Master Degree / Yüksek Lisans Tezleri

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

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Now showing 1 - 6 of 6
  • Master Thesis
    Investigation of Anticancer Properties of Novel Mdm2 Inhibitors
    (Izmir Institute of Technology, 2021) Özdemir, Sefayi Merve; Çağır, Ali
    Cancer is one major disease causing death worldwide. Current cancer treatments are not %100 effective to cure for patients, yet. Thereby, the synthesis and discovery of new therapeutics have been important to improve the survival period of the cancer patients. There are many strategies for synthesis of cancer therapeutics. One of the most important strategy for cancer treatment is the reactivation of p53. MDM2 is a negative regulator of p53 in cell, because it causes the inactivation of p53. In this thesis, the anticancer and MDM2 inhibitory properties of ezetimibe, desfluoro ezetimibe and intermediates during ezetimibe synthesis (named as SM2-9) and a side product from the synthesis of benidipine (named as SM1) on prostate cancer (LnCAP, wild-type p53), breast cancer (MCF7, wild type p53) and uterus cancer (HeLa, wild type nonfunctional p53) cells were investigated. For this purpose, the cytotoxic, cytostatic and apoptotic properties of these compounds were determined. Compounds SM2, SM3, SM4 and SM6 demonstrated cytotoxic effects, whereas compounds SM5, SM8 and SM9 had cytostatic effects on three cells. Compound SM7 had no effect on these cells, up to 100 μM concentration. Compounds SM1 had cytostatic effect on MCF7 cells, but it showed no activity on other cells. Compounds SM8 and SM9 had strong cytostatic activity. Thus, the apoptotic properties of these compounds were examined by caspases 3/7 activation and Annexin-V FITC assays. Besides, MDM2 inhibitor profiles of these compounds were investigated by fluorescence polarization assay. This study provides novel and potential molecules for drug discovery in cancer treatment
  • Master Thesis
    Investigation of Cytotoxic Properties of New Isoindol Derivatives in Lung and Cervical Cancers
    (Izmir Institute of Technology, 2019) Almusawi, Yasir; Şanlı Mohamed, Gülşah
    Cancer is one of the most common diseases in the world. Recently, there are many methods developed by researchers to treat this disease. One of these treatments is targeted for chemotherapy. It is preferred by researchers because it is less toxic and has fewer side effects than other cancer treatments. This study emphasizes the anticancer properties of the newly synthesized Isoindole derivatives. Thus, it was hoped to be a significant improvement based on new generation anticancer compounds with high efficacy and fewer side effects. The main objective of this study was to investigate the biological activity of seven newly synthesized Isoindole derivatives. The anticancer activity of these compounds was evaluated against HeLa (cervical carcinoma) and A549 (lung adenocarcinoma) cancer cell lines. This study is divided into three parts. Firstly, the cytotoxic activity of these compounds was determined by measuring the cell viability of each compound on HeLa and A549 cell lines. The main objective of this analysis is to measure the IC50 value of each compound and determine which compound is best to kill at least half of the cells. Secondly, the effects of programmed cell death and cell cycle were investigated for compounds with the best IC50 for each cell line by using Annexin V-FITC in flow cytometry. Finally, a scratch assay was performed to investigate the effect of these new Isoindole derivatives on cell migration.
  • Master Thesis
    Determination of Therapeutic Potential of Luteolin for Acute Lymphoblastic Leukemia Cells
    (Izmir Institute of Technology, 2019) Gürler, Sevim Beyza; Baran, Yusuf
    Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by increased level of immature lymphoblasts in bone marrow and peripheral blood. The developments of lymphoblasts are genetically/epigenetically inhibited. One of the most common genetic abnormalities in ALL is BCR/ABL translocation which regulates the several pathways related to proliferation, anti-apoptotic and drug resistance through its aberrant tyrosine kinase activity. Although the current treatment strategies include targeting BCR/ABL via tyrosine kinase inhibitors; complete remission, overall survival and mortality of Ph+ ALL patients are still worse as compared to Ph- ALL patients. Therefore, new strategies combined with current treatments are needed for Ph+ ALL patients who are qualified as high risk group of ALL. Different studies showed thatluteolin has anti-cancer and anti-tumor effects on wide range cancer types including breast, colon, lung cancer except ALL in both in vitro and in vivo. In this study, the dose and time dependent cytotoxic, apoptotic and cytostatic effects of luteolin on Philadelphia chromosome +ALL cells were determined for the first time. Besides, the effect of luteolin on cell growth and proliferation of two different healthy cell lines was shown. Moreover, the effect of luteolin on bioactive sphingolipids genes which regulate the several pathways including cell proliferation, apoptosis, drug resistance and senescence in cell was determined in Ph positive ALL cells for the first time. As a consequence, luteolin has cytotoxic, apoptotic and cytostatic effects on Ph positive ALL cells and bioactive sphingolipids genes are regulated in this therapeutic potential by luteolin.
