Ender Terzioglu

Publications (18)33.67 Total impact

• Article: A case of primary Sjögren’s syndrome with pulmonary-limited Wegener’s granulomatosis

  Veli Yazisiz, Irem Hicran Ozbudak, Ilknur Nizam, Funda Erbasan, Ali Berkant Avci, Omer Ozbudak, Ender Terzioglu
  [show abstract] [hide abstract]
  ABSTRACT: A 60-year-old woman had a history of dyspnea for 5–6weeks. The chest radiograph and computed tomography scans revealed bilateral patchy reticulonodular pattern. The patient had positive test results for antineutrophil cytoplasmic antibody against proteinase-3 (c-ANCA), antinuclear antibody and anti-Ro antibody. According to European Study Group on Classification Criteria for Sjögren’s Syndrome, the patient was diagnosed as primary Sjögren’s syndrome based on the presence of clinical features, positive findings on Schirmer’s test and parotis scintigraphy. Lung biopsy obtained by wedge resection showed granulomatous inflammation with extensive multinuclear giant cells involving the lung parenchyma and vascular structures. There was neither upper airway nor renal involvement. Thus, the patient was simultaneously diagnosed as pulmonary-limited Wegener’s granulomatosis. With this unique case, we would like to emphasize that the awareness of ANCA-associated vasculitis as a diagnostic possibility in primary Sjögren’s syndrome is important during the work-up of lung lesions. KeywordsAntineutrophil cytoplasmic antibody (ANCA)-Sjögren’s syndrome-Wegener’s granulomatosis
  Rheumatology International 04/2012; 30(9):1235-1238. · 1.88 Impact Factor
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  Available from: Arzu Didem Yalcin

  Article: CD40, CD45 CTLA-4 levels are elevated in healthy older adults.

  Arzu Didem Yalcin, Reginald M Gorczynski, Münevver Sarigül Kahraman, Mehtap Ulker Demirel, Ender Terzioglu
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  ABSTRACT: The immune system changes with age. In this study we characterized immune changes by performing immunologic screening profiles on ageing individuals. This study was performed at Akdeniz University, in the Faculty of Medicine, Department of Immunology. Healthy volunteers consisted of a younger group (22 donors) and an older group (45 individuals). All subjects had no serious health problems (i.e. chronic heart, lung, liver or immunological diseases) and were taking no prescribed medications. Flow cytometry analysis was used to evaluate CD3, CD4, CD8, CD16, CD19, CD28, CD40, CD45, CD56, CD80, CD86, CTLA-4 and ELISA for IL-1 beta, IL-2, IL-6, IL-10, IFN-gamma, TNF-alpha expression In addition, NK activity and induced cytokine expression (by bioassay and ELISA, respectively) were evaluated. No statistical differences were observed between the two groups in expression of CD3, CD8, CD19, CD80, CD86, CD16, CD 56, or CD28. A higher frequency of expression of CD4, CTLA-4, CD40, and CD45 was seen in older subjects by comparison with younger subjects. Cytokine profiles expressed by stimulated monocytes and lymphocytes from the two groups showed no difference in IL-1 beta, IL-2, IL-6, IL-10, TNF-alpha, and IFN-gamma production levels. We found increased expression levels of CD40 and CD45 levels in healthy older (age: 59.42 +/- 5.89) versus younger individuals (age: 30.32 +/- 2.29). CTLA-4 expression levels were also higher in older subjects, with no difference in CD28 expression levels between younger/older individuals.
  Clinical laboratory 01/2012; 58(5-6):449-56. · 0.90 Impact Factor
• Article: TRAIL Death Receptor4, Decoy Receptor1 and Decoy Receptor2 Expression on CD8+ T Cells Correlate with the Disease Severity in Patients with Rheumatoid Arthritis

