A5034713890- Nanoparticle-Based Drug Delivery
- Nanoplatforms for cancer theranostics
- Cell Adhesion Molecules Research
- DNA Repair Mechanisms
- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- Gold and Silver Nanoparticles Synthesis and Applications
- Genomics and Chromatin Dynamics
- Cancer Research and Treatments
- Drug Transport and Resistance Mechanisms
- 3D Printing in Biomedical Research
- NF-κB Signaling Pathways
- Cancer Immunotherapy and Biomarkers
- Barrier Structure and Function Studies
- RNA Interference and Gene Delivery
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Radiation Therapy and Dosimetry
- Carcinogens and Genotoxicity Assessment
- Protease and Inhibitor Mechanisms
- Radiopharmaceutical Chemistry and Applications
- Protein Kinase Regulation and GTPase Signaling
- Microfluidic and Bio-sensing Technologies
- Education Systems and Policy
- Cellular transport and secretion
Technical University of Denmark
2012-2024
University of Copenhagen
2023
Ørsted (Denmark)
2015-2021
Theranostics (New Zealand)
2020
Danish Geotechnical Society
2017
Interface (United States)
2014
California Institute of Technology
2009
University of Southern Denmark
2009
Danish Cancer Society
2004-2008
Lund University
2000-2004
We show that DNA double-strand breaks (DSBs) induce complex subcompartmentalization of genome surveillance regulators. Chromatin marked by gamma-H2AX is occupied ataxia telangiectasia-mutated (ATM) kinase, Mdc1, and 53BP1. In contrast, repair factors (Rad51, Rad52, BRCA2, FANCD2), ATM Rad-3-related (ATR) cascade (ATR, ATR interacting protein, replication protein A), the clamp (Rad17 -9) accumulate in subchromatin microcompartments delineated single-stranded (ssDNA). BRCA1 Mre11-Rad50-Nbs1...
Abstract Drug delivery to the brain is hampered by presence of blood-brain barrier, which excludes most molecules from freely diffusing into brain, and tightly regulates active transport mechanisms that ensure sufficient nutrients parenchyma. Harnessing possibility delivering neuroactive drugs way receptors already present on endothelium has been interest for many years. The transferrin receptor special since its expression limited as opposed peripheral endothelium. Here, we investigate...
53BP1 is a key component of the genome surveillance network activated by DNA double strand breaks (DSBs). Despite its known accumulation at DSB sites, spatiotemporal aspects interaction with DSBs and role other regulators in this process remain unclear. Here, we used real-time microscopy to study DSB-induced redistribution living cells. We show that within minutes after damage, becomes progressively, yet transiently, immobilized around DSB-flanking chromatin. Quantitative imaging single...
DNA double-strand breaks (DSBs) trigger accumulation of the MRE11-RAD50-Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex, whose retention on DSB-flanking chromatin facilitates survival. Chromatin MRN requires MDC1 adaptor protein, but mechanism behind MRN-MDC1 interaction is unknown. We show that NBS1 subunit interacts with N terminus enriched in Ser-Asp-Thr (SDT) repeats. This was constitutive and mediated by binding between phosphorylated SDT repeats phosphate-binding forkhead-associated...
Neutrophil apoptosis occurs both in the bloodstream and tissue is considered essential for resolution of an inflammatory process. Here, we show that p38–mitogen-activated protein kinase (MAPK) associates to caspase-8 caspase-3 during neutrophil p38-MAPK activity, previously shown be a survival signal these primary cells, correlates with levels phosphorylation. In vitro experiments, immunoprecipitated active phosphorylated inhibited activity p20 subunits caspase-3. Phosphopeptide mapping...
Rationale: The ability to treat invalidating neurological diseases is impeded by the presence of blood-brain barrier (BBB), which inhibits transport most blood-borne substances into brain parenchyma. Targeting transferrin receptor (TfR) on surface capillaries has been a popular strategy give preferential accumulation drugs or nanomedicines, but several aspects this targeting remain elusive. Here we report that TfR-targeted gold nanoparticles (AuNPs) can accumulate in and further across BBB...
Liposomal oxaliplatin remodels the tumor microenvironment and potentiate TLR-agonist–mediated immune responses in cancer.
The synthesis and biophysical characterization of four prodrug ether phospholipid conjugates are described. lipids prepared from the anticancer drug chlorambucil have C16 C18 chains with phosphatidylcholine or phosphatidylglycerol headgroups. All prodrugs ability to form unilamellar liposomes (86-125 nm) hydrolyzed by phospholipase A(2), resulting in release. Liposomal formulations displayed cytotoxicity toward HT-29, MT-3, ES-2 cancer cell lines presence IC(50) values 8-36 microM range.
