RADIOSENSITIVITY OF HUMAN GLIOMAS
RADIOSENSITIVITY OF HUMAN GLIOMAS
批准号:
6101544
负责人:
DENNIS F. DEEN
金额:
$8.09万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-06-08 至 2000-09-30
关键词:
中文摘要
除了手术,放射治疗是治疗恶性肿瘤最有效的方法。
脑瘤 尽管如此,约20%的多形性胶质母细胞瘤(GBM)进展
在放射治疗过程中,这表明这些病变是
抗辐射。 使用手术中获得的组织,我们将
开发用于识别这些肿瘤的实验室方法,并将
量化他们对辐射的反应 哺乳动物的辐射敏感性
在实验室中通过测量细胞杀伤来确定细胞的存活率。 然而,在这方面,
对于原发性肿瘤组织,这种方法存在问题,因为低
电镀效率和由此产生的选择研究一个非常小的
原始肿瘤细胞群的分数。 尝试开发
以脑肿瘤细胞存活率为终点的预测性分析,
失败. 我们认为,关键是要确定其他
定量测量可用于预测肿瘤对辐射的反应
疗法 我们建议评估固有的辐射反应的方法
更适合用于原发性肿瘤样本:DNA双链测定
脉冲场凝胶电泳显示链断裂; NA超螺旋变化
通过类核晕测定;和测量染色体断裂,
使用荧光原位杂交技术进行交换。 我们将
使用彗星试验测定所选肿瘤中的缺氧分数。 我们
将确定这些检测中的哪一个提供相关信息
关于人类脑肿瘤细胞的辐射反应,并建立
预测分析。
由于研究辐射敏感性的固有问题,
在自然环境之外的肿瘤中,我们将研究
低剂量放射治疗恶性脑肿瘤的可行性
术中能量X射线源,并间隔采集组织,
测量DNA损伤和修复以及肿瘤缺氧。 这可能是理想的
研究单个肿瘤对辐射敏感性的方法。 我们
具体目标是:1)确定最佳实验条件,
定量检测人脑肿瘤DNA损伤修复和缺氧分数
作为异种移植物模型生长的组织; 2)确定哪种测定
目的1中研究的结果显示,作为一种预测性试验,
异种移植模型中的体内辐射反应性; 3)测量DNA
新鲜GBM中的损伤和修复以及染色体断裂和交换
使用所选检测试剂盒的最佳条件检测样本; 4)
研究在手术中照射人脑肿瘤的可行性
允许能量X射线源和收获肿瘤组织用于分析
缺氧分数和DNA损伤和修复;以及,5)将缺氧分数与DNA损伤和修复相关联。
目标3中获得的结果,肿瘤的BUdR标记指数和
潜在倍增时间,遗传畸变,DNA修复活性
酶O/6-AT,并具有既定的临床预后指标,以及
放射治疗结果的临床测量。
英文摘要
Next to surgery, radiation is the most effective treatment for malignant
brain tumors. Nonetheless, -20% of glioblastoma multiforme (GBM) progress
during the course of radiation therapy, suggesting that these lesions are
resistant to radiation. Using tissues obtained during surgery, we will
develop laboratory methodologies for identifying these tumors, and will
quantify their response to radiation. Radiation sensitivity of mammalian
cells is determined in the laboratory by measuring cell killing. However,
for primary tumor tissue this approach is problematic because of low
plating efficiencies and the resultant selection for study of a very small
fraction of the original tumor cell population. Attempts to develop
predictive assays based on brain tumor cell survival as the end-point have
failed. We believe that it is crucial to determine whether other
quantitative measures can be used to predict tumor response to radiation
therapy. We propose to assess intrinsic radiation response with methods
more suitable for use in primary tumor samples: measurement of DNA double
strand breaks by pulsed field gel electrophoresis; NA supercoiling changes
by the nucleoid halo assay; and measurement of chromosomal breaks and
exchanges using fluorescence in situ hybridization techniques. We will
determine hypoxic fraction in selected tumors using the comet assay. We
will determine which of these assays provides relevant information
regarding the radiation response of human brain tumor cells and establish
predictive assays.
