Person: TOLUNAY, ŞAHSİNE
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TOLUNAY
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ŞAHSİNE
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Publication Correlation between ubiquitin e3 ligases (siahs) and heat shock protein 90 in breast cancer patients(Iranian Scientific Society Medical Entomology, 2022-08-01) Takanlou, Leila Sabour; Çeçener, Gülşah; Takanlou, Maryam Sabour; Nazlioglu, Hulya Ozturk; Unlu, Havva Tezcan; Isik, Ozgen; Egeli, Unal; Tunca, Berrin; Çubukcu, Erdem; Tolunay, Sahsine; Gokgoz, Mustafa Sehsuvar; Cecener, Gulsah; ÇEÇENER, GÜLŞAH; Nazlioglu, Hulya Ozturk; ÖZTÜRK NAZLIOĞLU, HÜLYA; Isik, Ozgen; IŞIK, ÖZGEN; Egeli, Unal; EGELİ, ÜNAL; Tunca, Berrin; TUNCA, BERRİN; Çubukcu, Erdem; ÇUBUKÇU, ERDEM; Tolunay, Sahsine; TOLUNAY, ŞAHSİNE; 0000-0002-1928-992X; 0000-0002-3820-424X; 0000-0002-1590-4833; 0000-0002-0910-4258; 0000-0002-9541-5035; 0000-0001-7904-883X; 0000-0002-1619-6680; KGL-6846-2024; AAH-1420-2021; GRE-6268-2022; AAW-9602-2020; GYU-0252-2022Background: Breast cancer is a heterogeneous disease and differences in the expression levels of the ER, PR, and HER2 the triplet of established biomarkers used for clinical decision-making have been reported among breast cancer patients. Furthermore, resistance to anti-estrogen and anti-HER2 therapies emerges in a considerable rate of breast cancer patients, and novel drug therapies are required. Several anomalous signaling pathways have been known in breast cancer have been known; heat shock protein 90 (HSP90) is one of the most plenty proteins in breast cells. The family of ubiquitin ligases such as SIAH1 and SIAH2 is known to specifically target misfolded proteins to the proteasome; also, they have been illustrated to play a role in RAS signaling and as an essential downstream signaling component required for EGFR/HER2 in breast cancer.Methods: The expression of SIAH2, HSP90, and HER2 was assessed by quantitative Real-Time PCR in 85 invasive ductal carcinoma breast tumor samples at Uludag University Hospital in Turkey during the years 2018-2019, and its association with the clinicopathologic variables of patients was evaluated.Results: HSP90, SIAH1, and SIAH2 were significantly (P=0.0271, P=0.022, and P=0.0311) upregulated tumor tissue of patients with breast cancer. Moreover, this study observed a significant association between the high expression of SIAH2/ HSP90 with ER status, high expression of HSP90 with Recurrence/ Metastasis, and high expression of SIAH2 with Ki-67 proliferation index.Conclusion: The HSP90 and SIAH2 expressions play a significant role in breast cancer development by combining the experimental and clinical data obtained from the literature.Publication Dynamic contrast-enhanced T1-weighted perfusion magnetic resonance imaging identifies glioblastoma immunohistochemical biomarkers via tumoral and peritumoral approach: A pilot study(Elsevier Science, 2019-04-09) Öztürk, Kerem; Soylu, Esra; Tolunay, Şahsine; Narter, Selin; Hakyemez, Bahattin; Özturk, Kerem; Soylu, Esra; TOLUNAY, ŞAHSİNE; NARTER, SELİN; HAKYEMEZ, BAHATTİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Radyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0001-9664-2347; 0000-0002-3425-0740; AAI-2318-2021; E-1228-2018; AAI-1612-2021; DSW-1175-2022; FOL-7699-2022OBJECTIVE: We aimed to evaluate the usefulness of dynamic contrast-enhanced T1-weighted perfusion magnetic resonance imaging (DCE-pMRI) to predict certain immunohistochemical (IHC) biomarkers of glioblastoma (GB) in this pilot study.METHODS: We retrospectively reviewed 36 patients (male/female, 25:11; mean age, 53 years; age range, 29-85 years) who had pretreatment DCE-pMRI with IHC analysis of their excised GBs. Regions of interest of the enhancing tumor (ER) and nonenhancing peritumoral region (NER) were used to calculate DCE-pMRI parameters of volume transfer constant, back flux constant, volume of the extravascular extracellular space, initial area under enhancement curve, and maximum slope. IHC biomarkers including