Browsing by Author "ÇEÇENER, GÜLŞAH"
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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 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 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 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 biodegradability and cellular activity of PCL/PLA and PCL/PLLA electrospun webs for tissue engineering applications(Wiley, 2023-07-25) Öztemur, Janset; Özdemir, Suzan; Tezcan-Ünlü, Havva; Çeçener, Gülşah; Sezgin, Hande; Yalçın-Enis, İpek; Tezcan-Ünlu, Havva; ÇEÇENER, GÜLŞAH; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; AAP-9988-2020; GYU-0252-2022Biodegradability and cellular activity are key performance indicators that should be prioritized for tissue engineering applications. Biopolymer selection, determination of necessary structural properties, and their synergistic interactions play an active role in obtaining the expected biodegradability and biological activity from scaffolds. In this study, it is aimed to produce electrospun webs with improved biocompatibility by blending polycaprolactone (PCL) with polylactic acid (PLA) and poly-l-lactide (PLLA), and examine the effect of biopolymer selection and blend ratio on the biodegradability and cellular activity of surfaces. In this context, fibrous webs are produced from PCL/PLA and PCL/PLLA blends with a weight ratio of 80/20 and 50/50 and pure polymers of PCL, PLA, and PLLA by electrospinning method and subjected to morphological and biological analyses. The biodegradation tests are carried out hydrolytically while the cell viability and cell proliferation analyses are performed with adult human primary dermal fibroblasts and human umbilical endothelial cells (HUVECs). The results show that the fiber diameters of the fabricated webs ranged from 0.747 to 1.685 mu m. At the end of the 5th month, it is observed that the biodegradation rates of the webs blended 50% with PLA and PLLA, in comparison to PCL ones, increase from 3.7% to 13.33% and 7.69%, respectively. On the other hand, cell culture results highlight that the addition of 20% PLA and PLLA improves the cellular activity of both cell types, but increased PLA or PLLA ratio in PCL webs has a negative effect as it makes the structure stiff and brittle.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 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-8333-2022Publication 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 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-7319-2021Publication 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-6078-2020Introduction: 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.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 RNA-based markers in biopsy cores with atypical small acinar proliferation: Predictive effect of T2E fusion positivity and MMP-2 upregulation for a subsequent prostate cancer diagnosis(Wiley, 2019-02-01) Eryılmaz, I. Ezgi; Vuruşkan, Berna Aytaç; Kaygısız, Onur; Egeli, Ünal; Tunca, Berrin; Kordan, Yakup; Çeçener, Gülşah; ERYILMAZ, IŞIL EZGİ; AYTAÇ VURUŞKAN, BERNA; KAYGISIZ, ONUR; TUNCA, BERRİN; ÇEÇENER, GÜLŞAH; 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.; 0000-0002-9790-7295; 0000-0001-7904-883X; 0000-0002-1619-6680; 0000-0002-9947-848X; 0000-0002-3820-424X; ABI-6078-2020; AAP-9988-2020; AAH-1420-2021; L-9439-2019; AAM-9726-2020; AAH-9746-2021; GWV-3548-2022Background Atypical small acinar proliferation (ASAP) is a precursor lesion of prostate cancer (PC), and PC develops from this suspicious focus or an unsampled malignant gland nearby. However, PC-related molecular alterations that could guide the timing of repeat biopsies and help monitor PC risk in ASAP-diagnosed patients have not been investigated. The purpose of this study was to first investigate the expression of seven different PC-related RNAs that included serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG) gene (TMPRSS2-ERG, T2E) fusion, alpha-methylacyl-CoA racemase (AMACR), kallikrein related peptidase 3 (KLK3), androgen receptor (AR), prostate cancer specific antigen 3 (PCA3), and matrix metalloproteinases (MMP)-2 and 9. Methods