Person: AKSOY, SEÇİL
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Publication DPYD c.1905+1G>A promotes fluoropyrimidine-induced anemia, a prognostic factor in disease-free survival, in colorectal cancer(Mary Ann Liebert, Inc, 2021-04-01) Deligönül, Adem; Aksoy, Seçil; Tezcan, Gülçin; Tunca, Berrin; Kanat, Özkan; Çubukcu, Erdem; Yılmazlar, Tuncay; Öztürk, Ersin; Egeli, Ünal; Çeçener, Gülşah; Alemdar, Adem; Evrensel, Türkkan; DELİGÖNÜL, ADEM; AKSOY, SEÇİL; TEZCAN, GÜLÇİN; TUNCA, BERRİN; Kanat, Özka; ÇUBUKÇU, ERDEM; YILMAZLAR, AHMET TUNCAY; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; ALEMDAR, ADEM; EVRENSEL, TÜRKKAN; Sağlık Bilimleri Enstitüsü; Tıbbi Onkoloji Ana Bilim Dalı; 0000-0002-6400-4911; 0000-0002-5956-8755; 0000-0002-1619-6680; 0000-0001-8593-5101; 0000-0001-7904-883X; 0000-0002-3820-424X; HIZ-7332-2022; AAH-1420-2021; AAH-3843-2020; ESM-4544-2022; JDG-0330-2023; ABI-6078-2020; CYM-0930-2022; ETP-1691-2022; CKK-3621-2022; AAP-9988-2020; EXZ-0745-2022Background and Aim: In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase (DPYD) gene variant, c.1905 + 1G>A, leads to intolerance to fluoropyrimidines. Due to the low frequency of this variant in many populations, the prevalence of fluoropyrimidine-induced hematologic side effects in CRC patients with the c.1905 + 1G>A variant is unclear. In this study, we investigated the prevalence of the DPYD c.1905 + 1 variants in a Turkish CRC cohort and the potential effects of these variants on fluoropyrimidine-induced hematologic side effects.Materials and Methods: The DPYD c.1905 + 1 variant was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis and confirmed by Sanger sequencing in peripheral blood samples of 100 CRC patients who received fluoropyrimidine-based chemotherapy and 60 healthy volunteers. The association of c.1905 + 1 variants with susceptibility to hematologic side effects was evaluated.Results: The DPYD c.1905 + 1G>A variant was more common in the CRC group than in the healthy control group (p = 0.001). The presence of the c.1905 + 1G>A variant was associated with thrombocytopenia (p = 0.039) and anemia (p = 0.035). CRC patients with fluoropyrimidine-induced anemia had shorter disease-free survival than CRC patients without fluoropyrimidine-induced anemia (p = 0.0009).Conclusions: Before administering fluoropyrimidine-based chemotherapy, genetic screening for the DPYD c.1905 + 1G>A variant should be performed with the aim of preventing anemia and anemia-induced complications in CRC patients.Publication Diabetes mellitus-mediated MALAT1 expression induces glioblastoma aggressiveness(Turkish Neurosurgical Soc, 2023-01-01) Kocaeli, Aysen Akkurt; Aksoy, Seçil A. K.; Erçelik, Melis; Tezcan, Gülçin; Tekin, Çağla; Kocaeli, Hasan; Bekar, Ahmet; Taşkapılıoğlu, Mevlüt Özgür; Tolunay, Şahsine; Tunca, Berrin; AKSOY, SEÇİL; Erçelik, Melis; TEZCAN, GÜLÇİN; Tekin, Çağla; KOCAELİ, HASAN; BEKAR, AHMET; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; TOLUNAY, ŞAHSİNE; TUNCA, BERRİN; Tıp Fakültesi; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0002-3760-9755; ADM-8457-2022; EUG-3329-2022; JJL-1176-2023; GDC-6329-2022; FDK-3229-2022; JWS-5881-2024; IRO-2619-2023; AAI-1612-2021; JXJ-7901-2024AIM: To describe the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in glioblastoma (GB) progression in patients concurrently diagnosed with diabetes mellitus (DM).MATERIAL and METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor samples of 47 patients diagnosed with GB only and 13 patients diagnosed with GB and DM (GB-DM) were enrolled in this study. Data for p53 and Ki67 immunohistochemical staining of the tumors and blood HbA1c levels of patients with DM were retrospectively collected. MALAT1 expression was assessed using quantitative real-time polymerase chain