Gunnur Deniz - Academia.edu (original) (raw)

Papers by Gunnur Deniz

Journal of Thoracic Oncology, Oct 1, 2018

Background: Lung cancer represents the second most frequent cause of death worldwide, and most co... more Background: Lung cancer represents the second most frequent cause of death worldwide, and most common subtype of lung cancer is nonsmall cell lung cancer (NSCLC). Recent trials showed that deficiencies in

BMC Nephrology, Jul 26, 2017

Background: Hemodialysis (HD) patients have increased risk of cardiovascular disease (CVD). Impai... more Background: Hemodialysis (HD) patients have increased risk of cardiovascular disease (CVD). Impaired stem cell health and adipocytokine metabolism may play important roles in the complex pathophysiological mechanisms of CVD in this patient population. We aimed to investigate the relationships between CD133+ cell counts, adipocytokines and parameters of endothelial dysfunction and atherosclerosis in HD patients. Methods: In 58 chronic HD patients (male/female:28/30, mean age:58 ± 14 years), serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin and resistin were measured by ELISA. Left ventricular mass index (LVMI), carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD) of the brachial artery were measured. CD133+ cells were counted by flow cytometry (BD FACSCalibur-BD Bioscience,CA). Results: CD133+ cell counts were inversely associated with FMD (r = −0.39, p = 0.007) and positively correlated with serum resistin (r = 0.45, p < 0.001) and serum TNF-α (r = 0.31, p = 0.02). Serum leptin levels were higher in high CD133 group compared to low CD133 group [32.37(12.74-72.29) vs 15.50(5.38-37.12)ng/mL, p = 0.03]. Serum leptin levels were correlated with TNF-α(r = 0.35, p = 0.009). Serum adiponectin levels were negatively correlated with serum leptin (r = −0.28, p = 0.03). Serum resistin levels were associated with TNF-α (r = 0.54, p < 0.001) and leptin (r = 0.29, p = 0.03). Serum IL-6 levels were significantly associated with LVMI (r = 0.31, p = 0.03). Serum IL-6 levels were significantly higher in patients with carotid plaque compared to patients without plaque [12.75(9.91-28.68) vs 8.27(5.97-14.04) pg/mL, p = 0.02]. In multiple linear regression analysis to determine the factors predicting LogFMD; dialysis vintage, LVMI and LogCD133+ cell counts were included as independent variables(R = 0.57, adjusted R-square = 0.27, p = 0.001). CD133+ cell count and LVMI were found to significantly predict FMD (p = 0.03 and p = 0.04 respectively). Conclusion: CD133+ cells were associated with inflammation and endothelial dysfunction in HD patients. Serum leptin, resistin and TNF-α levels were positively related to CD133+ cell count. Impaired regulation of undifferentiated stem cells and adipocytokines might contribute to endothelial dysfunction in HD patients.

Experimed, Dec 30, 2022

Objective: CD5 + CD19 + cells have a low proliferation capacity and elevated expression of anti-a... more Objective: CD5 + CD19 + cells have a low proliferation capacity and elevated expression of anti-apoptotic protein BCL-2, mostly in the G0/ G1 cell phase and accumulate in the pathogenesis of chronic lymphocytic leukemia (CLL). Natural killer (NK) cells have the ability to kill the intracellular pathogen-infected or cancer cells and secrete cytotoxic enzymes. This study evaluated the frequency, expression of cytotoxic enzymes, and intracellular cytokine levels of NK cells in CLL patients. Materials and Methods: In this study, peripheral blood mononuclear cells were isolated from peripheral blood samples of CLL patients (n=29) and healthy controls (n=16) by density gradient centrifugation method. The frequency of the total NK cells and the intracellular levels of perforin, granzyme, interferon (IFN)-γ, interleukin (IL)-21, IL-4 and IL-17 in NK cells were investigated. Results: Elevated total NK cell frequency were found in the CLL patients compared to the healthy controls, and negatively correlated with CD5 + CD19 + malign B cell frequency. Increased perforin expression was observed in patients' total NK cells. Additionally, increased levels of IL-17 and IL-21 in total NK cell of CLL patients were obtained compared to healthy subjects. Conclusion: The findings suggest that in the early stage of CLL, increased total NK cell frequency, and elevated perforin and IL-21 levels in NK cells might have a protective impact against the progression of the disease for CLL patients.

