Browsing by Author "Aksoy, Seçil Ak"
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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 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 Investigation of cerbb2 at mrna level in patients with gastric adenocarcinoma(Bayrakol Medical Publisher, 2022-06-01) Turhan, Ezgi Işıl; Aksoy, Seçil Ak; UĞRAŞ, NESRİN; IŞIK, ÖZGEN; AKSOY, SEÇİL; TUNCA, BERRİN; Tunca, Berrin; Işık, Özgen; Yerci, Ömer; YERCİ, ÖMER; Vuruşkan, Berna Aytaç; AYTAÇ VURUŞKAN, BERNA; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Klinik Biyoloji Anabilim Dalı.; 0000-0002-1619-6680; 0000-0002-9541-5035; ADM-8457-2022; AAW-9602-2020Aim: Gastric adenocarcinomas take place near the top regarding mortality due to cancer. This study aims to validate IHC results with the RT-PCR method and to evaluate their contribution to confirm the absolute score of CerbB2 situation in tissues. Material and Methods: We analyzed 80 gastric adenocarcinoma cases diagnosed in our clinic. The expression characteristics of the cases were evaluated using CerbB2 staining. Simultaneously, CerbB2 expression analyses were performed with the RT-PCR method. Results: Positive immunoreactivity was observed in 19 of 80 cases (23,75%) in the study conducted using CerbB2 antibody. While 14 of these cases (17.5%) demonstrated weak positive (2+), 5 of them (6.25%) demonstrated strong positive (3+) immunoreactivity. With the RT-PCR method, an increase in gene expression was observed in 12 of 14 weak positive cases (75%). In all 5 strong positive cases, on the other hand, high gene expression was determined. Between CerbB2 immunohistochemical findings and gene expression, 89% compatibility and a statistically significant relationship was determined. While an increase in CerbB2 gene expression, determined by Real Tirme PCR method, was not observed in 57 of 61 cases (96.6%) without CerbB2 immunoreactivity, 4 cases had an increase in CerbB2 expression in comparison to normal. In our study, a statistically significant relationship was determined between CerbB2 expression and Helicobacter pylori (H. pylori) that is a factor blamed for gastric cancer etiology. The relationship between CerbB2 expression and clinicopathologic prognostic factors has been statistically reviewed; no significant results have been found. Discussion: Our study has shown that RT-PCR is a method, which might be an alternative to IHC and in ISH methods. It is concluded that a statistically significant relationship might be determined between CerbB2 expression and clinicopathologic prognostic parameters by increasing the case number.Publication Liver-derived exosomes in liquid biopsies: Advantage before liver transplantation - a pilot study(Lippincott Williams & Wilkins, 2021-08-01) ; Aksoy, F.; AKSOY, FUAT; Aksoy, Seçil Ak; Tunca, B.; TUNCA, BERRİN; Kıyıcı, M.; Kaya, E.; Bursa Uludağ Üniversitesi.; 0000-0001-5808-9384; 0000-0002-1619-6680; HII-8895-2022; ADM-8457-2022Item MikroRNA-106a’nın yüksek ekspresyonu kolorektal kanserlerde mikrosatellit instablite durumu ile ilişkilidir(Bursa Uludağ Üniversitesi, 2021-07-09) Uğraş, Nesrin; Kanat, Özkan; Aksoy, Seçil Ak; Tunca, Berrin; Yılmazlar, Tuncay; Öztürk, Ersin; Aksoy, Fuat; Işık, Özgen; Yerci, Ömer; Mutlu, Melis; Tekin, Çağla; Bursa Uludağ Üniversitesi/İnegöl Meslek Yüksekokulu/İlk ve Acil Yardım Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genel Cerrahi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Patoloji Anabilim Dal.; 0000-0002-3760-9755; 0000-0002-1619-6680; 0000-0003-1924-0795; 0000-0001-8593-5101; 0000-0001-5808-9384; 0000-0002-9541-5035; 0000-0001-7118-5258; 0000-0002-6633-3428; 0000-0002-2568-3667Mikrosatellit instabilite (MSI), DNA tamir genlerindeki hatalardan kaynaklanan ve kolorektal kanserin (KRK) oluşmasına neden olan genetik bir durumdur. Sporadik KRK’larda MSI görülme sıklığı, prognoza olan etkisi literatürde çelişkilidir. Bununla birlikte MSI’ya sahip KRK’larda standart kemoterapi yetersiz kaldığı için yeni tedavi seçeneklerine ihtiyaç duyulmaktadır. micoRNA’lar (miRNA) kanserleşme sürecinde görev alan ve tanıda, prognozda ve tedavide belirteç olarak kullanılan küçük RNA molekülleridir. Mevcut çalışmada, Türk popülasyonuna ait sporadik gelişen KRK’larda MSI’nın görülme sıklığının tanımlanması ve bu tümörlerde miRNA’ların ekspresyon farklılıklarının belirlenmesi amaçlanmıştır. Çalışmada, sporadik KRK tanısı almış 63 hasta değerlendirildi. Hastalara ait arşiv tümör ve normal dokularından DNA ve RNA izolasyonları yapıldı. DNA örneklerinden fragment analizine dayalı MSI testi gerçekleştirildi. qRT-PCR kullanılarak 38 farklı miRNA’nın ekspresyon profili incelendi. 