Browsing by Author "Egeli, 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.
Akciğer tümörlerinde ve tümör cerrahi sınırındaki histopatolojik normal dokularda p53 ve c-myc genlerinin karsinogenik süreçteki rollerinin FISH yöntemiyle araştırılması
(Uludağ Üniversitesi, 2002-11-14) Yakut, Tahsin; Egeli, Ünal; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Tıbbi Biyoloji Anabilim Dalı.
Çalışmamızda radyoterapi ve kemoterapi almamış olan 53 akciğer kanserli hastanın primer tümör dokuları ve tümör dokularına komşu cerrahi sınır dokularındaki genetik değişiklikler, p53 tümör supressör genine ve c-myc onkogenine özgü problar ve bu genlerin üzerinde bulunduğu 17. ve 8. kromozomların sentromerik bölgelerine özgü problarla FISH yöntemi kullanılarak araştırıldı. 53 vakanın 5 1 'ini Küçük hücreli olmayan akciğer kanseri (KHOAK), 2'sini Küçük hücreli akciğer kanseri (KHAK) tümör dokuları oluşturmaktaydı. KHOAK'li 51 vakanın tümör dokularından, yedisinde p53 delesyonu, dördünde c-myc amplifikasyonu, ikisinde monozomi 17, üçünde ise trizomi 8 saptandı, altı vakanın tümör dokusundaysa yüksek oranda poliploidi mevcuttu. KHAK'li iki vakanın tümör dokularından birinde c-myc amplifikasyonu saptandı. 17. ve 8. kromozomun total kayıp yada fazlalıkları ve poliploidiler açısından bakıldığında akciğer tümörlerindeki genetik değişiklikler hem kalitatif hem de kantitatif olarak oldukça heterojenite göstermekteydi. Cerrahi sınır dokularında; iki vakada p53 delesyonu bir vakadaysa c-myc amplifikasyonu saptandı; bu vakalardan bir tanesinde metastaz, diğerinde metastazla birlikte rekürrens, hemde kısa yaşam süresi olması, cerrahi sınır dokularındaki değişikliklerin hastalığın seyri bakımından anlamlı bir bulgu olabileceğini göstermekteydi Gerek p53 delesyonu gerekse c-myc amplifikasyonlarının cerrahi sınır dokularında düşük oranda da olsa saptanmış olması, hastalığın rekürrens ve metastaz açısından takibinde önemli olduğu gibi patolojik evreleme yanında genetik evreleme yapılmasının da önemini işaret etmekteydi P53 delesyonunun düşük evreli vakalarda da görülmesi ve cerrahi sınır dokularında p53 delesyonunun (2/7), c-myc amplifikasyonuna göre (1/5) biraz daha fâzla oranda saptanması p53 patolojilerinin c-myc'ye göre daha erken evrelerde görüldüğü konusunda fikir vermekteydi. Yine çalışmamızın sonuçlan, c-myc amplifikasyonunun akciğer kanserli hastaların yaşam süresini kısaltması yönünde diğer tüm patolojilere oranla çok daha yüksek oranlarda etki sağladığım gösterdi (P<0.01).
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-1027-2021
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.
Analysis of chromosomal aberrations in shoe workers exposed long term to benzene
(Brıtısh Med Journal Publ Group, 1994) Türkel, Berrin; Egeli, Ünal; Bursa Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Genel Biyoloji Bölümü.
Cytogenetic analysis of peripheral blood lymphocytes was used to compare 58 shoe workers (57 men and one woman) exposed to benzene and 20 subjects selected from the general population not exposed to particular mutagenic or carcinogenic agents (control group). Frequencies of damaged cells, including gaps, breaks, and rearrangements (acentric fragment, deletion, translocation) were scored for both groups. The incidence of chromosomal aberrations (particularly chromatid gaps and breaks) in the exposed group was significantly higher than in the control group. There were no effects of smoking and only breaks were affected by alcohol. Nor was there a significant relation between the working period in the group exposed to benzene and frequency of chromosomal aberrations.
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; 6603810549
Hereditary 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.
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; 49762661900
The 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.
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; 55665145000
Recent 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.
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-5296-2021
Are there interchromosomal effects of chromosomal rearrangements on occurrence of aneuploidy in sperm nuclei of carriers?
(Springernature, 2002-05) Acar, Hasan; Yakut, Tahsin; Cora, Tülin; Kaynak, M. Fırat; Yıldırım, S.; Egeli, Ünal; Uludağ Üniversitesi/Tıp Fakültesi/Genetik ve Moleküler Biyoloji Anabilim Dalı.
