MACROPHAGES AND CYTOKINES IN BIOCHEMOTHERAPY OF MELANOMA
黑色素瘤生物化学治疗中的巨噬细胞和细胞因子
基本信息
- 批准号:2107640
- 负责人:
- 金额:$ 15.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1994
- 资助国家:美国
- 起止时间:1994-08-01 至 1998-05-31
- 项目状态:已结题
- 来源:
- 关键词:DNA damage DNA repair biopsy combination chemotherapy crosslink cytokine cytotoxic T lymphocyte enzyme linked immunosorbent assay free radical oxygen gene expression human therapy evaluation immunocytochemistry interferon gamma interleukin 1 interleukin 6 interleukin 8 leukocyte activation /transformation macrophage melanoma monocyte neoplasm /cancer chemotherapy neoplasm /cancer immunotherapy radioimmunoassay tumor necrosis factor alpha vascular endothelium
项目摘要
We hypothesize that the antitumor effect(s) od chemotherapy are enhanced
by responses to IL-2 and IFNalpha in human melanoma patients receiving
biochemotherapy. This proposal is centered around the analysis of a
randomized clinical trial which compares the efficacy of systemic
biochemotherapy vs. chemotherapy alone for advanced malignant melanoma.
Previous studies have suggested a >50% response from the biochemotherapy
group, therefore, we expect to elucidate changes that are relevant to a
successful therapeutic maneuver and which will provide insight into
response mechanism(s). This R01 is complemented by two others, one which
incorporates analysis of specific effects on the DNA of the patients
during therapy, and the other studying human melanoma models for direct
testing of agents. The working hypothesis of this proposal is that
biotherapy stimulates tumor infiltrating macrophages and/or endothelia
to produce oxidants which interfere with DNA repair in the tumor cells,
thereby augmenting the effect of chemotherapy.
Aim 1 will determine whether systemic measurements of macrophage
activation relate to pro-oxidant effects, and if either of these
parameters correlate with DNA interstrand crosslinks and/or patient
response to therapy. This will be accomplished by measuring neopterin
(by RIA), measurements of monocyte activation, immunostaining for
macrophages in the tumor, and plasma lipid peroxidation as an indicator
of pro-oxidant production during the clinical trial. We further
hypothesize that IL-1s are critical local mediators inducing the
production of oxygen radicals, and that in some patients IL-1 may already
be expressed by the tumor, while in others the biochemotherapy or
chemotherapy induces production. Aim 2 will test whether those patients
whose tumors are producing Il-1alpha or IL-1beta are those patients most
responsive to biochemotherapy or chemotherapy. Finally, using ELISA and
immunohistology evaluation of the systemic and local presence of
TNFalpha, IL-6, IFNlambda, and IL-8 will be performed. The final
hypothesis is that an explanation for the variability of patient response
to biochemotherapy or chemotherapy is due, in part, to the heterogeneity
of multiple cytokine expression from the tumor itself.
我们假设化疗的抗肿瘤作用会增强
通过接受治疗的人类黑色素瘤患者对 IL-2 和 IFNα 的反应
生物化疗。 该提案的核心是分析
比较系统性治疗效果的随机临床试验
生物化疗与单纯化疗治疗晚期恶性黑色素瘤的比较。
先前的研究表明,生物化疗的缓解率 >50%
因此,我们希望阐明与
成功的治疗策略将提供深入了解
响应机制。 该 R01 由另外两个补充,其中一个
纳入对患者 DNA 的具体影响的分析
在治疗期间,另一个研究人类黑色素瘤模型以直接
代理的测试。 该提案的工作假设是
生物疗法刺激肿瘤浸润巨噬细胞和/或内皮细胞
产生干扰肿瘤细胞 DNA 修复的氧化剂,
从而增强化疗的效果。
目标 1 将确定是否对巨噬细胞进行系统测量
激活与促氧化作用有关,如果其中任何一个
与 DNA 链间交联和/或患者相关的参数
对治疗的反应。 这将通过测量新蝶呤来完成
(通过 RIA)、单核细胞活化测量、免疫染色
肿瘤中的巨噬细胞,以血浆脂质过氧化为指标
临床试验期间促氧化剂产生的影响。 我们进一步
假设 IL-1 是诱导
氧自由基的产生,并且在某些患者中 IL-1 可能已经
由肿瘤表达,而在其他情况下则通过生物化疗或
化疗诱导产生。 目标 2 将测试这些患者是否
肿瘤产生 IL-1α 或 IL-1β 的患者是最常见的患者
对生物化疗或化疗有反应。 最后,使用 ELISA 和
免疫组织学评估全身和局部存在
将进行 TNFα、IL-6、IFNlambda 和 IL-8 检测。 决赛
假设是对患者反应变异性的解释
生物化疗或化疗的部分原因是异质性
肿瘤本身表达多种细胞因子。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ELIZABETH A GRIMM其他文献
ELIZABETH A GRIMM的其他文献
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{{ truncateString('ELIZABETH A GRIMM', 18)}}的其他基金
UT M.D. Anderson Cancer Center SPORE in Melanoma
UT M.D. 安德森癌症中心黑色素瘤孢子
- 批准号:
7912014 - 财政年份:2009
- 资助金额:
$ 15.75万 - 项目类别:
PROGNOSTIC SIGNIFICANCE AND ANALYSIS OF iNOS IN MELANOMA
黑色素瘤中 iNOS 的预后意义和分析
- 批准号:
6993428 - 财政年份:2004
- 资助金额:
$ 15.75万 - 项目类别:
UT M.D. Anderson Cancer Center SPORE in Melanoma
UT M.D. 安德森癌症中心黑色素瘤孢子
- 批准号:
6949451 - 财政年份:2004
- 资助金额:
$ 15.75万 - 项目类别:
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