Browsing by Author "Tezcan, Gülçin"
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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 Altered expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the formation of chronic Brucellosis(Hindawi, 2016-07-31) Budak, Ferah; Bal, Salih Haldun; Tezcan, Gülçin; Akalın, Halis; Göral, Güher; Oral, Haluk Barbaros; Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Klinik Mikrobiyoloji ve Enfeksiyon Hastalıkları Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Mikrobiyoloji Anabilim Dalı.; 0000-0003-0463-6818; 0000-0002-5956-8755; K-7285-2012; AAU-8952-2020; F-4657-2014; F-8554-2017; AAH-3843-2020; 6701913697; 57191480128; 25650627600; 57207553671; 6603453166; 7004498001Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10-30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-1393p were decreased (p< 0.05, fold change > 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis.Publication Association of cytotoxic T lymphocyte subsets with disease severity in Covid-19(Wiley, 2021-08-01) Kızmaz, Muhammed Ali; Çağan, Eren; Şimşek, Abdurrahman; Dombaz, Fatma; Tezcan, Gülçin; Aşan, Ali; Demir, H. İbrahim; Bal, S. Haldun; Ermiş, Diğdem Yöyen; Coşkun, Necmiye Funda; Akalın, E. Halis; Oral, Haluk Barbaros; Budak, Ferah; Kızmaz, Muhammed Ali; ŞİMŞEK, ABDURRAHMAN; Dombaz, Fatma; TEZCAN, GÜLÇİN; Demir, H. İbrahim; BAL, SALİH HALDUN; YÖYEN ERMİŞ, DİĞDEM; COŞKUN, NECMİYE FUNDA; AKALIN, EMİN HALİS; ORAL, HALUK BARBAROS; BUDAK, FERAH; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Göğüs Hastalıkları Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Klinik Mikrobiyoloji ve Enfeksiyon Hastalıkları Anabilim Dalı.; 0000-0001-5334-7911; 0000-0001-8850-0269; 0000-0001-7288-3250; 0000-0002-5956-8755; 0000-0002-8856-7356; 0000-0001-7585-7971; 0000-0003-3604-8826; 0000-0001-7530-1279; 0000-0003-0463-6818; 0000-0001-7625-9148; 0000-0003-3604-8826; HKN-2347-2023; IZP-9398-2023; AAH-3843-2020; F-4657-2014; AAG-7381-2021; K-7285-2012; AAU-8952-2020; DWR-5356-2022; GPN-1473-2022; KBR-5535-2024; GYL-2038-2022; AAD-1271-2019Item 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 Bitki özütlerinin anti-tümöral özelliklerinin glioblastom kök hücrelerinde araştırılması(Uludağ Üniversitesi, 2014-12-12) Tezcan, Gülçin; Tunca, Berrin; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Tıbbi Biyoloji Anabilim Dalı.Glioblastoma multiforme (GBM) yetişkinlerde en yaygın görülen, agresif özellikli bir beyin tümörüdür. GBM hastalarının tanı sonrası ortalama yaşam süresi 1 yıldan azdır. GBM tümörlerinin yapısında kanser kök hücrelerinin varlığı, hastaların uygulanan tedavilere direnç göstermesine ve tümörün nüksetmesine sebep olmaktadır. Bu nedenle GBM tedavisi için daha etkin yöntemlerin geliştirilmesine ihtiyaç duyulmaktadır. Günümüzde pek çok kanser türü için tedavi yöntemlerinin oluşturulmasında terapötik bitkilerden sıklıkla yararlanılmaktadır. Gerçekleştirilen çalışmada, Viscum album (ökse otu) özütü (VA), Vitis vinifera (üzüm) çekirdeği özütü (GSE), Olea europaea (zeytin) yaprağı özütü (OLE) ve Ficus carica (incir) sütü (FCL)'nün üç GBM hücre hattındaki ve GBM kök hücre (GSC) (+) primer tümör hücrelerindeki anti-kanser etkisinin hücre proliferasyonu, invazyonu ve ölümü açısından araştırılarak bu özütlerin GBM'de moleküler etki mekanizmasının açıklanabilmesi hedeflenmiştir. Elde edilen verilere göre, VA'nın hücre canlılığında yol açtığı değişimin doza bağlı olarak artan ya da azalan bir değişim olmadığı belirlenmiştir. GSE'nin ise ex-vivo koşullarda tümör invazyonunu arttırıcı yönde etki gösterdiği ortaya konmuştur. OLE'nin apoptoz ve