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Functional role of adrenomedullin (AM) and the gene related product (PAMP) in human pathology and physiology

机译:肾上腺髓质素(AM)和基因相关产物(PAMP)在人类病理和生理学中的功能作用

摘要

The methods of the present invention demonstrate that adrenomedullin (AM) is expressed in human cancer cell lines of diverse origin and functions as a universal autocrine growth factor driving neoplastic proliferation. The present invention provides for AM peptides and AM antibodies useful in therapeutic, pharmacologic and physiologic compositions. The present invention additionally provides for methods of diagnosis, treatment and prevention of disease utilizing compositions comprising the AM peptides and antibodies of the present invention. The methods of the present invention also provide for experimental models for use in identifying the role of AM in pancreatic physiology. The methods pertaining to rat isolated islets have show that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal antibody MoAb-G6, which neutralizes AM bioactivity, was show by the methods of the present invention to increase insulin release fivefold, an effect that was reversed by the addition of synthetic AM.
机译:本发明的方法证明肾上腺髓质素(AM)在人类起源的多种癌细胞系中表达,并作为驱动肿瘤增殖的通用自分泌生长因子起作用。本发明提供了可用于治疗,药理和生理学组合物中的AM肽和AM抗体。本发明还提供了利用包含本发明的AM肽和抗体的组合物诊断,治疗和预防疾病的方法。本发明的方法还提供了用于鉴定AM在胰腺生理中的作用的实验模型。关于大鼠分离的胰岛的方法已经表明,AM以剂量依赖的方式抑制胰岛素的分泌。通过本发明的方法显示出中和AM生物活性的单克隆抗体MoAb-G6将胰岛素释放增加了五倍,这种作用被添加合成AM所逆转。

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