Person: TEZCAN, GÜLÇİN
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TEZCAN
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GÜLÇİN
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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.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.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.Publication Tamoxifen reduces hepatocyte growth factor secretion in breast cancer cells with high nlrp3 expression(Wiley, 2022-06-01) Hamza, Shaimaa; Garanina, Ekaterina; Alsaadi, Mohammad; Rizvanov, Albert; Khaiboullina, Svetlana; TEZCAN, GÜLÇİN; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler.; AAH-3843-2020Publication DPYD c.1905+1G>A promotes fluoropyrimidine-induced anemia, a prognostic factor in disease-free survival, in colorectal cancer(Mary Ann Liebert, Inc, 2021-04-01) Deligönül, Adem; Aksoy, Seçil; Tezcan, Gülçin; Tunca, Berrin; Kanat, Özkan; Çubukcu, Erdem; Yılmazlar, Tuncay; Öztürk, Ersin; Egeli, Ünal; Çeçener, Gülşah; Alemdar, Adem; Evrensel, Türkkan; DELİGÖNÜL, ADEM; AKSOY, SEÇİL; TEZCAN, GÜLÇİN; TUNCA, BERRİN; Kanat, Özka; ÇUBUKÇU, ERDEM; YILMAZLAR, AHMET TUNCAY; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; ALEMDAR, ADEM; EVRENSEL, TÜRKKAN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Onkoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Onkoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü.; 0000-0002-6400-4911; 0000-0002-5956-8755; 0000-0002-1619-6680; 0000-0001-8593-5101; 0000-0001-7904-883X; 0000-0002-3820-424X; HIZ-7332-2022; AAH-1420-2021; AAH-3843-2020; ESM-4544-2022; JDG-0330-2023; ABI-6078-2020; CYM-0930-2022; ETP-1691-2022; CKK-3621-2022; AAP-9988-2020; EXZ-0745-2022Background and Aim: In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase (DPYD) gene variant, c.1905 + 1G>A, leads to intolerance to fluoropyrimidines. Due to the low frequency of this variant in many populations, the prevalence of fluoropyrimidine-induced hematologic side effects in CRC patients with the c.1905 + 1G>A variant is unclear. In this study, we investigated the prevalence of the DPYD c.1905 + 1 variants in a Turkish CRC cohort and the potential effects of these variants on fluoropyrimidine-induced hematologic side effects.Materials and Methods: The DPYD c.1905 + 1 variant was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis and confirmed by Sanger sequencing in peripheral blood samples of 100 CRC patients who received fluoropyrimidine-based chemotherapy and 60 healthy volunteers. The association of c.1905 + 1 variants with susceptibility to hematologic side effects was evaluated.Results: The DPYD c.1905 + 1G>A variant was more common in the CRC group than in the healthy control group (p = 0.001). The presence of the c.1905 + 1G>A variant was associated with thrombocytopenia (p = 0.039) and anemia (p = 0.035). CRC patients with fluoropyrimidine-induced anemia had shorter disease-free survival than CRC patients without fluoropyrimidine-induced anemia (p = 0.0009).Conclusions: Before administering fluoropyrimidine-based chemotherapy, genetic screening for the DPYD c.1905 + 1G>A variant should be performed with the aim of preventing anemia and anemia-induced complications in CRC patients.Publication Olea europaea leaf extract suppress stemness-characteristics of gastric cancer via long non-coding rnas(Elsevier Science Inc, 2022-01-04) Tekin, Çağla; Erçelik, Melis; Tezcan, Gülçin; Aksoy, Seçil Ak; Egeli, Ünal; Çeçener, Gülşah; Tunca, Berrin; Tekin, Çağla; Erçelik, Melis; TEZCAN, GÜLÇİN; Aksoy, Seçil Ak; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; 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.; 0000-0002-5956-8755; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-1619-6680; AAH-3843-2020; AAH-1420-2021; ADM-8457-2022; AAP-9988-2020; ABI-6078-2020; GDC-6329-2022; EUG-3329-2022Introduction: 5-Fluorouracil (5-FU) and Cisplatin (Cis) are insufficient to fight against stem-like cancer cell (CSC)-phenotype Gastric cancer (GC). Therefore, new therapeutic approaches are required to treat CSC-GC patients. Although the anticancer effect of Olea europaea leaf extract (OLE) has been described for multiple types of cancer, including GC, the potential of OLE to be used as a complementary to 5-FU and Cis to treat CSC-GC remains largely unknown. This study uniquely investigated the potential of OLE to be used as complementary to 5-FU-Cis therapy to alleviate the CSC-mediated aggressiveness of GC.Methods: The AGS cells, A GC cell line was treated with OLE-only and its combinations with 5-FU-Cis. Tumor aggressiveness, colony formation, and vascularization were analyzed using tumorsphere and clonogenic assays and ex-vivo analyses. In addition, their effect on the expression of CSC markers, including CD133, OCT4, NANOG, and SOX2 and LncRNA, PVT1, MALAT1, H19, and SNHG16, was investigated using RT-qPCR.Results: OLE-only and involvement of OLE to 5-FU+Cis treatment reduced the size of tumor-spheres (p < 0.0001), number of colonies (p < 0.0001), and vascularization. In addition, the OLE-5-FU-Cis combination decreased mRNA expression levels CSC markers and LncRNA, PVT1, H19, and SNHG16 expression levels compared to 5-FU+Cis (p < 0.05).Conclusion: OLE reduced the survival capacity of CSC phenotype cells by decreasing LncRNA PVT1, MALAT1, and H19 and facilitates the aggressive features of GC cells. Further analysis and validations are required; current findings suggest that OLE could be complementarily used to improve the effect of 5-FU+Cis therapy for GC.