IDENTIFYING THE ROLE OF INFLAMMATORY CYTOKINES IN SYMPTOM PRODUCTION

确定炎症细胞因子在症状产生中的作用

基本信息

项目摘要

Multiple myeloma (MM) is an incurable but treatable cancer. Patients with MM patients suffer from multiple symptoms caused by their disease and by aggressive treatment, such as autologous transplantation (AuSCT) and novel agents used for induction or maintenance therapy. Symptoms create a "symptom burden" that cause distress and that can compromise patient's function and cause treatment delays. There is increasing evidence that many of these symptoms may be caused by the deregulation of inflammatory cytokines and their precursors. Built on a large body of literature relating "sickness behavior" in animals (including pain, sleep disorder, reduced appetite, and decreased activity), we have developed the hypothesis that many cancer-related symptoms might be improved by modulating inflammatory pathways. We and others have shown that circulating inflammatory cytokines (such as interleukin (IL)-6 and TNF) are strongly linked to symptom severity. For example, we have shown that increased IL-6 is related to the severity of a cluster of symptoms during AuSCT in patients with MM. What is not known is whether suppression of these cytokines might reduce or prevent the prevalence and severity of treatment-related symptoms. The objectives of this project are: (i) To use hierarchical dynamic modeling to examine the hypothesis that increases in the levels of inflammatory cytokines and NF-KB drive increases in symptom development in patients with MM that are related to status of disease as well as during cancer therapy (Specific Aims i, 2, 3); (2) We also will use anticytokine agents (cytokine IL-6 antibody CNTO 328) and an NF-KB inhibitor (curcumin) in phase 2 placebo-controlled randomized clinical trials, to test the hypothesis that reduction of specific inflammatory cytokine levels and/or NF-KB activation will reduce symptom expression. This provides an experimental test of the role of specific inflammatory cytokines (IL-i, IL-6, and TNF-a) and their precursors (NF-KB) in symptom development (Specific Aims 2,3). Taken together, these Aims should provide a strong test of our central hypothesis that a causal relationship exists between inflammatory cytokines and symptom production in patients with MM. Our long-term objectives are to characterize the basic mechanisms underlying symptom burden (with particular focus on cytokines and immune mediators), and to provide a rationale for mechanism-driven symptom management. Having the ability to reduce symptom burden or even prevent these consequences from therapy would be of potential benefit to thousands of cancer patients by improving the tolerability of treatment and the quality of their survivorship. PERFORMANCE SITE(S) (organization, city, state) The University of Texas M. D. Anderson Cancer Center Houston, Texas Page 157
多发性骨髓瘤(MM)是一种无法治愈但可以治疗的癌症。MM患者患的是

项目成果

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CHARLES S CLEELAND其他文献

CHARLES S CLEELAND的其他文献

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{{ truncateString('CHARLES S CLEELAND', 18)}}的其他基金

Mechanisms of Symptoms of Multiple Myeloma and Its Therapy
多发性骨髓瘤的症状机制及其治疗
  • 批准号:
    7689330
  • 财政年份:
    2008
  • 资助金额:
    $ 29.84万
  • 项目类别:
Mechanisms of Symptoms of Multiple Myeloma and Its Therapy
多发性骨髓瘤的症状机制及其治疗
  • 批准号:
    8133404
  • 财政年份:
    2008
  • 资助金额:
    $ 29.84万
  • 项目类别:
Mechanisms of Symptoms of Multiple Myeloma and Its Therapy
多发性骨髓瘤的症状机制及其治疗
  • 批准号:
    8331191
  • 财政年份:
    2008
  • 资助金额:
    $ 29.84万
  • 项目类别:
Mechanisms of Symptoms of Multiple Myeloma and Its Therapy
多发性骨髓瘤的症状机制及其治疗
  • 批准号:
    7928995
  • 财政年份:
    2008
  • 资助金额:
    $ 29.84万
  • 项目类别:
Understanding the Impact of Multiple Symptoms: A Symptom Burden Consortium
了解多种症状的影响:症状负担联盟
  • 批准号:
    7169340
  • 财政年份:
    2006
  • 资助金额:
    $ 29.84万
  • 项目类别:
Mechanisms and Treatment of Cancer-Related Symptoms Conf
癌症相关症状的机制和治疗会议
  • 批准号:
    6941435
  • 财政年份:
    2005
  • 资助金额:
    $ 29.84万
  • 项目类别:
PAIN CONTROL METHODS-- EFFECTS OF MORPHINE, DISTRACTION, & MOOD CHANGES ON PAIN
疼痛控制方法——吗啡的作用、分散注意力、
  • 批准号:
    6309237
  • 财政年份:
    1999
  • 资助金额:
    $ 29.84万
  • 项目类别:
PRACTICE VARIATIONS IN PAIN CONTROL AT THE END OF LIFE
临终时疼痛控制的实践变化
  • 批准号:
    2796863
  • 财政年份:
    1998
  • 资助金额:
    $ 29.84万
  • 项目类别:
PAIN CONTROL METHODS--EFFECTS OF MORPHINE, DISTRACTION, & MOOD CHANGES
疼痛控制方法——吗啡的作用、分散注意力、
  • 批准号:
    6265673
  • 财政年份:
    1998
  • 资助金额:
    $ 29.84万
  • 项目类别:
LABORATORY STUDIES OF PAIN CONTROL METHODS
疼痛控制方法的实验室研究
  • 批准号:
    2115727
  • 财政年份:
    1996
  • 资助金额:
    $ 29.84万
  • 项目类别:
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