Because of the problems inherent in studying radiation sensitivity of
explanted tumors outside of their natural milieu, we will study the
feasibility of irradiating malignant brain tumors in situ with a low
energy X-ray source intraoperatively and harvesting tissue at intervals to
measure DNA damage and repair and tumor hypoxia. This may be the ideal
way to study the individual tumor's sensitivity to radiation. Our
specific aims are: 1) to define the optimal experimental conditions to
quantify DNA damage and repair and hypoxic fraction in human brain tumor
tissue grown as a xenograft model; 2) to determine which of the assays
studied in Aim 1 show(s) the most promise as a predictive assay for in
vivo radiation responsiveness in xenograft models; 3) to measure DNA
damage and repair and chromosome breaks and exchanges in fresh GBM
specimens using optimal conditions for the chosen assay(s); 4) to
investigate the feasibility of irradiating human brain tumors at surgery
with allow energy X-ray source and harvesting tumor tissue for assays of
hypoxic fraction and DNA damage and repair; and, 5) to correlate the
results obtained in Aim 3 with the tumor's BUdR labeling index and
potential doubling time, genetic aberrations, activity of the DNA repair
enzyme O/6-AT, and with established clinical indicators of prognosis, and
clinical measures of radiation therapy outcome.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
GENE THERAPY TARGETING HYPOXIC GLIOMA CELLS
-
批准号:6691054
-
项目类别:
-
资助金额:$31.16万
-
财政年份:2001
-
负责人:DENNIS F. DEEN
-
依托单位:
GENE THERAPY TARGETING HYPOXIC GLIOMA CELLS
-
批准号:6628447
-
项目类别:
-
资助金额:$31.16万
-
财政年份:2001
-
负责人:DENNIS F. DEEN
-
依托单位:
GENE THERAPY TARGETING HYPOXIC GLIOMA CELLS
-
批准号:6837142
-
项目类别:
-
资助金额:$31.16万
-
财政年份:2001
-
负责人:DENNIS F. DEEN
-
依托单位:
GENE THERAPY TARGETING HYPOXIC GLIOMA CELLS
-
批准号:6262526
-
项目类别:
-
资助金额:$28.04万
-
财政年份:2001
-
负责人:DENNIS F. DEEN
-
依托单位:
GENE THERAPY TARGETING HYPOXIC GLIOMA CELLS
-
批准号:6497974
-
项目类别:
-
资助金额:$28.04万
-
财政年份:2001
-
负责人:DENNIS F. DEEN
-
依托单位:
RADIOSENSITIVITY OF HUMAN GLIOMAS
-
批准号:6268685
-
项目类别:
-
资助金额:$23.87万
-
财政年份:1998
-
负责人:DENNIS F. DEEN
-
依托单位:
CORE--ANIMAL AND TISSUE BANK
-
批准号:6101548
-
项目类别:
-
资助金额:$8.09万
-
财政年份:1998
-
负责人:DENNIS F. DEEN
-
依托单位:
CORE--ANIMAL AND TISSUE BANK
-
批准号:6268689
-
项目类别:
-
资助金额:$23.87万
-
财政年份:1998
-
负责人:DENNIS F. DEEN
-
依托单位:
CORE--ANIMAL AND TISSUE BANK
-
批准号:6236090
-
项目类别:
-
资助金额:$23.15万
-
财政年份:1997
-
负责人:DENNIS F. DEEN
-
依托单位:
RADIOSENSITIVITY OF HUMAN GLIOMAS
-
批准号:6236086
-
项目类别:
-
资助金额:$23.15万
-
财政年份:1997
-
负责人:DENNIS F. DEEN
-
依托单位:
TAXOL/TAXOTERE RADIATION STUDIES IN BRAIN TUMOR CELLS
-
批准号:2700538
-
项目类别:
-
资助金额:$26.16万
-
财政年份:1996
-
负责人:DENNIS F. DEEN
-
依托单位:
TAXOL/TAXOTERE RADIATION STUDIES IN BRAIN TUMOR CELLS
-
批准号:2104691
-
项目类别:
-
资助金额:$24.45万
-
财政年份:1996
-
负责人:DENNIS F. DEEN
-
依托单位:
TAXOL/TAXOTERE RADIATION STUDIES IN BRAIN TUMOR CELLS
-
批准号:2414304
-
项目类别:
-
资助金额:$26.12万
-
财政年份:1996
-
负责人:DENNIS F. DEEN
-
依托单位:
EXPERIMENTAL THERAPEUTICS STUDY SECTION
-
批准号:3555387
-
项目类别:
-
资助金额:$7.9万
-
财政年份:1988
-
负责人:DENNIS F. DEEN
-
依托单位:
EXPERIMENTAL THERAPEUTICS STUDY SECTION
-
批准号:3555382
-
项目类别:
-
资助金额:$8.13万
-
财政年份:1988
-
负责人:DENNIS F. DEEN
-
依托单位:
EXPERIMENTAL THERAPEUTICS STUDY SECTION
-
批准号:3555380
-
项目类别:
-
资助金额:$6.1万
-
财政年份:1988
-
负责人:DENNIS F. DEEN
-
依托单位:
FACTORS AFFECTING BCNU/X-RAY INTERACTIONS IN VITRO
-
批准号:3184333
-
项目类别:
-
资助金额:$14.0万
-
财政年份:1986
-
负责人:DENNIS F. DEEN
-
依托单位:
FACTORS AFFECTING BCNU CYTOTOXICITY IN VITRO
-
批准号:3184330
-
项目类别:
-
资助金额:$16.96万
-
财政年份:1986
-
负责人:DENNIS F. DEEN
-
依托单位:
FACTORS AFFECTING BCNU/X-RAY INTERACTIONS IN VITRO
-
批准号:3184328
-
项目类别:
-
资助金额:$14.43万
-
财政年份:1986
-
负责人:DENNIS F. DEEN
-
依托单位:
FACTORS AFFECTING BCNU/X-RAY INTERACTIONS IN VITRO
-
批准号:3184331
-
项目类别:
-
资助金额:$13.58万
-
财政年份:1986
-
负责人:DENNIS F. DEEN
-
依托单位:
海外基金