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Therapeutic potential of demethylation agents and histone deaceytlase inhibitors in NK-cell lymphoma and leukemiaKam, Kevin., 甘季燐. January 2007 (has links)
published_or_final_version / Medical Sciences / Master / Master of Medical Sciences
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Acquired STAT4 deficiency as a consequence of cancer chemotherapyLupov, Ivan 16 August 2011 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / Signal Transducer and Activator of Transcription 4 (STAT4) is an important transcription factor activated by IL-12 signaling. Activated STAT4 is essential for Th1 cell differentiation, a process characterized by increased potential for interferon (IFN)-γ production. Defective IFN-γ production due to STAT4 deficiency occurs after autologous stem cell transplantation for lymphoma.
We have investigated the mechanisms of post-transplant STAT4 deficiency. The tumor-bearing state is ruled out to be the cause because STAT4 levels were not significantly different in peripheral blood mononuclear cells (PBMCs) obtained from lymphoma patients prior to treatment and healthy control subjects. The magnitude of the decrease in STAT4 levels corresponded with increasing intensity of chemotherapeutic treatment in vivo. Furthermore, treatment of normal PBMC cultures or a natural killer (NK) cell line with chemotherapy drugs in vitro also resulted in reduced STAT4 protein and reduced IL-12-induced IFN-γ production. Chemotherapy drugs are shown to have no impact on the stability of STAT4 mRNA, while steady-state levels of STAT4 transcripts are decreased in lymphoma patients.
Our findings demonstrated that chemotherapeutic drugs up-regulate the ubiquitination rates of the STAT4 protein, which in turn promotes its degradation via the proteasome-mediated pathway. Treatment with the proteasome inhibitor bortezomib largely reversed the chemotherapy-induced STAT4 deficiency. Thus, acquired STAT4 deficiency in lymphoma patients is a consequence of treatment with chemotherapy. These results have important implications for design of optimal immunotherapy for lymphoma.
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Molecular mechanisms of IL-2 mediated BCL10 nuclear localization and the therapeutic role of an anti-CD25 antibody in nasal NK-celllymphomaChan, Ka-kui, 陳家駒 January 2009 (has links)
published_or_final_version / Pathology / Doctoral / Doctor of Philosophy
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The effectiveness of a chemotherapy educational programme (CEP) for Leukaemia and Lymphoma patientsKwok, Suet-kei, Gladys., 郭雪琪. January 2004 (has links)
published_or_final_version / Nursing Studies / Master / Master of Nursing in Advanced Practice
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