Browsing by Author "Karatas, Omer F."

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Differential Expression of Stem Cell Markers and ABCG2 in Recurrent Prostate Cancer
(Wiley-Blackwell, 2014) Guzel, Esra; Karatas, Omer F.; Duz, Mehmet B.; Solak, Mustafa; Ittmann, Michael; Ozen, Mustafa
BACKGROUND. Prostate cancer (PCa) is the second most common tumor type related to mortality in males in the developed countries. Studies have demonstrated that therapeutic tools mostly ineffective to give positive outcome especially for PCa. Cancer stem cells are composed of a small cell population, which are supposed to have roles in tumorigenesis, metastasis, and tumor recurrence after chemo-radiotherapy. The aim of this research is to investigate expressions of stem cell markers in recurrent PCa and non-recurrent PCa tumors as well as in adjacent normal prostate tissues. METHODS. We compared the expression of important sternness regulators like SOX2, OCT4, KLF4, and ABCG2 in recurrent, non-recurrent PCa and adjacent normal tissue samples using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS. Our results demonstrated that SOX2 and OCT4 are strongly overexpressed in PCa samples. Recurrent PCa samples are markedly positive for stem cell markers SOX2, OCT4, and KLF4. Furthermore, non-recurrent PCa samples presented low levels of ABCG2, a multidrug resistance protein, compared to both normal and recurrent samples, which might be associated with chemo-sensitivity. CONCLUSIONS. Enhanced expression of ABCG2 and stem cell markers including SOX2, OCT4, and KLF4 in the recurrent PCa tissues postulates the suggestion that enrichment for cells with stem cell characteristics in these tissues might be playing a critical role for chemoresistance and recurrence of cancer. (C) 2014 Wiley Periodicals, Inc.
Identification of miRNAs Differentially Expressed in Prostatic Secretions of Patients with Prostate Cancer
(Wiley, 2015) Guzel, Esra; Karatas, Omer F.; Semercioz, Atilla; Ekici, Sinan; Aykan, Serdar; Yentur, Serhat; Ozen, Mustafa
Prostate cancer (PCa) is one of the leading causes of cancer deaths in men. Since there are limited treatment options available for the advanced tumors, there is an urgent need for novel diagnostic tools for PCa. Prostate secretion samples (PSS) from 23 PCa and 25 benign prostate hyperplasia (BPH) patients were obtained from Urology Department of Bagcilar Educational and Research Hospital (Istanbul). MicroRNA (miRNA) profiling of eight PSS (four from BPH, four from PCa patients) was performed using microarray. Four of significantly deregulated miRNAs were further confirmed using quantitative reverse-transcription PCR (qRT-PCR). Statistical analysis was performed using Student's t-test. ROC curves were plotted with SPSS-15.0. In this study, we aimed to identify a miRNA expression signature that could be used to distinguish PCa from BPH. MiRNA profiling of four PCa and four BPH patients with microarray revealed that miR-361-3p, miR-133b and miR-221 were significantly downregulated and miR-203 was upregulated in PSS of PCa patients. Further qRT-PCR analysis confirmed the altered expressions of these four miRNAs in PSS of 23 PCa and 25 BPH patients. Four miRNAs, together and individually have much power (AUC; 0.950) than PSA has (AUC; 0.463) to discriminate PCa from BPH patients. We have shown for the first time in the literature the presence of miRNAs in the PSS. We suggest PSS as a powerful non-invasive source for evaluation of prognosis in PCa, since prostate massages can be easily applied during routine examination. Our results showed that certain differentially expressed miRNAs in PSS could be used as diagnostics markers. What's new? The association of microRNAs (miRNAs) with cancer initiation, progression, and metastasis has fueled increasing interest in their potential as diagnostic and therapeutic markers. The current study aimed to identify an miRNA expression signature that could be used to distinguish prostate cancer from benign prostatic hyperplasia by using prostate secretions obtained from patients. MiRNAs were found to be present in the prostate secretion samples, with altered expression detected for four miRNAs in particular. The findings suggest that certain miRNAs may be powerful tools for aiding prostate cancer diagnosis.
