Browsing by Author "EGELİ, ÜNAL"

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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-6011-2022
Manganese (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.
An in vitro redox adaptation model for metastatic prostate cancer: Establishing, characterizing and cabazitaxel response evaluating
(Wiley, 2022-07-14) ERYILMAZ, IŞIL EZGİ; EGELİ, ÜNAL; Egeli, Ünal; Çeçener, Gülşah; ÇEÇENER, GÜLŞAH; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0001-7904-883X; 0000-0002-3820-424X; GWV-3548-2022; AAH-1420-2021
Little is known about the redox-adapted cancer cells for understanding their pharmacologically targetable features and chemotherapeutic responses. Thus, we present the first in vitro redox adaptation model for metastatic prostate cancer (mPC), LNCaP-hydrogen peroxide resistant (LNCaP-HPR), with enhanced oxidative stress resistance accompanying poor Cabazitaxel response. After establishing, the cells were characterized by comparing the viability, death, oxidative stress, total glutathione (GSH) levels and the mRNA and protein levels of the redox-sensitive transcription factors responsible for the adaptation, Nrf-2, NF-kappa B and HIF-1 alpha. Then, the apoptotic effect of Cabazitaxel was evaluated in LNCaP mPC, LNCaP-HPR and C4-2 metastatic castration-resistant (mCRPC) cells. In response to H2O2, viability, oxidative stress and the total GSH levels of LNCaP-HPR cells have confirmed the oxidative stress resistance. Nrf-2, NF-kappa B and HIF-1 alpha were upregulated in LNCaP-HPR cells, not in LNCaP, confirming that resistant cells were much less affected by exogenous oxidative stress. Unlike LNCaP, LNCaP-HPR cells were less sensitive to Cabazitaxel, as closer to the response of C4-2 mCRPC cells, indicating that redox adaptation decreased Cabazitaxel response. This is the first evaluated association between redox adaptation and poor Cabazitaxel response, suggesting that in vitro Cabazitaxel efficiency is affected by PC cells' endogenous oxidative stress tolerance.
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-9988-2020
Bu çalışma, 14-17 Mayıs 2015 tarihlerinde Valencia'da düzenlenen International Headache Congress of the International Headache Society'de bildiri olarak sunulmuştur.
Biomarker potential of urine miR-451 at different stages of diabetic nephropathy
(Omics Int Pvt Ltd, 2016-02-01) Sayılar, Emel Işıktaş; Güllülü, Mustafa; Tuncel, Ercan; Peynirci, Hande; Alemdar, Adem; Tunca, Berrin; Egeli, Ünal; Çeçener, Gülşah; Bayındır, Murat; Coşgun, Gökhan; Sayılar, Emel Işıktaş; GÜLLÜLÜ, MUSTAFA; Tuncel, Ercan; Peynirci, Hande; ALEMDAR, ADEM; TUNCA, BERRİN; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; Bayındır, Murat; Coşgun, Gökhan; Uludağ Üniversitesi/Tıp Fakültesi/Nefroloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Endokrinoloji ve Metabolizma Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Dahiliye Anabilim Dalı.; 0000-0002-1619-6680; 0000-0001-7904-883X; 0000-0002-3820-424X; W-2575-2017; CTG-8811-2022; EBN-7188-2022; GRY-0605-2022; ELA-3536-2022; ABI-6078-2020; AAH-1420-2021; AAP-9988-2020; CFN-0933-2022; ERH-7786-2022
Aims: To evaluate the potential of urinary miR-451 as a biomarker at different stages of diabetic nephropathy.Methods: A total of 45 subjects having stage 3 chronic kidney disease (n=15) or stage 5 chronic kidney disease (n=15) and 15 healthy volunteers were included. Data on patient demographics, laboratory findings [creatinine, estimated glomerular filtration rate, urinary protein excretion] target genes and functions of the selected MicroRNAs associated with diabetic nephropathy and fold differences in the level of MicroRNA expression in blood and urine and the correlation of urine and plasma MicroRNA expression with estimated glomerular filtration rate were recorded.Results: MiR-195 expression level among stage 3 chronic kidney disease patients was higher in plasma samples compared to the control group, while it was significantly lower in the urine samples (p=0.036). In the stage 5 chronic kidney disease patient group, while the expression level was significantly higher in the plasma samples (p=0.005), urine sample expression was lower but not significantly different than the control group. Compared to the controls, miR-451 expression level was higher in the plasma samples of stage 3 chronic kidney disease patients, but significantly lower in the urine samples (p=0.019). Among the stage 5 chronic kidney disease patients, there was significantly higher level of expression in plasma samples (p=0.007) and significantly lower expression in urine samples (p=0.022) than the control group.Conclusions: Our study is original with its investigation of MicroRNA expressions at different stages of chronic kidney disease. Especially the statistically significant changes in the expression of miR-195 and miR-451 make these MicroRNAs come forward as good noninvasive biomarker candidates.
