Article
Refine
Year of publication
- 2012 (218) (remove)
Document Type
- Article (218) (remove)
Has Fulltext
- yes (218)
Is part of the Bibliography
- no (218)
Keywords
- Apoptosis (3)
- Ubiquitination (3)
- apoptosis (3)
- inflammation (3)
- p53 (3)
- ADHD (2)
- BCR/ABL (2)
- Cognitive behavioral therapy (2)
- HIV (2)
- Herb induced liver injury (2)
- Herbal hepatotoxicity (2)
- PARK2 (2)
- Philadelphia chromosome (2)
- XIAP (2)
- acute lymphoblastic leukemia (2)
- angiogenesis (2)
- audiovisual (2)
- diagnosis (2)
- histone deacetylase inhibitor (2)
- inner ear (2)
- ubiquitin (2)
- 32D progenitor cells (1)
- 5-lipoxygenase (1)
- 9-aminoacridine (1)
- AA-amylodosis (1)
- ABT-737 (1)
- ADAM15 (1)
- Abl kinase inhibitors (1)
- Acute myeloid leukemia (1)
- Alcohol (1)
- Alcoholic liver disease (1)
- All-oral therapy (1)
- Allosteric inhibition (1)
- Anal cancer (1)
- Anatomic competence (1)
- Animal model (1)
- Antiviral therapy (1)
- Artemether-lumefantrine (1)
- Artemisinin-combination-therapy (1)
- Arthroscopy (1)
- BMSC (1)
- Bayesian (1)
- Bayesian model (1)
- Beratung (1)
- Best-practice model (1)
- Bone tumor (1)
- Burns (1)
- C1-INH (C1 inhibitor, C1-esterase inhibitor) (1)
- CIK cells (1)
- CNVs (1)
- Calcium gluconate (1)
- Cancer (1)
- Cartilage (1)
- Cartilage Biology (1)
- Case management (1)
- Cell Metabolism (1)
- Cell Migration (1)
- Chaperone (1)
- Chondrocytes (1)
- Chronic depression (1)
- Chronic hepatitis C (1)
- Chronic kidney disease (1)
- Communicable diseases (1)
- Concurrent chemoradiotherapy (1)
- Consensus (1)
- Critical pathway (1)
- DCM (1)
- Dendritic Cells (1)
- Devic disease (1)
- Devic syndrome (1)
- Diagnostic techniques and procedures (1)
- Digital subtraction angiography (1)
- Directly acting antiviral agent (1)
- Dissemination (1)
- Duchenne’s muscular dystrophy (1)
- E3 ligase (1)
- EEG-fMRI (1)
- EGFR (1)
- ETP-ALL (1)
- Education (1)
- Enteric nervous system (1)
- European Union (1)
- Ewing sarcoma (1)
- FLT3 (1)
- Fibrotest (1)
- Focal Adhesion Kinase (1)
- G3BP (1)
- GLUT1 (1)
- GWAS (1)
- Gastric cancer (1)
- Gene Regulation (1)
- Germany (1)
- Glioma (1)
- Glycolysis (1)
- HAE (1)
- HCV (1)
- Haploidentical stem cell transplantation (1)
- Hepatitis (1)
- Hepatitis C virus (1)
- Hepatotoxicity (1)
- Herbal medicine (1)
- Hereditary angioedema (1)
- Hodgkin lymphoma (1)
- Hydrofluoric acid (1)
- Hypoxia (1)
- IAP Proteins (1)
- IAP-IAP (1)
- IAPs (1)
- IVDU (1)
- Immunohistochemistry (1)
- Individualisierung des Studiums (1)
- Individuelle Studienbegleitung (1)
- Infection control (1)
- Innate Immunity (1)
- Interleukin (1)
- Interleukin-1 (1)
- Interleukin-22 (1)
- Interleukin-36 (1)
- KIR (1)
- Knee joint (1)
- Lack of immunity (1)
- Liver cirrhosis (1)
- Liver enzymes (1)
- Liver-related complications (1)
- MALAT1 (1)
- MAP Kinases (MAPKs) (1)
- MEG (1)
- MELD (1)
- ML-IAP (1)
- MLL (1)
- MSM (1)
- Macrophages (1)
- Malaria (1)
- Malariae (1)
- Medical (1)
- Medizin (1)
- Minimal residual disease (1)
- Mitochondria (1)
- Mitochondrial Apoptosis (1)
- Mitochondrial Metabolism (1)
- Mitochondrial Permeability Transition (1)
- Mitochondrial Transport (1)
- Modellprojekt, (1)
- Molecular Chaperone (1)
- Molecular marker (1)
