Person: BEKAR, AHMET
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BEKAR
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AHMET
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Publication Ct-guided percutaneous trigeminal tractotomy-nucleotomy for intractable craniofacial pain(Karger, 2020-09-01) Türkkan, Alper; Bekar, Ahmet; BEKAR, AHMET; Eser Ocak, Pınar; Taşkapılıoğlu, M. Özgür; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; OCAK, PINAR; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; 0000-0003-0132-9927; 0000-0001-5472-9065; ABX-9081-2022; ABB-8161-2020; AAI-2073-2021Object:In this report, we aimed to analyze the outcome results of our patients who underwent percutaneous trigeminal tractotomy (TR) and nucleotomy (NC) procedures, which are defined as destructive procedures targeting the descending trigeminal tractus and nucleus caudalis of the spinal trigeminal nucleus, respectively, for intractable craniofacial pain.Methods:The medical records of a total of 12 patients who underwent a total of 14 computed tomography (CT)-guided TR-NC procedures at our clinics between 2005 and 2017 were retrospectively reviewed.Results:A significant increase in patients' performance status (p= 0.015) as well as a significant decrease in the VAS score (p< 0.001) were achieved. Grade I pain relief (VAS = 0, no pain) was established in 66.7% of the patients, whereas grade II pain relief was observed in the remaining patients. Two of the patients suffered from recurrent pain after the initial procedure. Both patients underwent a second trigeminal TR-NC procedure, and grade I pain relief was re-established. The mean VAS score at 3-month follow-up was 1.4 +/- 1.1, whereas this score at 6-month follow-up was 2 +/- 1.3. The trigeminal TR-NC procedure resulted in a significant decrease in patients' VAS scores at 3- and 6-month follow-up visits compared with preoperative VAS scores (p< 0.001). Transient ataxia was noted in only one patient (8.3%) early after the procedure.Conclusions:The results presented in the current study support the efficacy of the percutaneous CT-guided trigeminal TR-NC procedure in the management of intractable facial pain in selected patients. The use of CT guidance allows direct visualization of the target area, thereby enhancing the safety and success of the procedure.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 Anti-apoptotic and anti-oxidant effects of systemic uridine treatment in an experimental model of sciatic nerve injury(Türk Nöroloji Derneği, 2021-01-01) Khezri, Marzieh Karimi; Turkkan, Alper; Khezri, Marzieh Karimi; Koç, Cansu; KOÇ, CANSU; Salman, Berna; SALMAN, BERNA; Levent, Pinar; Cakir, Aysen; Kafa, Ilker Mustafa; Cansev, Mehmet; Bekar, Ahmet; ÇAKIR, AYŞEN; KAFA, İLKER MUSTAFA; CANSEV, MEHMET; BEKAR, AHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmakoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Fizyoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0001-8309-0934; 0000-0003-2918-5064; AAA-4754-2022; ABX-9081-2022; A-6819-2018AIM: To investigate the anti-apoptotic and anti-oxidant effects of systemic uridine treatment in a rat model of sciatic nerve injury.MATERIAL and METHODS: Thirty-two adult male rats were equally randomized to Sham, Control, U100, and U500 groups. Sham rats received a sham operation by exposing the right sciatic nerve without transection, while those in the Control, U100, and U500 groups underwent right sciatic nerve transection followed by immediate primary anostomosis. Sham and Control groups received saline (0.9% NaCl) injections intraperitoneally (i.p.), while U100 and U500 groups received 100 mg/kg and 500 mg/kg uridine injections (i.p.), respectively, once a day for 7 days after the surgery. Rats in all the groups were sacrificed on the eighth day; sciatic nerve samples were analyzed for apoptosis by Western Blotting and for oxidation parameters including myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) by Enzyme-Linked Immunosorbent Assay (ELISA).RESULTS: Uridine treatment at the dose of 500 mg/kg significantly decreased as apoptosis determined by Caspase-3/Actin ratio and exhibited significant anti-oxidant effects as determined by decreased levels of MPO and MDA as well as increased levels of SOD, GPx, and CAT compared to controls. Uridine at 100 mg/kg was only found to decrease the Caspase-3/Actin ratio, although it significantly decreased MDA and increased CAT levels compared to controls.CONCLUSION: Treatment with uridine reduces apoptosis and oxidation in a rat model of sciatic nerve injury dose-dependently. Thus, uridine may be beneficial in peripheral nerve regeneration by exhibiting anti-apoptotic and anti-oxidant effects.Publication The immunohistochemical expression of c-met is an independent predictor of survival in patients with glioblastoma multiforme(Springer International Publishing Ag, 2014-02-01) Ölmez, O. F.; Çubukçu, E.; ÇUBUKÇU, ERDEM; Evrensel, T.; EVRENSEL, TÜRKKAN; Kurt, M.; Avcı, N.; Tolunay, S.; TOLUNAY, ŞAHSİNE; Bekar, Ahmet; BEKAR, AHMET; Deligönül, Adem; DELİGÖNÜL, ADEM; Hartavi, M.; Alkış, N.; Manavoğlu, O.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/ Onkoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/NöroPatoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Radyasyon Onkolojisi Anabilim Dalı.; ABX-9081-2022; AAJ-1027-2021; AAA-3961-2020; AAI-1612-2021Because the outcome of glioblastoma multiforme (GBM) remains dismal, there is an urgent need for a better molecular characterization of this malignancy. The aim of this prospective study was to investigate the prognostic impact of the expression of c-mesenchymal-epithelial transition (c-Met) a receptor tyrosine kinase implicated in expression growth, survival, motility/migration, and invasion in GMB patients managed according to the established diagnostic and therapeutic protocols.Between May 2003 and March 2011, a total of 69 patients (33 males and 36 females; mean age: 52.2 +/- A 12.9 years, age range: 23-81 years) referred to our Department for the surgical removal of GBM were evaluated immunohistochemically for c-Met expression. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures.Compared with c-Met- subjects (n = 38), c-Met+ subjects (n = 31) had both a significantly lower OS (15.3 +/- A 2.3 vs. 22.6 +/- A 2.5 months, respectively, p < 0.01) and PFS (12.3 +/- A 2.1 vs. 19.1 +/- A 2.6 months, respectively, p < 0.05). After allowance for potential confounders, multivariate Cox regression analysis identified c-Met+ as an independent predictor of both OS (hazard ratio = 1.7; 95 % confidence interval = 1.2-1.9, p < 0.01) and PFS (hazard ratio = 1.6; 95 % confidence interval = 1.1-2.3, p < 0.05).Our findings suggest that c-Met immunohistochemical expression is an independent predictor of outcomes in patients with GBM treated by standard of care.Publication NEAT1 Is a novel oncogenic LncRNA and correlated with miR-143 in pediatric oligodendrogliomas(Karger, 2021-03-19) Ak Aksoy, Seçil; Mutlu, Melis; Balçin, Rabia Nur; Taşkapılıoğlu, Mevlut Özgür; Tekin, Çağla; Kaya, Seçkin; Civan, Muhammet Nafi; Kocaeli, Hasan; Bekar, Ahmet; Eser Ocak, Pınar; Çeçener, Gülşah; Egeli, Ünal; Tolunay, Şahsine; Tunca, Berrin; Ak Aksoy, Seçil; Mutlu, Melis; BALÇIN, RABİA NUR; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; Tekin, Çağla; KAYA, İSMAİL SEÇKİN; Civan, Muhammet Nafi; KOCAELİ, HASAN; BEKAR, AHMET; Eser Ocak, Pınar; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; TOLUNAY, ŞAHSİNE; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/İnegöl Meslek Yüksekokulu.