Master Degree / Yüksek Lisans Tezleri

Permanent URI for this collectionhttps://hdl.handle.net/11147/3008

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Publisher: search.filters.publisher.01. Izmir Institute of TechnologySubject: search.filters.subject.Breast cancer

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Now showing 1 - 6 of 6
  • Master Thesis
    Development of Doxorubicin-Loaded Liposomes Self-Assembled With Polysaccharides for Breast Cancer Therapy
    (01. Izmir Institute of Technology, 2023) Kılıç Özdemir, Sevgi; Polat, Hürriyet; Kılıç Özdemir, Sevgi; Polat, Hürriyet; 04.01. Department of Chemistry; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 04. Faculty of Science; 01. Izmir Institute of Technology
    This thesis aimed to develop Tariquidar and Doxorubicin-loaded liposomes decorated by Fucoidan coating for breast cancer treatment. Fucoidan is a negatively charged polysaccharide with a special affinity to p-selectins expressed on MDA-MB-231 breast cancer cells and, at the same time, possesses anti-cancer activity. Different liposomes were prepared by extrusion method from the DSPC, Cholesterol, and cationic lipid DSTAP mixtures for coating negatively charged Fucoidan. The most stable liposomes with a size of 200 nm were obtained at a molar ratio of DSPC/Cholesterol/DSTAP:55/30/15, exhibiting a zeta potential above +30 mV. Tariquidar was encapsulated into the liposome bilayer by passive loading, and Doxorubicin into the core of the liposome by active loading. In the final step, liposomes were coated with Fucoidan by electrostatic interaction. Tariquidar loading was determined by UV-Vis spectrophotometry, indicating an optimum TRQ/Lipid molar ratio of 0.012 with encapsulation and loading efficiencies of 50% and 20%, respectively. Fluorescence spectrophotometry determined Doxorubicin loading, showing insignificant encapsulation efficiency change (exhibiting around 70%) by neither Tariquidar content in the bilayer nor DSTAP% in the formulation. An optimum amount of Fucoidan was determined by incubating the liposomes with varying amounts of fucoidan at different dilutions. Size and zeta potential measurements monitored the coating of liposomes with Fucoidan. Our finding showed that zeta potentials of liposomes go from positive to negative with increasing fucoidan, while no trend was observed in the size of liposomes. However, smaller sizes were observed when incubation was performed in diluted solutions.
  • Master Thesis
    Enhancement of Bioavailability of Vitamin D by Nano-Sized Delivery Systems
    (01. Izmir Institute of Technology, 2023) Bulmuş Zareie, Volga; Kılıç Özdemir, Sevgi; Kılıç Özdemir, Sevgi; Bulmuş Zareie, Esma Volga; 03.01. Department of Bioengineering; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of Technology
    Studies have indicated that Vitamin D (VitD) may decrease tumor invasiveness and propensity to metastasize. Cholecalciferol (VitD3) is the passive form of VitD3 and converts to active calcitriol through two-step hydroxylation reactions in the body, promoting binding to VitD-receptors (VDR). However, some breast cancer cells, especially MDA-MB-231, have very low levels of VDR. Besides, VitD3 suffers from first pass-effect of the liver which causes deactivation of VitD3. Therefore, new approaches are needed to increase VitD3 level in the cancerous sites. In this study, VitD3 was loaded into liposomes, which were subsequently coated by Fucoidan (FUC) to promote their binding to MDA-MB-231 cancer cells. Fucoidan strongly binds to P-selectins overexpressed in the breast cancer cells, blocking the cancer cells to adhere on the platelets to carry within the body, causing metastasis. Doxorubicin (DOX), being considered as the one of the most effective chemotherapeutic agents against breast cancer, was also loaded into liposomes in a similar manner. By liposomal encapsulations and fucoidan coating, it was aimed to deliver the all-cargo directly to the cancerous site and enhance the bioavailability of both agents at the target site. It was seen that liposomal VitD3 was more effective than free form to inhibit cell proliferation and, therapeutic potential of DOX increased with VitD3.VitD3 loaded FUC coated liposomes at optimized concentrations has a comparable effect with DOX-loaded liposomes with and without FUC coating. Overall, these results suggested that VitD3 and DOX loaded and FUC coated liposomes can be applied as combined therapy in cancer treatment.
  • Master Thesis
    Role of Human Aprataxin Protein in P53-Related Cellular Processes in Breast Cells
    (01. Izmir Institute of Technology, 2021) Doğan, Hülya; Yalçın Özuysal, Özden; Yalçın Özuysal, Özden; Yalçın Özuysal, Özden; 01. Izmir Institute of Technology; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science
