Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 106 for “"Preclinical models"”.
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The Use of Preclinical Models to Improve the Treatment of Retinoblastoma
<p>Rodent models play an essential role in the development of new chemotherapeutics and dosing regimes. It is often difficult to carryout a clinical study for pediatric cancers due to the small patient population. Retinoblastoma, a pediatric cancer of the eye, is one example of a pediatric cancer …
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Dynamic Contrast-Enhanced MR Microscopy: Functional Imaging in Preclinical Models of Cancer
… to implement in small-animal imaging. Existing preclinical DCE-MRI protocols acquire a limited number of slices resulting in potentially lost information in the third dimension. Furthermore, drug efficacy studies measuring the effect of an anti-angiogenic treatment, often compare the derived …
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Preclinical Models to Identify Molecular Drivers of Metastasis in Paediatric Musculoskeletal Cancer
… the 5-year survival rates to only 60-75%. Murine models are invaluable tools to study and improve the understanding of disease progression and pathogenesis. Several MS cancer cell lines have been characterised in vitro and in vivo, but a clinically relevant mouse model of musculoskeletal tumors …
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Membrane Stabilizing Copolymer Poloxamer 188 in Preclinical Models of Acute Myocardial Infarction Reperfusion
… to prevent membrane damage in several disease models including sickle cell anemia, muscular dystrophy, cardiac arrest and acute myocardial infarction. The predominant theme of this dissertation revolves around understanding the events that occur at reperfusion after acute myocardial infarction …
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Targeting anti-androgen resistance in prostate cancer using preclinical models with physiological nutrient levels
… with a novel combination therapy, 2D cancer models do not represent the complexity of 3D tumours. Future directions include testing this combination therapy with a physiological explant model utilising prostate cancer patient samples and murine xenografts derived from prostate cancer cell …
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Investigating the role of sestrin 1 and sestrin 2 in preclinical models of tuberculosis disease
… metabolic modulatory roles in various disease models including cardiomyopathy, mitochondrial dysfunction, insulin resistance, and neurodegenerative diseases. However, the potential role of these genes remains unknown in TB, and conducting infection studies would contribute novel information to …
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SMN DEFICIENCY INDUCES NEUROACTIVE AMINOACIDS DYSMETABOLISM: BRIDGING INSIGHTS FROM PRECLINICAL MODELS TO CLINICAL EVIDENCE IN SMA PATIENTS
… systems, integrating data from SMA mouse models, Drosophila, and patient biofluids. First, we show that excitatory amino acids, including L-glutamate, L-glutamine, D-serine, and D-aspartate, are dysregulated in the CNS and cerebrospinal fluid (CSF) of SMA, compromising glutamatergic …
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Studies of the efficacy of Ribonucleotide Reductase inhibition in preclinical models of Acute Myeloid Leukemia in combination with standard and novel therapeutics
Acute Myeloid Leukemia (AML) is an aggressive disease of the marrow with approximately 18,800 new cases each year. The elderly population represents the bulk of AML patients with a median age of onset of 70. More than 70% of AML patients are over the age of 60, and for this group the 5 year overall …
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BMI1 is a context-dependent tumor suppressor that is a barrier to dedifferentiation in non-small cell lung adenocarcinoma
Predictive value is expected when preclinical models of disease are used for research. However, not all models appropriately mimic the disease progression or the treatment paradigm in the clinic. This thesis addresses an epigenetic regulator, Bmi1, which acts in stem cells to maintain their …
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Development and characterization of immunogenic genetically engineered mouse models of pancreatic cancer
… of immune escape, we have characterized two preclinical models of immunogenic pancreatic ductal adenocarcinoma (PDAC). In order to dissect the endogenous antigen-specific T cell response in PDAC, lentivirus encoding the Cre recombinase and a tumor specific antigen (SIINFEKL, OVA[subscript …
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Identifying Image Derived Features of Radiation Therapy Response: Tumor and Normal Tissue
… of radiation-induced normal tissue injury. Using preclinical models, quantitative image features will be mined from MR and PET scans in radioresponsive and radioresistant tumors to establish universal and tumor-specific imaging markers of treatment response. Furthermore we will establish imaging …
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Autologous Proliferative and Immunobiological Modelling of Patient-Derived Clear Cell Renal Cell Carcinoma and Kidney Organoids
… to predict. This underscores the need for robust preclinical models of ccRCC-immunotherapy. Current models fail to recapitulate patient-specific tumour–immune interactions. To address this and enable testing the growing number of possible treatment combinations, I aimed to establish autologous …
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A TISSUE ENGINEERING APPROACH TO THE DEVELOPMENT OF AN IN VITRO 3D TUMOR MODEL FOR DRUG DELIVERY STUDIES
The lack of good preclinical models has hampered anticancer drug discovery. Standard preclinical protocols require the growth of cells in high throughput two-dimensional culture systems. Such in vitro drug testing methods yield drug efficacy results that differ greatly from animal models. It is …
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Utilizing the Immunomodulatory Effects of Electroporation for Treating Brain Tumors
… have demonstrated promising results, treating preclinical models of GBMs. It has been shown that low and high frequency irreversible electroporation treatments shift the immunosuppressive tumor microenvironment and reversibly open large areas of blood brain barrier (BBB). In this dissertation, …
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Leveraging Antibodies for Positron Emission Tomography and Near-Infrared Fluorescence Imaging of Cancer
… and use of antibody-based imaging agents in preclinical models of cancer. This work can be described as two-fold. In the first part, we investigated how the use of a glycans-specific bioconjugation strategy affects Fc gamma RI binding and why it results in improved <em>in vivo …
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Exploring Neural Activities in the Prefrontal Cortex of Fragile X Syndrome Mouse Models Using Electroencephalography
… to which these signatures are conserved in preclinical models—especially in female mice—remains unclear. This thesis aimed to characterize oscillatory alterations in female Fmr1 knockout (KO) mice on a C57BL/6J background and to evaluate whether EEG-derived metrics align with human findings. …
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Development of translational models for intervertebral disc degeneration using a comparative approach for canine and human patients
… dogs can serve as highly relevant and ethical preclinical models for both human and canine IVDD. Chondrodystrophic (CD) and non-chondrodystrophic (NCD) breeds of dogs show different phenotypes of IVDD, each of which mimic phenotypes described for human patients. The main goal for this PhD …
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Modelling pancreatic cancer in vivo with patient derived organoids & humanised mouse models for the investigation of immunotherapeutic treatment response
… at least in part, to the lack of representative preclinical models. Current preclinical models are heavily reliant on murine immune compartments or reconstitution with an allogeneic human immune system (HIS), and thus do not represent the immunophenotypic variations between patients. In this …
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