Functional role of adrenomedullin (am) and the gene-related...

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 14/575 (2006.01) A61K 38/08 (2006.01) A61K 38/10 (2006.01) A61K 38/22 (2006.01) A61K 39/395 (2006.01) C07H 21/04 (2006.01) C07K 7/06 (2006.01) C07K 7/08 (2006.01) C07K 16/26 (2006.01) G01N 33/53 (2006.01) G01N 33/74 (2006.01) A61K 38/00 (2006.01) A61K 39/00 (2006.01)

Patent

CA 2229741

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 shown that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal antibody MoAb-G6, which neutralizes AM bioactivity, was shown by the methods of the present invention to increase insulin release fivefold, an effect that was reversed by the addition of synthetic AM.

Les procédés de la présente inveniton metnent en évidence que l'adrénomédulline (AM) est exprimée dans des lignées cellulaires cancéreuses humaines d'origine et de fonctions diverses sous forme d'un facteur de croissance autocrine universel entraînant une prolifération néoplasique. La présente invention concerne de peptides et anticorps d'AM utilisés dans des compositions thérapeutiques, pharmacologiques et physiologiques. La présente invention concerne de plus des procédées de diagnostic, de traitement et de prévention de maladies, ces procédées mettant en oeuvre des compositions comprenant les peptides et anticorps d'AM. Les procédés de la présente invention s'appliquent également à des modèles expérimentaux destinés à être utilisés dans l'identification du rôle de l'AM en physiologie pancréatique. Les procédés relatifs aux îlots pancréatiques isolés chez le rat ont mis en évidence que l'AM inhibe la sécrétion de l'insuline de manière proportionnelle à la dose administrée. L'anticorps monoclonal MoAb-G6, qui neutralise la bioactivité d'AM, a permis de démontrer que la libération de l'insuline était multipliée par cinq, effet rendu contraire par l'addition d'AM synthétique.

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