Browsing by Author "Koc, Dogukan"

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Citation - WoS: 9
Citation - Scopus: 12
Brain-Derived Neurotrophic Factor in Bipolar Disorder: Associations With Age at Onset and Illness Duration
(Pergamon-Elsevier Science Ltd, 2021) Baykara, Burak; Koc, Dogukan; Resmi, Halil; Akan, Pinar; Tunca, Zeliha; Ozerdem, Aysegul; Ceylan, Deniz
Bipolar disorder (BD) is a heterogeneous disorder that contains neurodevelopmental differences. Defining homogeneous subgroups of BD patients by using age at onset (AAO) as a specifier may promote the classification of biomarkers. This study compares peripheral BDNF levels between pediatric and adult BD patients to investigate the associations between BDNF levels, AAO, and illness duration. We enrolled two groups of euthymic patients, those with pediatric BD (n = 39) and those with adult BD (n = 31), as well as a group of healthy controls (HCs) (n = 90). Participants were assessed using clinical measures and BDNF serum levels were obtained using ELISA. We observed that BDNF levels were comparable between adult BD and HCs, but were clearly lower in pediatric BD than in HCs. In adult BD with AAO ?30 years, BDNF levels were significantly higher than in adult BD with AAO <30 years. In pediatric BD, patients with prepubertal-onset had higher BDNF levels than those with pubertalonset. BDNF levels demonstrated the accuracy of being able to distinguish pediatric BD from healthy controls in a receiver operating characteristic (ROC) curve analysis (area under the curve [AUC] = 0.792). In adult BD, higher BDNF levels were associated with later disease onset, but this was not the case in pediatric BD. Finally, reduced BDNF levels were associated with illness duration in adult BD. The findings indicate that BDNF levels in BD patients are associated with AAO. BDNF may, therefore, potentially serve as a developmental marker in BD, when AAO is taken into account.
Citation - WoS: 14
Citation - Scopus: 14
Effect of Adipocyte-Secreted Factors on Epcam+/Cd133+hepatic Stem Cell Population
(Academic Press Inc Elsevier Science, 2016) Karagonlar, Zeynep Firtina; Koc, Dogukan; Sahin, Eren; Avci, Sanem Tercan; Yilmaz, Mustafa; Atabey, Nese; Erdal, Esra
Recent epidemiological studies have associated obesity with a variety of cancer types including HCC. However, the tumor initiating role of obesity in hepatocarcinogenesis is still unknown. The objective of this paper is to investigate the effect of adipocyte-secreted factors on EpCAM+/CD133+ cancer stern cells and to identify which factors play a role in modulating hepatic cancer stem cell behavior. Our results demonstrated that adipocyte-secreted factors affect motility and drug resistance of EpCAM+/CD133+ cells. When incubated with adipocyte conditioned media, EpCAM-F/CD133+ cells exhibited augmented motility and reduced sorafenib-induced apoptosis. Using array-based system, we identified secretion of several cytokines such as IL6, IL8 and MCP1 by cultured adipocytes and activation of c-Met, STAT3 and ERK1/2 signaling pathways in EpCAM-F/CD133+ cells incubated with adipocyte conditioned media. Treating EpCAM+/CD133+ cancer stem cells with IL6 receptor blocking antibody or c-Met inhibitor SU11274 both reduced the increase in motility; however SU11274 had greater effect on relieving protection from sorafenib-induced apoptosis. These results indicate that adipocyte-secreted factors might regulate cancer stem cell behavior through several signaling molecules including c-Met, STAT3 and ERK1/2 and inhibition of these signaling pathways offer novel strategies in targeting the effect of adipose derived cytokines in cancer. (C) 2016 Elsevier Inc. All rights reserved.
Citation - WoS: 78
Citation - Scopus: 109
Elevated Hepatocyte Growth Factor Expression as an Autocrine C-Met Activation Mechanism in Acquired Resistance To Sorafenib in Hepatocellular Carcinoma Cells
(Wiley, 2016) Karagonlar, Zeynep Firtina; Koc, Dogukan; Iscan, Evin; Erdal, Esra; Atabey, Nese
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the third leading cause of cancer-related deaths worldwide. Limitations in HCC treatment result due to poor prognosis and resistance against traditional radiotherapy and chemotherapies. The multikinase inhibitor sorafenib is the only FDA approved drug available for advanced HCC patients, and development of secondline treatment options for patients who cannot tolerate or develop resistance to sorafenib is an urgent medical need. In this study, we established sorafenib-resistant cells from Huh7 and Mahlavu cell lines by long-term sorafenib exposure. Sorafenib-resistant HCC cells acquired spindle-shape morphology, upregulated mesenchymal markers, and showed significant increase in both migration and invasion abilities compared to their parental counterparts. Moreover, after long-term sorafenib treatment, HCC cells showed induction of hepatocyte growth factor (HGF) synthesis and secretion along with increased levels of c-Met kinase and its active phosphorylated form, indicating autocrine activation of HGF/c-Met signaling. Importantly, the combined treatment of the resistant cells with c-Met kinase inhibitor SU11274 and HGF neutralizing antibody significantly reversed the increased invasion ability of the cells. The combined treatment also significantly augmented sorafenib-induced apoptosis, suggesting restoration of sorafenib sensitivity. These results describe, for the first time, compensatory upregulation of HGF synthesis leading to autocrine activation of HGF/c-Met signaling as a novel cellular strategy in the acquisition of sorafenib resistance. Therefore, we suggest that combinatorial therapeutic strategies with HGF and c-Met inhibitors comprise promising candidates for overcoming sorafenib resistance.
Peripheral Levels of Brain-Derived Neurotrophic Factor in Bipolar Disorder: Associations With Age at Onset and Illness Duration
(Wiley, 2020) Koc, Dogukan; Baykara, Burak; Tunca, Zeliha; Resmi, Halil; Ozerdem, Aysegul; Yalcin, Neslihan G.; Ceylan, Deniz
[Abstract Not Available]