Mikrobiyoloji Bulteni

Mikobakteriyel enfeksiyonlara karşı mendeliyen duyarlılık (MSMD) nadir gözlenen primer immün yete... more Mikobakteriyel enfeksiyonlara karşı mendeliyen duyarlılık (MSMD) nadir gözlenen primer immün yetersizlik (PİY) hastalığıdır. Günümüze kadar hastalarda 16'dan fazla genetik kusur tanımlanmış, en sık IL-12Rβ1 eksikliği gözlenmiştir. PİY tanısında genetik testlerin yanı sıra immünolojik testler de önem kazanmaktadır. Bu çalışmada MSMD hastalarında, hasta yakınlarında ve sağlıklı bireylerde IFN-γR1 ve IL-12Rβ1 ekspresyonlarının belirlenmesi yoluyla, MSMD tanısında hızlı ve güvenilir bir yöntem olarak akan hücre ölçer yönteminin yerinin değerlendirilmesi amaçlanmıştır. MSMD tanısı alan ve genetik tanısı doğrulanmış, klinik olarak uyumlu altı hasta ve altı hasta yakını ile 20 sağlıklı birey olmak üzere toplam 32 gönüllüde akan hücre ölçer ile lenfosit IFN-γR1 ve IL-12Rβ1 ekspresyon düzeyleri analiz edilmiştir. Sağlıklı bireylerde IFN-γR1 ve IL-12Rβ1 ekspresyonlarının normal dağılımı belirlenmiştir. Sağlıklı bireylerden elde edilen dağılım eğrileri normal dağılım olarak kabul edildiğinde, üç hasta ve bir hasta yakınında IL-12Rβ1 ekspresyon düzeyinin %1'in altında olduğu, STAT1 eksikliği tanısı alan hastanın IL-12Rβ1 ekspresyon seviyesinin yüksek olduğu bulunmuştur. Sağlıklı bireyler ile kıyaslandığında bir hastada IFN-γR1 ve IL-12Rβ1 ekspresyon seviyelerinde herhangi bir farklılık gözlenmezken, bir hastada IFN-γR1 ekspresyonun azaldığı

Journal of Complementary Medicine Research

Objectives: In this preliminary study, the in vitro effect of C-Vx in human PBMCs and the in vivo... more Objectives: In this preliminary study, the in vitro effect of C-Vx in human PBMCs and the in vivo effect of C-Vx in rats were investigated. Methods: The human part was analyzed in PBMCs isolated from healthy subjects. Apoptotic index, cytotoxic activity of CD8+ T and NK cells, and cell proliferation of CD3+, CD4+, CD8+ T and NK cells in response to different doses of C-Vx were investigated. Also the hematological and biochemical parameters of the rats administered subcutaneously in three different doses of C-Vx were monitored for 14-days. Results: Increased CD107a expression in response to C-Vx on NK cells but not on CD8+ T cells support the increasing of NK cell cytotoxicity. C-Vx alone was capable of triggering proliferation of T and NK cells. The PHA-induced proliferation of CD3+ and CD4+ T cells was diminished in response to C-Vx, while PHA-induced CD8+ T cell proliferation was up-regulated. PHA-triggered proliferation of total NK cells was enhanced with the existence of C-Vx. C...

World Journal of Surgical Oncology

High expression of immune checkpoint receptors (ICRs) in the tumor microenvironment regulates the... more High expression of immune checkpoint receptors (ICRs) in the tumor microenvironment regulates the anti-tumor response. In this study, the differential expressions of ICRs on tumor-infiltrating lymphocytes (TILs) in patients with early-stage breast cancer were investigated.The study included 32 patients who underwent surgery with a diagnosis of early-stage breast cancer between September 2018 and March 2020. TIL isolation was performed using a MACS tumor separation device and tumor separation kit. PD-1, CTLA-4, LAG-3, TIM-3, and TIGIT expression of cytotoxic T and natural killer (NK) cells on TILs and peripheral blood lymphocytes (PBLs) were determined by flow cytometry.Patients with a high Ki-67 index, high TIL density, and HER-2 positivity were more likely to have increased CD16+CD56dim NK cells on TILs. Patients with T2 tumors were more likely to have increased expression of PD-1, LAG-3, and TIGIT on tumor-infiltrating CD8+ cytotoxic T cells than those with T1 tumors. PD-1, CTLA-4...

Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients followin... more Multisystem inflammatory syndrome in children (MIS-C) evolves in some pediatric patients following acute infection with SARS-CoV-2 by hitherto unknown mechanisms. Whereas acute-COVID-19 severity and outcome were previously correlated with Notch4 expression on regulatory T (Treg) cells, here we show that the Treg cells in MIS-C are destabilized in association with increased Notch1 expression. Genetic analysis revealed that MIS-C patients were enriched in rare deleterious variant impacting inflammation and autoimmunity pathways, including dominant negative mutations in the Notch1 regulators NUMB and NUMBL. Notch1 signaling in Treg cells induced CD22, leading to their destabilization in an mTORC1 dependent manner and to the promotion of systemic inflammation. These results establish a Notch1-CD22 signaling axis that disrupts Treg cell function in MIS-C and point to distinct immune checkpoints controlled by individual Treg cell Notch receptors that shape the inflammatory outcome in SARS...

Istanbul University, 2020

International Immunopharmacology, 2022

Multiple efforts are currently underway to control and treat severe acute respiratory syndrome co... more Multiple efforts are currently underway to control and treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19) worldwide. Despite all efforts, the virus that emerged in Wuhan city has rapidly spread globally and led to a public health emergency of international concern (PHEIC) due to the lack of approved antiviral therapy. Nevertheless, SARS-CoV-2 has had a significant influence on the evolution of cellular therapeutic approaches. Adoptive immune cell therapy is innovative and offers either promising prophylactic or therapy for patients with moderate-to-severe COVID-19. This approach is aimed at developing safety and providing secure and effective therapy in combination with standard therapy for all COVID-19 infected individuals. Based on the effective results of previous studies on both inflammatory and autoimmune diseases, various immune cell therapies against COVID-19 have been reviewed and discussed. It must be considered that the application of cell therapy for treatment and to eliminate infected respiratory cells could result in excessive inflammation, so this treatment must be used in combination with other treatments, despite its many beneficial efforts.

Gunumuz modem toplumlarinda gittikce artan siklikta gorulen saglik problemlerinden biri olan meta... more Gunumuz modem toplumlarinda gittikce artan siklikta gorulen saglik problemlerinden biri olan metabolik sendrom (MS); insulin direnci, obezite, dislipidemi ve hipertansiyon sorunlarinin bir arada gelismesiyle ortaya cikmaktadir. Bu hastalik tablosunun ortaya cikisinda genetik yatkinliga ilaveten cevresel etmenler, hareketsiz yasam tarzi ve sagliksiz beslenme de rol oynamaktadir. Metabolik sendrom gelisiminin sonucu olarak kardiyovaskuler hastaliklar, yagli karaciger ve polikistik over sendromu gibi pek cok hastalik tablosu ortaya cikabilmektedir. Insan yasamini ciddi olarak tehdit etmekte olan metabolik sendromun gelisimsel kokeni ve fizyolojik mekanizmasim aydinlatmaya yonelik olarak dunya genelinde genis capta arastirmalar yapilmakta ve bu amacla deneysel hayvan modelleri siklikla kullanilmaktadir. Metabolik sendrom calismalarinda fare, sican, Yeni Gine kobayi, hamster ve koyun en cok tercih edilen deneysel hayvan turleri arasindadir. Bu hayvan modelleri icerisinde genetik olarak o...

