Person: KOCAELİ, HASAN
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KOCAELİ
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HASAN
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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; Bursa Uludağ Üniversitesi/İnegöl Meslek Yüksekokulu.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim 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 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; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahi Bölümü.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Medikal Biyoloji Bölümü.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Pataloji Anabilim 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 Reliability of CT angiography scoring systems used for brain death and the effect of cranial interventions on the results(Elsevier Science, 2021-04-19) Özpar, Rıfat; Tonkaz, Mehmet; Girgin, Nermin Kelebek; Bodur, Muhittin; Dinç, Yasemin; Kocaeli, Hasan; Hakyemez, Bahattin; ÖZPAR, RİFAT; TONKAZ, MEHMET; KELEBEK GİRGİN, NERMİN; BODUR, MUHİTTİN; DİNÇ, YASEMİN; KOCAELİ, HASAN; HAKYEMEZ, BAHATTİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Radyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Anesteziyoloji ve Reanimasyon Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Nörolojisi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahi Anabilim Dalı.; 0000-0001-6649-9287; 0000-0002-5882-1632; 0000-0002-2588-8195; 0000-0002-3425-0740; IUQ-6999-2023; JAN-9435-2023; AAH-5062-2021; AAH-2684-2021; DZJ-5260-2022; DTU-3148-2022; FDK-3229-2022; AAI-2318-2021Objective: To assess vascular opacifications, the efficiency, and interobserver agreement (IOA) of five different computed tomography angiography (CTA) brain death (BD) scoring systems in patients with and without cranial interventions, for determining alternative findings correctly supporting BD diagnosis by CTA even in cranial intervention presence. Methods: 45 patients clinically identified with BD and evaluated with CTA were included. IOA of five different scoring systems used for CTA BD diagnosis, the effect of intracranial interventions on scoring systems, and vascular opacification were evaluated. Results: IOA was almost perfect (Kappa = 0.843-0.911, p < 0.05) and substantial (Kappa = 0.771-0.776, p < 0.05) in all scoring systems. Significant relationships were observed between craniectomy presence and middle cerebral artery M4 segment and internal cerebral vein (ICV) opacification. No opacification was observed in straight sinus (SS) by observers in any of the craniectomized patients. Conclusion: IOA of CTA scoring systems is adequate. But a significant degree of false-negative results is observed due to ICV filling in craniectomy cases. Opacification presence in SS can give an idea of BD in these cases.Publication Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression(E-century Publishing Corp, 2014-01-01) Tezcan, Gülçin; Tunca, Berrin; Bekar, Ahmet; Budak, Ferah; Şahin, Saliha; Çeçener, Gülşah; Egeli, Ünal; Taşkapılıoğlu, Mevlut Özgür; Kocaeli, Hasan; Tolunay, Şahsine; Malyer, Hulusi; Demir, Cevdet; Tümen, Gülendam; TEZCAN, GÜLÇİN; TUNCA, BERRİN; BEKAR, AHMET; BUDAK, FERAH; ŞAHİN, SALİHA; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; KOCAELİ, HASAN; TOLUNAY, ŞAHSİNE; MALYER, HULUSİ; DEMİR, CEVDET; Tümen, Gülendam; Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahi Kliniği; Uludağ Üniversitesi/Tıp Fakültesi/Mikrobiyoloji Bölümü; Uludağ Üniversitesi/Tıp Fakültesi/Patholoji Bölümü; 0000-0002-5956-8755; 0000-0002-1619-6680; 0000-0001-7625-9148; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0001-5472-9065; 0000-0002-9381-0410; ABA-2005-2020; F-8554-2017; ABX-9081-2022; AFR-1890-2022; F-4657-2014; AAH-3843-2020; AAI-1612-2021; ABI-6078-2020; IZP-9398-2023; AAW-5254-2020; AAP-9988-2020; AAH-2892-2021; ABB-8161-2020; AAH-1420-2021; ABI-6078-2020The stem-like cells of Glioblastoma multiforme (GBM) tumors (GSCs) are one of the important determinants of recurrence and drug resistance. The aims of the current study were to evaluate the anticancer effect of Olea europaea leaf extract (OLE) on GBM cell lines, the association between OLE and TMZ responses, and the effect of OLE and the OLE-TMZ combination in GSCs and to clarify the molecular mechanism of this effect on the expression of miRNAs related to cell death. The anti-proliferative activity of OLE and the effect of the OLE-TMZ combination were tested in the T98G, U-138MG and U-87MG GBM cell lines using WST-1 assay. The mechanism of cell death was analyzed with Annexin V/FITC and TUNEL assays. The effects of OLE on the expression levels of miR-181b, miR-153, miR-145 and miR-137 and potential mRNA targets were analyzed in GSCs using RT-qPCR. OLE exhibited anti-proliferative effects via apoptosis and necrosis in the GBM cell lines. In addition, OLE significantly induced the expression of miR-153, miR-145, and miR-137 and decreased the expression of the target genes of these miRNAs in GSCs (p < 0.05). OLE causes cell death in GBM cells with different TMZ responses, and this effect is synergistically increased when the cells are treated with a combination of OLE and TMZ. This is the first study to indicate that OLE may interfere with the pluripotency of GSCs by modulating miRNA expression. Further studies are required, but we suggest that OLE may have a potential for advanced therapeutic cancer drug studies in GBM.Publication Co-loading of Temozolomide with Oleuropein or rutin into polylactic acid core-shell nanofiber webs inhibit glioblastoma cell by controlled release(Elsevier, 2023-09-03) Erçelik, Melis; Tekin, Çağla; Parin, Fatma Nur; Mutlu, Büşra; Doğan, Hazal Yılmaz; Tezcan, Gülçin; Aksoy, Seçil Ak; Gürbüz, Melisa; Yıldırım, Kenan; Bekar, Ahmet; Kocaeli, Hasan; Taşkapılıoğlu, Mevlüt Özgür; Eser, Pınar; Tunca, Berrin; Erçelik, Melis; Tekin, Çağla; TEZCAN, GÜLÇİN; Aksoy, Seçil Ak; Gürbüz, Melisa; BEKAR, AHMET; KOCAELİ, HASAN; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; Eser, Pınar; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; Bursa Uludağ Üniversitesi/İnegöl Meslek Yüksekokulu.