TREATMENT OF OSTEOSARCOMA WITH INTEGRIN-PERTURBING DRUGS
TREATMENT OF OSTEOSARCOMA WITH INTEGRIN-PERTURBING DRUGS
批准号:
3202665
负责人:
VIRGIL L WOODS
金额:
$12.4万
依托单位国家:
美国
项目类别:
财政年份:
1993
资助国家:
美国
项目状态:
已结题
起止时间:
1993-09-30 至 1996-09-29
中文摘要
迫切需要更有效的治疗和缓和手段
英文摘要
There is a pressing need for more efficacious treatment and palliative
modalities for osteosarcoma as well as other solid tumors. Substantial
in vitro and in vivo evidence, derived primarily from the study of
cultured osteosarcoma and melanoma cell lines, indicates that integrin-
type cell surface receptors for extracellular matrices present on
malignant cells play critical roles in mediating the invasive and
metastatic properties of solid tumors. Peptides containing the Arg-Gly-
Asp (RGD) tripeptide sequence and certain integrin-specific monoclonal
antibodies can block the ligand binding site of many of the integrins.
These agents have found diverse applications ranging from wound healing
to treatment of heart attacks and some of these applications are
currently in clinical trials.
One promising use of these agents is to prevent tumor invasion and
metastasis. Model systems employing animal tumors have shown that these
agents can inhibit tumor invasion and lung implantation of intravenously
administered murine tumor cells. While many anti-human integrin
monoclonal antibodies had been produced by ourselves and others, few
monoclonals reactive with murine integrins are available and therefore
the ability of anti-integrin monoclonals to modulate human tumor invasion
and metastasis in vivo is untested. Further exploration of the potential
clinical utility of integrin-reactive peptides as anti-tumor drugs has
been hindered by the fact that the peptides utilized to date have
relatively low affinities for the critical integrins, and their blood
half-lives are short. The purpose of this project is to test our
improved forms of anti-integrin peptides and monoclonal antibodies for
their ability to modulate the in vivo invasiveness and metastatic ability
of human primary osteosarcoma. These agents as well as our next
generation of anti-integrin reagents will be produced and tested for
their ability to modulate in vivo growth and metastasis of human
osteosarcoma transplanted to athymic nude mice employing a novel
osteosarcoma orthotopic transplantation model we have developed. Peptide
and monoclonal antibody design will follow the same approaches that have
been extremely successful in the development of RGD peptides for the
inhibition of platelet aggregation. We anticipate that a new class of
anti-metastatic drugs will result from these studies and that these
agents will prove to be clinically useful as adjuncts to the treatment
of human osteosarcoma and other solid tumors.
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资助金额:$48.73万
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财政年份:2003
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Enhanced Crystallography of Cancer-Implicated Proteins
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资助金额:$85.91万
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财政年份:2003
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Enhanced Crystallography of Cancer-Implicated Proteins
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财政年份:2003
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依托单位:
TREATMENT OF OSTEOSARCOMA WITH INTEGRIN-PERTURBING DRUGS
-
批准号:2099212
-
项目类别:
-
资助金额:$13.4万
-
财政年份:1993
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负责人:VIRGIL L WOODS
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依托单位:
TREATMENT OF OSTEOSARCOMA WITH INTEGRIN-PERTURBING DRUGS
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批准号:2099211
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项目类别:
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资助金额:$12.64万
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财政年份:1993
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负责人:VIRGIL L WOODS
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依托单位:
STRUCTURE AND FUNCTION OF PLATELET GPIIB/IIIA
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批准号:3341506
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项目类别:
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资助金额:$18.69万
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财政年份:1983
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负责人:VIRGIL L WOODS
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依托单位:
STRUCTURE AND FUNCTION OF PLATELET GPIIB/IIIA
-
批准号:3341504
-
项目类别:
-
资助金额:$16.99万
-
财政年份:1983
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负责人:VIRGIL L WOODS
-
依托单位:
STRUCTURE AND FUNCTION OF PLATELET MEMBRANE GPIIB/IIIA
-
批准号:3341502
-
项目类别:
-
资助金额:$13.69万
-
财政年份:1983
-
负责人:VIRGIL L WOODS
-
依托单位:
STRUCTURE AND FUNCTION OF PLATELET GPIIB/IIIA
-
批准号:3341503
-
项目类别:
-
资助金额:$17.24万
-
财政年份:1983
-
负责人:VIRGIL L WOODS
-
依托单位:
STRUCTURE AND FUNCTION OF PLATELET GPIIB/IIIA
-
批准号:3341505
-
项目类别:
-
资助金额:$18.2万
-
财政年份:1983
-
负责人:VIRGIL L WOODS
-
依托单位:
STRUCTURE AND FUNCTION OF PLATELET GPIIB/IIIA
-
批准号:3341501
-
项目类别:
-
资助金额:$16.66万
-
财政年份:1983
-
负责人:VIRGIL L WOODS
-
依托单位:
海外基金