Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Investigation of Malignant Melanoma Cancer and Cancer Stem Cells Using Optical Spectroscopy Techniques(01. Izmir Institute of Technology, 2024) Uslu, Bensu Rüya; Güler, GünnurKanser kök hücreleri, kök hücre ve progenitör hücrelerdeki akümüle mutasyonlardan kaynaklanan kanser hücrelerinin düşük bir yüzdesini oluşturmalarına rağmen kanserin tekrarından, tedaviye direnç göstermesinden ve metastazından büyük ölçüde sorumludurlar. Malign melanom yaygın bir kanserdir, ve insidansı, mortatalitesi ve morbitesi alarm verici seviyede artmaktadır. Bu çalışmanın amacı kanser kök hücrelerinin malign melanom modeli üzerinde titreşimsel spektroskopi ile incelenmesidir. Titreşimsel spektroskopi moleküllere dair hem nitel hem nicel bilgi verir. Yani hücrelerin biyokimyasal içeriği ve moleküllerin miktarı titreşimsel spektroskopi ile belirlenebilir. Dahası, deney grupları arasındaki ilişkiler ve spektral verinin istatistiksel önemi kaydedilen spektrumlara çok-değişkenli Analiz yöntemleri uygulanarak değerlendirilebilir. Titreşimsel spektroskopi, infrared ve Raman spektroskopileri, hücresel ve diğer biyolojik çalışmalarda yaygın olarak kullanılmaktadır ve başarılı sonuçlar elde edilmektedir. Bu çalışmada, kanser kök hücreleri, kök hücre olmayan kanser hücreleri ve bulk hücre popülasyonu hücreleri infrared ve Raman spektroskopileri ile incelenmiştir ve elde edilen veriler hücre döngüsünün 11, 24, 48 ve 72. saatlerinde çok-değişkenli yöntemlerle analiz edilmiştir. Sonuç olarak, üç grup arasındaki biyokimyasal ve biyofiziksel farklar farklı saatler için belirlenmiş ve hücrelerin hüçre döngüsüne ilişkin bilgiler elde edilmiştir. Bu çalışma titreşimsel spektroskopinin hücre karakterizasyonunda kullanılabileceğini ve çok-değişkenli analizlerle birleştirildiğinde spektrumlardan elde edilen bilginin ciddi ölçüde geliştirilebileceğini desteklemektedir.Master Thesis Synthesis of 1,5-Disubstituted 1,2,3-Triazole Modified Azacoumarins(01. Izmir Institute of Technology, 2022) Çetin, Başak; Çağır, AliCancer is a deadly disease that threatens human health and all life, and it is still a serious problem despite all scientific studies for more than half a century. Pharmacophores are a part of the structure of a drug (or drug candidate) responsible from the biological activity. This thesis is related with the synthesis of novel compounds having two well-known pharmacophore structures, 1,2,3-triazole and 1-azacoumarin. Both structures can be found in the structure of many biologically active molecules. Triazole modified coumarin derivatives are scarce in the literature. In this study, we aimed to improve the synthetic route toward the synthesis of 1- azacoumarin derivative modified by 1,2,3-triazole group at position 4-. Synthesis starts with the conversion of methyl 4-chloroanthranilate to the corresponding 4-OH azacoumarin. Then it is transferred into the 4-OTf group by simply addition of Tf group to OH under basic condition. After Sonogashira reaction and removal of TMS group 4- alkynyl-1-azacoumarin was produced. At this point, conversion of alkyne into 1,5- disubstituted 1,2,3-triazole was examined in the presence of Cp2Ni-Xantphos and RuCl(COD)Cp* catalytic systems but all of trials were failed probably due to the presence of ester group close to the reaction site. In further studies, design of the molecule will be reperformed and ester group will be moved over phenyl rings in order to test its biological activity over cancer cell lines.Master Thesis Quantitative Phase Analysis in Lensless Digital Inline Holographic Microscopy(01. Izmir Institute of Technology, 2021) Demir, Ali Aslan; Tekin, Hüseyin Cumhur; Varlıklı, CananComputational imaging modalities replace the bulky, complex, and expensive optical components of traditional imaging procedures with numerical reconstruction steps. Digital holographic microscopy is one of the most prominent ones with the possibility of obtaining quantitative phase information by measuring the phase shift change caused by the refractive index of objects. In the lensless digital holographic microscopy system, a pinhole and a light-emitting diode are sufficient to create a holographic pattern on the camera sensor. Here, the optimization of a digital lensless inline holographic microscopy setup was performed to obtain optimal phase value. Also, to retrieve the lost phase information during the recording step, the numerical solution was performed with the single and multi-shot