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Cancer stem cells in metastasis therapy

Aydemir Çoban, E. | Şahin, Fikrettin

Book Part | 2018 | Advances in Experimental Medicine and Biology1089 , pp.97 - 113

Tumors consists of subpopulation of cells in which each subtype has contributes to tumor progression. Specifically one subtype known as cancer stem cells are associated with the initiation, progression, resistance to conventional therapies and metastasis. Metastasis is leading cause of cancer related deaths. Overall it is important to consider cancer as a whole in which a mutated cell proliferating indefinitely and forming its hierarchy consisting of subgroups with different molecular signatures. To be able to target this disease we need to evaluate every step including initiation, progression, survival, angiogenesis and finally mig . . .ration and repopulation. Cancer stem cells do play vital roles in each step however when metastasis can be stopped or eliminated we talk about saving a life or improving its quality. Considering how deeply these cancer stem like cells affect the tumor life and metastasis it is crucial to develop effective strategies against them. Metastatic cascade can also be directed by membrane derived vesicles specifically exosomes. Several studies show the role of exosomes in mediating cellular migration and pre-metastatic niche formation. During this chapter we wanted to explain in detail how the metastasis occur in tumor and how cancer stem cells contribute into the development of metastatic cascade and possibly suggest therapeutic approaches against cancer stem cells. © Springer Nature Switzerland AG 2018 Daha fazlası Daha az

Cytoglobin inhibits migration through PI3K/AKT/mTOR pathway in fibroblast cells

Demirci, S. | Doğan, A. | Apdik, H. | Tuysuz, E.C. | Gulluoglu, S. | Bayrak, O.F. | Şahin, Fikrettin

Article | 2018 | Molecular and Cellular Biochemistry437 ( 01.02.2020 ) , pp.133 - 142

Cell proliferation and migration are crucial in many physiological processes including development, cancer, tissue repair, and wound healing. Cell migration is regulated by several signaling molecules. Identification of genes related to cell migration is required to understand molecular mechanism of non-healing chronic wounds which is a major concern in clinics. In the current study, the role of cytoglobin (CYGB) gene in fıbroblast cell migration and proliferation was described. L929 mouse fibroblast cells were transduced with lentiviral particles for CYGB and GFP, and analyzed for cell proliferation and migration ability. Fibroblas . . .t cells overexpressing CYGB displayed decreased cell proliferation, colony formation capacity, and cell migration. Phosphorylation levels of mTOR and two downstream effectors S6 and 4E-BP1 which take part in PI3K/AKT/mTOR signaling declined in CYGB-overexpressing cells. Microarray analysis indicated that CYGB overexpression leads to downregulation of cell proliferation, migration, and tumor growth associated genes in L929 cell line. This study demonstrated the role of CYGB in fibroblast cell motility and proliferation. CYGB could be a promising candidate for further studies as a potential target for diseases related to cell migration such as cancer and chronic wound treatment. © 2017, Springer Science+Business Media, LLC Daha fazlası Daha az

A role of T cell subsets in the immun dysfunction of schizophrenia

Sahbaz, C | Zibandeh, N | Kurtulmus, A | Kirpinar, I | Şahin, Fikrettin | Akkoc, T

Conference Object | 2018 | EUROPEAN PSYCHIATRY48 , pp.133 - 142

Immunomodulatory behavior of mesenchymal stem cells

Taşlı, P.N. | Bozkurt, B.T. | Kırbaş, O.K. | Deniz-Hızlı, A.A. | Şahin, Fikrettin

Book Part | 2018 | Advances in Experimental Medicine and Biology1119 , pp.73 - 84

