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 23 for “"Chronic myeloid leukaemia"”.
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Proteasome inhibition in chronic myeloid leukaemia
CML is treated effectively with TKI, however two key problems remain - the insensitivity of CM HSC to TKI and the emergence of TKI-resistant BCR-ABL mutations. BCR-ABL activity is associated with increased proteasome activity and PI are cytotoxic against CML cell lines. We demonstrate that …
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Long-term effects of imatinib on cognition in chronic myeloid leukaemia
… rapidly endorsed as a first line treatment for chronic myeloid leukaemia (CML) in the chronic, accelerated, and blastic phases. The survival advantage demonstrated by this target kinase inhibitor has meant that patients are now treated with this agent on a long-term basis. There is a growing …
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The analysis of Bcr-Abl—Nox signalling in chronic myeloid leukaemia
Chronic Myeloid Leukaemia (CML) is a myeloproliferative disorder characterised by increased proliferation of haematopoietic stem cells. CML results following generation of the chimeric protein Bcr-Abl, a constitutively active tyrosine kinase which induces oncogenesis in part by promoting increased …
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A therapeutic approach to chronic myeloid leukaemia using short hairpin RNA molecules
Chronic myeloid leukaemia (CML) was one of the first cancers to be linked to a chromosomal abnormality, the Philadelphia chromosome. This chromosome results in a translocation between chromosomes 9 and 22, where the ABL gene on chromosome 9, a tyrosine kinase, is translocated to the BCR gene region …
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Investigating a co-operative link between TGF-β and Lyn kinase in Chronic Myeloid Leukaemia
Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterised by uncontrolled proliferation of haematopoietic cells driven by the fusion gene Bcr-Abl. The advent of a mechanism specific kinase inhibitor, Imatinib, targeting the constitutively active Bcr-Abl kinase has paved the way …
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Prognostic markers associated with tyrosine kinase inhibitor treatment response and maintenance of treatment free remission in chronic myeloid leukaemia
Treatment outcomes in Chronic Phase Chronic Myeloid Leukaemia (CP-CML) have dramatically improved with the introduction of highly active tyrosine kinase inhibitors (TKIs). However, treatment responses are highly heterogeneous. The aim of this thesis is to identify prognostic markers that may help …
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Repurposing Alzheimer’s disease medications in a drug combination for the study of the crosstalk between cell apoptosis and autophagy in the modulation of cell death in chronic myeloid leukaemia
… AD drugs for the treatment of cancers such as chronic myeloid leukaemia (CML). This requires the understanding of the possible interconnection between CML and AD at the molecular level. The overall aim of this research was to study the crosstalk between cell apoptosis and autophagy in the …
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Frequency of leukemia types and flowcytometric immunophenotypic characterization of acute lymphoblastic leukemia presenting at the university teaching hospital, Lusaka
The Frequency of Leukaemia types vary in different geographical locations and between age groups and gender. The diagnosis of Leukaemia at UTH is done by Morphological examination of blood or bone marrow smears only. Immunophenotyping is a further diagnostic tool that can be performed to diagnose …
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Frequency of leukemia types and flowcytometric immunophenotypic characterization of acute lymphoblastic leukemia presenting at the university teaching hospital, Lusaka
The Frequency of Leukaemia types vary in different geographical locations and between age groups and gender. The diagnosis of Leukaemia at UTH is done by Morphological examination of blood or bone marrow smears only. Immunophenotyping is a further diagnostic tool that can be performed to diagnose …
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The isolation and characterisation of MHC-presented peptides from CML-derived cell-lines, with a focus on post-translational modification
… of which the bcr:abl fusion kinase found in chronic myeloid leukaemia is a classic example. As phosphopeptides are known to be presented by both the MHC class-I and class- II pathways, against which specific CD4+ and CD8+ T cell responses may be generated, study of MHC-presented …
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Antioxidant pathways and human leukaemia chemotherapeutic sensitivity
… cancers: eg imatinib has effectively eradicated chronic myeloid leukaemia (CML) morbidity. However, acute myeloid leukaemia (AML) remains essentially incurable for the vast majority of patients. The current gold-standard treatment for AML has remained relatively unchanged for decades, consisting …
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The regulation of the oncogenic STAT transcription factors by the non receptor tyrosine kinase and Cdc42 effector ACK
… haematological disease cell lines. In the K562 chronic myeloid leukaemia cell line, ACK is identified to interact with STAT5 and by cell line engineering was confirmed to contribute to the nuclear pool of transcriptionally active STAT5. By thorough bioinformatic analysis, the true contribution …
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Omics analysis in understanding disease mechanisms
… mechanisms during treatment with a case study in Chronic Myeloid Leukaemia (CML). This chapter not only unveiled pathways integral to CML biology under novel combination therapies but also identified more promising targets. Thirdly, the utility of time-series untargeted metabolomics in studying …
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A Molecular Cytogenetic Profile of the Chronic Myeloproliferative Disorders
The Chronic Myeloproliferative Disorders (CMPD) form a continuum of malignancies, the molecular pathogenesis of which remains obscure. Chronic Myeloid Leukaemia (CML) is the only disorder with a recognisable pathogenomic abnormality, the Ph chromosome. The remaining disorders have as yet, no …
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Exploring the Role of PKD Enzymes in the Innate and Adaptive cells of the Mammalian Immune System
… known if this is true for PKD in cells of the myeloid lineage, including dendritic cells (DCs) and macrophages or in myeloid malignancies such as chronic myeloid leukaemia (CML). Moreover, the literature on the role of PKD is complicated by the use of dual and non-specific pharmacological …
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Identification and functional characterisation of gene fusions in human cancer cell lines
… such as EML4-ALK in lung cancer and BCR-ABL1 in chronic myeloid leukaemia have already led to changes in clinical care. However, important questions remain about the role of gene fusions in promoting oncogenic phenotypes and their relevance in drug response. In this study, I combine RNA …
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Detection of the calreticulin type 1 and type 2 mutations in a group of myeloproliferative neoplasm patients using molecular methods
… neoplasms (MPN), formerly referred to as chronic myeloproliferative disorders, are a group of haematopoietic stem cell disorders that are characterized by clonal proliferation of one or more mature myeloid lineages. The group of disorders, now classified as the classic MPNs, include …
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Control tools for flow chemistry processing and their application to the synthesis of bromodomain inhibitors
… kinase inhibitor used for the treatment of chronic myeloid leukaemia, are prepared. A “catch-react-release” technique for solid-phase synthesis is used, with computer-controlled operation of the reactors. In Chapter 3, a two-step procedure for the synthesis of piperazine-2-carboxamide, a …
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Impact of CYP2C8 single nucleotide polymorphisms on in-vitro metabolism of imatinib to N-desmethyl imatinib
… is a first line therapy for the treatment of chronic myeloid leukaemia (CML). Treatment with imatinib must be continuous and indefinite for most patients to maintain disease control. Despite excellent efficacy and tolerability, up to 50% of CML patients discontinue imatinib due to lack of …
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Defining CP-CML patient subsets associated with poor imatinib uptake and response.
… the treatment outcome for the majority of chronic phase chronic myeloid leukaemia (CP-CML) patients. Although most patients will achieve excellent clinical (haematological, cytogenetic and molecular) responses on imatinib, it is clear that a subset of patients will respond poorly, or fail …
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