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahisi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0001-5472-9065; 0000-0002-4256-2250; 0000-0003-0132-9927; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-1619-6680; ADM-8457-2022; FPB-0403-2022; GXV-3107-2022; AAW-5254-2020; GDC-6329-2022; JGS-1849-2023; HKP-0793-2023; FDK-3229-2022; CGB-7869-2022; AAI-2073-2021; AAP-9988-2020; AAH-1420-2021; AAI-1612-2021; ABI-6078-2020Introduction: The noncoding RNAs (ncRNAs) play a role in biological processes of various cancers including gliomas. The majority of these transcripts are uniquely expressed in differentiated tissues or specific glioma types. Pediatric oligodendroglioma (POG) is a rare subtype of diffuse glioma and accounts for <1% of pediatric brain tumors. Because histologically POG resembles adult OG, the same treatment is applied as adults. However, the significance in predicting outcomes in POG patients is unclear. In this study, we aimed to investigate the prognostic significance of expression -profiles of microRNA (miRNA) and long noncoding RNA -(LncRNA) in POGs. Methods: We investigated the levels of 13 known miRNAs and 6 LncRNAs in tumor samples from 9 patients with primary POG by using RT-PCR and analyzed their association with outcomes. Results: The expression levels of miR-21, miR-106a, miR-10b, and LncRNA NEAT1 were higher, and the expression level of miR-143 was lower in POG tissues compared with normal brain tissues (p = 0.006, p = 0.032, p = 0.034, p = 0.002, and p = 0.001, respectively). High levels of NEAT1 and low expression of miR-143 were associated with decreased probability of short disease-free survival (p = 0.018 and p = 0.022, respectively). Discussion: NEAT1 and miR-143 levels could serve as reciprocal prognostic predictors of disease progression in patients with POG. New treatment models to regulate the expression levels of NEAT1 and miR-143 will bring a new approach to the therapy of POG.Publication Uridine treatment improves nerve regeneration and functional recovery in a rat model of sciatic nerve injury(Turkish Neurosurgical Soc, 2022-01-01) Khezri, Marzieh Karimi; Türkkan, Alper; KOÇ, CANSU; Salman, Berna; SALMAN, BERNA; Levent, Pınar; Çakır, Aysen; ÇAKIR, AYŞEN; CANSEV, MEHMET; KAFA, İLKER MUSTAFA; Bekar, Ahmet; BEKAR, AHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Anatomi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Farmaoloji Anabilim Dalı.; 0000-0002-6097-5585; 0000-0001-8309-0934; 0000-0003-2918-5064; A-6819-2018; ABX-9081-2022AIM: To investigate the regenerative potential and long-term functional effects of uridine treatment in a rat model of sciatic nerve injury.MATERIAL and METHODS: Male Sprague-Dawley rats were randomized to receive sham surgery plus saline (Sham group), right sciatic nerve transection and primary repair plus saline (Control group), right sciatic nerve transection, and primary repair plus 500 mg/kg uridine (Uridine group). Saline or uridine was injected intraperitoneally (i.p.) for seven days, and the rats were monitored for 12 weeks after surgery. We evaluated electrophysiological and functional recovery using electromyography (EMG) and sciatic functional index (SFI) at six and 12 weeks, respectively. At 12 weeks, rats were decapitated and their right sciatic nerves were examined in macroscopic and histomorphologic manners.RESULTS: Functional evaluation by SFI and sciatic nerve conduction velocity analyzed by EMG both decreased in the Control group but recovered in the Uridine group 12 weeks after surgery. Additionally, upon experiment completion, Uridine treatment was observed to enhance nerve adherence, separability scores, and the number of myelinated axons.CONCLUSION: These results reveal that short-term Uridine treatment provides morphological and electrophysiological benefits, which are represented by long-term functional improvement in a rat model of sciatic nerve injury. These findings validate and extend our knowledge on Uridine's regenerative effects in peripheral nerve injuries.Publication A rare cause of epilepsy: Ulegyria revisited in a series of 10 patients(Sage Publications, 2021-09-17) Demir, Aylin Bican; Eser, Pınar; Bekar, Ahmet; Hakyemez, Bahattin; Bora, İbrahim; BİCAN DEMİR, AYLİN; Eser, Pınar; BEKAR, AHMET; HAKYEMEZ, BAHATTİN; BORA, İBRAHİM HAKKI; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı/Epilepsi Merkezi.