Kernforschungszentrum Karlsruhe Gmbh

Universitaet Karlsruhe

Deutsches Krebsforschungszentrum

Boehringer Ingelheim International Gmbh

Boehringer Ingelheim Pharmaceuticals, Inc.

Forschungszentrum Karlsruhe Gmbh

Krebsforschungszentrum

Georg-Speyter-Haus Chemotherapeutisches Forschungsinstitut

Peter Herrlich

Helmut Ponta

Achim Wenzel

Siegfried Matzku

Ursula Guenthert

Kim Untae

Karl-Heinz Heider

Thorsten Heinzel

Jonathan Sleeman

Margot Zoller

Peter Dall

Martin Göttlicher

Bernd Groner

Steven T Pals

The present invention relates to the use of the drug valproic acid and derivatives thereof as inhibitors of enzymes having histone deacetylase activity. The invention also relates to the use of those compounds for the manufacture of a medicament for the treatment of diseases which are associated with hypoacetylation of histones or in which induction of hyperacetylation has a beneficial effect for example by induction of differentiation and/or apoptosis in transformed cells.

Valproic acid and derivatives thereof as histone deacetylase inhibitors

The present invention relates to a novel composition for identifying and suppressing the growth of tumor cells, which comprises antibodies which react with proteins having N-glycosidically bonded saccharides.

Agent for identifying and treating metastasizing tumors

Process for detecting a variant CD44 gene product

The present invention relates to a method of reducing or suppressing an immune response with antibodies specific for variants of the glycoprotein CD44. The invention further relates to a method of preventing or treating an immunoregulatory disorder or disease with these antibodies.

Methods to suppress an immune response with variant CD44-specific

The inventon relates to antibodies that react with a variant epilope in the extracellular region of a variant CD44 polypeptide, wherein the variant epitope has the amino acid sequence: I S S T I S T T P R A P D H T K Q N Q D W T Q W N P S H S N P E V L L Q T T T R M T D V D R N G T T A Y E G N W N P E A H P P L I H H E H H E E E E T P H S T S T I O A T P S S T T E E T A T Q K E Q W F G N R W H E G Y R Q T P R E D S H S T T G T A A A S A H T S H P M Q G R T T P S P E D S S W T D F F N P I S H P M G R G H Q A G R R (residues 53-219 of SEQ ID NO:4). Methods of using the antibodies to identify variant epitopes also are provided.

Antibodies that react with variant CD44 surface proteins

A monoclonal antibody (MAb1.1ASML) directed against a surface glycoprotein of the metastasizing rat pancreatic carcinoma cell line BSp73ASML, was used to identify and isolate a complementary DNA (cDNA) clone capable of encoding for a glycoprotein with partial homology to CD44, a presumed adhesion molecule. This clone, which was subsequently designated pMeta-1, contains an additional extracellular domain of 162 amino acids inserted into the CD44 protein between amino acid positions 223 and 247 (by analogy to human and murine CD44). This new variant was expressed only in the metastasizing cell lines of two rat tumors, the pancreatic carcinoma BSp73 and the mammary adenocarcinoma 13762NF; it was not expressed in non-metastasizing tumor cell lines nor in normal rat tissues. Overexpression of pMeta-1 in the nonmetastasizing BSp73AS cell line suffices to establish full metastatic behavior. The variant-specific rat CD44 sequence was used to isolate a cDNA clone encoding for a human homologue as well.

Human and rat variants of glycoprotein CD44 containing an additional

DNA encoding variant CD44 surface proteins associated with metastatic

Growing community of inventors

Karlsruhe, Germany

Peter Herrlich