Yazar "Ozdas, Sibel" seçeneğine göre listele

Listeleniyor 1 - 12 / 12
  • [ X ]
    Öğe
    Antioxidant, cytotoxic, anti-migratory, and pro-apoptotic effects of Bolanthus turcicus extracts on head and neck cancer cells
    (Springer, 2024) Ozdas, Sibel; Canatar, Ipek; Ozdas, Talih; Sarialtin, Sezen Yilmaz; Agca, Asli Can; Koc, Murat
    Purpose Investigation of various plant extracts using in-vitro/in-vivo assays has emerged as a promising avenue for identifying potential pharmacophores that can be developed into therapeutic drugs. This study aims to assess the bioactive compounds and antioxidant capacity of the Bolanthus turcicus (B. turcicus) and to investigate the effects on head and neck cancer (HNC) cell lines. Methods Methanol (MeOH), ethyl acetate (EA) and aqueous (Aq) extracts were prepared from B. turcicus, and the amount of total phenolic content (TPC) and total flavonoid content (TFC) in the extracts were analyzed by the Folin-Ciocalteu and Aluminum chloride method, respectively. In addition, the total antioxidant capacity and iron reducing potential of B. turcicus extracts were determined by the Phosphomolybdenum and Ferric ion reducing antioxidant power (FRAP) method. The effect of B. turcicus on HEp-2, SCC-90, SCC-9, FaDu HNC cell viability, motility, and cell-nuclear morphology was evaluated by MTT, scratch-wound healing assay, and Pllalloidin-DAPI staining, respectively. The effect of B. turcicus on the expression of CASP-3, BAX, and BCL-2 genes at the mRNA, protein, and intracellular level was evaluated by quantitative PCR (qPCR), western blot, and immunofluorescence staining. Moreover, Annexin V-FITC/PI, was used in flow cytometry to investigate the effect of B. turcicus on apoptosis. Results The MeOH extract exhibited the highest phenolic content, flavonoid content and antioxidant activity (p < 0.05 for all). HNC cells treated with extracts indicated delayed wound healing and decreased motility (p < 0.05 for all). Analysis of annexin V-PI staining indicated that the B. turcicus extracts induced apoptosis but not viability and necrosis in the HNC cell (p < 0.05 for all). Moreover, qPCR data regarding the apoptotic mechanism showed that the extracts could induce apoptosis by upregulation of pro-apoptotic CASP-3 and BAX genes and downregulation of anti-apoptotic BCL-2 gene (p < 0.05 for all). The expression of protein and intracellular levels of CASP-3 and BAX were increased, while the BCL-2 was decreased in cells treated with the extracts (p < 0.05 for all). In addition, diffuse pycnosis and DNA condensation in HNC cell nuclei, confirming apoptotic cell death (p < 0.05 for all). Conclusion This study data indicated that B. turcicus extracts have antioxidant, cytotoxic, anti-migratory and pro-apoptotic activity. In conclusion, it has been shown that B. turcicus can be used as a potential therapeutic agent against HNC.
  • [ X ]
    Öğe
    Association of Toll-Like Receptor Polymorphisms With Nasal Polyposis
    (Sage Publications Inc, 2021) Kesici, Gulin Gokcen; Kaytez, Kargin Selda; Ozdas, Talih; Ozdas, Sibel
    Nasal polyposis is a disease characterized with chronic inflammation of the nasal mucosa. Toll-like receptors (TLRs) are defined as essential receptors of the innate immune system and may play in the development of nasal polyposis. A total of 71 patients with nasal polyposis and 74 healthy controls were included in this study. Three single-nucleotide polymorphisms (SNPs); TLR2 (2258 A>G), TLR4 (896 A>G), and TLR4 (1196 C>T) were analyzed in all patients. The degree of pair-wise linkage disequilibrium and the genotype and haplotype analyses were conducted using regression in this logistic model and the Multifactor Dimensionality Reduction (MDR) software package was used to construct all possible interactions among different genotype variants belonging to the TLR gene. There was significant difference in genotype and allele frequencies of the TLR4 (1196 C>T) polymorphism between the nasal polyposis and control groups (0.017). Also, it was observed that the probability of nasal polyposis was 62.7% in the presence of TLR4 (1196 C>T) polymorphism with asthma (P= .007). As a conclusion, this study showed that TLR4 and TLR2 polymorphisms were predisposing factors for nasal polyposis. Further functional studies investigating the consequences of loss of TLR function are needed.
