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| 1 | Telmisartan induces melanoma cell apoptosis and synergizes with vemurafenib in vitro by altering cell bioenergetics显示文摘Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents a serious challenge and new approaches for melanoma treatment are urgently needed. The objective of this study was to examine the effects of telmisartan, an AGTR1 inhibitor and a partial agonist of PPARγ, on melanoma cells as a potential agent for repurposing in melanoma treatment.Methods: Expression of AGTR1 and PPARγ m RNA in melanoma patient tumor samples was examined in publicly available datasets and confirmed in melanoma cell lines by qRT-PCR. A panel of melanoma cell lines was tested in viability, apoptosis and metabolic assays in presence of telmisartan by flow cytometry and immunocytochemistry. A cytotoxic effect of combinations of telmisartan and targeted therapy vemurafenib was examined using the Chou-Talalay combination index method.Results: Both AGTR1 and PPARγ mRNA were expressed in melanoma patient tumor samples and decreased compared to the expression in the healthy skin. In vitro, we found that telmisartan decreased melanoma cell viability by inducing cell apoptosis.Increased glucose uptake, but not utilization, in the presence of telmisartan caused the fission of mitochondria and release of reactive oxygen species. Telmisartan altered the cell bioenergetics, thereby synergizing with vemurafenib in vitro, and even sensitized vemurafenib-resistant cells to the treatment.Conclusions: Given that the effective doses of telmisartan examined in our study can be administered to patients and that telmisartan is a widely used and safe antihypertensive drug, our findings provide the scientific rationale for testing its efficacy in treatment of melanoma progression. | Jelena Grahovac Tatjana Srdic-Rajic Juan Francisco Santibanez Marijana Pavlovic Milena Cavic Sinisa Radulovic1 | 2019 | Cancer Biology & Medicine2019，16，2： | 3 |
| 2 | Optimization of aerodynamic properties of high-speed trains with CFD and response surface models显示文摘 | Krajnovic Sinisa | 2009 | The Aerodynamics of Heavy Vehicles II: Trucks Buses and Trains2009，41，： | 1 |
| 3 | Substrate Specificity of Rhomboid Intramembrane Proteases Is Governed by Helix-Breaking Residues in the Substrate Transmembrane Domain显示文摘 | Sinisa Urban Matthew Freeman | 2003 | Molecular Cell2003，，6： | 1 |
| 4 | Regulated Intracellular Ligand Transport and Proteolysis Control EGF Signal Activation in Drosophila显示文摘 | Jeffrey R. Lee Sinisa Urban Clare F. Garvey Matthew Freeman | 2001 | Cell2001，，2： | 1 |
| 5 | Drosophila Rhomboid-1 Defines a Family of Putative Intramembrane Serine Proteases显示文摘 | Sinisa Urban Jeffrey R. Lee Matthew Freeman | 2001 | Cell2001，，2： | 1 |
| 6 | Ikaros in hematopoiesis and leukemia显示文摘Ikaros is a gene whose activity is essential for normal hematopoiesis.Ikaros acts as a master regulator of lymphoid and myeloid development as well as a tumor suppressor.In cells,Ikaros regulates gene expression via chromatin remodeling.During the past 15 years tremendous advances have been made in understanding the role of Ikaros in hematopoiesis and leukemogenesis.In this Topic Highlights series of reviews,several groups of international experts in this field summarize the experimental data that is shaping the emerging picture of Ikaros function at the biochemical and cellular levels.The articles provide detailed analyses of recent scientific advancements and present models that will serve as a basis for future studies aimed at developing a better understanding of normal hematopoiesis and hematological malignancies and at accelerating the application of this knowledge in clinical practice. | Sinisa Dovat | 2011 | World Journal of Biological Chemistry2011，2，6： | 1 |
| 7 | An overview of biomass energy utilization in Vojvodina 显示文摘 | Sinisa N Dodic Stevan D Popov Jelena M Dodie | 2010 | Renewable and Sustainable Energy Reviews2010，14，1： | 1 |