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Birimi.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahi Anabilim Dalı.; 0000-0002-1640-6035; 0000-0003-0132-9927; 0000-0002-1619-6680; ABX-9081-2022; AAI-2073-2021; HKM-7750-2023; EUG-3329-2022; GDC-6329-2022; JJL-1176-2023; JJH-2235-2023; CGB-7869-2022; FDK-3229-2022; IRO-2619-2023Glioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) coreshell nanofiber webs were encapsulated with OL (PLA(OL)), rutin (PLA(rutin)), and TMZ (PLA(TMZ)) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core -shell structures with an average diameter between 133 +/- 30.7-139 +/- 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLA(OL) and PLA(TMZ) suppressed GB cell viability with a controlled release that increased over 120 h, while PLA(rutin) caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nanowebs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells.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; Bursa Uludağ Üniversitesi/İnegöl Meslek Yüksekokulu.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim 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 Variations of perforating arteries of anterior communicating artery in cases with anterior communicating artery aneurysms: A cadaveric anatomical study(Springer Wien, 2022-05-26) Kuytu, Turgut; Kocaeli, Hasan; KOCAELİ, HASAN; Korfalı, Ender; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroşürji Anabilim Dalı.Purpose In terms of postoperative morbidity and mortality, preservation of the perforating arteries branching from the anterior communicating artery (ACoA) during clipping is particularly imperative in patients with ACoA aneurysm. In the present study, we aimed to investigate whether perforating arteries originated from ACoA were pushed away in a different location in patients with ACoA aneurysm. Furthermore, if they did so, we aimed to identify the direction in which they were dislocated and how the perforating arteries could be preserved during clipping. Methods Herein, we categorized 40 brains obtained from cadavers into two groups. The first (n = 26) and second (n = 14) groups included cases without and with ACoA aneurysms, respectively. After completing the preparation procedure, the brains were dissected using surgical microscope and the relevant anatomical region was examined and photographed. Finally, statistical analyses were performed on the data and the results were documented. Results In the aneurysms with posterior and superior projections, the perforators appeared to be pushed away inferiorly and were frequently noted at the anteroinferior part of the aneurysm neck. Most of the cases, where one of the A1s was larger at one side, the perforating arteries arose from the larger A1 side. Conclusion The mortality and morbidity associated with damage to the perforators can be reduced by approaching the patient from the dominant A1 side and pursuing the perforators primarily at the anteroinferior part of the aneurysm neck in the aneurysms with superior and posterior projections.Publication The gently pull-back technique for neck bypass in treatment of wide-necked internal carotid artery aneurysms: A report of three cases and review of the literature(Sage Publications Inc, 2015-12-01) Kaçar, Emre; Hakyemez, Bahattin; NAS, ÖMER FATİH; Nas, Ömer F.; KAYA, AHMET TUFAN; Kaya, Ahmet; Erdoğan, Cüneyt; Kocaeli, Hasan; KOCAELİ, HASAN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Radyoloji Anabilim Dalı.; 0000-0002-8813-6513; AAG-8561-2021; AAS-5392-2021Neck bypass failure in endovascular treatment of wide-necked internal carotid artery (ICA) aneurysms may adversely affect the technical success of the procedure. We used the gently pull-back technique to bypass the aneurysm neck and access the distal parent artery during endovascular treatment in patients with wide-necked ICA aneurysms. In this technique, a loop was made in the aneurysm and the distal parent artery was reached by using a small diameter microguidewire and a microcatheter. After providing reliable distal access, the microguidewire was removed and the whole system which consists of the microcatheter was gently pulled back. Finally the microcatheter was straightened and the aneurysm neck was passed. After crossing the aneurysm neck, a flow-diverting stent treatment and stent-assisted coiling were performed in three cases with wide-necked ICA aneurysm. The gently pull-back technique is a simple and effective method which requires no extra intravascular device and helps to bypass the aneurysm neck through a small diameter microguidewire and a microcatheter. This technique may be useful for neck aneurysm bypass in endovascular treatment of wide-necked ICA aneurysms.Publication Targeting Mfsd2a in hemorrhagic cerebrovascular diseases(Springer, 2022-03-29) Eser, Pınar; Taşkapılıoğlu, Mevlüt Özgür; Kocaeli, Hasan; Eser, Pınar; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; KOCAELİ, HASAN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahisi Anabilim Dalı; 0000-0003-0132-9927; 0000-0001-5472-9065; AAI-2073-2021; FDK-3229-2022