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Öğe Antagonistic effect of oxytocin and tacrolimus combination on adipose tissue – derived mesenchymal stem cells antagonistic effect of oxytocin and tacrolimus: Antagonistic effect of oxytocin and tacrolimus(Elsevier Masson SAS, 2018) Sir G.; Goker Bagca B.; Yigitturk G.; Cavusoglu T.; Biray Avci C.; Gunduz C.; Uyanikgil Y.Tacrolimus (FK506) is a chemotherapeutic agent, which uses calcineurin pathway via inhibiting the stimulation of T cells to prevent the formation of immune response in the recipient individual in organ transplants. FK506 is mainly metabolized in the liver by cytochrome P450 enzyme system and is known that it has high toxic effects on different cells. Mesenchymal stem cells (MSCs) have recently gained importance since their potential to be used in cellular therapy and tissue regeneration. In some clinical cases, MSCs are transferred into the patient after the organ transplantations in order to support the treatment. Because of their immunomodulatory actions and assistance to the regeneration, popularity of MSCs have been increasing recently. However, since immunosuppressive agents have a potential cytotoxic and apoptotic effect on MSCs, researches have attempted to use it as a combination with an agent that alleviates these effects. Oxytocin (OT) is primarily acting as a neuromodulator in humans and is a peptide hormone secreted by the pituitary gland of the neurohypophysis. OT has such effects on cells as to confer resistance against oxidative stress on cells and to increase the proliferation and help regeneration. Studies on the active substance of FK506 were aimed to investigate the cytotoxic effects on human adipose tissue derived MSCs. The purpose of this study was to determine the cytotoxic, apoptotic and morphological effects of FK506, an immunosuppressive agent, on adipose tissue - derived MSC (ADMSC) which has the potential to be used for immune suppression. In addition, it was aimed to determine whether the agent could reduce the cytotoxic, apoptotic, and morphological effects on ADMSCs when used in combination with OT. For this purpose, the cytotoxic effects of the FK506 and OT on ADMSCs were determined by time and dose dependent manner by the WST-1 test. Isobologram analysis was evaluated using the WST-1 test according to IC50 values of FK506 and OT. The apoptotic effects of the agents on the ADMSCs were determined by the Annexin V method. Immunofluorescence staining was performed to determine morphological changes. Changes in the levels of oxidative stress markers were measured by colorimetric and flourometric methods using lipid peroxidation, superoxide dismutase activity, catalase activity and glutathione peroxidase assays. The IC50 values of FK506 and OT on ADMSCs were calculated as 17.44 µM and 13.43 µM, respectively.FK506 and OT were found to have antagonistic activity on ADMSCs (CI value of the combination was 1.24). The effects of the agents individually and in combination on the levels of apoptosis and oxidative stress markers have been evaluated. When the results obtained from the study are evaluated, the adipose- tissue derived mesenchymal stem cells used with takrolimus and oxytocin combination have a potential for novel treatment approaches. © 2017 Elsevier Masson SASÖğe Association of osteopontin and tumor necrosis factor-? levels with insulin resistance in obese patients with obstructive sleep apnea syndrome(2011) Sarac F.; Basoglu O.K.; Gunduz C.; Bayrak H.; Biray Avci C.; Akcicek F.Objective: The aims of this study were to compare the tumor necrosis factor (TNF)-? and osteopontin levels, to identify the relationship between insulin resistance (IR) and osteopontin levels in obese patients with and without obstructive sleep apnea syndrome (OSAS). Method: The study population included 62 obese patients (35 males, 27 females) with OSAS and was compared with 26 obese patients (16 males, 10 females) without OSAS as a control group. Polysomnographic evaluation, spirometric tests and arterial blood gas sampling were performed on the obese patients with OSAS. Plasma levels of TNF-? and osteopontin were measured by enzyme-linked immunosorbent assays during the process. IR was estimated using the homeostasis model assessment (HOMA). Results: Mean plasma levels of fasting glucose, insulin, HOMA, liver function test, hematocrit, leukocyte, TSH, free T 4, fibrinogen, TNF-?, and osteopontin were similar in the 2 groups. In patients with OSAS, mean osteopontin levels were positively correlated with mean fasting insulin levels (r=0.306, p=0.01), HOMA (r=0.299, p=0.01), apnea-hypopnea index (r=0.377, p=0.03) and Epworth Sleepiness Scale (r=0.299, p=0.01). However, mean TNF-? levels were negatively correlated with Epworth Sleepiness Scale (r=-0.298, p=0.01) in the patients with OSAS. Conclusions: It was observed that TNF-? and osteopontin levels showed no difference between obese patients with and without OSAS. However, osteopontin levels increased with fasting insulin, IR, OSAS severity, and daytime sleepiness. ©2011, Editrice Kurtis.