Ki-67 labeling index, epidermal growth factor receptor (EGFR), oligodendrocyte transcription factor 2 (OLIG2), isocitrate dehydrogenase 1 (IDH1), and p53 mutation status were determined. The imaging metrics of GB with IHC markers were compared using the Kruskal-Wallis test and Spearman correlation analysis.RESULTS: Among 30 patients with available IDH1 status, 14 patients (46.6%) had IDH1 mutation. EGFR amplification was present in 24/36 (66.6%) patients. Mean Ki-67 labeling index was 29% (range, 1.5%-80%). p53 mutation was present in 20/36 GBs (55%), whereas OLIG2 expression was positive in 29/36 GBs (80.5%). Various DCE-pMRI parameters gathered from the ER and NER were significantly correlated with IDH1 mutation, EGFR amplification, and OLIG2 expression (P < 0.05). Ki-67 labeling index showed a strong positive correlation with initial area under enhancement curve (r = 0.619; P < 0.001).CONCLUSIONS: DCE-pMRI could determine surrogate IHC biomarkers in GB via tumoral and peritumoral approach, potential targets for individualized treatment protocols.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 Long non-coding rnas as a predictive markers of group 3 medulloblastomas(Taylor & Francis, 2021-08-28) Mutlu, Melis; Tekin, Çağla; Ak Aksoy, Seçil; Taşkapılıoğlu, Mevlüt Özgur; Kaya, Seçkin; Balcin, Rabia Nur; Ocak, Pınar Eser; Bekar, Ahmet; Tolunay, Şahsine; Tunca, Berrin; Mutlu, Melis; Tekin, Çağla; Ak Aksoy, Seçil; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; KAYA, İSMAİL SEÇKİN; BALÇIN, RABİA NUR; OCAK, PINAR; BEKAR, AHMET; TOLUNAY, ŞAHSİNE; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/İnegöl Meslek Yüksekokulu.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0001-5472-9065; 0000-0002-4256-2250; 0000-0003-0132-9927; 0000-0002-1619-6680; GXV-3107-2022; AAI-2073-2021; ADM-8457-2022; ABX-9081-2022; FPB-0403-2022; GDC-6329-2022; AAW-5254-2020; JGS-1849-2023; FDK-3229-2022; AAI-1612-2021Objective The appropriate treatments for the different molecular subgroups of medulloblastomas are challenging to determine. Hence, this study aimed to examine the expression profiles of long non-coding RNAs (LncRNAs) to determine a marker that may be important for treatment selection in these subgroups. Methods Changes in the expression of LncRNAs in the tissues of patients with medulloblastoma, which are classified into four subgroups according to their clinical characteristics and gene expression profiles, were examined via reverse transcription polymerase chain reaction. Moreover, there association with patient prognosis was evaluated. Results The expression levels of MALAT1 and SNGH16 were significantly higher in patients with group 3 medulloblastoma than in those with other subtypes. Patients with high expression levels of MALAT1 and SNGH16 had a relatively shorter overall survival than those with low expression levels. Conclusions Patients with group 3 medulloblastoma have a high MALAT1 level, which is associated with poor prognosis. Therefore, MALAT1 can be a new therapeutic target in medulloblastoma.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 Phyllodes tumor of the breast: A clinicopathological evaluation of 55 cases(Aves, 2020-01-01) Hasdemir, Seçil; Tolunay, Şahsine; Özşen, Mine; Gökgöz, Mustafa Şehsuvar; HASDEMİR, SEÇİL; TOLUNAY, ŞAHSİNE; ÖZŞEN, MİNE; GÖKGÖZ, MUSTAFA ŞEHSUVAR; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Meme Cerrahisi Anabilim Dalı; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı; 0000-0003-1769-7484; 0000-0002-9038-0515; 0000-0002-5771-7649; 0000-0003-1394-2630; GBY-7549-2022; AAI-1612-2021; AAI-1609-2021; JKX-1058-2023Objective: Phyllodes tumors are biphasic tumors consisting of epithelial and stromal components that account for less than 1% of all breast tumors. According to the World Health Organization (WHO) phyllodes tumors are classified into three categories as benign, borderline and malignant. It has been reported that these tumors are usually benign and both the stromal component and the epithelial component may progress