Micrornas as Prognostic Markers in Prostate Cancer
(Wiley, 2019) Suer, Ilknur; Guzel, Esra; Karatas, Omer F.; Creighton, Chad J.; Ittmann, Michael; Ozen, Mustafa
Background Prostate cancer (PCa) is the most commonly diagnosed malignancy in men who are especially over the age of 50 years in the western countries. Currently used therapeutic modalities mostly fail to give positive clinical outcomes and nearly 30% of the PCa patients eventually develop clinical recurrence. Therefore, understanding the underlying mechanisms of PCa progression is of paramount importance to help determining the course of disease. In this study, we aimed at profiling the differentially expressed microRNAs in recurrent PCa samples. Methods We profiled the microRNA expression of 20 recurrent and 20 non-recurrent PCa patients with microRNA microarray, and validated the differential expression of significantly deregulated microRNAs in 40 recurrent and 39 non-recurrent PCa specimens using quantitative reverse-transcription PCR (qRT-PCR). Data were statistically analyzed using two-sided Student's t-test, Pearson Correlation test, Receiver operating characteristic (ROC) analysis. Results Our results demonstrated that a total of 682 probes were significantly deregulated in recurrent versus non-recurrent PCa specimen comparison. Among those, we confirmed the significant downregulation of miR-424 and upregulation of miR-572 with further qRT-PCR analysis in a larger sample set. Further ROC analysis showed that these microRNAs have enough power to distinguish recurrent specimens from non-recurrent ones on their own. Conclusions Here, we report that differential expression of miR-424 and miR-572 in recurrent PCa specimens can serve as novel biomarkers for prediction of PCa progression.
Mode of Action of Carboplatin Via Activating P53/miR145 Axis in Head and Neck Cancers
(Wiley, 2020) Kilic, Ahsen; Barlak, Neslisah; Sanli, Fatma; Aytatli, Abdulmelik; Capik, Ozel; Karatas, Omer F.
Objectives In this study, we aimed at investigating the expressions of miR-145 and its well-characterized direct targets on carboplatin treatment. Study Design Laboratory study. Methods The effect of carboplatin and miR-145 on the proliferative capacity of head and neck squamous cell carcinoma cells was evaluated using Cell Viability Detection Kit-8. Expressions of miR-145 and its targets were evaluated using quantitative real-time polymerase chain reaction on carboplatin treatment and p53 inhibition. Western blot was used to measure the levels of p53 and its acetylated versions in cells treated with carboplatin and/or pifithrin-alpha. Results We demonstrated that carboplatin induced the expression of miR-145 in a dose-dependent manner and suppressed the expressions of miR-145 direct targets. In addition, we showed that inhibition of p53 by pifithrin-alpha in carboplatin-treated cells reduced miR-145 expression and reversed the suppression of miR-145 direct targets. Conclusions Considering all these findings together, one of the proposed mechanisms of carboplatin to kill cells might be the induction of miR-145 and deregulation of its targets in parallel, via p53 activation, which happens through carboplatin's DNA-damaging property. To the best of our knowledge, these findings are the first to reveal the relationship between carboplatin and miR-145 in cancer cells. Level of Evidence NA Laryngoscope, 2019
Novel POC1A Mutation in Primordial Dwarfism Reveals New Insights for Centriole Biogenesis
(Oxford Univ Press, 2015) Koparir, Asuman; Karatas, Omer F.; Yuceturk, Betul; Yuksel, Bayram; Bayrak, Ali O.; Gerdan, Omer F.; Ozen, Mustafa
POC1A encodes a WD repeat protein localizing to centrioles and spindle poles and is associated with short stature, onychodysplasia, facial dysmorphismand hypotrichosis (SOFT) syndrome. These main features are related to the defect in cell proliferation of chondrocytes in growth plate. In the current study, we aimed at identifying the molecular basis of two patients with primordial dwarfism (PD) in a single family through utilization of whole-exome sequencing. A novel homozygous p.T120A missense mutation was detected in POC1A in both patients, a known causative gene of SOFT syndrome, and confirmed using Sanger sequencing. To test the pathogenicity of the detected mutation, primary fibroblast cultures obtained from the patients and a control individual were used. For evaluating the global gene expression profile of cells carrying p.T120A mutation in POC1A, we performed the gene expression array and compared their expression profiles to those of control fibroblast cells. The gene expression array analysis showed that 4800 transcript probes were significantly deregulated in cells with p.T120A mutation in comparison to the control. GO term association results showed that deregulated genes are mostly involved in the extracellular matrix and cytoskeleton. Furthermore, the p.T120A missense mutation in POC1A caused the formation of abnormal mitotic spindle structure, including supernumerary centrosomes, and changes in POC1A were accompanied by alterations in another centrosome-associated WD repeat protein p80-katanin. As a result, we identified a novel mutation in POC1A of patients with PD and showed that this mutation causes the formation of multiple numbers of centrioles and multipolar spindles with abnormal chromosome arrangement.
