The here presented technology provides an apparatus for 4Pi STED which allows to generate a three-dimensional light intensity distribution comprising a very steep light intensity gradient between the areas of minimum and maximum light intensity.
Labeled oligonucleotides are used in research and for diagnostic, therapeutic and industrial applications. Researchers from the DKFZ and the Heidelberg University developed a fast method for post-synthetic multiple orthogonal labeling of oligonucleotides by combining the inverse Diels-Alder reaction with the well-known copper-catalyzed azide-alkyne cycloaddition.
Endostatin is an antiangiogenic protein first discovered in Folkman's laboratory at Childrens Hospital, Harvard Medical School, and Boston. The antitumor properties of this protein are well established. Nowever, the amount of protein required for injection in patients was beyond production feasibility due to the poor pharmacokinetics of endostatin monomer. We have shown that the problem of poor pharmacokinetics can be solved by using the Fc domain of IgG being conjugated to endostatin, a component of all monoclonal antibodies approved for patients with a number of diseases including cancer. As a result of employing Fc-endostatin, the half-life in mice was increased to 2 weeks instead of 2 hours for endostatin alone, consistent with pharmacokinetics of monoclonal antibodies.
Efficient treatment strategy based on antigen-armed antibodies (AgAbs). After AgAb treatment Epstein-Barr virus-transformed B cell lines and various Burkitt’s lymphoma cell lines were able to present antigens that efficiently induce T cell activation.
Synchronization and control of linear accelerator, multi-leaf collimator, gantry system, patient support system and x-ray beam generation system at the same time is difficult to establish, particularly with hard real-time requirements. The presented technology comprises a control unit consisting of standardized programmable logic controllers for real-time operation of all subsystems of a radiation therapy device. Thus, the technology allows precise and dynamic patient treatment with high time resolution.
Several limitations restrict conventional Fluorescence recovery after photobleaching (FRAP) application. Examples are: 1) Low temporal resolution, which prohibits measurements of faster processes 2) FRAP evaluation schemes cannot include spatial constraints imposed by the cellular environment on protein mobility 3) FRAP ignores the sequential nature of the bleaching and image acquisition process. In order to overcome these limitations of conventional FRAP DKFZ researchers developed a novel FRAP based method called 3PEA (Pixel-wise Photobleaching Profile Evolution Analysis). The advantages of 3PEA are e.g.: accurate mobility measurements of fast, slow, and immobile proteins and fast determination of effective diffusion coefficients. The presented technology is thought to be suitable for use in all confocal laser scanning microscopes (no additional hardware is needed) and would allow automated high throughput FRAP experiments.
Virus-like particles (VLPs) of EBV, completely devoid of viral DNA, for the prevention of infectious mononucleosis (IM) and EBV-associated diseases like lymphomas often developed in patients with immunosuppression.
In 50-80% OPSCC patients human papilloma virus (HPV) can be detected. These patients have an improved survival and would benefit from deescalate cancer treatment. The technology provides a reliable marker based on RNA pattern.
DKFZ inventors identified the Wnt secretion protein Evi/Gpr177 as new target, which is strikingly upregulated during glioma tumorigenesis in a stage-independent way and which correlated with poor prognosis. Silencing of the Evi/Gpr177 protein significantly inhibited glioma cell proliferation and migration. Additionally an inhibitory antibody against Evi/Gpr177 was invented that significantly reduced Wnt Evi/Gpr177 gene response.
Currently, multi leaf collimators (MLC) are established and state of the art in numerous devices for radiotherapy used for cancer treatment. However, the established MLC comprising 80 and more leafs require an enormous space at the level of the leaves for corresponding drive and controlling elements if realized with normal electric motors. Since space is very limited within the head of linear accelerators the invention proposes a new small and convenient driving/controlling device based on piezoelectricity, which is directly coupled to the leaves and their driving rods.
The multi-leaf collimator MLC for radiation therapy has leaves where the positions of the leaves are determined by measuring a magnetic field. This allows determining the leaf position with enhanced precision, and is at the same time robust to perturbations or disturbances. The magnetic sensor may comprise a magnetic encoder that varies in a predefined pattern along a lengthwise direction of the magnetic element, in particular according to a step function. The technology can be used for a new generation of especially compact and small MLC. The Hall effect sensor does not interfere with therapeutic beam and the contact-free measurements does not affected by friction or abrasive wear.
Current technologies for radiologically guided interventions leave the interventionalist with a high degree of uncertainty regarding the position of his instruments and the surrounding tissue/organs. We developed a true 4D imaging providing a full control in three spatial dimensions including temporal changes during interventions suitable for MRI and CT (single shot for lower radiation dose).
We developed a new concept for on-patient visualization of anatomical data acquired with an arbitrary modality (typically CT or MRI). The method is based on a mobile device consisting of a flat display and a Time-of-Flight (ToF) camera which can be moved along the patient to provide a view on internal anatomical structures via augmented reality. For this purpose, the pose of the mobile device, which represents the viewing direction of the user, is continuously estimated by registering (i.e., aligning) the ToF data acquired during the visualization process with the patient surface extracted from the 3D medical data set. During camera pose estimation, a custom-designed algorithm accounts for the camera specific localization errors.
Branched-Chain-Aminotransferase-1 (BCAT1) as diagnostic marker for tumors and mutations of Isocitrate-Dehydrogenase-1 (IDH1) and IDH2. Researchers at DKFZ developed an immunohistochemical assay to classify tumors based on differences in the metabolism of branched chain amino acids. In brain tumors the assay distinguishes tumors harboring mutations in either the IDH1 or IDH2 genes or both from tumors with wild type IDH1 and IDH2 genes. This way the IDH1 status and activity of branched chain amino acid metabolism can be determined using tissue slides. The specificity of the immunohistochemical lDH1 and IDH2 status analysis is significantly increased from about 92% in known methods to 100% in our method. The assay allows the fast and reliable diagnostic and prognostic classification of tumors based on the activity of branched chain amino acid metabolism.
Cardiac hypertrophy is characterized by a global increase in transcription and protein per cell. Cyclin-dependent kinase 9 (CDK9) is the main driver for transcription and is necessary for hypertrophy in cardiomyocytes. DKFZ scientists have shown that wogonin is a potent inhibitor of CDK9 with no or very low toxicity to normal tissues. Wogonin can be used for preventing cardiac hypertrophy.
The Wnt signaling pathway plays an important role in the regulation of cell proliferation and differentiation. Aberrant activation of the Wnt signaling pathway is known to promote uncontrolled cell growth and survival. Compound library screening and med-chem based structure activity improvement revealed potent Wnt signaling inhibitors that selectively affected carcinoma cell lines. In addition, further experiments proved these compounds to induce apoptosis.
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