Ludwig Institute for Cancer Research Limited

Ulf G Hellman

Carl-Henrik Heldin

Christer Wernstedt

Kohei Miyazono

Hidenori Ichijo

Lars Ronnstrand

Fumimaro Takaku

Bengt Westermark

Leonel Jorge Gonez

Jan Saras

Fuyuki Ishikawa

Maria Andersson

Gudrun Backstrom

Ulla Engstrom

Arne Stman

Ulf Eriksson

Petra Franzen

Andras Simon

Lena Claesson-Welsh

Anders Olofsson

Marta Lomnytska

Pontus Aspenstrom

Anna Dubrovska

Anita Moren

Tetsuto Kanzaki

Nataliya Volodko

Pontus Aspenstr&ouml;m

Petra Franz&eacute;n

Flemming S Vassbotn

Serhiy Souchelnytskyi

Carl-Hendrik Heldin

Plasma samples of ovarian and breast cancer patients were used to search for markers of cancer, using two-dimensional gel electrophoresis and MALDI TOF mass spectrometry. Truncated forms of cytosolic serine hydroxymethyl transferase (cSHMT), T-box transcription factor 3 (Tbx3) and utrophin were aberrantly expressed in samples from cancer patients, as compared to samples from noncancer cases. Aberrant expression of proteins was validated by immunoblotting of plasma samples with specific antibodies to cSHMT, Tbx3 and utrophin. A cohort of 79 breast and 39 ovarian cancer patients, and 31 individuals who were either healthy or had noncancerous conditions was studied. We observed increased expression of truncated cSHMT, Tbx3 and utrophin in plasma samples obtained from patients at early stages of disease. The results indicate that cSHMT, Tbx3, utrophin and truncated forms thereof can be used as components of multiparameter monitoring of ovarian and breast cancer.

Protein markers for the diagnosis and prognosis of ovarian and breast cancer

The invention describes nucleic acids encoding the PARG protein, including fragments and biologically functional variants thereof. Also included are polypeptides and fragments thereof encoded by such nucleic acids, and antibodies relating thereto. Methods and products for using such nucleic acids and polypeptides also are provided.

PARG, a GTPase activating protein which interacts with PTPL1

Isolated nucleic acid molecules encoding PARG, a GTPase activating

Platelet-derived endothelial cell growth factor (PD-ECGF) is a 45 kDa endothelial cell mitogen that has been purified to homogeneity from human platelets. It does not bind to heparin and does not stimulate the proliferation of fibroblasts, in contrast to other endothelial mitogens of the fibroblast growth factor (FGF) family. PD-ECGF appears to be the only endothelial cell growth factor in human platelets and recent data indicate that it has angiogenic activity in vitro, i.e., the ability to stimulate the formation of new blood vessels and chemotactic activity, in vitro. The present invention provides a homogeneous PD-ECGF in substantially greater yields than available in the past, the primary structure of PD-ECGF, antibodies against PD-ECGF, clones of its cDNA, and variants thereof. The invention also provides a therapeutic preparation of PD-ECGF.

Peptides derived from endothelial cell growth factor

The invention relates to a family of substantially pure, receptor like TGF-.beta.1 binding glycoproteins. These molecules are characterized by molecular masses of 160 kd, 70-80 kd, and 30-40 kd as determined by SDS-PAGE, and the ability to bind the TGF-.beta.1 molecule. This family of molecules is useful in identifying and/or quantifying TGF-.beta.1 in a sample, as well as inhibiting its effect on cells. Also described are nucleic acid sequences which code for the protein monomer making up the molecules.

Isolated nucleic acid encoding receptor-like TGF-.beta.1 binding protein

In accordance with this invention, an RPE cell membrane associated protein which has a molecular weight of about 32 kd, as determined by SDS-PAGE, has now been discovered. This protein, referred to an 'p32,' forms an oligomeric protein complex with the previously characterized p63 protein, a component of the membrane receptor for RBP. A nucleic acid molecule which codes for the p32 protein has also been isolated and sequence analysis shows that the p32 protein belongs to the family of short chain alcohol dehydrogenases, and exhibits 11-cis retinol dehydrogenase activity, the enzyme which catalyzes conversion of 11-cis-retinol into 11-cis retinaldehyde.

Isolated nucleic acid molecule which codes for a 32 kDa protein having

Substantially pure receptor like TFG-.beta.1 binding molecules

The invention describes antagonists for PDGF. The antagonists contain amino acids, and may be monomers or dimers. Especially preferred are dimers which bind the PDGF receptors, but prevent dimerization of the bound receptors. Dimerization is necessary for PDGF effect, hence the antagonistic effect. Also described are nucleic acid sequences for making the antagonists, as well as cell lines transfected with the material.

Platelet derived growth factor antagonists

The invention described PDGF modifiers. These are peptides which are derived from wild type PDGF monomers, and function as either agonists or antagonists. Various uses of these are described, as well as recombinant means of production. PDGF-B agonists comprising amino acids 97-180 of the PDGF-B monomer having the cysteines at amino acid residues 124 and 133 substituted, nucleic acid molecules encoding the agonists, plasmids, transformed host cells, and methods for causing receptor dimerization and autophosphorylation in a cell having PDGF-.beta. receptors on its surface comprising administering the PDGF-B agonist form part of the invention.

Platelet derived growth factor agonists

The invention relates to a family of substantially pure, receptor like TGF-.beta.1 binding glycoproteins. These molecules are characterized by molecular masses of 160 kd, 70-80 kd, and 30-40 kd as determined by SDS-PAGE, and the ability to bind the TGF-.beta.1 molecule. This family of molecules is useful in identifying and/or quantifying TGF-.beta.1 in a sample, as well as inhibiting its effect on cells.

Substantially pure receptor like TGF-.beta. 1 binding molecules and uses

DNA encoding platelet derived endothelial cell growth factor (PD-ECGF)

Purified protein known as platelet TGF-.beta.1-BP (transforming growth factor-.beta.1-binding protein) is described. The protein is useful for purposes such as the production of antisera which are useful in identifying complexes containing the binding protein, as well as in formation of labeled probes. Also described are purified DNA which expresses the protein, as well as messenger RNA translated into the protein. The protein contains 16 epidermal growth factors (EGF) like repeats, and 3 repeats not found in other proteins. The DNA for the protein is found to contain consensus sequences for hydroxylation of asparagine/aspartic acid residues, and, in the purified protein beta hydroxylated asparagine residues were found.

Isolated nucleotide sequence expressing human transforming growth

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Uppsala, Sweden

Ulf G Hellman