TR Dizin İndeksli Yayınlar Koleksiyonu / TR Dizin Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14365/4
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Article Upregulated Acute Systemic Inflammation-Related Genes Based on Endotoxin Exposure Provide ‘Survival Benefit’ or Create ‘High Risk of Death’ in Leukaemia and Colon Cancer(Istanbul University, 2024-07-10) Duran, Gizem Ayna; Duran, Assist. Prof. Dr. Gizem Ayna; Ayna Duran, GizemObjective: Although endotoxin exposure has been shown to trigger innate immune responses and promote cancer, it has also been shown to prevent cancer formation. In our study, survival analysis was performed to determine whether the upregulated genes triggered by endotoxins have hazardous effects on cancers or provide a survival benefit. Materials and Methods: Gene intensity values of control and bacterial endotoxin-administered individuals were obtained from the Gene Expression Omnibus database. Using the R "Linear Models for Microarray Data" package, differentially expressed gene analyses were conducted to determine genes that differ between healthy and bacterial endotoxin-administered samples. "ShinyGo 0.80" web-based tool was used to determine the disease types indicated by these genes. The "Kaplan-Meier Plotter" web-based tool was used to conduct survival analysis. Results: Genes that create an innate immune response to bacterial endotoxin exposure and are upregulated differently than in individuals without exposure were identified. According to gene enrichment analyses, the two main types of cancer identified were leukaemia/lymoma and colon cancer. We detected that MLF1, STAT5B, and BCL3 genes led to poor survival; however, the ARHGAP26 gene was protective for acute myeloid leukaemia patients. In the case of colon cancer, SMAD7 and TLR2 genes were determined as leading to "high risk of death". Conclusion: Once the systemic inflammation-related genes identified in our study are confirmed through laboratory experiments in samples taken from solid tissue in the case of colon cancer and at the level of genes obtained from blood samples in leukemias, genetically targeted treatments will also be possible.Article Bioinformatics Based Drug Repurposing Approach for Breast and Gynecological Cancers: RECQL4/FAM13C Genes Address Common Hub Genes and Drugs(Galenos Publ House, 2025-01-02) Duran, Gizem Ayna; Duran, Assist. Prof. Dr. Gizem AynaObjective: The prevalence of breast cancer and gynaecological cancers is high, and these cancer types can occur consecutively as secondary cancers. The aim of our study is to determine the genes commonly expressed in these cancers and to identify the common hub genes and drug components. Materials and Methods: Gene intensity values of breast cancer, gynaecological cancers such as cervical, ovarian and endometrial cancers were used from the Gene Expression Omnibus database Affymetrix Human Genome U133 Plus 2.0 Array project. Using the linear modelling method included in the R LIMMA package, genes that differ between healthy individuals and cancer patients were identified. Hub genes were determined using cytoHubba in Cytoscape program. “ShinyGo 0.80” tool was used to determine the disease-specific biological KEGG pathways. Drug.MATADOR from the ShinyGo 0.80 tool was used to predict drug-target relationships. Results: The RecQ Like Helicase 4 and Family with Sequence Similarity 13 Member C genes were found to be similarly expressed in breast cancer and gynaecological cancers. Upon KEGG pathway analyses with hub genes, Drug.MATADOR analysis with hub genes related to cancer related pathways was performed. We have determined these gene/drug interactions: NBN (targeted by Hydroxyurea), EP300 (targeted by Acetylcarnitine) and MAPK14 (targeted by Salicylate and Dibutyryl cyclic AMP). Conclusion: The drugs associated with hub genes determined in our study are not routinely used in cancer treatment. Our study offers the opportunity to identify the target genes of drugs used in breast and gynaecological cancers with the drug repurposing approach.Research Project İnsan Genomunda Bulunan G-dörtlülerinin Sınıflandırılarak Korunmuş