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TEZCAN, GÜLÇİN

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TEZCAN

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GÜLÇİN

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  • 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-0745-2022
    Background and Aim: In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase (DPYD) gene variant, c.1905 + 1G>A, leads to intolerance to fluoropyrimidines. Due to the low frequency of this variant in many populations, the prevalence of fluoropyrimidine-induced hematologic side effects in CRC patients with the c.1905 + 1G>A variant is unclear. In this study, we investigated the prevalence of the DPYD c.1905 + 1 variants in a Turkish CRC cohort and the potential effects of these variants on fluoropyrimidine-induced hematologic side effects.Materials and Methods: The DPYD c.1905 + 1 variant was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis and confirmed by Sanger sequencing in peripheral blood samples of 100 CRC patients who received fluoropyrimidine-based chemotherapy and 60 healthy volunteers. The association of c.1905 + 1 variants with susceptibility to hematologic side effects was evaluated.Results: The DPYD c.1905 + 1G>A variant was more common in the CRC group than in the healthy control group (p = 0.001). The presence of the c.1905 + 1G>A variant was associated with thrombocytopenia (p = 0.039) and anemia (p = 0.035). CRC patients with fluoropyrimidine-induced anemia had shorter disease-free survival than CRC patients without fluoropyrimidine-induced anemia (p = 0.0009).Conclusions: Before administering fluoropyrimidine-based chemotherapy, genetic screening for the DPYD c.1905 + 1G>A variant should be performed with the aim of preventing anemia and anemia-induced complications in CRC patients.
  • Publication
    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-0005-2022
  • 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-1271-2019
  • Publication
    The age-dependent role of Th22, Tc22, and Tc17 cells in the severity of pneumonia in COVID-19 immunopathogenesis
    (Wiley, 2021-08) Şimşek, Abdurrahman; Çağan, Eren; Kızmaz, Muhammed Ali; Dombaz, Fatma; Tezcan, Gülçin; Asan, Ali; Demir, H. İbrahim; Bal, S. Haldun; Ermiş, Diğdem Yoyen; Demirdöğen, Ezgi; Heper, Yasemin; Akalın, E. Halis; Oral, Haluk Barbaros; Budak, Ferah; ŞİMŞEK, ABDURRAHMAN; TEZCAN, GÜLÇİN; BAL, SALİH HALDUN; DEMİRDÖĞEN, EZGİ; BUDAK, FERAH; HEPER, YASEMİN; AKALIN, EMİN HALİS; Kızmaz, Muhammed Ali; Dombaz, Fatma; YÖYEN ERMİŞ, DİĞDEM; ORAL, HALUK BARBAROS; Bursa Uludağ Üniversitesi/Tıp Fakültesi; 0000-0001-8850-0269; 0000-0001-5334-7911; 0000-0001-7288-3250; 0000-0002-5956-8755; 0000-0002-7400-9089; 0000-0001-7625-9148; AAG-7381-2021; HKN-2347-2023; DWR-5356-2022; KBR-5535-2024; GYL-2038-2022; AAH-9812-2021; CTY-9474-2022; AAU-8952-2020; IZP-9398-2023; K-7285-2012; AAH-3843-2020
  • Publication
    Therapeutic potential of pharmacological targeting nlrp3 inflammasome complex in cancer
    (Frontiers Media Sa, 2021-02-03) Garanina, Ekaterina E.; Alsaadi, Mohammad; Gilazieva, Zarema E.; Martinova, Ekaterina, V; Markelova, Maria, I; Arkhipova, Svetlana S.; Hamza, Shaimaa; McIntyre, Alan; Rizvanov, Albert A.; Khaiboullina, Svetlana F.; Tezcan, Gulcin; TEZCAN, GÜLÇİN; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi.; 0000-0002-5956-8755; 0000-0001-7445-2091; 0000-0002-4082-515X; 0000-0002-5012-4760; 0000-0002-4791-7292; 0000-0002-9427-5739; AAH-3843-2020; H-4486-2013; HTO-8900-2023; AAE-4652-2022; AAP-5140-2021; W-9788-2018; P-4183-2017
