Browsing by Author "Degirmenci, M"
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Item Factors Affecting QT Dispersion During Hemodialysis in End-Stage Renal Disease PatientsAlici, T; Tekçe, H; Degirmenci, M; Özgür, B; Kürsat, SAim: To investigate the situation of the cardiac arrhythmia in the cases within the chronic haemodialysis program and its pathogenesis. Materials and Method: Sixty-four patients who admitted to the department of nephrology in our hospital with chronic renal failure requiring haemodialysis were taken into our study. In order to determine and asses the QT dispersion before and after haemodialysis, conventional ECG records with 12 derivations were taken. Results: Pre-haemodialysis QT and QTc dispersion were calculated as 49.6 +/- 24 msn and 57 +/- 29 msn; post-haemodialysis QT and QTc dispersion were calculated as 75 +/- 33 msn and 93 +/- 38 msn, reflecting significant changes (p<0.001). Of the electrolyte values taken before and after haemodialysis, K+ was shown to have a significant change (p<0.001). Positive correlation was observed between the decrease in K+ and the increase in QT dispersion (p<0.05). Negative correlation was observed between the QT dispersion increase and the amount of ultrafiltration (p<0.05). Discussion: QT and QTc dispersion increases were affected by the decrease in K+ value and the amount of ultrafiltration that occurred during haemodialysis. This indicates that the gradual reduction in K+ and optimization of ultrafiltration levels will increase the threshold of arrhythmia being one of the causes of cardiac mortality.Item Combined gossypol and zoledronic acid treatment results in synergistic induction of cell death and regulates angiogenic molecules in ovarian cancer cellsAtmaca, H; Gorumlu, G; Karaca, B; Degirmenci, M; Tunali, D; Cirak, Y; Purcu, DU; Uzunoglu, S; Karabulut, B; Sanli, UA; Uslu, RIn the present study, we aimed to evaluate the possible synergistic, cytotoxic effects of combination treatment of gossypol and zoledronic acid, in human ovarian cancer cell lines, OVCAR-3 and MDAH-2774, and to elucidate the role of this novel combination treatment on angiogenesis-related molecules in ovarian cancer. The XTT cell viability assay was used for showing cytotoxicity. Both DNA fragmentation by ELISA assay and caspase 3/7 activity measurement were used for demonstrating apoptosis. To elucidate the angiogenic molecules affected by combination treatment, mRNA levels of angiogenic molecules were measured using the Human Angiogenesis RT2 Profiler (TM) PCR Array (SuperArray, Frederick, MD) in ovarian cancer cell lines, OVCAR-3 and MDAH-2774. The combined treatment resulted in significant, synergistic cytotoxicity, and induced apoptosis. This effect was observed to happen in a dose- and time-dependent manner. Moreover, the combination treatment of 10 mu M gossypol and 5 mu M zoledronic acid resulted in significant down-regulation (>= thee-fold) in mRNA levels of some pivotal angiogenic molecules in OVCAR-3 and MDAH-2774 cells as compared to the untreated control. However, this effect was different in the two ovarian cancer cell lines observed. Gossypol, in combination with zoledronic acid, may provide a rational treatment option for ovarian cancer, not only by direct inhibition of cell proliferation, but also inhibition of angiogenesis-related molecules.Item In-vitro Evaluation of Effects of Mesenchymal Stem Cells on TLR3, TLR7/8 and TLR9-activated Natural Killer CellsOzdemir, AT; Kirmaz, C; Ozdemir, RBO; Degirmenci, P; Oztatlici, M; Degirmenci, MObjectives: In this study, it was aimed to investigate the immunomodulatory effects of Mesenchymal stem cells (MSCs) on Natural Killer (NK) cells activated by Toll-like receptor (TLR) agonists. Methods: MDA-MB-231, MCF-7 and NK-92 cells were induced with TLR3, TLR7/8 and TLR9 agonists and co-cultured with MSCs. Alterations in IFN-gamma, TNF-alpha, Granzyme-b and Perforin expressions were determined by qPCR method, CD69 and CD107a expressions were determined by flow cytometry, and cytotoxicity was determined by MTT-assay. Results: All TLR agonists significantly increased the expressions of the