  Atil Bisgin, Ender Terzioglu, Cigdem Aydin, Burcak Yoldas, Veli Yazisiz, Nilufer Balci, Huseyin Bagci, Reginald M Gorczynski, Cezmi A Akdis, Salih Sanlioglu
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  ABSTRACT: BACKGROUND: Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development. METHODS: The expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis. RESULTS: While no change was detected in the ratio of CD4+ to CD8+ T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+ and CD8+ T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4+ T cells, were positively correlated with patients' DAS scores. CONCLUSIONS: Our data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis.
  BMC Musculoskeletal Disorders - BMC MUSCULOSKELET DISORD. 01/2010; 11(1):192-9.
• Source

  Available from: Atil Bisgin

  Article: TRAIL death receptor-4, decoy receptor-1 and decoy receptor-2 expression on CD8+ T cells correlate with the disease severity in patients with rheumatoid arthritis.

  Atil Bisgin, Ender Terzioglu, Cigdem Aydin, Burcak Yoldas, Veli Yazisiz, Nilufer Balci, Huseyin Bagci, Reginald M Gorczynski, Cezmi A Akdis, Salih Sanlioglu
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  ABSTRACT: Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development. The expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis. While no change was detected in the ratio of CD4+ to CD8+ T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+ and CD8+ T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4+ T cells, were positively correlated with patients' DAS scores. Our data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis.
  BMC Musculoskeletal Disorders 01/2010; 11:192. · 1.58 Impact Factor
• Article: Lung involvement in patients with primary Sjögren's syndrome: what are the predictors?

  Veli Yazisiz, Gokhan Arslan, Irem Hicran Ozbudak, Sema Turker, Funda Erbasan, Ali Berkant Avci, Omer Ozbudak, Ender Terzioglu
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  ABSTRACT: The aim of this study was to investigate the prevalence, predictors and radiological findings of primary Sjögren's syndrome (pSS)-associated lung involvement. This retrospective cohort study included 123 patients with demographic, clinical, laboratory and radiological data who were diagnosed with pSS. Lung involvement was defined based on the presence of pulmonary signs/symptoms and/or impaired pulmonary function tests along with alterations in high-resolution computerized tomography (HRCT). Thirty patients (24.4%) had pulmonary signs/symptoms at the initial presentation and/or during the follow-up period. Based on the criteria, 14 patients (11.4%) were defined as having pSS with lung involvement. The smoking rate, male/female ratio and the mean ages were found to be higher in patients with lung involvement (P < 0.05). Positive IgM-rheumatoid factor (RF), anti-La and anti-Ro results, the presence of hypergammaglobulinemia and lymphopenia had high specificity despite the low sensitivity rates to detect pSS-associated lung disease. A significant difference was found in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) results between the patients with and without lung involvement. Impaired FEV(1) had high specificity and positive predictive value compared to impaired FVC, particularly in non-smoker patients. The most frequent HRCT finding was ground-glass attenuation (64.3%). Other common findings were bronchiectasis, reticular pattern and honeycombing. The lesions involved predominantly the lower lobes. In conclusion, the presence of hypergammaglobulinemia and lymphopenia, positivity for RF, anti-La and anti-Ro, and impaired (FVC) and/or FEV(1) values could be the predictive parameters with a high specificity despite the low sensitivity rates. Smoking history, male gender and age are also risk factors. These parameters may be helpful to distinguish pSS-associated lung involvement from lung disorders unrelated to pSS.
  Rheumatology International 10/2009; 30(10):1317-24. · 1.88 Impact Factor
• Article: A case of primary Sjögren's syndrome with pulmonary-limited Wegener's granulomatosis.