- Molecular therapy (1)
- Motility disorder (1)
- Musculoskeletal ultrasound (1)
- NF-κB (1)
- NMO-IgG (1)
- NOTCH1 (1)
- NOXA (1)
- NSG mice (1)
- Neuromyelitis optica (1)
- Non-falciparum (1)
- Null responder (1)
- Occupational Accidents (1)
- Oral anticoagulation (1)
- Outcome (1)
- Ovale (1)
- P600 (1)
- PARK6 (1)
- PARK7 (1)
- PI3K (1)
- PUMA (1)
- Paracoccus denitrificans (1)
- Parkinson's disease (1)
- Patient isolation (1)
- Pediatric (1)
- Pelargonium sidoides (1)
- Pelargonium sidoides questionable hepatotoxicity (1)
- Pentose Pathway (1)
- Performing Artists (1)
- Pharmacovigilance (1)
- Phase-IV research (1)
- Poliomyelitis (1)
- Prevention (1)
- Prognostic (1)
- Proteasome (1)
- Protein Structure (1)
- Protein-Protein Interactions (1)
- Psychodynamic psychotherapy (1)
- Quality, performance, safety and outcomes (1)
- RAF (1)
- RIP (1)
- RITA (1)
- RNA-templated DNA repair (1)
- Rabbit (1)
- Rac1 (1)
- Radiofrequency ablation (1)
- Ramón y Cajal (1)
- Randomized controlled trial (1)
- Remission (1)
- Rhabdomyosarcoma (1)
- Rho GTPases (1)
- RhoA (1)
- RhoGTPases (1)
- SVR (1)
- Safety (1)
- Seroepidemiology (1)
- Sex (1)
- Shoulder joint (1)
- Signal Transduction (1)
- Signaling (1)
- Skin fibroblast (1)
- Small bowel atresia (1)
- Smooth muscle (1)
- Social phobia (1)
- Students (1)
- Studium mit Kind (1)
- Survival (1)
- Survivin (1)
- T-ALL (1)
- T-bet (1)
- TGFβ (1)
- TIGAR (1)
- TRAIL (1)
- Toll-like receptor (1)
- Trail (1)
- Training (1)
- Transient elastography (1)
- Treatment (1)
- Tumor therapy (1)
- Ubiquitin Ligase (1)
- Ubiquitin signaling (1)
- Ubiquitin-binding module (1)
- Ubiquitylation (1)
- VEGF (1)
- VX-2 (1)
- Vaccination (1)
- Vasospasm (1)
- Warburg effect (1)
- Wnt (1)
- X-ray Crystallography (1)
- Xenorhabdus (1)
- acute lymphatic leukemia (1)
- acute myeloid leukemia (1)
- adaptation (1)
- adhesion (1)
- allosteric inhibition (1)
- alpha band (1)
- ambiguity (1)
- amoeboid (1)
- anorexia nervosa (1)
- aortic stenosis (1)
- aquaporin-4 (AQP4) antibody (1)
- auditory cortex (1)
- autoantigen (1)
- autoimmunity (1)
- axon (1)
- beads (1)
- beta band (1)
- betulinic acid (1)
- bistable (1)
- blood consumption (1)
- blood safety (1)
- bone (1)
- bone substitutes (1)
- brain networks (1)
- brain oscillations (1)
- cART (1)
- cIAP1 (1)
- cancer (1)
- cancer cell malignancy (1)
- cancer cells (1)
- cardiolipin (1)
- cell death (1)
- cell migration (1)
- cerebello-dentato-thalamo-cortical pathway (1)
- cerebellum (1)
- cerebrospinal fluid (1)
- chemotherapy-resistance (1)
- child (1)
- children (1)
- cholecystectomy (1)
- chromatin immunoprecipitation (1)
- circadian rhythms (1)
- clinical features (1)
- co-infection (1)
- coaching (1)
- cochlea (1)
- colorectal cancer (1)
- combination immunotherapy (1)
- conventional laparoscopic (1)
- corneas (1)
- cyclic depsipeptide (1)
- deafness (1)
- dendrite (1)
- deswelling (1)
- discontinuous dose dependency (1)
- donor deferral (1)
- donor recruitment (1)
- donor retention (1)
- doxorubicin (1)
- drug resistance (1)
- dynamic connectivity (1)
- epidemiology (1)
- epidermal growth factor (1)
- epigenetics (1)
- esterification (1)
- executive control (1)
- extracellular matrix (1)
- eye movement (1)