  • Master Thesis
    Synergistic Apoptotic Effects of Bortezomib and Methylstat Inhibitor on Different Multiple Myeloma Cell Lines
    (Izmir Institute of Technology, 2015) Kacı, Fatma Necmiye; Baran, Yusuf; Saydam, Güray
    Multiple myeloma is one of the common hematological malignancies that affects plasma cells. Bortezomib, proteasome inhibitor, is an anticancer agent used for the treatment of multiple myeloma while methylstat is a demethylase inhibitor having anticancer potential. In this study, we investigated antiproliferative and apoptotic effects of methylstat alone or in combination with bortezomib. We also examined the genes involved in methylstat induced apoptosis. Cytotoxic effects of bortezomib and methylstat on U266 and ARH77 cells were demonstrated by MTT cell proliferation assay. To understand the apoptotic effects of these agents, loss of mitochondrial membrane potential was investigated by JC-1 method while phosphatidylserine localization was investigated by Annexin V assay. Cell cycle analysis in response to Bortezomib and Methylstat alone or in their combination were measured by flow cytometry. Changes in expression profiles of 84 genes underlying apoptosis, cell cycle control, DNA damage repair, and invasion and metastasis in response to Methylstat were determined by PCR Array. Our results demonstrated that both bortezomib and methylstat have antiproliferative and aoptotic effects in a time and dose dependent manner. Combination of bortezomib and methylstat induced apoptosis significantly as compared to any agent alone. In conclusion, we suggest methylstat as candidate agent for the treatment of MM after in vivo analyses.
  • Master Thesis
    Investigation of Stilbene-Fused Chalcone and Flavanone Derivatives for Their Cytotoxic and Anti-Cancer Properties
    (Izmir Institute of Technology, 2012) Odacı, Burcu; Çağır, Ali
    Stilbene, chalcone and flavanones are three major classes of molecules, which can be found in plants as secondary metabolites. Derivatives of those may possess variety of biological activities. In this study it is aimed to synthesize a hybrid molecule which may show the biological activities of both flavanone and stilbene, or chalcone and stilbene simultaneously. For this purpose previously synthesized 11 simple chalcone, flavanone and stilbene derivatives and 31 stilbene-fused chalcones and stilbene-fused flavanones were tested for their cytotoxic activities in prostate cancer cell line (PC-3) and breast cancer cell line (MCF-7) by using MTT assay. Then aromatase inhibition properties of simple chalcones, flavanones, stilbenes, stilbene-fused chalcones and stilbene-fused flavanones were studied. Results of the study were evaluated in potential of the hybrid system to carry out more than one biological activity and mimicking performance of the simple ones. Results indicate that tested simple chalcone and flavanone derivatives are more cytotoxic than simple stilbenes in both cancer cell lines. On the contrary, simple stilbene structures were much more successful in aromatase inhibition assays. Cytotoxic activity profiles of stilbene-fused chalcones in cancer cells show that those molecules mostly mimic the simple chalcone structures. On the other hand, flavanones lost their cytotoxic activities when they were fused with stilbenes. In addition, aromatase inhibition assay showed that stilbene-fused chalcones again do mimic the simple chalcones but not simple stilbenes. In the same assays, stilbene-fused flavanones may mimic both simple flavanones and simple stilbenes by depending on the type and position of the substituent in terminal aromatic rings.
  • Master Thesis
    Deciphering 5-Fluorouracil Mediated Molecular Mechanisms Required for Cell Death
    (Izmir Institute of Technology, 2011) Can, Geylani; Baran, Yusuf
    The chemotherapy agent 5-Fluorouracil (5-FU) is an antimetabolite that has been in use to treat several cancers for decades. In cells, it is converted into three distinct fluoro-based nucleotide analogues which interfere with DNA-synthesis and repair leading to impairment of the genome and, eventually apoptotic cell death. Current knowledge also state that 5-FU induced damage is signaling through a p53-dependent induction of death inducing complex (DISC) formation and further caspase-8 activation in certain cell types and members of the TNF-receptor family has been proposes to be required for the process. Here, we introduce calcium (Ca2+) as a messenger for p53 activation in the cellular response triggered by 5-FU. Using a combination of pharmacological and genetic approaches, we show that treatment of cultured colon carcinoma cells stimulates entry of extracellular Ca2+ through L-type plasma membrane channels and that this event direct posttranslational phosphorylation of at least two specific p53 serine residues (ser15 and ser33) by means of Calmodulin (CaM) activity. Obstructing this pathway by the Ca2+-chelator BAPTA or by two different inhibitors of CaM efficiently blocks 5-FU-induced cell death. The fact that a widely used therapeutic drug, such as 5-FU, is signaling by these means could provide new therapeutic intervention points, or specify new combinatorial treatment regimes.