  Veli Yazisiz, Irem Hicran Ozbudak, Ilknur Nizam, Funda Erbasan, Ali Berkant Avci, Omer Ozbudak, Ender Terzioglu
  [show abstract] [hide abstract]
  ABSTRACT: A 60-year-old woman had a history of dyspnea for 5-6 weeks. The chest radiograph and computed tomography scans revealed bilateral patchy reticulonodular pattern. The patient had positive test results for antineutrophil cytoplasmic antibody against proteinase-3 (c-ANCA), antinuclear antibody and anti-Ro antibody. According to European Study Group on Classification Criteria for Sjögren's Syndrome, the patient was diagnosed as primary Sjögren's syndrome based on the presence of clinical features, positive findings on Schirmer's test and parotis scintigraphy. Lung biopsy obtained by wedge resection showed granulomatous inflammation with extensive multinuclear giant cells involving the lung parenchyma and vascular structures. There was neither upper airway nor renal involvement. Thus, the patient was simultaneously diagnosed as pulmonary-limited Wegener's granulomatosis. With this unique case, we would like to emphasize that the awareness of ANCA-associated vasculitis as a diagnostic possibility in primary Sjögren's syndrome is important during the work-up of lung lesions.
  Rheumatology International 08/2009; 30(9):1235-8. · 1.88 Impact Factor
• Article: Platelet-activating factor and P-selectin activities in thrombotic and nonthrombotic Behçet's patients.

  S Ercan Tunc, Kenan Aksu, Gokhan Keser, Fahrettin Oksel, Eker Doganavsargil, Timur Pirildar, Tufan Turk, Ender Terzioglu, Afig Huseyinov
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  ABSTRACT: The aim of this study was to compare plasma Platelet-activating factor (PAF) and P-selectin (CD62P) activities in Behçet's disease patients with and without thrombosis. In this cross-sectional and descriptive study, 30 consecutive Behçet's patients were included, 15 of them with venous thrombosis. All patients were also divided into two subgroups according to the presence or absence of clinical activity. Plasma PAF levels, basal and Ca++ ionophore (A23187)-induced leukocyte (cellular) PAF activities, and platelet-rich plasma DeltaCD62P activity (the mean fluorescent density difference between CD62P phycoerythrin-positive and -negative stains) were evaluated. In the thrombotic group, plasma PAF (P=0.001), basal leukocyte PAF (P=0.017), induced leukocyte PAF (P=0.024), and DeltaCD62P (P=0.023) levels were significantly higher than in the nonthrombotic group. In the whole group of Behçet's patients, there was a positive correlation between plasma PAF and DeltaCD62P levels (r=0.533, P=0.002). When we compared clinically active and inactive patients with respect to the above parameters, there was no significant difference, irrespective of thrombosis. Plasma PAF (P=0.001), basal leukocyte PAF (P=0.004), and DeltaCD62P (P=0.038) levels were significantly higher in the presence of both clinical activity and thrombosis than of clinical activity alone. Platelet-activating factor and CD62P may contribute to endothelial injury and thrombosis development in Behçet's disease. These two parameters seem related to the presence of thrombosis rather than clinical activity.
  Rheumatology International 07/2005; 25(5):326-31. · 1.88 Impact Factor
• Article: Platelet-activating factor and P-selectin activities in thrombotic and nonthrombotic Behçet’s patients