- familiengerechte Hochschule (1)
- family-friendly universities (1)
- fibrosis (1)
- free leptin index (FLI) (1)
- functional magnetic resonance imaging (1)
- genetic rearrangements (1)
- growth factor (1)
- guidelines (1)
- hair cell (1)
- health related quality of life (1)
- hearing loss (1)
- heart (1)
- hepatitis C (1)
- hepatotoxicity (1)
- hereditary angioedema (1)
- histone acetylation (1)
- homing (1)
- hormone (1)
- human (1)
- human cytomegalovirus (1)
- human knockout model (1)
- hysteresis (1)
- iPS (1)
- immune modulation (1)
- immune tolerance (1)
- immunotherapy (1)
- individualized solutions (1)
- infection (1)
- inflammasome (1)
- integrins (1)
- international (1)
- intraarterial therapy (1)
- invasion (1)
- keratoplasty (1)
- knockout mouse (1)
- laminins (1)
- language (1)
- learning (1)
- learning curve (1)
- leptin, leptin receptor (sOB-R) (1)
- lethal toxin (1)
- leukemia (1)
- leukemia; solid tumors (1)
- liver (1)
- liver metastases (1)
- long non-coding RNA (1)
- long-term infection (1)
- longitudinally extensive transverse myelitis (1)
- low-dose radiation therapy (1)
- magnetic resonance imaging (1)
- management (1)
- matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (1)
- medical studies (1)
- medications (1)
- melatonin (1)
- memory (1)
- mesenchymal (1)
- microglia (1)
- microkeratome (1)
- migration (1)
- minimally invasive cardiac surgery (1)
- mitochondria (1)
- modeling (1)
- molecular characteristics (1)
- molecular therapy (1)
- motion capture (1)
- motor cortex (1)
- multisensory integration (1)
- nanoparticle (1)
- natural killer cells (1)
- natural product (1)
- nerve injury (1)
- neuroblastoma (1)
- neuroinflammation (1)
- non - pharmacological anti-infective measures (1)
- nutlin-3 (1)
- oncomodulation (1)
- organ of Corti (1)
- osteogenesis (1)
- p53 activator (1)
- pain, dorsal root ganglia (1)
- paired associative stimulation (1)
- parenting students (1)
- peginterferon (1)
- perceptual memory (1)
- perfusion (1)
- phase coupling (1)
- pineal (1)
- plasticity (1)
- postoperative complications (1)
- preclinical (1)
- preeclampsia (1)
- premature transcript termination (1)
- preparation (1)
- procedural safety (1)
- prostate cancer (1)
- proteases (1)
- proteoglycan (1)
- pyramidal cell (1)
- radiation (1)
- recurrent chromosomal translocations (1)
- recurrent optic neuritis (1)
- resting state (1)
- rhabdomyosarcoma (1)
- rolipram (1)
- sepsis (1)
- serotonin (1)
- single-port cholecystectomy (1)
- skeletal muscle (1)
- spike-timing dependent-like plasticity (1)
- spinal cord (1)
- spiral ganglion (1)
- spiral ganglion cell (1)
- squamous cell carcinoma of head and neck (1)
- syntax (1)
- szentiamide (1)
- task set (1)
- task-switching training (1)
- therapy (1)
- toxin B (1)
- training transfer (1)
- transapical aortic valve replacement (1)
- transcranial magnetic stimulation (1)
- trichostatin A (1)
- tumor growth in xenografts (1)
- tumour immunology (1)
- yeast (1)
- zebrafish (1)
- zinc (1)
- “gatekeeper” mutation T315I (1)
Institute
- Medizin (218) (remove)