PC-related RNAs were evaluated using a real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) system in pathologically ASAP-diagnosed prostate biopsy cores from 55 patients presenting with a normal digital rectal examination and a PSA level of 4-10 ng/mL. Results We detected that positive T2E fusion status (P = 0.013) and the expression of AMACR (P = 0.016), AR (P = 0.016) and MMP-2 (P = 0.013) were independently and significantly associated with PC risk in ASAP patients. There were also several statistically significant correlations between expression levels. Additionally, we demonstrated that T2E fusion positive ASAP patients with higher MMP-2 expression were more likely to be diagnosed with PC at a subsequent biopsy during the follow-up period (P = 0.003). Conclusions Although, more clinical validations are needed for the stratification of PC risk in ASAP-diagnosed biopsy cores, our current results indicate that the coexistence of T2E fusion positivity with MMP-2 upregulation may help clinicians adjust their biopsy timetable and/or assessment of PC risk in ASAP-diagnosed patients with a PSA level of 4-10 ng/mL.Publication The anticancer effect of inula viscosa methanol extract by miRNSs' re-regulation: An in vitro study on human malignant melanoma cells(Taylor, 2021-02-04) Çolak, Dilara Kamer; Egeli, Ünal; Eryılmaz, Işıl Ezgi; Aybastıer, Önder; Malyer, Hulusi; Çeçener, Gülşah; Tunca, Berrin; Çolak, Dilara Kamer; EGELİ, ÜNAL; ERYILMAZ, IŞIL EZGİ; AYBASTIER, ÖNDER; MALYER, HULUSİ; ÇEÇENER, GÜLŞAH; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Tıbbi Biyoloji Bölümü; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Analitik Kimya Bölümü; 0000-0001-7904-883X; 0000-0002-0380-1992; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0002-3316-316X; GWV-3548-2022; AAH-1420-2021; HXB-1173-2023; X-4621-2018; DDS-8738-2022; AAP-9988-2020; ABI-6078-2020Alternative and natural therapies are needed for malignant melanoma (MM), the most deadly skin cancer type due to chemotherapy's limited effect. In the present study, we evaluated the anticancer potentials of Inula viscosa methanol and water extracts (IVM and IVW) on MM cells, A2058 and MeWo, and normal fibroblasts. After the chromatographic and antioxidant activity analysis, their antiproliferative effects were determined with the increasing doses for 24-72 h. IVM induced more cell death in a dose and time-dependent manner in MM cells compared to IVW. This effect was probably due to the higher amount of phenolics in it. IVM significantly induced more apoptotic death in MM cells than fibroblasts (p < 0.01), which was also supported morphologically. IVM also caused cell cycle arrest at G0/G1 and G2/M phases in A2058 and MeWo, respectively, and suppressed the migration ability of MM cells (p < 0.01). Additionally, IVM was found to have significant potential in regulating MM-related miRNAs, upregulating miR-579 and miR-524, and downregulating miR-191 and miR-193, in MM cells (p < 0.05, p < 0.01). As a result, the anticancer effect of IVM via regulating miRNAs' expression has been demonstrated for the first time. Thus, IVM, with these potentials, may be a promising candidate for MM treatment.Publication The expression and prognostic value of miR-146a and miR-155 in Turkish patients with multiple sclerosis(Taylor & Francis, 2022-03-04) Sarıdaş, Furkan; Ünlü, Havva Tezcan; Çeçener, Gülşah; Egeli, Ünal; Takanlou, Maryam Sabour; Takanlou, Leila Sabour; Tunca, Berrin; Zarifoğlu, Mehmet; Turan, Ömer Faruk; Taşkapılıoğlu, Özlem; SARIDAŞ, FURKAN; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; TUNCA, BERRİN; ZARİFOĞLU, MEHMET; TURAN, ÖMER FARUK; Takanlou, Maryam Sabour; Takanlou, Leila Sabour; Taşkapılıoğlu, Özlem; 0000-0001-5945-2317; 0000-0002-0910-4258; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-1590-4833; 0000-0002-6361-7150; 0000-0002-1619-6680; HSB-2700-2023; GYU-0252-2022; AAP-9988-2020; AAH-1420-2021; KGL-6846-2024; GRE-6268-2022; ABI-6078-2020; EHN-5825-2022; JDI-6091-2023; EBA-4926-2022Multiple sclerosis (MS) is an inflammatory, autoimmune demyelinating, and neurodegenerative disorder of the central nervous system. Interactions