  S. Ercan Tunc, Kenan Aksu, Gokhan Keser, Fahrettin Oksel, Eker Doganavsargil, Timur Pirildar, Tufan Turk, Ender Terzioglu, Afig Huseyinov
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  ABSTRACT: ObjectiveThe aim of this study was to compare plasma Platelet-activating factor (PAF) and P-selectin (CD62P) activities in Behets disease patients with and without thrombosis.MethodsIn this cross-sectional and descriptive study, 30 consecutive Behets patients were included, 15 of them with venous thrombosis. All patients were also divided into two subgroups according to the presence or absence of clinical activity. Plasma PAF levels, basal and Ca++ ionophore (A23187)-induced leukocyte (cellular) PAF activities, and platelet-rich plasma CD62P activity (the mean fluorescent density difference between CD62P phycoerythrin-positive and -negative stains) were evaluated.ResultsIn the thrombotic group, plasma PAF (P=0.001), basal leukocyte PAF (P=0.017), induced leukocyte PAF (P=0.024), and CD62P (P=0.023) levels were significantly higher than in the nonthrombotic group. In the whole group of Behets patients, there was a positive correlation between plasma PAF and CD62P levels (r=0.533, P=0.002). When we compared clinically active and inactive patients with respect to the above parameters, there was no significant difference, irrespective of thrombosis. Plasma PAF (P=0.001), basal leukocyte PAF (P=0.004), and CD62P (P=0.038) levels were significantly higher in the presence of both clinical activity and thrombosis than of clinical activity alone.ConclusionPlatelet-activating factor and CD62P may contribute to endothelial injury and thrombosis development in Behets disease. These two parameters seem related to the presence of thrombosis rather than clinical activity.
  Rheumatology International 06/2005; 25(5):326-331. · 1.88 Impact Factor
• Source

  Available from: ahter dilsad Sanlioglu

  Article: Fundamental principals of tumor necrosis factor-alpha gene therapy approach and implications for patients with lung carcinoma.

  Ahter D Sanlioglu, Cigdem Aydin, Hakan Bozcuk, Ender Terzioglu, Salih Sanlioglu
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  ABSTRACT: Apoptosis, known as programmed cell death, is defined as a cell's preferred form of death under hectic conditions through genetically conserved and complex pathways. There is a decisive balance between stimulatory and inhibitory signaling pathways to maintain homeostasis in cells. In order to shift the balance towards apoptosis, the modulation of both apoptotic and anti-apoptotic pathways represents an attractive target for cancer therapeutics. Currently, chemotherapy and radiotherapy are among the most commonly used treatment modalities against lung cancer. Tumor suppressor gene, p53, is required in order for both of these treatment methods to work as anti-tumor agents. As a result, tumors lacking p53 display resistance to both chemotherapy and radiotherapy. However, death ligands induce apoptosis regardless of p53 status of cells. Thus, these methods constitute a complementary therapeutic approach to currently employed conventional treatment modalities. At present, death ligands are being evaluated as potential cancer therapeutic agents. Since resistance to tumor necrosis factor (TNF)-alpha-mediated apoptosis represented an obstacle for the treatment of patients with lung carcinoma in the earlier attempts, an extensive research was recently initiated to understand molecular mechanism of TNF-alpha signaling. NF-kappaB transcription factors have been demonstrated to modulate the apoptotic program, mostly as blockers of apoptosis in different cell types. In this review, we concentrate on the current progress in the understanding of TNF-alpha-mediated apoptosis for lung carcinoma. Representative models of NF-kappaB-inhibiting gene therapy strategies from various labs including ours are also provided as examples of up-to-date approaches to defeat TNF resistance. In order to give the reader better understanding and appreciation of such approaches, previously unpublished in vivo assays are also incorporated into this review. Current progress in clinical trials using adenovirus-mediated delivery of TNF-alpha is also discussed.
  Lung Cancer 06/2004; 44(2):199-211. · 3.43 Impact Factor
• Article: Effect of portal venous injection of donor spleen cells on skin allograft survival in rat.

