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GÜLLÜ AMURAN, GÖKÇE

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GÜLLÜ AMURAN

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GÖKÇE

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20202
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    Response Assessment With Molecular Characterization of Circulating Tumor Cells and Plasma MicroRNA Profiling in Patients With Locally Advanced Breast Cancer During Neoadjuvant Chemotherapy
    (CIG MEDIA GROUP, LP, 2020) ERZİK, CAN; Akkiprik, Mustafa; Koca, Sinan; Ugurlu, M. Umit; Ekren, Ruchan; Eyuboglu, Irem Peker; Alan, Ozkan; Erzik, Can; Amuran, Gokce Gullu; Telli, Tugba Akin; Gulluoglu, M. Bahadir; Sezerman, Ugur; Yumuk, Perran Fulden
    Peripheral blood samples from 36 patients with locally advanced breast cancer who had undergone neoadjuvant chemotherapy were collected for circulating tumor cell (CTC) and plasma microRNA (miR) analysis. Pretreatment CTC and ALDH1 positivity (P = .0245) correlated, with miR-146b-5p and miR-199a-5p accompanied by CTC positivity. CTC and miR profiling of serial samples during neoadjuvant chemotherapy appears to be a very useful in predicting cure and clinical course. Background: Cells detaching from the primary tumor site are metastasis initiator cells, and the detection of CTC, known as liquid biopsy, is an important test of biomarkers of cancer progression. We investigated the molecular characterization of circulating tumor cells (CTCs), profiled the plasma microRNA (miR) content, and analyzed the relationship with the clinical outcomes by sampling the peripheral blood from patients with locally advanced breast cancer before and after neoadjuvant chemotherapy. Patients and Methods: Markers of breast cancer, epithelial-mesenchymal transition (EMT), drug resistance, and stem cells were used for CTC isolation and characterization. Plasma miR profiles were obtained from selected patients with CTC positivity determined using next-generation sequencing. Resutts: The proportion of CTC, EMT, and stem cell marker positivity was 16.7%, 8.3%, and 25% before and 18.2%, 15.2%, and 9.1% after treatment, respectively. A significant correlation was found between the pretreatment CTCs and ALDH1 positivity (P= .0245). These CTCs with stemness properties were observed in most hormone receptor-positive, human epidermal growth factor receptor 2 -negative cases and were also present with a high incidence in cases of early metastasis. miR-146b-5p and miR-199a-5p, which are involved in metastasis, invasion, and EMT, were accompanied by CTC positivity, and miR-4646-3p was associated with the development of early metastasis. Conclusions: Molecular characterization of CTCs and miR profiling of serial samples from patients with locally advanced breast cancer during neoadjuvant chemotherapy appears to be a very useful in predicting cure and clinical course and might be a key to developing new targeted therapies. (C) 2020 Elsevier Inc. All rights reserved.
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    Urinary micro-RNA expressions and protein concentrations may differentiate bladder cancer patients from healthy controls
    (SPRINGER, 2020) ILGIN, CAN; Amuran, Gokce Gullu; Tinay, Ilker; Filinte, Deniz; Ilgin, Can; Eyuboglu, Irem Peker; Akkiprik, Mustafa
    Purpose To determine expression differences of urine exosomal miR-19b1-5p, 21-5p, 136-3p, 139-5p, 210-3p and concentration differences of urinary BLCA-4, NMP22, APE1/Ref1, CRK, VIM between bladder cancer, follow-up patients, and control samples, to evaluate diagnostic importance of these differences and establish a diagnostic panel for bladder cancer. Methods Urine samples of 59 bladder cancer patients, 34 healthy controls, and 12 follow-up patients without recurrence were enrolled to this study. Real-time PCR and ELISA were performed to determine urine exosomal miR-19b1-5p, 21-5p, 136-3p, 139-5p, 210-3p expressions and urinary BLCA-4, NMP22, APE1/Ref1, CRK, VIM, creatinine concentrations. Logistic regression analyses were performed to determine the diagnostic panel, the sensitivity, and specificity of the panel assessed by the ROC curve analysis. p values < 0.05 were considered statistically significant. Results In bladder cancer risk groups, mir-139, -136, -19 and 210 expressions or positivity were found to be different and concentrations of urinary Ape1/Ref1, BLCA4, CRK, and VIM increased by twofold on average compared to healthy controls. Logistic regression and ROC analyses revealed that panel could differentiate bladder cancer patients from healthy controls with 80% sensitivity and 88% specificity (AUC = 0.899), low-risk patients from controls with 93% sensitivity and 95.5% specificity (AUC = 0.976). Despite the low number of samples, our findings suggest that urine exosomal miR-19b1-5p, 136-3p, 139-5p expression, and urinary APE1/Ref1, BLCA-4, CRK concentrations are promising candidates in terms of bladder cancer diagnosis. Conclusions Although our panel has great sensitivity for early detection of BC, it needs to be validated in larger populations.