Browsing by Author "Altun, Zekiye"

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Citation - WoS: 19
Citation - Scopus: 22
Chaperonin (hsp60) and Annexin-2 Are Candidate Biomarkers for Non-Small Cell Lung Carcinoma
(Lippincott Williams & Wilkins, 2017) Agababaoglu, Ismail; Onen, Ahmet; Demir, Ayse Banu; Aktas, Safiye; Altun, Zekiye; Ersoz, Hasan; Sanli, Aydin
Background: Lung cancer is responsible of 12.4% and 17.6% of all newly diagnosed cancer cases and mortality due to cancer, respectively, and 5-year survival rate despite all improved treatment options is 15%. This survival rate reaches 66% in the Stage 1 and surgically treated patients. Early diagnosis which could not be definitely and commonly achieved yet is extremely critical in obtaining high survival rate in this disease. For this reason; proteomic differences were evaluated using matrix assisted laser desorption ionization (MALDI) mass spectrometry in the subgroups of lung adenocarcinoma and squamous cell carcinoma. Methods: Fresh tissue samples of 36 malignant cases involving 83.3% (n= 30) men and 16.7% (n= 6) women patients were distributed into 2 groups as early and end stage lung cancer and each group were composed of subgroups including 18 squamous cell carcinoma (9 early stage cases, 9 end stage cases) and 18 adenocarcinoma cases (9 early stage cases, 9 end stage cases). The fresh tissues obtained from the tumoral and matched normal sites after surgical intervention. The differences in protein expression levels were determined by comparing proteomic changes in each patient. Results: In the subgroups of advanced stage adenocarcinoma; tumoral tissue revealed differences in expression of 2 proteins compared with normal parenchymal tissue. Of those; difference in protein expression in heat shock protein 60 (HSP60) was found statistically significant (P= 0.0001). Subgroups of early and advanced stage squamos cell carcinoma have differed in certain 20 protein expression of normal tissue and diseased squamos cell carcinoma. Of those, increased protein expression level of only annexin-2 protein was found statistically significant (P= 0.002). No significant difference was detected in early and advanced stage protein expressions of the tumoral tissues in the subgroups of adenocarcinoma and squamous cell carcinoma. Conclusions: We conclude that with respect to early diagnosis of lung cancer that HSP60 and annexin-2 proteins are the important biomarkers in the subgroups of adenocarcinoma and squamous cell carcinoma. We also consider that these 2 proteins are molecules which may provide critical contribution in evaluation of prognosis, metastatic potential, response to treatment, and in establishment of differential diagnosis between adenocarcinoma and squamous cell carcinoma.
Determination of a New Biomarker at the Level of Gene Alteration in Cisplatin Ototoxicity
(MDPI, 2025) Kizmazoglu, Deniz; Erol, Aylin; Aktas, Tekincan Cagri; Olgun, Yuksel; Demir, Ayse Banu; Altun, Zekiye; Olgun, Nur
Cisplatin is an alkylating chemotherapeutic drug used in the treatment of many pediatric solid tumors, and cisplatin ototoxicity is characterized by sensorineural, bilateral, irreversible, and progressive hearing loss. The aim of this study is to identify biomarkers that may serve as predictors of cisplatin-induced ototoxicity in pediatric cancers. In our preliminary study, patients with severe hearing loss were analyzed using the comparative genomic hybridization (CGH) method. Mutations were identified in the following genes: ADAM6, SIX3, GNAS, NDUFV1, H19, DEFA4, and ZIM2. Based on these data, we aimed to investigate the mutation status of these candidate genes in a larger population of pediatric cancer patients treated with cisplatin. DNA samples were extracted from the mononuclear cells of peripheral blood samples obtained from 82 patients. These genes were analyzed using the RT-PCR technique, and ototoxicity was assessed using the Brock and Muenster classifications. Hearing loss was detected in 28% of patients; 76.8% and 23.2% had mild and severe hearing loss, respectively. A significant correlation was found between ZIM2 gene amplification and the presence of ototoxicity (rho = 0.461, p = 0.003), especially in advanced-stage cancer patients with severe hearing loss (rho = 0.38, p = 0.017). Our findings suggest that ZIM2 is a promising biomarker for predicting cisplatin ototoxicity.
Development of a New Biomarker at the Level of Gene Change in Cisplatin Ototoxicity
(Wiley, 2023) Kızmazoğlu, Deniz; Erol, Aylın; Aktaş, Tekincan; Olgun, Yüksel; Demir, Ayşe; Altun, Zekiye; Aktaş, Safiye
[No abstract available]
Citation - WoS: 2
Differences in the Differential Expression of Micrornas Between Patients With Familial Multiple Sclerosis and Those With Sporadic Multiple Sclerosis
(Galenos Publ House, 2023) Güllüoğlu, Halil; Uysal, Hasan Armağan; Poyraz, Turan; Altun, Zekiye; Kaya, Derya; Özcelik, Pınar; İdiman, Egemen; Poyraz, Turan
Objective: Multiple sclerosis (MS) is a heterogeneous disease with clinical and immunological features. Most MS cases occur sporadically, but a considerable proportion of patients have a family history of MS. The etiology and pathophysiology of MS remain unclear. Recent epidemiological and gene expression studies have indicated that dysregulation of microRNAs (miRNAs) may play a role in MS pathogenesis. This study aimed to evaluate the differential expression of miRNAs in sporadic MS (sMS) and familial MS Materials and Methods: This cross-section, single-center study was conducted in 20 FMS and 10 sMS patients and 8 healthy controls. The patients were in the remission. In total, 2,549 miRNA genes were screened in the blood mononuclear cells from the whole blood samples of MS patients depending on miRBase 21. Differential expression of miRNAs in MS patients was identified compared with the control group, and miRNAs with a fold change >= 2 were validated using reverse transcription-polymerase chain reaction. Differentially expressed miRNAs were then compared between FMS and sMS patients. Results: Initial findings showed that miR-5100 and hsa-miR-16-2-3p were increased and miR-432-3p was decreased in FMS compared with sMS, whereas miR-548-aa, hsa-miR-142-3p, and miR-451-b were increased in both sMS and FMS, but miR-548-v was increased only in sMS. Some miRNAs showed the same expression patterns in both groups. Conclusion: Differential expression of certain miRNAs may be a useful biomarker in the diagnosis of MS. This study showed that miRNAs may discriminate between FMS and sMS cases and MS subtypes, as indicated in earlier studies.
