Browsing by Subject "complementary DNA"
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Item Overcoming drug resistance in hormone-and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination(2010) Cengiz E.; Karaca B.; Kucukzeybek Y.; Gorumlu G.; Gul M.K.; Erten C.; Atmaca H.; Uzunoglu S.; Karabulut B.; Sanli U.A.; Uslu R.Drug resistance is a significant challenge of daily oncology practice. Docetaxel and gossypol both have antitumoral activity in hormone-refractory prostate cancer (HRPC). Our results revealed that docetaxel and gossypol were synergistically cytotoxic and apoptotic in PC-3 cells in a dose-and time-dependent manner. We further investigated the expression profiles of genes involved in drug resistance and metabolism with a Human Cancer Drug Resistance and Metabolism PCR Array® (SuperArray). Six of the 84 genes that are known to regulate drug resistance, metabolism, cell cycle, DNA repair and oncogenesis were downregulated C3-fold change by the combination treatment. These results may be important in devising mechanism-based and targeted therapeutic strategies for prostate cancer, especially in devising combination therapy for drug resistant prostate cancers. © Springer Science+Business Media B.V. 2009.Item Expression profiling of stem cell signaling alters with spheroid formation in CD133high/CD44high prostate cancer stem cells(Spandidos Publications, 2014) Oktem G.; Bilir A.; Uslu R.; Inan S.V.; Demiray S.B.; Atmaca H.; Ayla S.; Sercan O.; Uysal A.Cancer stem cells (CSC) isolated from multiple tumor types differentiate in vivo and in vitro when cultured in serum; however, the factors responsible for their differentiation have not yet been identified. The first aim of the present study was to identify CD133high/CD44high DU145 prostate CSCs and compare their profiles with non-CSCs as bulk counterparts of the population. Subsequently, the two populations continued to be three-dimensional multicellular spheroids. Differentiation was then investigated with stem cell-related genomic characteristics. Polymerase chain reaction array analyses of cell cycle regulation, embryonic and mesenchymal cell lineage-related markers, and telomerase reverse transcriptase (TERT) and Notch signaling were performed. Immunohistochemistry of CD117, Notch1, Jagged1, Delta1, Sox2, c-Myc, Oct4, KLF4, CD90 and SSEA1 were determined in CSC and non-CSC monolayer and spheroid subcultures. Significant gene alterations were observed in the CD133high/CD44high population when cultured as a monolayer and continued as spheroid. In this group, marked gene upregulation was determined in collagen type 9 α1, Islet1 and cyclin D2. Jagged1, Delta-like 3 and Notch1 were respectively upregulated genes in the Notch signaling pathway. According to immunoreactivity, the staining density of Jagged1, Sox2, Oct4 and Klf-4 increased significantly in CSC spheroids. Isolated CSCs alter their cellular characterization over the course of time and exhibit a differentiation profile while maintaining their former surface antigens at a level of transcription or translation. The current study suggested that this differentiation process may be a mechanism responsible for the malignant process and tumor growth.Item Programmed cell death ligand-1 expression in gastroenteropancreatic neuroendocrine tumors(Zerbinis Publications, 2019) Oktay E.; Yalcin G.D.; Ekmekci S.; Kahraman D.S.; Yalcin A.; Degirmenci M.; Dirican A.; Altin Z.; Ozdemir O.; Surmeli Z.; Diniz G.; Ayhan S.; Bulut G.; Erdogan A.; Uslu R.Purpose: 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-L1 and mRNA was evaluated with IHC. Results: The expression of PD-L1 was significantly associated with the high-grade classification (p=0.012). PD-L1 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. © 2019 Zerbinis Publications. All rights reserved.Item Evaluation of serum MicroRNA expression profiles in patients with panic disorder(Taylor and Francis Ltd., 2019) Çökmüş F.P.; Özmen E.; Alkin T.; Batir M.B.; Çam F.S.BACKGROUND: Studies on the role of microRNAs (miRNA) in anxiety disorders are limited. We aimed to determine the availability of miRNAs as biomarkers in serum and to demonstrate the changes of miRNAs expression in patients with panic disorder (PD). METHODS: Thirty-five patients with PD and 35 healthy controls (HC) were evaluated with Structured Clinical Interview for DSM Disorders-I (SCID-I) and Panic Disorder Severity Scale (PDSS). In each group miRNA expression analysis was performed in venous blood by the Real-time Polymerase Chain Reaction (RT–PCR) method for genetic evaluation. RESULTS: Compared with the HC group, eight miRNA expression levels were found different in the PD group. Five of them were upregulated and three of them were downregulated. There was no correlation between the levels of miRNA expression with PDSS total score and PDSS sub-items. However, miR-1297 and miR-4465 expression levels were significantly different between the two groups. LIMITATIONS: There are some limitations in this research. Firstly the number of samples is small. Another limitation of our study is that the presence of medical illness and continuous drug use were not excluded when PD and HC groups were selected. CONCLUSIONS: Our research is the first miRNA expression study in patients with PD which excluded psychotropic use and additional psychiatric disorders. In the PD group, miR-1297 and miR-4465 expression was upregulated than compared to the HC group. miR-1297 and miR-4465 regulate the GABAA gene regions that affect GABA A receptor subtypes that thought to play a role in the aetiology of PD. © 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Item TRP Channels in Tension-Type Headache: A Pilot Study; [Gerilim Tipi Baş Ağrısında TRP Kanalları: Pilot Çalışma](Turkish Neurosurgical Society, 2021) Gemici Y.