Browsing by Author "TUNCA, BERRİN"
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Publication A novel [Mn2(μ-(C6H5)2CHCOO)2(bipy)4](bipy)(ClO4)2 complex loaded solid lipid nanoparticles: Synthesis, characterization and in vitro cytotoxicity on MCF-7 breast cancer cells(Taylor & Francis Ltd, 2016-09-01) Kani, İbrahim; Dikmen, Gökhan; Eskiler, G. Güney; Çeçener, Gülşah; Egeli, Ünal; Tunca, Berrin; EGELİ, ÜNAL; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-2088-9914; 0000-0002-3820-424X; 0000-0003-0304-3527; 0000-0001-7904-883X; 0000-0002-1619-6680; ABI-6078-2020; AAP-9988-2020; AAH-1420-2021; AAB-6011-2022Manganese (Mn)-based complexes have been drawing attention due to the fact that they are more effective than other metal complexes. However, the use of Mn(II)-based complexes in medicine remains limited because of certain side effects. The aim of this study was to investigate the cytotoxic and apoptotic effects of a novel Mn(II) complex [Mn-2(mu-(C6H5)(2)CHCOO)(2)(bipy)(4)](bipy)(ClO4)(2) and Mn(II) complex loaded solid lipid nanoparticles (SLNs) on MCF-7 and HUVEC control cells. The average diameter of Mn(II) complex was about 1120 +/- 2.43nm, while the average particle size of Mn(II) complex-SLNs was approximate to 340 +/- 2.27nm. The cytotoxic effects of Mn(II) complex and Mn(II)-SLNs were 86.8 and 66.4%, respectively (p<.05). Additionally, both Mn(II) complex (39.25%) and Mn(II)-SLNs (38.05%) induced apoptosis and increased the arrest of G(0)/G(1) phase. However, Mn(II) complex exerted toxic effects on the HUVEC control cell (63.4%), whereas no toxic effects was observed when treated with Mn(II)-SLNs at 150M. As a consequence, SLNs might be potentially used for metal-based complexes in the treatment of cancer due to reducing size and toxic effects of metal-based complexes.Publication Association of MDR1 C3435tTpolymorphism and antiepileptic prophylactic therapy response in Turkish migraine patients (preliminary results)(Sage Publications, 2015-05-01) Zarifoğlu, M.; Atasayar, G.; Eryılmaz, E.; Egeli, U.; Çeçener, G.; Tunca, B.; Ak, S.; Yıldırım, O.; Karlı, N.; Kapılıoğlu, O. Tas; ZARİFOĞLU, MEHMET; ATASAYAR, GÜLFER; ERYILMAZ, EMRE; EGELİ, ÜNAL; TUNCA, BERRİN; AK, SEMİH; YILDIRIM, ÖZNUR; KARLI, NEJDET; KAPILIOĞLU, TAŞ; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0001-6919-9423; ABI-6078-2020; AAH-1420-2021; AAP-9988-2020Bu çalışma, 14-17 Mayıs 2015 tarihlerinde Valencia'da düzenlenen International Headache Congress of the International Headache Society'de bildiri olarak sunulmuştur.Publication BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile(Wiley, 2019-05-01) Eskiler, Gamze Güney; Çeçener, Gülşah; Egeli, Ünal; Tunca, Berrin; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-1619-6680; AAP-9988-2020; ABI-6078-2020; AAH-1420-2021The objective of the present study was to elucidate the effect of BMN 673 (talozoparib) on BRCA1 mutant (HCC1937) and wild-type (MDA-MB-231) triple negative breast cancer (TNBC). The in vitro cytotoxicity results indicated that BMN 673 had considerable inhibitory effects on HCC1937 and MDA-MB-231 cell lines by inducing apoptosis, multicaspase activity, G2/M arrest, and altering the expression levels of apoptosis-related genes (P < 0.01). Additionally, BMN 673 indicated no toxicity on MCF-10A control cells until a certain concentration and incubation time. However, BMN 673, a novel and selective poly ADP ribose polymerase inhibitor, was more potent in TNBC cells bearing BRCA1 mutant than those with wild-type BRCA1. In conclusion, our study, for the first time, demonstrated a molecular mechanism of the induction of apoptosis by BMN 673 in TNBC with different genetic profile. However, further investigations regarding the exact molecular