رسالة جامعية
Aberrations in Cytokine Signaling in Leukemia: Variations in Phosphorylation and O-GlcNAcylation
| العنوان: | Aberrations in Cytokine Signaling in Leukemia: Variations in Phosphorylation and O-GlcNAcylation |
|---|---|
| المؤلفون: | Tomic, Jelena |
| المساهمون: | Spaner, David |
| سنة النشر: | 2012 |
| المجموعة: | Theses Canada / Thèses Canada (Library and Archives Canada) |
| مصطلحات موضوعية: | Chronic Lymphocytic Leukemia, Immunogenicity, Interferon (IFN), Signal Transducer and Activator of Transcription (STAT) 1, STAT3, Reactive Oxygen Species (ROS), Tumor suppressor p53, phosphatases, Toll-like receptor (TLR)-7 agonist, phorbol esters, immunosuppressive cytokines, O-GlcNAc, Hexosamine Biosynthetic Pathway (HBP), Glucosamine, Resveratrol, Friend Erythroleukemia, RL2 antibody, cancer vaccines, IL-2, tumor immunosuppression, phosphorylation, O-GlcNAcylation, cytotoxic T lymphocytes (CTLs), Ataxia telangiectasia mutated (ATM), Antigen presenting cell (APC), Immunotherapy, OGT, OGase, glucose, tumor metabolism |
| الوصف: | Tumor-induced immunosuppression can occur by multiple mechanisms, each posing a significant obstacle to immunotherapy. Evidence presented in this dissertation suggests that aberrant cytokine signaling, as a result of altered metabolism of Chronic Lymphocytic Leukemia (CLL) cells, confers a selective advantage for tumor survival and growth. Cells from CLL patients with aggressive disease (as indicated by high-risk cytogenetics) were found to exhibit prolongation in Interferon (IFN)-induced STAT3 phosphorylation, and increased levels of reactive oxygen species (ROS) in these cells reflected these signaling processes. Changes in the relative balance of phospho-STAT3 and phospho-STAT1 levels, in response to combinations of IL-2 + Toll-like receptor (TLR)-7 agonist + phorbol esters, as well as IFN, were associated with the immunosuppressive and immunogenic states of CLL cells. In addition, immunosuppressive leukemic cells were found to express high levels of proteins with O-linked N-acetylglucosamine (O-GlcNAc) modifications, due to increased metabolic activity through the Hexosamine Biosynthetic Pathway (HBP), which caused impaired intracellular signaling responses and affected disease progression. A conclusion of the studies presented here is that the intrinsic immunosuppressive properties of leukemic cells may be overcome by agents such as Resveratrol that target metabolic pathways of these cells. |
| نوع الوثيقة: | thesis |
| اللغة: | English |
| العلاقة: | http://hdl.handle.net/1807/32829Test |
| الإتاحة: | http://hdl.handle.net/1807/32829Test |
| رقم الانضمام: | edsbas.CCAF96C8 |
| قاعدة البيانات: | BASE |
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edsbas BASE edsbas.CCAF96C8 696 3 Dissertation/ Thesis dissertation 695.984252929688 |
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