Person: ERYILMAZ, IŞIL EZGİ
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ERYILMAZ
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IŞIL EZGİ
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Publication The cytotoxic effect of usnic acid in malignant melanoma cells with different genomic profiles in the BRAF aspect(Verduci Publisher, 2022-01-01) Çolakoğlu, C.; Hacıefendi, A.; Eryılmaz, I. E.; Eskiler, G. G.; Egeli, U.; Çeçener, G.; Çolakoğlu , Ceyda; ERYILMAZ, IŞIL EZGİ; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; Tıp Fakültesi; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0002-7471-5071; AEZ-2955-2022; GWV-3548-2022; AAH-1420-2021; AAP-9988-2020Objective: Malignant melanoma (MM) is the most aggressive skin cancer and treatment options are still limited in the late stages, generally accompanied by BRAF mutations. Usnic acid (UA), a well-known traditional lichen metabolite, has a promising and selective antitumoral activity. However, the effects of UA on MM cells with different genomic profiles in the BRAF aspect have not been investigated yet. In this study, we evaluated the effect of UA on BRAFV600E mutated-A2058 and wild-type MeWo cells.Materials and Methods: In the UA-treated cells, viability and cell death analysis were performed by using WST-1 and Annexin-V assays. Then, the death-related morphological changes were visualized by acridine orange(AO)/ethidium bromide (EB) staining. The cell cycle regulatory effect of UA was determined. Finally, time-dependent detection of acidic vesicular organelles (AVOs) was performed by live-cell imaging.Results: While MeWo viability significantly reduced to 53.8% and 28.6%, A2058 viability was detected as 61.3% and 50.3% at 50 and 100 mu M UA for 48 h. Thus, MeWo cells were found to be more sensitive to UA. Annexin-V and morphological analysis results showed that UA triggered mainly a vacuole-dependent cell death by the formation of AVOs, instead of apoptosis, in the MM cells. This effect was prominent in A2058 compared to MeWo. UA also slightly triggered apoptosis in MeWo cells. Thus, the cell cycle regulatory effect of UA on MM cells changed based on the cell death type triggered.Conclusions: Our results suggest that UA exerts the cytotoxic effects on MM cells by inducing vacuole-dependent cell death, most probably autophagy, and the UA response of MM cells with a different genomic profile in the BRAF aspect varies.Publication The regulatory effect of cabazitaxel on epithelial-mesenchymal transition in metastatic prostate cancer(Wolters Kluwer Medknow Publications, 2023-01-01) Eskiler, Gamze Guney; ERYILMAZ, IŞIL EZGİ; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; Tıp Fakültesi; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0002-2088-9914; AAB-6011-2022Introduction:Epithelial-mesenchymal transition (EMT) is a critical mechanism that promotes cancer cells to metastasis. Therefore, EMT regulation has become an important target in anticancer therapy approaches in recent years. However, in metastatic prostate cancer (PC), the EMT regulatory effect has not fully understood for cabazitaxel (Cbx), a third line taxane-based chemotherapeutic for metastatic castration-resistant PC.Aim:In this study, we investigated the antimetastatic and EMT-regulatory effects of Cbx on hormone-sensitive metastatic PC cells.Materials and Methods:The anticancer effects of Cbx were assessed by WST-1 and Annexin V analysis. The antimetastatic effect of Cbx was evaluated by wound healing and quantitative reverse transcription polymerase chain reaction through EMT-mesenchymal-to-epithelial transition (MET) markers as well as EMT-repressor microRNAs (miRNAs) in Cbx-treated LNCaP cells.Results:Our results showed that, in addition to its apoptotic and anti-migratory activities, Cbx exhibited the EMT-repressor effects