  Eray Kara, Içöz Gökhan, Murat Dayangaç, Ozer Ilkgül, Hikmet Ertan, Yaman Tokat, Ender Terzioglu
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  ABSTRACT: Pretransplantation injection of donor lymphohaemopoetic cells via portal venous route has been shown to improve allograft survival in mice. In the present study, the effect of perioperative portal venous administration of donor splenocytes on skin graft survival was investigated in comparison with intravenous administration of spleen cells in Swiss albino rat skin transplant model. Using a single-donor survival study, skin allograft recipients received either no treatment, a single transfusion of donor spleen cells via portal vein or a single transfusion of donor splenocytes into vena cava. Spleen cell transfusion consisted 25x10(6) viable cells in a volume of 1ml given just before skin grafting. Skin graft survival was assessed by macroscopic appearance. Rejection was defined as the first day on which the entire surface of the graft was necrotic. Histologically necrosis, increased connective tissue, vascularity and polymorphonuclear leucocyte (PNL) infiltration were evaluated under light microscopy. In this survival study of skin allografts, with the injection of viable spleen cells into portal vein concomitant to skin grafting, significant prolongation of mean allograft survival was induced (20.3 days), compared with untreated recipients (6.5 days, P<0.001). In the histopathologic evaluation, less PNL infiltration, necrosis, increased vascularity and connective tissue repair were observed in vena porta group with no statistical significance. It may be possible to develop protocols to induce transplantation tolerance based on the historical concept of donor specific antigen administration. However, it appears that donor spleen cell transfusion alone is not sufficient to prevent graft rejection. Thus, more efficient combination treatments are required to induce a state of durable tolerance.
  The Indian journal of medical research 04/2004; 119(3):110-4. · 1.84 Impact Factor
• Article: T cell subpopulations and IL-2R in vitiligo.

  Kamer Gunduz, Gunseli Ozturk, Ender Terzioglu, Filiz Sebik
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  ABSTRACT: Immunological alterations have been implicated in the etiopathogenesis of vitiligo. The aim of this study was to determine peripheral lymphocyte subpopulations and interleukin-2 receptor (IL-2R) in patients with vitiligo. Forty-five vitiligo patients (24 female, 21 male) and 34 healthy controls (11 female, 23 male) were included into the study. Eight (17.8%) of the patients had the segmental type, and 37 (82.2%) had generalized vitiligo. The disease was active in 25 (55.6%) patients; the other 20 (44.4%) patients had static vitiligo. Flow cytometry was used to determine the percentages of total T-lymphocytes, B-lymphocytes, helper/inducer T cells, suppressor/cytotoxic T cells, natural killer (NK) cells, activated T cells and interleukin-2 receptor (IL-2R) with the use of CD3, CD19, CD4, CD8, CD16, HLA-DR and CD25 monoclonal antibodies, respectively. The mean value of helper T cells showed a significant difference (p=0.01) between the two groups with the value being 32.5% in patients and 38.1% in control subjects. CD4/CD8 was significantly lower in vitiligo patients (p=0.04). There was also a statistically significant difference in the mean percentage of activated T cells between vitiligo patients and control subjects (4.7 and 8.1, respectively; p=0.001). No statistically significant differences were found when the values were compared between segmental and generalized vitiligo patients, or between active and static cases. In conclusion, T helper/inducer cells, CD4/CD8 ratio and activated (HLA-DR+) T cells are decreased in vitiligo patients, suggesting a role for changes in cellular immunity.
  The Journal of Dermatology 03/2004; 31(2):94-7. · 1.49 Impact Factor
• Article: Biochemical and morphological characteristics of selenite-induced apoptosis in human hepatoma Hep G2 cells.

  Handan Ak Celik, Hikmet Hakan Aydin, Remziye Deveci, Ender Terzioglu, Sabire Karacali, Guray Saydam, Ulus Akarca, Yucel Batur
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  ABSTRACT: Selenium is a cellular growth inhibitor in many mammary tumor cells. To comprehend the mechanism for the selenium-induced cell death, we examined the effects of sodium selenite, which has been one of the most extensively investigated selenium compounds, in human hepatoma Hep G2 cells.Cell viability gradually decreased after treatment with sodium selenite within the concentration range of 10-50 microM. Low (10 mM) selenite has shown a high-percentage laddering pattern compared to the high (25 microM) cytotoxic selenium concentration in agarose gel electrophoresis. G2/M-phase enrichment was also concentration dependent. The most consistent transmission electron microscopic finding was the existence of large lysosomes. Based on these data, we hypothesize that sodium selenite predominantly shows its apoptotic effect over hydrogen selenite accumulation.
  Biological Trace Element Research 02/2004; 99(1-3):27-40. · 1.92 Impact Factor
• Article: Characterization of the cellular response during apoptosis induction in cadmium-treated Hep G2 human hepatoma cells.

