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Öğe Anticancer Effects of the Organosilicon Multidrug Resistance Modulator SILA 421(BENTHAM SCIENCE PUBL LTD, 2012) Olszewski, Ulrike; Zeillinger, Robert; Kars, Meltem Demirel; Zalatnai, Attila; Molnar, Jozsef; Hamilton, Gerhard1,3-dimethyl-1,3-bis(4-fluorophenyl)-1,3-bis{3-[1(4-butylpiperazinyl)]-propyl}-disiloxan-tetrahydrochlorid (SILA 421) is a compound that was developed as modulator of the ABC cassette transporter P-glycoprotein. Furthermore, it exerted antimicrobial toxicity, vascular effects, downregulation of chaperone induction and plasmid curing in bacterial cells. Here, this drug was found to possess cytotoxic activity against a panel of human cancer cell lines that do not overexpress P-gp, with 50% inhibitory concentrations ranging between 1.75 +/- 0.38 mu M for GLC14 small cell lung cancer and 34.00 +/- 4.75 mu M for PC-3 prostate cancer cells. HL-60 leukemia and MDA-MB-435 breast cancer cells exhibited cell cycle arrest and apoptotic cell death in response to SILA 421. Assessment of global gene expression of SILA 421-treated HL-60 cells was employed to identify cellular pathways affected by the compound and revealed disturbance of DNA replication, transcription and production of apparently misfolded proteins. Endoplasmatic reticulum stress and downregulation of cell cycle, cellular repair mechanisms and growth factor-related signaling cascades eventually resulted in induction of apoptosis in this cell line. In addition to the well established P-gp inhibitory effect of SILA compounds, reversal of resistance to taxanes, which had been reported for SILA 421 and the related molecule SILA 409, may be linked to downregulation of gene expression of kinesins. Interference with DNA replication and transcription seems to be the common denominator of antimicrobial activity and plasmid curing, as well as anticancer toxicity in human cell lines. Thus, in consideration of the full range of putative cellular targets found in the present work, the application of these SILA compounds for treatment of tumors should be further evaluated.Öğe Biocompatible multi-walled carbon nanotube-CdTe quantum dot-polymer hybrids for medical applications(ELSEVIER SCIENCE BV, 2015) Baslak, Canan; Kars, Meltem Demirel; Karaman, Mustafa; Kus, Mahmut; Cengeloglu, Yunus; Ersoz, MustafaHerein we report the synthesis of polymer coated quantum dots (QDs)-carbon nanotube composite material with high biocompatibility and low cellular toxicity. The synthesized multi-walled carbon nanotube (MWCNT)-QD-(-poly(glycidyl methacrylate)) (pGMA) hybrids were characterized using X-ray photoelectron spectroscopy, laser scanning confocal microscopy, transmission electron microscopy and scanning electron microscopy. The results showed that quantum dots were well-distributed on nanotube surfaces in high density. The toxicological assessments of QDs and MWCNT-QD-polymer hybrids in human mammary carcinoma cells and their fluorescence imaging in living cell system were carried out. MWCNT-QD-polymer hybrids possess intense red fluorescence signal under confocal microscopy and good fluorescence stability over 6-h exposure in living cell system. The toxicity comparison of QDs and MWCNT-QD-polymer hybrids has shown that the existence of PGMA thin coating on MWCNT-QD hybrid surface decreased the cellular toxicity and increased biocompatibility. (C) 2014 Elsevier B.V. All rights reserved.Öğe Biocompatible yogurt carbon dots: evaluation of utilization for medical applications(SPRINGER, 2017) Dinç, Saliha; Kara, Meryem; Kars, Meltem Demirel; Aykul, Fatmanur; Çiçekci, Hacer; Akkuş, MehmetIn this study, carbon dots (CDs) were produced from yogurt, a fermented milk product, via microwave-assisted process (800 W) in 30 min without using any additional chemical agents. Yogurt CDs had outstanding nitrogen and oxygen ratios. These dots were monodisperse and about 2 nm sized. The toxicological assessments of yogurt carbon dots in human cancer cells and normal epithelial cells and their fluorescence imaging in living cell system were carried out. Yogurt carbon dots had intense fluorescent signal under confocal microscopy and good fluorescence stability in living cell system. The resulting yogurt carbon dots exhibited high biocompatibility up to 7.1 mg/mL CD concentration which may find utilization in medical applications such as cellular tracking, imaging and drug delivery. Yogurt carbon dots have potential to be good diagnostic agents to visualize cancer cells which may be developed as a therapeutic carrier.