  • [ X ]
    Öğe
    Association of Ugrp2 gene polymorphisms with adenoid hypertrophy in the pediatric population
    (Assoc Brasileira Otorrinolaringologia & Cirurgia Cervicofacial, 2018) Atilla, Mahmut Hunturk; Ozdas, Sibel; Ozdas, Talih; Bastimur, Sibel; Muz, Sami Engin; Oz, Isilay; Kurt, Kenan
    Introduction: Adenoid hypertrophy is a condition that presents itself as the chronic enlargement of adenoid tissues; it is frequently observed in the pediatric population. The Ugrp2 gene, a member of the secretoglobin superfamily, encodes a low-molecular weight protein that functions in the differentiation of upper airway epithelial cells. However, little is known about the association of Ugrp2 genetic variations with adenoid hypertrophy. Objective: The aim of this study is to investigate the association of single nucleotide polymorphisms in the Ugrp2 gene with adenoid hypertrophy and its related phenotypes. Methods: A total of 219 children, comprising 114 patients suffering from adenoid hypertrophy and 105 healthy patients without adenoid hypertrophy, were enrolled in this study. Genotypes of the Ugrp2 gene were determined by DNA sequencing. Results: We identified four single nucleotide polymorphisms (IVS1-189G>A, IVS1-89T>G, c.201delC, and IVS2-15G>A) in the Ugrp2 gene. Our genotype analysis showed that the Ugrp2 (IVS1-89T>G) TG and (c.201delC) CdelC genotypes and their minor alleles were associated with a considerable increase in the risk of adenoid hypertrophy compared with the controls (p = 0.012, p = 0.009, p = 0.013, and p = 0.037, respectively). Furthermore, Ugrp2 (GTdelCG, GTdelCA) haplotypes were significantly associated with adenoid hypertrophy (four single nucleotide polymorphisms ordered from 5' to 3'; p = 0.0001). Polymorfism-Polymorfism interaction analysis indicated a strong interaction between combined genotypes of the Ugrp2 gene contributing to adenoid hypertrophy, as well as an increased chance of its diagnosis (p < 0.0001). In addition, diplotypes carrying the mutant Ugrp2 (c.201delC) allele were strongly associated with an increased risk of adenoid hypertrophy with asthma and with allergies (p = 0.003 and p = 0.0007, respectively). Conclusion: Some single nucleotide polymorphisms and their combinations in the Ugrp2 gene are associated with an increased risk of developing adenoid hypertrophy. Therefore, we tried to underline the importance of genetic factors associated with adenoid hypertrophy and its related clinical phenotypes. (C) 2017 Associacao Brasileira de Otorrinolaringologia e Cirurgia C ervico-Facial. Published by Elsevier Editora Ltda.
  • [ X ]
    Öğe
    Combinations of Interleukin-10 Gene Promoter Polymorphisms with -1082A, -819T, -592A Minor Allele are Associated with Sinonasal Polyposis.
