Master Degree / Yüksek Lisans Tezleri

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

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Department: search.filters.department.Thesis (Master)--İzmir Institute of Technology, BioengineeringSubject: search.filters.subject.Breast cancer

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Now showing 1 - 9 of 9
  • Master Thesis
    Development of Doxorubicin-Loaded Liposomes Self-Assembled With Polysaccharides for Breast Cancer Therapy
    (01. Izmir Institute of Technology, 2023) Önol, Ayşenur Başar; Kılıç Özdemir, Sevgi; Polat, Hürriyet
    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) Sağlam, Ezgi İrem; Kılıç Özdemir, Sevgi; Bulmuş Zareie, Esma Volga
    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
    Increasing Doxorubicin (dox) Release From Liposomes
    (Izmir Institute of Technology, 2019) Hanoğlu, Berçem Dilan; Özdemir, Ekrem; Altun, Zekiye Sultan
    Cancer is the second most common cause of death in the world and its incidence is increasing day by day. Doxorubicin (DOX) is an anthracycline group drug frequently used in many cancer treatments including breast cancer. However, free DOX has many harmful side effects and need to be encapsulated into nanocarrier such as liposomes. Although liposomal DOX has many advantages over its free form, liposomal DOX has undesirable side effects such as hand and foot syndrome. In this thesis, it was aimed to develop a more effective liposomal DOX delivery and release systems. Liposomes were prepared with alkaline solutions containing tris, sodium carbonate, ammonium chloride, and ammonium sulfate. DOX loading into liposomes and the percentage of release from liposomes were examined. A loading efficiency of about 80% was achieved, while the release was found to be below 13% at room temperature. The release of DOX was found to be enhanced from liposomes in the presence of ammonia (NH3), whose content was dependent on pH. Temperature was also found an important parameter and enhances DOX release at higher temperatures than the phase transition temperature of the lipid. A two-component liposomal system was proposed where ammonia (NH3) would be released from one liposome and enhance the DOX release from other liposomes. It was found that temperature, pH, and ammonia (NH3) concentration affected DOX release from liposomes. As a result, DOX was successfully loaded into liposomes and ready to study their effect on breast cancer cells.
  • Master Thesis
    Cellular Mechanosensing at a Distance
    (Izmir Institute of Technology, 2019) Can, Ali; Pesen Okvur, Devrim; Özçivici, Engin
    The goal of the project is to determine differences in mechanical sensing at a distance between breast cancer cells and normal mammary epithelial cells. To achieve this goal, we aim to: 1. Optimize the device for mechanical sensing at a distance 2. Determine the effect of mechanical sensing at a distance on cell proliferation 3. Determine the effect of mechanical sensing at a distance on cell migration 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 microenvironment comprises of cancer and normal cells, extracellular matrix, soluble biological and chemical factors. Biochemical aspects of the interactions of cancer cells with the constituents of the microenvironment are widely studied whereas biophysical studies are at limited numbers. There is increasing evidence that extracellular matrix can change the mechanics and function of cancer and stroma cells. It has been observed that cancer cells show different responses to soft and stiff tissues they are in direct contact with than normal cells. However, it is not known whether the distance at which cancer cells can feel the stiffness of a distant tissue is longer, the same or shorter than that of normal cells. The hypothesis we will test in this project is as follows: The distance at which cancer cells can feel the stiffness of a distant tissue is shorter than that of normal cells.
  • Master Thesis
    Evaluation of Biophysical Aspedts of Cancer Using Lab-On Chip Devices
    (Izmir Institute of Technology, 2019) Tahmaz, İsmail; Pesen Okvur, Devrim; Sürmeli, Nur Başak
    Breast cancer metastasis is really crucial point from cancer related deaths. As cancer cells from primary tumor are travelling through blood, they hang on to blood vessel and finally they exit from blood vessel into secondary site where is extracellular matrix and/or tissue/organ. This process commonly known as extravasation. Cancer cells sometimes can be highly aggressive when it exposed to hypoxia referred low oxygen amount by activating HIF1α. This transcription factor is activated in malignant cells, normal cells and endothelial cells in blood vessel when oxygen amount decreased to certain levels and it induce several genes expression such as VEGF, LOX, Angiopoietin-like-4 etc. In this study we investigated effect of HIF1α which is hypoxia indicator on breast cancer extravasation by comparing to normal oxygen level. This study represents both anemic hypoxia physiologically and lead to understand underlying mechanism of extravasation into extracellular matrix related to low oxygen circulating through blood. In addition to HIF1α effects, dynamic perfusion mimicking blood flow was applied to determine effects on extravasation. For this purpose, lab-on-a chip device was utilized for real time visualization. In conclusion, although hypoxia is giving permission MDAMB231 to extravasate because of reshaping of vascular geometry, less extravasated cancer cells observed in matrix during hypoxia under both static and flow condition when compared to normoxic and static conditions. Moreover, it was shown that flow triggers extravasation distance in normoxia against static condition and normal breast epithelial cells extravasated away in hypoxia comparing breast cancer cells by means of flow.