The enhanced permeability and retention (EPR) effect increases tumor accumulation of liposomal chemotherapy should, in theory, increase anticancer effects lower toxicity. Unfortunately, has generally not met the expected potential, perhaps because EPR is ubiquitous. PET imaging using radiolabeled liposomes can identify cancers positive for effect. In current study, we show clinical canine cancer patients that repeated with (64Cu-liposome) induces accelerated blood clearance (ABC) phenomenon....
Secretory phospholipase A2 (sPLA2) is an interesting enzyme for triggered liposomal drug delivery to tumor tissue due the overexpression of sPLA2 in cancerous tissue. A system based on release therapeutics from sPLA2-sensitive liposomes constituted pro anticancer ether lipids, which become cytotoxic upon sPLA2-catalyzed hydrolysis has previously been established. To optimize rate lipids and thereby optimizing profile drugs liposomes, we have synthesized a thio-ester lipid. Liposomes this...
<p>This knowledge round-up addresses the question: What ought to be prioritized by non-profit organizations for meaningful civic connections Indigenous and Black young people? The answer this question is our Hearts + Minds theory of change mapped out in paper.</p>
<p>This knowledge round-up addresses the question: What ought to be prioritized by non-profit organizations for meaningful civic connections Indigenous and Black young people? The answer this question is our Hearts + Minds theory of change mapped out in paper.</p>
In this work, we have developed a microfluidic cytotoxicity assay for cell culture and detection platform, which enables both fluid handling electrochemical/optical detection. The cytotoxic effect of anticancer drugs doxorubicin (DOX), oxaliplatin (OX) as well OX-loaded liposomes, targeted drug delivery, was evaluated using real-time impedance monitoring. time-dependent DOX on HeLa cells monitored found to delayed onset in microfluidics compared with static conditions based data obtained our...
A common event in optic neuropathies is the loss of axons and death retinal ganglion cells (RGCs) resulting irreversible blindness. Mammalian target rapamycin (mTOR) signaling pathway agonists have been shown to foster axon regeneration RGC survival animal models nerve damage. However, many challenges remain developing therapies that exploit cell growth tissue remodeling including (i) activating/inhibiting pathways synergistically, (ii) avoiding tumorigenesis, (iii) ensuring appropriate...
Within the field of nanoparticle-assisted photothermal cancer therapy, focus has mostly been on developing novel heat-generating nanoparticles with right optical and dimensional properties. Comparison evaluation their performance in tumor-bearing animals are commonly assessed by changes tumor volume; however, this is usually a late-occurring event. This study implements 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging to perform early treatment outcome therapy....
In human neutrophils, β2 integrin engagement mediated a decrease in GTP-bound Rac1 and Rac2. Pretreatment of neutrophils with LY294002 or PP1 (inhibiting phosphatidylinositol 3-kinase (PI 3-kinase) Src kinases, respectively) partly reversed the integrin-induced down-regulation Rac activities. contrast, integrins induced stimulation Cdc42 that was independent family members. The PI dependence integrin-mediated could be explained by an enhanced Rac-GAP activity, since this activity blocked...
Abstract We found that engagement of β2 integrins on human neutrophils induced activation RhoA, as indicated by the increased ratio GTP:GTP + GDP recovered RhoA and translocation to a membrane fraction. The clustering also time-dependent increase in bound which correlated with integrin-induced p190RhoGAP. p190RhoGAP was completely blocked [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] (PP1), selective inhibitor Src family tyrosine kinases. However, did not basal...
The Cdc14 family of dual specificity phosphatases regulates key mitotic events in the eukaryotic cell cycle. Although extensively characterized yeast, little is known about function mammalian members. Here we report a genetic substrate-trapping system designed to identify substrates human Cdc14A (hCdc14A) phosphatase. Using this approach, RN-tre, GTPase-activating protein for Rab5 GTPase, as novel physiological target hCdc14A. As protein, RN-tre has previously been implicated control...
Surgery is still the first-line treatment for multiple solid cancers. However, recurrence a common issue, especially when dealing with aggressive tumors or that are difficult to completely remove due their location. Getting clear surgical margins can be challenging, but strategies combining surgery other anti-cancer therapies potentially improve outcome. Photothermal therapy (PTT) technique relies on photoabsorbing agents, such as gold nanoparticles, transform light into local hyperthermia....