through the prominent downregulation of matrix metalloproteinase-9 and Snail levels as EMT-promoting factors, and the significant upregulation of the certain miRNAs, including miR-205, miR-524, and miR-124, which play a role in EMT-repressing by targeting regulators of the EMT-associated genes.Conclusion:Although further evaluations are needed to improve the findings, we showed that, in addition to its classical taxane function, Cbx has a regulatory effect on EMT-MET cycling in hormone-sensitive metastatic PC.Publication RNA-based markers in biopsy cores with atypical small acinar proliferation: Predictive effect of T2E fusion positivity and MMP-2 upregulation for a subsequent prostate cancer diagnosis(Wiley, 2019-02-01) Eryılmaz, I. Ezgi; Vuruşkan, Berna Aytaç; Kaygısız, Onur; Egeli, Ünal; Tunca, Berrin; Kordan, Yakup; Çeçener, Gülşah; ERYILMAZ, IŞIL EZGİ; AYTAÇ VURUŞKAN, BERNA; KAYGISIZ, ONUR; TUNCA, BERRİN; ÇEÇENER, GÜLŞAH; Tıp Fakültesi; Tıbbi Patoloji Ana Bilim Dalı; 0000-0002-9790-7295; 0000-0001-7904-883X; 0000-0002-1619-6680; 0000-0002-9947-848X; 0000-0002-3820-424X; ABI-6078-2020; AAP-9988-2020; AAH-1420-2021; L-9439-2019; AAM-9726-2020; AAH-9746-2021; GWV-3548-2022Background Atypical small acinar proliferation (ASAP) is a precursor lesion of prostate cancer (PC), and PC develops from this suspicious focus or an unsampled malignant gland nearby. However, PC-related molecular alterations that could guide the timing of repeat biopsies and help monitor PC risk in ASAP-diagnosed patients have not been investigated. The purpose of this study was to first investigate the expression of seven different PC-related RNAs that included serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG) gene (TMPRSS2-ERG, T2E) fusion, alpha-methylacyl-CoA racemase (AMACR), kallikrein related peptidase 3 (KLK3), androgen receptor (AR), prostate cancer specific antigen 3 (PCA3), and matrix metalloproteinases (MMP)-2 and 9. Methods PC-related RNAs were evaluated using a real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) system in pathologically ASAP-diagnosed prostate biopsy cores from 55 patients presenting with a normal digital rectal examination and a PSA level of 4-10 ng/mL. Results We detected that positive T2E fusion status (P = 0.013) and the expression of AMACR (P = 0.016), AR (P = 0.016) and MMP-2 (P = 0.013) were independently and significantly associated with PC risk in ASAP patients. There were also several statistically significant correlations between expression levels. Additionally, we demonstrated that T2E fusion positive ASAP patients with higher MMP-2 expression were more likely to be diagnosed with PC at a subsequent biopsy during the follow-up period (P = 0.003). Conclusions Although, more clinical validations are needed for the stratification of PC risk in ASAP-diagnosed biopsy cores, our current results indicate that the coexistence of T2E fusion positivity with MMP-2 upregulation may help clinicians adjust their biopsy timetable and/or assessment of PC risk in ASAP-diagnosed patients with a PSA level of 4-10 ng/mL.Publication The role of the dopamine β-hydroxylase functional polymorphism in patients with early-onset parkinson's disease in the Turkish population(Turkish Neurological Soc, 2021-03-01) Erer, Sevda; Eryılmaz, Işıl Ezgi; Çolak, Dilara Kamer; Egeli, Ünal; Çeçener, Gülşah; Tunca, Berrin; Karakuş, Ece; Çolakoğlu, Beril; Tokçaer, Ayşe Bora; Saka, Esen; Demirkıran, Meltem; Akbostancı, Cenk; Zarifoğlu, Mehmet; Doğu, Okan; Kaleagasi, Hakan; Kenangil, Gülay; Çakmur, Raif; Elibol, Bülent; ERER ÖZBEK, ÇİĞDEM SEVDA; ERYILMAZ, IŞIL EZGİ; Çolak, Dilara Kamer; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; TUNCA, BERRİN; Karakuş, Ece; ZARİFOĞLU, MEHMET; Tıp Fakültesi; Nöroloji Ana Bilim Dalı; 0000-0001-7904-883X; 0000-0002-3316-316X; 0000-0002-2274-3230; 