Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Permanent URI for this collectionhttps://hdl.handle.net/11147/9
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Review Citation - WoS: 9Citation - Scopus: 7Micrornas and Long Non-Coding Rnas as Novel Targets in Anti-Cancer Drug Development(Bentham Science Publishers, 2023) Çetinkaya, Melisa; Baran, YusufNon-coding RNAs comprise the majority of RNAs that have been transcribed from the human genome, and these non-coding RNAs have essential regulatory roles in the cellular processes. They have been discovered to influence the expression of the genes, including tumor-suppressive and oncogenes, that establish the non-coding RNAs as novel targets for anti-cancer drug development. Among non-coding RNAs, microRNAs have been extensively studied in terms of cancer biology, and some microRNA-based therapeutics have been reached in clinical studies. Even though most of the research regarding targeting non-coding RNAs for anti-cancer drug development focused on microRNAs, long non-coding RNAs have also started to gain importance as potential therapeutic targets for cancer therapy. In this chapter, the strategies and importance of targeting microRNAs and long non-coding RNAs will be described, along with the clinical studies that involve microRNA-based cancer therapeutics and preclinical studies that involve long non-coding RNA-based therapeutics. Finally, the delivery strategies that have great importance in the effective delivery of the non-coding RNA-based cancer therapeutics, hence the therapy's effectiveness, will be described.Conference Object Peptıde Targeted Core Cross-lınked Mıcelles For Dox Delıvery To Her2 Expressıng Cancer Cells(Mary Ann Liebert, 2022) Bayram, Nazende Nur; Ulu, Gizem Tuğçe; Gürdap, Seda; İşoğlu, İsmail Alper; Baran, Yusuf; Dinçer İşoğlu, SevilIn this study, we prepared a novel targeted and extra stable micellar nanocarrier that can facilitate intracellular drug release. First, ((N-3-sulfopropyl-N, N-dimethylammonium)ethyl methacrylate was synthesized by RAFT polymerization, and it was followed by copolymerization of macroCTA with AEM in the presence of an aciddegradable cross-linker. Then, a peptide estimated by phage display for HER-2 recognition was incorporated into these core cross-linked micelles with carbodiimide reaction.Conference Object Jak/Stat Signalling Pathway Genes in the Regulation of Tyrosine Kinase Inhibitors Induced and Clinical Process in Chronic Myeloid Leukemia Patients(Elsevier, 2014) Kiraz, Yağmur; Kartal Yandım, Melis; Kozanoğlu, İlknur; Özdoğu, Hakan; Pişkin, I.; Özcan, Mehmet Ali; Saydam, Göksel; Şahin, Fahri; Avcu, Ferit; Ural, Ali Uğur; Ünal, Ali; Baran, Yusuf[No abstract available]Conference Object Targeting Sphingosine Kinase-1/Spingosine-1-phosphate Receptor 2 Signalling Pathway To Overcome T315i Mutation in 32dcl3 Cells(Elsevier Ltd., 2014) Adan Gökbulut, Aysun; Öğretmen, Besim; Baran, YusufThe main problem in chronic myeloid leukemia patients is the development of resistance against tyrosine kinase inhibitors. The expression of BCR-ABL1 having T315 mutation is responsible for the development of nilotinib resistance. The alterations in sphingolipid signalling pathway is a significant BCR-ABL1-dependent resistance mechanism. Recently, we showed that sphingosine kinase-1 (SK-1)/sphingosine-1 phosphate (S1P)-mediated drug resistance is transduced via sphingosine-1 phosphate receptor 2 (S1P2) that inhibits protein phosphatase 2A (PP2A), causing increased stability of BCR-ABL1. However, specific signaling cascade involved in this process remain unkown. In this study, BCR-ABL1 expressing 32Dcl3 cells, 32D-p210Bcr-Abl(wt) and 32D-p210Bcr-Abl (T315I) were used. The antiproliferative effects of nilotinib, SK-1 inhibitor (PF-543), S1P2 inhibitor (JTE-013), phospholipase C inhibitor (U-73122) and nilotinib/PF-543 and nilotinib/JTE-013 combinations on wt and resistant cells were determined by MTT assay. Isobologram analysis was performed using CompuSyn program.Conference Object Therapeutic Potential of Fisetin, Vitexin and Hesperetin on Chronic Myeloid Leukemia Cells(Elsevier Ltd., 2014) Adan Gökbulut, Aysun; Baran, YusufIn Chronic Myeloid Leukemia (CML) treatment, despite therapeutic efficacy of tyrosine kinase inhibitors, resistance development and side effects cause problems. Fisetin, vitexin and hesperetin are plant-derived flavonoids. In this study, therapeutic potentials of fisetin, vitexin and hesperetin were determined in CML cells. Cytotoxic effects of flavonoids were determined by MTT assay while apoptotic effects were determined by changes in caspase- 3 activity, loss of mitochondrial membrane potential (MMP) and Annexin V/PI double staining. Cytostatic effects of the flavonoids were evaluated by propidium iodide staining using flow cytometry.Conference Object A Novel Biomarker for Drug Resistance in Chronic Myeloid Leukemia: Microrna-17(Elsevier Ltd., 2014) Baran, Yusuf; Fıratlıgil, Burcu; Kartal Yandım, Melis; Kiraz, Yağmur; Kozanoğlu, İlknur; Özdoğu, Hakan; Ünal, AlimiRNAs are single stranded small RNA molecules (20–22 nt), which do not have ability to code for proteins. These types of RNAs play significant roles on gene regulation through inhibition of their target genes. In animals, most of miRNAs show their translational inhibitor effect on target mRNAs by semi-complementation to 3’UTR sequences of mRNAs and deadenylation that cause degradation of these mRNAs. The importance of miRNAs is increasing in cancer diagnosis and treatment since they are one of the major