    (2018) Ozdas, Sibel
    Sinonasal polyposis (SP) is an inflammatory disease involving multiple etiologies andpathogenesis. The disarray of Interleukin (IL)-10 is associated with a raised immunopathologicalresponse during the progression of many autoimmune diseases as well as theresponse to infection. We studied the possible role of the single nucleotide polymorphisms(SNPs) in IL-10 gene and their genotypic combinations in the SP pathogenesis. The IL-10’spromoter was genotyped in 200 participants (100 patients and 100 controls). The sites thatwere encompassed -1082, -819, and -592 SNP regions of extracted DNAs were analyzedby sequencing for polymorphisms. The IL-10 gene promoter polymorphisms with -1082A,-819T, -592A minor alleles, their heterozygotes and homozygotes mutant genotypes hadsignificantly higher risks for SP (P<0.05). Also, haplotype analysis demonstrated that theGTC, ACC, and GCA haplotypes in IL-10 were high-risk of SP but ATA was only incontrols (P= 0.007). Also, the multifactor dimensionality reduction (MDR) analysis indicatedthat the IL-10-1082_-819 and -1082_-819_-592 were the best predictive modelsfor SP with 66.6% and 69% accuracy, respectively. IL-10 genotypic variations and theircombinations are linked with a high-risk for the SP development in the Turkish population.The IL-10 genetic polymorphisms may lend to SP by altering the arrangement of the geneexpression, affecting the severity of the inflammatory response.
  • [ X ]
    Öğe
    CRM1 expression: association with high prognostic value in laryngeal cancer
    (Tubitak Scientific & Technological Research Council Turkey, 2023) Ozdas, Talih; Ozdas, Sibel; Canatar, Ipek; Coskun, Erdal; Senyurt, Elif Burcu; Gorgulu, Orhan
    Background/aim: Laryngeal cancer is a very common malignant tumor of the head and neck. While laryngeal cancer does not show any obvious early symptoms, it tends to have a poor prognosis in advanced clinical stages. Chromosome region maintenance 1 (CRM1) mediates the nuclear export of some RNAs, major and tumor suppressor proteins and has been associated with the pathogenesis of many tumors. However, the clinicopathological significance of CRM1 gene expression in laryngeal cancer has not been clarified yet. Therefore, this study aims to detect the expression of CRM1 in laryngeal cancer and to investigate its relationship with clinicopathological parameters and prognosis. Materials and methods: CRM1 expression in matched tumor and normal tissues obtained from 43 laryngeal cancer patients were evaluated intracellular for protein and mRNA levels by immunohistochemical staining (IHC), western-blot, and quantitative real-time RT-PCR (qRT-PCR), respectively. Results: IHC, western-blot, and qRT-PCR analyses showed that CRM1 expression was significantly increased in laryngeal cancer tissue compared to normal tissue. Increased expression of CRM1 has been associated with poor prognostic clinicopathological features, including advanced tumor stage, increased tumor invasion, larger tumor size, positive lymph node metastasis, distant metastasis, and invasive histological type by IHC, western-blot, and qRT-PCR. Kaplan-Meier survival analysis showed that patients with high expression of CRM1 exhibited lower overall survival compared to those with low expression (Log-rank = 7.16, p = 0.007). According to the The Cancer Genome Atlas (TCGA) datasets, elevated CRM1 expression in head and neck cancer including cases of squamous cell laryngeal origin is associated with advanced tumor stage and histological grade (p > 0.05, for all). Conclusion: Consequently, CRM1 plays an important role in laryngeal cancer and may serve as an indicator and prognostic factor for poor overall survival in laryngeal cancer patients.
  • [ X ]
    Öğe
    Crm1 knockdown by specific small interfering RNA reduces cell proliferation and induces apoptosis in head and neck cancer cell lines
    (Tubitak Scientific & Technological Research Council Turkey, 2018) Ozdas, Sibel; Ozdas, Talih
    Head and neck squamous cell carcinoma (HNSCC) is the most common and most aggressive type of head and neck cancer. Current approaches for the treatment of HNSCC are not sufficient to increase the patient survival or to reduce the high recurrence rate. Consequently, there is a need to explore the molecular characteristics of this cancer in order to discover potential therapeutic target molecules. The overexpression of chromosome region maintenance 1 (Crm1), responsible for the transport of different classes of macromolecules from the nuclear membrane to the cytoplasm, in various cancer cells has made it an attractive target molecule in cancer research. It has been reported that transcription factors, which are the target cargo proteins of Crm1, have critical roles in regulating intracellular processes via their expression levels and functions, which in turn are regulated by the cell cycle and signaling proteins. Previous findings show that head and neck cancer cells overexpress Crm1 and that these cells become highly dependent on Crm1 function. The results of this study show that after decreasing Crm1 expression levels in HNSCC cells through either treatment with specific Crm1 RNA interference (siRNA) or the selective Crm1 inhibitor leptomycin B (LMB), cell viability, proliferation, migration, and wound-healing abilities decreased, suppressing tumorigenic properties through the induction of apoptosis. Crm1 is a powerful diagnostic biomarker because of its central role in cancerogenesis, and it has a high potential for the development of targeted Crm1 molecules or synthetic agents, such as LMB, as well as for the improvement of the clinical features in head and neck cancer.
