PRE TARGETED THERAPY USING THE NOVEL TACHYKININ (NK) REC
PRE TARGETED THERAPY USING THE NOVEL TACHYKININ (NK) REC
批准号:
6175066
负责人:
ROSALYN D BLUMENTHAL
金额:
$14.25万
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-07-01 至 2002-06-30
关键词:
athymic mouse autoradiography breast neoplasms cell line combination cancer therapy cytokine doxorubicin female indium inhibitor /antagonist neoplasm /cancer chemotherapy neoplasm /cancer radionuclide therapy neuropeptide receptor nonhuman therapy evaluation paclitaxel radionuclides stimulant /agonist substance P women's health
中文摘要
描述:(申请人的描述)
这些研究的长期目标是开发肽靶向的用途
新的神经内分泌神经激肽(NK)受体系统,
在乳腺癌中组成型过表达。未标记的P物质(SP),或
将在体外评价选择性结合NK-1或NK-2的类似物
和体内。俄歇发射放射性核素(例如,IN-111)将被螯合,
NK-受体靶向剂。在载体的细胞内化后,In-111
预期具有显著的放射性毒性作用,
转化为体内肿瘤生长控制效果。这些研究已经
细分为四个假设驱动的目标。为了实现既定目标,我们
将:(1)利用培养的乳腺癌细胞系建立合适的载体
治疗剂的NK受体系统。的体外细胞毒性
未缀合的SP激动剂和拮抗剂(氨基末端片段6-11,
CP-96,345)进行评价。结果将与运营商进行比较
含有放射性铟。结合亲和力、内化率和细胞
将确定放射性核素的保留。(2)确定是否
NK-1和NK-2结合位点的数量受暴露于细胞因子的影响
(e.g., IFN α、IL-1、IL-6)或化疗(例如,紫杉醇、阿霉素)。(三)
建立NK导向载体在乳腺肿瘤中的体内生物分布
异种移植摄取将使用全组织计数、全
动物成像和组织切片的显微放射自显影。(4)评价
基于SP的载体在皮下乳腺肿瘤模型中的治疗功效
和微转移(心内MDA-231)乳腺模型。潜在GI和
将通过监测体重变化和白色
血细胞和血小板计数。还将监测小鼠是否可能
神经毒性
英文摘要
DESCRIPTION: (Applicant's Description)
The long-term goal of these studies is to develop the use of peptide taraeting
for the novel neuroendocrine neurokinin (NK) receptor system, which is
constitutively overexpressed in breast cancer. Unlabeled substance P (SP), or
analogues that selectively bind either NK-1 or NK-2 will be evaluated in vitro
and in vivo. Auger-emitting radionuclides (e.g., IN-111) will be chelates to
NK-Receptor targeting agents. Upon cell internalization of the carrier, In-111
is expected to have substantial radiotoxic effects, which are expected to
translate into tumor growth controt effects in vivo. The studies have been
subdivided into four hypothesis-driven aims. To achieve our stated goal, we
will: (1) Use cultured breast cancer lines to establish an appropriate carrier
of therapeutic agents to the NK-receptor system. The in vitro cytotoxicity of
unconjugated SP agonist and antagonists (amino terminal fragment 6-11,
CP-96,345) will be evaluated. Results will be compared with carriers
containing radioindium. Binding affinity, internalization rate, and cell
retention of the radionuclide will be established. (2) Determine whether the
number of NK-1 and NK-2 binding sites is affected by exposure to cytokines
(e.g., IFNa, IL-1, IL-6) or chemotherapy (e.g., taxol, doxorubicin). (3)
Establish the biodistribution of NK-directed carriers in vivo in breast tumor
xenografts. Uptake will be determined using whole tissue counting, whole
animal imaging and microautoradiography of tissue sections. (4) Evaluate the
therapeutic efficacy of SP-based carriers in a subcutaneous breast tumor model
and a micrometastatic (intracardiac MDA-231) breast model. Potential GI and
marrow toxicity will be assessed by monitoring body weight changes and white
blood cell and platelet counts. Mice will also be monitored for possible
neurotoxicity.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Animal Studies
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批准号:7728853
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项目类别:
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资助金额:$19.51万
-
财政年份:2008
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负责人:ROSALYN D BLUMENTHAL
-
依托单位:
Chronobiological Principles to Maximize Efficacy of Alt*
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批准号:6570707
