Cancerforskningsfondet Af 1989

Cancerforskningsfonden Af 1989

Cancerforskiningsfonden Af 1989

Charles Pyke

Vincent Ellis

Niels Behrendt

Ettore Appella

Eeva-Marjatta Salonen

Michael Ploug

Keld Dano Slashed

Ross W Stephens

Francesco Blasi

Maria Vittoria Cubellis

Hannele Tapiovaara

Ann Louring Roldan

Maria Teresa Masucci

Antti Vaheri

Peter Kristensen

Nils Bruenner

Keld Dan&oslash;

Ebbe Ro Slashednne

Wolf-Dieter Schleuning

Keld Dano

Ebbe Ronne

Lisbeth Birk M&oslash;ller

Leif Ro Lund

Lisbeth Birk Mo Slashedller

Jari Pollanen

Leif R&oslash;ge Lund

L&aacute;szlo Patthy

Ebbe R&oslash;nne

Jan Gr&oslash;ndahl-Hansen

Gunilla Hoyer-Hansen

Laszlo Patthy

John R&oslash;mer

Wd Schleuning

Helle Pedersen

Nils Br&uuml;nner

Heine H&oslash;i Hansen

Gunilla Ho slashedyer-Hansen

Jari P&ouml;ll&auml;nen

Activation of plasminogen to plasmin is inhibited by preventing the binding of a receptor binding form of urokinase-type plasminogen activator to a urokinase-type plasminogen activator receptor in a mammal, thereby preventing the urokinase-type plasminogen activator from converting plasminogen into plasmin. DNA fragments which encode for soluble, active fragments of the urokinase-type plasminogen activator receptor are provided.

Urokinase-type plasminogen activator receptor

The present invention relates to methods for inhibiting malignant tumour growth, invasion and/or metastasis in a patient, the method comprising suppressing the inhibitory activity of an inhibitor of a protease or of a non-proteolytic matrix-degrading enzyme (IPNME) in malignant tumour tissue or potential malignant tumour tissue. The suppression may be brought about by administering compounds interacting with the IPNME, but also administration of compounds interacting with transcription of genes encoding the IPNME is a possibility. The invention also relates to methods of selecting and identifying compounds in the therapeutical methods, as well of the use of such compounds in the treatment of malignancies.

Suppression of inhibitors

A monoclonal or polyclonal antibody directed against urokinase plasminogen activator receptor (u-PAR), or a subsequence, analogue or glycosylation variant thereof. Antibodies are disclosed which react with free u-PAR or with complexes between u-PA and u-PAR and which are capable of 1) catching u-PAR in ELISA, or 2) detecting u-PAR, e.g. in blotting, or 3) in radioimmunoprecipitation assay precipitate purified u-PAR in intact or fragment form, or 4) is useful for immunohistochemical detection of u-PAR, e.g. in immunostaining of cancer cells, such as in tissue sections at the invasive front, or 5) inhibits the binding of pro-u-PA and active u-PA and thereby inhibits cell surface plasminogen activation. Methods are disclosed 1) for detecting or quantifying u-PAR, 2) for targeting a diagnostic to a cell containing a u-PAR on the surface, 3) for preventing or counteracting proteolytic activity in a mammal. Methods for for selecting a substance suitable for inhibiting u-PA/u-PAR interaction, for preventing or counteracting localized proteolytical activity in a mammal, for inhibiting the invasion and/or metastasis comprise the use of the antibodies and of nude mice inoculated with human cancer cells which are known to invade and/or metastasize in mice and having a distinct color, f.x. obtained by means of an enzyme and a chromogenic substrate for the enzyme, the color being different from the cells of the mouse.

Antibodies and their use

Activation of plasminogen to plasma is inhibited by preventing the binding of a receptor binding form of urokinase-type plasminogen activator to a urokinase-type plasminogen activator receptor in a mammal, thereby preventing the urokinase-type plasminogen activator from converting plasminogen into plasmin. DNA fragments which encode for soluble, active fragments of the urokinase-type plasminogen activator are provided.

Vectors and methods for recombinant production of uPA-binding fragments

Urokinase-type plasminogen activator receptor antibodies

Growing community of inventors

Søborg, Denmark

Charles Pyke