The use of Mesenchymal Stem Cells (MSCs) in the treatment of diseases where immunomodulation impacts therapy is increasing steadily. Recent studies aim to achieve effective use of MSCs in treatment of Graft versus Host Disease (GvHD), Crohn’s disease and organ transplantations. The molecular mechanisms governing immunomodulatory properties of MSCs have not been fully understood, although current studies are indicating progress. Especially, in vitro studies and animal models provide a major contribution to our knowledge in clinical use of MSCs. The immunosuppressive and immune-enhancer properties of MSCs are –typically- determined wi . . .th respect to type and concentrations of soluble molecules found in their physiological environment. In mammals the immune system protects the organism -not only- from certain microorganisms, but also from any entity that it recognizes as foreign, including its own cells when it is received as a threat. This protection can sometimes occur by increasing the number of immune cells and sometimes by suppressing a pathologically hyper-induced immunological response. In particular, realization of the bi-directional effect of MSCs on immune cells has placed substantial emphasis on this area of research. This chapter focuses on the interaction of MSCs with the immune cells, the bilateral role of these interactions, and whether studies that aim to understand these interactions can yield promising results in terms of developing improved use of MSCs in treatment. © Springer International Publishing AG, part of Springer Nature 2018 Daha fazlası Daha az

Anticancer activity of Schiff base-Poloxamer P85 combination against kidney cancer

Dogan, A | Demirci, S | Telci, D | Canikyan, S | Kongur, M | Dede, B | Şahin, Fikrettin

Article | 2018 | INTERNATIONAL UROLOGY AND NEPHROLOGY50 ( 2 ) , pp.247 - 255

Renal cell carcinoma (RCC) accounts for approximately 80% of the primary renal cancers, and current treatment strategies are not sufficient to provide a certain solution. Since there are not many treatment options, interest in discovery of alternative drugs has increased. In the current study, anticancer activity of a novel heterodinuclear Cu(II)-Mn(II) complex (Schiff base-SB) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (pluronic) P85 was tested against RCC. Cell viability, apoptosis and gene expression analysis were conducted in vitro by using Renca cells. The results revealed that the SB-P85 . . . combination decreased cell proliferation by increasing the apoptotic gene expressions and apoptosis. Renca-injected BALB/c mice were used to mimic early stage of RCC model. Treatment with SB-P85 combination suppressed tumor formation and growth compared to baseline. Overall, SB-P85 showed promising anticancer activity against RCC in vitro and in vivo Daha fazlası Daha az

Anticancer activity of Schiff base–Poloxamer P85 combination against kidney cancer

Doğan, A. | Demirci, S. | Telci, D. | Canikyan, S. | Kongur, M. | Dede, B. | Şahin, Fikrettin

Article | 2018 | International Urology and Nephrology50 ( 2 ) , pp.247 - 255

Purpose: Renal cell carcinoma (RCC) accounts for approximately 80% of the primary renal cancers, and current treatment strategies are not sufficient to provide a certain solution. Since there are not many treatment options, interest in discovery of alternative drugs has increased. Methods: In the current study, anticancer activity of a novel heterodinuclear Cu(II)–Mn(II) complex (Schiff base—SB) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (pluronic) P85 was tested against RCC. Cell viability, apoptosis and gene expression analysis were conducted in vitro by using Renca cells. Results: The resul . . .ts revealed that the SB–P85 combination decreased cell proliferation by increasing the apoptotic gene expressions and apoptosis. Renca-injected BALB/c mice were used to mimic early stage of RCC model. Treatment with SB–P85 combination suppressed tumor formation and growth compared to baseline. Conclusion: Overall, SB–P85 showed promising anticancer activity against RCC in vitro and in vivo. © 2017, Springer Science+Business Media B.V., part of Springer Nature Daha fazlası Daha az

Role of Adipose-Derived Stem Cells in Wound Healing: An Update from Isolation to Transplantation

Demirci, S. | Doğan, A. | Şahin, Fikrettin

Book Part | 2018 | Wound Healing: Stem Cells Repair and Restorations, Basic and Clinical Aspects , pp.133 - 147

