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 36 for “"pre-clinical models"”.
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Tissue-Engineered Annulus Fibrosus Repair and Nucleus Pulposus Augmentation in Pre-Clinical Models of Intervertebral Disc Degeneration
… goal to treat patients with IVD herniations and prevent further degeneration. To bring tissue-engineered repair strategies to the clinic, it is imperative to understand what has already been investigated, what biomaterials and strategies are successful, and what challenges remain (Chapter 1). …
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Targeted therapies in mantle cell lymphoma
… cell lymphoma (MCL) is characterized by the presence of the t(11 ;14)(g13 ;g32) translocation which results in cyclin Dl over-expression. MCL is one of the most difficult lymphoproliferative disorders to manage with a median survival rate of 43 months from diagnosis. The poor prognosis …
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HISTONE LYSINE METHYLTRANSFERASE NSD3 GOVERNS TRANSCRIPTIONAL PROGRAMS THAT DRIVE PANCREATIC NEUROENDOCRINE TUMORS (PANNETS)
… Thus, there is a critical need to uncover novel precision therapeutics for PanNET patients. Additionally, pre-clinical models that more accurately represent disease are an urgent necessity for translational studies.</p> <p>This dissertation directly addresses these challenges by identifying …
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Identifying Molecular Targets and Validating Novel Therapies For Ovarian Cancer
… options for cancer patients, however accurately predicting what re-purposed targeted therapy will be effective remains challenging. To address this need, we developed a Therapy Predicting Tool (TPT) that accurately predicts the beneficial therapeutic effect of clinically relevant targeted …
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Impact of Tumor Cell Expressed CD38 on Metastasis and Immune Evasion in Breast Cancer
… murine tumors are enriched in CD38, an immunesuppressive molecule associated with worse clinical outcomes in liquid malignancies but relatively understudied in solid tumors such as breast cancers. Hence, we sought to investigate the role of CD38 in hybrid EM-driven metastasis using pre-clinical …
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Yap1 Expression Predicts Sensitivity to Dual Akt/P70S6K Inhibition In Ovarian and Uterine Malignancies
… Design: </strong>Orthotopic murine models of ovarian and uterine cancer were utilized to study the effect of MSC2363318A on survival and regression. Moreover, <em>in vitro</em> experiments (MTT, Western blot analysis, plasmid transfection, and reverse phase protein array [RPPA]) were …
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Validation of AXL as a Therapeutic Target in Pancreatic Cancer
… that is associated with persistent immune suppression. AXL, a member of the TAM (TYRO3, AXL, MERTK) receptor tyrosine kinase family, has been identified as a critical factor that drives metastasis and immune suppression in many cancer types. Here we demonstrate that AXL-deficient PDA bearing …
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Treatment During Abstinence from Methamphetamine in a Rat Model of Methamphetamine Use Disorder
… as well as having anti-inflammatory action. In pre-clinical models, phosphodiesterase inhibitors can reduce behaviors associated with the self-administration of drugs of abuse if given directly before tests of relapse-like behavior. However, they have not been examined in the more clinically …
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Characterization of the Dunkin Hartley guinea pig as a non-transgenic and multimorbid model of brain aging
… to identify any effective cures, treatments, or preventative strategies. Historically, AD/ADRD research is conducted using genetically engineered pre-clinical models, that express a specific brain aging pathology. Recent discoveries, however, have identified a dynamic whole-body "inflammaging" …
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Characterisation of genetic and epigenetic aberrations in paediatric high grade glioma
… in part due to lack of well-characterised pre-clinical models, is a great challenge in the development of novel therapies. Analysis of paired cell culture/biopsy samples in this study revealed that paediatric HGG short-term cell cultures retain many of the tumour characteristics in vivo. …
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An agonist-antagonist myoneural interface for proprioception from a neurally-controlled prosthesis
Humans have the ability to precisely sense the position, speed, and torque of their body parts. This sense is known as proprioception, and is essential to human motor control. In the many attempts to create human-mechatronic interactions, there is still no robust, repeatable methodology to reflect …
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The Role of Age and Model Severity on Cortical Vascular Response Following Traumatic Brain Injury
… of disability and mortality in children, several pre-clinical models have been developed using rodents at a variety of different ages; however, key brain maturation events are overlooked that leave some age groups more or less vulnerable to injury. Thus, there has been a large emphasis on …
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The role of tumor-associated macrophages in pancreatic cancer
… integrated therapies have been investigated in pre-clinical models. However, only limited success was obtained when these drugs or ideals translated into clinic trials. PaC is resistant to immune checkpoint therapy, but the underlying mechanisms are largely unknown. In this study, comparative …
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The role of tissue-resident immune cells in PanIN to PDAC progression
… current immunotherapies, largely due to local suppression of anti-tumour immunity. Tissue-resident group 2 innate lymphoid cells (ILC2) are emerging as important immune modulators of the cancer microenvironment, although their role in PDAC remains contentious with both pro- and anti-cancer roles …
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Mitochondrial Metabolism in Ischaemia Reperfusion Injury
… of graft function and survival. There are no clinically approved pharmacological therapies available to ameliorate the effects of IR injury in organ transplantation or other ischaemic pathologies. Many candidate drugs found to be promising in pre-clinical models fail to show efficacy in …
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Selective Degradation of Aggregated Tau Protein Via Vectored Nanobody-TRIM21 RING Fusion Constructs
… in therapeutic development. Whilst promising in pre-clinical models, tau targeting antibodies have performed poorly in clinical trials, potentially due to low target engagement. Such antibodies rarely access the intracellular domain where the majority of tau aggregates reside. However, recent …
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Dissecting the impact of SMAD4 loss and KRAS mutations in pancreatic ductal adenocarcinoma
… shown to shape stromal composition. Lack of representation of complex genetic profiles in pre-clinical models of PDAC, which focus on Kras G12D and Trp53 mutations, alongside limited consideration of CAF heterogeneity, have potentially contributed to largely inefficient treatment options for …
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Visualization of Local Anesthetic in the Pterygomandibular Space (PMS): Educational Module for Inferior Alveolar Nerve Blocks (IANBs)
… throughout their careers. Local anesthetic prevents the depolarization of neurons, thus blocking the transmission of nerve impulses to the brain and ultimately the perception of pain. Inferior alveolar nerve (IAN) blocks have the highest incidence of failure of any block injections, ranging …
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Understanding factors affecting tendon healing: Characterising the role of obesity on tendon healing and homeostasis and augmenting its effects with growth factors
… cuff tears. Diet-induced obesity (DIO) in rodent models were used to investigate obesity’s effects on tendon homeostasis and healing after surgery and understand the impact of maternal diet on adult offspring tendon properties. The influence of body mass index (BMI) on tendon cell function was …
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Developing Novel Models and Therapeutics for ZFTA-RELA Ependymoma
… prognosis. Although genetically modified mouse models (GEMM) of cancers are useful for understanding the biology and treatment of cancer, no GEMMs of ependymoma have been generated: current models require invasive intracranial injection of cells or gene constructs during embryogenesis. This …
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