- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Histone Deacetylase Inhibitors Research
- Peptidase Inhibition and Analysis
- Diet and metabolism studies
- Virus-based gene therapy research
- Adipose Tissue and Metabolism
- Hormonal and reproductive studies
- Cancer Research and Treatments
- Amino Acid Enzymes and Metabolism
- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Estrogen and related hormone effects
- PI3K/AKT/mTOR signaling in cancer
- Epigenetics and DNA Methylation
- Radiopharmaceutical Chemistry and Applications
- Sexual Differentiation and Disorders
- Poxvirus research and outbreaks
- Veterinary Oncology Research
- Alkaloids: synthesis and pharmacology
- Folate and B Vitamins Research
- Liver Disease Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Traditional and Medicinal Uses of Annonaceae
Helmholtz Zentrum München
2016-2025
Helmholtz Association of German Research Centres
2023
Karus Therapeutics (United Kingdom)
2007-2021
University of Würzburg
2011-2021
University of Southampton
2002-2007
Cancer Research UK
2007
Middlemore Hospital
1999-2001
University of Auckland
1999
Enteric glial cells (EGCs) are the main constituent of enteric nervous system and share similarities with astrocytes from central including their reactivity to an inflammatory microenvironment. Previous studies on EGC pathophysiology have specifically focused mucosal glia activation its contribution processes observed in gut bowel disease (IBD) patients. In contrast knowledge is scarce intestinal inflammation not locally restricted mucosa but systemically affecting intestine effect overall...
Glycolysis and fatty acid synthesis are highly active in cancer cells through cytosolic citrate metabolism, with intracellular primarily derived from either glucose or glutamine via the tricarboxylic cycle. We show here that extracellular is supplied to a plasma membrane-specific variant of mitochondrial transporter (pmCiC). Metabolomic analysis revealed uptake broadly affected cell metabolism citrate-dependent metabolic pathways. Treatment gluconate specifically blocked pmCiC decreased...
Inhibition of histone deacetylase 6 (HDAC6) is predicted to deliver both direct antitumor activity and modulation the immune response. This study describes development a novel HDAC6 inhibitor.KA2507 was characterized in HDAC biochemical cellular target engagement assays preclinical efficacy models melanoma colorectal cancer. In phase I study, KA2507 administered orally using 3+3 dose-escalation design (NCT03008018).KA2507 potent selective inhibitor (biochemical IC50 = 2.5 nmol/L)....
The FK228 and spiruchostatin bicyclic depsipeptide natural products are among the most potent histone deacetylase (HDAC) inhibitors known. Although is in advanced clinical trials, complexity of has precluded mechanistic studies discovery structure−activity relationships. By total synthesis, we have prepared first analogues. Our results prove that dehydrobutyrine residue not essential, other residues can be substituted without loss HDAC inhibitory activity. Conformational restriction by...
Abstract Metabolomic analyses in epidemiological studies have demonstrated a strong sexual dimorphism for most metabolites. Cross-sex hormone treatment (CSH) transgender individuals enables the study of metabolites cross-gender setting. Targeted metabolomic profiling serum fasting transmen and transwomen at baseline following 12 months CSH (N = 20/group) was performed. Changes 186 metabolite ratios were determined by targeted metabolomics analysis based on ESI-LC-MS/MS. RandomForest (RF)...
Citrate is important for lipid synthesis and epigenetic regulation in addition to ATP production. We have previously reported that cancer cells import extracellular citrate via the pmCiC transporter support their metabolism. Here, we show first time supplied by cancer-associated stroma (CAS) also release one of latter’s major metabolic tasks. from CAS controlled through cross-cellular communication. The availability regulated cytokine profile, metabolism features cellular invasion. Moreover,...
Virotherapy on the basis of oncolytic vaccinia virus (VACV) strains is a novel approach for canine cancer therapy. Here we describe, first time, characterization and use VACV strain GLV-5b451 expressing anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as therapeutic agent against different cancers. Cell culture data demonstrated that efficiently infected destroyed all four tested cell lines including: mammary carcinoma (MTH52c), adenoma (ZMTH3), prostate...
This study compared metabolite shifts induced by training for, participation in, and recovery from a marathon race competition among athletes divided into three groups based on fitness (relative maximum oxygen uptake (VO2max)) performance levels (net running time). Plasma samples 76 male runners participating in the Munich Marathon were analyzed for using targeted metabolomics panel. For entire cohort of runners, pronounced increases measured immediately after plasma concentrations...