  Hikmet Hakan Aydin, Handan Ak Celik, Remziye Deveci, Ender Terzioglu, Sabire Karacali, Nihal Mete, Ulus Akarca, Yücel Batur
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  ABSTRACT: Cadmium is a toxic transition heavy metal of continuing occupational and environmental concern, with a wide variety of adverse effects on regulation of gene expression and cellular signal transduction pathways. Injury to cells by cadmium leads to a complex series of events that can culminate in the death of the cell. It has been reported that cadmium induces apoptosis in many cell lines. However, the morphological characteristics leading to apoptosis or subsequent regeneration in cells exposed to cadmium have not been clarified. We evaluated whether human hepatoma cells maintained in culture undergo apoptosis when exposed to cadmium. Cytotoxic activity of cadmium on Hep G2 cells determined using 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide assay. A DNA ladder assay was performed by electrophoresis. Cell cycle analysis was quantified by flow cytometry. Nuclear morphology was studied by fluorescence microscopy after staining with propidium iodide and Hoechst 33342. Morphologic alterations in culture hepatocytes treated with CdCl2 were observed by transmission electron microscopy. We have demonstrated that apoptosis is a major mode of elimination of damaged HepG2 cells in cadmium toxicity and it precedes necrosis.
  Biological Trace Element Research 12/2003; 95(2):139-53. · 1.92 Impact Factor
• Article: Involvement of protein phosphatase 2A in interferon-alpha-2b-induced apoptosis in K562 human chronic myelogenous leukaemia cells.

  Guray Saydam, Hikmet Hakan Aydin, Fahri Sahin, Nur Selvi, Gulperi Oktem, Ender Terzioglu, Filiz Buyukkececi, Serdar Bedii Omay
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  ABSTRACT: Interferon-alpha (IFN-alpha)-2b is known to have antiproliferative effects on hematological malignant cells, especially chronic myelogenous leukaemia (CML). However, it can induce cytogenetical remissions in a very small percentage of the patients. Also during interferon therapy, resistance can emerge in the CML clones. K562 is an in vitro model cell line transformed from a Ph positive CML patient. It can be induced to differentiate to granulocytic and/or monocytic lineages with certain molecules. IFN-alpha-2b generally exerts its effects on CML cells by Janus family kinases (Jak/Stat) pathway, mostly through tyrosine kinase system. However, there is almost no data on the relevance of serine/threonine (Ser/Thr) protein phosphatase (PP) system in the interferon induced signal transduction pathways. In this study, we investigated serine/threonine protein phosphatases in the IFN-alpha-2b induced K562 cytotoxicity. Trypan blue dye exclusion test and MTT assay were utilised for determining cytotoxicity. IC(50) of IFN-alpha-2b on K562 cells was found to be 600IU/ml. However, no differentiation was determined by analysis of cell surface antigen expressions. Serine/threonine protein phosphatase inhibitors calyculin A (Cal A) and okadaic acid (OKA) augmented the IFN-alpha-2b induced cytotoxicity. Apoptosis assay by the mono-oligonucleosome detection and acridine orange/propidium iodide dye revealed marked apoptosis underlying cytotoxicity. Phosphatase enzyme assay revealed a gradual increase in protein phosphatase 2A (PP2A) activity during interferon induced cytotoxicity. Conversely, immunoblots showed no change in the expression of PP2A catalytic and regulatory subunits. In conclusion, PP2A plays a role in IFN-alpha-2b induced apoptosis of K562 cells and should be investigated as a new window furthermore.
  Leukemia Research 09/2003; 27(8):709-17. · 2.92 Impact Factor
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  Available from: Ozlem Kucukoglu

  Article: Cytotoxic and inhibitory effects of 4,4'-dihydroxy chalcone (RVC-588) on proliferation of human leukemic HL-60 cells.

