Browsing by Author "Çeçener, Gülşah"
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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.Item Alterations of MiRNA expression in early-onset Turkish colorectal cancer patients' tumor tissues(Elsevier, 2012-07) Zorluoğlu, Abdullah; Ak, Seçil; Tunca, Berrin; Çeçener, Gülşah; Egeli, Ünal; Tezcan, Gülçin; Yılmazlar, Tuncay; Öztürk, Elif; Yerci, Ömer; Evrensel, Türkkan; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Onkoloji Anabilim Dalı.; 0000-0002-1619-6680; 0000-0002-9732-5340; F-8554-2017; ABI-6078-2020; AAH-3843-2020; AAH-3847-2021; AAJ-1027-2021Item Analysis of mismatch repair gene mutations in Turkish HNPCC patients(Springer, 2010-09) Pedroni, Monica; Borsi, Enrica; Zorluoğlu, Abdullah; Di Gregoria, Carmela; Ponz de Leon, Maurizio; Tunca, Berrin; Çeçener, Gülşah; Egeli, Ünal; Yılmazlar, Tuncay; Yerci, Ömer; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Patoloji Anabilim Dalı.; 0000-0001-7904-883X; 0000-0002-1619-6680; 0000-0002-3820-424X; AAH-1420-2021; ABI-6078-2020; AAP-9988-2020; 6602965754; 6508156530; 55665145000; 6701800362; 6603810549Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) is caused by the inheritance of a mutant allele of a DNA mismatch repair gene. We aimed to investigate types and frequencies of mismatch repair (MMR) gene mutations in Turkish patients with HNPCC and to identify specific biomarkers for early diagnosis of their non-symptomatic kindred's. The molecular characteristics of 28 Turkish colorectal cancer patients at high-risk for HNPCC were investigated by analysis of microsatellite instability (MSI), immunohistochemistry and methylation-specific PCR in order to select tumors for mutation analysis. Ten cases (35.7%) were classified as MSI (+). Lack of expression of the main MMR proteins was observed in MSI (+) tumors. Hypermethylation of the MLH1 promoter region was observed in one tumor. Nine Lynch syndrome cases showed novel germ-line alterations of the MMR gene: two frame-shifts (MLH1 c.1843dupC and MLH1 c.1743delG) and three missense mutations (MLH1 c.293G > C, MLH1 c.954_955delinsTA and MSH2 c.2210G > A). Unclassified variants were evaluated as likely to be pathogenic by using the in-silico analyses. In addition, the MSH2 c.2210G > A alteration could be considered as a founder mutation for the Turkish population due to its identification in five different Lynch syndrome families and absence in control group. The present study adds new information about MMR gene mutation types and their role in Lynch syndrome. This is the first detailed research on Turkish Lynch syndrome families.Item Analysis of p53 gene mutations in parapsoriasis(Wiley, 2006) Başkan, Emel Bülbül; Tunca, Berrin; Çeçener, Gülşah; Tunalı, S.; Egeli, Ünal; Sarıcaoğlu, H.; Adım, Şadıman Balaban; Uludağ Üniversitesi/Tıp Fakültesi/Dermatoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0002-0144-3263; 0000-0001-7904-883X; 0000-0002-1619-6680; AAH-1388-2021; AAH-1420-2021; ABI-6078-2020; 6602518817; 9280090300; 49762870600; 7004191748; 49762749200; 6603722836; 49762661900The histological diagnosis of the initial stages of Mycosis Fungoides (MF) have not yet been established by exact morphological criteria.1 The borderline between parapsoriasis and MF is not clear due to non-specific changes in the early stages of MF. The underlying molecular changes which may occur during progression or transition from parapsoriasis and early MF to advanced stages have not yet been clarified either.2 However, abnormalities of cell cycle control genes and well-defined tumour suppressor genes may contribute to the disease pathogenesis and progression. The p53 gene