    IntroductionDysregulation of NLRP3 inflammasome complex formation can promote chronic inflammation by increased release of IL-1 beta. However, the effect of NLRP3 complex formation on tumor progression remains controversial. Therefore, we sought to determine the effect of NLRP3 modulation on the growth of the different types of cancer cells, derived from lung, breast, and prostate cancers as well as neuroblastoma and glioblastoma in-vitro.MethodThe effect of Caspase 1 inhibitor (VX765) and combination of LPS/Nigericin on NLRP3 inflammasome activity was analyzed in A549 (lung cancer), MCF-7 (breast cancer), PC3 (prostate cancer), SH-SY5Y (neuroblastoma), and U138MG (glioblastoma) cells. Human fibroblasts were used as control cells. The effect of VX765 and LPS/Nigericin on NLRP3 expression was analyzed using western blot, while IL-1 beta and IL-18 secretion was detected by ELISA. Tumor cell viability and progression were determined using Annexin V, cell proliferation assay, LDH assay, sphere formation assay, transmission electron microscopy, and a multiplex cytokine assay. Also, angiogenesis was investigated by a tube formation assay. VEGF and MMPs secretion were detected by ELISA and a multiplex assay, respectively. Statistical analysis was done using one-way ANOVA with Tukey's analyses and Kruskal-Wallis one-way analysis of variance.ResultsLPS/Nigericin increased NRLP3 protein expression as well as IL-1 beta and IL-18 secretion in PC3 and U138MG cells compared to A549, MCF7, SH-SY5Y cells, and fibroblasts. In contrast, MIF expression was commonly found upregulated in A549, PC3, SH-SY5Y, and U138MG cells and fibroblasts after Nigericin treatment. Nigericin and a combination of LPS/Nigericin decreased the cell viability and proliferation. Also, LPS/Nigericin significantly increased tumorsphere size in PC3 and U138MG cells. In contrast, the sphere size was reduced in MCF7 and SH-SY5Y cells treated with LPS/Nigericin, while no effect was detected in A549 cells. VX765 increased secretion of CCL24 in A549, MCF7, PC3, and fibroblasts as well as CCL11 and CCL26 in SH-SY5Y cells. Also, VX765 significantly increased the production of VEGF and MMPs and stimulated angiogenesis in all tumor cell lines.DiscussionOur data suggest that NLRP3 activation using Nigericin could be a novel therapeutic approach to control the growth of tumors producing a low level of IL-1 beta and IL-18.
  • Publication
    Trapping miR-223 leads to overexpression of NLRP3 in colorectal cancer
    (Mary Ann Liebert, 2021-10) Hamza, S.; Garanina, E. E.; Tezcan, Gülçin; Rizvanov, A. A.; Khaiboullina, S. F.; TEZCAN, GÜLÇİN; 0000-0002-5956-8755; AAH-3843-2020
  • Publication
    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-3843-2020
    NLR 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
    microRNA-21 expression is elevated in esophageal adenocarcinoma after neoadjuvant chemotherapy
    (Taylor & Francis, 2015-01-01) İlhan-Mutlu, Ayşegül; Tezcan, Gülçin; Schoppmann, Sebastian F.; Preusser, Matthias; Spyridoula, Kommata; Karanikas, Georgios; Birner, Peter; TEZCAN, GÜLÇİN; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; 0000-0002-5956-8755; AAH-3843-2020
    We investigated whether microRNA-21 and microRNA-148a are predictive for neoadjuvant treatment in esophageal adenocarcinoma. Thirty-six patients with neoadjuvant therapy and surgical resection were included. FFPE tissue from biopsy and esophagectomy were analyzed using RT-qPCR. Results were correlated to histological tumor regression, histopathological variables, FDG-PET-CT and survival. MicroRNA-21 was significantly higher in esophagectomies than in corresponding biopsies (p = .027). No association of microRNA-21 or micro RNA-148a expression in tissue specimens with other clinical parameters was present. Although no influence of microRNA-21 and microRNA-148a on the response to neoadjuvant therapy was seen, upregulation of micro RNA-21 might represent an escape mechanism of tumor cells.
