A5087387263- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Microtubule and mitosis dynamics
- Prostate Cancer Treatment and Research
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Cancer Cells and Metastasis
- Peptidase Inhibition and Analysis
- Cancer Mechanisms and Therapy
- PI3K/AKT/mTOR signaling in cancer
- Glycosylation and Glycoproteins Research
- Mitochondrial Function and Pathology
- Mass Spectrometry Techniques and Applications
- PARP inhibition in cancer therapy
- Chronic Lymphocytic Leukemia Research
- Heat shock proteins research
- Lung Cancer Research Studies
- Pancreatic and Hepatic Oncology Research
- Cancer Treatment and Pharmacology
- Liver physiology and pathology
- Cell death mechanisms and regulation
- Computational Drug Discovery Methods
Nuvisan (Germany)
2022-2025
Bayer (Germany)
2010-2023
Boehringer Ingelheim (Germany)
2012
Prometheus Biosciences (United States)
2010
Bayer (United States)
2010
Prometheus (United States)
2010
Heidelberg University
2001
Duke University Hospital
2001
Duke Medical Center
2001
La Jolla Institute for Immunology
2000-2001
Abstract Background Circulating tumour cells (CTCs) have shown prognostic relevance in metastatic breast, prostate, colon and pancreatic cancer. For further development of CTCs as a biomarker, we compared the performance different protocols for CTC detection murine breast cancer xenograft models (MDA-MB-231, MDA-MB-468 KPL-4). Blood samples were taken from bearing animals (20 to 200 mm 2 ) analysed using 1. an epithelial marker based enrichment method (AdnaTest), 2. antibody independent...
During apoptosis, cytochrome c is released into the cytosol as outer membrane of mitochondria becomes permeable, and this acts to trigger caspase activation. The consequences release for mitochondrial metabolism are unclear. Using single-cell analysis, we found that when activity inhibited, permeabilization causes a rapid depolarization transmembrane potential, which recovers original levels over next 30–60 min then maintained. After permeabilization, can use cytoplasmic maintain potential...
Proapoptotic members of the Bcl-2 protein family, including Bid and Bax, can activate apoptosis by directly interacting with mitochondria to cause cytochrome c translocation from intermembrane space into cytoplasm, thereby triggering Apaf-1–mediated caspase activation. Under some circumstances, when activation is blocked, cells recover translocation; this suggests that apoptotic may not always suffer catastrophic damage arising process release. We now show recombinant Bax complete loss...
The use of circulating tumor cells (CTC) as "liquid biopsy" is limited by the very low yield CTCs available for subsequent analyses. Most in vitro approaches rely on small sample volumes (5-10 mL).Here, we used a novel approach, GILUPI CellCollector, which enables an vivo isolation from peripheral blood. In total, 50 lung cancer patients were screened two device applications before and after therapy (n = 185 applications).By isolation, 58% (108/185) positive ≥1 CTC (median, 5 CTCs; range,...
Abstract Purpose: Prostate-specific membrane antigen (PSMA) is an attractive target for radionuclide therapy of metastatic castration-resistant prostate cancer (mCRPC). PSMA-targeted alpha (TAT) has shown early signs activity in patients with refractory to beta radiation. We describe a novel, antibody-based TAT, the thorium-227 conjugate PSMA-TTC (BAY 2315497) consisting alpha-particle emitter complexed by 3,2-HOPO chelator covalently linked fully human PSMA-targeting antibody. Experimental...
Monopolar spindle 1 (Mps1) has been shown to function as the key kinase that activates assembly checkpoint (SAC) secure proper distribution of chromosomes daughter cells. Here, we report structure and functional characterization two novel selective Mps1 inhibitors, BAY 1161909 1217389, derived from structurally distinct chemical classes. 1217389 inhibited activity with IC50 values below 10 nmol/L while showing an excellent selectivity profile. In cellular mechanistic assays, both inhibitors...
// Tobias M. Gorges 1, * , Sabine Riethdorf Oliver von Ahsen 2, Paulina Nastały 1 Katharina Röck Marcel Boede 3 Sven Peine 4 Andra Kuske Elke Schmid 2 Christoph Kneip Frank König Marion Rudolph Klaus Pantel Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany BPH-DD-TRG-CIPL-Biomarker Research, Bayer Pharma AG, Berlin, ATURO, Urology Practice, Transfusion Medicine, Shared first authorship Correspondence to: Pantel, e-mail: pantel@uke.de Keywords:...
Prostate cancer is a frequent malignancy in older men and has very high 5‐year survival rate if diagnosed early. The prognosis much less promising the tumor already spread outside prostate gland. Targeted treatments mainly aim at blocking androgen receptor (AR) signaling initially show good efficacy. However, progression due to AR‐dependent AR‐independent mechanisms often observed after some time, novel treatment strategies are urgently needed. Dysregulation of PI3K/AKT/mTOR pathway advanced...
Since surgical removal remains the only cure for pancreatic cancer, early detection is of utmost importance. Circulating biomarkers have potential as diagnostic tool which typically causes clinical symptoms in advanced stage. Because their high prevalence KRAS proto-oncogene, GTPase [KRAS (previous name: Kirsten rat sarcoma viral oncogene homolog)] mutations may be used to identify tumor-derived circulating plasma DNA. Here we tested sensitivity chip based digital PCR tumor DNA (ctDNA) stage...