plays an important role in the control of cell death and proliferation, inducing cell cycle arrest and/ or apoptosis in response to various cellular stress, and alterations of the p53 gene are commonly associated with malignant transformation.3 The p53 gene mutations, one of the most common genetic alterations in human cancers, have been described in several types of haemato logic malignancies.4 By contrast, only a few studies have focused on p53 abnormalities in various categories of T-cell lymphomas and to the best of our knowledge, parasoriasis has not been studied so far.5–10 Studies of p53 protein expression in primary cutaneous T-cell lymphoma have shown to be increased in the late stages of the dis ease. This prompted us to investigate the incidence of p53 gene mutations in parapsoriasis and its role in the pathogenesis.Item The anticancer activity of complex [Cu-2(mu-(C6H5)(2)CHCOO)(3)(bipy)(2))](ClO4) -solid lipid nanoparticles on MCF-7 cells(Bentham Science, 2016-12-01) Kani, İbrahim; Dikmen, Gökhan; Eskiler, Gamze Güney; Çeçener, Gülşah; Tunca, Berrin; Egeli, Ünal; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0001-7904-883X; 0000-0002-2088-9914; 0000-0002-1619-6680; 0000-0002-3820-424X; AAH-1420-2021; AAB-6011-2022; ABI-6078-2020; AAP-9988-2020; 57190947987; 6508156530; 6602965754; 55665145000Recent studies have focused on the potential use of metal-based complexes for the treatment of cancer. However, there are some limitations of metal-based ligands for the treatment of cancer due to their toxic effects. In the present study, a novel bimetallic Cu(II) complex, [Cu-2(mu-(C6H5)(2)CHCOO)(3) (bipy)(2))](ClO4), has firstly been synthesized and characterized by FT-IR, and X-ray crystallography. Furthermore, Cu(II) complex-loaded solid lipid nanoparticles (SLNs) were initially prepared by hot homogenization method to overcome their toxic effects. After characterization, comparative cytotoxic and apoptotic activities of the complex and Cu(II) complex-SLNs on human breast cancer cells (MCF-7) and human umbilical vein endothelial cells (HUVEC) were determined. Cu(II) complex demonstrated considerable in vitro cytotoxic effects on MCF-7 (p<0.05) and induced apoptotic cell death (88.02 +/- 3.95%) of MCF-7 cells. But, the complex has also toxic effects (69.5%) on HUVEC control cells. For this purpose, Cu(II) complex-loaded solid lipid nanoparticles (SLN) were firstly produced, with a distrubution range of 190 +/- 1.45 nm to 350 +/- 1.72 nm and zeta potentials of -27.4 +/- 1.98 mV and -18.2 +/- 1.07 mV, respectively. The scanning electron microscopy (SEM) images of SLNs were also obtained. In vitro studies have shown that Cu(II) complex-SLNs help in reducing the side effect of Cu(II) complex (29.9%) on HUVEC control cells. Therefore, metal based complex might potentially be used for cancer treatment through nanoparticle based drug delivery systems.Item Apoptotic effects of taxol and radiation an the intestinal kript cells of swiss-albino mice(Elsevier, 1999-09) Özkan, Lütfi; Özuysal, Sema; Egeli, Ünal; Balım, S.; Tunca, Berrin; Aydemir, Nilufer Cinkiliç; Çeçener, Gülşah; Engin, Kayıhan; Uludağ Üniversitesi/Tıp Fakültesi/Radyasyon Onkolojisi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-1619-6680; 0000-0002-3595-6286; ABI-6078-2020; AAH-5296-2021Item Association BRCA mutation status between BMN 673 (talazoparib), an oral PARP inhibitor, in triple-negative breast cancer(Elsevier, 2018-09) Eskiler, Gamze Güney; Çeçener, Gülşah; Egeli, Ünal; Tunca, Berrin; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-1619-6680; 0000-0001-7904-883X; 0000-0002-3820-424X; ABI-6078-2020; AAH-1420-2021Item Association