Adipose tissue serves as an alternative mesenchymal cell source with comparable proliferation, growth factor expression, and differentiation capacity. A large body of work has suggested that adipose-derived stem cells (ADSCs) would be used in various regeneration applications. Due to having remarkable therapeutic potential, ADSCs would also be a putative therapy for non-healing wounds, which is a growing clinical concern for especially aged populations with systemic diseases such as obesity and diabetes. This chapter aims to highlight beneficial effects of ADSCs on acute and chronic wound healing by reviewing preclinical studies and . . . clinical trials from the perspective of direct differentiation, paracrine signaling, cell recruitment, scaffold combination, and preconditioning. In addition, possible action of a mechanism for wound healing promoting activity of ADSCs will be explained in detail along with addressing efficacy and safety issues. © 2018 John Wiley & Sons, Inc. All rights reserved Daha fazlası Daha az

Acquisition of 3D Natural Scaffold by Decellularization

Demirkanli, S.A. | Kadioglu, D. | Tuna, B.G. | Etemoglu, S. | Kiratll, B. | Şahin, Fikrettin | Utku, F.S.

Conference Object | 2018 | 2017 21st National Biomedical Engineering Meeting, BIYOMUT 2017 , pp.133 - 147

Regenerative Medicine and Tissue Engineering has been gaining critical importance in the medical sector, specifically in cancer and organ-tissue losses. Laboratory studies have been conducted on tissue and organ generation using whole organ decellularization and recellularization techniques. In this study, whole rat pancreas has been decellularized by perfusion and imaged using confocal microscopy. Whole rat pancreas tissue has been divided into control and exerimental groups and decellularized using hypotonic, hypertonic and detergent solutions. The tissues, imbedded in Tissue Tech and frozen at -20 , have been prepared as 30 micro . . .meter sections, dyed using DAPI for confocal microscopic imaging of the cell nuclei. It has been demonstrated that the cell nuclei imaged in the control group have been removed as a result of the decellularization process. These findings indicate that the collagenous tissue has been preserved to a large extent. With the imaging of the serial sections, 3D reconstruction of decellularized pancreas can be obtained. © 2017 IEEE Daha fazlası Daha az

Role of Lymphocyte Subsets and T-Cell Profiles in the Immune Dysfunction of Schizophrenia

Sahbaz, C | Zibandeyeh, N | Kurtulmus, A | Avaroglu, G | Kirpinar, I | Şahin, Fikrettin | Akkoc, T

Conference Object | 2018 | BIOLOGICAL PSYCHIATRY83 ( 9 ) , pp.133 - 147

The Repair of Furcal Perforations in Different Diameters with Biodentine, MTA, and IRM Repair Materials: A Laboratory Study Using an E. Faecalis Leakage Model

Övsay, E. | Kaptan, R.F. | Şahin, Fikrettin

Article | 2018 | BioMed Research International2018 , pp.133 - 147

The aim of this study is to evaluate the microleakage of repair materials MTA, IRM, and Biodentine applied on furcal perforations with different diameters. One hundred and forty extracted human teeth were used in this study. The teeth were divided into 2 main groups (60 teeth in each) which were then divided into 3 subgroups (n=20). The remaining 20 teeth were divided into 2 groups (10 in each) to serve as controls. The furcal areas of the teeth were perforated with #2 cylindrical burs in Group 1 whereas perforations were made using #4 cylindrical burs in Group 2. Each subgroup of both Groups 1 and 2 received ProRoot MTA (ProRoot, U . . .SA), Biodentine (Septodont), or IRM (Dentsply, USA) to repair the perforations. An experimental set-up was established to contaminate repaired perforations with E. Faecalis (ATCC29212). The turbidity of bacteria was observed on the 7th, 15th, 30th, and 45th days. The data was analysed by chi-square test (p>0.05). The number of bacteria in the group perforated by bur #2 and closed by MTA was found to be lower than the other groups on the 7th day (p0.05). ProRoot MTA was found to be more successful in the prevention of bacterial leakage compared to IRM and Biodentine in smaller perforations during the 1st week. © 2018 E. Övsay et al Daha fazlası Daha az