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-3843-2020We 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 Crispr: A diagnostic tool for diseases(Springer, 2023-11-21) Khan, Sami Ullah; Stolbunova, Kristina A.; Shnakhova, Lidiya M.; Kabwe, Emmanuel; TEZCAN, GÜLÇİN; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi.; AAJ-4645-2020The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins are adaptive immune system found in bacteria and archaea. This system targets the genomes of invading pathogens in the bacteria for degradation and incorporates the fragments in the CRISPR cassettes. Because of its capacity to detect DNA and RNA, CRISPR/Cas system has emerged as a significant technique in molecular biology and has been adapted for genome editing. Also, it is been used in pathogen diagnostics, gene therapy, epigenetic regulation, and library construction. Although, CRISPR Cas system techniques have some limitations, they are the most promising diagnostic methods of the modern science and make it easy to use when combined with other techniques such as isothermal nucleic acid technique. Diagnostic methods such as real-time qPCR and isothermal nucleic acid amplification rely on a chain of reactions to detect pathogens. A single error in the preparation or experimental process can result in non-specific amplification. Furthermore, qPCR techniques are costly because they require skilled personnel and state-of-the-art equipment to carry out a series of procedures. Therefore, there is an urgent need to develop diagnostic methods that are simple and fast to utilize, particularly at the point of treatment. To answer this call, in the past decade, CRISPR/Cas system tools have been developing and actively used in detecting nucleic acids in pathogenic materials. In this review, we will shed light on the discovery of CRISPR/Cas and the CRISPR/Cas adaptive immune systems. Here, we will present a brief history of the classification of CRISPR/Cas systems, their applications in disease control, CRISPR/Cas13 nomenclature, and diagnostic tools. Additionally, we will discuss how the CRISPR/Cas13 system can detect noninfectious diseases. Further, we will conclude with the broader impact of CRISPR technologies on preventing pathogens, a serious human health threat.Publication Olea europaea leaf phenolics oleuropein, hydroxytyrosol, tyrosol, and rutin Induce apoptosis and additionally affect temozolomide against glioblastoma: In particular, oleuropein inhibits spheroid growth by attenuating stem-like cell phenotype(Mdpi, 2023-02-01) Erçelik, Melis; Tekin, Çağla; Tezcan, Gülçin; Aksoy, Seçil Ak; Bekar, Ahmet; Kocaeli, Hasan; Taşkapılıoğlu, Mevlüt Özgür; Eser, Pınar; Tunca, Berrin; Erçelik, Melis; Tekin, Çağla; TEZCAN, GÜLÇİN; Aksoy, Seçil Ak; 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.; 0000-0002-5956-8755; 0000-0001-5472-9065; 0000-0003-0132-9927; 0000-0002-1619-6680; EUG-3329-2022; GDC-6329-2022; AAH-3843-2020; ADM-8457-2022; CGB-7869-2022; FDK-3229-2022; AAW-5254-2020; AAI-2073-2021; ABI-6078-2020The effects of Olea europaea leaf extract (OLE) phenolics, including oleuropein (OL), hydroxytyrosol (HT), tyrosol (TYR), and rutin against glioblastoma (GB), independently and in combination with temozolomide (TMZ), were investigated in T98G and A172 cells. Cell growth was assessed by WST-1, real-time cell analysis, colony formation, and cell cycle distribution assays. A dual acridine orange propidium iodide (AO/PI) staining and annexin V assay determined cell viability. A sphere-forming assay, an intracellular oxidative stress assay, and the RNA expression of CD133 and OCT4 investigated the GB stem-like cell (GSC) phenotype. A scratch wound-healing assay evaluated migration capacity. OL was as effective as OLE in terms of apoptosis promotion (p < 0.001) and GSC inhibition (p < 0.001). HT inhibited cell viability, GSC phenotype, and migration rate (p < 0.001), but its anti-GB effect was less than the total effect of OLE alone. Rutin decreased reactive oxygen species production and inhibited colony formation and cell migration (p < 0.001). TYR demonstrated the least effect. The additive effects of OL, HT, TYR and rutin with TMZ were significant (p < 0.001). Our data suggest that OL may represent a novel therapeutic approach against GB cells, while HT and rutin show promise in increasing the efficacy of TMZ therapy.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
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