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 25 for “"Patient-derived xenografts"”.
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Tumour ecology of breast cancer patient-derived xenografts
… and dynamic ways. Descriptive studies in patient material, although extremely informative, often lack the temporal and spatial resolution needed to fully recapitulate this variability. Mouse models represent a natural complement to these correlative analyses, allowing longitudinal and …
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An Investigation into the Vascular Phenotypes of Breast Patient- Derived Xenografts
… in a preclinical setting but also throughout a patient’s treatment regime, particularly in breast cancer management. Thus 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 …
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Investigation of metabolism in glioblastoma patient-derived xenografts using deuterium metabolic imaging
… used to study glucose and acetate metabolism in patient-derived xenografts (PDX) of glioblastoma in mice and rats respectively. Using 2H-labelled glucose, I showed that despite exhibiting the same concentration of glucose within the tumour, glycolytic PDX subtypes produced more labelled lactate …
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DEGRADATION OF XIAP AS A NOVEL TREATMENT STRATEGY IN HIGH-RISK NEUROBLASTOMA
… of high-risk MYCN-amplified neuroblastoma patient-derived xenografts. Collectively, this presents the degradation of XIAP mediated by ARTS mimetics as a potential therapeutic strategy for treatment of neuroblastoma, specifically aggressive high-risk MYCN-amplified disease which …
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Imaging Glioblastoma metabolism using mass spectrometry imaging
… I identified three metabolic signatures in patient GB tumours: glycolytic, oxidative and a mixed glycolytic/oxidative phenotype. These phenotypes do not correlate with microenvironmental characteristics such as proliferation rate, immune cell infiltration, hypoxia, or vascularisation. …
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Consequences of Pathogenic Mitochondrial DNA Mutations in Cancer Progression
… by the establishment of a collection of patient tumor xenograft models with varied mtDNA status. Chapter two details the development of a new cytoplasmic hybrid (cybrid) generation method that simplifies the creation of transmitochondrial cybrids and enables transplantation of any mtDNA …
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Dissecting The Mechanisms of Venetoclax Resistance In Myelodysplastic Syndromes
… therapy. However, only 50 percent of the patients respond, with transient effects and no approved second-line treatment options after their diseases progress to acute myeloid leukemia (AML). The mechanisms that govern HMA failure are unknown. Recently, we unveiled that MDS are maintained …
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Hijacking Cancer Signaling: First-in-class JPRK-targeting Ligands for Fibrolamellar Hepatocellular Carcinoma
… and >500-fold selective drug candidates in patient derived xenografts. Fibrolamellar hepatocellular carcinoma is a rare un-treated liver cancer driven by a fusion kinase known as JPRK, a mutant of protein kinase A (PKA). Targeting this fusion kinase selectively is challenging due to the …
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Modulation of Pi3K-Akt Pathway In Colorectal Cancer
… MK2206 monotherapy has been ineffective in CRC patients. We investigated the impact of MK2206 on pharmacodynamic (PD) markers and signaling pathways using reverse phase protein array (RPPA) on (1) paired tumor biopsies from a clinical trial of MK2206 in PI3K-altered metastatic CRC, (2) …
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INFERRING TUMOR PROPERTIES FROM GENE EXPRESSION DATA
… spanning primary tumors, metastases, CTCs, patient-derived xenografts (PDXs), cancer cell lines and organoids. We demonstrate that by adopting a specific training composition and data processing approach, we can achieve high performance across different onco-types, including CTCs, suggesting …
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Preclinical Evaluation of Immunomodulatory Effects of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers
… human tumor cells in vitro and in vivo in HPV+ patient derived xenografts (PDX) mouse models. We hypothesized that Aurora kinase inhibition mediated HPV+ cancer cell apoptosis would lead to immunogenic cell death (ICD) that would promote antitumor efficacy of immune checkpoint therapy. The …
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Multiomic Analyses Reveal Epigenomic Alterations and New Targets of Polycomb Repressive Complex 2 in Schwann Lineage Cells and Malignant Peripheral Nerve Sheath Tumors
… in 5-13% of Neurofibromatosis Type I (NF1) patients. It is thought that MPNSTs develop from benign precursors. However, the existing histologically defined stages in MPNST development need improvement. Commonly, MPNSTs harbor defects in PRC2 components EED or SUZ12, leading to loss of …
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Computational Approaches to Understand Chemoresistance & Tumor Evolution Using Longitudinal Clinical Data and Lineage Tracing
… chemo-resistance, and use longitudinally tracked patient biopsies to interrogate patterns of response and evolution under chemotherapy. We performed comprehensive molecular profiling using pre-treatment core needle biopsies from 300 TNBC patients treated neoadjuvantly to understand features …
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Ribonucleotide Reductase Subunit Switching in Hepatoblastoma Drug Response and Relapse
… 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 ribonucleotides to …
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Evaluating metabolism in human renal cancer using novel surgical models
… and approaches to study metabolism *in vivo*, in patients have yet to be widely established in RCC and furthermore, there is a lack of clinically relevant models of RCC metabolism locally. The aim of this thesis was to develop novel models of RCC to evaluate metabolism using isotopic tracer …
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Genome-scale Precision Proteomics Identifies Cancer Signaling Networks and Therapeutic Vulnerabilities
… tyrosine kinase (RTK) oncogenes, platelet-derived growth factor receptor alpha (PDGFRA) and neurotrophic receptor tyrosine kinase 1 (NTRK1), analyzing 13,860 proteins (11,941 genes) and 30,431 phosphosites by mass spectrometry. Systems biology approaches identified numerous functional …
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Imaging Metabolic Signatures in High Grade Serous Ovarian Cancer
… metabolic differences were observed between patients and between different tumour deposits within the same patient. Here I compared the use of <sup>13</sup>C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized [1-<sup>13</sup>C]pyruvate metabolism and positron emission …
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A Microfluidic Tissue Array (µFTA) For Personalized Medicine using Tumor Biopsies
… degree of individualization possible, such that patients with similar genetic makeup and cancer cell surface markers can register a dissimilar response to hormone or chemotherapy. Effective experimental drugs for an individual may be shelved from being available due to a lack of beneficial …
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Investigating heterogeneity and mechanisms of resistance in paediatric B-cell non-Hodgkin lymphoma
… alone accounting for 38% of NHL diagnoses in patients under 15 years. Outcomes have improved significantly in recent years with the introduction of intensive multi-agent chemotherapy, followed by the addition of Rituximab, resulting in a survival rate exceeding 90%. Despite this, those …
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