Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Examination of Therapeutic Potential of Luteolin on Acute Lymphoblastic Leukemia Cells and Changes in Macromolecules(01. Izmir Institute of Technology, 2023) Baran, Yusuf; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyAcute lymphoblastic leukemia (ALL) is a genetic disease that arises from the various recurrent genetic alterations blocking the differentiation of the precursor B-and T-cells, resulting in the aberrant proliferation and survival of immature lymphoblasts within the peripheral blood and bone marrow. T-ALL is an aggressive type of ALL, and the current treatment strategies, including the high-intensity combination chemotherapy, result in different side effects which are difficult to accept or ultimately lead to the death of patients as substantial toxicity of those chemotherapeutics is known to healthy cells alongside with the cancer cells. Therefore, there is a need to identify nontoxic, costeffective, potent, and readily available treatment options for T-ALL patients. One alternative option is the flavonoids in cancer therapeutics, which are secondary metabolites of plants mainly responsible for plants' colors and flower aromas. Luteolin is an extensively researched member of the flavonoids with anticancer properties shown in various cancer types, except for the T-ALL. This study demonstrated Luteolin's time- and dose-dependent antiproliferative, cytostatic, and apoptotic effects on T-ALL cells for the first time in the literature. Also, the macromolecular changes caused in response to Luteolin treatment in T-ALL cells were examined for the first time. As a consequence, it was found that Luteolin had antiproliferative, apoptotic, and cytostatic effects on T-ALL cells, suggesting its therapeutic potential and was demonstrated to cause an increase in the lipid-to-protein ratio and the hydrocarbon chain length of the lipid acyl chains in a dose-dependent manner on T-ALL cells.Master Thesis Determination of Therapeutic Effects of Multifunctional Antibody and Peptide Micelle-Based Nanocarriers on Breast Cancer Cells(01. Izmir Institute of Technology, 2021) Abdulhadi, Nusaibah Abdulsalam Abdulhad; Baran, Yusuf; Baran, Yusuf; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyBreast cancer is the most prevalent type of cancer and a major cause of death among women globally. Currently, many treatments are developed to reduce breast cancer death risks. Targeting therapy represents an advanced and successful approach. It provides targeting specific tumor sites by using specific ligands and modifying physicochemical characterization of nanocarriers to increase drug efficiency. In this study, we aim to determine and compare the therapeutic effects of doxorubicin (DOX)- loaded nanocarrier that was synthesized by using two properties a core cross-linked and pH sensitivity to increase drug stability and DOX releasing at the tumor site. The effects of DOX-loaded micelles (DM), HER2 targeting peptide (LTVSPWY)-conjugated-DOX-loaded micelles (DMP), and antibody (Herceptin) conjugated-DOX-loaded-micelles (DMA) on HER2 positive SKBR-3 cell line and HER2 negative MCF-10A normal epithelial breast cell line were determined by using cytotoxic, apoptotic, cytostatic, and genotoxic assays. According to the cytotoxic assay, the IC50 value of DM, DMA, and DMP were 0.71-, 0.49-, 0.34-µM, respectively. Additionally, the fluorescence image showed higher DOX uptake by SKBR-3 cells treated with DMP. According to the apoptotic assays, the mitochondrial membrane potential on SKBR-3 cells with treated DMP decreased as well as higher apoptosis and necrosis rate that was regulated by Bcl-2, Pro-Caspase-3, PARP1, Bax, Bak, and Bcl-xL. Besides, the application of DMP caused cell cycle arrest at the G2/M phase. Lastly, DNA damage was observed in response to DMP determined by comet assay. This study provides a novel and effective therapeutic option for breast cancer through using this nanocarrier system with targeting properties.