of MDR1, CYP2D6, and CYP2C19 gene polymorphisms with prophylactic migraine treatment response(Elsevier, 2016-05-11) Atasayar, Gülfer; Eryılmaz, Işıl Ezgi; Karlı, Necdet; Egeli, Ünal; Zarifoğlu, Mehmet; Çeçener, Gülşah; Taşkapılıoğlu, Özlem; Tunca, Berrin; Yıldırım, Öznur; Ak, Seçil; Tezcan, Gülçin; Can, Fatma Ezgi; Uludağ Üniversitesi/Tıp Fakültesi/Nöroloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı.; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0002-3316-316X; 0000-0001-7904-883X; 0000-0002-1953-7735; 0000-0002-5956-8755; ABI-6078-2020; AAP-9988-2020; AAH-1656-2021; GWV-3548-2022; AAH-3843-2020; F-8554-2017; AAH-1420-2021; 57189387392; 57189380840; 6506587942; 55665145000; 6603411305; 6508156530; 23037226400; 6602965754; 57189390647; 55253485700; 25650627600; 56689608500Prophylactic therapy response varies in migraine patients. The present study investigated the relationship between the resistance to the drugs commonly used in prophylactic therapy and the possible polymorphic variants of proteins involved in the metabolism of these drugs. Migraine patients with the MDR1 3435TT genotype exhibited a better treatment response to topiramate than migraine patients with the CC and CT genotypes (p = 0.020). The MDR1 C3435T polymorphism was also found to be a higher risk factor for topiramate treatment failure in a comparison of the number of days with migraine (beta(2) = 1.152, p = 0.015). However, there was no significant relationship between the treatment response to topiramate and either the CYP2D6 or CYP2C19 polymorphism, and there were no significant correlations between the treatment responses to amitriptyline, propranolol, and valproic acid and the MDR1, CYP2D6 and CYP2C19 gene polymorphisms. This is the first study to investigate the effect of the polymorphic variants on prophylactic therapy response in migraine patients.Item Association of PALB2 sequence variants with the risk of early-onset breast cancer in patients from Turkey(Springer, 2016-08-16) Çeçener, Gülşah; Eskiler, Gamze Güney; Egeli, Ünal; Tunca, Berrin; Alemdar, Adem; Gökgöz, Şehsuvar; Taşdelen, İsmet; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; 0000-0002-3820-424X; 0000-0002-2088-9914; 0000-0002-1619-6680; 0000-0001-7904-883X; AAP-9988-2020; AAB-6011-2022; ABI-6078-2020; HIZ-7332-2022; AAH-1420-2021; 6508156530; 57190947987; 55665145000; 6602965754; 57190943001; 6603238737; 9637821500The PALB2 gene, has been accepted as a moderate-penetrance gene associated with breast cancer susceptibility and this gene product is involved in the DNA damage repair pathway via co-localization with BRCA2. Germline PALB2 mutations are associated with an increased breast cancer risk. However, the prevalence of the diverse types of PALB2 variants depend on the population. Thus, the aim of the present study was to determine, for the first time, the prevalence of PALB2 variants in a Turkish population of BRCA1/BRCA2-negative early-onset patients with breast cancer. In total, 223 Turkish patients with BRCA1/BRCA2 negative early-onset breast cancer and 60 unaffected women were included in the study. All the coding exons and intron/exon boundaries of PALB2 were subjected to mutational analysis by heteroduplex analysis (HDA) and DNA sequencing. Eighteen PALB2 variants were found in breast cancer patients within the Turkish population. Three variants (c.271G>A, c.404C>A and c.2981T>A) have not been previously reported. In addition, nine intronic variants were described, and this study is the first to describe the c.1685-44T>A intronic variant. The prevalence of possible pathogenic PALB2 variants was found to be 4.03 % in BRCA1/2-negative Turkish