Freeze Injure and Antioxidant Enzyme Activity of Grapevine (Vitis Vinifera) Under Bio-Boron Fertilizer Applications

Köse, C. | Güneş, A. | Kaya, Ö. | Kıtır, N. | Turan, M. | Şahin, Fikrettin

Article | 2018 | Erwerbs-Obstbau60 , pp.3 - 10

This study was conducted to determine the effects of plant growth promoting bacteria (PGPR) and boron (Bio-B) on the plant freeze injury, antioxidant enzyme activity and fruit yield of grapevine cultivar. The experimental plot was a completely randomized design with 5 replicates. As a trial model Bio-B and control were used as fertilizer agent. Bio-B fertilizer has been applied in different ways as soil?+ foliar, soil and foliar application methods to grapevine plants. Data through 2 years trials results showed that the use of Bio-B significantly decreased freeze injury and increased antioxidant enzyme activity of grapevine leaf. Th . . .e highest damage rate at control group occurred with -20?°C and 94.89% ratio. In the same temperature degree at grape plant, the damage ratio of the Bio-B application from soil decreased by 21.55%; the application from leaf by 25.53% and with the application from soil?+ leaf by 26.24%. In addition to this, compared with control, in the CAT, POD and SOD enzyme activities increases occurred with the ratios as 28.57%, 22.05% and 39.25%, respectively. Generally, as results of this study under field conditions, Bio-B fertilizer application decreased freeze injure and increased antioxidant enzyme activity of the grapevine plant. © 2018, Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature Daha fazlası Daha az

Synthesis, molecular docking and anticancer activity of diflunisal derivatives as cyclooxygenase enzyme inhibitors

Coşkun, G.P. | Djikic, T. | Hayal, T.B. | Türkel, N. | Yelekçi, K. | Şahin, Fikrettin | Küçükgüzel, Ş.G.

Article | 2018 | Molecules23 ( 8 ) , pp.3 - 10

Cyclooxygenase enzymes play a vital role in inflammatory pathways in the human body. Apart from their relation with inflammation, the additional involvement of COX-2 enzyme with cancer activity was recently discovered. In some cancer types the level of COX-2 enzyme is increased indicating that this enzyme could be a suitable target for cancer therapy. Based on these findings, we have synthesized some new diflunisal thiosemicarbazides and 1,2,4-triazoles and tested them against androgen-independent prostate adenocarcinoma (PC-3), colon carcinoma (HCT-116), human breast cancer (T47D), breast carcinoma (MCF7) and human embryonic kidney . . . (HEK-293) cell lines. Specifically, the diflunisal and thiosemicarbazide functionality are combined during the synthesis of original compounds anticipating a potency enhancement. Compounds 6, 10, 15 and 16 did not show cytotoxic effects for the HEK293 cell line. Among them, compounds 15 and 16 demonstrated anticancer activity for the breast cancer cell line T47D, whereas compounds 6 and 10 which are thiosemicarbazide derivatives displayed anti-tumourigenic activity against the PC-3 cell line, consistent with the literature. However, no activity was observed for the HCT-116 cancer cell line with the tested thiosemicarbazide derivatives. Only compound 16 displayed activity against the HCT-116 cell line. Therefore, it was speculated that the diflunisal and thiosemicarbazide functionalities potentiate anticancer activity on prostate cancer and the thiosemicarbazide functionality decreases the anticancer activity of diflunisal on colon cancer cell lines. In order to gain insight into the anticancer activity and COX-2 inhibition, molecular docking studies were carried out for COX-1 and COX-2 enzymes utilizing the newly synthesized compounds 15, and 16. Both 15 and 16 showed high selectivity and affinity toward COX-2 isozyme over COX-1, which is in agreement with the experimental results. © 2018 by the authors Daha fazlası Daha az

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