Immunology Letters, 2021

Primary immune deficiencies (PID) are known to be more than 400 genetic defects caused by the imp... more Primary immune deficiencies (PID) are known to be more than 400 genetic defects caused by the impairment in development and/or functions of the immune system. Common Variable Immunodeficiency (CVID), Ataxia Telangiectasia (AT) and Agammaglobulinemia (AG) are examples of the most common immunodeficiency syndrome. Natural killer (NK) cells are a component of innate immune system and play a major role in the host-rejection of both tumors and virally infected cells. iNKT cells have a role in autoimmune and infectious diseases and controlling of tumor rejection. In this study, NK and iNKT cells and their functions, and intracellular cytokine amount are aimed to determine in patients that suffer CVID, AT and AG. NKp30, NKp46, NKG2D, perforin and granzyme mRNA expression levels were analyzed using RT-PCR. Receptors, cytokine amount of NK cell subset and iNKT were analyzed by flow cytometry. Decreased CD3+ T and elevated NK cell subset in pediatric AT were found. Expression of NKp44 was decreased in adult AG, but not in pediatric patients. Low NKp44 expression in CD3-CD16+CD56dim NK cell subset was found in pediatric AT patients. High HLA-DR, perforin and granzyme expression were found in CD3-CD16+CD56dim NK cell subset of pediatric CVID and AT patients. Alteration of the number of NK subsets, NK receptor expression and cytokine production were observed in pediatric patients compared to healthy subjects.

Allergy, 2020

BackgroundLittle is known about the diagnostic approaches for immediate hypersensitivity reaction... more BackgroundLittle is known about the diagnostic approaches for immediate hypersensitivity reactions (IHRs) due to 5‐nitroimidazole antibiotics. The aim was to evaluate the usefulness of in vivo tests and basophil activation test (BAT) for the diagnosis of IHRs due to metronidazole and ornidazole and to determine possible cross‐reactivity in between.MethodsForty‐nine patients with a clear history of IHRs due to these drugs and 20 healthy subjects who were known to tolerate these drugs were included. Skin tests (STs) and single‐blind placebo‐controlled drug provocation tests (SBPCDPTs) were performed with both drugs whereas BAT was applied only with the culprit drug.ResultsThe most and least common reaction types were urticaria/angioedema (34.7%) and anaphylaxis (14.3%), respectively. SBPCDPTs were positive in 15 out of 47 patients, and only 7 had positive STs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of STs for metronidazole/ornida...

Immunological Investigations, 2020

CD55 and CD59 are complement regulatory proteins suggested to be related with progression of diab... more CD55 and CD59 are complement regulatory proteins suggested to be related with progression of diabetes and its complications. The stromal cell-derived factor 1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR-4) are chemokine proteins. We aimed to investigate the relation of CD55 and CD59 expression levels and polymorphisms of SDF-1 and CXCR-4 with type 2 diabetes mellitus (T2DM) and its complications. Seventy-five T2DM patients and 73 controls were enrolled. Expression levels of CD55 and CD59 were measured by FACS Calibur; qRT-PCR was used to determine SDF-1 and CXCR-4 gene polymorphisms. CD55 and CD59 expressions in patients with nephropathy, retinopathy and cardiovascular disease were significantly lower than controls. Frequency of CXCR-4 T allele carrying was high in patients and created 1.6 fold risk for the disease (p = .07). CXCR-4 a allele carriers had decreased nephropathy; although there was no statistical significance in carrying CXCR-4 T allele, presence of nephropathy was approximately 2 times higher (p = .254). The nephropathy risk increased 10-fold in CXCR-4 TT genotype carriers (p = .02). All SDF-1 CC genotype carriers had retinopathy, so, it was considered that the CC genotype was effective in retinopathy development (p = .031). For the presence of cardiovascular disease, significant difference was observed for SDF-1 genotypes. Increased cardiovascular risk of 5-and 1.9-fold in SDF-1 T (p = .007) and CXCR-4 T (p = .216) allele carriers, respectively, was observed. We suggest that CD55 and CD59 protein levels and SDF-1 and CXCR-4 have predictive importance in process, complications and tendency of T2DM.

