A5064476636- Cancer therapeutics and mechanisms
- CAR-T cell therapy research
- PARP inhibition in cancer therapy
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Muon and positron interactions and applications
- DNA and Nucleic Acid Chemistry
- Advanced NMR Techniques and Applications
- Bone health and treatments
- Advanced Biosensing Techniques and Applications
- Economic and Social Issues
- Cancer Research and Treatments
- Pulmonary Hypertension Research and Treatments
- Liver physiology and pathology
- Cancer Immunotherapy and Biomarkers
- Cell Image Analysis Techniques
- Sociology and Education Studies
- Viral Infections and Immunology Research
- Sarcoma Diagnosis and Treatment
- Bone and Joint Diseases
- Safe Handling of Antineoplastic Drugs
- Synthesis and Characterization of Heterocyclic Compounds
- Cancer, Hypoxia, and Metabolism
- Computational Drug Discovery Methods
- Microfluidic and Capillary Electrophoresis Applications
Roche (Switzerland)
2013-2025
Canadian Standards Association
2023-2025
Standard Bio (Norway)
2023-2024
Johnson & Johnson (Switzerland)
2024
Princess Margaret Cancer Centre
2021-2023
University Health Network
2022-2023
University of Toronto
2023
Laboratory of Molecular Genetics
2023
Actelion (Switzerland)
2012-2022
Frederick National Laboratory for Cancer Research
2012-2018
Two populations of membrane-bound replication complexes were isolated from poliovirus-infected HEp-2 cells by sucrose gradient centrifugation. The two fractions show similar ultrastructural features: the complex is enclosed in a rosettelike shell virus-induced vesicles and contains very tightly packed second membrane system (compact membranes). vesicular fraction, which bands 30% sucrose, replicative intermediate (RI) 36S RNA. fraction banding 45% only minute amounts RI mainly RNA,...
Introducing nonnative metal ions or metal-containing prosthetic groups into a protein can dramatically expand the repertoire of its functionalities and thus range applications. Particularly challenging is control substrate-binding reaction selectivity such as enantioselectivity. To meet this challenge, both non-covalent single-point attachments complexes have been demonstrated previously. Since template did not evolve to bind artificial tightly in single conformation, efforts restrict...
Despite the availability of efficacious drugs, success treating hypertension is limited by patients' inconsistent drug intake. Immunization against angiotensin II may offer a valuable alternative to conventional drugs for treatment hypertension, because vaccines induce relatively long-lasting effects and do not require daily dosing. Here we describe preclinical development phase I clinical trial testing virus-like particle (VLP)-based antihypertensive vaccine.An II-derived peptide was...
Abstract Camptothecin and its derivatives, topotecan irinotecan, are specific topoisomerase I (Top1) inhibitors potent anticancer drugs killing cancer cells by producing replication-associated DNA double-strand breaks, the indenoisoquinoline LMP-400 (indotecan) is a novel Top1 inhibitor in clinical trial. To develop drug combinations, we conducted synthetic lethal siRNA screen using library that targets nearly 7,000 human genes. Depletion of ATR, main transducer replication stress, came as...
Abstract Topoisomerase I (Top1) is a proven target for cancer therapeutics, and the level of Top1 in tumors has been used as biomarker chemotherapeutic efficacy. In this study, we report development validation two-site enzyme chemiluminescent immunoassay Top1, which to measure levels NCI-60 cell line panel. ranged from 0.9 9.8 ng/mL/μg protein extract these lines. Levels varied both within between types but were generally highest colon leukemia lines lowest central nervous system renal mRNA...
To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6-month period in patients with systemic sclerosis (SSc).In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) we evaluated 623 SSc from 59 centers (14 countries). Patients were stratified into 2 groups: DU history group no group. At enrollment, underwent detailed evaluation assessment of demographic characteristics, status,...