nekroz yoluyla GBM hücre hatlarında hücre ölümüne yol açtığı ve miR-137, miR-145 ve miR-153 ekspresyonlarını etkileyerek GSC (+) tümörlerde temozolomid (TMZ)'in etkinliğini arttırdığı gösterilmiştir. FCL'nin ise let-7d ekspresyonunu düzenleyerek GBM hücre hatlarında invazyonun kontrolünde rol oynadığı, GSC (+) hücrelerde ise TMZ direncinin azalmasına yol açtığı gözlenmiştir. Mevcut çalışma, OLE'nin miRNA regülasyonu yoluyla GSC(+) hücrelerde puluripotentliği azalttığını ortaya koyan ilk çalışmadır. Ayrıca, gerçekleştirilen çalışmada FCL'nin GBM hücre hatlarındaki anti-invazif etkisi ve GSC (+) hücrelerde TMZ direncini azaltıcı etkisi ilk kez gösterilmiştir. İleri araştırmalar gerekmekle birlikte, mevcut bulgular OLE ve FCL'nin GBM tedavisi ile ilgili ilaç araştırmaları için potansiyel birer aday özüt olabileceklerini desteklemektedir.Publication Blocking the hormone receptors modulates NLRP3 in LPS-primed breast cancer cells(Mdpi, 2023-03-01) Hamza, Shaimaa; Garanina, Ekaterina E. E.; Alsaadi, Mohammad; Khaiboullina, Svetlana F. F.; Tezcan, Gülçin; TEZCAN, GÜLÇİN; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; 0000-0002-5956-8755; AAH-3843-2020NOD-like receptor protein 3 (NLRP3) may contribute to the growth and propagation of breast cancer (BC). The effect of estrogen receptor-alpha (ER-alpha), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) on NLRP3 activation in BC remains unknown. Additionally, our knowledge of the effect of blocking these receptors on NLRP3 expression is limited. We used GEPIA, UALCAN, and the Human Protein Atlas for transcriptomic profiling of NLRP3 in BC. Lipopolysaccharide (LPS) and adenosine 5 '-triphosphate (ATP) were used to activate NLRP3 in luminal A MCF-7 and in TNBC MDA-MB-231 and HCC1806 cells. Tamoxifen (Tx), mifepristone (mife), and trastuzumab (Tmab) were used to block ER-alpha, PR, and HER2, respectively, on inflammasome activation in LPS-primed MCF7 cells. The transcript level of NLRP3 was correlated with ER-alpha encoding gene ESR1 in luminal A (ER-alpha(+), PR+) and TNBC tumors. NLRP3 protein expression was higher in untreated and LPS/ATP-treated MDA-MB-231 cells than in MCF7 cells. LPS/ATP-mediated NLRP3 activation reduced cell proliferation and recovery of wound healing in both BC cell lines. LPS/ATP treatment prevented spheroid formation in MDA-MB-231 cells but did not affect MCF7. HGF, IL-3, IL-8, M-CSF, MCP-1, and SCGF-b cytokines were secreted in both MDA-MB-231 and MCF7 cells in response to LPS/ATP treatment. Tx (ER-alpha inhibition) promoted NLRP3 activation and increased migration and sphere formation after LPS treatment of MCF7 cells. Tx-mediated activation of NLRP3 was associated with increased secretion of IL-8 and SCGF-b compared to LPS-only-treated MCF7 cells. In contrast, Tmab (Her2 inhibition) had a limited effect on NLRP3 activation in LPS-treated MCF7 cells. Mife (PR inhibition) opposed NLRP3 activation in LPS-primed MCF7 cells. We have found that Tx increased the expression of NLRP3 in LPS-primed MCF7. These data suggest a link between blocking ER-alpha and activation of NLRP3, which was associated with increased aggressiveness of the ER-alpha(+) BC cells.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.Item 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.Publication Co-loading of Temozolomide with Oleuropein or rutin into polylactic acid core-shell nanofiber webs inhibit glioblastoma cell by controlled release(Elsevier, 2023-09-03) Erçelik, Melis; Tekin, Çağla; Parin, Fatma Nur; Mutlu, Büşra; Doğan, Hazal Yılmaz; Tezcan, Gülçin; Aksoy, Seçil Ak; Gürbüz, Melisa; Yıldırım, Kenan; Bekar, Ahmet; Kocaeli, Hasan; Taşkapılıoğlu, Mevlüt Özgür; Eser, Pınar; Tunca, Berrin; Erçelik, Melis; Tekin, Çağla; TEZCAN, GÜLÇİN; Aksoy, Seçil Ak; Gürbüz, Melisa; BEKAR, AHMET; KOCAELİ, HASAN; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; Eser, Pınar; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; Bursa Uludağ Üniversitesi/İnegöl Meslek Yüksekokulu.