mechanisms underlying BMN 673-inducing apoptotic death and gene-cell line associations are required.Publication Cancer stem cell markers in pancreatic ductal adenocarcinoma(Oxford Univ Press, 2018-10-01) Aksoy, Fuat; Kaya, Ekrem; Egeli, Ünal; Dündar, Halit Ziya; Taşar, Pınar; Aksoy, Seçil; Özen, Yılmaz; Tunca, Berrin; Çeçener, Gülşah; Yerci, Ömer; AKSOY, FUAT; KAYA, EKREM; EGELİ, ÜNAL; DÜNDAR, HALİT ZİYA; TAŞAR, PINAR; AKSOY, SEÇİL; ÖZEN, YILMAZ; TUNCA, BERRİN; ÇEÇENER, GÜLŞAH; YERCİ, ÖMER; 0000-0002-9562-4195; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Bölümü; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Biyoloji Bölümü; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Bölümü; 0000-0001-5808-9384; 0000-0001-7904-883X; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0002-3820-424X; AAH-1420-2021; AAH-3847-2021; ADM-8457-2022; HII-8895-2022; ABI-6078-2020; AAG-7319-2021; EWI-3634-2022; IIC-9825-2023; FOQ-1792-2022; AAP-9988-2020Publication 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 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 Contribution of functional dopamine D2 and D3 receptor variants to motor and non-motor symptoms of early onset Parkinson's disease(Elsevier, 2020-09-28) Eryılmaz, Işıl Ezgi; Erer, Sevda; Zarifoğlu, Mehmet; Egeli, Ünal; Karakuş, Ece; Yurdacan, Beste; Çeçener, Gülşah; Tunca, Berrin; Çolakoğlu, Beril; Tokcaer, Ayşe Bora; Saka, Esen; Demirkıran, Meltem; Akbostancı, Cenk; Doğu, Okan; Kaleağası, Hakan; Kenangil, Gülay; Çakmur, Raif; Elibol, Bülent; ERYILMAZ, IŞIL EZGİ; ERER ÖZBEK, ÇİĞDEM SEVDA; ZARİFOĞLU, MEHMET; EGELİ, ÜNAL; Karakuş, Ece; Yurdacan, Beste; ÇEÇENER, GÜLŞAH; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi.; 0000-0002-3316-316X; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-1619-6680; GWV-3548-2022; DVY-9744-2022; EHN-5825-2022; AAH-1420-2021; FDA-2023-2022; AEA-0144-2022; AAP-9988-2020; ABI-6078-2020In the present study, we focused on investigating the contribution of functional dopamine D2 and D3 receptor variants to motor and/or non-motor symptoms of early onset Parkinson's disease (EOPD). Three functional single nucleotide polymorphisms (SNPs), DRD3 rs6280, DRD2 rs2283265 and DRD2 rs1076560, were genotyped in 128 Turkish EOPD patients and then, statistical analysis was conducted for the potential impacts of SNPs on clinical parameters. All three SNPs were found to be statistically significant in terms of PD-related pain: DRD3 [rs6280; risk allele "T" for pain; p = 0.031; odds ratio (OR)=4.25], DRD2 [rs2283265; risk allele "A" for pain; p = 0.001; OR=8.47] and, DRD2 [rs1076560; risk allele "A" for pain; p = 0.022; OR=4.58]. Additionally, bilateral disease [p = 0.011; OR=5.10] and gender [risk group "female"; p = 0.003; OR=8.53] were also identified as significant univariate risk factors for PD-related pain. Based on logistic regression analysis conducted with the significant univariate risk factors, this the first report to clarify that a female patient with bilateral PD and DRD2 rs2283265 polymorphism has a significant risk for PD-related pain. Our findings might contribute to improve life quality by offering treatment options for pain in PD patients with these clinical and genetic features.