Öğe DRUG RESISTANCE RESTRICTS THE EFFICACY OF SHORT TERM LOW DOSE MITOMYCIN-C TREATMENT IN UMUC-3 BLADDER CANCER CELLS(INIESTARES, S.A., 2018) Gul, Murat; Goktas, Serdar; Kars, Meltem Demirel; Kaynar, MehmetOBJECTIVE: Mitomycin-c (MMC) is the most used intravesical adjuvant agent in non-muscle invasive bladder cancer to prevent recurrence. However, a consensus on about appropriate dosage and treatment schedule of MMC is lacking. We, therefore, aimed to evaluate the most appropriate MMC dosage using an in vitro model of high-grade human bladder cancer. METHODS: UMUC-3 cells, a model for high-grade bladder cancer, were exposed to MMC in different time courses to assess its toxicological effects. XTT cell proliferation kit was used to evaluate the effect of MMC on the proliferation of UMUC-3 cell line. Gene expression analysis for the MDR1, BCL2 and ANXA5 genes was performed by Real-time PCR and flow cytometry analysis were conducted to evaluate the cell death mechanism and acquired resistance after MMC exposure. An ANXA5 kit was used to detect apoptotic cells, and 7-AAD was used to detect necrotic cells. RESULTS: Cell proliferation was prevented to a large extent (IC50, 0.175-0.081 mg/mL) and cytotoxic effects were observed after 5 mu g/mL and 10 mu g/mL MMC administrations for 1 and 2-h, after the 4th and 2nd dose cycles, respectively. Moreover, cell death was observed at 5 mu g/mL and 10 mu/mL MMC applications for 1-h and 2-h by the sixth and second week, respectively. Flow cytometry exhibits increased subpopulation of drug-extruding UMUC-3 cells after a single dose of MMC for 1-h. MMC did not increase the number of apoptotic or necrotic cells; yet, MDR1 (multiple drug resistance) and ANXA5 (apoptotic) expression levels were increased and BCL2 (anti-apoptotic) expression was decreased. Limitations: In-vitro nature of the study and working with only one cell culture are inherit limitations of this project. CONCLUSION: A single dose of MMC administration for 1 or 2-h results in drug-resistance. If maintenance treatment is administered for one hour, it should be continued throughout a 6-week period.Öğe Effect of Nerium oleander distillate on MCF-7 breast cancer cell lines(CURRENT BIOLOGY LTD, 2011) Kars, Meltem Demirel; Kars, Gokhan; Gunduz, Ufuk; Uney, Kamil; Bas, Ahmet Levent[Abstract not Available]Öğe The effects of trastuzumab, paclitaxel, and carboplatin on HER2-positive cancer stem cells that are isolated from primary breast cancer cultures: a preliminary report(AMER ASSOC CANCER RESEARCH, 2015) Artac, Mehmet; Kayadibi, Gozde; Ceylan, Ayca; Kars, Meltem Demirel; Artac, Hasibe; Cakir, Murat; Boruban, Cem[Abstract not Available]Öğe Femtosecond laser induced photodynamic therapy on 5-ALA treated SKMEL-30 cells: An efficient theranostic strategy to combat melanoma(ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2014) Kars, Meltem Demirel; Kara, Reyhan; Gundogdu, Yasemin; Kepceoglu, Abdullah; Kilic, Hamdi SukurPurpose: Photodynamic therapy (PDT) is a type of photo-chemotherapy that is based on the application of photosensitizer and irradiation of the region by laser sources. Photosensitizer and light interaction will develop reactive oxygen radicals ( O-1(2)) in the cells and elimination of cells by apoptosis or necrosis. Methods: Metastatic skin cancer cells SKMEL-30 were treated by 5-ALA in dark and then they were irradiated by 90-femtosecond (fs) laser with different pulse powers for different durations. The effects of 5-ALA mediated photodynamic therapy on the cells were determined by XTT proliferation kit and by flow cytometry measurements of Annexin V, 7-AAD and mitochondrial membrane potential alterations. Fluorescent accumulation of protoporphyrin IX was investigated by fluorometry and confocal laser microscope. Results: The viability tests for SKMEL-30 cells treated with different 5-ALA doses and femtosecond laser power and durations demonstrated that 635 nm, 45 mW pulse energy at 90 fs laser pulse applications for 60 sec to 1 mM 5-ALA exposed cells decreased the cell proliferation by 30%. Flow cytometric measurements exhibit that PDT caused 63% of mitochondria membrane potential alteration, 30% of cell death in the population by apoptosis and 39% of cells by necrosis. There was 1 mM 5-ALA exposure that also exhibited about 32% accumulation of fluorescence in the cells. Conclusion: The pretreatment of the cells with the precursor 5-ALA lets the imaging due to increased protoporphyrin IX fluorescence. This treatment method may be proposed as an effective theranostic strategy for melanoma because of its rapid and effective anticancer consequences. (C) 2014 Elsevier Masson SAS. All rights reserved.