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-1420-2021
The 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.
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-9988-2020
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-2073-2021
AIM: 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.
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-6078-2020
In 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.
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-0252-2022
Background: 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.
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-0745-2022
Background 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.
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-6078-2020
Introduction: 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.
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 Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0002-3316-316X; GWV-3548-2022; EKN-8251-2022; AAH-1420-2021; AAP-9988-2020; AEA-0144-2022; HXB-1173-2023; ABI-6078-2020
Introduction: 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.
Investigation for aneuploidy of chromosomes 7, 9, 10, 17 and p53 gene deletions between low and high grade glial tumors using interphase fish technique
(Wiley, 2004-09-01) Yakut, T.; Bekar, A.; Egeli, U.; Doygun, M; Ercan, İ.; Yiğit, B; Oğul, E; Yakut, Tahsin; BEKAR, AHMET; EGELİ, ÜNAL; Doygun, Muammer; ERCAN, İLKER; Yiğit, Barbaros; Oğul, Erhan; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji ve Genetik Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Sinir Cerrahisi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı.; 0000-0001-7904-883X; 0000-0002-2382-290X; GIS-1493-2022; CGB-7869-2022; AAH-1420-2021; EWX-6327-2022; ABF-2367-2020; EHO-7411-2022; FPJ-1350-2022
We investigated for aneuploidy of chromosomes 7, 9, 10, 17, and p53 gene deletions in 36 glial tumor tissues, using interphase fluorescence in situ hybridization (FISH), and compared the frequencies of abnormalities between low and high grade tumors. Among the 13 low grade tumors; 1 had trisomy 7, 1 had monosomy 9, 2 had monosomy 10, 1 had monosomy 17, 1 had p53 deletion, and among the 23 high grade tumors; 10 had trisomy 7, 1 had monosomy 9, 7 had monosomy 10, 2 had monosomy 17, 6 had p53 deletion. The results indicated that neither aneuploidy of chromosome 9, nor chromosome 17 are prominent findings between low or high grade of glial tumors, although high-grade glial tumors have higher rates of trisomy 7 (43.5%), monosomy 10 (30.4%) and p53 (26%) deletion than low-grade ones. Statistical results showed significant difference between trisomy 7 and high grade astrocytomas (p = 0.031). Considering these chromosomal abnormalities we suggest that trisomy 7, loss of chromosome 10 and alterations of the p53 gene have important role associated with glial tumor development and trisomy 7 is the most important genetic changes associated with glial tumor progression.
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-6078-2020
Investigation of miR-146a expression profiles in fecal samples of patients with multiple sclerosis for early diagnosis and treatment
(Wolters Kluwer Medknow Publications, 2023-04-01) Ünlü, Havva Tezcan; Sarıdaş, Furkan; Taşkapılıoğlu, Özlem; Çeçener, Gülşah; Egeli, Ünal; Turan, Ömer Faruk; Tunca, Berrin; Zarifoğlu, Mehmet; Ünlü, Havva Tezcan; SARIDAŞ, FURKAN; Taşkapılıoğlu, Özlem; TURAN, ÖMER FARUK; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; TUNCA, BERRİN; ZARİFOĞLU, MEHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; 0000-0002-0910-4258; 0000-0001-5945-2317; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-1619-6680; GYU-0252-2022; HSB-2700-2023; EBA-4926-2022; AAP-9988-2020; AAH-1420-2021; JDI-6091-2023; ABI-6078-2020; EHN-5825-2022
Introduction: Recent research into multiple sclerosis (MS) has focused on the role of microRNAs (miRNAs) in the development of the disease. This study was designed to analyze miR-146a expression in whole blood and fecal samples of patients with MS. The study aimed to analyze clinical data using the miR-146a expression values obtained. Subjects and Methods: This study included patients with relapsing-remitting MS (RRMS) (n = 53), clinically isolated syndrome (CIS) (n = 15), and healthy controls (n = 26). Total RNA was isolated from the participants' whole blood and fecal samples. RNA extraction was performed using QIAamp RNA Blood Mini Kits for blood samples and RNeasy PowerMicrobiome Kits for feces. miR-146a expressions were studied using real-time polymerase chain reaction. Finally, relative expression was correlated with clinicopathologic factors. Results: MiR-146a expression was significantly decreased in the whole blood (P < 0.001) and fecal samples (P = 0.036) of patients with RRMS. There was no significant difference in the miR-146a expression rate between patients with CIS and controls. Moreover, the miR-146a expression level in patients with RRMS was decreased compared with those with CIS (P < 0.001). A significant association was determined between miR-146a expression and sex in blood samples. When sex stratification was applied to expression values obtained from fecal samples, miR-146a expression was downregulated only in females (P = 0.008). Discussion: miRNAs play an essential role in maintaining the stable course of MS, and this process has some sex-specific differences. Expression of fecal miR-146a may be used as a biomarker to diagnose and predict prognosis in patients with RRMS.