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 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 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; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Onkoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Onkoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü.; 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 Early-stage colon cancer with high malat1 expression is associated with the 5-fluorouracil resistance and future metastasis(Springer, 2022-07-06) Öztürk, Ersin; Aksoy, Seçil Ak; Tunca, Berrin; TUNCA, BERRİN; Erçelik, Melis; Tezcan, Gulcin; TEZCAN, GÜLÇİN; Çeçener, Gülşah; ÇEÇENER, GÜLŞAH; UĞRAŞ, NESRİN; YILMAZLAR, AHMET TUNCAY; Yerci, Omer; YERCİ, ÖMER; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0002-1619-6680; 0000-0002-5956-8755; 0000-0001-8593-5101; 0000-0002-3820-424X; ADM-8457-2022; AAH-3843-2020Background This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC). Methods and Results The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients. To confirm the findings in-vitro, 5FU-resistant HT29 cells were generated by subjecting HT-29 cells to the increasing concentrations of 5FU for 6 months. The 5FU resistance was observed in WST-1 and Annexin V analyses. The colony formation and wound healing assays were assessed to determine the metastatic properties of the cells. Expression levels of LncRNAs and mRNA of EMT-related genes were determined by RT-PCR. The role of LncRNA on metastasis and 5FU sensitivity were confirmed in pcDNA3.0-PTENP1 and si-MALAT1 expressed 5FU-resistant HT29 cell lineages. Results High MALAT1 (p = 0.0002) and low PTENP1 (p = 0.0044) expressions were significantly associated with 5-FU resistance and tumor relapse in stage I/II CC. The invasiveness and colony-forming characteristics of 5-FU-resistant cell lineages were higher as compared to the parent HT-29. Moreover, the expression of MALAT1 (p = 0.0009) was increased while the expression of PTENP1 (p = 0.0158) decreased in 5FU-resistant-HT-29 cells. Si-MALAT1 treatment increased cell sensitivity to 5FU, whereas it decreased invasive behaviors of 5 FU-resistant-HT-29 cells. Conclusion MALAT1 may be a biomarker in predicting recurrence in early-stage CC. Our findings suggest that a cell-based therapy to target MALAT1 could be established for these patients to prevent metastasis and 5-FU resistance.Publication Evaluation of the clinical features accompanied by the gene mutations the 2 novel PSEN1 variants in a Turkish early-onset alzheimer disease cohort(Lippincott Williams & Wilkins, 2021-07-01) Eryılmaz, Işıl E.; Bakar, Mustafa; Egeli, Ünal; Çeçener, Gülşah; Yurdacan, Beste; Çolak, Dilara K.; Tunca, Berrin; ERYILMAZ, IŞIL EZGİ; BAKAR, HACI MUSTAFA; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; Yurdacan, Beste; Çolak, Dilara K.; TUNCA, BERRİN; Bursa Uludağ Üniversite/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0002-1619-6680; GWV-3548-2022; AEA-0144-2022; AAH-1420-2021; EKN-8251-2022; AAP-9988-2020; HXB-1173-2023; ABI-6078-2020Introduction: Early-onset Alzheimer disease (EOAD) is an earlier Alzheimer disease form which is characterized by the mutations in the amyloid precursor protein, presenilin-1/2 (PSEN1/2), and triggering receptor expressed on myeloid cells 2 (TREM2). However, it is still necessary to report mutational screening in multiethnic groups to improve the genetic background of EOAD due to the variant classification challenge. Methods: We performed targeted sequencing for the amyloid precursor protein, PSEN1, PSEN2, and TREM2 genes in 74 patients and 1 family diagnosed with EOAD. Results: Among the detected variants, 8 were coding and 6 were noncoding in 15 of 74 patients. In PSEN1, 2 pathogenic coding variants (T274K and L364P) detected in 2 patients were novel and 3 coding variants (G183V, E318G, and L219P) detected in 2 patients were previously reported. We found 4 patients with the compound heterozygosity for the PSEN2 A23= and N43= and a family with the coexistence of them, and 1 patient with TREM2 Y38C. The coding variation frequency was 12.1%. In silico analysis indicated pathogenic potentials and clinical interpretations of the detected variants. Conclusion: Our study reveals the rare gene