The Role of ATP-Binding Cassette Transporter Genes in the Progression of Prostate Cancer
(Wiley, 2016) Karatas, Omer F.; Guzel, Esra; Duz, Mehmet B.; Ittmann, Michael; Ozen, Mustafa
BACKGROUNDProstate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of cancer-related death among men in developed countries. There is no clear evidence showing the success of current screening tests in reducing mortality of PCa. In this study, we aimed to profile expressions of nine ABC transporters, ABCA5, ABCB1, ABCB6, ABCC1, ABCC2, ABCC3, ABCC5, ABCC10, and ABCF2, in recurrent, non-recurrent PCa and normal prostate tissues. METHODSA total of 77 (39 recurrent, 38 non-recurrent) radical prostatectomy and 20 normal prostate samples, obtained from Baylor College of Medicine Prostate Cancer program, were included into the study and divided into two independent groups as test and validation sample sets. Differential expression of selected ABC transporters was assessed using quantitative real-time PCR (qRT-PCR). Pearson's correlation test, receiver operating characteristics (ROC) analysis and Kaplan-Meier test were used for statistical analysis. RESULTSQRT-PCR results demonstrated the elevated expression of ABCA5, ABCB1, ABCB6, ABCC1, and ABCC2 as well as reduced expression of ABCC3 in PCa samples compared to normal prostate tissues. In addition, we found deregulation of ABCB1, ABCB6, ABCC3, and ABCC10 in recurrent PCa samples and validated differential expression of ABCB6, ABCC3, and ABCC10 in recurrent PCa compared to non-recurrent PCa. Pearson's correlation, ROC and Kaplan-Meier analysis revealed the power of these three ABC transporters for estimating prognosis of PCa. CONCLUSIONSWe demonstrated differential expression of ABC transporters both in tumor versus normal and recurrent versus non-recurrent comparisons. Our data suggest ABCB6, ABCC3, and ABCC10 as valuable predictors of PCa progression. Prostate 76:434-444, 2016. (c) 2015 Wiley Periodicals, Inc.
The Roles of ATP-Binding Cassette Transporter A1 and Its Substrate Cholesterol in Head and Neck Cancers
(Wiley, 2023) Sanli, Fatma; Karatas, Omer F.
Head and neck cancer (HNC), which is among the deadliest malignancies, is the seventh most common cancer worldwide. How cholesterol homeostasis is linked to human cancers has long been a source of curiosity. One of the few proteins that are involved in cholesterol homeostasis is ATP-binding cassette transporter A1 (ABCA1), which is broadly expressed in numerous tissues. ABCA1 increases cholesterol efflux, inhibits cholesterol deposition in cells, and modulates anticancer activities. Therefore, it is not surprising that decreased ABCA1 activity and altered cholesterol homeostasis are implicated in the patho-physiology of HNCs. In this review, we focus on the role of cholesterol metabolism in the patho-physiology and progression of HNCs, with an emphasis on biological effects of ABCA1 transporters. We also review therapeutic approaches targeting cholesterol metabolism, as well as how combining such approaches with existing anticancer treatments may have synergistic effects and therefore open up new therapeutic avenues.
Synthesis and Biological Evaluation of 3,5-Diaryl Derivatives as Potential Antiprostate Cancer Agents
(Wiley-V C H Verlag Gmbh, 2021) Anil, Derya; Caykoylu, Emine U.; Sanli, Fatma; Gambacorta, Nicola; Karatas, Omer F.; Nicolotti, Orazio; Burmaoglu, Serdar
Prostate cancer is the most frequently diagnosed tumor in men and the second leading cause of cancer-associated mortality in most developed countries. 3,5-Diaryl substituted pyrazole derivatives (20-28) were prepared starting from related chalcones and biologically evaluated for in vitro growth inhibition activity against PC3 and DU145 human prostate cancer cell lines. Compounds 23, 26, and 28 were found to be more potent as compared to the other halogen-substituted derivatives. Especially, the 2-bromo-substituted pyrazole derivative (26) was found to be more potent against PC3 and DU145 cells. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2) are known to be expressed in DU145 and PC3 cancer cells. The binding mode of the most selective compound 26 toward EGFR and VEGFR2 was investigated by employing docking simulations based on GLIDE standard precision (-5.912 and -6.949 kcal/mol, respectively).