DIFFERENT FORMS OF PROSTATE-SPECIFIC ANTIGEN IN CANCER
癌症中不同形式的前列腺特异性抗原
基本信息
- 批准号:2414269
- 负责人:
- 金额:$ 8.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1993
- 资助国家:美国
- 起止时间:1993-05-01 至 1999-02-28
- 项目状态:已结题
- 来源:
- 关键词:SDS polyacrylamide gel electrophoresis alpha 1 antitrypsin antibody specificity biomarker chemical synthesis chymotrypsin chymotrypsin inhibitor diagnosis design /evaluation early diagnosis enzyme activity enzyme biosynthesis enzyme complex enzyme linked immunosorbent assay human subject immunochemistry isozymes laboratory mouse laboratory rabbit macroglobulins neoplasm /cancer diagnosis neoplasm /cancer genetics nucleic acid sequence oncoproteins prostate neoplasms prostate specific antigen protein sequence semen serum trypsin inhibitors western blottings zymogens
项目摘要
Prostate cancer is a major form of cancer in U.S. males. Prostate
specific antigen (PSA) serum levels provide a good marker for prostate
cancer, but assay of total serum PSA alone cannot distinguish early
cancer from a number of other prostatic diseases. Numerous invasive and
expensive procedures may be required for diagnosis. Preliminary results
of the applicant indicate that PSA exists in different forms in semen and
in serum and that different PSA forms are found in the sera of different
patients. This proposal requests funding to establish a new independent
research area for the applicant, in which the various forms of PSA will
be identified, assayed in a large number of patients with borderline
elevations of total PSA, and correlated to the diagnosis. The long-term
goal is to provide the biochemical and immunochemical basis for clinical
assays of forms of PSA that distinguish early prostate cancer from other
conditions that cause modestly elevated PSA. It is hypothesized: a) that
PSA as an enzyme may have a different role in prostate cancer than in
benign conditions of the prostate or prostatitis; b) that the enzyme PSA
is secreted in inactive zymogen form, activated under particular
pathophysiological conditions, and inactivated by proteolytic cleavage or
by combining with available protease inhibitors to form complexes; c)
that the local environment and the type of epithelial cells that secrete
PSA differ in prostate cancer compared to other syndromes; d) that the
activators, proteolytic enzymes and inhibitors to which PSA is exposed
differ in cancer compared to other syndromes; e) that the time elapsed
between secretion of PSA and its translocation to the blood differs in
cancer versus other syndromes; f) that the spectrum of enzymes and
inhibitors in prostatic fluid is different from that of blood; and g)
that all of the above lead to the generation of different forms of PSA in
prostate cancer from those found in other syndromes. The applicant's
previous experience in elucidating the molecular forms and inhibitors of
other enzymes can be readily applied to the identification and
measurement of different forms of PSA in patients. The specific aims
include: 1) isolation of PSA from semen, characterization of its
reactivity with various protease inhibitors, and preparation of standard
PSA-inhibitor complexes; 2) development of sandwich ELISA assays for PSA
complexes with any significant inhibitors, including
alpha1-antichymotrypsin, protein C inhibitor, alpha2-macroglobulin, and
others that may be identified, using standard complexes; 3)
identification of different forms of PSA in semen and in blood by
immunoblot analysis and sequencing studies; 4) development of antibodies
and ELISA-assays specific for particular forms or sequences of PSA; 5)
application of immunoblot analysis, sandwich ELISAS and other assays
which are developed to large numbers of patient sera, especially those in
the borderline PSA range; and 6) correlation of the spectrum and levels
of different PSA forms to patient diagnosis to establish clinical
usefulness of the assays. The proposed studies also provide novel basic
knowledge about PSA and its inhibitors that may help to understand the
physiological function and regulation of this enzyme.
