A5043567502- Cancer, Hypoxia, and Metabolism
- Amino Acid Enzymes and Metabolism
- Medical Imaging Techniques and Applications
- Radiopharmaceutical Chemistry and Applications
- Alkaloids: synthesis and pharmacology
- Glioma Diagnosis and Treatment
- Amyotrophic Lateral Sclerosis Research
- Berberine and alkaloids research
- Drug Transport and Resistance Mechanisms
- Epigenetics and DNA Methylation
- Carbohydrate Chemistry and Synthesis
- Neuroscience and Neuropharmacology Research
- Fluorine in Organic Chemistry
- Lanthanide and Transition Metal Complexes
- Neurotransmitter Receptor Influence on Behavior
- Biological Activity of Diterpenoids and Biflavonoids
- Neuroendocrine regulation and behavior
- Cholinesterase and Neurodegenerative Diseases
- HER2/EGFR in Cancer Research
- Nicotinic Acetylcholine Receptors Study
- Silymarin and Mushroom Poisoning
- Biochemical Analysis and Sensing Techniques
- NF-κB Signaling Pathways
- Phytoestrogen effects and research
- Neuroinflammation and Neurodegeneration Mechanisms
TRIUMF
2016-2023
Spinal Cord Injury BC
2023
Terry Fox Research Institute
2023
BC Cancer Agency
2017-2019
University of British Columbia
2016-2019
Mario Negri Institute for Pharmacological Research
2003-2009
University of Bologna
2009
The RAS family of proto-oncogenes are among the most commonly mutated genes in human cancers and predict poor clinical outcome. Several mechanisms underlying oncogenic transformation well documented, including constitutive signaling through RAF-MEK-ERK proproliferative pathway as PI3K-AKT prosurvival pathway. Notably, control redox balance has also been proposed to contribute transformation. However, how homeostasis between reactive oxygen species (ROS) antioxidants, which have opposing...
A mild and selective photocatalytic C–H 18F-fluorination reaction has been developed that provides direct access to 18F-fluorinated amino acids. The biodistribution uptake of three 18F-labeled leucine analogues via LAT1 mediated transport in several cancer cell lines is reported. Positron emission tomography imaging mice bearing PC3 (prostate) or U87 (glioma) xenografts using 5-[18F]-fluorohomoleucine showed high tumor excellent visualization, highlighting the utility this strategy for rapid...
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder involving the selective degeneration of motor neurons. In small proportion patients, ALS caused by mutations in copper/zinc superoxide dismutase (SOD1), and mice overexpressing SOD1(G93A) mutant develop syndrome that closely resembles human disease. Excitotoxicity mediated glutamate AMPA receptors has been suggested to be implicated susceptibility neurons occurring ALS. mice, we found levels GluR2 subunit, which plays...
Microdialysis was used to study the acute and chronic effects of escitalopram (S‐citalopram; ESCIT) citalopram (CIT), together with 5‐HT 1A receptor antagonist WAY100,635 ( N ‐[2‐[methoxyphenyl)‐1‐piperazinyl]ethyl]‐ ‐(2‐pyridinyl) cyclohexane carboxamide trihydrochloride) agonist 8‐hydroxy‐2‐(di‐ n ‐propylamino)tetralin (8‐OH‐DPAT), on extracellular 5‐hydroxytryptamine (5‐HT) levels in rat prefrontal cortex. Extracellular rose 234 298% basal values after subcutaneous (s.c.) doses 0.15 0.63...
The site-selective fluorination of unactivated C(sp3)-H bonds provides unique opportunities to rapidly alter drug properties or generate radiotracers for positron emission tomography (PET) imaging. Toward this goal, photoactivated decatungstate (DT) is capable generating carbon radicals through hydrogen atom transfer that subsequently undergo by reaction with N-fluorobenzenesulfonimide (NFSI) [18F]NFSI. This process enables a wide range aliphatic compounds, though rates can be highly...