regulators of genes such as oncogenes, tumor suppressor genes. miR-17 is an oncogenic miRNA that suppress the activation of tumor suppressor genes like CDKN1A, p21 and E2F1. Based on previous information, we aimed to determine the correlation between expression levels of miR-17 microRNA in newly diagnosed, tyrosine kinase inhibitors treated and drug resistant CML patients.Conference Object Cytotoxic and Apoptotic Effects of Fisetin, Hesperetin and Vitexinon Acute Promyelocytic Leukemia Cells(Elsevier Ltd., 2014) Adan Gökbulut, Aysun; Baran, YusufAcute Promyelocytic Leukaemia (APL) is characterized by abnormal accumulation of immature granulocytes in the bone marrow and the blood stream. To date, there is no definitive treatment strategy. Fisetin, hesperetin and vitexin are flavanoids found in fruits and vegetables. Their anticancer properties have been studied on several cancer types. In this study, we aimed to examine the cytotoxic, cytostatic and apoptotic effects of fisetin, hesperetin and vitexin on Acute Promyelocytic Leukaemia cells. Cytotoxic effects were evaluated by MTT assay while apoptotic effects of these flavonoids were examined by changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP) and Annexin V/PI double staining. Cytostatic effects of the flavonoids were evaluated by propidium iodide staining using flow cytometry.Article Citation - WoS: 6Citation - Scopus: 6Therapeutic Potentials of Inhibition of Jumonji C Domain-Containing Demethylases in Acute Myeloid Leukemia(Aves, 2020) Koca, Duygu; Hastar, Nurcan; Engür, Selin; Kiraz, Yağmur; Ulu, Gizem Tuğçe; Çekdemir, Demet; Baran, YusufAcute myeloid leukemia (AML) is a complex disease affected by both genetic and epigenetic factors. Histone methylation and demethylation are types of epigenetic modification in chromatin remodeling and gene expression. Abnormal expression of histone demethylases is indicated in many types of cancer including AML. Although many commercial drugs are available to treat AML, an absolute cure has not been discovered yet. However, inhibition of demethylases could be a potential cure for AML. Methylstat is a chemical agent that inhibits the Jumonji C domain-containing demethylases.Article Citation - WoS: 3Citation - Scopus: 3A Minimally Invasive Transfer Method of Mesenchymal Stem Cells To the Intact Periodontal Ligament of Rat Teeth: a Preliminary Study(TÜBİTAK, 2018) Gül Amuk, Nisa; Kurt, Gökmen; Kartal Yandım, Melis; Adan, Aysun; Baran, YusufThe aim of this study was to introduce a minimally invasive procedure for mesenchymal stem cell (MSC) transfer into the intact periodontal ligament (PDL) of the molar teeth in rats. Ten 12-week-old Wistar albino rats were used for this preliminary study. MSCs were obtained from bones of two animals and were labeled with green fluorescent protein (GFP). Four animals were randomly selected for MSC injection, while 4 animals served as a control group. Samples were prepared for histological analysis, Cox-2 mRNA expression polymerase chain reaction analysis, and fluorescent microscopy evaluation. The number of total cells, number of osteoclastic cells, and Cox-2 mRNA expression levels of the periodontal tissue of teeth were calculated. The number of total cells was increased with MSC injections in PDL significantly (P < 0.001). The number of osteoclastic cells and Cox-2 mRNA expression were found to be similar for the two groups. GFP-labeled MSCs were observed with an expected luminescence on the smear samples of the PDL with transferred MSCs. The results of this preliminary study demonstrate successful evidence of transferring MSCs to intact FIX in a nonsurgical way and offer a minimally invasive procedure for transfer of MSCs to periodontal tissues.Article Citation - WoS: 426Citation - Scopus: 470Cell Proliferation and Cytotoxicity Assays(Bentham Science Publishers, 2016) Adan, Aysun; Kiraz, Yağmur; Baran, YusufCell viability is defined as the number of healthy cells in a sample and proliferation of cells is a vital indicator for understanding the mechanisms in action of certain genes, proteins and pathways involved cell survival or death after exposing to toxic agents. Generally, methods used to determine viability are also common for the detection of cell proliferation. Cell cytotoxicity and proliferation assays are generally used for drug screening to detect whether the test molecules have effects on cell proliferation or display direct cytotoxic effects. Regardless of the type of cell-based assay being used, it is important to know how many viable cells are remaining at the end of the experiment. There are a variety of assay methods based on various cell functions such as enzyme activity, cell membrane permeability, cell adherence, ATP production, co-enzyme production, and nucleotide uptake activity. These methods could be basically classified into different categories: (I) dye exclusion methods such as trypan blue dye exclusion assay, (II) methods based on metabolic activity, (III) ATP assay, (IV) sulforhodamine B assay, (V) protease viability marker assay, (VI) clonogenic cell survival assay, (VII) DNA synthesis cell proliferation assays and (V) raman micro-spectroscopy. In order to choose the optimal viability assay, the cell type, applied culture conditions, and the specific questions being asked should be considered in detail. This particular review aims to provide an overview of common cell proliferation and cytotoxicity assays together with their own advantages and disadvantages, their methodologies, comparisons and intended purposes.