A5102800109- HIV Research and Treatment
- Metal complexes synthesis and properties
- Ferrocene Chemistry and Applications
- Click Chemistry and Applications
- N-Heterocyclic Carbenes in Organic and Inorganic Chemistry
- vaccines and immunoinformatics approaches
- Hepatitis B Virus Studies
- Vaccine Coverage and Hesitancy
- Organometallic Complex Synthesis and Catalysis
- HIV/AIDS Research and Interventions
- Advanced biosensing and bioanalysis techniques
- Polyomavirus and related diseases
- Supramolecular Chemistry and Complexes
- Sociology and Education Studies
- Immune cells in cancer
- Transgenic Plants and Applications
- Full-Duplex Wireless Communications
- Glioma Diagnosis and Treatment
- Virology and Viral Diseases
- DNA and Nucleic Acid Chemistry
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Analytical chemistry methods development
- Nanocluster Synthesis and Applications
German Cancer Research Center
2009-2025
Heidelberg University
2009-2025
Technical University of Munich
2018-2024
Universität Hamburg
1998-2024
University Medical Center Hamburg-Eppendorf
2011-2024
Roche (Switzerland)
2024
Hebrew University of Jerusalem
2020-2023
DKFZ-ZMBH Alliance
2009-2023
Technische Universität Braunschweig
2012-2022
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2022
Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed evaluate contribution of patient-specific immune microenvironment response licensed yellow fever 17D (YF-17D) an cohort.
ABSTRACT A double-blind randomized phase I trial was conducted in human immunodeficiency virus type 1 (HIV-1)-negative subjects receiving vaccines vectored by plasmid DNA and modified vaccinia Ankara (MVA) expressing HIV-1 p24/p17 gag linked to a string of CD8 + T-cell epitopes. The had two groups. One group received either doses MVA.HIVA (2× MVA.HIVA) ( n = 8) or placebo placebo) 4). second 2× pTHr.HIVA followed one dose 3× In the pTHr.HIVA-MVA.HIVA group, HIV-1-specific responses peaked...
The immunogenicities of candidate DNA- and modified vaccinia virus Ankara (MVA)-vectored human immunodeficiency (HIV) vaccines were evaluated on their own in a prime-boost regimen phase I clinical trials healthy uninfected individuals the United Kingdom. Given current lack approaches capable inducing broad HIV-neutralizing antibodies, pTHr.HIVA DNA MVA.HIVA focus solely induction cell-mediated immunity. expressed common immunogen, HIVA, which consists consensus HIV-1 clade A Gag p24/p17...
Background DNA-based vaccines have been safe but weakly immunogenic in humans to date. Methods and Findings We sought determine the safety, tolerability, immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by vivo electroporation (EP) Phase-1, double-blind, randomized placebo-controlled trial healthy volunteers. Eight volunteers each received 0.2 mg, 1 or 4 mg ADVAX saline placebo via EP, standard intramuscular injection at weeks 0 8. A third...
Contrast material is generally well tolerated although approximately 1% of patients who receive low-osmolar nonionic contrast will develop anaphylaxis symptoms. Because most anaphylactic reactions are mild and nonallergic, clinically mimicking immunoglobulin E (IgE)-mediated allergy, diagnostic skin testing has been discussed controversially in the past prophylactic pretreatment drug regimens recommended instead. In 6 years, all with material-induced have subjected to allergologic procedures...
Gold complexes with N-heterocyclic carbene (NHC) ligands represent a promising class of metallodrugs for the treatment cancer or infectious diseases. In this report, synthesis and biological evaluation halogen-containing NHC-AuI -Cl are described. The 1 5 a-5 f displayed good cytotoxic activity against tumor cells, cellular uptake studies suggested that an intact Au-NHC fragment is essential accumulation high amounts both metal NHC ligand. However, bioavailability was negatively affected by...
Proliferation of interstitial fibroblasts is a hallmark progressive renal fibrosis commonly resulting in chronic kidney failure. The intermediate-conductance Ca 2+ -activated K + channel (K 3.1) has been proposed to promote mitogenesis several cell types and contribute disease states characterized by excessive proliferation. Here, we hypothesized that 3.1 activity pivotal for fibroblast proliferation deficiency or pharmacological blockade suppresses development fibrosis. We found mitogenic...
ABSTRACT Interference with tumor suppressor pathways by polyomavirus-encoded antigens (T-Ags) can result in transformation. Consequently, it is thought that T-Ags encoded Merkel cell polyomavirus (MCPyV), a virus integrated ∼90% of all carcinoma (MCC) cases, are major contributors to tumorigenesis. The MCPyV large T-Ag (LT-Ag) has preserved the key functional domains present family members but also acquired unique regions flank LxCxE motif. As these may mediate functions, or modulate those...