variants including novel ones from the Turkish EOAD cohort and provides to clinicians the list of detected variants in the screened genes, which may also be useful for accurate genetic counseling.Publication Identification and management of Lynch syndrome in the Middle East and North African countries: outcome of a survey in 12 countries(Springer, 2020-10-06) Sina, Mohammad; Ghorbanoghli, Zeinab; Abedrabbo, Amal; Al-Mulla, Fahd; Ben Sghaier, Rihab; Buisine, Marie-Pierre; Cortas, George; Goshayeshi, Ladan; Hadjisavvas, Andreas; Hammoudeh, Wail; Hamoudi, Waseem; Jabari, Carol; Loizidou, Maria A.; Majidzadeh-A, Keivan; Marafie, Makia J.; Muslumov, Gurbankhan; Rifai, Laila; Seir, Rania Abu; Talaat, Suzan M.; Tunca, Berrin; Ziada-Bouchaar, Hadia; Velthuizen, Mary E.; Sharara, Ala I.; Ahadova, Aysel; Georgiou, Demetra; Vasen, Hans F. A.; Middle East Netw; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-1619-6680; ABI-6078-2020Background Lynch syndrome (LS), the most common inherited form of colorectal cancer (CRC), is responsible for 3% of all cases of CRC. LS is caused by a mismatch repair gene defect and is characterized by a high risk for CRC, endometrial cancer and several other cancers. Identification of LS is of utmost importance because colonoscopic surveillance substantially improves a patient's prognosis. Recently, a network of physicians in Middle Eastern and North African (ME/NA) countries was established to improve the identification and management of LS families. The aim of the present survey was to evaluate current healthcare for families with LS in this region. Methods A questionnaire was developed that addressed the following issues: availability of clinical management guidelines for LS; attention paid to family history of cancer; availability of genetic services for identification and diagnosis of LS; and assessment of knowledge of LS surveillance. Members of the network and authors of recent papers on LS from ME/NA and neighbouring countries were invited to participate in the survey and complete the online questionnaire. Results A total of 55 individuals were invited and 19 respondents from twelve countries including Algeria, Azerbaijan, Cyprus, Egypt, Iran, Jordan, Kuwait, Lebanon, Morocco, Palestine, Tunisia, and Turkey completed the questionnaire. The results showed that family history of CRC is considered in less than half of the surveyed countries. Guidelines for the management of LS are available in three out of twelve countries. The identification and selection of families for genetic testing were based on clinical criteria (Amsterdam criteria II or Revised Bethesda criteria) in most countries, and only one country performed universal screening. In most of the surveyed countries genetic services were available in few hospitals or only in a research setting. However, surveillance of LS families was offered in the majority of countries and most frequently consisted of regular colonoscopy. Conclusion The identification and management of LS in ME/NA countries are suboptimal and as a result most LS families in the region remain undetected. Future efforts should focus on increasing awareness of LS amongst both the general population and doctors, and on the improvement of the infrastructure in these countries.Publication Investigation of apc mutations of a patient with fap and her family members by heterodublex analyses(Nature Publishing Group, 2002-05-01) Menigatti, M; Benatti, P; Pedroni, M; Scarselli, A; Borghi, F; Sala, E; Yerci, O; de Leon, MP; TUNCA, BERRİN; Çeçener, Gülşah; YILMAZLAR, AHMET TUNCAY; ÇEÇENER, GÜLŞAH; Yılmazlar, Tuncay; Zorluoglu, A; EGELİ, ÜNAL; Yerci, Ömer; YERCİ, ÖMER; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Medikal Biyoloji ve Genetik