  • Publication
    Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression
    (E-century Publishing Corp, 2014-01-01) Tezcan, Gülçin; Tunca, Berrin; Bekar, Ahmet; Budak, Ferah; Şahin, Saliha; Çeçener, Gülşah; Egeli, Ünal; Taşkapılıoğlu, Mevlut Özgür; Kocaeli, Hasan; Tolunay, Şahsine; Malyer, Hulusi; Demir, Cevdet; Tümen, Gülendam; TEZCAN, GÜLÇİN; TUNCA, BERRİN; BEKAR, AHMET; BUDAK, FERAH; ŞAHİN, SALİHA; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; KOCAELİ, HASAN; TOLUNAY, ŞAHSİNE; MALYER, HULUSİ; DEMİR, CEVDET; Tümen, Gülendam; Uludağ Üniversitesi/Tıp Fakültesi/Beyin Cerrahi Kliniği; Uludağ Üniversitesi/Tıp Fakültesi/Mikrobiyoloji Bölümü; Uludağ Üniversitesi/Tıp Fakültesi/Patholoji Bölümü; 0000-0002-5956-8755; 0000-0002-1619-6680; 0000-0001-7625-9148; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0001-5472-9065; 0000-0002-9381-0410; ABA-2005-2020; F-8554-2017; ABX-9081-2022; AFR-1890-2022; F-4657-2014; AAH-3843-2020; AAI-1612-2021; ABI-6078-2020; IZP-9398-2023; AAW-5254-2020; AAP-9988-2020; AAH-2892-2021; ABB-8161-2020; AAH-1420-2021; ABI-6078-2020
    The stem-like cells of Glioblastoma multiforme (GBM) tumors (GSCs) are one of the important determinants of recurrence and drug resistance. The aims of the current study were to evaluate the anticancer effect of Olea europaea leaf extract (OLE) on GBM cell lines, the association between OLE and TMZ responses, and the effect of OLE and the OLE-TMZ combination in GSCs and to clarify the molecular mechanism of this effect on the expression of miRNAs related to cell death. The anti-proliferative activity of OLE and the effect of the OLE-TMZ combination were tested in the T98G, U-138MG and U-87MG GBM cell lines using WST-1 assay. The mechanism of cell death was analyzed with Annexin V/FITC and TUNEL assays. The effects of OLE on the expression levels of miR-181b, miR-153, miR-145 and miR-137 and potential mRNA targets were analyzed in GSCs using RT-qPCR. OLE exhibited anti-proliferative effects via apoptosis and necrosis in the GBM cell lines. In addition, OLE significantly induced the expression of miR-153, miR-145, and miR-137 and decreased the expression of the target genes of these miRNAs in GSCs (p < 0.05). OLE causes cell death in GBM cells with different TMZ responses, and this effect is synergistically increased when the cells are treated with a combination of OLE and TMZ. This is the first study to indicate that OLE may interfere with the pluripotency of GSCs by modulating miRNA expression. Further studies are required, but we suggest that OLE may have a potential for advanced therapeutic cancer drug studies in GBM.
  • Publication
    Microrna expression pattern modulates temozolomide response in gbm tumors with cancer stem cells
    (Springer/plenum Publishers, 2014-07-01) Preusser, Matthias; Berghoff, Anna Sophie; Ricken, Gerda; Tezcan, Gülçin; TEZCAN, GÜLÇİN; EGELİ, ÜNAL; Bekar, Ahmet; BEKAR, AHMET; KOCAELİ, HASAN; TUNCA, BERRİN; Tunca, Berrin; Çeçener, Gülşah; ÇEÇENER, GÜLŞAH; Budak, Ferah; BUDAK, FERAH; TAŞKAPILIOĞLU, MEVLÜT ÖZGÜR; Taşkapılıoğlu, Mevlüt Özgür; Tolunay, Şahsine; TOLUNAY, ŞAHSİNE; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Medikal Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Mikrobiyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroşurji Anabilim Dalı.; 0000-0002-5956-8755; 0000-0002-1619-6680; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0003-0388-7965; 0000-0001-7625-9148; 0000-0001-5472-9065; F-4657-2014; IZP-9398-2023; AAH-3843-2020; ABB-8161-2020; AAI-1612-2021; ABX-9081-2022; ABI-6078-2020; AAH-1420-2021; AAW-5254-2020; F-8554-2017; AAP-9988-2020
    Temozolomide (TMZ) is widely used to treat glioblastoma multiforme (GBM). Although the MGMT gene methylation status is postulated to correlate with TMZ response, some patients with a methylated MGMT gene still do not benefit from TMZ therapy. Cancer stem cells (CSCs) may be one of the causes of therapeutic resistance, but the molecular mechanism underlying this resistance is unclear. microRNA (miRNA) deregulation has been recognized as another chemoresistance modulating mechanism. Thus, we aimed to evaluate the miRNA expression patterns associated with chemoresistance that is dependent on the CSC status in GBM tumors to identify therapeutic biomarkers. CSCs were identified in 5 of 20 patients' tumor tissues using magnetic separation. CSC (+) tumors displayed a significant induction of CpG island methylation in the MGMT gene promoter (p = 0.009). Using real-time reverse transcription polymerase chain reaction (qRT-PCR), 9 miRNAs related to GBM (mir-181b, miR-153, miR-137, miR-145, miR-10a, miR-10b, let-7d, miR-9, and miR-455-3p), which are associated with cell cycle and invasion was analyzed in tumor samples. Low miR-181b and high miR-455-3p expression levels were detected (p = 0.053, p = 0.004; respectively) in CSC (+) tumors. Analysis revealed a significant correlation between miR-455-3p expression and Smad2 protein levels as analyzed by immunohistochemistry in CSC (+) tumors (p = 0.002). Thus, miR-455-3p may be involved in TMZ resistance in MGMT methylated CSC (+) GBM patients. Further studies and evaluations are required, but this miRNA may provide novel therapeutic molecular targets for GBM treatment and new directions for the development of anticancer drugs.