Inhibitor of apoptosis (IAPs) proteins are characterized by the presence of evolutionarily conserved baculoviral inhibitor of apoptosis repeat (BIR) domains, predominantly known for their role in inhibiting caspases and, thereby, apoptosis. We have shown previously that multi-BIR domain-containing IAPs, cellular IAPs, and X-linked IAP can control tumor cell migration by directly regulating the protein stability of C-RAF kinase. Here, we extend our observations to a single BIR domain containing IAP family member melanoma-IAP (ML-IAP). We show that ML-IAP can directly bind to C-RAF and that ML-IAP depletion leads to an increase in C-RAF protein levels, MAPK activation, and cell migration in melanoma cells. Thus, our results unveil a thus far unknown role for ML-IAP in controlling C-RAF stability and cell migration.
ADAM15 protein amplifies focal adhesion kinase phosphorylation under genotoxic stress conditions
(2012)
ADAM15, a disintegrin and metalloproteinase, is capable of counteracting genotoxic stress-induced apoptosis by the suppression of caspase-3 activation. A cell line expressing the membrane-bound ADAM15 without its cytoplasmic tail, however, lost this anti-apoptotic property, suggesting a crucial role of the intracellular domain as a scaffold for recruitment of survival signal-transducing kinases. Accordingly, an enhanced phosphorylation of FAK at Tyr-397, Tyr-576, and Tyr-861 was detected upon genotoxic stress by camptothecin in ADAM15-transfected T/C28a4 cells, but not in transfectants expressing an ADAM15 mutant without the cytoplasmic tail. Accordingly, a specific binding of the cytoplasmic ADAM15 domain to the C terminus of FAK could be shown by mammalian two-hybrid, pulldown, and far Western studies. In cells expressing full-length ADAM15, a concomitant activation of Src at Tyr-416 was detected upon camptothecin exposure. Cells transfected with a chimeric construct consisting of the extracellular IL-2 receptor α-chain and the cytoplasmic ADAM15 domain were IL-2-stimulated to prove that the ADAM15 tail can transduce a percepted extracellular signal to enhance FAK and Src phosphorylation. Our studies further demonstrate Src binding to FAK but not a direct Src interaction with ADAM15, suggesting FAK as a critical intracellular adaptor for ADAM15-dependent enhancement of FAK/Src activation. Moreover, the apoptosis induction elicited by specific inhibitors (PP2, FAK 14 inhibitor) of FAK/Src signaling was significantly reduced by ADAM15 expression. The newly uncovered counter-regulatory response to genotoxic stress in a chondrocytic survival pathway is potentially also relevant to apoptosis resistance in neoplastic growth.
Background: Radiofrequency ablation is a minimal invasive therapy in the treatment of bone metastases. In this study we present a new ablation system enabling an ablation in multiple directions and with an adaptable size and shape.
Material and methods: VX-2 tumor was used for the induction of experimental bone metastases in the femur of six New Zealand white rabbits. X-ray imaging as well as CT and MRI scans before and after treatment was carried out. After detecting bone tumor, radiofrequency ablation was performed. The ablation instrument contained a 10 g bipolar, articulated extendable electrode and a proprietary generator with an impedance controlled algorithm. All bones and the soft tissue were examined histologically.