0000-0003-4968-2826; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0003-2982-0961; GWV-3548-2022; AAH-1420-2021; DVY-9744-2022; JIP-4494-2023; AAP-9988-2020; ABI-6078-2020; FDA-2023-2022; EHN-5825-2022Objective: A functional single nucleotide polymorphism, rs1611115, in the dopamine beta-hydroxylase (DBH) gene, is reported to regulate plasma enzyme activity levels. Mere, we report the first evaluation of this association in patients with early-onset Parkinson's disease (EOPD) and healthy controls in the Turkish population.Materials and Methods: We evaluated the DBH rs1611115 polymorphism in 114 (64 male and 50 female) Turkish patients with EOPD and 58 sex- and age-matched healthy controls from the Turkish population. A total of 27.2% (n=31) of our patients who had any variation including pathogenic or non-pathogenic missense, non-sense and/or intronic variation with unknown significance in EOPD genes were grouped as "variation-positive EOPD". A total of 50.8% (n=58) of our patients were grouped as "variation and family history-negative EOPD" and the possible contribution of the DBH rs1611115 polymorphism to EOPD pathogenesis was evaluated in this group.Results: There was no significant difference in the genotypic and allelic frequencies of DBH rs1611115 between patients with EOPD and controls. To our knowledge, this is the first evaluation of the DBH rs1611115 polymorphism in patients with EOPD and ethnically matched controls in the Turkish population.Conclusion: Some previous studies have reported conflicting association results between DBH rs1611115 polymorphism and PD pathogenesis in different ethnic groups. Therefore, further studies are needed to evaluate dopamine metabolism-related generic variants and to determine their possible roles in EOPD susceptibility in the Turkish population.Publication The molecular consequences of the novel speckle-type POZ protein (SPOP) gene mutations at the protein level: A prostate cancer perspective(Springernature, 2022-04-01) Eryılmaz, Işıl Ezgi; Vuruşkan, Berna Aytaç; Kaygısız, Onur; Çeçener, Gülşah; Egeli, Ünal; Vuruşkan, Hakan; ERYILMAZ, IŞIL EZGİ; AYTAÇ VURUŞKAN, BERNA; KAYGISIZ, ONUR; ÇEÇENER, GÜLŞAH; VURUŞKAN, HAKAN; EGELİ, ÜNAL; Tıp Fakültesi; 0000-0002-9790-7295; 0000-0002-3820-424X; 0000-0001-7904-883X; GWV-3548-2022; L-9439-2019; AAH-1420-2021; AAP-9988-2020; EEJ-1452-2022; EFH-9523-2022Publication The anticancer effect of inula viscosa methanol extract by miRNSs' re-regulation: An in vitro study on human malignant melanoma cells(Taylor, 2021-02-04) Çolak, Dilara Kamer; Egeli, Ünal; Eryılmaz, Işıl Ezgi; Aybastıer, Önder; Malyer, Hulusi; Çeçener, Gülşah; Tunca, Berrin; Çolak, Dilara Kamer; EGELİ, ÜNAL; ERYILMAZ, IŞIL EZGİ; AYBASTIER, ÖNDER; MALYER, HULUSİ; ÇEÇENER, GÜLŞAH; TUNCA, BERRİN; Fen Edebiyat Fakültesi; Analitik Kimya Bölümü; 0000-0001-7904-883X; 0000-0002-0380-1992; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0002-3316-316X; GWV-3548-2022; AAH-1420-2021; HXB-1173-2023; X-4621-2018; DDS-8738-2022; AAP-9988-2020; ABI-6078-2020Alternative and natural therapies are needed for malignant melanoma (MM), the most deadly skin cancer type due to chemotherapy's limited effect. In the present study, we evaluated the anticancer potentials of Inula viscosa methanol and water extracts (IVM and IVW) on MM cells, A2058 and MeWo, and normal fibroblasts. After the chromatographic and antioxidant activity analysis, their antiproliferative effects were determined with the increasing doses for 24-72 h. IVM induced more cell death in a dose and time-dependent manner in MM cells compared to IVW. This effect was probably due to the higher amount of phenolics in it. IVM significantly induced more apoptotic death in MM cells than fibroblasts (p < 0.01), which was also supported morphologically. IVM also caused cell