The cystine transporter (system x<sub>C</sub><sup>−</sup>) is an antiporter of and glutamate. It has relatively low basal expression in most tissues becomes upregulated cells under oxidative stress (OS) as one the genes expressed response to antioxidant element promoter. We have developed <sup>18</sup>F-5-fluoroaminosuberic acid (FASu), a PET tracer that targets system x<sub>C</sub><sup>−</sup>. goal this study was evaluate <sup>18</sup>F-FASu specific gauge for x<sub>C</sub><sup>−</sup>...
Prostaglandin E2 (PGE2) acts via its EP4 receptor as a cytokine amplifier (e.g., interleukin [IL]-6) and induces the differentiation expansion of inflammatory T-helper (Th) lymphocytes. These mechanisms play key role in onset progression rheumatoid arthritis (RA). We present pharmacological characterisation CR6086, novel antagonist, provide evidence for potential disease-modifying anti-rheumatic drug (DMARD). CR6086 affinity pharmacodynamics were studied EP4-expressing HEK293 cells by...
The synthesis and the biological characterization of novel highly selective pyrroloquinoxaline 5-HT3 receptor (5-HT3R) ligands are described. In functional in vivo studies quinoxalines modulated cardiac parameters by direct interaction with myocardial 5-HT3Rs. potent 5-HT3R 4h 4n modulate chronotropy (right atrium) but not inotropy (left at level, being antagonist partial agonist, respectively. Preliminary pharmacokinetic indicate that (S)-4n 4a, representatives ligands, possess poor...
Previous structure-activity relationship studies in the search for a potent, noncompetitive alpha-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor antagonist led to 2,3-dimethyl-6-phenyl-12H-[1,3]dioxolo[4,5-h]imidazo[1,2-c][2,3]benzodiazepine (ZK 187638). However, first synthesis had some drawbacks regarding reagents, processes, and overall yield, which furthermore decreased when was scaled up. Therefore, we now report new synthetic route this compound requires fewer...
The large, neutral L-type amino acid transporters (LAT1–LAT4) are sodium-independent that widely distributed throughout the body. LAT expression levels increased in many types of cancer, and their increases as cancers progress, leading to high high-grade tumors metastases. Because key role overexpression radiolabeled substrates promising candidates for nuclear imaging malignancies not well revealed by conventional radiotracers. goal this study was examine structure–activity relationships a...
Post-menopausal women under treatment with levothyroxine for their medical conditions may take concomitantly dietary supplements containing soy isoflavones in combination to treat post-menopausal symptoms. The aim of this study was investigate the effect a fixed on oral bioavailability female volunteers.12 healthy female, who were stable as replacement/supplementation therapy hypothyroidism, received single recommended dose food supplement 60 mg (>19% genistin and daidzin) (test) 6 h later...
Amentoflavone crosses the blood-brain barrier in vitro but did not inhibit benzodiazepine binding vivo suggesting poor brain permeability. This prompted us to examine its distribution mice. After Hypericum perforatum and Gingko biloba extracts concentrations were below limit of quantification. Levels consistently detected only after intraperitoneal amentoflavone (10 mg/kg), with mean brain-to-plasma ratio about 0.02. These possibly related compounds contribution from residual blood, any case...
An increasing number of positron emission tomography (PET) radiotracers are being developed that modelled on various amino acids to better understand disease in a manner is complementary traditional glycolysis-targeting [18 F]-fluorodeoxyglucose. Since chiral centers ubiquitous acids, generating an optically pure radiolabeled acid important for patient dose, image quality and understanding the physiology behaviour. Past studies radiosynthesis seldom address impact reaction conditions their...
Objectives: This study was aimed at investigating the potential of herbal exctracts, berberine and monacolin, administered in combination recommended dose, to generate clinically relevant inhibition CYP (cytochromes P450) enzyme system after a single oral administration human healthy volunteers.Methods: Twelve male volunteers received five-probe drug cocktail alone (reference) or with monacolin (test), randomized, open label, crossover fashion.Plasma concentrations components, caffeine...