IFN-gamma, TNF-alpha, Granzyme-b, Perforin, CD69 and CD107a in-vitro. We determined that the cytokine, cytotoxic molecules, and activation markers of NK-92 cells interacting with breast tumor cells significantly increased by TLR3 and TLR9 agonists. However, suppression rather than activation occurred on the NK-92 cells due to the simultaneous induction of the immunosuppressive effects of MSCs by these agonists. On the other hand, the TLR7/8 agonists provided a low NK-92 induction, however, the inhibitory effects of MSCs were not triggered. Therefore, it provided a more significant activation than TLR3 and TLR9 agonists. Conclusion: Our findings suggested that TLR7/8 agonists may be a better choice to induce antitumor effects of NK cells in a tumor tissue rich in MSCs.Item Allergic rhinitis and its relationship with autoimmune thyroid diseasesDegirmenci, PB; Kirmaz, C; Oz, D; Bilgir, F; Ozmen, B; Degirmenci, M; Colak, H; Yilmaz, H; Ozyurt, BBackground: Autoimmune thyroid diseases are the most common of all autoimmune diseases. In the literature, Hashimoto thyroiditis (HT) is considered to be a T-helper (Th) type 1 dominant condition, and Graves disease is considered a Th2-dominant condition. Objective: The aim of this study was to highlight a new aspect of the relationships among Th cell subgroups by determining the incidence of autoimmune thyroid disease in patients with allergic rhinitis (AR). Methods: Patients were diagnosed with AR based on their medical histories, physical examinations, and skin-prick test results in an outpatient clinic. The levels of free triiodothyronine, free thyroxine, thyroid-stimulating hormone, thyroid peroxidase antibodies, and thyroglobulin antibodies were measured in peripheral blood samples from all study subjects. Results: A total of 1239 patients with AR and 700 consecutive, age- and sex-matched healthy subjects were included in the study. Thyroid function tests showed that 1037 patients with AR (83.7%) had normal thyroid function, 171 (13.8%) had euthyroid HT, and 31 (2.5%) had hypothyroid HT. Among the control subjects, thyroid function test results showed that 688 subjects (98.2%) had normal thyroid function, 10 subjects (1.4%) had euthyroid HT, and 2 subjects(0.4%) had hypothyroid HT. Conclusion: The incidence of HT in the general population is 1.5%; in contrast, it was observed in 16.3% of our patients with AR, which represented a much higher rate than that in the overall population. Graves disease was not detected in our study subjects. A high incidence of HT in patients with AR, in which Th2 responses are dominant, indicates that further studies of the relationships among atopy, autoimmune diseases, and Th cell subgroups are needed.Item Cyclic lymphocytic vasculitis associated with chronic lymphocytic leukemiaÇabuk, M; Inanir, I; Türkdogan, P; Ceylan, C; Degirmenci, M; Türel, A; Özdemir, ELymphocytic cutaneous vasculitis associated with a haematological malignancy has rarely been reported. Here, we describe a 61 year-old woman with chronic lymphocytic leukemia (CLL) who presented with cutaneous lesions on both hands. These lesions improved after all combination chemotherapy courses and recurred before each course. Repetitive skin biopsies revealed lymphocytic vasculitis. After 7 courses of chemotherapy, she had a complete remission. Skin lesions disappeared and did not recur. The cyclic pattern of lymphocytic vasculitis and its relation with CLL disease activity are interesting clinical features in this case.Item Zoledronic acid increases cytotoxicity by inducing apoptosis in hormone and docetaxel-resistant prostate cancer cell linesVarol, U; Degirmenci, M; Karaca, B; Atmaca, H; Kisim, A; Uzunoglu, S; Sezgin, C; Sanli, UA; Uslu, ROur aim was to investigate the possible synergistic/additive cytotoxic and apoptotic effects of combination of docetaxel and zoledronic acid (ZA), in PC-3 hormone-refractory prostate cancer cells (HRPC), as well as their docetaxel-resistant sublines. We established a docetaxel-resistant cell line (PC-3R) from PC-3 prostate cancer cells, by intermittent exposure to increasing concentrations of docetaxel in vitro. We then examined the effect of ZA and docetaxel on cell proliferation in both PC-3 and PC-3R prostate cancer cells. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 enzyme activity were measured to verify apoptosis. According to our results, docetaxel and ZA were found to be synergistically cytotoxic and apoptotic in both PC-3 and docetaxel-resistant PC-3R cells, in a dose- and time-dependent manner. Combined treatment with docetaxel and ZA synergistically inhibited PC-3 cell growth in vitro through an enhanced induction of cell death, compared with either agent alone; this result was also evident on PC-3R cells. Moreover, we have also demonstrated that apoptosis was induced in prostate cancer cells exposed to these drugs by a concentration-dependent increase in DNA fragmentation and caspase 3/7 enzyme activity. We concluded that ZA, either with docetaxel or not, might still exert some cytotoxicity even in docetaxel-resistant cells. From the clinical perspective, when the clinician decided to change the treatment in the post-docetaxel setting, continuing or combination with ZA may be an effective therapeutic approach for the treatment of HRPC patients.Item Docetaxel in combination with octreotide shows synergistic apoptotic effect by increasing SSTR2 and SSTR5 expression levels in prostate and breast cancer cell linesKaraca, B; Degirmenci, M; Ozveren, A; Atmaca, H; Bozkurt, E; Karabulut, B; Sanli, UA; Uslu, RDocetaxel (DTX) is widely used for the treatment of metastatic prostate and breast cancers. Despite the clinical success of DTX, drug-related cumulative toxicity restricts its clinical use in cancer therapy. Thus, there is an urgent need for new therapeutic options. Octreotide (OCT) is a synthetic somatostatin analog that induces apoptosis in different cancer cell lines in vitro. In this study, we investigated the possible synergistic apoptotic effects of DTX in combination with OCT in prostate and breast cancer cell lines. The XTT cell viability assay was used to determine cytotoxicity. Apoptosis was evaluated by Cell Death Detection ELISA(Plus) Kit. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. Levels of SSTR2 and SSTR5 proteins were determined by western blot analysis. DTX and OCT combination induced apoptosis in both breast and prostate cancer cells in a concentration- and time-dependent manner. Moreover, combination treatment resulted in inhibition of anti-apoptotic proteins such as Bcl-2 and Bcl-xL and induction of pro-apoptotic proteins Bax, Cytochrome c and IAPs in all of the tested cancer cell lines. SSTR2 and SSTR5 protein levels were induced as compared to any agent alone. These results indicate that this combination treatment is a significant inducer of apoptosis in a synergistic manner in breast and prostate cancer cells. This strong synergism helps to lower the dose of DTX in both types of cancers, thus letting DTX to be used for longer periods by delaying resistance development and lesser side effects.Item Octreotide in combination with AT-101 induces cytotoxicity and apoptosis through up-regulation of somatostatin receptors 2 and 5 in DU-145 prostate cancer cellsDegirmenci, M; Erdogan, AP; Bulut, G; Atmaca, H; Uzunoglu, S; Karaca, B; Karabulut, B; Uslu, RProstate cancer (PCa) is the most common type of cancer among males. Although survival rate of early-stage PCa is high, treatment options are very limited for recurrent disease. In this study, the possible synergistic cytotoxic and apoptotic effect of octreotide in combination with AT-101 was investigated in DU-145 hormone and drug refractory prostate cancer cell line. To enlighten the action mechanisms of the combination treatment, expression levels of somatostatin receptors 2 and 5 (SSTR2 and SSTR5) were also investigated. Cell viability was measured by XTT assay. Apoptosis was assessed through DNA fragmentation analysis and caspase 3/7 assay. mRNA and protein levels of SSTR2 and SSTR5 were evaluated by qRT-PCR and western blot analysis, respectively. Octreotide in combination with AT-101 inhibited cell viability and induced apoptosis synergistically in DU-145 cells as compared to any agent alone. Combination