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Deney Hayvanları Yetiştirme ve Araştırma Birimi.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahi Anabilim Dalı.; 0000-0002-1640-6035; 0000-0003-0132-9927; 0000-0002-1619-6680; ABX-9081-2022; AAI-2073-2021; HKM-7750-2023; EUG-3329-2022; GDC-6329-2022; JJL-1176-2023; JJH-2235-2023; CGB-7869-2022; FDK-3229-2022; IRO-2619-2023Glioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) coreshell nanofiber webs were encapsulated with OL (PLA(OL)), rutin (PLA(rutin)), and TMZ (PLA(TMZ)) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core -shell structures with an average diameter between 133 +/- 30.7-139 +/- 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLA(OL) and PLA(TMZ) suppressed GB cell viability with a controlled release that increased over 120 h, while PLA(rutin) caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nanowebs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells.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.Publication Diabetes mellitus-mediated MALAT1 expression induces glioblastoma aggressiveness(Turkish Neurosurgical Soc, 2023-01-01) Kocaeli, Aysen Akkurt; Aksoy, Seçil A. K.; Erçelik, Melis; Tezcan, Gülçin; Tekin, Çağla; Kocaeli, Hasan; Bekar, Ahmet; Taşkapılıoğlu, Mevlüt Özgür; Tolunay, Şahsine; Tunca, Berrin; AKSOY, SEÇİL; Erçelik, Melis; TEZCAN, GÜLÇİN; Tekin, Çağla; KOCAELİ, HASAN; BEKAR, AHMET; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; TOLUNAY, ŞAHSİNE; TUNCA, BERRİN; Bursa Uludağ Üniversitesi/İnegöl Meslek Yüksekokulu.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0002-3760-9755; ADM-8457-2022; EUG-3329-2022; JJL-1176-2023; GDC-6329-2022; FDK-3229-2022; JWS-5881-2024; IRO-2619-2023; AAI-1612-2021; JXJ-7901-2024AIM: To describe the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in glioblastoma (GB) progression in patients concurrently diagnosed with diabetes mellitus (DM).MATERIAL and METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor samples of 47 patients diagnosed with GB only and 13 patients diagnosed with GB and DM (GB-DM) were enrolled in this study. Data for p53 and Ki67 immunohistochemical staining of the tumors and blood HbA1c levels of patients with DM were retrospectively collected. MALAT1 expression was assessed using quantitative real-time polymerase chain reaction.RESULTS: The coexistence of GB and DM induced the nuclear expression of p53 and Ki67 compared with GB only. MALAT1 expression was higher in GB-DM tumors than in GB only tumors. The expression of MALAT1 and HbA1c levels were positively correlated. Additionally, MALAT1 was positively correlated with tumoral p53 and Ki67. The disease-free survival of patients with GB-DM with high MALAT1 expression was shorter than that of those diagnosed with GB only and with a lower MALAT1 expression.CONCLUSION: Our findings suggest that one of the mechanisms of the facilitating effect of DM on GB tumor aggressiveness is via MALAT1 expression.Item Distinct MiRNA expression patterns in among breast tumors of patients carried and non-carried germ-line BRCA mutations(Elsevier, 2012-07) Alder, H. J.; Huebner, Kay; Ertürk, Elif; Çeçener, Gülşah; Tunca, Berrin; Egeli, Ünal; Tezcan, Gülçin; Gökgöz, Şehsuvar; Taşdelen, İsmet; Tolunay, Şahsine; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0001-7904-883X; 