patients with early-onset breast cancer. Different variants of PALB2 have been reported in the literature, and the prevalence of these variants could different for each population. This is the first study to investigate the prevalence of PALB2 variants in Turkish patients with early-onset breast cancer.Item Benign ve malign meme hastalarına ait meme dokularında FHIT gen mutasyonlarının araştırılması(Uludağ Üniversitesi, 2005-05-26) Çeçener, Gülşah; Egeli, Ünal; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Tıbbi Biyoloji Anabilim Dalı.Bu çalışmada, malign ve benign meme hastalarında Fragile Histidine Triad (FHIT) gen mutasyonlan araştırıldı. 67 malign ve 1 6 benign dokuda kodlanan ekzonlarm (5-9) "Single Strand Conformational Polymorphism (SSCP)" ve "Heteroduplex (HDA)" analizleri ve bunların DNA dizi analizleri sonucunda 4 farklı dizi değişimi belirlendi. Meme dokularında FHTT gen mutasyonlan % 18.1 (15/83) oranında belirlendi. İki benign ve dört malign hastada (%7.23 oranında) 88. kodonda GCC(Ala)-»GCT(Ala) (7.ekzon) ve yedi malign hastada (%8.43 oranında) 9. intronda insA (5'uç+17nükleotid) iki sessiz muîasyon belirlendi. Bir malign hastada (%1.2 oranında) CAG(Gln)-»ACA(Thr) dönüşümüne neden olan 90. kodondaki insA (7. ekzon) ve yine bir malign hastada (%1.2 oranında) 197. kodonda GTG(Val)-»TGA(stop) dönüşümüne neden olan kodon 146 delT (9. ekzon) çerçeve kayması mutasyonlan tanımlandı. Bu çerçeve kayması mutasyonlar iki malign hastada premature stop kodon oluşumuna neden olmaktadır ve meme kanserinde ilk kez belirlenen çerçeve kayması mutasyonlardır. Sonuç olarak, mevcut çalışmada FHIT geninde çeşitli mutasyonlar belirlendi. Bu mutasyonların genellikle sessiz tip mutasyonlar olduğu gözlendi. Bu durumun FHIT genini evrim boyunca korunmasında etkili olabileceği düşünüldü. Ayrıca, bu gende belirlenen iki yeni çerçeve kayması tip mutasyonun meme kanseri gelişiminde önemli olabileceği kanısına varıldı. Ancak, belirlenen mutasyonlar ile prognoz arasında bir ilişki kurulamadı. Bunun sonucunda, daha ileri çalışmalarla FHIT geninin yanında meme kanserinde etkili olabileceği düşünülen diğer gen mutasyonlarının ve gen ekspresyonlarının birlikte değerlendirilmesi önerilmektedir.Item Berrak hücreli tip renal hücreli karsinom'da RNA temelli biyobelirteçlerin biyoinformatik ve moleküler analiz yöntemleri ile araştırılması(Bursa Uludağ Üniversitesi, 2020-08-10) Ünal, Ufuk; Çeçener, Gülşah; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Tıbbi Biyoloji Anabilim Dalı.Berrak hücreli tip renal hücreli karsinom (BHTRHK) Dünya çapında yılda 75.000 kişiden fazla ölüme neden olmaktadır. Son yıllarda BHTRHK oluşumunda rol oynayan genlerin ve mikroRNA (miRNA)'ların işlevlerinin anlaşılmaya başlanması, moleküler patolojisinin aydınlatılmasını hem de yeni moleküler hedefe yönelik tedavilerin geliştirilmesine olanak sağlamaktadır. Tez çalışmasında global veri bankalarından elde edilen 6.056 BHTRHK hasta verisinin in silico analizleri yapılarak; BHTRHK gelişiminde rolü potansiyel olan aday genler ve bu genleri hedef alan miRNA'lar arasından belirlenen; VHL, KAT5 ve HIF1A'nın ve miR-22, miR-138 ve miR-223'ün ekspresyon analizleri 100 BHTRHK hastasının parafinize edilmiş tümör ve normal dokularında gerçekleştirildi. Elde edilen in silico analizlere ait nicel veriler; normalite testi, t-testi, X2, korelasyon testi ve ROC analizi ile değerlendirildi. Hastaların tümör ve normal dokularına ait gen ve miRNA ifade farklılıkları karşılaştırıldığında ise; VHL'de -0,39 kat azalma (p=0,4419), HIF1A'da 1,23 kat artma (p=0,0402), KAT5'de 1,88 kat artma (p=0,001), miR-223'de 0,97 kat artma (p=0,0458), miR-138'de -3,84 kat azalma (p<0.0001) ve