phase retrieval methods. Then, human breast adenocarcinoma (MDA-MB-231) and human myeloid leukemia (U937) cells were analyzed to obtain phase shift, perimeter, and circularity values. These parameters were used to obtain a quantitative differentiation model to replace the traditional labeling or visual confirmation steps with a direct analysis manner. The analysis of respective cells with the classification, object detection, and conditional generative adversarial models can be used directly with pre-trained weights to lessen the computational workloads. With this study, the quantitative analysis with lensless holographic microscopy setup was shown to be a label-free differentiation mechanism to separate cancer cells from monocytes cells which could be used for the early diagnosis of cancer. Also, the proposed method has the potential to be used to identify other cells with links to the diagnosis of different diseases.Master Thesis Studies Toward the Asymmetric Synthesis of Ester Functionalized Novel 1,4-Oxazepine Derivatives(01. Izmir Institute of Technology, 2021) Bozoğlu, Hülya; Çağır, AliThe MDM2/p53 is one of the most widely studied protein-protein interaction because of being a valuable target for the development of novel anticancer agents. MDM2 protein is the natural inhibitor of p53 protein which act as a tumor suppressor. When MDM2 is overexpressed, damaged DNA is allowed to replicate and therefore cancerous cells can be generated because p53 has lost of its activity. For this reason; maintaining the activity of wild-type p53 through inhibition of MDM2 can stop the proliferation of cancer cells. New drugs that inhibit this interaction are important for the treatment of cancer. The aim of the study is synthesize chiral 1,4-oxazepine-5-one derivatives. (R)-2-amino-2-(4-chlorophenyl)acetic acid was used as starting material for the synthesis. The first step was a trityl protection of amine with trityl chloride. Trityl protected amino acid was reduced to N-Trt amino alcohol with LiAlH4 then oxidized to aldehyde by using Dess-Martin periodinane. The resulting aldehyde was reacted with 3-chlorophenylmagnesium bromide. Up to this part of the synthesis, reactions were performed successfully. Then trityl group was removed by TFA and amino alcohol was obtained. Then addition of several α,β-unsaturated carbonyls to the deprotected amino alcohol was studied by coupling reagents such as HATU. Afterwards we performed some intramolecular cyclization attempts but all cyclization attempts were failed.Master Thesis In-Vitro Evaluation Cytotoxic Potential of Novel Isoindole Derivatives on Various Cancer Cell Lines(01. Izmir Institute of Technology, 2021) Yemeztaşlıca Yetişkin, Egehan; Gülşah Şanlı MohamedCancer, which is the disease of our age, arises because of a very complex set of mechanisms. Especially with the proliferation of cancer disease and the increase in cancer-related deaths, it has a great impact on the development of drug studies by improving existing treatments or researching new treatment methods. Cantharidine and its analogs are natural anhydrides with an inhibitory effect on protein phosphatases. However, they are not included in cancer therapies due to their toxicity. In recent studies, it has been found that derivatives of cantharidin as isoindole-1,3-dione and its derivatives have anticancer effects. The main purpose of this study to investigate the effects of four different drugs, which are newly synthesized isoindole derivatives for use in cancer treatment, on different cancer cells. The cytotoxic effects of drugs on A549 (human lung adenocarcinoma), HeLa (human cervical carcinoma), PC3 (human prostate carcinoma), MCF-7 (human breast carcinoma), and Caco-2 (human colorectal carcinoma) cell lines were investigated by the MTT assay method, and the optimum incubation time was determined, then IC50 values were calculated. Then, the IC50 concentrations of the drugs were applied at 48 hours, which is the optimum incubation period, and apoptotic stages and cell cycle stages were compared using flow cytometry to understand whether the drugs have a suppressive function in cancer development. Scratch assay was performed to investigate the migration effect of drugs on cells. The results showed that the drugs are suppressive to cancer cells and can be used for therapeutic purposes in the future.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, GülistanBreast 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.