0000-0002-1619-6680; AAI-1612-2021; AAH-3843-2020; AAK-3371-2021; AAH-1420-2021; F-8554-2017; ABI-6078-2020Publication Doxycycline attenuates cancer cell growth by suppressing NLRP3-mediated inflammation(Mdpi, 2021-08-24) Alsaadi, Mohammad; Tezcan, Gülçin; Garanina, Ekaterina E.; Hamza, Shaimaa; McIntyre, Alan; Rizvanov, Albert A.; Khaiboullina, Svetlana F.; TEZCAN, GÜLÇİN; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; 0000-0002-5956-8755; AAH-3843-2020NLR family pyrin domain containing 3 (NLRP3) inflammasome formation is triggered by the damaged mitochondria releasing reactive oxygen species. Doxycycline was shown to regulate inflammation; however, its effect on NLRP3 in cancer remains largely unknown. Therefore, we sought to determine the effect of doxycycline on NLRP3 regulation in cancer using an in vitro model. NLRP3 was activated in a prostate cancer cell line (PC3) and a lung cancer cell line (A549) before treatment with doxycycline. Inflammasome activation was assessed by analyzing RNA expression of NLRP3, Pro-CASP-1, and Pro-IL1 beta using RT-qPCR. Additionally, NLPR3 protein expression and IL-1 beta secretion were analyzed using Western blot and ELISA, respectively. Tumor cell viability was determined using Annexin V staining and a cell proliferation assay. Cytokine secretion was analyzed using a 41Plex assay for human cytokines. Data were analyzed using one-way ANOVA model with Tukey's post hoc tests. Doxycycline treatment decreased NLRP3 formation in PC3 and A549 cells compared to untreated and LPS only treated cells (p < 0.05). Doxycycline also decreased proliferation and caused cell death through apoptosis, a response that differed to the LPS-Nigericin mediated pyroptosis. Our findings suggest that doxycycline inhibits LPS priming of NLRP3 and reduces tumor progression through early apoptosis in cancer.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.Item Evaluating of BRCA1 and BRCA2 Germ-line mutations and BRCA risk assessment of mutation carriers in Turkish breast cancer patients(Elsevier, 2012-07) Çeçener, Gülşah; Egeli, Ünal; Tunca, Berrin; Ertürk, Elif; Gökgöz, Şehsuvar; Taşdelen, İsmet; Ak, Seçil; Demirdoğen, Elif; Tezcan, Gülçin; Bayram, Nuran; 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.; 0000-0002-3820-424X; 0000-0001-5492-184X; 0000-0001-7904-883X; 0000-0002-1619-6680; AAG-9068-2021; AAH-1420-2021; AAK-3371-2021; AAH-3843-2020; ABI-6078-2020; F-8554-2017Item Evaluation of genetic variations in miRNA-binding sites of BRCA1 and BRCA2 genes as risk factors for the development of early-onset and/or familial breast cancer(Asian Pacific Organization Cancer Prevention, 2014) Ertürk, Elif; Çeçener, Gülşah; Polatkan, Volkan; Gökgöz, Şehsuvar; Egeli, Ünal; Tunca, Berrin Türkei; Tezcan, Gülçin; Demirdöğen, Elif; Ak, Seçil; Taşdelen, İsmet; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; 0000-0002-1619-6680; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-5956-8755; ABI-6078-2020; F-8554-2017; AAK-3371-2021; AAH-1420-2021; AAH-3843-2020; AAP-9988-2020; 50261655300; 6508156530; 56399309200; 6603238737; 55665145000; 6602965754; 25650627600; 25644460900; 55253485700; 9637821500Although genetic markers identifying women at an increased risk of developing breast cancer exist, the majority of inherited risk factors remain elusive. Mutations in the BRCA1/BRCA2 gene confer a substantial increase in breast cancer risk, yet routine clinical genetic screening is limited to the coding regions and intronexon boundaries, precluding the