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AKKİPRİK, MUSTAFA

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AKKİPRİK

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MUSTAFA

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20202
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Author: GÜLLÜOĞLU, MAHMUT BAHADIR × Subject: Breast cancer ×

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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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    PIK3CA and TP53 MUTATIONS and SALL4, PTEN and PIK3R1 GENE EXPRESSION LEVELS in BREAST CANCER
    (WALTER DE GRUYTER GMBH, 2020) KAYA, HANDAN; Dirican, Ebubekir; Seven, Ipek Erbarut; Kaya, Handan; Ugurlu, M. Umit; Peker, Irem; Gulluoglu, Bahadir M.; Ozer, Ayse; Akkiprik, Mustafa
    Objective: A high frequency of PI3K signalling pathway abnormalities and TP53 mutations are critical in the development and progression of breast cancer (BCa). We aimed to detect PIK3CA and TP53 mutations via an expression analysis of PIK3R1, PTEN and SALL4 and correlate the expression of these genes with clinical parameters of BCa. Materials and methods: PIK3CA and TP53 mutations in BCa samples were analysed by High-Resolution Melting (HRM) analysis, followed by Sanger sequencing, and the expression levels of PIK3R1, PTEN and SALL4 were evaluated by RT-PCR methods. Results: The frequency of PIK3CA and TP53 mutations was 42% and 38% according to the HRM and Sanger sequencing. There was a significantly high frequency of these mutations in ER(+), N0 and HER2(-) tumour samples. PIK3R1 and PTEN expression levels were high in tumour samples, whereas SALL4 expression was low. In patients with TP53 mutations, PIK3R1 expression was low, and this finding was statistically significant. PIK3R1 and PTEN expression levels showed statistically significant, respectively in G3 grades, ER(+), (PR)(+), HER2(+) and ER(+). Conclusions: We suggest that these candidate genes could be potential prognostic biomarkers of BCa and that they should be considered in the evaluation of clinical parameters of BCa.