miR-22'de -1,17 kat azalma (p=0,0309) belirlendi. Ayrıca, VHL geninde yapılan DNA dizi analizi sonucunda hastaların %26'sında değişim saptanmıştır. Western blot analiz sonucunda ise, VHL'de değişim görülmez iken KAT5 protein miktarında artma belirlenmiştir (p=0,048). Elde edilen bulgular hastaların klinikopatolojik verileri ile karşılaştırıldığında; VHL gen ifadesi ile tanısal değeri olan CD10 (p=0,047), LMWCK (p=0,004), CK19 (p=0,025) ve PAS (p=0,034) değerleri ile istatistiksel olarak anlamlılık göstermiştir. HIF1A ve KAT5 ifadeleri ise LMWCK ile ilişki ilişkilidir (p=0,018, p=0,018). İlgili genleri hedef alan miRNA'lar arasında yer alan miR-22'nin ifade farklılığı perirenal yağ doku invazyonu (p=0,003), fuhramn derecesi (p=0,037) ve patoloji tümör evresi (p=0,038) ile, miR-138 ifadesi farklılığı ise perirenal yağ doku invazyonu (p=0,05) ile istatistiksel olarak anlamlı ilişki göstermiştir. Tez çalışması kapsamında BHTRHK gelişiminde rolü potansiyel genetik ve epigenetik değişimler araştırılarak elde edilen bulgular ışığında, BHTRHK'da kötü prognozun belirlenebilmesi için mir-22 ve mir-138'ün ifade düzeylerindeki farklılıkların biyobelirteç olma potansiyeli mevcuttur. Ayrıca mir-22 ve mir-138'ün potansiyel terapötik hedef olarak kullanılabilirliğine ait ön verilerin elde edilmesi, hedefe yönelik tedavilerin geliştirilmesini içeren ileri çalışmalara temel oluşturmaktadır. Mevcut tez çalışması, kötü prognoza sahip BHTRHK'lu hastaların moleküler biyobelirteçler ile ayırt edilerek bireye özgü etkin tedavi modellerinin geliştirilmesine katkı sağlar niteliktedir.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.Item BRCA mutations cause reduction in miR-200c expression in triple negative breast cancer(Elsevier, 2015-02-10) Ertürk, Elif; Çeçener, Gülşah; Tezcan, Gülçin; Egeli, Ünal; Tunca, Berrin; Gökgöz, Şehsuvar; Tolunay, Şahsine; Taşdelen, İsmet; Uludağ Üniversitesi/Sağlık Meslek Yükseokulu/Tıbbi Laboratuvar Teknikleri Programı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Patoloji Anabilim Dalı.; 0000-0001-7668-796X; 0000-0002-3820-424X; 0000-0002-5956-8755; 0000-0001-7904-883X; 0000-0002-1619-6680; 0000-0003-1394-2630; 0000-0002-9038-0515; AAK-3371-2021; AAP-9988-2020; AAH-3843-2020; AAH-1420-2021; ABI-6078-2020; EXK-4525-2022; AAI-1612-2021; EBN-1186-2022; 50261655300; 6508156530; 25650627600; 55665145000; 6602965754; 6603238737; 6602604390; 9637821500Triple negative breast cancer (TNBC) is the most aggressive and poorly understood subclass of breast cancer (BC). Over the recent years, miRNA expression studies have been providing certain detailed overview that aberrant expression of miRNAs is associated with TNBC. Although TNBC tumors are strongly connected with loss of function of BRCA genes, there is no knowledge about the effect of BRCA mutation status on miRNA expressions in TNBC cases. The aims of this study were to evaluate the expression profile of miRNAs that plays role in TNBC progression and the role of BRCA mutations in their regulation. The expression level of BC associated 13 miRNAs was analyzed in 7 BRCA mutations positive, 6 BRCA mutations negative TNBC cases and 20 non-tumoral tissues using RT-PCR. According to RT2 Profiler PCR Array Data Analysis, let-7a expression was 4.67 fold reduced in TNBCs as compared to normal tissues (P = 0.031). In addition, miR-200c expression was 5.75 fold reduced in BRCA mutation positive TNBC tumors (P = 0.005). Analysis revealed a negative correlation between miR-200c and VEGFA expressions (r = -468). Thus, miR-200c may be involved in invasion and metastasis in TNBC cases with BRCA mutation. In this study we provide the knowledge on the first report of association