  • [ X ]
    Öğe
    Differentially expressed Secretoglobin 1C1 gene in nasal polyposis
    (C M B Assoc, 2018) Ozdas, Sibel; Ozdas, Talih
    Nasal polyps (NP) are the most common pathological change that occurs in the nasal mucosa and is characterized by mucosal inflammation. Although its etiology and pathogenesis have not been clearly explained, its pathophysiology is arranged by the balance between pro-inflammatory and anti-inflammatory cytokines. The Secretoglobin 1C1 gene synthesizes odor molecule binding proteins (OBPs) in the nasal mucosa and regulates some cytokines. The Secretoglobin 1C1 gene expression could be disrupted by polymorphisms that may act as a possible cause of a disruption in the regulation of the promotor of the gene. Therefore, the main aim of this study was to determine the effects of Secretoglobin 1C1 gene promotor polymorphisms on the gene expression in NP. In this study, to determine the relationship between the Secretoglobin 1C1 gene promotor polymorphisms and the gene expression, the levels of 48 subjects were sequenced (24 patients with NP and 22 controls without sinonasal disease). The levels' expression of Secretoglobin 1C1 in the subjects' nasal mucosa was also detected using RT-PCR. In this study, the level of Secretoglobin 1C1's expression increased in NP (P=0.003). Three polymorphisms were detected in the Secretoglobin 1C1 gene's promotor. The rs113795008 and rs2280540 variations were significantly high in NP (P=0.005, P=0.045). The the rs113795008 homozygous mutant type genotype (G/G) was associated with a high mRNA expression level of Secretoglobin 1C1 in NP (P=0.009). A correlation was found between a high level of Secretoglobin 1C1 expression and its promotor polymorphism, which thus might increase and/or contribute to the susceptibility of developing NP in the Turkish population. These findings suggested that promotor variations in the function of the Secretoglobin 1C1 gene can alter the gene expression biology in NP.
  • [ X ]
    Öğe
    Nuclear entrapment of p33ING1b by inhibition of exportin-1: A trigger of apoptosis in head and neck squamous cell cancer
    (C M B Assoc, 2018) Ozdas, Sibel
    The effect of deregulation of nuclear export mediated by exportin-L with consequent cellular mislocalization of p33(ING1b), a member of the tumor suppressor gene family, has not been previously investigated in head and neck squamous cell cancer (IINSCC). We evaluated the effect of reversing cytoplasmic p33(ING1b) localization through inhibition of exportin-1 by leptomycin B (LMB) and the effect of nuclear entrapment of p33(ING1b) on molecular alterations in primary and metastatic IINSCC lines. The expression and location of exportin-1 and p33(ING1b) We re analyzed by a quantitative real-time reverse transcription polymerase chain reaction PCR (qRT-PCR), a Western blot, and iminunostaining. Cell proliferation and migration assays were conducted to determine the effect of exportin-1 inhibition on the cell lines. Exportin-1 was overexpressed in metastatic FINSCC, whereas p33(ING1) was poorly expressed. Exportin-1 inhibition induced nuclear entrapment and upregulation of p33(ING1b), extensive apoptosis, and growth arrest. It also suppressed cell migration. Cytoplasmic p33(ING1b)-mediated regulation of cell growth and nuclear entrapment of p33(ING1b) via inhibition of exportin-1 may be a key mechanism for inducing IINSCC apoptosis.