treatment increased both SSTR2 and SSTR5 mRNA and protein levels in DU-145 cells. The data suggest that this combination therapy may be a good candidate for patients with advanced metastatic PCa do not respond to androgen deprivation.Item Investigating the Correlation Between Long-Term Response in Patients with Metastatic HER2+Breast Cancer and the Activity of Regulatory T Cells: A Retrospective StudyDegirmenci, M; Diniz, G; Kahraman, DS; Sahbazlar, M; Koral, L; Varol, U; Uslu, RBackground: Trastuzumab is commonly utilized in the management of metastatic HER2-positive breast cancer. Our main goal was to examine the clinical outcomes and immune markers of patients who received trastuzumab and chemotherapy treatment. Methods: Between 1995 and 2012, a total of 98 patients diagnosed with metastatic HER2-positive breast cancer were retrospectively analyzed at Ege University Hospital and Tepecik Training and Research Hospital. The clinicopathological characteristics and clinical outcomes of the patients were assessed, and the associations between response rates, survival and the immune profiles of tumor infiltrating lymphocytes were statistically evaluated. Results: The average age of patients at the time of diagnosis was 50.1 +/- 10.3 (ranging from 30 to 79) years. The mean follow-up period for all patients was 97.9 +/- 53.8 months. Among the patients, complete response was observed in 24.5%, partial response in 61.2%, and stable disease in 8.2% of cases. The average progression-free survival was 50.3 +/- 26.9 months (ranging from 1 to 163 months), and the average overall survival was 88.8 +/- 59.4 months (ranging from 12 to 272 months). After analyzing all cases, it was found that patients who were younger (p=0.006), exhibited higher CD3-positivity (p=0.041), presented with higher FOXP3-positivity (p=0.025), showed complete or at least partial response to treatment (p=0.008), and experienced a long-term response to trastuzumab (and chemotherapy) treatment had longer survival (p=0.001). Conclusion: Patients with HER2-positive breast cancer, who initially respond positively to palliative trastuzumab and chemotherapy treatment, can achieve long-term tumor remission lasting for several years.Item Programmed cell death ligand-1 expression in gastroentero-pancreatic neuroendocrine tumorsOktay, E; Yalcin, GD; Ekmekci, S; Kahraman, DS; Yalcin, A; Degirmenci, M; Dirican, A; Altin, Z; Ozdemir, O; Surmeli, Z; Diniz, G; Ayhan, S; Bulut, G; Erdogan, A; Uslu, RPurpose: Gastroenteropancreatic tumors (GEPNETs) is a heterogeneous disease with variable clinical course. While promising therapeutic options exist for other adult cancers, there are no new molecular-based treatments developed for GEPNETs. One of the main targets of cancer immunotherapy is the Programmed Cell Death Ligand-1 (PD-L1) pathway. Our purpose was to investigate the profile of PD-L1 expression in different organs of GEPNETs and compare the conventional immunohistochemistry (IHC) with the RNA expression analysis via real time polymerase chain reaction (RT-PCR) in order to determine which patients might be appropriate for immune check point-targeted therapy. Methods: A total of 59 surgically or endoscopically resected GEPNET tissues were retrospectively collected. The expression of PD-LI and mRNA was evaluated with IHC. Results: The expression of PD-L1 was significantly associated with the high-grade classification (p=0.012). PD-LI mRNA expression in tumor samples appeared to be higher compared to the corresponding normal tissues. In appendix, stomach and small intestine, the expression of PD-L1 mRNA was higher in the tumor tissues compared to the respective controls. In pancreas and colon, control tissues tend to have a higher PD-L1 mRNA expression compared to tumor tissues. PD-L1 mRNA expression was higher in GEP carcinomas (p=0.0031). Conclusion: RT-PCR was found to be more sensitive in detecting PD-L1 expression than conventional IHC. This study may provide an important starting point and useful background information for future research about immunotherapy for appendix, stomach and small intestine neuroendocrine carcinomas.