identification of mutations in noncoding and untranslated regions. Because 3' untranslated region (3' UTR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we aimed to determine genetic variation in the 3' UTR of BRCA1/BRCA2 in familial and early-onset breast cancer patients with and without mutations in the coding regions of BRCA1/BRCA2 and to identify specific 3' UTR variants that may be risk factors for cancer development. The 3' UTRs of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis and DNA sequencing in 100 patients from 46 BRCA1/2 families, 54 non-BRCA1/2 families, and 47 geographically matched controls. Two polymorphisms were identified. SNPs c.* 1287C>T (rs12516) (BRCA1) and c.* 105A>C (rs15869) (BRCA2) were identified in 27% and 24% of patients, respectively. These 2 variants were also identified in controls with no family history of cancer (23.4% and 23.4%, respectively). In comparison to variations in the 3' UTR region of the BRCA1/2 genes and the BRCA1/2 mutational status in patients, there was a statistically significant relationship between the BRCA1 gene polymorphism c.* 1287C>T (rs12516) and BRCA1 mutations (p=0.035) by Fisher's Exact Test. SNP c.* 1287C>T (rs12516) of the BRCA1 gene may have potential use as a genetic marker of an increased risk of developing breast cancer and likely represents a non-coding sequence variation in BRCA1 that impacts BRCA1 function and leads to increased early-onset and/or familial breast cancer risk in the Turkish population.Item Evaluation of microRNA expression profiles in triple-negative (ER, PR and Her2/neu) breast cancer patients with and without germ-line BRCA mutations(Elsevier, 2014-07) Ertürk, Elif; Çeçener, Gülşah; Egeli, Ünal; Tunca, Berrin; Tezcan, Gülçin; Gökgöz, S.; Tolunay, Şahsine; Taşdelen, İsmet; Uludağ Üniversitesi/Sağlık Hizmetleri Meslek Yüksekokulu.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0001-7904-883X; 0000-0002-5956-8755; 0000-0002-1619-6680; AAI-1612-2021; AAH-1420-2021; AAH-3843-2020; ABI-6078-2020; AAK-3371-2021Publication Evaluation of the roles of regulatory B (Breg) cells and B cell exhaustion in COVID-19(Wiley, 2021-08-01) Budak, Ferah; Çağan, Eren; Kızmaz, Muhammed Ali; Şimşek, Abdurrahman; Dombaz, Fatma; Tezcan, Gülçin; Asan, Ali; Bal, S. Haldun; Ermiş, Diğdem Yöyen; Demir, H. İbrahim; Ediger, Dane; Yılmaz, Emel; Oral, Haluk Barbaros; Akalın, E. Halis; BUDAK, FERAH; Kızmaz, Muhammed Ali; ŞİMŞEK, ABDURRAHMAN; Dombaz, Fatma; TEZCAN, GÜLÇİN; BAL, SALİH HALDUN; YÖYEN ERMİŞ, DİĞDEM; Demir, H. İbrahim; EDİGER, DANE; YILMAZ, EMEL; ORAL, HALUK BARBAROS; AKALIN, EMİN HALİS; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Göğüs Hastalıkları Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Klinik Mikrobiyoloji ve Enfeksiyon Hastalıkları Anabilim Dalı.; 0000-0001-7625-9148; 0000-0001-5334-7911; 0000-0001-8850-0269; 0000-0001-7288-3250; 0000-0002-5956-8755; 0000-0002-8856-7356; 0000-0001-7585-7971; 0000-0002-2954-4293; 0000-0003-1785-3539; 0000-0003-0463-6818; 0000-0001-7530-1279; AAG-7381-2021; AAH-3843-2020; K-7285-2012; F-4657-2014; IZP-9398-2023; AAU-8952-2020; HKN-2347-2023; DWR-5356-2022; KBR-5535-2024; GYL-2038-2022; GPN-1473-2022; AAE-9142-2019; GDP-0005-2022Item The expression level of MACC1 in early stage CRC patients of Turkish population(Elsevier, 2014) Ceylan, Semih; Ak, Semih; Tunca, Berrin; Öztürk, Emel; Tezcan, Gülçin; Çeçener, Gülşah; Egeli, Ünal; Yılmazlar, Tuncay; Yerci, Ömer; Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-5956-8755; 0000-0002-1619-6680; AAH-3847-2021; F-8554-2017; ABI-6078-2020
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