  • [ X ]
    Öğe
    Pterostilbene protects cochlea from ototoxicity in streptozotocin-induced diabetic rats by inhibiting apoptosis
    (Public Library Science, 2020) Ozdas, Sibel; Tastekin, Bora; Gurgen, Seren G.; Ozdas, Talih; Pelit, Aykut; Erkan, Sanem O.; Tuhanioglu, Birgul
    Diabetes mellitus (DM) causes ototoxicity by inducing oxidative stress, microangiopathy, and apoptosis in the cochlear sensory hair cells. The natural anti-oxidant pterostilbene (PTS) (trans-3,5-dimethoxy-4-hydroxystylbene) has been reported to relieve oxidative stress and apoptosis in DM, but its role in diabetic-induced ototoxicity is unclear. This study aimed to investigate the effects of dose-dependent PTS on the cochlear cells of streptozotocin (STZ)-induced diabetic rats. The study included 30 albino male Wistar rats that were randomized into five groups: non-diabetic control (Control), diabetic control (DM), and diabetic rats treated with intraperitoneal PTS at 10, 20, or 40 mg/kg/day during the four-week experimental period (DM + PTS10, DM + PTS20, and DM + PTS40). Distortion product otoacoustic emission (DPOAE) tests were performed at the beginning and end of the study. At the end of the experimental period, apoptosis in the rat cochlea was investigated using caspase-8, cytochrome-c, and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL). Quantitative real-time polymerase chain reaction was used to assess the mRNA expression levels of the following genes:CASP-3, BCL-associated X protein (BAX), andBCL-2. Body weight, blood glucose, serum insulin, and malondialdehyde (MDA) levels in the rat groups were evaluated. The mean DPOAE amplitude in the DM group was significantly lower than the means of the other groups (0.9-8 kHz; P < 0.001 for all). A dose-dependent increase of the mean DPOAE amplitudes was observed with PTS treatment (P < 0.05 for all). The Caspase-8 and Cytochrome-c protein expressions and the number of TUNEL-positive cells in the hair cells of the Corti organs of the DM rat group were significantly higher than those of the PTS treatment and control groups (DM > DM + PTS10 > DM + PTS20 > DM + PTS40 > Control; P < 0.05 for all). PTS treatment also reduced cell apoptosis in a dose-dependent manner by increasing the mRNA expression of the anti-apoptosisBCL2gene and by decreasing the mRNA expressions of both the pro-apoptosisBAXgene and its effectorCASP-3and the ratio ofBAX/BCL-2in a dose-dependent manner (P < 0.05 compared to DM for all). PTS treatment significantly improved the metabolic parameters of the diabetic rats, such as body weight, blood glucose, serum insulin, and MDA levels, consistent with our other findings (P < 0.05 compared to DM for all). PTS decreased the cochlear damage caused by diabetes, as confirmed by DPOAE, biochemical, histopathological, immunohistochemical, and molecular findings. This study reports the first in vivo findings to suggest that PTS may be a protective therapeutic agent against diabetes-induced ototoxicity.
  • [ X ]
    Öğe
    Pterostilbene suppresses head and neck cancer cell proliferation via induction of apoptosis
    (Tubitak Scientific & Technological Research Council Turkey, 2024) Ozdas, Talih; Ozdas, Sibel; Canatar, Ipek; Kaypak, Erdem
    Background/aim: Head and neck cancer (HNC) is one of the most prevalent causes of death worldwide, and so discovering anticancer agents for its treatment is very important. Pterostilbene (PS) is a trans-stilbene reported to be beneficial in managing various cancers. The objective of the study was to evaluate the cytotoxic, antiproliferative, proapoptotic, and antimigrative effect of PS on HEp-2, SCC-90, SCC-9, FaDu, and Detroit-551 cell lines. Materials and methods: MTT and live/dead assays were employed to assess cell viability, while a cell migration test was performed to evaluate wound healing capacity. The mRNA, protein, and intracellular expression levels of CASP-3, BAX, and BCL-2 genes were evaluated by real-time PCR, western blotting, and immunofluorescence staining. Annexin V-PI staining was conducted to assess the amounts of viable, apoptotic, and necrotic cells. Results: The results revealed that PS displayed cytotoxic, antiproliferative activity in a dose-dependent manner in HNC cells by upregulating CASP-3 and BCL-2 while downregulating BCL-2 in the apoptotic pathway. The proapoptotic properties were confirmed by the annexin-V-IP results. Moreover, PS displayed a significant suppressive efficacy on the migration capacity of HNC cells. Conclusion: The present study provides proof that PS has the prospective to be improved as an attractive anticancer agent against HNC following advanced studies.