Anabilim Dalı.; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0001-7904-883X; AAH-1420-2021; ABI-6078-2020Publication 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; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Klinik Biyoloji Anabilim 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 Investigation of VHL gene associated with miR-223 in clear cell renal cell carcinoma(Springer, 2021-11-26) Ünal, Ufuk; Çeçener, Gülşah; Ünlü, Havva Tezcan; Vuruşkan, Berna Aytaç; Erdem, Ecem Efendi; Egeli, Ünal; Nazlıoğlu, Hülya Öztürk; Kaygısız, Onur; Tunca, Berrin; Vuruşkan, Hakan; Ünal, Ufuk; ÇEÇENER, GÜLŞAH; Ünlü, Havva Tezcan; AYTAÇ VURUŞKAN, BERNA; Erdem, Ecem Efendi; EGELİ, ÜNAL; ÖZTÜRK NAZLIOĞLU, HÜLYA; KAYGISIZ, ONUR; TUNCA, BERRİN; VURUŞKAN, HAKAN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Patoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Üroloji Anabilim Dalı.; 0000-0003-4913-3616; 0000-0002-3820-424X; 0000-0002-0910-4258; 0000-0001-7904-883X; 0000-0002-9790-7295; 0000-0002-1619-6680; AAH-1420-2021; L-9439-2019; GYU-0252-2022; ABC-1357-2020; AAP-9988-2020; GYU-0252-2022; EEJ-1452-2022; ESY-2704-2022; FLN-9596-2022; ABI-6078-2020; EFH-9523-2022Background Clear cell type renal cell carcinoma (ccRCC) is the most common renal cell carcinoma (RCC). In this study, we examined the expressions of VHL and miR-223 in ccRCC patients' tissues to investigate the possible role in the development of ccRCC.Methods and results This study collected five expression profiles (GSE36139, GSE3, GSE73731, GSE40435, and GSE26032) from Gene Omnibus Data. Expressions of VHL and miR-223 in paraffinized tumor and normal tissues of 100 Turkish patients' ccRCC tissues were determined by bioinformatic data mining and real-time quantitative polymerase chain reaction (qRT-PCR). The VHL gene was subjected to mutational analysis by DNA sequencing, and pVHL was analyzed using western blotting. Our study's t-test and Pearson correlation analysis showed that VHL gene expression in tumoral tissues with a - 0.39-fold decrease was not significantly lower than normal tissues (p = 0.441), and a 0.97-fold increase miR-223 (p = 0.045) was determined by real-time PCR. Also, as a result of DNA sequence analysis performed in the VHL gene, it was found that 26% of the patients have mutations. The mutations for (VHL):c.60C>A (p.Val20=) and (VHL):c.467delA (p.Tyr156Leu) was detected for the first time in Turkish patients.Conclusions The present study demonstrated that the differences in the expression levels of miR-223 have the potential to be biomarkers to determine the poor prognosis in ccRCC.Publication Liver-derived exosomes in liquid biopsies: Advantage before liver transplantation - a pilot study(Lippincott Williams & Wilkins, 2021-08-01) ; Aksoy, F.; AKSOY, FUAT; Aksoy, Seçil Ak; Tunca, B.; TUNCA, BERRİN; Kıyıcı, M.; Kaya, E.; Bursa Uludağ Üniversitesi.; 0000-0001-5808-9384; 0000-0002-1619-6680; HII-8895-2022; ADM-8457-2022Publication 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 MDR1 C3435t polymorphism predicts anti-epileptic prophylactic therapy response in Turkish migraine patients(Elsevier, 2015-10-15) Atasayar, Gülfer; Ezgi, Eryılmaz Işil; Yıldırım, Y. Öznur; Karlı, N.; Ünal, Ersin; Gülşah, Çeçener; Mehmet, Zileli; Berrin, Tuğrul; Gülçin, T.; Özlem, Temelli; ERYILMAZ, IŞIL EZGİ; Atasayar, G.; Yıldırım, Y. Öznur; Karlı, N.; ÜNAL, EDA; ÇEÇENER, GÜLŞAH; Mehmet, Zileli; TUNCA, BERRİN; Gülçin, T.; Özlem, Temelli; Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Bölümü; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Bölümü; 0000-0002-3183-9592; CEW-6612-2022; COE-7420-2022; IQE-9004-2023; JDE-9380-2023; CFN-0407-2022; EWA-9478-2022; DGE-3419-2022; EMJ-3438-2022; EYK-4124-2022; FSF-8333-2022