63 hastada MSI görülme oranı %23.8 olarak belirlendi. MSI ve mikrosatellit stabil (MSS) tümörler karşılaştırıldığında, MSI tümörlerde, miR-124 ve miR-106a’nın yüksek ve miR-145’in ise düşük ekspresyon gösterdiği belirlendi (p<0.05). Bununla birlikte miR-106a’nın yüksek ekspresyonunun cerrahi sonrası nüks gelişimi ile ilişkili olduğu saptandı (p=0.002). Elde edilen bulgular ışığında miR-106a’nın özellikle MSI genotipine sahip KRK tümörlerde hedeflenmesi ile KRK hastalarında yeni tedavi protokollerinin oluşturularak nüks oluşumunun engellenebileceğini öngörülmüştür.Item Olea europaea leaf extract and bevacizumab synergistically exhibit beneficial efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis and invasion in vitro(Elsevier, 2017-04-10) Tezcan, Gülçin; Taşkapılıoğlu, Mevlut Özgür; Tunca, Berrin; Bekar, Ahmet; Demirci, Hilal; Kocaeli, Hasan; Aksoy, Seçil Ak; Egeli, Ünal; Cecener, Gülşah; Tolunay, Şahsine; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Nöroşirürji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Patoloji Anabilim Dalı.; 0000-0001-5472-9065; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0002-5956-8755; 0000-0001-7904-883X; AAI-1612-2021; AAH-1420-2021; ABB-8161-2020; AAH-3843-2020; AAW-5254-2020; ABI-6078-2020; AAP-9988-2020; 25650627600; 25936798300; 6602965754; 6603677218; 57193932262; 6603500567; 57193933334; 55665145000; 6508156530; 6602604390Patients with glioblastoma multiforme (GBM) that are cancer stem-cell-positive (GSC [+]) essentially cannot benefit from anti-angiogenic or anti-invasive therapy. In the present study, the potential anti-angiogenic and anti-invasive effects of Olea europaea (olive) leaf extract (OLE) were tested using GSC (+) tumours. OLE (2 mg/mL) caused a significant reduction in tumour weight, vascularisation, invasiveness and migration (p = 0.0001, p < 0.001, p = 0.004; respectively) that was associated with reducing the expression of VEGFA, MMP-2 and MMP-9. This effect was synergistically increased in combination with bevacizumab. Therefore, our current findings may contribute to research on drugs that inhibit the invasiveness of GBM.Publication Olea europaea leaf extract decreases tumour size by affecting the LncRNA expression status in glioblastoma 3D cell cultures(Elsevier, 2021-05-21) Mutlu, Melis; Tunca, Berrin; Aksoy, Seçil Ak; Tekin, Çağla; Çeçener, Gülşah; Egeli, Ünal; Mutlu, Melis; TUNCA, BERRİN; AKSOY, SEÇİL; Tekin, Çağla; ÇEÇENER, GÜLŞAH; EGELİ, ÜNAL; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Biyoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/İnegöl Meslek Yüksekokulu.; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0001-7904-883X; AAH-1420-2021; ADM-8457-2022; FPB-0403-2022; GDC-6329-2022; AAP-9988-2020; ABI-6078-2020Introduction: Glioblastoma (GB) is the most aggressive primary brain tumour. Temozolomide (TMZ) is a chemotherapy drug used in the treatment of GB. Despite treatment with TMZ, the prognosis of GB is poor. This study aimed to demonstrate the ability of Olea europaea leaf extract (OLE) alone and in combination with TMZ to suppress tumour aggressiveness by evaluating long non-coding RNA (LncRNA) and cancer stem cell (CSC) markers in GB cells using a three-dimensional (3D) model. Methods: The Real-time PCR (RT-PCR) method was used to determine the effects of OLE on LncRNA and CSC markers associated with tumour aggressiveness. To explore the effect of OLE on tumour size, a 3D model was developed. Results: It was found that OLE suppressed tumour aggressiveness with inhibited the MALAT1, SOX2 and NANOG ( p < 0.05). OLE + TMZ also inhibited MALAT1, LOXL1-AS1, PVT1 and H19 ( p < 0.05) and OCT4, NANOG, SOX2 and CD133 ( p < 0.05). In addition, to reduce tumour aggressiveness in a 3D cell culture, the use of OLE and OLE + TMZ has been supported (47.11-fold, p < 0.0001 and 18.04-fold, p < 0.0001, respectively). Conclusion: OLE may be a potential therapeutic agent that can be used in the treatment of GB, as it has been shown to reduce tumour size and increase the effect of TMZ.Item Oleuropein modulates glioblastoma miRNA pattern different from Olea europaea leaf extract(Sage Publications, 2019-09) Tezcan, Gülçin; Aksoy, Seçil Ak; Tunca, Seçil Berrin; Bekar, Ahmet; Mutlu, Melis; Çeçener, Gülşah; Egeli, Ünal; Kocaeli, Hasan; Demirci, Hilal; Taşkapılıoğlu, Mevlüt