前列腺癌是美国男性癌症的主要形式。 前列腺
特定的抗原(PSA)血清水平为前列腺提供了良好的标记
癌症,但仅对血清PSA的总测定无法尽早区分
来自许多其他前列腺疾病的癌症。 许多侵入性和
诊断可能需要昂贵的程序。 初步结果
申请人表明PSA以不同形式存在于精液中,
在血清中,在不同的血清中发现了不同的PSA形式
患者。 该提案要求资金建立新的独立
申请人的研究区域,其中各种形式的PSA将会
被识别,在大量边缘患者中进行测定
总PSA的升高,与诊断相关。 长期
目标是为临床提供生化和免疫化学基础
将早期前列腺癌与其他其他PSA形式的测定
导致PSA升高的条件。 它是假设的:a)
PSA作为酶在前列腺癌中可能具有不同的作用
前列腺炎或前列腺炎的良性疾病; b)酶PSA
以非活性的酶原形式分泌,在特定下激活
病理生理状况,并被蛋白水解裂解灭活或
通过与可用的蛋白酶抑制剂结合形成复合物; c)
那是当地环境和分泌的上皮细胞的类型
与其他综合征相比,前列腺癌的PSA不同。 d)那个
暴露于PSA的激活剂,蛋白水解酶和抑制剂
与其他综合征相比,癌症不同; e)时间过去了
在PSA的分泌与血液的易位之间有所不同
癌症与其他综合症; f)酶和
前列腺液中的抑制剂与血液不同。和g)
以上所有这些都导致产生不同形式的PSA
从其他综合征中发现的前列腺癌。 申请人的
以前阐明分子形式和抑制剂的经验
其他酶可以很容易地应用于识别和
在患者中测量不同形式的PSA。 具体目标
包括:1)从精液中隔离PSA,其表征
与各种蛋白酶抑制剂的反应性,并制备标准
PSA抑制剂复合物; 2)开发PSA的三明治ELISA分析
与任何明显抑制剂的复合物,包括
α1-抗胰蛋白酶,蛋白C抑制剂,α2-巨球蛋白和
使用标准复合物可以识别的其他人; 3)
通过
免疫印迹分析和测序研究; 4)开发抗体
和elisa--指定PSA的特定形式或序列; 5)
免疫印迹分析,三明治ELISA和其他测定的应用
这些开发到大量患者血清,尤其是那些
边界PSA范围; 6)光谱和水平的相关性
患者诊断的不同PSA形式以建立临床
测定的有用性。 拟议的研究还提供了新的基本
有关PSA及其抑制剂的知识,可能有助于了解
该酶的生理功能和调节。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('MARY J HEEB', 18)}}的其他基金
New Aspects of Protein S Anticoagulant Activity
Protein S 抗凝活性的新方面
- 批准号:
7524692 - 财政年份:2008
- 资助金额:
$ 8.8万 - 项目类别:
New Aspects of Protein S Anticoagulant Activity
Protein S 抗凝活性的新方面
- 批准号:
7895735 - 财政年份:2008
- 资助金额:
$ 8.8万 - 项目类别:
New Aspects of Protein S Anticoagulant Activity
Protein S 抗凝活性的新方面
- 批准号:
7664967 - 财政年份:2008
- 资助金额:
$ 8.8万 - 项目类别:
FORMS OF PROSTATE SPECIFIC ANTIGEN AND HK2 IN CANCER
癌症中前列腺特异性抗原和 HK2 的形式
- 批准号:
6150143 - 财政年份:1993
- 资助金额:
$ 8.8万 - 项目类别:
DIFFERENT FORMS OF PROSTATE-SPECIFIC ANTIGEN IN CANCER
癌症中不同形式的前列腺特异性抗原
- 批准号:
2100587 - 财政年份:1993
- 资助金额:
$ 8.8万 - 项目类别:
DIFFERENT FORMS OF PROSTATE-SPECIFIC ANTIGEN IN CANCER
癌症中不同形式的前列腺特异性抗原
- 批准号:
3460768 - 财政年份:1993
- 资助金额:
$ 8.8万 - 项目类别:
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