EXPERIMENTAL THERAPEUTICS
EXPERIMENTAL THERAPEUTICS
批准号:
6203324
负责人:
MALCOLM A. MOORE
金额:
$15.02万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1999
资助国家:
美国
项目状态:
已结题
起止时间:
1999-09-17 至 2000-08-31
关键词:
cell growth regulation clone cells cooperative study disease /disorder model dosage drug discovery /isolation drug metabolism enzyme activity enzyme inhibitors human tissue laboratory mouse leukemia metastasis neoplasm /cancer chemotherapy neoplasm /cancer pharmacology nonhuman therapy evaluation nucleic acid hybridization pharmacokinetics telomerase telomere xenotransplantation
中文摘要
恶性生长导致肿瘤负担不断增加
英文摘要
Malignant growth leads to an unremitting increase in tumor burden
despite treatment with antineoplastic agents. Treatment advances have
been largely empirical, with improvements in surgical technique and
the delivery of radiation therapy, leading to combined modality
therapies that have improved outcomes for many patients. Loss of
normal growth regulatory mechanisms and infinite replicative capacity
are common features of many human malignancies. Successful targeting
of the process whereby malignant cells become or maintain an immortal
state should be an effective strategy for a number of cancers.
Telomerase inhibition represents a new paradigm for, the treatment of
human malignancies. As stated in Specific Aim 3, we will select and
characterize human tumor cell lines and pathologic tumor samples from
patients with representative tumor types of different stages for
telomerase activity and telomere length. In Specific Aim 6, an in
vitro evaluation of compounds identified in the high throughput screen
will be examined against normal, tumor, and leukemia cell lines
representative of the clinical profile studied in Specific Aim 3 to
complement in vitro studies that will be conducted at Geron.
Specifically, experiments will be conducted using cell lines and
cultured primary tumors to examine the effects of a telomerase
inhibitor on growth kinetics, telomerase activity, and telomere
length. In Specific Aim 7 an assay will be developed for the detection
of a candidate telomerase inhibitor(s) in biological materials.
Pharmacology, drug metabolism, and pharmacokinetic studies will be
conducted in order to optimize the bioavailability and activity of the
compound in anticipation of performing animal experiments. In Specific
Aim 8 we will select compounds showing in vitro efficacy and evaluate
their effects on normal, and immunocompromised mice transplanted with
tumor cell lines, primary tumors, or leukemias. Dosing schedules will
be optimized and different routes of administration (p.o., i.v,, i.p.,
s.c.) will be evaluated. The capacity of telomerase inhibitors to
block the development of tumors, to regress established tumors with
or without chemotherapy, and/or to prevent metastasis will be
measured. Quantitative measurements of tumor burden and residual
disease will be determined by sensitive serologic, fluorescence,
chromophilic, or molecular techniques. Telomerase levels and telomere
length will be measured in control and treated tumors as a function
of growth rate and time.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Development of SL-101, An Immunotoxin that Targets Cancer Stem Cells