Öğe Noncoding way of the metastasis(Elsevier, 2022) Goker Bagca B.; Kusoglu A.; Cesmeli S.; Biray Avci C.According to the World Health Organization statistics, the second leading cause of death globally is cancer. Together with this, metastasis is viewed as the leading cause of cancer death in patients with the disease due to the lack of treatment modalities for malignant tumors. One of the key mechanisms related to cancer metastasis is the epithelial-mesenchymal transition which enables epithelial cancer cells to gain mesenchymal cancer cell properties with elevated migration and invasion capacity that make it easy to spread distant tissues and survive from harsh conditions. Studies indicate that metastatic cancer cells have a gene expression signature that ensures those cells have increased migratory capacity as well as increased survival rate in circulation. Recently, the relationship of metastasis with two types of noncoding RNAs (ncRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) has been getting attention. In this chapter, the role of miRNAs and lncRNAs and treatment strategies regarding the role of ncRNAs in metastasis biology will be evaluated. © 2022 Elsevier Inc. All rights reserved.Öğe Photodynamic therapy and nuclear imaging activities of zinc phthalocyanine-integrated TiO 2 nanoparticles in breast and cervical tumors(Blackwell Publishing Ltd, 2018) Yurt F.; Ocakoglu K.; Ince M.; Colak S.G.; Er O.; Soylu H.M.; Gunduz C.; Biray Avci C.; Caliskan Kurt C.In recent years, phthalocyanines (Pcs) have been widely used as photosensitizer in photodynamic therapy applications. Because of their strong absorptions in the near-infrared region (640–700 nm). The integration of phthalocyanine derivatives to a nanoparticle is expected to be efficient way to improve the activity of the photosensitizer on the targeted tissue. It is known that the integrated molecules not only show better accumulation on tumor tissue but also reduce toxicity in healthy tissues. In this study, the ZnPc molecule was synthesized and integrated to the TiO 2 nanoparticle, to investigate the potential of PDT and its cytotoxicity. Additionally, ZnPc and ZnPc-TiO 2 molecules were labeled with 131 I and it was aimed to put forth the nuclear imaging/therapy potentials of 131 I labeled ZnPc/ZnPc-TiO 2 by determining in vitro uptakes in mouse mammary carcinoma (EMT6), human cervical adenocarcinoma (HeLa). In result of our study, it was observed that the radiolabeling yields of the synthesized ZnPc and ZnPc-TiO 2 with 131 I were quite high. In vitro uptake studies shown that 131 I-ZnPc-TiO 2 could be a potential agent for nuclear imaging/treatment of breast and cervical cancers. According to PDT results, ZnPc-TiO 2 might have as to be a potential PDT agent in the treatment of cervical tumor. ZnPc and ZnPc-TiO 2 might be used as theranostic agents. © 2017 John Wiley & Sons A/SÖğe Propofol orchestrates long non-coding RNAs in MCF7 cells, unraveling new avenues for breast cancer intervention(Elsevier Masson s.r.l., 2024) Biray Avci C.; Edgunlu T.G.; Suzek T.; Ozates N.P.; Goker Bagca B.; Demirtas Bilgic A.; Ozdemir C.Long non-coding RNAs (lncRNAs) play a dynamic role in gene expression regulation and serve as potential therapeutic targets in breast cancer. The anticancer effect of propofol, an anesthetic agent, has been proven, but its interaction with lncRNAs has not been adequately investigated. This study aims to reveal the interactions between propofol and lncRNAs and contribute to the understanding of its therapeutic potential in the treatment of breast cancer. We evaluated the effects of propofol on cell viability, apoptosis, and mitochondrial membrane potential in MCF7 cells. The study used qRT-PCR to analyze cancer-related lncRNA expressions following propofol treatment; this was supported by RNA-RNA interaction predictions and in silico functional analysis using selected datasets and the R cluster Profiler GSEABase package. Propofol showed a cytotoxic effect at higher doses in MCF7 breast cancer cells, inducing necrosis. Propofol regulated (IGF2-AS, MRPL23-AS1, PANDAR, HULC) and down-regulated (IWT1-AS, HOXA-AS2, H19, GACAT1, MIAT) the expression levels of various lncRNAs in MCF7 cells. Our research revealed complex interactions of MALAT1 lncRNA with both upregulated and downregulated genes. Additionally, three rRNA genes (LSU-rRNA, RNA45SN3, and SSU-rRNA) were identified to interact with both groups of lncRNAs. Propofol potentially targets chemotherapy resistance by regulating UCA1, LINC-RoR1, and MEG3. Wikipathways' pathway enrichment analysis identified two downregulated lncRNAs, UCA1 and LINC-RoR1, and an upregulated MEG3, implicated in lncRNA-mediated chemotherapeutic resistance mechanisms. Our study illuminates the intricate interplay of lncRNAs and their potential contribution to propofol's anti-cancer effects in breast cancer, offering new avenues for therapeutic exploration and advancement. © 2024
