German Cancer Research Center | Date: 2017-04-12
A fluorescence microscope instrument (1) includes a light source (2) providing light (3) to be directed to a sample (4); a detector (5) detecting fluorescence light (5) emitted out of the sample (4); an objective (7) focusing the light (3) from the light source (2) into a focal area within the sample (4) and collecting the fluorescence light (6) emitted out of the focal area to be detected by the detector (5); and a beam path separator (9) arranged in a beam path of the light (3) from the light source (2) between the light source (2) and the objective (7) and in a beam path of the fluorescence light (6) between the objective (7) and the detector (5). Wavelengths of the light (3) to be directed to the sample (4) and of the light (6) to be detected by the detector fall into a range of wavelengths extending from a low end wavelength over at least 20 % of the low end wavelength. The beam path separator (9) separates the beam path of the fluorescence light (6) from the beam path of the light (3) from the light source (2) in that it is transferable between a first state in which it is transparent for light of any wavelength falling in the range of wavelengths and coming along the beam path of the light (3) from the light source (2), and a second state in which it is transparent for light of any wavelength falling in the range of wavelengths and coming along the beam path of the fluorescence light (6) from the sample (4).
German Cancer Research Center and University of Heidelberg | Date: 2016-08-25
The present invention relates to a recombinant virus of the family Paramyxoviridae, comprising at least one expressible polynucleotide encoding a multispecific binding polypeptide, said multispecific binding polypeptide comprising a first binding domain binding to a surface molecule of an immune cell with antitumor activity, preferably a lymphocyte, more preferably a T cell or a dendritic cell, and a second binding domain binding to a tumor-associated antigen; to a polynucleotide encoding the same, and to a kit comprising the same. Moreover, the present invention relates to a method for treating cancer in a subject afflicted with cancer, comprising contacting said subject with a recombinant virus of the family Paramyxoviridae of the invention, and thereby, treating cancer in a subject afflicted with cancer.
German Cancer Research Center and Queen Mary, University of London | Date: 2016-12-21
The present invention pertains to the field of cancer diagnosis. Specifically, it relates to a method for diagnosing pancreas cancer in a subject comprising the steps of determining in a sample of a subject suspected to suffer from pancreas cancer the amount of at least one biomarker selected from the biomarkers shown in Table 1 and comparing the said amount of the at least one biomarker with a reference, whereby pancreas cancer is to be diagnosed. The present invention also contemplates a method for identifying whether a subject is in need of a pancreas cancer therapy comprising the steps of the aforementioned methods and the further step of identifying a subject in need of a pancreas cancer therapy if said subject is to be diagnosed to suffer from pancreas cancer. Contemplated are, furthermore, diagnostic devices and kits for carrying out said methods.
German Cancer Research Center | Date: 2017-02-10
The present invention relates to the finding that Syndecans (Sdc) are receptors of Rspondin-2 (Rspo2) and Rspondin-3 (Rspo3). Thus, the present invention relates to the identification of Rspo2, Rspo3 and/or Sdc activity modulators by determining if a test compound has the ability to modulate the binding of an Rspo2 and/or Rspo3 polypeptide to an Sdc polypeptide. Further, the invention refers to novel uses for antagonists of Rspo2 and/or Rspo3 in the treatment of Sdc-associated disorders and for Sdc antagonists in the treatment of Rspo2- and/or Rspo3-associated disorders.
German Cancer Research Center | Date: 2017-05-17
Described are HCBI (Healthy Cattle Blood Isolate), MSBI (Multiple Sclerosis Brain Isolate), MSSI (Multiple Sclerosis Serum Isolate) and CMI (Cow Milk Isolate) nucleotide sequences as well as probes and primers comprising part of said nucleotide sequences and antibodies against polypeptides encoded by said nucleotide sequences. Said compounds are useful as early markers for the future development of cancer and diseases of the CNS (Multiple sclerosis MS, Prion-linked diseases, amyotrophic lateral sclerosis, transmissible spongiforme encephalitis, Parkinsons disease, Alzheimer disease) and should represent targets for treatment and prevention.
Niehrs C.,German Cancer Research Center |
Niehrs C.,Institute of Molecular Biology
Nature Reviews Molecular Cell Biology | Year: 2012
30 years after the identification of WNTs, their signal transduction has become increasingly complex, with the discovery of more than 15 receptors and co-receptors in seven protein families. The recent discovery of three receptor classes for the R-spondin family of WNT agonists further adds to this complexity. What emerges is an intricate network of receptors that form higher-order ligand-receptor complexes routing downstream signalling. These are regulated both extracellularly by agonists such as R-spondin and intracellularly by post-translational modifications such as phosphorylation, proteolytic processing and endocytosis. © 2012 Macmillan Publishers Limited. All rights reserved.
