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 11 of 11 for “"pre-clinical development"”.
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Pre-Clinical Development Of Aav Mediated Gene Therapy For Familial Lecithin Cholesterol Acyltransferase Deficiency
… KO/ human ApoA-I transgenic mice using AAV8 expressing human LCAT. AAV8-TBG-hLCAT induces significant increases in plasma % cholesterol esterified at a dose as low as 3e9 GC per mouse, which is approximately equivalent to 1.5e11 GC per kg. We also characterize the first gain-of-function variant …
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Pre-clinical development of cyclodextrin-based nanoparticles for oral delivery of protein/peptide drugs-in vitro and in vivo evaluation
… of the gastrointestinal tract, the possible pre-systemic degradation by enzymes, the wide range of pH and the poor permeability of the intestinal mucosa. The application of nanosystems, specifically cyclodextrin-based nanoparticles (NPs) to overcome these barriers is the focus of this …
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Engineered E. Coli That Detect and Respond to Gut Inflammation Through Nitric Oxide Sensing
… in synthetic biology have allowed for the development of re-programmed microorganisms that perform useful tasks in areas like fuel production, bioremediation, and medicine. Several engineered microorganisms are in pre-clinical development for the treatment of human diseases, but may face …
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Development and Characterization of A Bi-Specific Antibody Targeting Hla-A2/Pr1
… new therapeutics are much needed. Here, we present novel therapeutic strategy targeting myeloid leukemia antigen, HLA-A2 restricted peptide PR1.Previously, we have conducted pre-clinical development and humanization of a T cell receptor-like monoclonal antibody (h8F4) that targets PR1/HLA-A2 …
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In vitro and in vivo investigation of the anticancer activity and mechanism of disulfiram in malignant mesothelioma
Background Malignant Mesothelioma (MM) represents an asbestos-related insidious and invasive neoplasm with a long latency period. MM carries a dismal prognosis as most patients have irresectable disease or are ineligible for surgery due to medical comorbidities or old age, leaving chemotherapy and …
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Targeting survival pathways in cancer stem cells
… progeny are crucial for an optimal pre-clinical development of molecular targeted agents. We isolated breast CSCs from surgically resected primary breast tumors. A first round of experiments was designed in order to determine whether our clones met the operative criteria to be …
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Identification of determinants of sensitivity to duocarmycin analogues: A class of potent anti-cancer drugs
Duocarmycin analogues are currently in pre-clinical development as hypoxia-activated prodrugs and as so-called payloads for antibody-drug conjugates for the treatment of cancer. Although the mechanism of action (MOA) of duocarmycins has been elucidated as DNA minor groove alkylation, not much is …
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Utilising recombinant TAPBPR technology to investigate MHC class I peptide editing and therapeutic applications
… immune response to infection and malignancy by presenting peptides to CD8+ T cells. Optimal peptide:MHC-I complexes are generated in the MHC-I antigen processing and presentation pathway. In this pathway, TAPBPR shapes the presented peptidome by catalysing peptide exchange on MHC-I molecules and …
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Identifying Merozoite Targets of Protective Immunity Against <i>Plasmodium falciparum</i> Malaria
… immunity, first to severe, then to uncomplicated clinical episodes of malaria, and finally to high parasite densities, provides hope that a vaccine is achievable. Immunoglobulins have been identified as a key component of naturally acquired immunity and identifying the targets and mechanisms by …
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Investigating permeation of anti-mycobacterial agents in Mycobacterium tuberculosis and M. tuberculosis-infected macrophages in vitro as a model for early stage tuberculosis drug discovery
… challenge to current strategies employed in the development of anti-TB drugs is the complexity in TB disease pathology which presents as a wide spectrum of lesions in patients presenting with the disease. These lesions occur at different anatomical loci in the same individual and at different …
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Behavioural, genetic and epigenetic determinants of white matter pathology in a new mouse model of chronic cerebral hypoperfusion
Recent clinical studies suggest that white matter pathology rather than grey matter abnormality is the major neurobiological substrate of age- related cognitive decline during “healthy” aging. According to this hypothesis, cerebrovascular (e.g. chronic cerebral hypoperfusion) and molecular (e.g. …