to malignancy. In this descriptive study, it was aimed to present the cases of phyllodes tumor and to evaluate the clinicopathological features of these tumors in the light of the literature.Materials and Methods: In our study, 55 cases of phyllodes tumor diagnosed between 2005-2018 in the Department of Medical Pathology were retrospectively studied. A total of 55 cases were included in the study.Results: All cases were female with a mean age of 39.7+15.2 years. Fifty-seven tumors diagnosed in 55 cases were classed as benign in 20 cases (35.1%), borderline in 14 cases (24.6%) and malignant phyllodes tumors in 23 cases (40.3%). Ductal carcinoma in situ (solid and cribriform type) were detected in one case with malignant phyllodes tumor, whereas invasive ductal carcinoma was detected in one case. Bilateral ductal carcinoma in situ was present in the patient with invasive ductal carcinoma.Conclusion: These tumors which rapidly grow into large masses can be clinically and pathologically confused with benign lesions, macroscopic and microscopic evaluation of concomitant in situ-invasive carcinomas should be considered. Phyllodes tumors have an important role in breast surgery and pathology.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 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 Microrna expression pattern modulates temozolomide response in gbm tumors with cancer stem cells(Springer/plenum Publishers, 2014-07-01) Preusser, Matthias; Berghoff, Anna Sophie; Ricken, Gerda; Tezcan, Gülçin; TEZCAN, GÜLÇİN; EGELİ, ÜNAL; Bekar, Ahmet; BEKAR, AHMET; KOCAELİ, HASAN; TUNCA, BERRİN; Tunca, Berrin; Çeçener, Gülşah; ÇEÇENER, GÜLŞAH; Budak, Ferah; BUDAK, FERAH; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; Taşkapılıoğlu, Mevlüt Özgür; Tolunay, Şahsine; TOLUNAY, ŞAHSİNE; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Medikal Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Mikrobiyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroşurji Anabilim Dalı.; 0000-0002-5956-8755; 0000-0002-1619-6680; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0003-0388-7965; 0000-0001-7625-9148; 0000-0001-5472-9065; F-4657-2014; IZP-9398-2023; AAH-3843-2020; ABB-8161-2020; AAI-1612-2021; ABX-9081-2022; ABI-6078-2020; AAH-1420-2021; AAW-5254-2020; F-8554-2017; AAP-9988-2020Temozolomide (TMZ) is widely used to treat glioblastoma multiforme (GBM). Although the MGMT gene methylation status is postulated to correlate with TMZ response, some patients with a methylated MGMT gene still do not benefit from TMZ therapy. Cancer stem cells (CSCs) may be one of the causes of therapeutic resistance, but the molecular mechanism underlying this resistance is unclear. microRNA (miRNA) deregulation has been recognized as another chemoresistance modulating mechanism. Thus, we aimed to evaluate the miRNA expression patterns associated with chemoresistance that is dependent on the CSC status in GBM tumors to identify therapeutic biomarkers. CSCs were identified in 5 of 20 patients' tumor tissues using magnetic separation. CSC (+) tumors displayed a significant induction of CpG island methylation in the MGMT gene promoter (p = 0.009). Using real-time reverse transcription polymerase chain reaction (qRT-PCR), 9 miRNAs related to GBM (mir-181b, miR-153, miR-137, miR-145, miR-10a, miR-10b, let-7d, miR-9, and miR-455-3p), which are associated with cell cycle and invasion was analyzed in tumor samples. Low miR-181b and high miR-455-3p expression levels were detected (p = 0.053, p = 0.004; respectively) in CSC (+) tumors. Analysis revealed a significant correlation between miR-455-3p expression and Smad2 protein levels as analyzed by immunohistochemistry in CSC (+) tumors (p = 0.002). Thus, miR-455-3p may be involved in TMZ resistance in MGMT methylated CSC (+) GBM patients. Further studies and evaluations are required, but this miRNA may provide novel therapeutic molecular targets for GBM treatment and new directions for the development of anticancer drugs.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.