  Guray Saydam, H Hakan Aydin, Fahri Sahin, Ozlem Kucukoglu, Ercin Erciyas, Ender Terzioglu, Filiz Buyukkececi, Serdar Bedii Omay
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  ABSTRACT: Chalcones have been identified as interesting compounds with cytotoxic and tumor reducing properties. In the present study, the biological activity of synthetic chalcones on myeloid leukemic cells was investigated. Human myeloid HL-60 leukemia cells were exposed to 1-20 micro M chemicals for 0-96h. The viability of the cells was measured using trypan blue dye exclusion method. 4,4'-Dihydroxy chalcone (RVC-588) was selected for further experiments to determine characteristics of cytotoxicity among other compounds. The data show that cell viability decreased after treatment and IC(50) value was approximately 2 micro M for RVC-588. Cell differentiation was analyzed with cytofluorometry by changes in expression of glicoprotein surface markers CD11b/Mac-1, CD11c and CD14 together with morphological analysis. A maximum level of expression changes was determined at 72h but these changes were not statistically significant to show the differentiation of HL-60 cells to mature myeloid and/or monocytoid cells. Apoptotic DNA degradation was evaluated and quantitated using sensitive enzyme-linked immunoabsorbant (ELISA) method. Using this technique, a maximum level of apoptosis 1.2-fold higher than control was observed in cultures exposed for 48h to 2 micro M RVC-588. The DNA ladder assay was subsequently used to determine DNA breaks qualitatively. After 24h, the cells exposed to 2 micro M RVC-588 was shown to have cytotoxic-late apoptotic ladder pattern compared to control cells. These data demonstrate that RVC-588 has a high cytotoxic and antitumor activity in HL-60 cells among other chemicals we synthesized. Although the mechanism by which RVC-588 initiated cell death in these cells is presently not known and apoptotic mechanisms are likely to play less role compared to other chalcone analogues reported previously.
  Leukemia Research 02/2003; 27(1):57-64. · 2.92 Impact Factor
• Article: Arsenic trioxide and methylprednisolone use different signal transduction pathways in leukemic differentiation.

  Safak Yuksel, Guray Saydam, Ruchan Uslu, Ulus Ali Sanli, Ender Terzioglu, Filiz Buyukececi, Serdar Bedii Omay
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  ABSTRACT: Certain cell lines like HL 60 and K 562 are utilised as leukemic cell models for leukemogenesis research, which differentiate along the granulocytic and/or monocytic pathway when treated with certain inducer molecules. High dose methylprednisolone treatment has been shown to induce in vivo and in vitro differentiation of myeloid leukemia cells to mature granulocytes in patients with acute promyelocytic leukemia (APL) and other subtypes of acute myeloid leukemia (AML). Arsenic trioxide (As(2)O(3)) has been confirmed to have remission induction effects on APL. However, there are conflicting results on the effects with other AML subtypes. Also, it has been well established that the reversible phosphorylation of proteins is a major regulatory mechanism in the signal transduction pathways that control cell growth and differentiation. Serine/threonine protein phosphatases (PP) are major components of phosphorylation. In this study, we investigated the effect of As(2)O(3) on HL 60 and K 562 myeloid leukemic differentiation and compared the signalling cascades of the two inducers with respect to serine/threonine PP 1 and 2A. We utilised PP1 and PP2A inhibitors okadaic acid and calyculin A. In contrast to methylprednisolone, there was no effect of phosphatase inhibitors on As(2)O(3)-induced leukemic differentiation. Incomplete leukemic differentiation occurred with lower As(2)O(3) concentration as 10(-6)M. Unlike As(2)O(3), methylprednisolone induced complete granulocytic and/or monocytic differentiation of HL 60 and K 562 cells via upregulation of PP2A regulatory subunits. Therefore, As(2)O(3) and methylprednisolone are promising agents that have the potential to be used together in myeloid leukemic differentiation therapy.
  Leukemia Research 05/2002; 26(4):391-8. · 2.92 Impact Factor
• Article: The systemic cellular immune response in the Helicobacter pylori-associated duodenal ulcer and chronic antral gastritis.