Turkish Journal of Biochemistry, 2018

Objectives The role of oral bacteria in the etiopathogenesis of odontogenic cysts (OC) is controv... more Objectives The role of oral bacteria in the etiopathogenesis of odontogenic cysts (OC) is controversial. Immune response is regulated by the cytokines secreted during infection. This study aims to describe the association in between bacteria and levels of cytokines in OC. Methods Infected OC fluid samples were obtained from 25 odontogenic keratocysts and 14 radicular cysts (RC). Bacteria detection was performed by polymerase chain reaction on bacterial 16S rRNA genes. Cytokine levels in OC fluids were determined using “luminex” method. Results Porphyromonas gingivalis was the most common bacteria in all samples (41.03%). Bacteria species number was higher in RCs. The significant difference was detected in terms of interleukine (IL)-1β levels to the number of bacteria contained in cyst fluids (p<0.05). IL1-β level of cyst fluid group containing three or more species of bacteria increased compared with cyst fluid group containing two types of bacteria (p<0.05). IL-1β level was h...

Clinical and Translational Allergy, 2016

Background: Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious, life... more Background: Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious, life threatening severe immune-mediated cutaneous reactions with mortality ranging from 10 to 30 %. The commonest causes are drugs. SJS/TEN is characterised by widespread epidermal detachment due to keratinocyte cell death. Increased concentrations of cytotoxic molecules may act as potential serum biomarkers of SJS/TEN. However, to date no mechanism based biomarker has been validated for diagnostic utility in this field. HMGB1 is a well-validated biomarker of cell death and inflammation. This study investigated whether HMGB1 represents a valid, utilisable biomarkers for drug-induced SJS/TEN. Materials and methods: Serum samples from nevirapine-treated Malawian HIV patients (27 MPE, 12 DRESS, 12 SJS/TEN cases and matched tolerant controls) were analysed for total HMGB1 by ELISA. Novel mass-spectrometric protocols were also used to analyse posttranslationally modified forms of HMGB1. In addition serum from 20 Taiwanese SJS patients (five carbamazepine, eight allopurinol, five phenytoin, two sulfamethoxazole) both during and post-reaction were analysed for HMGB1 isoforms. Results: There was a significant elevation of mean total serum HMGB1 at time of reaction in patients with nevirapine-induced MPE (6.0 ng/ ml), HSS (6.3 ng/ml) and SJS/TEN (15.9 ng/ml) compared to tolerant controls at weeks (1.3 ng/ml) (p < 0.001). Analysis of post-translationally modified isoforms of the HMGB1 in the different phenotypes (Fig. 1) showed patients with MPE and DRESS had elevation the acetylated form of HMGB1 which is a marker of innate immunity. By contrast, SJS/ TEN patient sera contained comparable levels of acetylated HMGB1, but also had very high levels of the non-acetylated form, which is associated with cell death/tissue injury. The tolerant control patients had low levels of the unacetylated form. This pattern of HMGB1 isoform elevation was replicated in the Taiwanese SJS cohort. As patients recovered, the total HMGB1 concentrations went down, although there was still significant elevation of the sulphonyl (partially reduced) HMGB1 isoform which has no known immune function and may represent a marker of innate immunity returning to "steady state". Conclusions: In conclusion, our data suggest that post-translationally modified HMGB1 may represent mechanism-based diagnostic and prognostic markers for drug-induced SJS/TEN. This needs to be studied in more patients.

TheScientificWorldJournal, 2012

Cyclooxygenase (COX) inhibitors, already widely used for the treatment of pain and inflammation, ... more Cyclooxygenase (COX) inhibitors, already widely used for the treatment of pain and inflammation, are considered as promising compounds for the prevention and treatment of neoplasia. The aim of our study was to determine the direct antiproliferative effects of nonsteroidal anti-inflammatory drugs (NSAIDs), piroxicam and deracoxib, at a variety of concentrations as both single and combined treatments on canine mammary carcinoma cell line CMT-U27 and to understand the mechanisms of cell death. MTT assay was performed to determine cell viability, and flow cytometric analyses were performed to evaluate apoptosis and cell cycle alterations. Significant decrease in cell viability was observed at high concentrations of piroxicam and deracoxib in both single and combined treatments after 72 h incubation. Combined treatment produced a significantly greater inhibition than that caused by either agent alone. Also apoptotic cell number was increased by both drugs at the cytotoxic concentrations....