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Radyoloji Anabilim Dalı.; 0000-0001-6739-8605; 0000-0003-0132-9927; 0000-0002-3425-0740; ABX-9081-2022; AAI-2073-2021; V-7170-2017; AAI-2318-2021; ENI-7759-2022Introduction. Ulegyria results from perinatal hypoxic-ischemic brain injury in term infants. The specific mushroom-shaped configuration of ulegyria results from small atrophic circumvolutions at the bottom of a sulcus underlying an intact gyral apex. Clinically, ulegyria is generally associated with epilepsy. Here, we aimed to delineate the characteristics of patients with ulegyria and the epileptic seizures they experience. Material and methods. Medical records including radiology and pathology reports, video-electroencephalographic (EEG) analysis, operative notes, hospital progress and outpatient clinic notes were reviewed retrospectively in a total of 10 ulegyria patients. Results. Patients ages ranged between 24 and 58 years (mean, 32 +/- 9.8 years). Past medical history was confirmed for neonatal asphyxia in 2 (20%). Neurological examination was remarkable for spastic hemiparesis in 1 (10%) patient with perisylvian ulegyria and for visual field deficits in 2 patients (20%) with occipital ulegyria. Ulegyria most commonly involved the temporoparietal region (n = 5, 50%) followed by the perisylvian area (n = 2, 20%). Except the one with bilateral perisylvian ulegyria, all patients had unilateral lesions (n = 9, 90%). Hippocampal sclerosis accompanied ulegyria in 2 patients (20%). All patients experienced epileptic seizures. Mean age at seizure onset was 8.8 +/- 5.4 years (range, 2-20 years). Interictal scalp EEG and EEG-video monitoring records demonstrated temporoparietal and frontotemporal activities in 5 (50%) and 2 (20%) patients, respectively. The seizures were successfully controlled by antiepileptic medication in 8 patients (n = 8, 80%). The remaining 2 patients (%20) with concomitant hippocampal sclerosis required microsurgical resection of the seizure foci due to medically resistant seizures. Discussion. Ulegyria is easily recognized with its unique magnetic resonance imaging characteristics and clinical presentation in the majority of cases. It is highly associated with either medically resistant or medically controllable epileptic seizures. The treatment strategy depends on the age at onset and extends of the lesion that has a significant impact on the severity of the clinical picture.Publication Creutzfeldt-jakob disease: Report of four cases and review of the literature(De Gruyter Poland Sp Zoo, 2015-05-01) Özatalay, Fatma; ZARİFOĞLU, MEHMET; Tolunay, Şahsine; TOLUNAY, ŞAHSİNE; Özgün, Gonca; Zarifoğlu, Mehmet; BEKAR, AHMET; Bekar, Ahmet; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroşurji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; KGL-6139-2024; AAI-1612-2021; ABX-9081-2022Creutzfeldt-Jakob disease is a very rare, progressive neurodegenerative disorder that is incurable and always fatal. It is one of the transmissible spongiform encephalopathies caused by prions. Multiple vacuoles in neuropil and neuronal loss in the gray matter gives the classical sponge-like appearance of brain and are responsible for the typical clinical symptoms.In this report, we present 4 cases referred to the neurology department of Uludag University with neurological symptoms. Patients were evaluated with electroencephalogram and magnetic resonance imaging, and performed brain biopsies for further investigation. For definitive diagnosis of Creutzfeldt-Jakob disease, accumulation of prion protein in brain was detected immunohistochemically. Patients died within weeks in consequence of rapid progression of the disease.Although Creutzfeldt-Jakob disease is an infrequent disorder, when a patient presents with characteristic clinical symptoms such as rapidly progressive dementia with myoclonus, the diagnosis of Creutzfeldt-Jakob disease should be taken into consideration.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.
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