Results: All animals developed local bone tumor. Mean duration until first osteolytic lesions on CT-scans was 48±14 days. The mean lesion area was 26 mm(2). No systemic tumor spread was seen. 6 radiofrequency procedures were carried out with a mean application time of 6 min±2:30 and an average temperature in the region of effect of 55 °C±4. MRI imaging demonstrated an ablation zone of 23±6 mm around the electrode. Histopathology showed an extensive heat necrosis with no remaining tumor cells in the ablation area.
Conclusion: Radiofrequency ablation is a quickly developing treatment option on the field of minimal invasive bone tumor therapy. The electrode enables an ablation adapted to size and shape of the metastases. Further clinical studies are necessary to test and enhance this radiofrequency system.
We proposed previously that closure of voltage-dependent anion channels (VDAC) in the mitochondrial outer membrane after ethanol exposure leads to suppression of mitochondrial metabolite exchange. Because ureagenesis requires extensive mitochondrial metabolite exchange, we characterized the effect of ethanol and its metabolite, acetaldehyde (AcAld), on total and ureagenic respiration in cultured rat hepatocytes. Ureagenic substrates increased cellular respiration from 15.8 ± 0.9 nmol O(2)/min/10(6) cells (base line) to 29.4 ± 1.7 nmol O(2)/min/10(6) cells in about 30 min. Ethanol (0-200 mM) suppressed extra respiration after ureagenic substrates (ureagenic respiration) by up to 51% but not base line respiration. Urea formation also declined proportionately. Inhibition of alcohol dehydrogenase, cytochrome P450 2E1, and catalase with 4-methylpyrazole, trans-1,2-dichloroethylene, and 3-amino-1,2,3-triazole restored ethanol-suppressed ureagenic respiration by 46, 37, and 66%, respectively. By contrast, inhibition of aldehyde dehydrogenase with phenethyl isothiocyanate increased the inhibitory effect of ethanol on ureagenic respiration by an additional 60%. AcAld, an intermediate product of ethanol oxidation, suppressed ureagenic respiration with an apparent IC(50) of 125 μM. AcAld also inhibited entry of 3-kDa rhodamine-conjugated dextran in the mitochondrial intermembrane space of digitonin-permeabilized hepatocytes, indicative of VDAC closure. In conclusion, AcAld, derived from ethanol metabolism, suppresses ureagenesis in hepatocytes mediated by closure of VDAC.
Searching for new strategies to trigger apoptosis in rhabdomyosarcoma (RMS), we investigated the effect of two novel classes of apoptosis-targeting agents, i.e. monoclonal antibodies against TNF-related apoptosis-inducing ligand (TRAIL) receptor 1 (mapatumumab) and TRAIL receptor 2 (lexatumumab) and small-molecule inhibitors of inhibitor of apoptosis (IAP) proteins. Here, we report that IAP inhibitors synergized with lexatumumab, but not with mapatumumab, to reduce cell viability and to induce apoptosis in several RMS cell lines in a highly synergistic manner (combination index <0.1). Cotreatment-induced apoptosis was accompanied by enhanced activation of caspase-8, -9, and -3; loss of mitochondrial membrane potential; and caspase-dependent apoptosis. In addition, IAP inhibitor and lexatumumab cooperated to stimulate the assembly of a cytosolic complex containing RIP1, FADD, and caspase-8. Importantly, knockdown of RIP1 by RNA interference prevented the formation of the RIP1·FADD·caspase-8 complex and inhibited subsequent activation of caspase-8, -9, and -3; loss of mitochondrial membrane potential; and apoptosis upon treatment with IAP inhibitor and lexatumumab. In addition, RIP1 silencing rescued clonogenic survival of cells treated with the combination of lexatumumab and IAP inhibitor, thus underscoring the critical role of RIP1 in cotreatment-induced apoptosis. By comparison, the TNFα-blocking antibody Enbrel had no effect on IAP inhibitor/lexatumumab-induced apoptosis, indicating that an autocrine TNFα loop is dispensable. By demonstrating that IAP inhibitors and lexatumumab synergistically trigger apoptosis in a RIP1-dependent but TNFα-independent manner in RMS cells, our findings substantially advance our understanding of IAP inhibitor-mediated regulation of TRAIL-induced cell death.