Assessment of molecular events in squamous and non-squamous cell lung carcinoma
(Elsevier Ireland, 2006) Schulten, Hans-Jürgen; Demir, Adalet; Frank, Derk; Danner, Bernd; Kahler, Elke; Gunawan, Bastian; Ürer, Nur; Fuezesi, Laszlo; Yakut, Tahsin; Egeli, Ünal; Gebitekin, Cengiz; Öztürk, Hülya; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Göğüs Cerrahisi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0001-7904-883X; AAH-1420-2021
Although considerable knowledge exists on the tumor biology of lung cancer, there is still a need to assess molecular events for the clinical management of the disease. We studied the pattern of chromosomal imbalances in 45 non-small cell Lung carcinomas (NSCLC) by comparative genomic hybridization (CGH) and correlated the results with clinicopathological features including immunohistochemical (IHC) expression of the epidermal. growth factor receptor (EGFR). Twenty-one tumors were squamous cell carcinomas (SCC) and 24 non-squamous cell lung carcinomas (NSCC) comprising 9 adenocarcinomas (ADC), 9 large cell carcinomas (LCC), 4 sarcomatoid carcinomas and 2 adenosquamous carcinomas. The mean number of individual imbalances was 7.1 for SCC (mean gains, 3.8; mean tosses, 3.4) and 6.4 for NSCC (mean gains, 4.5; mean tosses, 1.9). Several individual imbalances correlated significantly with increasing number of imbalances, that were +1q, -3p, +3q, -5q, -8p, +8q, +7p, +12p, and +14q. Altogether, the most frequent imbalances were +3q (49%), +5p (49%), -5q (36%), +8q (29%), -8p (24%), -3p (22%), +7p (22%), +12p (22%), +14q (20%), +18p (20%), +1q (18%), and +7q (18%). Among these, +3q and +18p correlated significantly with SCC, and +5p and +14q with NSCC. Remarkably, overlapping imbalances included +3q26, +7p11 in SCC and +1q21, +3q24, +12p11, and +14q12 in NSCC. EGFR expression was higher in SCC than in NSCC and correlated with +3q in the entire series. In addition, +12p correlated significantly with disease progress with the exception of nodal involvement in NSCC as well as with disease progress, regardless of nodal involvement, in the entire series. In conclusion, the present study contributes to the molecular biological characterization of NSCLC histological subtypes and through evaluation of molecular events to the recently emergent focus on novel markers for lung cancer treatment.
Association between the anticancer efficacy of cabazitaxel and toll-like receptor 4 mediating signaling pathways in metastatic castration-resistant prostate cancer cells
(SAGE Publications, 2021-07) Güney, Gamze Eskiler; Özkan, Asuman Deveci; Eryılmaz, Işıl Ezgi; Egeli, Ünal; Cecener, Gülşah; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı; https://orcid.org/0000-0002-3316-316X; GWV-3548-2022; 57189380840; 55665145000; 6508156530
Background: We evaluated the effect of cabazitaxel (CAB) as a third-line taxane on Toll-like receptor 4 (TLR4)-mediated signaling pathways, especially NF-κB activity, in metastatic castration-resistant prostate cancer (mCRPC) cells. Methods: CAB cytotoxicity was determined by WST-1 assay. To assess the relationship between CAB efficacy and TLR4 signaling pathways, RT-PCR, western blot and immunofluorescence analysis were performed. Additionally, CAB-mediated apoptotic cell death was assessed by Annexin V and RT-PCR analysis. Results: Our results demonstrated that CAB exerted considerably cytotoxic and apoptotic effects on PC-3 mCRPC cells (p < 0.05). CAB treatment altered TLR4 expression level in a dose-dependent manner. Furthermore, 1 nM CAB treatment significantly induced NF-κB activity through p65 nuclear localization and increased the expression level of caspase-3, Bax and p53. Interestingly, total apoptotic cell death and IRF3 protein levels were increased at 5 nM concentration of CAB despite a decrease in the levels of both NF-κB and pro-apoptotic genes. Conclusions: Therefore, NF-κB activity may be a potential target for the efficacy of CAB in mCRPC cells.
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-1420-2021
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; 56689608500
Prophylactic 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.
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; 9637821500
The 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.
Ayakkabı işçilerinde sitogenetik incelemeler
(Uludağ Üniversitesi, 1993-02-10) Tunca, Berrin; Egeli, Ünal; Uludağ Üniversitesi/Fen Bilimleri Enstitüsü/Biyoloji Anabilim Dalı.
Çalışmamızda biri kadın, diğerleri erkek olan toplam 58 ayakkabı işçisi ve rasgele olarak seçilmiş biç bir mutajen ve kanserojen ajana maruz kalmamış 20 kişilik kontrol grubu üzerinde periferik kan lenfositleriyle, sitogenetik analiz yöntemi kullanılmıştır. Her iki grupta da, gap, kırık, asentrik fragman, rearrangement ve poliploididen oluşan hücresel hasarın sıklığı araştırılmıştır. Kromozomal hasar (Özellikle kromatid gap ve kırıkları) kontrol grubuna oranla, etkilenen grupta anlamlı bir şekilde yüksek bulunmuştur. Ayakkabı işçileri ve kontrol grubunu oluşturan bireylerin sigara kullanımları ve alkol alışkanlıkları hem kendi içlerinde hem de diğer grupla karşılaştırılmış, her iki durumda da karşılaşılmış her iki kriterler arasında bir ilişki bulunamamıştır. Ayrıca, çalışmaları sırasında benzenden etkilenme süresi ile kromozomal hasarın sıklığı arasında da anlamlı bir ilişki bulunamamıştır.
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.
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.
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; 9637821500
Triple 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.