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-9523-2022
Background 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.
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-9988-2020
Temozolomide (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.
MicroRNA-21 functions as a prognosis predictor in head of pancreas tumor
(Oxford Univ Press, 2018-03-01) Aksoy, Fuat; Aksoy, Savaş; Tunca, Berrin; Dündar, Halit Ziya; Sarkut, Pınar; Özen, Y.; Egeli, Ünal; Çeçener, Gülşah; Yerci, Ömer; Kaya, Ekrem; AKSOY, FUAT; Aksoy, Savaş; TUNCA, BERRİN; DÜNDAR, HALİT ZİYA; Sarkut, Pınar; Özen, Y.; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; YERCİ, ÖMER; KAYA, EKREM; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Bölümü; Bursa Uludağ Üniversitesi/Tıp Fakültesi; 0000-0001-5808-9384; 0000-0002-1619-6680; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-9562-4195; AAH-3847-2021; HII-8895-2022; AAH-1420-2021; ABI-6078-2020; CAV-8845-2022; EWI-3634-2022; HKB-5363-2023; FOQ-1792-2022; AAP-9988-2020; AAG-7319-2021
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-6078-2020
Introduction: 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.
Olea europaea leaf extract decreases tumour size by affecting the LncRNA expression status in glioblastoma 3D cell cultures
(Elsevier, 2021-05-21) Mutlu, Melis; Tunca, Berrin; Aksoy, Seçil Ak; Tekin, Çağla; Çeçener, Gülşah; Egeli, Ünal; Mutlu, Melis; TUNCA, BERRİN; AKSOY, SEÇİL; Tekin, Çağla; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/İnegöl Meslek Yüksekokulu.; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0001-7904-883X; AAH-1420-2021; ADM-8457-2022; FPB-0403-2022; GDC-6329-2022; AAP-9988-2020; ABI-6078-2020
Introduction: Glioblastoma (GB) is the most aggressive primary brain tumour. Temozolomide (TMZ) is a chemotherapy drug used in the treatment of GB. Despite treatment with TMZ, the prognosis of GB is poor. This study aimed to demonstrate the ability of Olea europaea leaf extract (OLE) alone and in combination with TMZ to suppress tumour aggressiveness by evaluating long non-coding RNA (LncRNA) and cancer stem cell (CSC) markers in GB cells using a three-dimensional (3D) model. Methods: The Real-time PCR (RT-PCR) method was used to determine the effects of OLE on LncRNA and CSC markers associated with tumour aggressiveness. To explore the effect of OLE on tumour size, a 3D model was developed. Results: It was found that OLE suppressed tumour aggressiveness with inhibited the MALAT1, SOX2 and NANOG ( p < 0.05). OLE + TMZ also inhibited MALAT1, LOXL1-AS1, PVT1 and H19 ( p < 0.05) and OCT4, NANOG, SOX2 and CD133 ( p < 0.05). In addition, to reduce tumour aggressiveness in a 3D cell culture, the use of OLE and OLE + TMZ has been supported (47.11-fold, p < 0.0001 and 18.04-fold, p < 0.0001, respectively). Conclusion: OLE may be a potential therapeutic agent that can be used in the treatment of GB, as it has been shown to reduce tumour size and increase the effect of TMZ.