Fiegler N.,German Cancer Research Center
Blood | Year: 2013
Natural killer (NK) cells are central effector cells during innate immune responses against cancer. Natural cytotoxicity receptors expressed by NK cells such as NKp30 are involved in the recognition of transformed cells. Recently, the novel B7 family member B7-H6, which is expressed on the cell surface of various tumor cells including hematological malignancies, was identified as an activating ligand for NKp30. To investigate expression and regulation of B7-H6, we generated monoclonal antibodies. Our study reveals that B7-H6 surface protein and messenger RNA (mRNA) expression in various tumor cell lines was downregulated upon treatment with pan- or class I histone deacetylase inhibitors (HDACi) as well as after small interfering RNA-mediated knockdown of the class I histone deacetylases (HDAC) 2 or 3. B7-H6 downregulation was associated with decreased B7-H6 reporter activity and reduced histone acetylation at the B7-H6 promoter. In certain primary lymphoma and hepatocellular carcinoma samples, B7-H6 mRNA levels were elevated and correlated with HDAC3 expression. Finally, downregulation of B7-H6 on tumor cells by HDACi reduced NKp30-dependent effector functions of NK cells. Thus, we identified a novel mechanism that governs B7-H6 expression in tumor cells that has implications for potential cancer treatments combining immunotherapy with HDACi.
Niehrs C.,German Cancer Research Center
Development | Year: 2010
The regulation of body axis specification in the common ancestor of bilaterians remains controversial. BMP signaling appears to be an ancient program for patterning the secondary, or dorsoventral, body axis, but any such program for the primary, or anteroposterior, body axis is debated. Recent work in invertebrates indicates that posterior Wnt/β-catenin signaling is such a mechanism and that it evolutionarily predates the cnidarian-bilaterian split. Here, I argue that a Cartesian coordinate system of positional information set up by gradients of perpendicular Wnt and BMP signaling is conserved in bilaterians, orchestrates body axis patterning and contributes to both the relative invariance and diversity of body forms.
Schulz A.,German Cancer Research Center
Blood | Year: 2013
Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental stimuli for their survival, provided for example by monocyte-derived nurse-like cells (NLCs). The immunomodulatory drug lenalidomide shows therapeutic effects in subgroups of CLL patients, and is believed to act via the microenvironment. To investigate the effects of lenalidomide on the survival support of NLCs, cocultures of monocytes and CLL cells were treated for 14 days with lenalidomide, which resulted in significantly decreased viability of CLL cells. Among the changes induced by this drug, we observed reduced expression of HLA-DR in NLCs as well as increased secretion of interleukin-10 (IL-10), indicating an altered inflammatory milieu in the cocultures. The increase in IL-10 levels lead to an induction of STAT1 phosphorylation in CLL cells and to enhanced cell-surface expression of intercellular adhesion molecule 1 and altered expression of cytoskeletal and migration-related genes. Chemotaxis assays with lenalidomide-treated CLL cells revealed an impaired migration capability. Our data show that lenalidomide reduces the survival support of NLCs for CLL cells in vitro, suggesting that this drug affects the myeloid microenvironment in CLL in vivo. Furthermore, lenalidomide acts on the migratory potential of CLL cells, which may affect circulation and homing of CLL cells in vivo.
von Deimling A.,German Cancer Research Center
Acta neuropathologica communications | Year: 2014
BACKGROUND: IDH mutations frequently occur in diffuse gliomas and result in a neo-enzymatic activity that results in reduction of α-ketoglutarate to D-2-hydroxyglutarate. In gliomas, the frequency of IDH1 mutations in codon 132 increases in the order R132L-R132S-R132G-R132C-R132H with R132H constituting more than 90% of all IDH1 mutations.RESULTS: We determined the levels of D-2-hydroxyglutarate in glioma tissues with IDH1 mutations. D-2-hydroxyglutarate levels increased in the order of R132H-R132C-R132S/R132G/R132L. We expressed and purified IDH1 wild type and mutant protein for biochemical characterization. Enzyme kinetics of mutant IDH protein correlated well with D-2-hydroxyglutarate production in cells with R132H exhibiting the highest and R132L the lowest KM for α-ketoglutarate. Addition of D-2-hydroxyglutarate to the medium of cell lines revealed an inhibitory effect at higher concentrations. Migration of LN229 increased at lower D-2-hydroxyglutarate concentrations while higher concentrations showed no effect.CONCLUSION: These findings may suggest natural selection against the rare IDH1R132 mutations in human glioma due to toxicity caused by high levels of D-2-hydroxyglutarate.