// Seong Joo Koo 1 , Amaury E. Fernández-Montalván Volker Badock Christopher J. Ott 2, 3, 4 Simon Holton Oliver von Ahsen Joern Toedling Sarah Vittori 3 James Bradner 4, 5 Mátyás Gorjánácz Drug Discovery, Bayer Pharma AG, Berlin, Germany 2 Center for the Science of Therapeutics, Broad Institute, Cambridge, MA, USA Department Medical Oncology, Dana-Farber Cancer Boston, Medicine, Harvard School, Present address: Novartis Institute BioMedical Research,...
BackgroundEndothelial dysfunction is involved in several cardiovascular diseases. Elevated levels of circulating endothelial cells (CECs) and low progenitor (EPCs) have been described different conditions, suggesting their potential use as diagnostic biomarkers for dysfunction. Compared to typical peripheral blood leukocyte subsets, CECs EPCs occur at very frequency. The reliable identification characterization a prerequisite clinical use, however, validated method this purpose still missing...
The catalytic function of BUB1 is required for chromosome arm resolution and positioning the chromosomal passenger complex spindle attachment errors plays only a minor role in assembly checkpoint activation. Here, we present identification preclinical pharmacologic profile first kinase inhibitor with good bioavailability.The Bayer compound library was screened inhibitors medicinal chemistry efforts to improve target affinity physicochemical pharmacokinetic parameters resulting BAY 1816032...
The enormous cellular complexity of the brain is a major obstacle for gene expression profiling neurological disease models, because physiologically relevant changes transcription in specific neuronal subset are likely to be lost presence other neurons and glia. We solved this problem transgenic mice by labeling genetically defined cells with nuclear variant GFP. When combined laser-directed microdissection, intact RNA from unfixed, freeze-dried sections can isolated, which prerequisite...
C4.4A (LYPD3) has been identified as a cancer- and metastasis-associated internalizing cell surface protein that is expressed in non-small lung cancer (NSCLC), with particularly high prevalence the squamous carcinoma (SCC) subtype. With exception of skin keratinocytes esophageal endothelial cells, expression scarce normal tissues, presenting an opportunity to selectively treat cancers C4.4A-directed antibody-drug conjugate (ADC). We have generated BAY 1129980 (C4.4A-ADC), ADC consisting...
Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a surface receptor, is expressed on normal epithelial tissue and highly in cancers of high unmet medical need, such as non-small lung, pancreatic, colorectal cancer. CEACAM receptors undergo homo- heterophilic interactions thereby regulating homeostasis angiogenesis, cancer, tumor invasion metastasis. CEACAM6 expression malignant plasma cells inhibits antitumor activity T cells, we hypothesize similar function cancer cells....
Abstract Immunotherapy has emerged as a promising cancer treatment strategy, including approaches such immune checkpoint inhibitors (ICIs), cytokine-based therapies, chimeric antigen receptor (CAR) T-cell oncolytic viruses, vaccines, and combination treatments. ICIs CAR-T-cells have revolutionized therapy, significantly enhancing the landscape for variety of cancers. However, despite encouraging results in preclinical models, translating novel therapies into clinical success remains...
Interaction of preproteins with the heat shock protein Hsp70 in mitochondrial matrix is required for driving transport across inner membrane. Binding mt-Hsp70 to Mim44 membrane import site seems be an essential part ATP-dependent reaction cycle. However, available results on role played by ATP are controversial. Here we demonstrate that mt-Hsp70•Mim44 complex contains ADP and a nonhydrolyzable analog dissociates presence potassium ions. The previously reported requirement hydrolysis...
The signal recognition particle (SRP) is a cytoplasmic RNA-protein complex that targets proteins to the rough endoplasmic reticulum. Although SRP functions in cytoplasm, RNA microinjection and cDNA transfection experiments animal cells, as well genetic analyses yeast, have indicated assembles nucleus. Nonetheless, mechanisms responsible for nuclear-cytoplasmic transport of are largely unknown. Here we show 19 kDa protein subunit mammalian SRP, SRP19, was efficiently imported into nucleus...
Abstract Cerebral ischaemia induces transcriptional changes in a number of pathophysiologically important genes. Here we have systematically studied gene expression after 90 min and 24 h permanent focal the mouse by an advanced fragment display technique (restriction‐mediated differential display). We identified 56 transcriptionally altered genes, many which provide novel hints to ischaemic pathophysiology. Particularly interesting were two pro‐apoptotic genes (Grim19 Tdag51), whose role...
Abstract: T-cell-mediated processes play an essential role in the pathogenesis of several inflammatory skin diseases such as atopic dermatitis, allergic contact dermatitis and psoriasis. The aim this study was to investigate IL-2-inducible tyrosine kinase (Itk), enzyme acting downstream T-cell receptor (TCR), T-cell-dependent inflammation using three approaches. Itk knockout mice display significantly reduced symptoms mouse models acute subacute hypersensitivity (CHS) reactions. Systemic...