Abstract: The present invention pertains to methods for classifying tumorous diseases based on their specific genomic DNA methylation profile. The invention provides a method that allows for a classification of a tumor sample obtained from a patient by analysing a multitude, preferably genome wide, collection of CpG positions by comparison to a classification rule derived from a set of methylation data acquired from pre-classified tumor species. The invention is in particular useful for classifying brain tumor samples since brain tumors are characterized by a large variety of distinct tumor species which have different prognostic values and require in the clinic a for each species developed treatment regime.

Abstract: Described is a pharmaceutical composition comprising (a) a parvovirus and (b) an Bcl-2 inhibitor and the use of said composition for treatment of cancer, e.g., a solid tumor. Preferred inhibitors are the BH3 mimetics ABT-737 and ABT-199.

Abstract: Described is a pharmaceutical composition comprising (a) a parvovirus and (b) bevacizumab and the use of said composition for treatment of cancer, e.g., a solid tumor.

Abstract: The present invention relates to modulators, in particular inhibitors, of TSC22D4 activity or expression and their uses for the prevention, treatment, and/or regulation of insulin resistance, metabolic syndrome and/or diabetes and/or for improving insulin sensitivity in mammal. The present invention further relates to screening methods in order to identify these modulators, the use of modulators as identified in the diagnosis of these diseases, as well as kits, comprising materials for performing the methods according to the present invention.

Abstract: The present invention relates to hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) which are versatile vehicles for the specific delivery of compounds to the liver, preferably to hepatocytes, in vitro as well as in vivo. Any kind of compound, but in particular drugs, such as interferons, viral reverse transcriptase inhibitors or core assembly inhibitors, and/or labels can be specifically targeted to the liver and so be enriched in the liver. This liver targeting can further be used for the targeted diagnosis, prevention and/or treatment of liver diseases or disorders, such as hepatitis, malaria, hepatocellular carcinoma (HCC), as well as for the prevention of HAV, HBV, HCV and/or HDV infection. The present invention relates to pharmaceutical compositions comprising said hydrophobic modified preS-derived peptide(s) and the compound(s) to be specifically delivered to the liver.

Abstract: Described is a vaccine for prevention and treatment of cancer characterized by microsatellite instability (MSI). The vaccine contains an MSI-specific frameshift peptide (FSP) generating humoral and cellular responses against tumor cells or a nucleic acid encoding said FSP. The vaccine of the present invention is particularly useful for the prevention/treatment of colorectal cancer, endometrial cancer, gastric cancer or small bowel cancer.

Abstract: The present invention relates to a binding polypeptide specifically binding to the amino acid sequence W-V-N-X1-F-Y-X2 (SEQ ID NO: 1), wherein X1 represents any amino acid, preferably Q or P, and wherein X2 represents any amino acid, preferably, T or S in a norovirus polypeptide. The present invention further relates to polynucleotide encoding a binding polypeptide of the present invention an to a host cell comprising the same or the polynucleotide of the invention. The present invention further relates to a method of detecting the presence of a norovirus capsid polypeptide in a sample and to kits, devices, and uses making use of the binding peptide of the invention.

Abstract: The present invention relates to hydrophobic modified preS-derived peptides of hepatitis B virus (HBV) which are derived from a HBV preS consensus sequence and are N-terminal preferably acylated and optional C-terminal modified. These hydrophobic modified preS-derived peptides of HBV are very effective HBV entry inhibitors as well as HDV entry inhibitors and are, thus, suitable for the inhibition of HBV and/or HDV infection, prevention of primary HBV and/or HDV infection as well as treatment of (chronic) hepatitis B and/or D. The present invention further relates to pharmaceutical and vaccine compositions comprising these hydrophobic modified preS-derived peptides of HBV.

Abstract: A method for non-invasive observations of a fundus using an ophthalmoscope is provided. The method includes illuminating a retinal region of an eye by projecting an illumination pattern of illumination light onto the retinal region, at least one of detecting a portion of fluorescent light emitted from the retinal region and detecting a portion of illumination light reflected from the retinal region, thereby capturing a series of images of the retinal region at a plurality of different relative positions of the retinal region with respect to the illumination pattern projected onto the retinal region, wherein between the capturing of at least two images of the series the relative position of the retinal region with respect to the illumination pattern projected onto the retinal region is shifted in a non-controlled manner, and processing the captured images to extract a sub-resolution image of the retinal region.

Abstract: The present invention relates to a method for detecting (D)-2-hydroxyglutarate or (D)-2-hydroxyadipic acid in a sample, the method comprising the steps of: a) contacting a sample with a reagent mixture, wherein said reagent mixture comprises: (i) a solvent, (ii) a dye having an oxidized state and a reduced state, wherein the reduced state can be distinguished from the oxidized state and wherein the dye is initially present in the oxidized state, (iii) an electron transfer agent, (iv) a (D)-2-hydroxyglutarate dehydrogenase enzyme, and (v) a cofactor; and b) detecting (D)-2-hydroxyglutarate or (D)-2-hydroxyadipic acid by measuring the production of the reduced state of the dye. The invention further pertains to a method for diagnosing and/or monitoring a (D)-2-hydroxy-glutarate-associated disease in a subject. Encompassed by the invention is also a method for diagnosing a mutation in an isocitrate dehydrogenase (IDH) gene or in a (D)-2-hydroxyglutarate (D2HG) dehydrogenase enzyme gene in a subject.