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批准号:7219249
-
项目类别:
-
资助金额:$17.48万
-
财政年份:2006
-
负责人:MALCOLM A. MOORE
-
依托单位:
CORE--STEM CELL
-
批准号:6668361
-
项目类别:
-
资助金额:$19.94万
-
财政年份:2002
-
负责人:MALCOLM A. MOORE
-
依托单位:
CORE--STEM CELL
-
批准号:6501590
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项目类别:
-
资助金额:$19.94万
-
财政年份:2001
-
负责人:MALCOLM A. MOORE
-
依托单位:
ADENOVECTORS FOR DELIVERY OF HEMATOPOIETIC GROWTH FACTORS AND RECEPTORS
-
批准号:6501114
-
项目类别:
-
资助金额:$12.63万
-
财政年份:2001
-
负责人:MALCOLM A. MOORE
-
依托单位:
CORE--STEM CELL
-
批准号:6365784
-
项目类别:
-
资助金额:$19.94万
-
财政年份:2000
-
负责人:MALCOLM A. MOORE
-
依托单位:
ADENOVECTORS FOR DELIVERY OF HEMATOPOIETIC GROWTH FACTORS AND RECEPTORS
-
批准号:6355594
-
项目类别:
-
资助金额:$28.77万
-
财政年份:2000
-
负责人:MALCOLM A. MOORE
-
依托单位:
FACTORS INFLUENCING STEM CELL AND PLATELET PRODUCTION
-
批准号:6490619
-
项目类别:
-
资助金额:$34.19万
-
财政年份:1999
-
负责人:MALCOLM A. MOORE
-
依托单位:
FACTORS INFLUENCING STEM CELL AND PLATELET PRODUCTION
-
批准号:6343629
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项目类别:
-
资助金额:$33.32万
-
财政年份:1999
-
负责人:MALCOLM A. MOORE
-
依托单位:
FACTORS INFLUENCING STEM CELL AND PLATELET PRODUCTION
-
批准号:6139299
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项目类别:
-
资助金额:$32.49万
-
财政年份:1999
-
负责人:MALCOLM A. MOORE
-
依托单位:
ADENOVECTORS FOR DELIVERY OF HEMATOPOIETIC GROWTH FACTORS AND RECEPTORS
-
批准号:6258920
-
项目类别:
-
资助金额:$12.87万
-
财政年份:1999
-
负责人:MALCOLM A. MOORE
-
依托单位:
FACTORS INFLUENCING STEM CELL AND PLATELET PRODUCTION
-
批准号:2729734
-
项目类别:
-
资助金额:$33.1万
-
财政年份:1999
-
负责人:MALCOLM A. MOORE
-
依托单位:
ADENOVECTORS FOR DELIVERY OF HEMATOPOIETIC GROWTH FACTORS AND RECEPTORS
-
批准号:6110876
-
项目类别:
-
资助金额:$12.87万
-
财政年份:1998
-
负责人:MALCOLM A. MOORE
-
依托单位:
EXPERIMENTAL THERAPEUTICS
-
批准号:6103093
-
项目类别:
-
资助金额:$15.02万
-
财政年份:1998
-
负责人:MALCOLM A. MOORE
-
依托单位:
EXPERIMENTAL THERAPEUTICS
-
批准号:6237586
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项目类别:
-
资助金额:$14.44万
-
财政年份:1997
-
负责人:MALCOLM A. MOORE
-
依托单位:
ADENOVECTORS FOR DELIVERY OF HEMATOPOIETIC GROWTH FACTORS AND RECEPTORS
-
批准号:6242841
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项目类别:
-
资助金额:$13.2万
-
财政年份:1997
-
负责人:MALCOLM A. MOORE
-
依托单位:
STEM CELL ISOLATION CHARACTERIZATION AND AMPLIFICATION
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批准号:3365674
-
项目类别:
-
资助金额:$33.89万
-
财政年份:1991
-
负责人:MALCOLM A. MOORE
-
依托单位:
STEM CELL ISOLATION CHARACTERIZATION AND AMPLIFICATION
-
批准号:3365673
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项目类别:
-
资助金额:$32.58万
-
财政年份:1991
-
负责人:MALCOLM A. MOORE
-
依托单位:
STEM CELL ISOLATION CHARACTERIZATION AND AMPLIFICATION
-
批准号:2223030
-
项目类别:
-
资助金额:$33.43万
-
财政年份:1991
-
负责人:MALCOLM A. MOORE
-
依托单位:
STEM CELL ISOLATION CHARACTERIZATION AND AMPLIFICATION
-
批准号:3365672
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项目类别:
-
资助金额:$30.81万
-
财政年份:1991
-
负责人:MALCOLM A. MOORE
-
依托单位:
RETROVIRAL GENE TRANSFER INTO HUMAN PROGENITORS
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批准号:3243859
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项目类别:
-
资助金额:$23.96万
-
财政年份:1990
-
负责人:MALCOLM A. MOORE
-
依托单位:
海外基金