Motiflerin Keşfi ve Varyantlarının Analizi(2019) Kaplan, Oktay İsmail; Doluca, OsmanDNA motifileri proteinlerin amino asit dizilerinin saklanmasının yanı sıra genlerin regülasyonunda görev alan kısa DNA dizileridir. Bu diziler transkripsiyon faktörleri ya da diğer enzimlerle etkileşim göstererek gen regülasyonunda rol alabilmektedirler. Bu motiflerden bazıları DNA’nın bilindik 2 zincirli B-formun haricindeki sıradışı formlarını alarak bu etkileşimi tetikleyebilmektedirler. Bu sıradışı formlardan biri de G-dörtlüsü olarak bilinen, guanince zengin DNA yada RNA dizilerince oluşturulabilen yapılardır. G-dörtlüleri kendi aralarında birçok yapısal farklılık gösterebilen ve bu nedenle farklı rollere sahip bir yapı grubudur. Bu yapılar özellikle promotor bölgesi gibi regülasyonda etkili bölgelerde oluşarak transkripsiyonu etkileyebilmektedirler. Ancak bu yapıların tespiti ve rolleri konusunda çalışmalar devam etmekle beraber insan genomunda tahmin edilen 700.000’in üzerindeki G-dörtlüsünün rollerinin ve analizlerinin yapılması zaman ve emek alan bir süreçtir. Bu nedenle biyoenformatik yöntemler ile ön analiz ve tahminler yapılması ilgi çekmekte, varsa bu yapılardaki patojenik etkilerinin ortaya çıkarılması için tıbbi anlamda değer taşımaktadır. Bu çalışmada TÜBİTAK desteği ile Gdörtlülerinin tahmininden, sınıflandırılması ve ilişkilendirilmiş patojenik varyasyonların tespitine kadar gerekli bir seri biyoenformatik teknikler geliştirilmiş ve insan genomu için uygulanmıştır. İlk aşamada G-dörtlüsü tahmini için yeni bir algoritma geliştirilmiş ve başarısı yayınlanan makale ve bildiriler ile gösterilmiştir. Ardından insan genomunda tahmin edilen G-dörtlüleri bulunmuş, sınıflandırılarak farklı G-dörtlüsü motifleri ortaya çıkarılmıştır. Bulunan G-dörtlülerin patojenik etkisi bilinen varyasyonlar ile eşleştirilmiş ve bu varyasyonların etkisinin G-dörtlüsü yapısını etkileyerek gerçekleşip gerçekleşmediğinin tartışılabilmesi için yapısal değişimler deneysel olarak araştırılmıştır. Bulunan sonuçlar gerçekten bazı G-dörtlülerinin patojenik varyasyonlar sonucu yapısal olarak değişebildiğini göstermiştir.Article Citation - WoS: 5Effect of Flavopiridol on Cell Cycle, Apoptosis and Biomolecule Structure Changes in Breast Cancer Stem Cells(Galenos Publ House, 2020-07-01) Acikgoz, Eda; Guler, Gunnur; Oktem, GulperiObjective: Cancer stem cells (CSCs) are a small population in cancer, which are responsible for therapeutic resistance, relapse and metastasis. Flavopiridol has antitumor activity against various types of cancer cells. The mechanism of action of flavopiridol on CD44+/CD24- breast CSCs has not yet been fully elucidated. The aim of this study was to evaluate the mechanism of action of flavopiridol on breast CSCs (BCSC) in terms of apoptosis, cell cycle and biomolecular changes. Methods: In human breast cancer, cells with CD44+/CD24-markers were isolated from MCF-7 cell line using flow cytometry. The induction of apoptosis was investigated by Annexin-V. The effect of flavopiridol on cell cycle arrest was determined and the percent of cell populations at G0/G1, S and G2/M cycles were identified. The effect of the drug on three-dimensional cell cultures was investigated using a multicellular tumor spheroid model. In addition, the effect of flavopiridol on biomolecules has been evaluated using Fourier transform infrared (FTIR) spectroscopy, which has recently been used effectively in various scientific fields. Results: Flavopiridol especially induced early apoptosis. Cell cycle analyses revealed that flavopiridol induced cell cycle arrest in G0/G1 phase. Decreased number and diameter of spheroids was observed following flavopiridol treatment. ATR-FTIR data showed that treatment with flavopiridol led to significant changes in nucleic acids. Conclusion: According to the data obtained in this study, flavopiridol exhibits anticancer effects by altering the structure/expression level of nucleic acids and changing cell cycle progression and inducing apoptosis. These finding reveals that flavopiridol can be an effective antitumor agent for the treatment of breast cancer after in vivo and phase studies are completed.