reaction.RESULTS: The coexistence of GB and DM induced the nuclear expression of p53 and Ki67 compared with GB only. MALAT1 expression was higher in GB-DM tumors than in GB only tumors. The expression of MALAT1 and HbA1c levels were positively correlated. Additionally, MALAT1 was positively correlated with tumoral p53 and Ki67. The disease-free survival of patients with GB-DM with high MALAT1 expression was shorter than that of those diagnosed with GB only and with a lower MALAT1 expression.CONCLUSION: Our findings suggest that one of the mechanisms of the facilitating effect of DM on GB tumor aggressiveness is via MALAT1 expression.Publication Frequency of azole resistance in clinical and environmental strains of aspergillus fumigatus in Turkey: A multicentre study(Oxford Univ Press, 2022-04-21) Ener, Beyza; Ergin, Çağrı; Gülmez, Dolunay; Ağca, Harun; Tikvesli, Melek; Aksoy, Seçil Ak; Otkun, Müşerref; Sığ, Ali Korhan; Ogunc, Dilara; Özhak, Betil; Topaç, Tuncay; Özdemir, Aslı; Metin, Dilek Yeşim; Polat, Suleyha Hilmioğlu; Öz, Yasemin; Koç, Nedret; Atalay, Mustafa Altay; Erturan, Zayre; Birinci, Asuman; Cerikçioğlu, Nilgün; Timur, Demet; Eksi, Fahriye; Genç, Gonca Erköse; Fındık, Duygu; Gürcan, Şaban; Kalkancı, Ayşe; Arıkan-Akdagli, Sevtap; ENER, BEYZA; AĞCA, HARUN; AKSOY, SEÇİL; TİMUR, DEMET; İnegöl Meslek Yüksekokulu; Mikrobiyoloji Ana Bilim Dalı; 0000-0002-2651-2034; AAG-8523-2021; AAH-8540-2021; DZV-6739-2022; ISU-9626-2023Objectives Aspergillus fumigatus causes several diseases in humans and azole resistance in A. fumigatus strains is an important issue. The aim of this multicentre epidemiological study was to investigate the prevalence of azole resistance in clinical and environmental A. fumigatus isolates in Turkey. Methods Twenty-one centres participated in this study from 1 May 2018 to 1 October 2019. One participant from each centre was asked to collect environmental and clinical A. fumigatus isolates. Azole resistance was screened for using EUCAST agar screening methodology (EUCAST E.DEF 10.1) and was confirmed by the EUCAST E.DEF 9.3 reference microdilution method. Isolates with a phenotypic resistance pattern were sequenced for the cyp51A gene and microsatellite genotyping was used to determine the genetic relationships between the resistant strains. Results In total, resistance was found in 1.3% of the strains that were isolated from environmental samples and 3.3% of the strains that were isolated from clinical samples. Mutations in the cyp51A gene were detected in 9 (47.4%) of the 19 azole-resistant isolates, all of which were found to be TR34/L98H mutations. Microsatellite genotyping clearly differentiated the strains with the TR34/L98H mutation in the cyp51A gene from the strains with no mutation in this gene. Conclusions The rate of observed azole resistance of A. fumigatus isolates was low in this study, but the fact that more than half of the examined strains had the wild-type cyp51A gene supports the idea that other mechanisms of resistance are gradually increasing.Publication Olea europaea leaf extract decreases tumour size by affecting the LncRNA expression status in glioblastoma 3D cell cultures(Elsevier, 2021-05-21) Mutlu, Melis; Tunca, Berrin; Aksoy, Seçil Ak; Tekin, Çağla; Çeçener, Gülşah; Egeli, Ünal; Mutlu, Melis; TUNCA, BERRİN; AKSOY, SEÇİL; Tekin, Çağla; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; İnegöl Meslek Yüksekokulu; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0001-7904-883X; AAH-1420-2021; ADM-8457-2022; FPB-0403-2022; GDC-6329-2022; AAP-9988-2020; ABI-6078-2020Introduction: Glioblastoma (GB) is the most aggressive primary brain tumour. Temozolomide (TMZ) is a chemotherapy drug used in the treatment of GB. Despite treatment with TMZ, the prognosis of GB is poor. This study aimed