Browsing by Author "TEZCAN, GÜLÇİN"
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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-1271-2019Publication 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 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.Publication Early-stage colon cancer with high malat1 expression is associated with the 5-fluorouracil resistance and future metastasis(Springer, 2022-07-06) Öztürk, Ersin; Aksoy, Seçil Ak; Tunca, Berrin; TUNCA, BERRİN; Erçelik, Melis; Tezcan, Gulcin; TEZCAN, GÜLÇİN; Çeçener, Gülşah; ÇEÇENER, GÜLŞAH; UĞRAŞ, NESRİN; YILMAZLAR, AHMET TUNCAY; Yerci, Omer; YERCİ, ÖMER; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0002-1619-6680; 0000-0002-5956-8755; 0000-0001-8593-5101; 0000-0002-3820-424X; ADM-8457-2022; AAH-3843-2020Background This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC). Methods and Results The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients. To confirm the findings in-vitro, 5FU-resistant HT29 cells were generated by subjecting HT-29 cells to the increasing concentrations of 5FU for 6 months. The 5FU resistance was observed in WST-1 and Annexin V analyses. The colony formation and wound healing assays were assessed to determine the metastatic properties of the cells. Expression levels of LncRNAs and mRNA of EMT-related genes were determined by RT-PCR. The role of LncRNA on metastasis and 5FU sensitivity were confirmed in pcDNA3.0-PTENP1 and si-MALAT1 expressed 5FU-resistant HT29 cell lineages. Results High MALAT1 (p = 0.0002) and low PTENP1 (p = 0.0044) expressions were significantly associated with 5-FU resistance and tumor relapse in stage I/II CC. The invasiveness and colony-forming characteristics of 5-FU-resistant cell lineages were higher as compared to the parent HT-29. Moreover, the expression of MALAT1 (p = 0.0009) was increased while the expression of PTENP1 (p = 0.0158) decreased in 5FU-resistant-HT-29 cells. Si-MALAT1 treatment increased cell sensitivity to 5FU, whereas it decreased invasive behaviors of 5 FU-resistant-HT-29 cells. Conclusion MALAT1 may be a biomarker in predicting recurrence in early-stage CC. Our findings suggest that a cell-based therapy to target MALAT1 could be established for these patients to prevent metastasis and 5-FU resistance.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-0005-2022Publication 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-9988-2020Temozolomide (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.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 Olea europaea L. leaf extract Attenuates Temozolomide-induced senescence-associated secretion phenotype in glioblastoma(Galenos Yayınevi, 2023-04-01) Erçelik, Melis; Tunca, Berrin; Ak Aksoy, Seçil; Tekin, Çağla; Tezcan, Gülçin; Erçelik, Melis; TUNCA, BERRİN; Ak Aksoy, Seçil; Tekin, Çağla; TEZCAN, GÜLÇİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/İnegöl Meslek Yüksekokulu.; Bursa Uludağ Üniversitesi/Diş Hekimliği Fakültesi/Temel Bilimler Bölümü.; 0000-0002-1619-6680; 0000-0002-5956-8755; AAH-3843-2020; ABI-6078-2020; JKU-0358-2023; IVC-4516-2023; JKO-1775-2023Objectives: The purpose of this study was to investigate the effect of Olea europaea L. leaf extract (OLE) on senescence and senescence-associated secretory phenotype (SASP) caused by temozolomide (TMZ) in glioblastoma (GB).Materials and Methods: A senescence beta-galactosidase assay and a colony formation assay were used to determine the effects of OLE, TMZ, and OLE + TMZ on the cellular senescence and aggressiveness of GB cell lines T98G and U87MG. mRNA expression levels of p53, a senescence factor, interleukin (IL)-6, matrix metalloproteinases (MMP)-9, and nuclear factor kappa B1 (NF-kappa B1) as SASP factors and Bcl-2 and Bax as senolytic markers were assessed using quantitative reverse transcription-real-time polymerase chain reaction. Cells were double-stained with acridine orange and propidium iodide to observe the cell morphology.Results: TMZ increased the senescence rate of GB cells (p<0.001). Besides, OLE + TMZ reduced the proportion of senescent cells (p<0.001) and their capability to form colonies compared to TMZ-only-treated cells. Additionally, OLE + TMZ co-treatment elevated the mRNA expression levels of MMP-9, IL-6, NF-kappa B1, p53, and the Bax/Bcl-2 ratio compared to TMZ-only treatment. Especially in U87MG cells, involvement of OLE in TMZ treatments increased more than six times in the Bax/Bcl-2 ratio compared to TMZ-only, which induced the apoptosis-like morphological features (p<0.0001).Conclusion: Collectively, our findings presented the inhibitory effect of OLE on TMZ-mediated SASP-factor production in GB and, accordingly, its potential contribution to elongate the time of recurrence.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-6078-2020The 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 Olea europaea leaf extract improves the treatment response of GBM stem cells by modulating miRNA expression(E-century Publishing Corp, 2014-01-01) Tümen, Gülendam; TUNCA, BERRİN; TEZCAN, GÜLÇİN; Tunca, Berrin; Bekar, Ahmet; BEKAR, AHMET; Budak, Ferah; BUDAK, FERAH; Egeli, Ünal; Taşkapılıoğlu, Mevlüt Özgür; Kocaeli, Hasan; Tolunay, Şahsine; Malyer, Hulusi; Demir, Cevdet; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Biyokimya Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Mikrobiyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 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-1420-2021The 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 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 Tamoxifen suppresses nlrp3 priming via mir-223 in breast cancer independently from erα(Springernature, 2022-12-15) Hamza, Shaimaa; Garanina, Ekaterina E.; Khaiboullina, Svetlana F.; Tezcan, Gülçin; TEZCAN, GÜLÇİN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Temel Bilimler Anabilim Dalı.; 0000-0002-5012-4760; 0000-0002-5956-8755; AAH-3843-2020Publication 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-3843-2020Publication 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-4183-2017IntroductionDysregulation 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