between environmental factors, predisposition genes, and determining genes appear to be involved in its etiology. Epigenetic mechanisms such as microRNA-mediated gene regulation can determine the susceptibility and severity of autoimmune diseases. Therefore, to determine the role of miR-146a and miR-155 in MS and its developmental stages, the expression levels in the serum of MS and clinically isolated syndrome (CIS) patients were compared with those of healthy controls. In the present study, the expression levels of miR-146a and miR-155 were assessed using quantitative Real-Time PCR in blood samples of 15 CIS patients and 61 relapsing-remitting multiple sclerosis (RRMS) patients alongside 32 healthy patients as controls. Furthermore, any associations with the clinicopathologic variables of the patients were also evaluated. Dysregulations were found only in the miR-146a and miR-155 expressions in the RRMS-Control group. When the RRMS patients were evaluated in terms of the characteristics of sex, annual attack rate, age of diagnosis, duration of follow-up, and immunomodulatory treatments used, no significant differences were observed. However, significant dysregulations were identified in miRNA expression in the vitamin D level, EDSS values, and the number of attacks. ROC curve analysis showed that miR-146a and miR-155 were significant in the RRMS-Control group for the area under the curve (AUC). It is possible that miR-146a may be associated with vitamin D deficiency and disease disability, while miR-155 may be associated with the number of attacks.Publication The role of the dopamine β-hydroxylase functional polymorphism in patients with early-onset parkinson's disease in the Turkish population(Turkish Neurological Soc, 2021-03-01) Erer, Sevda; Eryılmaz, Işıl Ezgi; Çolak, Dilara Kamer; Egeli, Ünal; Çeçener, Gülşah; Tunca, Berrin; Karakuş, Ece; Çolakoğlu, Beril; Tokçaer, Ayşe Bora; Saka, Esen; Demirkıran, Meltem; Akbostancı, Cenk; Zarifoğlu, Mehmet; Doğu, Okan; Kaleagasi, Hakan; Kenangil, Gülay; Çakmur, Raif; Elibol, Bülent; ERER ÖZBEK, ÇİĞDEM SEVDA; ERYILMAZ, IŞIL EZGİ; Çolak, Dilara Kamer; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; TUNCA, BERRİN; Karakuş, Ece; ZARİFOĞLU, MEHMET; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi.; 0000-0001-7904-883X; 0000-0002-3316-316X; 0000-0002-2274-3230; 0000-0003-4968-2826; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0003-2982-0961; GWV-3548-2022; AAH-1420-2021; DVY-9744-2022; JIP-4494-2023; AAP-9988-2020; ABI-6078-2020; FDA-2023-2022; EHN-5825-2022Objective: A functional single nucleotide polymorphism, rs1611115, in the dopamine beta-hydroxylase (DBH) gene, is reported to regulate plasma enzyme activity levels. Mere, we report the first evaluation of this association in patients with early-onset Parkinson's disease (EOPD) and healthy controls in the Turkish population.Materials and Methods: We evaluated the DBH rs1611115 polymorphism in 114 (64 male and 50 female) Turkish patients with EOPD and 58 sex- and age-matched healthy controls from the Turkish population. A total of 27.2% (n=31) of our patients who had any variation including pathogenic or non-pathogenic missense, non-sense and/or intronic variation with unknown significance in EOPD genes were grouped as "variation-positive EOPD". A total of 50.8% (n=58) of our patients were grouped as "variation and family history-negative EOPD" and the possible contribution of the DBH rs1611115 polymorphism to EOPD pathogenesis was evaluated in this group.Results: There was no significant difference in the genotypic and allelic frequencies of DBH rs1611115 between patients with EOPD and controls. To our knowledge, this is the first evaluation of the DBH rs1611115 polymorphism in patients with EOPD and ethnically matched controls in the Turkish population.Conclusion: Some previous studies have reported conflicting association results between DBH rs1611115 polymorphism and PD pathogenesis in different ethnic groups. Therefore, further studies are needed to evaluate dopamine metabolism-related generic variants and to determine their possible roles in EOPD susceptibility in the Turkish population.