The highly conserved non-structural protein 2C of picornaviruses is involved in viral genome replication and encapsidation the rearrangement intracellular structures. binds RNA, has nucleoside triphosphatase activity, shares three motifs with superfamily III helicases. Motifs "A" "B" are nucleotide triphosphate (NTP) binding hydrolysis, whereas a function for motif "C" not yet been demonstrated. Poliovirus RNA inhibited by millimolar concentrations guanidine hydrochloride (GdnHCl)....
Cysteine plays a key role as metal ligand in metalloproteins. In all well-recognized cases, however, it is the anionic cysteinate that coordinates. Several cysteinate-ligated heme proteins are known, but some fail to retain thiolate ligation ferrous state, possibly following protonation form neutral cysteine. Ligation by cysteine thiol has not been documented. To establish spectroscopic signatures for such systems, we have prepared five-coordinate adducts of myoglobin H94G cavity mutant with...
Circulating tumor cells (CTC) in peripheral blood of patients potentially represent a fraction solid available for more frequent pharmacodynamic assessment drug action than is possible using biopsy. However, currently CTC assays are limited to cell membrane antigens. Here, we describe an assay that directly examines changes levels the nuclear DNA damage marker gammaH2AX individual CTCs treated with chemotherapeutic agents.An Alexa Fluor 488-conjugated monoclonal antibody and epithelial...
Continuous infusion of epoprostenol is the treatment choice in patients with pulmonary arterial hypertension functional classes III to IV. However, this treatment's limitations include instability at room temperature. A new formulation offers improved storage conditions and patient convenience. The EPITOME-2 trial was an open-label, prospective, multicenter, single-arm, phase IIIb study. Patients on long-term, stable therapy were transitioned from glycine mannitol excipients (Flolan;...
<b><i>Background:</i></b> Developments in the field of digital measures and digitally derived endpoints demand greater attention on globally aligned approaches to enhance measure acceptance by regulatory authorities health technology assessment (HTA) bodies for decision-making. In order maximize value global drug development programs ensure study teams regulators are referring same items, alignment concepts, definitions, terminology is required. This a fast-moving...
ABSTRACT Southampton virus (SHV) is a member of the Norwalk-like viruses (NLVs), one four genera family Caliciviridae . The genome SHV contains three open reading frames (ORFs). ORF 1 encodes polyprotein that autocatalytically processed into six proteins, which p41. p41 shares sequence motifs with protein 2C picornaviruses and superfamily 3 helicases. We have expressed in bacteria. Purified exhibited nucleoside triphosphate (NTP)-binding NTP hydrolysis activities. NTPase activity was not...
ABSTRACT Protein 2C ATPase of picornaviruses is involved in the rearrangement host cell organelles, viral RNA replication, and encapsidation. However, biochemical molecular mechanisms by which engages these processes are not known. To characterize functional domains , we have focused on a cysteine-rich motif near carboxy terminus poliovirus . This region, well conserved among enteroviruses rhinoviruses displaying an amino acid arrangement resembling zinc finger motifs, was studied genetic...
Humoral immune responses are thought to be enhanced by complement-mediated recruitment of the CD21-CD19-CD81 coreceptor complex into B cell antigen receptor (BCR) complex, which lowers threshold activation and increases survival proliferative capacity responding cells. To investigate role CD21-CD35 complement receptors in generation memory, we analyzed response against viral particles derived from bacteriophage Qbeta mice deficient (Cr2(-/-)). Despite highly efficient induction early...
Because topoisomerase 1 (TOP1) is critical for the relaxation of DNA supercoils and because it target anticancer activity camptothecins, we assessed TOP1 transcript levels in 60 cell line panel (the NCI-60) National Cancer Institute's drug screen. expression varied over a 5.7-fold range across NCI-60. HCT116 colon MCF-7 breast cancer cells were highest expressers; SK-MEL-28 melanoma HS578T carcinoma lowest. mRNA was highly correlated with Top1 protein levels, indicating that transcripts...