries with a better institutional quality, better infrastructural conditions and in former UK colonies
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