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 19 of 19 for “"PDX models"”.
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Developing canine osteosarcoma and human non-small cell lung cancer PDX models to study immunotherapies targeting canine and human T cells
… work focused on developing novel experimental models implanting both human and dog tumor samples infiltrated with autologous tumor lymphocytes as subcutaneous xenografts into mice that lack their own immune system. This specific model allows us to further test our Fabs specific for human or …
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An Investigation into the Vascular Phenotypes of Breast Patient- Derived Xenografts
… far there has been a reliance on cell-line mouse models to provide insight into tumour vascular phenotypes captured with PAI. As a result, several questions remain regarding the sensitivity of PAI to discriminate between patient vascular phenotypes, and which vascular features are important to …
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A Context-Forward In Vivo Functional Genomics Platform For Target Discovery and Establishing Vulnerability Context In Pancreatic Cancer
… oncogenic signaling across our tumor models, and ii) establish a disease-specific co-expression network to delineate transcriptional signatures underlying PDAC diversity. Utilizing an <em>in vivo</em> functional genomics platform, we developed custom libraries to first characterize and …
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Allogeneic Double Negative T cell Therapy as a Novel Treatment for AML Patients
… the leukemia load in patient-derived xenograft (PDX) models. Unlike CD4+ and CD8+ conventional T (Tconv) cells, DNTs do not attack normal allogeneic cells and normal xenogeneic tissues in vitro and in xenograft models. Further, potentials of using allogeneic DNTs as an off-the-shelf adoptive cell …
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Epithelial to Mesenchymal Transition As A Predictor of Response to Polo-Like Kinase 1 Inhibition-Induced Apoptosis In Non-Small Cell Lung Carcinoma
… <em>in vivo</em> in patient derived-xenograft (PDX) models as well as orthotopic mouse models in which the EMT properties are manipulable by modulating the miR200/ZEB1 axis. To facilitate analysis of these <em>in vivo</em> studies, we developed a novel semi-automated method of metastatic lung …
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Using Tissue Morphology to Infer Intra-Tumor Variation in Molecular State and Response
… this across a range of cohorts including in PDX models. In CRC, we sought to use early radiation-induced changes in tissue morphology to better understand response to radiation therapy, for which we currently lack any biomarkers. To this end, we developed a novel deep learning framework to …
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Development of novel antibody-targeted nanoparticle strategies for treatment of pancreatic cancer
… of reducing cell viability in all 4 cell line models treated. Notably this reduction did not correlate with DR5 surface expression but was consistent with observations in the literature. The reduction of viability was promising and the addition camptothecin improved this potency. The combined …
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Computational Approaches to Understand Chemoresistance & Tumor Evolution Using Longitudinal Clinical Data and Lineage Tracing
… early passage PDAC patient-derived xenografts (PDX) models. These models were used to identify the fitness landscape of individual tumor lineages under three different drugs. High-throughput isolation and profiling of resistant and sensitive lineages were used to establish, and profile them …
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Ribonucleotide Reductase Subunit Switching in Hepatoblastoma Drug Response and Relapse
… HB. Our recent work on HB mouse and organoid models, patient-derived xenografts (PDX) and primary patient samples revealed a significant upregulation of ribonucleotide reductase (RNR) subunit M2 (RRM2) in high-risk HB. RNR is the sole enzymatic complex in mammal cells that converts …
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ALK in the pathogenesis of cancer
… largely focused on cell line-based models whereby in vitro culture conditions may cause rapid phenotypic and genotypic divergence of patient-derived cells from the originating tumour, we developed two paediatric ALK+ ALCL patient-derived xenograft (PDX) models from liquid biopsy …
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Signaling at the Tumor-Immune Interface in Glioblastoma
… oncolytic virus (OV). In patient derived tumor (PDX) models in mice, mice treated with OV have increased antigen presentation, pointing to the use of OV therapy to reshape the tumor micro-environment to a more inflammatory state. Finally, tissue obtained from serial biopsies of GBM patients …
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Biomarkers of Genome Instability and Disease Progression in Ovarian Cancer
… (ctDNA) monitoring in patient derived xenograft (PDX) mice using sWGS and copy number analyses. We illustrate the feasibility of this approach and show its sensitivity for modelling treatment response in pre-clinical studies. This provides an important opportunity to study copy number driven …
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Integration of Biomedical Imaging and Translational Approaches For Management of Head and Neck Cancer
… <em>in vivo</em> validation using orthotopic and PDX models. Among these drugs, HDAC inhibitor and LBH-589 showed the most effective tumor growth inhibition that can be used in future clinical trials.</p>
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RNA Therapeutics for Fibrolamellar Hepatocellular Carcinoma
… cells in vitro and in patient derived xenograft models of FLC in mice. These results show that DNAJB1::PRKACA has a pivotal role in tumor formation, maintenance, and progression and that FLC is oncogenically dependent on DNAJB1::PRKACA. This validates DNAJB1::PRKACA as a therapeutic target. To …
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Dissecting the molecular mechanisms of therapeutic resistance in cancer
… of CDK4/6 inhibitor, palbocilib in two GBM PDX and one MPNST PDX models. The GBM6 model activated EGFR signaling upon treatment with palbociclib whereas the GBM22 and MPNST3 models activated SFKs and PDGFRa signaling in resistant tumors. Across all three PDX tumor models, treatment with …
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Tracking Treatment Response and Resistance to Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer.
… in pancreatic patient-derived xenograft (PDX) tumors; and 2. The use of shRNA technology on pancreatic PDX tumors can elucidate synthetic lethal partners to overcome therapeutic resistance to PARP inhibition. To test this hypothesis, I set out to first further characterize the hereditary …
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CELLULAR AND MOLECULAR MECHANISMS OF CHEMORESISTANCE IN ACUTE MYELOID LEUKEMIA
… withdrawal. However, a lack of robust in vivo models of clinical chemoresistance in human AML hinders our understanding of these mechanisms. To address this, I aimed to generate in vivo models of truly chemoresistant AML to investigate non-genetic mechanisms of chemotherapy resistance. I …
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Studying the Transcriptional and Epigenetic Perturbations of Haematopathologies Expressing NPM1-ALK
… mediators was applied to several in vitro models. Such models included cell lines representing ALK-driven malignancies (ALCL, DLBCL, NSCLC, and NB) as well as ex vivo primary patient-derived lines (notably an ALK-TKI sensitive primary patient-derived ALCL model, a second ALK-TKI resistant …
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The Role and Immunogenicity of CBFA2T3-GLIS2 in Pediatric Acute Megakaryoblastic Leukemia
… these knowledge gaps, I developed two mouse models to study transcriptional regulation by the CBFA2T3-GLIS2 fusion oncogene and the ability of the immune system to recognize this malignancy with a goal of identifying therapeutic vulnerabilities for future translational studies. To understand …