Özgür; Uludağ Üniversitesi/Tıp Fakültesi; 0000-0002-3760-9755; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0001-7904-883X; 0000-0001-5472-9065; AAH-8540-2021; ABI-6078-2020; CGB-7869-2022; FPB-0403-2022; AAP-9988-2020; AAH-1420-2021; FDK-3229-2022; CNW-1571-2022; AAW-5254-2020; 36668149100; 6602965754; 6603677218; 57212065763; 6508156530; 55665145000; 6603500567; 57193932262; 25936798300Glioblastoma (GBM) is the most prevalent and deadliest subtype of glioma. Despite current innovations in existing therapeutic modalities, GBM remains incurable, and alternative therapies are required. Previously, we demonstrated that Olea europaea leaf extract (OLE) kills GBM cells by modulating miR-181b, miR-137, miR-153 and Let-7d expression. However, although oleuropein (OL) is the main compound in OLE, its role in the antitumour effect of OLE remains unknown. This study determined the effect of OL on GBM cell line T98G and compared the results with our previous findings regarding the effect of OLE on the same cell line. The antiproliferative activity of OL and its effect on temozolomide (TMZ) response were tested inT98G cells using WST-1 assay. OL inhibition was evaluated using one-way analysis of variance with Tukey's post hoc test. The effect of OL on miR-181b, miR-137, miR-153 and Let-7d expression was assessed using quantitative reverse transcription polymerase chain reaction. Fold differences in expression between untreated, OL or OL + TMZ-treated samples were calculated using 2(-Delta Ct) method. Significance was evaluated using an independent sample t-test. Treatment with 277.5 and 555 mu M OL resulted in 39.51% and 75.40% reductions in T98G cells within 24 h. Coadministration of 325 mu M TMZ and 277.5 or 555 mu M, OL caused 2.08- and 2.83-fold increases, respectively, in the therapeutic effect of TMZ. OL + TMZ significantly increased microRNA expression, particularly Let-7d, than OLE. In conclusion, OL has an antitumour effect on GBM cells mainly via regulation of Let-7d expression. The present results also indicate other minor compounds in OLE play important anticancer roles.Item Overexpression of miR-21 Is Associated With Recurrence in Patients With Hepatitis B Virus-Mediated Hepatocellular Carcinoma Undergoing Liver Transplantation(Elsevier, 2019-05) Dündar, Halit Ziya; Aksoy, Fuat; Aksoy, Seçil Ak; Taşar, Pınar; Uǧraş, Nesrin; Tunca, Berrin Türkei; Egeli, Ünal; Çeçener, Gülşah; Yerci, Ömer; Kaya, Ekrem; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Cerrahi Tıp Bilimleri/Genel Cerrahi Bölümü.; 0000-0001-5808-9384; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0001-7904-883X; HII-8895-2022; ABI-6078-2020; AAP-9988-2020; AAH-2716-2021; AAH-1420-2021; 55453773300; 57208705658; 57193933334; 57208702845; 55386535600; 6602965754; 55665145000; 6508156530; 6603810549; 7004568109Liver transplantation (LT) is the best treatment option for hepatitis B virus (HBV)e mediated hepatocellular carcinoma (HCC). Nevertheless, recurrence is the most important issue after LT. The aims of the present study were to evaluate the relation of dysregulated expression of microRNAs (miRNAs) in recurrence formation in HBV-mediated HCC cases. A total of 42 HBV-mediated HCC patients were evaluated in this study. Among 21 miRNAs, the expression level of miR-106a and miR-21 were higher and miR-143 and miR145 were lower in patients with HCC compared with noncancerous liver tissues (P = .0388, P = .0214, P = .0321, and P = .002, respectively). Compared with nonrecurrent patients, the expression level of miR-21 was 3.54-fold higher and miR-145 was 2.42-fold lower in patients with recurrence during the 5-year follow-up (P = .004 and P = .032; respectively). In addition, according to multivariate Cox regression analysis, the overexpression of miR-21 was found to be a prognostic indicator in HBV-mediated HCC patients (P = .002). In conclusion, we show a significant association between high expression of miR-21 and recurrence in HBV-mediated HCC. Therefore, up-regulation of miR-21 could serve as a promising prognostic marker for HCC.Publication Tumor-derived exosomal mir-21 induces recurrence in liver cancer(Wiley, 2021-08-01) Aksoy, Fuat; Kaya, Ekrem; Dündar, Halit Ziya; Aksoy, Seçil Ak; Tunca, Berrin; AKSOY, FUAT; KAYA, EKREM; DÜNDAR, HALİT ZİYA; AKSOY, SEÇİL; TUNCA, BERRİN; Bursa Uludağ Üniversitesi.; 0000-0001-5808-9384; 0000-0002-1619-6680; 0000-0002-9562-4195; ADM-8457-2022; HII-8895-2022; AAG-7319-2021; EWI-3634-2022; ABI-6078-2020