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项目类别:
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资助金额:$29.25万
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财政年份:2003
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负责人:ROSALYN D BLUMENTHAL
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依托单位:
PRE-CLINICAL COMBINATION CHEMO- AND RADIOANTIBODY THERAP
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批准号:6725403
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项目类别:
-
资助金额:$97.71万
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财政年份:2002
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负责人:ROSALYN D BLUMENTHAL
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依托单位:
PRE-CLINICAL COMBINATION CHEMO/RADIOANTIBODY THERAPY
-
批准号:6376968
-
项目类别:
-
资助金额:$94.87万
-
财政年份:2002
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负责人:ROSALYN D BLUMENTHAL
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依托单位:
PRE-CLINICAL COMBINATION CHEMO- AND RADIOANTIBODY THERAP
-
批准号:6620132
-
项目类别:
-
资助金额:$92.24万
-
财政年份:2002
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
CORE--ANIMAL LABORATORY
-
批准号:6300383
-
项目类别:
-
资助金额:$29.24万
-
财政年份:2000
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负责人:ROSALYN D BLUMENTHAL
-
依托单位:
EFFECT OF TARGETED LOW DOSE RADIATION TREATMENT ON TUMOR OXYGENATION
-
批准号:6353194
-
项目类别:
-
资助金额:$1.22万
-
财政年份:2000
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
PRE TARGETED THERAPY USING THE NOVEL TACHYKININ (NK) REC
-
批准号:6378018
-
项目类别:
-
资助金额:$14.25万
-
财政年份:2000
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
FACTORS IN COMBINED RADIOIMMUNOTHERAPY AND CHEMOTHERAPY IN CANCER MANAGEMENT
-
批准号:6300386
-
项目类别:
-
资助金额:$29.24万
-
财政年份:2000
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
CORE--ANIMAL LABORATORY
-
批准号:6102693
-
项目类别:
-
资助金额:$29.24万
-
财政年份:1999
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
FACTORS IN COMBINED RADIOIMMUNOTHERAPY AND CHEMOTHERAPY IN CANCER MANAGEMENT
-
批准号:6102688
-
项目类别:
-
资助金额:$29.24万
-
财政年份:1999
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
EFFECT OF TARGETED LOW DOSE RADIATION TREATMENT ON TUMOR OXYGENATION
-
批准号:6206520
-
项目类别:
-
资助金额:$1.22万
-
财政年份:1999
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
FACTORS IN COMBINED RADIOIMMUNOTHERAPY AND CHEMOTHERAPY IN CANCER MANAGEMENT
-
批准号:6269480
-
项目类别:
-
资助金额:$28.13万
-
财政年份:1998
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
CORE--ANIMAL LABORATORY
-
批准号:6269485
-
项目类别:
-
资助金额:$28.13万
-
财政年份:1998
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
EFFECT OF TARGETED LOW DOSE RADIATION TREATMENT ON TUMOR OXYGENATION
-
批准号:6123362
-
项目类别:
-
资助金额:$1.3万
-
财政年份:1998
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
CORE--ANIMAL LABORATORY
-
批准号:6237205
-
项目类别:
-
资助金额:$27.01万
-
财政年份:1997
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
FACTORS IN COMBINED RADIOIMMUNOTHERAPY AND CHEMOTHERAPY IN CANCER MANAGEMENT
-
批准号:6237200
-
项目类别:
-
资助金额:$27.01万
-
财政年份:1997
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
RADIOIMMUNOTHERAPY AND TUMOR VASCULAR PHYSIOLOGY
-
批准号:2101530
-
项目类别:
-
资助金额:$15.75万
-
财政年份:1994
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
RADIOIMMUNOTHERAPY AND TUMOR VASCULAR PHYSIOLOGY
-
批准号:6137523
-
项目类别:
-
资助金额:$28.03万
-
财政年份:1994
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负责人:ROSALYN D BLUMENTHAL
-
依托单位:
RADIOIMMUNOTHERAPY AND TUMOR VASCULAR PHYSIOLOGY
-
批准号:2101529
-
项目类别:
-
资助金额:$11.08万
-
财政年份:1994
-
负责人:ROSALYN D BLUMENTHAL
-
依托单位:
海外基金