cycle arrest at G0/G1 and G2/M phases in A2058 and MeWo, respectively, and suppressed the migration ability of MM cells (p < 0.01). Additionally, IVM was found to have significant potential in regulating MM-related miRNAs, upregulating miR-579 and miR-524, and downregulating miR-191 and miR-193, in MM cells (p < 0.05, p < 0.01). As a result, the anticancer effect of IVM via regulating miRNAs' expression has been demonstrated for the first time. Thus, IVM, with these potentials, may be a promising candidate for MM treatment.Publication Evaluation of the clinical features accompanied by the gene mutations the 2 novel PSEN1 variants in a Turkish early-onset alzheimer disease cohort(Lippincott Williams & Wilkins, 2021-07-01) Eryılmaz, Işıl E.; Bakar, Mustafa; Egeli, Ünal; Çeçener, Gülşah; Yurdacan, Beste; Çolak, Dilara K.; Tunca, Berrin; ERYILMAZ, IŞIL EZGİ; BAKAR, HACI MUSTAFA; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; Yurdacan, Beste; Çolak, Dilara K.; TUNCA, BERRİN; Tıp Fakültesi; Nöroloji Ana Bilim Dalı; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-1619-6680; 0000-0002-3820-424X; 0000-0002-1619-6680; GWV-3548-2022; AEA-0144-2022; AAH-1420-2021; EKN-8251-2022; AAP-9988-2020; HXB-1173-2023; ABI-6078-2020Introduction: Early-onset Alzheimer disease (EOAD) is an earlier Alzheimer disease form which is characterized by the mutations in the amyloid precursor protein, presenilin-1/2 (PSEN1/2), and triggering receptor expressed on myeloid cells 2 (TREM2). However, it is still necessary to report mutational screening in multiethnic groups to improve the genetic background of EOAD due to the variant classification challenge. Methods: We performed targeted sequencing for the amyloid precursor protein, PSEN1, PSEN2, and TREM2 genes in 74 patients and 1 family diagnosed with EOAD. Results: Among the detected variants, 8 were coding and 6 were noncoding in 15 of 74 patients. In PSEN1, 2 pathogenic coding variants (T274K and L364P) detected in 2 patients were novel and 3 coding variants (G183V, E318G, and L219P) detected in 2 patients were previously reported. We found 4 patients with the compound heterozygosity for the PSEN2 A23= and N43= and a family with the coexistence of them, and 1 patient with TREM2 Y38C. The coding variation frequency was 12.1%. In silico analysis indicated pathogenic potentials and clinical interpretations of the detected variants. Conclusion: Our study reveals the rare gene variants including novel ones from the Turkish EOAD cohort and provides to clinicians the list of detected variants in the screened genes, which may also be useful for accurate genetic counseling.Publication Contribution of functional dopamine D2 and D3 receptor variants to motor and non-motor symptoms of early onset Parkinson's disease(Elsevier, 2020-09-28) Eryılmaz, Işıl Ezgi; Erer, Sevda; Zarifoğlu, Mehmet; Egeli, Ünal; Karakuş, Ece; Yurdacan, Beste; Çeçener, Gülşah; Tunca, Berrin; Çolakoğlu, Beril; Tokcaer, Ayşe Bora; Saka, Esen; Demirkıran, Meltem; Akbostancı, Cenk; Doğu, Okan; Kaleağası, Hakan; Kenangil, Gülay; Çakmur, Raif; Elibol, Bülent; ERYILMAZ, IŞIL EZGİ; ERER ÖZBEK, ÇİĞDEM SEVDA; ZARİFOĞLU, MEHMET; EGELİ, ÜNAL; Karakuş, Ece; Yurdacan, Beste; ÇEÇENER, GÜLŞAH; TUNCA, BERRİN; Tıp Fakültesi; Nöroloji Ana Bilim Dalı; 0000-0002-3316-316X; 0000-0001-7904-883X; 0000-0002-3820-424X; 0000-0002-1619-6680; GWV-3548-2022; DVY-9744-2022; EHN-5825-2022; AAH-1420-2021; FDA-2023-2022; AEA-0144-2022; AAP-9988-2020; ABI-6078-2020In the present study, we focused on investigating the contribution of functional dopamine D2 and D3 receptor variants to motor and/or non-motor symptoms of early onset Parkinson's disease (EOPD). Three functional single nucleotide polymorphisms (SNPs), DRD3 rs6280, DRD2 rs2283265 and DRD2 rs1076560, were genotyped in 128 Turkish EOPD patients and