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Öğe Characterization of cancer stem cell properties and identification of invasion as well as metastatic process in head and neck cancer(Amer Assoc Cancer Research, 2015) Gunduz, Mehmet; Hatipoglu, Omer Faruk; Gunduz, Esra; Cetin, Elif Nihan; Uctepe, Eyyup; Cigdem, Sadik; Grenman, Reidar[Abstract Not Available]Öğe Investigation of the effects of 5-fluorouracil and thymoquinone on head and neck cancer stem cells(Canadian Soc Clinical Investigation, 2015) Acar, Muradiye; Gunduz, Mehmet; Ocak, Tarik; Gurses, Hacer Esra; Cetin, Elif Nihan; Ceylan, Furkan Sacit; Sefa, AlperenPurpose: A subpopulation of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC) play a critical role in invasion, metastasis, and tumour recurrence post-therapy. 5-Fluorouracil (5-FU) is a pyrimidine analogue that is used in the treatment of HNSCC. Thymoquinone (TQ), found in Cumin (Nigella sativa) seed oil, has anti-diabetic, anti-oxidant, anti-inflammatory, and antitumour effects. The purpose of this study was to examine the effects of 5-FU and TQ on CSCs. Methods: ALDH1 (+) cells were isolated from the HNSCC cell line UT-SCC-74A using magnetic activated cell sorting (MACS) and sphere formation was confirmed. Real-time RTPCR revealed was used to measure expression levels of a number of stem cell markers, including OCT4, SOX2, and KLF-4. To investigate the effects of the therapeutic agents, 5-FU and TQ, concentration-dependent assay procedures were used and cell viability after treatment was measured using XTT assay. Results: ALDH1 (+) cells formed spheres while the ALDH1 (-) cells did not. Real-time RT-PCR revealed that a number of stem cell markers, including OCT4, SOX2, and KLF-4, were up-regulated in the CSCs. XTT results showed that, when given alone at a dose of 50 ng/mL, neither agent had a statistically significant cytotoxic effect on CSCs. However, when dosed in combination, TQ and 5-FU had a synergistic effect on CSC cytotoxicity. Conclusion: We report the effects of TQ and 5-FU on CSCs in HNSCC.Öğe Pharmaco-epigenomics(Springer India, 2013) Gündüz, Mehmet; Acar, Muradiye; Erdogan, Kubra; Cetin, Elif Nihan; Gündüz, EsraEpigenetic modifications are defined as the study of heritable changes in phenotype that do not involve alterations in the DNA sequence. DNA methylation, posttranslational modifi cations of the histone proteins, and miRNAs are regulating the expression of genes as well as drug- metabolizing genes. Epigenetic regulation is essential for normal developmental and cellular processes. Conversely, abnormal epigenetic regulation is a character of complex diseases, including cancer, hematological malignancies, psychiatric disorders, and other diseases. Pharmaco-epigenomics is a novel discipline and involves the study of epigenetic factors in the interpersonal variation to drugs. Epigenetic biomarkers can be used to diagnose disease, estimate disease progression, or predict interpersonal variations in response to therapy. Unlike genetic alterations, changes in epigenetic machinery are reversible, and this reversible characteristic makes them an attractive therapeutic targets. © 2018 Elsevier B.V., All rights reserved.Öğe Relationship between cytosine-adenine repeat polymorphism of ADAMTS9 gene and clinical and radiologic severity of knee osteoarthritis(Wiley, 2018) Gok, Kevser; Cemeroglu, Ozlem; Cakirbay, Hasim; Gunduz, Esra; Acar, Muradiye; Cetin, Elif Nihan; Gunduz, MehmetObjectiveThe aim of this study is to determine the role of cytosine-adenine (CA) micro-satellite repeat sequence of ADAMTS9 gene on the development and progression of osteoarthritis (OA). MethodsA total of 110 participants, including those with primary knee OA and healthy controls were enrolled in the study. Patients were stratified into two groups using the Kellgren-Lawrence staging (K-L staging) as group 1 for controls and mild OA and group 2 for moderate and severe OA. Genetic analyses were performed to determine the CA repeat length in ADAMTS9 gene. ResultsTwenty CA repeats were found to be statistically significant for differentiating groups 1 and 2 (P = 0.020). Age was the most significant risk factor involved, followed by 20 CA repeats and body mass index (P < 0.05). CA repeat length of 20 showed a 6.1-fold increase in probability for having OA at stage 3 or 4 compared to those of CA repeat length of < 20 (P = 0.004). In conclusion, the CA repeat length of 20 has a six-fold increase in probability for having severe OA. ConclusionADAMTS9 gene CA repeat polymorphism may be used to determine the prognosis for OA radiologic progression. Being the first in the literature reporting the CA repeat in the promotor region of ADAMTS9 gene in patients with OA, our study could be highlighted further in future research with larger sample size.Öğe The effects of hypericin on ADAMTS and p53 gene expression in MCF-7 breast cancer cells(Imprimatur Publications, 2014) Acar, Muradiye; Ocak, Zeynep; Erdogan, Kubra; Cetin, Elif Nihan; Hatipoglu, Omer Faruk; Uyeturk, Ummugul; Gunduz, EsraPurpose: The purpose of this study was to determine the effects of hypericin on MCF-7 (Michigan Cancer Foundation-7) breast cancer cells, as it is known to exert an antitumor effect on the expression and regulation of ADAMTS1, 3, 10 and the p53 gene in breast cancer cells. Methods: MFC-7 cells were cultured and subjected separately to various doses (1, 5 and 7.5 mu g/mL) hypericin. After 24 hrs, RNA was isolated and transcribed into cDNA. Expression analysis was performed by real time (RT)-PCR and cell survival was determined by the XTT assay. Results: While the expression of ADAMTS1 in MFC-7 cells decreased to 0.04-fold after exposure to 1 mu g/mL hypericin, the expression increased by 5.6- and 36-fold with 5 and 7.5 mu g/mL, respectively. Furthermore, ADAMTS3 expression in MCF7 cells increased 3.9-fold with the use of 5 mu g/mL of hypericin. These concentrations of hypericin did not lead to significant changes in the expression of ADAMTS10 and the p53 gene. Viability of cancer cells as evaluated by the XTT assay showed that hypericin concentration of 7.5 mu g/mL led to increased apoptosis of cancer cells. Conclusion: The increase in ADAMTS1 expression may prevent metastasis or facilitate the development of an adjuvant factor with tumor-suppressive effects. Hypericin may therefore exert its antitumor and apoptotic effects in MFC-7 cells via ADAMTS1 and ADAMTS3.