Abstract: The present invention relates to the field of cell-based therapeutics. Specifically, the invention is concerned with a composition comprising a macrophage overexpressing interleukin 10 (IL-10) from transfected IL-10 encoding mRNA for use as a medicament. Moreover, a method for manufacturing a medicament for treating and/or preventing inflammation or a disease or disorder associated therewith comprising the steps of obtaining a macrophage from a sample of said subject, transfecting mRNA encoding IL-10 into said macrophage, and formulating said macrophage in a composition suitable for administration to the said subject, whereby the medicament is manufactured. Finally, a kit is provided for manufacturing such a medicament.

Abstract: Compounds of formula (IIc); wherein X3 and X4 independently from each other are N or CR8 wherein R8 may be same or different; Y1, Y2, Y3 and Y4 independently from each other are N or CR9 wherein R9 may be same or different and wherein up to 3 of the group Y1, Y2, Y3 and Y4 may be N; their solvates, hydrates, and pharmaceutically acceptable salts, their use for modulating the Wnt signalling pathway activity and their use as a medicament, preferably for the treatment of cancer.

Abstract: The present invention relates to Abhydrolase containing domain 5 (ABHD5) and N-terminal fragments of HDAC4 (HDAC4-NT) and variants of the aforementioned peptides for the treatment and prevention of heart failure. The present invention further provides vectors for the cardiomyocyte-specific expression of said peptides and a test system comprising ABHD5 for the identification of novel compounds which are useful for the treatment of heart failure.

Abstract: In summary, the present invention concerns a method for multiple orthogonal labelling of oligonucleotides, preferably RNA or DNA, by simultaneously performing the inverse Diels-Alder reaction (DAinv) and the copper-catalyzed click reaction (CuAAC), wherein the method is employed in a single step by just adding the different reaction components together and incubating the aqueous reaction mixture preferably for one hour at room temperature. In detail, the reaction components are one or more N3-modified labels, a copper compound, a stabilizing ligand, a reducing agent and one or more electron-deficient label-modified dienes that are added together with an at least double-modified oligonucleotide having one more nucleotides containing one or more N3-reactive groups and one or more electron-rich dienophiles, wherein a terminal alkyne moiety is preferably used as N3-reactive group(s) and a frans-cyclooctene moiety or norbornene is preferably used as electron-rich dienophile(s), more preferably frans-cyclooctene.

Abstract: The present invention relates to the field of cell-based therapeutics. Specifically, the invention is concerned with a composition comprising a macrophage overexpressing interleukin 10 (IL-10) from transfected IL-10 encoding mRNA for use as a medicament. Moreover, a method for manufacturing a medicament for treating and/or preventing inflammation or a disease or disorder associated therewith comprising the steps of obtaining a macrophage from a sample of said subject, transfecting mRNA encoding IL-10 into said macrophage, and formulating said macrophage in a composition suitable for administration to the said subject, whereby the medicament is manufactured. Finally, a kit is provided for manufacturing such a medicament.

Abstract: The present invention relates to the field of diagnostic tests and diagnostic tools. Specifically, contemplated is to a method for diagnosing cancer in a sample of a subject suspected to suffer from cancer comprising contacting the sample with an antibody which specifically binds to the epitope characterized by SEQ ID NO 1 on a BRAF polypeptide under conditions which allow for binding of said antibody to the epitope and determining binding of the antibody to the epitope, whereby cancer is diagnosed. Further contemplated are antibodies which specifically bind to the epitope characterized by SEQ ID NO 1 on a BRAF polypeptide and a device or kit comprising such antibodies.

Abstract: The present invention concerns the field of cancer therapy. In particular, it relates to an antagonist of a B-type plexin which prevents the interaction of the B-type plexin with ErbB-2 for use as a medicament, in particular, for treating metastasizing cancer. The present invention also contemplates a method for identifying an antagonist which prevents the interaction of a B-type plexin with ErbB-2. Finally, the invention provides for a polynucleotide encoding a B-type plexin polypeptide which lacks a functional intracellular domain and the said polypeptide.

Abstract: The invention relates to compounds and methods useful in detection and therapy of HPV-associated diseases. The invention is based on the elucidation of a mechanism by which replication of HPVs occurs in naturally infected tissues and cells. Moreover it is based on the identification of distinct epigenetic changes of the viral genome in infected cells that allows promotion of the affected cells to precancerous and cancerous cells. The invention therefore provides methods of diagnosing neoplasias and their precursor lesions as well as methods of preventing the development of malignancies or inhibiting tumor growth.

Abstract: The present invention relates to a method for determining a clearance normalized amount of a metabolite disease biomarker in a sample including the steps of (a) determining the amount of the disease biomarker in at least a first type of sample of a subject suspected to suffer from the disease, (b) determining the amount of a kidney function biomarker which correlates with the glomerular filtration rate (GFR) in the said at least first type of sample, and (c) determining a clearance normalized amount for the metabolite disease biomarker by normalizing the amount determined for the metabolite disease biomarker in step (a) to the amount of the kidney function biomarker determined in step (b). Moreover, the invention also relates to a method for diagnosing a disease in a subject suspected to suffer therefrom and to a device for determining a clearance normalized amount of a metabolite disease biomarker in a sample.

Abstract: The present invention concerns the field of cancer therapy. In particular, it relates to an antagonist of a B-type plexin which prevents the interaction of the B-type plexin with ErbB-2 for use as a medicament, in particular, for treating metastasizing cancer. The present invention also contemplates a method for identifying an antagonist which prevents the interaction of a B-type plexin with ErbB-2. Finally, the invention provides for a polynucleotide encoding a B-type plexin polypeptide which lacks a functional intracellular domain and the said polypeptide.