The Sry-related protein Sox10 is selectively expressed in neural crest cells during early stages of development and glial the peripheral central nervous systems late adult. Mutation gene leads to defects Dominant megacolon mouse mutant combined Waardenburg-Hirschsprung syndrome humans. Here, we have studied four mutations found date patients both context rat human cDNA. Unlike protein, which failed show transcriptional activity on its own, displayed a weak, but reproducible, as activator....
Background We conducted a double-blind, randomized, placebo-controlled Phase I study of recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B Env subtypes A, C, given alone or as boost following DNA plasmid vaccine the same proteins plus Nef, in 114 healthy HIV-uninfected African adults. Methodology/Principal Findings Volunteers were randomized to 4 groups receiving rAd5 intramuscularly at dosage levels 1×1010 1×1011 particle units (PU)...
Abstract Gold complexes with N-heterocyclic carbene (NHC) ligands have been attracting major attention in medicinal inorganic chemistry based on their favorable antiproliferative effects and the structural versatility of coordinated NHC ligands. Here we present a novel complex type (NHC)2Au+, which represents substantially improved selective TrxR inhibitor compared to close analogues. The is highly stable various solutions over 96 hours, however, comparative cellular uptake studies indicate...
Biscarbene gold(<sc>i</sc>) complexes were prepared and evaluated for their effects against cancer cells pathogenic bacteria.
A novel alkynyl phosphane gold(I) complex (trimethylphosphane)(3-(1,3-dimethylxanthine-7-yl)prop-1-yn-1-yl)gold(I) 1 displayed mutiple biological activites including selective proliferation inhibitory, anti-metastatic, and anti-angiogenic effects. The also induced effects related to aneuploidy in HCT-116 colon carcinoma cells, which might be mainly ascribed the dysfunction of mitochondrial bioenergetics downregulation glycolysis. Induction beyond a critical level can provide an effective...
"Multi-action" Pt(IV) derivatives of cisplatin with combretastatin A4 (CA4) bioactive ligands that are conjugated to by carbonate unique because the ligand (IC50 < 10 nM) is dramatically 1000-folds more cytotoxic than in vitro. The Pt(IV)-CA4 prodrugs were as CA4 itself, indicating platinum moiety probably plays an insignificant role triggering cytotoxicity, suggesting complexes act for rather true multi-action prodrugs. In vivo tests (Lewis lung carcinoma) show ctc-[Pt(NH3)2(PhB)(CA4)Cl2]...
The biomedical application of discrete supramolecular metal-based structures, specifically self-assembled metallacages, is still an emergent field study. Capitalizing on the knowledge gained in recent years development 3-dimensional (3D) metallacages as novel drug delivery systems and theranostic agents, we explore here possibility to target [Pd2L4]4+ cages (L = 3,5-bis(3-ethynylpyridine)phenyl ligand) brain. In detail, a new water-soluble homoleptic cage (CPepH3) tethered blood brain...
The isocitrate dehydrogenase (IDH) gene is recurrently mutated in adult diffuse gliomas. IDH-mutant gliomas are categorized into oligodendrogliomas and astrocytomas, each with unique pathological features. Here, we use single-nucleus RNA ATAC sequencing to compare the molecular heterogeneity of these glioma subtypes. In addition astrocyte-like, oligodendrocyte progenitor-like, cycling tumor subpopulations, a population enriched for ribosomal genes translation elongation factors primarily...
Abstract Au I ‐carbene and Pt IV −Au prodrugs display low to sub‐μM activity against several cancer cell lines overcome cisplatin (cisPt) resistance. Linking a cisPt‐derived (phenylbutyrate) complex ‐phenylimidazolylidene 2 , yielded the most potent prodrug. While in vivo tests Lewis Lung Carcinoma showed that prodrug (phenylbutyrate)‐Au ( 7 ) 1 : co‐administration of cisPt: phenylbutyrate: efficiently inhibited tumor growth (≈95 %), much better than (75 %) or cisPt (84 exhibited only 5 %...
Treatment of triple-negative breast cancer (TNBC) has long been a medical challenge because the lack effective therapeutic targets. Targeting lipid, carbohydrate, and nucleotide metabolism pathways recently proven as promising option in view three heterogeneous metabolic-pathway-based TNBC subtypes. Here, we present multimodal anticancer platinum(II) complex, named Pt(II)caffeine, with novel mode action involving simultaneous mitochondrial damage, inhibition metabolic pathways, promotion...