then, statistical analysis was conducted for the potential impacts of SNPs on clinical parameters. All three SNPs were found to be statistically significant in terms of PD-related pain: DRD3 [rs6280; risk allele "T" for pain; p = 0.031; odds ratio (OR)=4.25], DRD2 [rs2283265; risk allele "A" for pain; p = 0.001; OR=8.47] and, DRD2 [rs1076560; risk allele "A" for pain; p = 0.022; OR=4.58]. Additionally, bilateral disease [p = 0.011; OR=5.10] and gender [risk group "female"; p = 0.003; OR=8.53] were also identified as significant univariate risk factors for PD-related pain. Based on logistic regression analysis conducted with the significant univariate risk factors, this the first report to clarify that a female patient with bilateral PD and DRD2 rs2283265 polymorphism has a significant risk for PD-related pain. Our findings might contribute to improve life quality by offering treatment options for pain in PD patients with these clinical and genetic features.Publication The cytotoxic and antitumoral effects of Remdesivir, an antiviral RdRp inhibitor, on different cancer cells in vitro(Korean Society Toxicogenomics & Toxicoproteomics-kstt, 2023-07-22) Eryılmaz, Işıl Ezgi; Bergel, Ceyda Çolakoğlu; Egeli, Ünal; Çeçener, Gülşah; ERYILMAZ, IŞIL EZGİ; Bergel, Ceyda Çolakoğlu; EGELİ, ÜNAL; ÇEÇENER, GÜLŞAH; Tıp Fakültesi; Tıbbi Biyoloji Ana Bilim Dalı; 0000-0002-7471-5071; 0000-0001-7904-883X; 0000-0002-3820-424X; GWV-3548-2022; AEZ-2955-2022; AAH-1420-2021; AAP-9988-2020BackgroundPrevious studies have shown similarities in the metabolism of cancer cells and parasites, suggesting that antiparasitic drugs may be used as anticancer agents. Remdesivir (Rem), an RdRp inhibitor, has been recently used in SARS-CoV-2 pandemic. Although the apoptotic effect of Rem has been demonstrated on the SKOV3 ovarian cancer cell line, its cytotoxic effect has not been analyzed in different cancer cells.ObjectiveWe aimed to evaluate its cell death-inducing effects on PC3 prostate cancer, HepG2 hepatocellular carcinoma, and A2058 malignant melanoma cells for the first time, using WST-1, Annexin V, cell cycle analysis, AO/EB staining, live-cell imaging, TEM, and gene expression analysis.ResultsRem treatment at 10, 25, and 50 & mu;M significantly decreased cell viability in all cancer cells (p < 0.01). While Rem triggered apoptosis in PC3, vacuole-dependent cell death was detected in HepG2 cells by visualizing the cells with TEM and time-dependent live-cell imaging. Moreover, both forms of cell death were triggered together in A2058. The formation of AVOs were observed more after 12 h and 24 h in HepG2 and A2058 cells, respectively. Additionally, Rem significantly induced cell cycle arrest in the G2/M (p < 0.01). Finally, the mRNA levels of autophagic markers, Atg12, Atg5, p62, Beclin, and LC3, were significantly increased in A2058 and HepG2 (p < 0.01) compared to control groups.ConclusionsOur results suggest that Rem has promising cytotoxic effects on various cancer cells. However, it triggers different types of cell death in different cancer types, indicating that further studies should focus on clarifying the molecular mechanism of the specific action of Rem.Publication MDR1 C3435t polymorphism predicts anti-epileptic prophylactic therapy response in Turkish migraine patients(Elsevier, 2015-10-15) Atasayar, Gülfer; Ezgi, Eryılmaz Işil; Yıldırım, Y. Öznur; Karlı, N.; Ünal, Ersin; Gülşah, Çeçener; Mehmet, Zileli; Berrin, Tuğrul; Gülçin, T.; Özlem, Temelli; ERYILMAZ, IŞIL EZGİ; Atasayar, G.; Yıldırım, Y. Öznur; Karlı, N.; ÜNAL, EDA; ÇEÇENER, GÜLŞAH; Mehmet, Zileli; TUNCA, BERRİN; Gülçin, T.; Özlem, Temelli; Tıp Fakültesi; Nöroloji Bölümü; 0000-0002-3183-9592; CEW-6612-2022; COE-7420-2022; IQE-9004-2023; JDE-9380-2023; CFN-0407-2022; EWA-9478-2022; DGE-3419-2022; EMJ-3438-2022; EYK-4124-2022; FSF-8333-2022