Öğe Implications from a pharmacogenomic analysis: Nerium oleander leaf distillate supplemented diet regulates cholesterol metabolism in rats(TAYLOR & FRANCIS LTD, 2014) Kars, Meltem Demirel; Odabasi, Burcu Asena; Kars, Gokhan; Uney, Kamil; Bagci, Yavuz; Bas, Ahmet LeventContext: Despite the usage of Nerium oleander L. (Apocynaceae) for anticancer studies and traditional remediation, the regulatory effect of N. oleander leaf distillate on cholesterol metabolism is not disclosed sufficiently. Objective: Cholesterol is an important biological molecule and the synthesis rate is regulated by the amount of cholesterol uptake from the diet. The aim of this study was to investigate the regulation of cholesterol metabolism in response to a high-fat diet (HFD) and the effects of N. oleander leaf distillate-supplemented diet (NOHFD) in rats. Materials and methods: Microarray technology was used to clarify the regulation of cholesterol mechanism in HFD and NOHFD-fed rats (375 mu g/0.5 mL distilled water applied by gavage). The treatment period was 90 days. Rat liver tissues were used for microarray analysis using the Affymetrix GeneChip Rat Genome platform. Results of groups were statistically analyzed with the Partek 6.6 bioinformatic program. Results: The HFD group exhibited alterations in the expression levels of about 1945 genes with respect to the normal diet (ND) group. The results showed that expression levels of 47 genes were altered related to cholesterol metabolism in HFD and NOHFD groups. The expression levels of seven genes in the NOHFD group were significantly closer to those in the ND group than those of the HFD group. Discussion and conclusion: To conclude, findings suggest that N. oleander leaf distillate-supplemented food has considerable beneficial effects on cholesterol metabolism-related gene expression levels.Öğe A microarray based expression profiling of paclitaxel and vincristine resistant MCF-7 cells(ELSEVIER SCIENCE BV, 2011) Kars, Meltem Demirel; Iseri, Ozlem Darcansoy; Gunduz, UfukResistance to the broad spectrum of chemotherapeutic agents in cancer cell lines and tumors has been called multiple drug resistance (MDR). In this study, the molecular mechanisms of resistance to two anticancer agents (paclitaxel and vincristine) in mammary carcinoma cell line MCF-7 were investigated. Drug resistant sublines to paclitaxel (MCF-7/Pac) and vincristine (MCF-7/Vinc) that were developed from sensitive MCF-7 cells (MCF-7/S) were used. cDNA microarray analysis was performed for the RNA samples of sensitive and resistant cells in duplicate experiments. GeneSpring GX 7.3.1 Software was used in data analysis. The results indicated that the upregulation of MDR] gene is the dominating mechanism of the paclitaxel and vincristine drug resistance. Additionally the upregulation of the genes encoding the detoxifying enzymes (i.e. GSTP1) was observed. Significant downregulation of apoptotic genes (i.e. PDCD2/4/6/8) and upregulation of some cell cycle regulatory genes (CDKN2A, CCNA2 etc.) was seen which may be in close relation to MDR in breast cancer. Drug resistant cancer cells exhibit different gene expression patterns depending on drug treatment, and each drug resistance phenotype is probably genetically different. Further functional studies are needed to demonstrate the complete set of genes contributing to the drug resistance phenotype in breast cancer cells. (C) 2011 Elsevier B.V. All rights reserved.Öğe Production and Characterization of Titanium (Ti), Platinum (Pt) and Tantalum (Ta) Thin Films for Native DNA Biosensors(AMER INST PHYSICS, 2017) Genc, Eminegul; Kepceoglu, Abdullah; Gezgin, Serap Yigit; Kars, Meltem Demirel; Kilic, Hamdi SukurThe use of the femtosecond (fs) laser pulses for ablation applications have several advantageous and Laser Induced Forward Transfer (LIFT) is an ablation-driven transfer process. The use of fs laser pulses for LIFT is gaining a great attraction nowadays. The most of the Direct Writing (DW) methods are laser based techniques and the LIFT technique is the one of them. This spectacular technique allows high resolution without lithographic processes. In this study, we have grown Ti, Pt and Ta thin films on the microscope slides by Pulse Laser Deposition (PLD) teclmique using Nd:YAG laser in the high vacuum condition. As a result, thin films produced in this work is a good candidate to produce native DNA biosensors based on LIFT teclmique.