| 8 | Membrane fouling daring cross-flow microfiltration of polyporus squamosus fermentation broth显示文摘 | Darko M Krstic Sinisa L Markov Miodrag N Teki | 2001 | Biochemical Engineering Journal2001，19，： | 1 |
| 9 | Photokilling Squamous Carcinoma Cells SCCVII with Ultrafine Particles of Selected Metal Oxides显示文摘 | Sinisa Ivankovic Marijan Gotic Mislav Jurin | 2003 | J Sol-gel Sci Technol2003，27，： | 1 |
| 10 | Ikaros isoforms:The saga continues显示文摘Through alternate splicing,the Ikaros gene produces multiple proteins.Ikaros is essential for normal hematopoiesis and possesses tumor suppressor activity.Ikaros isoforms interact to form dimers and potentially multimeric complexes.Diverse Ikaros complexes produced by the presence of different Ikaros isoforms are hypothesized to confer distinct functions.Small dominantnegative Ikaros isoforms have been shown to inhibit the tumor suppressor activity of full-length Ikaros.Here,we describe how Ikaros activity is regulated by the coordinated expression of the largest Ikaros isoforms IK-1 and IK-H.Although IK-1 is described as full-length Ikaros,IK-H is the longest Ikaros isoform.IK-H,which includes residues coded by exon 3B (60 bp that lie between exons 3 and 4),is abundant in human but not murine hematopoietic cells.Specific residues that lie within the 20 amino acids encoded by exon 3B give IK-H DNA-binding characteristics that are distinct from those of IK-1.Moreover,IK-H can potentiate or inhibit the ability of IK-1 to bind DNA.IK-H binds to the regulatory regions of genes that are upregulated by Ikaros,but not genes that are repressed by Ikaros.Although IK-1 localizes to pericentromeric heterochromatin,IK-H can be found in both pericentromeric and non-pericentromeric locations.Anti-silencing activity of gamma satellite DNA has been shown to depend on the binding of IK-H,but not other Ikaros isoforms.The unique features of IK-H,its influence on Ikaros activity,and the lack of IK-H expression in mice suggest that Ikaros function in humans may be more complex and possibly distinct from that in mice. | Laura A Perez-Casellas Aleksandar Savic Sinisa Dovat | 2011 | World Journal of Biological Chemistry2011，2，6： | 1 |
| 11 | In vivo fiber tractography using DT-MRI data 显示文摘 | Basser P J Sinisa Pajevic Carlo Pierpaoli | 2000 | Magnetic Resonance in Medicine2000，44，： | 1 |
| 12 | A vision system for intelligent mission profiles of micro air vehicles显示文摘 | Todorovic Sinisa Nechyba M C | 2004 | IEEE Transaction on Vehicular Technology2004，53，6： | 1 |
| 13 | Convex structure, normal structure and a fixed point theorem in intuitionistic fuzzy metric spaces 显示文摘 | SINISA N J | 2009 | Chaos Solitons and Fractals2009，41，1： | 1 |
| 14 | Dynamic Strain Aging and Plastic instabilities显示文摘 | Mesarovic and Sinisa Dj | 1995 | Journal of the Mechanics and Physics of Solids1995，43，5： | 1 |
| 15 | The association of serum neutrophil markers and acute coronary syndrome显示文摘 | Alfakry H Sinisa J Paju S | 2012 | Scand J Immunol2012，76，2： | 1 |
| 16 | Large Eddy Simulation of Flows Around Ground Vehicles and Other Bluff Bodies显示文摘 | SINISA K | 2009 | Philosophi- cal Transactions of the Royal Society2009，367，28： | 1 |
| 17 | Research of Security Threats in the Use of Modern Terminal Device显示文摘 | Dragan P Sinisa H Vladimir R | 2012 | DAAAM2012，23，1： | 1 |
| 18 | Adaptive Boosting for SAR Automatic Target Recognition显示文摘 | Sun Yijun Liu Zhipeng Todorovic Sinisa Li Jian | 2007 | IEEE Transactions on Aerospace and Electronic Systems2007，43，1： | 1 |
| 19 | An outbreak of food poisoning in a kindergarten caused by milk powder containing toxigenic Bacillus sub-tilis and Bacillus licheniformis 显示文摘 | PAVIC SINISA BRETT | 2005 | Archiv fUr Lebensmittelhygiene2005，56，1： | 1 |
| 20 | Dynamic strain aging and plastic instabilities显示文摘 | Sinisa D J Mesarovic | 1995 | J Mech Phys Solids1995，3，5： | 1 |
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