between microRNA-200c and BRCA mutations in TNBC. Further studies and evaluations are required, but this miRNA may provide novel therapeutic molecular targets for TNBC treatment and new directions for the development of anticancer drugs.Publication BRCA1/2 germline mutations and their clinical importance in Turkish breast cancer patients(Taylor & Francis Inc, 2014-10-01) Çeçener, Gülşah; Egeli, Ünal; Tunca, Berrin; Ertürk, Elif; Ak, Seçil; Gökgöz, Şehsuvar; Taşdelen, İsmet; Tezcan, Gülçin; Demirdoğen, Elif; Bayram, Nuran; Avcı, Nilüfer; Evrensel, Türkkan; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı; Uludağ Üniversitesi/İktisadi ve İdari Bilimler Fakültesi/Ekonometri Anabilim Dalı; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-1619-6680; 0000-0002-3760-9755; 0000-0002-5956-8755; F-8554-2017; AAH-3843-2020; ABI-6078-2020; AAP-9988-2020; AAK-3371-2021; ADM-8457-2022; AAJ-1027-2021; JFK-4021-2023; AAH-1420-2021; JQI-3400-2023; JDE-9426-2023; EXK-4525-2022; EBN-1186-2022; ERW-8812-2022; CCT-7946-2022BRCA1/BRCA2 genes were screened in 117 patients with breast cancer by sequencing. Fourteen percent of patients tested positive for BRCA1/BRCA2 mutations. Four frame shift mutations, four pathogenic missense mutations, and 25 different sequence variations were detected. BRCA mutation positivity was significantly associated with Ki67 (p =.001). BRCA protein expressions were decreased in the patients harboring important mutations and polymorphisms (BRCA1; P508stop, V1740G, Q1182R, Q1756P and BRCA2; V2466A) related with disease. Our findings contribute significantly to the types of germline BRCA1/BRCA2 mutations and their biological effects in Turkish women. These data could help guide the management of BRCA1/BRCA2 mutation-carrying patients when considering breast-conserving therapy.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-9988-2020Item CK19, CK20, EGFR and HER2 status of circulating tumor cells in patients with breast cancer(Sage Publications, 2012) Tunca, Berrin; Egeli, Ünal; Çeçener, Gülşah; Tezcan, Gülçin; Gökgöz, Şehsuvar; Taşdelen, İsmet; Bayram, Nuran; Tolunay, Şahsine; Umut, Görkem; Demirdöğen, Elif; Ertürk, Elif; Ak, Seçil; Çetintaş, Sibel; Evrensel, Türkkan; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Uludağ Üniversitesi/İktisadi ve İdari Bilimler Fakültesi/Ekonometri Bölümü.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Radyasyon Onkolojisi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Onkoloji Anabilim Dalı.; 0000-0001-5492-184X; 0000-0002-9732-5340; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-1619-6680; 0000-0002-5956-8755; 0000-0002-9038-0515; 0000-0002-4483-9284; AAG-9068-2021; AAA-7047-2020; AAH-3843-2020; AAJ-1027-2021; AAP-9988-2020; AAH-1420-2021; ABI-6078-2020; AAI-1612-2021; F-8554-2017; 6602965754; 55665145000; 6508156530; 25650627600; 6603238737; 9637821500; 13609585600; 6602604390; 37058220200; 25644460900; 50261655300; 55253485700; 6505881756; 6603942124Aims and background. The major cause of death in breast cancer patients is metastasis. Various biomarkers have been used for the early detection of circulating tumor cells in the peripheral blood of breast cancer patients. The aims of the current study were to analyze circulating tumor cells in the blood of breast cancer patients by investigating EGFR, CK19, CK20 and HER2 expression profiles and to evaluate their prognostic importance. Methods. CK19, CK20 and EGFR gene expression profiles were evaluated in the blood samples of 84 female patients with primary invasive ductal breast cancer and 20 healthy female volunteers using SYBR green-based real-time qPCR assays. HER2 expression analyses