A5091214681- Biochemical and Molecular Research
- Blood Coagulation and Thrombosis Mechanisms
- Cancer Immunotherapy and Biomarkers
- HIV/AIDS drug development and treatment
- Folate and B Vitamins Research
- Renin-Angiotensin System Studies
- Nitric Oxide and Endothelin Effects
- Amino Acid Enzymes and Metabolism
- Biopolymer Synthesis and Applications
- Apelin-related biomedical research
- Synthesis and Characterization of Heterocyclic Compounds
- Chronic Myeloid Leukemia Treatments
- Acute Lymphoblastic Leukemia research
- Chemical Synthesis and Analysis
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Chronic Lymphocytic Leukemia Research
- Advanced Breast Cancer Therapies
- Ferroptosis and cancer prognosis
- Click Chemistry and Applications
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Synthesis and Reactions of Organic Compounds
- Quinazolinone synthesis and applications
- Fluorine in Organic Chemistry
- Eicosanoids and Hypertension Pharmacology
- Cardiovascular Disease and Adiposity
Western University
2018-2024
Massachusetts General Hospital
2022-2024
Harvard University
2024
Broad Institute
2023-2024
Massachusetts Institute of Technology
2023
Center for Cancer Research
2023
North Carolina State University
2022
MGH Institute of Health Professions
2022
Akoya Biosciences (United States)
2021
Howard University
2020
The classical antifolate N-{4-[(2,4-diamino-5-ethyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)sulfanyl]benzoyl}-l-glutamic acid (2) and 15 nonclassical analogues (3−17) were synthesized as potential dihydrofolate reductase (DHFR) inhibitors antitumor agents. 5-Ethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine (20) served the key intermediate to which various aryl thiols a heteroaryl thiol appended at 6-position via an oxidative addition reaction. analogue 2 was by coupling benzoic derivative 18 with...
Rat liver folylpolyglutamate synthetase was partially purified and its reaction products were characterized.The preparation contained no conjugase activity.Gel filtration analysis revealed a molecular weight of 69,000.The optimally active at pH 8.4 (37"C), required mercaptoethanol monovalent cation, highly specific for L-glutamate.Only purine nucleoside triphosphates served as the energy source reaction; ATP dATP gave best activity.All naturally occurring folates (including...
Systemic pharmacologic treatments may be indicated in conditions which the distribution of muscle overactivity is diffuse. Antispastic drugs act CNS either by suppression excitation (glutamate) enhancement inhibition (GABA, glycine), or a combination two. Only four are currently approved US FDA as antispactic agents: baclofen, diazepam, dantrolene sodium, and tizanidine. However, there number other available with proven antispastic action. This chapter reviews pharmacology, physiology...
Determinants of methotrexate (MTX) resistance in cell lines resistant to short, but not continuous, MTX exposure were investigated since such may have relevance clinical resistance. CCRF-CEM R30dm (R30dm), cloned from R30/6 (a MTX-resistant subline the human leukemia line), had growth characteristics similar CCRF-CEM. was a 24-h levels as high 300 microM sensitive continuous exposure. stable for greater than 68 weeks absence selective pressure. Initial velocities transport comparable and...
Abstract Purpose: In both the IMpassion 130 trial in metastatic setting and Keynote 522 neoadjuvant setting, patients with triple-negative breast cancer (TNBC) showed benefit from PD-1 axis immunotherapy. Here, we assess PD-L1 expression on tumor immune cells using quantitative immunofluorescence to association durvalumab concurrent chemotherapy TNBC. Experimental Design: Pretreatment core needle biopsies (n = 69) were obtained who participated a phase I/II clinical (NCT02489448). The final...
Background Emerging data suggest predictive biomarkers based on the spatial arrangement of cells or coexpression patterns in tissue sections will play an important role precision immuno-oncology. Multiplexed immunofluorescence (mIF) is ideally suited to such assessments. Standardization and validation end-to-end workflow that supports multisite trials clinical laboratory processes are vital. Six institutions collaborated to: (1) optimize automated six-plex assay focused PD-1/PD-L1 axis, (2)...
Endothelium-derived hyperpolarizing factor (EDHF) is defined as the non-nitric oxide (NO) and non-prostacyclin (PGI2) substance that mediates endothelium-dependent hyperpolarization (EDH) of vascular smooth muscle cells (VSMC). Although both NO PGI2 have been demonstrated to hyperpolarize VSMC by cGMP- cAMP-dependent mechanisms, respectively, in case cGMP-independent a considerable body evidence suggests an additional cellular mechanism must exist EDH. Despite intensive investigation, there...
Spasticity is a velocity-dependent increase in stretch reflex activity. It one of the forms muscle overactivity that may affect patients with damage to central nervous system. monitoring relevant function because degree spasticity reflect intensity other disabling types overactivity, such as unwanted antagonistic co-contractions, permanent activity absence any or volitional command (spastic dystonia), inappropriate responses cutaneous vegetative inputs. In addition, spasticity, like can...
A peptide corresponding to a proteinase-activated receptor 2 (PAR<sub>2</sub>)-activating with an N-terminal furoyl group modification, 2-furoyl-LIGRLO-NH<sub>2</sub>, was assessed for PAR<sub>2</sub>-dependent and -independent biological activities. 2-Furoyl-LIGRLO-NH<sub>2</sub> equally effective 10 25 times more potent than SLIGRLNH<sub>2</sub> increasing intracellular calcium in cultured human rat PAR<sub>2</sub>-expressing cells, respectively. In bioassays of tissue PAR<sub>2</sub>...
Endothelium-derived hyperpolarizing factor (EDHF) is defined as the non-nitric oxide (NO) and non-prostacyclin (PGI 2 ) substance that mediates endothelium-dependent hyperpolarization (EDH) of vascular smooth muscle cells (VSMC). Although both NO PGI have been demonstrated to hyperpolarize VSMC by cGMP- cAMP-dependent mechanisms, respectively, in case cGMP-independent a considerable body evidence suggests an additional cellular mechanism must exist EDH. Despite intensive investigation, there...
Lipoprotein lipase (LPL) hydrolyzes circulating triglycerides (TGs), releasing fatty acids (FA) and promoting lipid storage in white adipose tissue (WAT). However, the mechanisms regulating LPL its relationship with development of hypertriglyceridemia are largely unknown. WAT from obese humans exhibited high PAR2 expression, which was inversely correlated gene. Decreased expression also elevated plasma TG levels, suggesting that might regulate by downregulating LPL. In mice, aging palmitic...
Activation of PAR2 in second‐order mesenteric arteriole (MA) rings from C57BL/6J, NOS3 (−/−) and mice was assessed for the contributions NO, cyclo‐oxygenases, guanylyl cyclase, adenylyl K + channel activation to vascular smooth muscle relaxation. agonist, SLIGRL‐NH 2 (0.1 30 μ M ), induced relaxation cirazoline‐precontracted MA C57BL/6J (−/−), but not mice. Maximal (E max ) partially reduced by a combination L ‐ G N‐nitroarginine methyl ester ( ‐NAME),...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTYeast diphosphopyridine nucleotide specific isocitrate dehydrogenase. Regulation of activity and unidirectional catalysisLarry D. Barnes, John J. McGuire, Daniel E. AtkinsonCite this: Biochemistry 1972, 11, 23, 4322–4329Publication Date (Print):November 1, 1972Publication History Published online1 May 2002Published inissue 1 November 1972https://pubs.acs.org/doi/10.1021/bi00773a019https://doi.org/10.1021/bi00773a019research-articleACS...