Metabolomics and lipidomics are pivotal in understanding phenotypic variations beyond genomics. However, quantification comparability of mass spectrometry (MS)-derived data challenging. Standardised assays can enhance comparability, enabling applications multi-center epidemiological clinical studies. Here we evaluated the performance reproducibility MxP® Quant 500 kit across 14 laboratories. The allows 634 different metabolites from 26 compound classes using triple quadrupole MS. Each...
cis-Solamin (1) and its diastereoisomer 14 have been synthesized in 13 steps using the diastereoselective permanganate-promoted oxidative cyclization of 1,5-dienes to create tetrahydrofuran diol core. Notably, no protecting groups are required during stages fragment assembly.
The drug-minded protein interaction database (DrumPID) has been designed to provide fast, tailored information on drugs and their networks including indications, targets side-targets. Starting queries include compound, target interactions organism-specific families. Furthermore, drug name, chemical structures SMILES notation, affected proteins (potential targets), organisms as well diseases can be queried various combinations refinement of searches. Drugs are analyzed in detail with...
Background Sex hormones and sex hormone-binding globulin (SHBG) may play a role in fatty liver development. We sought to examine the association of various endogenous hormones, including testosterone (T), SHBG with fat using complementary observational Mendelian randomization (MR) analyses. Methods The analysis included total 2,239 participants (mean age 60 years; 35% postmenopausal women) from population-based KORA study (average follow-up time: 6.5 years). conducted linear regression...
Xenobiotics represent an environmental stress and as such are a source for antibiotics, including the isoquinoline (IQ) compound IQ-143. Here, we demonstrate utility of complementary analysis both host pathogen datasets in assessing bacterial adaptation to IQ-143, synthetic analog novel type N,C-coupled naphthyl-isoquinoline alkaloid ancisheynine. Metabolite measurements, gene expression data functional assays were combined with metabolic modeling assess effects IQ-143 on Staphylococcus...
In the past, different bacterial species have been tested for cancer therapy in preclinical and clinical studies. The success of is mainly dependent on ability utilized bacteria to overcome host immune defense system colonize tumors initiate tumor-specific immunity. recent years, several groups demonstrated that gut microbiome plays an important role modulation response has impact therapeutic responses murine models cohorts human patients. Here we analyzed tumor colonization by Escherichia...
Sex hormone-binding globulin (SHBG) and androgens have been associated with mortality in women men, but controversy still exists. Our objective was to investigate associations of SHBG all-cause cause-specific men women.1006 709 peri- postmenopausal (age range: 45-82 years) from the German population-based KORA F4 cohort study were followed-up for a median 8.7 years.SHBG measured an immunoassay, total testosterone (TT) dihydrotestosterone (DHT) mass-spectrometry serum samples we calculated...
Relationships between endogenous female sex hormones and glycemic traits remain understudied, especially in men. We examined whether 17α-hydroxyprogesterone (17-OHP), progesterone, estradiol (E2), free (fE2) were associated with deterioration.921 mainly middle-aged elderly men 390 perimenopausal/postmenopausal women from the German population-based Cooperative Health Research Region of Augsburg (KORA) F4/FF4 cohort study followed up for a median 6.4 years. Sex measured at baseline using mass...
Summary Aims Type 2 diabetes mellitus and its complications are common among Polynesians in New Zealand. This study investigated the mortality from indigenous Maori recent migrants South Pacific. Methods Death certificates other reports were collected to enumerate those who had died an across‐community cohort of 765 diabetic patients aged 40–79 years 1991. Five year status was ascertained 99.7% death obtained 129 (88%) 146 died. Diabetes missed 36% certificates. Results Compared Europeans...
This study investigates impaired awareness of hypoglycaemia (IAH), a complication insulin therapy affecting 20-40% individuals with type 1 diabetes. The exact pathophysiology is unclear, therefore we sought to identify metabolic signatures in IAH elucidate potential pathophysiological pathways. Plasma samples from 578 the Dutch diabetes biomarker cohort, 67 and 108 without (NAH) were analysed using targeted metabolomics Biocrates AbsoluteIDQ p180 assay. Eleven metabolites significantly...