were conducted in 46 patients who had an HER2-positive primary tumor and in 30 healthy women to determine the cutoff level of positivity. Results. The positive rates of CK20, EGFR, CK19 and HER2 mRNA expression in the peripheral blood were 28.57% (24/84), 20.23% (17/84), 5.95% (5/84) and 2.17% (1/46), respectively. The high positive ratio of CK20 mRNA expression in the peripheral blood of breast cancer was identified for the first time in the current study. Significant differences were identified in CK20 expression status and several clinical parameters related with aggressiveness of tumors using a binary logistic regression analysis. Higher CK20-positive levels were observed in patients who had lymph node metastasis and advanced-grade primary tumors, which were estrogen receptor-negative. We have demonstrated that CK20 may be a novel biomarker that is useful to identify circulating tumor cells and predict breast cancer progression. Conclusions. The results suggest that the investigation of CK20 mRNA with other biomarkers in the peripheral blood of breast cancer patients may be useful to monitor the presence of disseminated tumor cells in the blood circulation and to predict the prognosis of breast cancer.Item The clinical significance of lncRNA DANCR in upper rectal adenocarcinoma(Elsevier, 2018-03) Aksoy, Fuat; Aksoy, Savaş; Tunca, Berrin; Işık, Özgen; Öztürk, Erman; Yılmazlar, Tuncay; Yerci, Ömer; Egeli, Ünal; Çeçener, Gülşah; Uludağ Üniversitesi/Tıp Fakültesi/Göğüs Cerrahisi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0001-5808-9384; 0000-0002-1619-6680; 0000-0002-9541-5035; 0000-0001-7904-883X; HII-8895-2022; CAV-8845-2022; ABI-6078-2020; ABH-2238-2021; DJS-4895-2022; CKK-3621-2022; AAH-3847-2021; AAH-1420-2021; AAP-9988-2020Item Clinicopathologic features and genetic characteristics of the BRCA1/2 mutation in Turkish breast cancer patients(Elsevier Science, 2019-10-14) Eskiler, Gamze Güney; Çeçener, Gülşah; Takanlou, Leila Sabour; Takanlou, Maryam Sabour; Egeli, Ünal; Aksoy, Seçil; Ünal, Ufuk; Tezcan, Havva; Eryılmaz, Işıl Ezgi; Gökgöz, Mustafa Şehsuvar; Tunca, Berrin; Çubukçu, Erdem; Evrensel, Türkkan; Çetintaş, Sibel; Taşdelen, İsmet; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji ve Genetik Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Onkoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Radyasyon Onkolojisi Anabilim Dalı.; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0002-3760-9755; 0000-0003-4913-3616; 0000-0002-3316-316X; 0000-0002-1619-6680; 0000-0002-9732-5340; GGI-6227-2022; EAS-6830-2022; GYU-0252-2022; EWY-5692-2022; ETP-1691-2022; EOI-5652-2022; EBN-1186-2022; 6508156530; 57211585974; 57211582304; 55665145000; 57193933334; 57211584917; 57211580953; 57189380840; 57203870909; 6602965754; 53986153800; 6603942124; 6505881756; 9637821500The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with breast carcinoma. In this study, a total of 603 breast cancer subjects from Turkey were screened for BRCA1/BRCA2 mutations using HDA and Sanger sequencing. In the present study, 21 BRCA1 and BRCA2 pathogenic variants were detected in 30 patients and BRCA1/2 mutations were significantly associated with a family history of breast/ovarian cancer. Analysis of overall survival for BRCA1/BRCA2 mutation carriers showed a trend for poor overall survival only in BRCA1 carriers, although this was not statistically significant in BRCA1 and BRCA2 mutation carriers. The c.5266dupC mutation is one of the most frequently reported mutations in BRCA1 and was identified in five breast cancer patients in our study. The most common BRCA2 gene mutations in the present study were c.8940delA and