  Hakan Yuceyar, Murat Saruc, Ali Kokuludag, Ender Terzioglu, Gamze Goksel, Aydin Isisag
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  ABSTRACT: The exact pathogenesis of Helicobacter pylori infection is not fully understood. This study aims to evaluate the specific subset composition of peripheral blood lymphocytes in patients with H. pylori-positive duodenal ulcer n = 14), chronic antral gastritis n = 28), since reports so far have led to inconclusive and conflicting results. 42 patients with dyspepsia and 50 controls underwent the following procedures: 1) gastroscopy and gastric biopsy (five specimens) 2) histology, 3) serologic test for anti-H. pylori antibodies IgG (Pyloriset EIA-G, Orion Diagnostica) and anticytotoxin associated gene A (cag A) IgG antibodies (VIVA Diagnositika by ELISA), 4) analysis of the peripheral blood lymphocytes using monoclonal antibodies reacting with lymphocyte cell surface antigens (anti-CD3, anti-CD19, anti-CD4, anti-CD8, anti-CD16 + CD56, anti-HLA DR) by flow-cytometry (Becton-Dickinson) to detect possible changes in the lymphocytes subpopulations in patients with duodenal ulcer and chronic antral gastritis. We found no alteration in total T and B lymphocytes and CD4+ T, CD8+ T lymphocytes and natural killer cells of both duodenal ulcer and chronic antral gastritis patients compared to normal persons. Although there was a slight increase in the proportion of active T lymphocytes in duodenal ulcer and chronic antral gastritis groups comparing to healthy subjects the difference was not statistically significant. These data indicate that there is no systemic alteration in the specific immune system in response to H. pylori in patients with duodenal ulcer and chronic antral gastritis.
  Hepato-gastroenterology 49(46):1177-9. · 0.66 Impact Factor
• Article: Serum transforming growth factor-beta1(TGF-beta1) in patients with cirrhosis, chronic hepatitis B and chronic hepatitis C [corrected].

  Cengiz Kirmaz, Ender Terzioglu, Omer Topalak, Papatya Bayrak, Ozge Yilmaz, Galip Ersoz, Filiz Sebik
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  ABSTRACT: Chronic liver disease and cirrhosis are two of the most important health problems according to current gastroenterology literature. Based on the recent developments in the field of immunology, advanced follow-up and treatment modalities have been introduced for these disorders. Immune defence against viral infections depends on effective cellular immune responses derived mainly from Th1-related cytokines. Th2 type immune responses can inhibit efficient immune function by secretion of several cytokines such as IL-10, TGF-beta1. In this particular study, we determined the serum levels of TGF-beta1, which plays a role in immune suppression and induction of tissue fibrosis. We evaluated the role of TGF-beta1 in the pathogenesis of chronic liver disease and cirrhosis. Fourteen chronic hepatitis B (CHB), 12 chronic hepatitis C (CHC) patients and 21 cirrhotic patients were enrolled in the study. The control group consisted of ten healthy people. Serum TGF-beta1 levels were higher in both cirrhosis and CHC group when compared to those in CHB and control groups (P < 0.05). Although serum TGF-beta1 levels in the cirrhosis group were higher than that in the CHC group, the difference was not statistically significant. In conclusion, elevated TGF-beta1 levels in patients with CHC and cirrhosis may have a role in the pathogenesis and chronicity of these diseases.
  European cytokine network 15(2):112-6. · 1.73 Impact Factor