Citation - WoS: 6
The Role of Cancer Stem Cells in Immunotherapy for Bladder Cancer: an in Vitro Study
(Elsevier Science Inc, 2020) Ozcan, Yegane; Caglar, Fulya; Celik, Serdar; Demir, Ayse Banu; Ercetin, Ayse Pinar; Altun, Zekiye; Aktas, Safiye
Objective: Bladder cancer is characterized by frequent recurrence and progression. CD44+ cancer stem cells (CSCs) might be one of the main reasons for recurrence. Although Bacillus Calmette Guerin (BCG) has become a gold standard immunotherapy, after treatment recurrence frequently occur. Based on this knowledge, the aim of this study was to evaluate the changes in cytokine and chemokine expressions in bladder cancer and CSCs cultures in vitro with BCG only and in combination with IL2 and lymphocyte (MNCs) applications. Material and methods: In this study, 3 cell lines of human bladder cancer cells with different characteristics (T24, 5637, and JMSU-1) and CD44+ bladder CSCs isolated by magnetic bead isolation (Miltenyl Magtech) were used. Bladder cancer cell lines and bladder CSCs in complete medium were cultured under humidified conditions of 37 degrees C temperature in 5% CO2. BCG only and its combination with IL2 and MNCs were applied to bladder cancer cell lines and bladder CSCs for 24, 48, and 72 hours. Annexin V-PI was used to detect the percentages of apoptotic and necrotic cells in treatment groups and control groups. After treatments, total RNAs were isolated and converted to cDNA for each group and controls. Quantitative fold changes in terms of gene expression were measured by RT2 PCR array and fold changes for expression levels of genes were compared among groups. Eighty-four genes were analyzed in standard array of chemokines and cytokines (Biorad). Results: BCG treatment with 7.32 mu g/ml dose alone and in combination with IL2 (1000 IU/ml) and MNCs (1000 cells/ml) were found to be most effective on bladder cancer cells. When BCG and its combinations were applied to CSCs of the 3 cell lines, BCG treatment showed cytotoxic effect on CSCs as well as cancer cells. CSCs of 3 cell lines over expressed CXCL5, CCL8, CNTF, and CSF2 compared with cancer cells. Cancer cells over expressed IL6, TNSFF11, FASLG, and CXCL9 compared with CSCs. In all 3 cell lines, BCG application increased expression of CXCL5 and LTB and also decreased CCL20 and IL6. When BCG was combined with IL2 and MNCs, CXCL10, CXCL5, and IFNG were increased and CXCL12, IL6, and TNSF11 were decreased. BCG treatment of CSCs caused increases in ADIPOQ, CXCL10, and XCL1 and a decrease in CCL8. When IL2 and MNCs were combined with BCG, the expression of many cytokines and chemokines decreased. Conclusion: BCG treatment changes the expression of many cytokines and chemokines in bladder cancer. The expression differs in 3 different cell lines and their CSCs. Immune modulation of each case differs from each other. The effectivity of BCG-based immunotherapy in bladder cancer on CSCs might decrease in combination with IL2. Our results indicate that recurrence after BCG treatment for bladder cancer may not occur mainly based on the CSCs hypothesis considering bladder cancer occurs at different loci of surface epithelium. (C) 2020 Elsevier Inc. All rights reserved.
Citation - WoS: 1
Superoxide Dismutase 2 Protein Levels in Blood May Act as a Prognostic Marker for High-Risk Neuroblastoma Patients
(Dokuz Eylul Univ Inst Health Sciences, 2023) Demir, Ayse Banu; Altun, Zekiye; Aktas, Safiye; Olgun, Nur
Purpose: Determination of proteomic differences plays an important role in biomarker investigations. Due to its heterogenic molecular background, identification of certain biomarkers is still a demand both for diagnosis and prognosis of neuroblastoma. In this study, it is aimed to identify marker proteins/mechanisms that may play role in neuroblastoma prognosis. Material and Methods: Real-time PCR analyses were performed for 2p24.3, 11q23, 1p36 and 17q25 status from tumor samples of the patients to determine the risk groups. A proteomic approach was used for different risk groups of the disease by using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF/TOF) approach. Mononuclear cell pools from blood samples of patients for different risk groups were constructed and protein expression changes for different groups were identified. Results: Manganese-superoxide dismutase (SOD2) protein was found to significantly increase in high -risk group of neuroblastoma patients. Conclusion: Our results showed that SOD2 may play an important role in neuroblastoma progression and be a candidate prognostic peripheral blood marker for neuroblastoma patients.