to demonstrate the ability of Olea europaea leaf extract (OLE) alone and in combination with TMZ to suppress tumour aggressiveness by evaluating long non-coding RNA (LncRNA) and cancer stem cell (CSC) markers in GB cells using a three-dimensional (3D) model. Methods: The Real-time PCR (RT-PCR) method was used to determine the effects of OLE on LncRNA and CSC markers associated with tumour aggressiveness. To explore the effect of OLE on tumour size, a 3D model was developed. Results: It was found that OLE suppressed tumour aggressiveness with inhibited the MALAT1, SOX2 and NANOG ( p < 0.05). OLE + TMZ also inhibited MALAT1, LOXL1-AS1, PVT1 and H19 ( p < 0.05) and OCT4, NANOG, SOX2 and CD133 ( p < 0.05). In addition, to reduce tumour aggressiveness in a 3D cell culture, the use of OLE and OLE + TMZ has been supported (47.11-fold, p < 0.0001 and 18.04-fold, p < 0.0001, respectively). Conclusion: OLE may be a potential therapeutic agent that can be used in the treatment of GB, as it has been shown to reduce tumour size and increase the effect of TMZ.Publication High expression of SNGH16 is a candidate predictive marker of regional therapy resistance in hepatocellular carcinoma(Lippincott Williams & Wilkins, 2023-09-01) Aksoy, F.; Aksoy, S. Ak; Erçelik, M.; Tekin, C.; Tunca, B.; Gürlüler, E.; Kaya, E.; Aksoy, F.; AKSOY, SEÇİL; Erçelik, M.; Tekin, C.; TUNCA, BERRİN; GÜRLÜLER, ERCÜMENT; Kaya, E.; Tıp Fakültesi; 0000-0002-3760-9755 ; 0000-0003-0366-2424; 0000-0002-1619-6680; GNK-2142-2022; ADM-8457-2022; LRB-6135-2024; GDC-6329-2022; ABI-6078-2020; JQS-8451-2023; FDC-0395-2022Publication Investigation of cerbb2 at mrna level in patients with gastric adenocarcinoma(Bayrakol Medical Publisher, 2022-06-01) Turhan, Ezgi Işıl; Aksoy, Seçil Ak; UĞRAŞ, NESRİN; IŞIK, ÖZGEN; AKSOY, SEÇİL; TUNCA, BERRİN; Tunca, Berrin; Işık, Özgen; Yerci, Ömer; YERCİ, ÖMER; Vuruşkan, Berna Aytaç; AYTAÇ VURUŞKAN, BERNA; Tıp Fakültesi; Genel Cerrahi Ana Bilim Dalı; 0000-0002-1619-6680; 0000-0002-9541-5035; ADM-8457-2022; AAW-9602-2020Aim: Gastric adenocarcinomas take place near the top regarding mortality due to cancer. This study aims to validate IHC results with the RT-PCR method and to evaluate their contribution to confirm the absolute score of CerbB2 situation in tissues. Material and Methods: We analyzed 80 gastric adenocarcinoma cases diagnosed in our clinic. The expression characteristics of the cases were evaluated using CerbB2 staining. Simultaneously, CerbB2 expression analyses were performed with the RT-PCR method. Results: Positive immunoreactivity was observed in 19 of 80 cases (23,75%) in the study conducted using CerbB2 antibody. While 14 of these cases (17.5%) demonstrated weak positive (2+), 5 of them (6.25%) demonstrated strong positive (3+) immunoreactivity. With the RT-PCR method, an increase in gene expression was observed in 12 of 14 weak positive cases (75%). In all 5 strong positive cases, on the other hand, high gene expression was determined. Between CerbB2 immunohistochemical findings and gene expression, 89% compatibility and a statistically significant relationship was determined. While an increase in CerbB2 gene expression, determined by Real Tirme PCR method, was not observed in 57 of 61 cases (96.6%) without CerbB2 immunoreactivity, 4 cases had an increase in CerbB2 expression in comparison to normal. In our study, a statistically significant relationship was determined between CerbB2 expression and Helicobacter pylori (H. pylori) that is a factor blamed for gastric cancer etiology. The relationship between CerbB2 expression and clinicopathologic prognostic factors has been statistically reviewed; no significant results have been found. Discussion: Our study has shown that RT-PCR is a method, which might be an alternative to IHC and in ISH