A simple and fast method of lipid analysis of isolated intact mitochondria by means of MALDI-TOF mass spectrometry is described. Mitochondria isolated from bovine heart and yeast have been employed to set up and validate the new method of lipid analysis. The mitochondrial suspension is directly applied over the target and, after drying, covered by a thin layer of the 9-aminoacridine matrix solution. The lipid profiles acquired with this procedure contain all peaks previously obtained by analyzing the lipid extracts of isolated mitochondria by TLC and/or mass spectrometry. The novel procedure allows the quick, simple, precise, and accurate analysis of membrane lipids, utilizing only a tiny amount of isolated organelle; it has also been tested with intact membranes of the bacterium Paracoccus denitrificans for its evolutionary link to present-day mitochondria. The method is of general validity for the lipid analysis of other cell fractions and isolated organelles.
The demand to develop convergent technology platforms, such as bio-functionalized medical devices, is rapidly increasing. However, the loss of biological function of the effector molecules during sterilization represents a significant and general problem. Therefore, we have developed and characterized a nano-coating (NC) formulation capable of maintaining the functionality of proteins on biological-device combination products. As a proof of concept, the NC preserved the structural and functional integrity of an otherwise highly fragile antibody immobilized on polyurethane during deleterious sterilizing irradiation (≥ 25 kGy). The NC procedure enables straight-forward terminal sterilization of bio-functionalized materials while preserving optimal conditioning of the bioactive surface.
Altered metabolism in tumor cells is increasingly recognized as a core component of the neoplastic phenotype. Because p53 has emerged as a master metabolic regulator, we hypothesized that the presence of wild-type p53 in glioblastoma cells could confer a selective advantage to these cells under the adverse conditions of the glioma microenvironment. Here, we report on the effects of the p53-dependent effector Tp53-induced glycolysis and apoptosis regulator (TIGAR) on hypoxia-induced cell death. We demonstrate that TIGAR is overexpressed in glioblastomas and that ectopic expression of TIGAR reduces cell death induced by glucose and oxygen restriction. Metabolic analyses revealed that TIGAR inhibits glycolysis and promotes respiration. Further, generation of reactive oxygen species (ROS) levels was reduced whereas levels of reduced glutathione were elevated in TIGAR-expressing cells. Finally, inhibiting the transketolase isoenzyme transketolase-like 1 (TKTL1) by siRNA reversed theses effects of TIGAR. These findings suggest that glioma cells benefit from TIGAR expression by (i) improving energy yield from glucose via increased respiration and (ii) enhancing defense mechanisms against ROS. Targeting metabolic regulators such as TIGAR may therefore be a valuable strategy to enhance glioma cell sensitivity toward spontaneously occurring or therapy-induced starvation conditions or ROS-inducing therapeutic approaches.
Introduction. Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin.
Material and methods. Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa2a (40KD) 180 or 90 Mg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns.
Results. The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication.
Conclusion. Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439).
Introduction: We report on successful endovascular treatment of a hydrofluoric acid burn to the hand.
Report: A worker complained of severe pain in the fingers D II to D V after injury with 60% hydrofluoric acid. A digital subtraction angiography showed vasospasm of the common palmar digital artery. We selectively applied 20% calcium gluconate intra-arterially.
After treatment all arteries were perfused. Alprostadil, acetylsalicylic acid and clopidogrel were administered in conjunction. Pain symptoms improved and sensory and motor functions were restored.
Discussion: Immediate angiography and intra-arterial application of calcium gluconate are recommended to treat hydrofluoric acid burn to a limb.