İ.; Taşcı İ.; Durmuş K.; Koç A.Tension-type headache (TTH) affects many individuals worldwide. Although the exact pathogenesis of TTH remains unclear, central, and peripheral mechanisms are considered to play a role in TTH 1. This pilot study aimed to investigate the role of transient receptor potential (TRP) channels in the development or chronic inflammation in TTH and to discuss the findings in the light of literature. This pilot study included a patient group comprising three patients with episodic TTH and three patients with chronic TTH (CTTH) aged 18-40 years with no comorbidities and a control group of three patients with no headache. Peripheral blood samples were obtained from all the participants, and both RNA and cDNA were isolated on the same day. The mRNA levels of pain-related TRP channels [TRPA1, TRP vanilloid-1 (TRPV1), TRPV3, TRPV4, TRPM3, and TRPM8] were measured by reverse transcriptase (RT)-quantititave polymerase chain reaction method and were normalized with the levels of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) transcript. Results were analyzed using statistical methods. All three groups were comparable with regard to demographic characteristics. No significant difference was found among the groups with regard to the mRNA levels of the TRP channels normalized by GAPDH, whereas the TRPM8 expression levels were not significantly lower in the CTTH group than in other groups (p=0.066). This study revealed that TRPM8 is likely to have a role in the pathogenesis of TTH, and this role of TRPM8 may be investigated by further studies. © 2021 by Turkish Neurological Society Turkish Journal of Neurology published by Galenos Publishing House.Item Cyclophosphamide suppresses spermatogenesis in the testis of mice through downregulation of miR-34b and miR-34c(John Wiley and Sons Inc, 2021) Özbilgin M.K.; Demirören S.; Üçöz M.; Oztatlici M.Cyclophosphamide (CP) is commonly used as an anticancer agent but has been associated with high toxicity in several organs, including the testes. In this study, we aimed to evaluate the effects of CP-induced testicular toxicity, using glial cell line-derived neurotrophic factor (GDNF), occludin and transforming growth factor beta 3 (TGF-β3) primary antibodies, and miR-34b and miR-34c expressions. Eighteen young Balb/c male mice were divided into three groups. The control group received no treatment. The mice of CP group were injected 100 mg kg-1 day-1 CP for 5 days, and the same amount of saline was injected in the sham group. The animals were sacrificed 24 hr after the last injection. Immunohistochemical analysis of testicular tissues showed a decrease in both spermatogenic germ cell count and also GDNF, occludin expressions, but an increase in TGF-β3 expression in the CP group compared to the others group. The expressions of miR-34b and miR-34c were examined by qPCR technique, a significant decrease was observed in tissue samples in the CP-treated group. The expression of GDNF, occludin and TGF-β3 plays an important role in testicular injury caused by CP, and the decrease in the expression of miR-34b/c in tissue samples may be an important marker for the detection of testicular damage. © 2021 Wiley-VCH GmbHItem Newly Synthesized Benzimidazoles Inhibit Vascular Endothelial Growth Factor and Matrix Metalloproteinase-2 and-9 Levels in Prostate Cancer Cells(Bentham Science Publishers, 2022) Ilhan S.; Dilekci G.; Guner A.; Bektas H.Background: Investigating the effects of newly synthesized agents on various molecular mechanisms to understand their mechanism of action is an important step of pre-clinical screening. Benzimidazoles are composed of a unique fused benzene and imidazole ring and have attracted great attention due to their broad bioactivities, including antitumor. Objective: In the current study, we reported the synthesis of novel benzimidazole derivatives and investigated the pos-sible cytotoxic and anti-angiogenic effects on human prostate cancer and umbilical vein endothelial cells (HUVECs). Methods: MTT assay was used to assess cell viability. A scratch assay was conducted to monitor the migration of cells. mRNA expression levels of VEGF, MMP-2, and MMP-9 were evaluated using qPCR. Changes in protein levels were evaluated by western blotting. Results: Compound G1, having a chlorine moiety, showed a potent cytotoxic activity on both prostate cancer cells and HUVECs, and inhibited cell migration via decreasing the mRNA and protein levels of key angiogenesis-related molecules such as VEGF, MMP-2, and MMP-9. Conclusion: These results suggest that newly synthesized G1 may be a novel anti-angiogenic agent for prostate cancer treatment. © 2022 Bentham Science Publishers.