c.9097dupA, which were found in seven patients. We found mostly BRCA1 and BRCA2 mutation carriers in those patients who showed hormone-positive features. In conclusion, our data showed differences in the distribution of the mutation spectrum of BRCA1 and BRCA2 in Turkey.Item Coexistence of MACC1 and NM23-H1 dysregulation and tumor budding promise early prognostic evidence for recurrence risk of early-stage colon cancer(Wiley, 2018-02) Öztürk, Ersin; Aksoy, Seçil A. K.; Uǧraş, Nesrin; Tunca, Berrin; Ceylan, Serkan; Tezcan, Gülçin; Yılmazlar, Tuncay; Yerci, Ömer; Egeli, Ünal; Çeçener, Gülşah; Uludağ Üniversitesi/Tıp FakültesiGenel Cerrahi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0001-7904-883X; 0000-0002-5956-8755; 0000-0002-3820-424X; 0000-0002-3760-9755; 0000-0002-1619-6680; AAH-1420-2021; AAH-3843-2020; AAP-9988-2020; ADM-8457-2022; AAH-2716-2021; ABI-6078-2020; 35070171400; 36668149100; 55386535600; 6602965754; 57200378423; 25650627600; 6701800362; 6603810549; 55665145000; 6508156530The tumor-node-metastasis (TNM) classification, the presence of a mucinous component, and signet ring cells are well-known criteria for identifying patients at a high risk for recurrence and determining the therapeutic approach for early-stage colon cancer (eCC). Nevertheless, recurrence can unexpectedly occur in some eCC cases after surgical resection. The aims of the present study were to evaluate the relation of dysregulated MACC1, c-MET, and NM23-H1 expression with the histopathological features of tumors in recurrence formation in eCC cases. A total of 100 sporadic eCC patients without poor prognosis factors were evaluated in this study. The relationship between the altered expression of MACC1, c-MET, and NM23-H1 and pathological microenvironmental features, including the presence of tumor budding and desmoplasia, were assessed. The primary outcomes, including 5-year overall survival (OS) and disease-free survival (DFS), were also measured. Compared with nonrecurrent patients, the expression level of MACC1 was 8.27-fold higher, and NM23-H1 was 11.36-fold lower in patients with recurrence during the 5-year follow-up (p = 0.0345 and p=0.0301, respectively). In addition, the coexistence of high MACC1 and low NM23-H1 expression and tumor budding was associated with short OS (p < 0.001). We suggest that the combination of reduced NM23-H1, induced MACC1, and the presence of tumor budding are promising biomarkers for the prediction of recurrence and may aid the stratification of patients with stage II colon cancer for adjuvant chemotherapy.Item Common fragile site expression and genetic predisposition to breast cancer(Wiley-Liss, 1998) Çeçener, Gülşah; Egeli, Ünal; Taşdelen, İsmet; Tunca, Berrin; Duman, H.; Kızıl, Ayhan; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; 0000-0002-3820-424X; 0000-0002-1619-6680; AAP-9988-2020; ABI-6078-2020The expression of common fragile sites induced by aphidicolin and caffeine was evaluated on prometaphase obtained from the peripheral blood lymphocytes of 35 women with breast cancer, their 35 clinically healthy female family members, and 20 sex- and age-matched normal controls. As a result of the cytogenetic and statistical evaluation, the number of damaged cells, chromosomal aberrations, and expression frequencies of fragile sites detected in patients with breast cancer and their first-degree relatives were found to be significantly higher than those in the control group. Our findings indicate an increased genetic instability in women with breast carcinomas and their relatives. Therefore, fragile sites may be used as a reliable marker for defining genetic susceptibility to cancer in general.