    Aprataxin encoded by APTX, which is the human homolog of yeast HNT3, reverses adenylation damages emerged from abortive DNA ligation during ribonucleotide and base excision repair. Thus, it corrects AMP-modified nucleic acid termini and protects genome integrity as a DNA ligase "proofreader". Role of HNT3, which is a candidate p53-related gene, against DNA oxidative and alkylating damage indicates its antioxidant importance. Besides, previous studies demonstrated that absence of Aprataxin gives rise to ROS generation and oxidative stress in addition to mitochondrial dysfunction. Also, role of Aprataxin in drug and radiotherapy sensitivity was shown in many cancer. Since conformation of cysteine residues in p53 DNA-binding domain can be modified by oxidizing environment, functionality can be influenced by defective APTX. Although p53-Aprataxin interaction has been shown by co-immunoprecipitation, effects of APTX on p53 pathway were not studied. Aim of this study is to investigate Aprataxin-driven changes in p53-regulated processes in p53 wild-type cells through. According to results, Aprataxin overexpression leads to cell cycle arrest in low stress levels. However, it triggers cell death against induced stress in MCF10A cells. Moreover, apoptotic assay on MCF10A APTX Crispr cells indicated elevated level of basal cell death. Also, expression analysis of p53 targets in APTX knockdown MCF7 cells revealed that extrinsic apoptosis pathway might be induced. Consequently, these results help us to gain insight into how Aprataxin affects activity of p53 pathway. Further investigation providing stress accumulation based assays and protein level analysis is needed to figure out whether resulting changes are p53-dependent or not.
  • Master Thesis
    Investigating the Effect of Human Sacm1l Gene in the P53 Wild Type Breast Epithelial Mcf10a and Breast Cancer Mcf7 Cells
    (01. Izmir Institute of Technology, 2021) Efe, Eda; Yalçın Özuysal, Özden; Yalçın Özuysal, Özden; Yalçın Özuysal, Özden; 01. Izmir Institute of Technology; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science
    p53, tumor suppressor protein, plays role in the regulation of many cellular processes. Thus, p53 activity is controlled by a series of mechanisms, one of which is a redox reaction. However, redox regulation of p53 is not well defined in the literature. As a candidate of antioxidant, Sac1 gene mutation resulted in decreased levels of human p53 protein in transformed yeast, but the human homolog of Sac1 (SACM1L) has not been studied yet. SACM1L is known to function as a phosphoinositide phosphatase, hydrolyzes PI4P in the Golgi and ER. Previous studies demonstrated SACM1L depletion in HeLa cells led to decreased viability and arrest at the G2/M phase. However, no data were found on the association between the SACM1L and either directly p53 or p53 mediated cellular processes. We aimed to investigate the role of SACM1L in p53 controlled cellular processes like cell cycle and apoptosis in p53 wild type (wt) breast epithelial cells MCF10A and breast cancer cells MCF7 in the presence or absence of SACM1L gene. We demonstrated that SACM1L knockout MCF7 cells were arrested in the G1 phase, and number of proliferating cells was reduced, whereas overexpression of SACM1L did not change the proliferation, and cell cycle. Further, the rate of apoptosis was increased in SACM1L overexpressing and knockout MCF10A and MCF7 cells, supported by the findings of transcriptional analysis for p53 target genes. In conclusion, the greatest effect of SACM1L was observed in the apoptosis, but the underlying mechanisms are still unclear and must be further studied.
  • 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 Technology
    Breast 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.
  • Master Thesis
    Time Dependent Expression and Localization of Connexin 32: Implication in Epithelial To Mesenchymal Transition of Mammary Epithelial Mcf10a and Triple Negative Breast Cancer Mda Mb 231 Cells
    (01. Izmir Institute of Technology, 2020) Ünal, Yağmur Ceren; Meşe Özçivici, Gülistan; Meşe Özçivici, Gülistan; 01. Izmir Institute of Technology; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science
    Breast cancer is the most frequent and the second leading cause of cancer-related deaths among women worldwide. Epithelial to mesenchymal transition (EMT) is critical driving force in metastasis. Connexins as a basic subunit of gap junctions indicate critical roles in regulation of EMT. In addition to Cx26 and Cx43, Cx32 is associated with breast cancer and elevated levels of Cx32 has been reported in lymph node metastasis compared to primary breast cancer while the role of Cx32 in breast cancer is still elusive. Here we aimed to shed light on the effect of Cx32 on breast cancer. Our study suggested that Cx32 acquired mesenchymal morphology and decreased proliferation in MCF10A cells but not in MDA MB 231 cells. To further elucidate whether Cx32 indicate these changes through EMT, EMT markers were examined and subsequently it was revealed that Cx32 expression was strongly correlated with increased E-cadherin and Vimentin in MCF10A cells while decreased E-cadherin and Snail in MDA MB 231 cells. Importantly majority of Cx32 did not localize to the plasma membrane and indicated dynamic changes in a day dependent manner in both MCF10A and MDA MB 231 cells. Moreover, day dependent expression and localization of Cx32 revealed strong correlation with Zeb2 expression in MCF10A cells. In conclusion, Cx32 indicated differential effects in regulation of EMT between MCF10A and MDA MB 231 cells. It was the first time that the role of Cx32 on EMT was investigated in breast cancer and differential localization of Cx32 was identified.