Master Degree / Yüksek Lisans Tezleri

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

Browse

Filters

2019 - 201912020 - 20223

Settings

COAR Access Rights: search.filters.coarAccessRights.embargoed accessSubject: search.filters.subject.Breast cancer

Search Results

Now showing 1 - 4 of 4
  • Master Thesis
    Investigation of the Interactions Between Cancer Cells and the Microenvironment at the Cellular Level
    (Izmir Institute of Technology, 2022) Yöndem, Eyüp; Pesen Okvur, Devrim; Pesen Okvur, Devrim
    Breast cancer is the most frequently diagnosed cancer type and the first leading cause of cancer-related deaths in women. Breast tumor mass is not only harboring cancer cells but also several types of stromal cells, including fibroblasts. While all of these stromal cells may have a calamitous effect on cancer progression, fibroblasts which make up nearly 80% of tumor mass present unique characteristics such as extensive extracellular matrix (ECM) production. In the context of tumors, the activated cells are referred to as cancer-associated fibroblasts (CAF), expressing several markers such as αSMA, FSP1, FAP, vimentin, and PDGFRβ. However, an in-depth understanding of the transdifferentiation of fibroblasts to CAFs is lacking. ECM components may change when cells become cancerous, which can alter cell behavior, facilitating proliferation, differentiation, and migration. Decellularized ECM(dECM) has recently been considered one of the tools to study in-vitro cell-ECM interaction. In this work, we utilized cancer cell-derived ECM(ccECM) to investigate its effect on the differentiation of the fibroblast to CAFs by compering decellularization methods called the extraction buffer and the freeze-thaw cycle. Our study suggested that ccECM from MDA-MB-231 impacted the fibroblasts' behavior from proliferation to differentiation via its ECM components, including fibronectin and laminin. The fibroblasts cultured on ccECM showed increased CAFs markers indicated above. Overall, ccECM could be one of the intermediate steps in fibroblast differentiation, but in the future, the factors present in ccECM should be scrutinized to understand the mechanisms behind this effect.
  • Master Thesis
    Role of Human Aprataxin Protein in P53-Related Cellular Processes in Breast Cells
    (01. Izmir Institute of Technology, 2021) Doğan, Hülya; Doğan, Hülya; Yalçın Özuysal, Özden; Yalçın Özuysal, Özden
    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; Efe, Eda; Yalçın Özuysal, Özden; Yalçın Özuysal, Özden
    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
    Lab-on-a-chip devices for drug screening
    (Izmir Institute of Technology, 2019) Gökçe, Begüm; Pesen Okvur, Devrim; Çağır, Ali
    Breast cancer is one of the cancers with the highest incidence and mortality rates in women in Turkey as well as in the world. Tumor micro environment comprises of cancer and normal cells, extracellular matrix, soluble biological and chemical factors. Research has shown that cell shape, adhesion, migration, response to growth factors and drugs are different in 2D and 3D culture. Today, only 8 out of 100 anti-cancer clinical trial gives effective results. 3D cell culture systems have shown to be a necessary step between in vitro, in vivo and clinical studies. Therefore, it is necessary to better understand the interactions of cancer cells with their micro environment, for which new cell culture setups are required. The most apparent disadvantage of widely used 3D cell culture setups is the lack of stromal cells. The systems to be developed should both provide a 3D environment and comprise multiple cell types. The drug screen in 3D tri-culture method with a lab-on-a-chip device, that will be developed in this study will be able to answer these needs. Cell lines that represent different breast cancer types alone or together with stromal cells were cultured in 3D in the to be developed lab-on-a-chip; by determining the effects of drugs with different targets on the viability and distribution of cells, a drug screening method is developed.