  • [ X ]
    Öğe
    Significant association between SCGB1D4 gene polymorphisms and susceptibility to adenoid hypertrophy in a pediatric population
    (Tubitak Scientific & Technological Research Council Turkey, 2017) Ozdas, Talih; Ozdas, Sibel; Babademez, Mehmet Ali; Muz, Sami Engin; Atilla, M. Hunturk; Bastimur, Sibel; Izbirak, Afife
    Background/aim: Adenoid hypertrophy (AH) is chronic enlargement of the adenoid tissue. The pathophysiology of the disease is unclear. We analyzed SCGB1D4 gene polymorphisms in order to determine the effect of the variants or their genetic combinations on AH. Materials and methods: We genotyped the SCGB1D4 (IIS) gene in 167 participants (95 children with AH and 72 controls) by performing DNA sequencing in blood samples. Results: We genotyped three single nucleotide polymorphisms (SNPs). In the analysis, we found that in the presence of those SNPs and the minor alleles of individual SNPs four haplotypes were associated with an increased risk of AH. In addition, those SNPs were significantly associated with asthma, allergy, sleep-disordered breathing, AH grade + 4, and a high level of IgE. As indicated on multifactor dimensionality reduction analysis, single-locus (rs35328961), two-locus (rs35328961_rs56196602), and three-locus models (rs200327820_rs35328961_rs56196602) had the highest synergistic interaction effect on AH. The three-factor model was also significantly associated with some genotypes of rs35328961 and allergic-asthmatic AH. Conclusion: SNPs of SCGB1D4 and their combinations are associated with an increased risk for developing AH. We highlighted the importance of genetic factors on AH and AH-related clinical phenotypes.
  • [ X ]
    Öğe
    The common genetic variants of toll-like receptor and susceptibility to adenoid hypertrophy: a hospital-based cohort study
    (Tubitak Scientific & Technological Research Council Turkey, 2016) Babademez, Mehmet Ali; Ozdas, Talih; Ozdas, Sibel
    Background/aim: Adenoid hypertrophy (AH) is one of the most frequent pediatric disorders. The aim of this study was to investigate the effects of TLR2-R753Q, TLR4-T399I, and TLR4-D299G polymorphisms in children with AH. Materials and methods: The variants of the TLR gene were determined by restriction fragment length polymorphism (PCR-RFLP) analysis in 60 patients with AH and in 50 healthy children. Data were analyzed with SNPStats and multifactor dimensionality reduction (MDR) software. Results: We found that the presence of the G allele, the AG+GG and AG genotypes at TLR4-D299G, and the GGT haplotype were associated with AH in children (P = 0.013, P = 0.02, P = 0.038, and P = 0.001, respectively). On the contrary, no association was found between TLR2-R753Q and predisposition to AH. The CT genotype at TLR4-T399I showed a sex-specific association with AH, occurring only in boys with allergies (P = 0.0048). In addition, MDR analysis indicated a strong synergy between TLR gene markers contributing to AH. Allergic children with the diplotypes that included minor alleles of TLR4-D299G or TLR4-T399I had about a 4-fold increased risk for AH. Conclusion: Common genetic variants of the gene encoding the TLR4 protein may have differential effects on AH and the presence of sex-specific allergy.