Phd Degree / Doktora

Permanent URI for this collectionhttps://hdl.handle.net/11147/2869

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

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Now showing 1 - 4 of 4
  • Doctoral Thesis
    Multi-organ-on-a-chip for cancer drug testing
    (Izmir Institute of Technology, 2022) Mohammed, Abdurehman Eshete; Pesen Okvur, Devrim; Erdal Bağrıyanık, Şerife Esra
    Cancer is one of the devastating and fatal severe diseases worldwide that kills millions of people every year. Globally cancer is the second leading cause of death after cardiovascular disease and was responsible for 10 million deaths in 2020. Breast cancer is one of the predominant cancers in females and is the cause of more than half a million females death each year. The primary cause of cancer patients' death is cancer metastasis. Triple-negative BREAST cancer (TNBC) is mainly treated by chemotherapy. In the current drug discovery and development processes, the efficacy and toxicity of chemotherapies identify using 2D and animal testing but not simulating the in vivo microenvironment. This research designed multiorgan-on-a-chip with liver and breast cell line compartments, and drug PKPD modeling was done by Monolix software. In this research, a unique multiorgan-on-a-chip (MOC) was designed and fabricated, generated experimental PK and PD data using the new MOC device, and modeled and simulated PK and PD using the experimental data. To conclude, we developed a new multiorgan-on-a-chip (MOC) platform used for PKPD modeling and PKPD simulations that would be helpful in the preclinical research to evaluate the effectiveness and toxicity of drugs. In the future, using calceinAM, a fluorescent cell viability dye, generating PD data for each cell type and determining side effects of doxorubicin in each cell line is essential. Adding more organs to the MOC, such as heart tissue, to study the cytotoxicity of doxorubicin in different organs gives more efficient data for PKPD modeling.
  • Doctoral Thesis
    Engineering Target Tissue in Lab-On Devices for Predicting Homing Choices of Metastatic Cancer
    (Izmir Institute of Technology, 2020) Batı Ayaz, Gizem; Pesen Okvur, Devrim; Yavuz, Oktay
    The metastatic cascade of cancer results in the extravasation of the tumor to other parts of the body. Metastasis is the leading cause of cancer related deaths. Breast cancer is the most common cancer in women, and lung is one of the organs with the most metastasis. For this reason, it is critical to engineer a tissue microenvironment that includes complex cell-cell interactions with co-culture of endothelial, epithelial and stromal cells, and the invasion and extravasation steps of metastasis can be observed for early diagnosis of metastasis. Vascularization is the critical step for engineering the tissues. The in vitro models used today are insufficient to create the tissue environment closest to in vivo conditions. Recently developed lab-on-a-chip platforms provide suitable environments for mimicking the in vivo structure in tissue engineering studies. In this research: -Different lab-on-a-chip devices fabricated to engineer breast and lung target tissues. -For the first time, epithelial, fibroblast and endothelial cells were tri-cultured and breast and lung tissue environments were engineering with microvasculature. -Different gel, media and cell numbers have been optimized for engineering of breast and lung tissue environments with microvascularization. -Different matrix environments have been optimized to observe invasion and/or extravasation steps separately or together.
  • Doctoral Thesis
    Investigating the Role of Connexin 32 in Breast Cancer
    (Izmir Institute of Technology, 2020) Uğur, Deniz; Meşe Özçivici, Gülistan
    Connexins (Cx) are primary components of gap junctions, selectively allowing molecules to be exchanged between adjacent cells. Along with their channel forming functions, connexins play variety of roles in different stages in tumorigenesis, both dependent and independent of gap junctions in connexin and cancer dependent manner. Cytoplasmic accumulation of Cx32 was shown in some breast cancers; and compared to the primary tumors Cx32 is further upregulated in metastasis. However, the complete picture for the role of Cx32 in breast cancer remains to be elusive. Through overexpressing Cx32, its functions in breast cancer cells were investigated in Hs578T and MCF7 breast cancer cells. Cx32 overexpression increased cellular proliferation with significant increase in S phase in Hs578T cells with no significant change on MCF7 cells. Cx32 overexpression did not induce hemichannel activity in neither cell; it reduced gap junctional functions in Hs578T cells. Cx32 in both cells localized in cytoplasm did not form intercellular plaques, and decreased Cx43 expression. Cx32 overexpression reduced the migration and invasion capacity in both cells and in Hs578T cells showed reduction of mesenchymal and increase of epithelial marker expressions. In conclusion, Cx32 increases proliferation and decreases communication in Hs578T cells while not affecting MCF7 cells. It decreases aggressiveness and metastatic potential for both cell lines. Due to changes in gap junctional functions, Cx32 might be acting in relation to GJIC in Hs578T cells and outside of it in MCF7 cells. All in all, presence of Cx32 made Hs578T cells act similar to endogenously Cx32 expressing MCF7 cells.
  • Doctoral Thesis
    Invetigation of Mechanical Vibration Effects on Breast Cancer Cells
    (Izmir Institute of Technology, 2018) Olçum Uzan, Melis; Özçivici, Engin; Erdal Bağrıyanık, Şerife Esra
    In this doctoral dissertation, low magnitude mechanical signals (LMMS, <1g in magnitude) were used to test the stress shielding model hypothesized on breast cancer cells. The hypothesis was that the breast cancer cells will be sensitive to mechanical vibrations and will respond to these vibrations. It was similarly used to test the adipogenic differentiation of Lamin A/C knockdown (by siRNA) bone marrow-derived mesenchymal stem cells. It is known that Lamin A/C plays a role in the nucleus and intracellular organization in these cells and affects gene expression by chromatin regulation. The hypothesis was that if these cells are deprived of the organization for the nucleus, they will be sensitive to mechanical vibrations, but that the mechanical vibrations cannot restore the effect of lamin A/C on gene regulation. We investigated the effects of high-frequency low-density mechanical signals (LMMS) on cell proliferation, apoptosis, cell cycle, protein expression, differentiation, cytoskeleton and phenotypic change processes. According to findings, LMMS caused cell cycle arrest in the aggressive type of breast cancer cells and slowed proliferation. Non-aggressive breast cancer has not responded to LMMS. In mammary epithelial cells, LMMS has not shown an effect that triggers proliferation. In the mesenchymal stem cell model, Lamin A/C knockdown accelerated adipogenic differentiation. Although LMMS in these cells decreased the rate of adipogenic differentiation, it was not sufficient to restore the baseline.