methods. It is concluded that a statistically significant relationship might be determined between CerbB2 expression and clinicopathologic prognostic parameters by increasing the case number.Publication Coexistence of TERT C228T mutation and MALAT1 dysregulation in primary glioblastoma: new prognostic and therapeutic targets(Taylor & Francis, 2021-06-21) Ak Aksoy, Seçil; Mutlu, Melis; Tunca, Berrin; Kocaeli, Hasan; Taşkapılıoğlu, Mevlüt Özgür; Bekar, Ahmet; Tekin, Çağla; Arğadal, Ömer Gökay; Civan, Muhammet Nafi; Kaya, İsmail Seçkin; Ocak, Pınar Eser; Tolunay, Şahsine; AKSOY, SEÇİL; Mutlu, Melis; TUNCA, BERRİN; KOCAELİ, HASAN; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; BEKAR, AHMET; Tekin, Çağla; ARGADAL, ÖMER GÖKAY; Civan, Muhammet Nafi; KAYA, İSMAİL SEÇKİN; OCAK, PINAR; TOLUNAY, ŞAHSİNE; Tıp Fakültesi; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0002-1619-6680; 0000-0001-5472-9065; 0000-0003-0132-9927; 0000-0002-5126-1548; ADM-8457-2022; ABX-9081-2022; AAI-2073-2021; FPB-0403-2022; ABI-6078-2020; FDK-3229-2022; AAW-5254-2020; GDC-6329-2022; CCA-2925-2022; HKP-0793-2023; ILC-4543-2023; AAI-1612-2021Objective: This study was designed to conduct molecular classification based on IDH1/2, TERT, ATRX, and DAXX changes in pediatric and adult primary glioblastoma (GB) and to analyze the potential interaction of LncRNA MALAT1 in the determined homogeneous subgroups. Methods: We analyzed the expression profiles of ATRX/DAXX and MALAT1 using the qRT-PCR method and IDH and TERT mutation status using DNA sequencing analysis in 85 primary pediatric and adult GB patients. Results: IDH1 mutation was observed in 5 (5.88%) and TERT mutation in 65 (76.47%) primary pediatric and adult GB patients. ATRX and DAXX were detected in 18 (21.18%) and 7 (8.24%) patients. TERT mutation and loss of ATRX/DAXX were associated with short overall survival (p < 0.001, p < 0.001, respectively). Patients carrying especially TERT C228T mutation had worse prognosis (p < 0.001). Six subgroups were obtained from the genetic analysis. Among the subgroups, MALAT1 was highly expressed in group A that had a single TERT mutation as compared to that in groups D and E (p = 0.001 and p < 0.001, respectively); further, high MALAT1 expression was associated with worse prognosis in patients with C228T mutation (p < 0.001). Conclusions: Our findings highlight that the presence of TERT C228T mutation and expression of MALAT1 can be used as primary targets during the follow-up of primary GB patients and in the development of new treatment strategies.Publication Concurrent presence of diabetes affects the GLUT3 programming of glucose metabolism in glioblastoma(Verduci Publisher, 2023-01-01) Kocaeli, A. A.; Tekin, C.; Erçelik, M.; Tezcan, G.; Aksoy, S. A.; Kocaeli, H.; Bekar, A.; Taşkapılıoğlu, M. O.; Tolunay, S.; Tunca, B.; Tekin, Cumhur; Erçelik, Melis; TEZCAN, GÜLÇİN; AKSOY, SEÇİL; KOCAELİ, HASAN; BEKAR, AHMET; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; TOLUNAY, ŞAHSİNE; TUNCA, BERRİN; İnegöl Meslek Yüksekokulu; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0002-5956-8755 ; 0000-0003-0366-2424 ; 0000-0002-3760-9755; 0000-0002-1619-6680; GQE-0790-2022; LRB-6135-2024; AAH-3843-2020; ADM-8457-2022; FDK-3229-2022; IAW-7368-2023; IRO-2619-2023; CDQ-8165-2022; ABI-6078-2020OBJECTIVE: Diabetes mellitus (DM)-mediated impaired glucose metabolism in-crease in the glioblastoma (GB) risk by inducing hyperglycemia and hyperinsulinemia. An inte-gral membrane transport protein, glucose trans-porter 3 (GLUT3) facilitates glucose transport in -to GB tumor cells. We aimed to explore the reg-ulation of GLUT3 in GB tumors of patients who were concurrently diagnosed with DM. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from 93 GB patients and retrospective-ly analyzed. Of the total, 15 patients were con-currently diagnosed with DM (GB-DM). The role of GLUT3 in tumor aggressiveness was evalu-ated by analyzing its correlation with Ki67, P53 expression, !ALAT1 expression, and peripher-al blood hemoglobin A1C (HbA1c) level. T98G cells were treated with empagliflozin and met-formin to modulate GLUT3. The RNA expres-sion of GLUT3, SOX2, and !ALAT1 was analyzed by real-time qPCR. The lactate levels of T98G cells were measured by Cobas c502 analyzer. A scratch wound assay was performed to investi-gate the migration rate of T98G cells. RESULTS: GLUT3 expression was lower in GB-DM tumors than in GB-only tumors. In GB-DM, the expression of tumoral GLUT3 and pe-ripheral blood glycated hemoglobin (HbA1c) lev-els were negatively correlated with P53 and Ki67. A decreased GLUT3 shortened the disease-free survival duration in GB-DM patients. Empagli-flozin reduced GLUT3, while metformin-induced GLUT3 in T98G cells. The empagliflozin-medi-ated GLUT3 suppression induced SOX2 and !ALAT1 expressions and influenced the migra-tion capacity of T98G cells. CONCLUSIONS: Our findings suggest that the low GLUT3 expression of the tumors of GB-DM patients may induce the production of adenosine triphosphate (ATP) from cellular energy sources other than glucose metabo-lism. However, further studies are warranted to confirm these results.Publication Comparison of clinical and molecular wnt and shh subgroups in medulloblastoma tumor cases(Turkish Neurosurgical Soc, 2021-01-01) Kaya, Ismail Seckin; Aksoy, Secil; Mutlu, Melis; Tekin, Cagla; Taskapilioglu, Mevlut Ozgur; Tunca, Berrin; Civan, Muhammet Nafi; Ocak, Pinar Eser; Kocaeli, Hasan; Bekar, Ahmet; Egeli, Unal; Cecener, Gulsah; Tolunay, Sahsine; Kaya, Ismail Seckin; KAYA, İSMAİL SEÇKİN; Aksoy, Secil; AKSOY, SEÇİL; Mutlu, Melis; Tekin, Cagla; Taskapilioglu, Mevlut Ozgur; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; Tunca, Berrin; TUNCA, BERRİN; Civan, Muhammet Nafi; Ocak, Pinar Eser; Kocaeli, Hasan; KOCAELİ, HASAN; Bekar, Ahmet; BEKAR, AHMET; Egeli, Unal; EGELİ, ÜNAL; Cecener, Gulsah; ÇEÇENER, GÜLŞAH; Tolunay, Sahsine; TOLUNAY, ŞAHSİNE; Tıp Fakültesi; Pataloji Ana Bilim Dalı; 0000-0001-5472-9065; 0000-0002-1619-6680; 0000-0003-0132-9927; 0000-0001-7904-883X; 0000-0002-3820-424X; AAH-1420-2021; AAH-8540-2021; ABX-9081-2022; HKP-0793-2023; AAI-2073-2021AIM: To determine the Wnt and SHH subtypes at the molecular level, and to compare them clinically by examining the changes in CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression in the medulloblastoma of a Turkish population determined according to patient selection criteria. In this context, the clinical distinction between Wnt and SHH groups are realized by considering the age, gender, survival time, location of the lesion, and radiological features of the patients.MATERIAL and METHODS: Molecular separation was performed by RT-PCR analysis of CTNNB1, AXIN, PTCH1, SMO, SUFU, and GLI1 mRNA expression changes.RESULTS: About 17.8% and 22.2% of the cases were included in the Wnt and the SHH group, respectively. When comparing group differences based on clinical and molecular data, 72.7% and 66.6% of matches were observed in the Wnt and the SHH group, respectively.CONCLUSION: It has been revealed that molecular analysis and grouping of patients with medulloblastoma can provide support for clinically determined subgroups.Publication Tumor-derived exosomal mir-21 induces recurrence in liver cancer(Wiley, 2021-08-01) Aksoy, Fuat; Kaya, Ekrem; Dündar, Halit Ziya; Aksoy, Seçil Ak; Tunca, Berrin; AKSOY, FUAT; KAYA, EKREM; DÜNDAR, HALİT ZİYA; AKSOY, SEÇİL; TUNCA, BERRİN; Bursa Uludağ Üniversitesi; 0000-0001-5808-9384; 0000-0002-1619-6680; 0000-0002-9562-4195; ADM-8457-2022; HII-8895-2022; AAG-7319-2021; EWI-3634-2022; ABI-6078-2020