  • Master Thesis
    Mimicking the Tumor Microenvironment in Lab-On Devices
    (Izmir Institute of Technology, 2019) Bilgen, Müge; Pesen Okvur, Devrim; Sürmeli, Nur Başak
    Breast cancer is one of the cancers with the highest incidence and mortality rates in women in the world. The leading cause of death for cancer patients is tumor metastasis. Cancer cells can extravasate the blood vessel, go through the distant organs and form the metastasis. Tumor microenvironment comprises of cancer and normal cells, extracellular matrix, soluble biological and chemical factors. Biochemical aspects of the interactions of cancer cells with the constituents of the microenvironment are widely studied whereas biophysical studies are at limited numbers. There is increasing evidence that extracellular matrix can change the mechanics and function of cancer and stroma cells. It has been observed that cancer cells show different responses to soft and stiff tissues they are in direct contact with than normal cells. New cell culture setups should be developed to better understand the interactions of cancer cells with their microenvironment. To develop a three dimensional (3D) in vitro model will allow the study of stiffness which is one of the mechanical features of extracellular matrix features first, 3D (dimensional) Controlled in vitro Microenvironments (CivMs) that mimic a blood vessel and its neighboring tissue in vivo will be fabricated using UV lithography. Monolayer which was formed by endothelial cells play a role in pathophysiological processes, so it shows a barrier role between both blood and tissues. To form a blood vessel bEnd.3 cell line was used. Collagen which is the most abundant protein in connective tissues were used to mimic extracellular matrix. pH value of collagen was changed and represented two different stiffness value. Here, the in vitro model we define as controlled in vitro microenvironments (CivM) is a lab-on-a-chip (LOC) application. In this microenvironment; MDA-MB-231 cells which are known to be invasive and MCF10A which is normal mammary epithelial cells were used as control. LOC devices were used to investigate cancer cell extravasation which is the prominent step of metastasis and extracellular matrix relation.
  • 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.
  • Master Thesis
    Interactions of Cancer Cells and Macrophages on the Egf-Egfr Axis: Chemotaxis, Haptotaxis or Direct Contact?
    (Izmir Institute of Technology, 2017) Önal, Sevgi; Pesen Okvur, Devrim; Bulmuş Zareie, Esma Volga
    Breast cancer cells (BCC) and macrophages are known to interact via epidermal growth factor (EGF) produced by macrophages and colony stimulating factor-1 (CSF-1) produced by BCC. Despite contradictory findings, this interaction is perceived as a paracrine loop. Yet, the underlying mechanism of interaction remains unclear. Here, we investigated interactions of BCC with macrophages in 2D and 3D. BCC did not show chemotaxis to macrophages in custom designed 3D cell-on-a-chip devices, which was in agreement with ELISA results showing that macrophage-derived-EGF was not secreted into macrophage-conditioned-medium. Live cell imaging of BCC in the presence and absence of iressa showed that macrophages but not macrophage-derivedmatrix modulated adhesion and motility of BCC in 2D. 3D co-culture experiments in matrigel and collagen showed that BCC changed their multicellular organization in the presence of macrophages. In custom designed 3D co-culture cell-on-a-chip devices, macrophages reduced and promoted migration of BCC in matrigel and collagen, respectively. Furthermore, adherent but not suspended BCC endocytosed EGFR when in contact with macrophages. Collectively, our data revealed that macrophages showed chemotaxis towards BCC-derived-CSF-1 whereas BCC required direct contact to interact with macrophage-derived-EGF. We propose that the interaction between cancer cells and macrophages is a paracrine-juxtacrine loop of CSF-1 and EGF, respectively.
  • Master Thesis
    Comparison Od Side Effects of Anti-Cancer Drugs in 2d and 3d And, Classical and Cell-On Cultures
    (Izmir Institute of Technology, 2016) Kankale, Deniz; Pesen Okvur, Devrim; Çağır, Ali
    The studies that aim to assess the effects of drugs developed against cancer at the cellular level use multiwell plates. However, these classical systems fail to reproduce the in-vivo like microenvironment necessary for realistic assessment. In addition, classical cell culture systems use high amount of materials increasing cost. On the other hand, lab-on-a-chip systems use minimal volumes of reagents and more importantly can mimic the in-vivo microenvironment via spatial and temporal control. Furthermore, it is known that cell response to drugs can be very different in 2D and 3D cell culture setups. Doxorubicin is a widely used anticancer drug. Here, doxorubicin uptake by highly metastatic human breast cancer cell line MDA-MB-231 and normal mammary epithelial cell line MCF10A were investigated using 2D and 3D, classical and cell-on-a-chip cultures. Drug uptake at 24, 48 and 72 hours various concentrations of the drug determined by measuring signal intensities from fluorescence microscopy images of cells. For cell viability assay, cells were stained with dapi and two cell lines were compared in systems. According to results, it was observed that 3D cell culture environment in chip provides more in-vivo like environment with less reagent consumption and cell viability is not correlated only with drug uptake.