Person: AKKİPRİK, MUSTAFA
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AKKİPRİK
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MUSTAFA
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Publication Metadata only 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 FuldenPeripheral 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.Publication Metadata only Functional and clinical significance of SALL4 in breast cancer(SAGE PUBLICATIONS LTD, 2016) AKKİPRİK, MUSTAFA; Dirican, Ebubekir; Akkiprik, MustafaThe gene encoding Sal-like 4 (Drosophila) (SALL4) is a zinc-finger transcriptional factor and a vertebrate orthologous of the Drosophila gene spalt (sal), which is upregulated in some cancers. SALL4 is expressed in the early developmental stages of Drosophila. Moreover, murine SALL4 plays a vital role in protecting the properties of embryonic stem (ES) cells and guiding the outcome of the primal inner cell mass by interacting with OCT4 and NANOG. SALL4 in ES cells and tumor cells is known as a regulator for controlling cell growth, proliferation, and apoptosis. However, the downstream goals of SALL4 remain largely uncharted. SALL4 expression has been detected in various cancers, including a subset (30 %) of solid tumors, such as breast cancer (BCa), ovarian cancer, gastric cancer, Wilms tumor, and germ cell tumors. A study has reported that SALL4 expression is commonly upregulated in human breast tumors (similar to 86 %) and that overregulation of this gene is often linked to tumor progression. In this review, we provide an overview concerning the role of SALL4 in BCa development and progression. Furthermore, this review may identify some drugs/inhibitors for the development of BCa-specific therapies by targeting SALL4. In the future, SALL4 may be a new biomarker as a diagnostic/therapeutic target of BCa, which would be a new direction in targeted BCa therapy. To our knowledge, this is the first review of the role of SALL4 in BCa development and progression.Publication Metadata only Mutation distributions and clinical correlations of PIK3CA gene mutations in breast cancer(SAGE PUBLICATIONS LTD, 2016) AKKİPRİK, MUSTAFA; Dirican, Ebubekir; Akkiprik, Mustafa; Ozer, AyseBreast cancer (BCa) is the most common cancer and the second cause of death among women. Phosphoinositide 3-kinase (PI3K) signaling pathway has a crucial role in the cellular processes such as cell survival, growth, division, and motility. Moreover, oncogenic mutations in the PI3K pathway generally involve the activation phosphatidylinositol-4,5-bisphosphate 3-kinase-catalytic subunit alpha (PIK3CA) mutation which has been identified in numerous BCa subtypes. In this review, correlations between PIK3CA mutations and their clinicopathological parameters on BCa will be described. It is reported that PIK3CA mutations which have been localized mostly on exon 9 and 20 hot spots are detected 25-40 % in BCa. This relatively high frequency can offer an advantage for choosing the best treatment options for BCa. PIK3CA mutations may be used as biomarkers and have been major focus of drug development in cancer with the first clinical trials of PI3K pathway inhibitors currently in progress. Screening of PIK3CA gene mutations might be useful genetic tests for targeted therapeutics or diagnosis. Increasing data about PIK3CA mutations and its clinical correlations with BCa will help to introduce new clinical applications in the near future.Publication Metadata only 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, MustafaObjective: 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.Publication Metadata only Analysis of p53 Gene Polymorphisms and Protein Over-expression in Patients with Breast Cancer(SPRINGER, 2009) KAYA, HANDAN; Akkiprik, Mustafa; Sonmez, Ozgur; Gulluoglu, Bahadir M.; Caglar, Hale B.; Kaya, Handan; Demirkalem, Pakize; Abacioglu, Ufuk; Sengoz, Meric; Sav, Aydin; Ozer, Aysep53 polymorphic variants play an important role in the determination of tumor phenotype and characteristics in breast cancer. In this study, we examined three common polymorphisms in p53 gene and their haplotype combinations to assess their potential association with inherited predisposition to breast cancer development, in relations with the protein over-expression and patients' demographic data. A total of 99 patients with breast cancer and 107 age-matched healthy controls were included in the study. Genotypes were determined using PCR-RFLP and DNA sequencing techniques. Evaluation of p53 protein overexpression was also examined by immunohistochemistry. Among three polymorphisms, increased codon 72 Pro allele frequency (p=0.0067) and the presence of Pro allele were found to be significantly associated with breast cancer (p=0.013). A significant risk was also found in subjects with combinations of specific haplotypes and genotypes. Most of breast cancer women especially younger than 50 years carry at least one p53 polymorphism (p=0.001). There was no any association between these three p53 polymorphisms and the protein over-expression, separately or in interaction, with breast cancer. In conclusion, presence of proline allele at codon 72 alone, and its special combinations with other two polymorphisms appear to be a significant risk factor for breast cancer. Determination of well-known p53 polymorphisms might be a good predictor for breast cancer development especially in women younger than 50 years.Publication Open Access Correlation between plasma ccfDNA, mtDNA changes, CTCs, and epithelial-mesenchymal transition in breast cancer patients undergoing NACT(2024-01-01) PEKER EYÜBOĞLU, İREM; GÜLLÜ AMURAN, GÖKÇE; YUMUK, PERRAN FULDEN; AKKİPRİK, MUSTAFA; Çelik B., PEKER EYÜBOĞLU İ., Koca S., Ümit Uğurlu M., Alan Ö., GÜLLÜ AMURAN G., AKIN TELLİ T., Yumuk F., AKKİPRİK M.Background/aim: Breast cancer is the most prevalent cancer in women, emphasizing need for noninvasive blood biomarkers to aid in treatment selection. Previous studies have demonstrated elevated levels of plasma circulating cell-free DNA (ccfDNA) in breast cancer patients. Both ccfDNA and mitochondrial DNA (mtDNA) are fragments released into the bloodstream. In this study, we investigated effectiveness of ccfDNA and mtDNA as indicators of treatment response and explored their potential as monitoring biomarkers. Additionally, we compared these markers with circulating tumor cell (CTC) data and assessed their relationship with epithelialmesenchymal transition (EMT). Materials and methods: Thirty-six female breast cancer patients and 21 healthy females were included in the study. Quantitative polymerase chain reaction (qPCR) was performed on plasma samples to measure levels of ND1, ND4, ALU115, ALU247, and GAPDH, and DNA integrity was determined by calculating ratios of ALU247/ALU115 and ND4/ND1. Results: After treatment, patients had a significant decrease in ccfDNA levels and a significant increase in mtDNA copy number (mtDNAcn). However, there was no significant change in ccfDNA and mtDNA integrity. When comparing all groups, patients exhibited higher levels of ALU115 and ALU247 compared to controls. Moreover, patients demonstrated significantly lower ccfDNA integrity than controls. Conclusion: This study represents the first comprehensive investigation of plasma ccfDNA levels, mtDNAcn, and integrities collectively. Furthermore, it is the first study to explore the relationship between these markers and CTCs, cancer stem cell markers, treatment response, and metastatic status. Our findings suggest that plasma ccfDNA and mtDNA may serve as potential biomarkers for assessing chemotherapy response and can be employed alone or in combination with other biomarkers to monitor treatment efficacy in breast cancer patients. Key words: Breast cancer, ccfDNA, mtDNA, neoadjuvant therapy, EMT