Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
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| effect of provisioning on the temporal variation in the activity budget of urban long-tailed macaques (macaca fascicularis) in west sumatra, indonesia. | we studied the behavioral ecology of provisioned long-tailed macaques (macaca fascicularis) in padang, west sumatra, indonesia, to examine how temporal changes in food provisioning within a day affect macaque activity. we conducted a field survey from october 2015 to january 2016 at two different sites: gunung meru (gm) and gunung padang (gp), where macaques receive high and low provisioning, respectively. the time budgets of macaques significantly differed between study groups. at gm, macaques ... | 2018 | 30212833 |
| metabolism of c-met kinase inhibitors containing quinoline by aldehyde oxidase, electron donating, and steric hindrance effect. | some quinoline-containing c-met kinase inhibitors are aldehyde oxidase (ao) substrates. 3-substituted quinoline triazolopyridine analogs were synthesized to understand the electron-donating and steric hindrance effects on ao-mediated metabolism. metabolic stability studies for these quinoline analogs were carried out in liver cytosol from mice, rats, cynomolgus monkeys, and humans. several 3-n-substituted analogs were found to be unstable in monkey liver cytosolic incubations (half-life, <10 min ... | 2018 | 30209037 |
| comparative safety assessments of the biosimilar apz001 and erbitux in pre-clinical animal models. | to evaluate the toxicity of erbitux as well as its biosimilar apz001 antibody (apz001) in pre-clinical animal models including mice, rabbits and cynomolgus monkeys. | 2018 | 30208131 |
| the pituitary gland is a novel major site of action of metformin in non-human primates: a potential path to expand and integrate its metabolic actions. | biguanides are anti-hyperglycaemic agents used to treat diabetes by acting primarily on the liver, inhibiting hepatic gluconeogenesis. however, biguanides may target other key metabolic tissues to exert beneficial actions. as the "master endocrine gland", the pituitary is a true homeostatic sensor that controls whole body homeostasis and metabolism by integrating central and peripheral signals. however, whether the pituitary is a primary site of biguanides action in normal adult humans/primates ... | 2018 | 30205369 |
| novel fatty acyl apoe mimetic peptides have increased potency to reduce plasma cholesterol in mice and macaques. | ac-he18a-nh2 is a dual-domain apoe mimetic peptide that possesses the putative receptor binding domain from apoe (lrklrkrllr, denoted he; residues 141-150) covalently attached to lipid-associating peptide 18a. like apoe, ac-he18a-nh2 reduces plasma cholesterol in animal models and exhibits anti-inflammatory properties independent of its cholesterol-reducing effect. ac-he18a-nh2 has already undergone phase i clinical trials as a lipid-lowering agent. to explore the therapeutic potential more, we ... | 2018 | 30201630 |
| non-neutralizing antibodies increase endogenous circulating ang1 levels. | ang1 is a soluble ligand to receptor tie2, and increasing the circulating ang1 level may improve vascular stabilization under certain disease conditions. here, we found that the circulating ang1 level was significantly increased in cynomolgus monkeys treated with non-neutralizing anti-ang1 antibodies. improving the antibodies' pharmacokinetic properties by igg fc mutations further increased the circulating ang1 level. however, the mutations decreased the thermal stability of the molecules, which ... | 2019 | 30199300 |
| comparison of inhibitory neuromuscular transmission in the cynomolgus monkey ias and rectum: special emphasis on differences in purinergic transmission. | inhibitory neuromuscular transmission (nmt) was compared in the internal anal sphincter (ias) and rectum of the cynomolgus monkey, an animal with high gene sequence identity to humans. nitrergic nmt was present in both muscles while purinergic nmt was limited to the rectum and vipergic nmt to the ias. the profile for monkey ias more closely resembles humans than rodents. in both muscles, sk3 channels were localized to pdgfrα+ cells that were closely associated with nnos+ /vip+ nerves. gene expre ... | 2018 | 30198065 |
| comparison of efficacy and toxicity between botulinum toxin subtypes a1 and a2 in cynomolgus macaques. | botulinum toxin type a (subtype a1) is used as therapeutic agent for some neurological disorders causing spasticity. the toxin products have an upper dosage limit, and their adverse events, such as side effects of diffusion following high-dose administration, have become serious issues. therefore, a preparation with greater therapeutic efficacy at lower dosages and less diffusion in the body is desired. we have attempted to produce neurotoxin derived from subtype a2 (a2ntx), which has a differen ... | 2018 | 30193802 |
| replication deficient human adenovirus vector serotype 19a/64: immunogenicity in mice and female cynomolgus macaques. | the human adenovirus type 19a/64 (had19a) is a rare serotype in the human population that transduces human dendritic cells (dcs) and human muscle cells more efficiently than the well-characterized human adenovirus type 5 (had5). to further characterize the potential of this vector as a vaccine we designed replication deficient had19a, had5 and mva vectors expressing a papillomavirus (pv) antigen fused to the human mhc class ii associated invariant chain t cell adjuvant (hii) and investigated the ... | 2018 | 30190120 |
| [establishment of retinal disease models using non-human primates and its strategy for drug discovery]. | retinal diseases such as glaucoma, diabetic retinopathy, age-related macular degeneration and retinitis pigmentosa are the major causes of blindness. however, these pathological mechanisms remain to be elucidated, and development of new therapeutic agents has been desired. a large number of experimental animal models using rodents (rats and mice) have been used for the evaluations of the pathogenesis and novel therapeutic candidates in retinal diseases. however, the anatomy of the retina in rode ... | 2018 | 30185732 |
| preclinical pharmacokinetics and pharmacodynamics of dcll9718a: an antibody-drug conjugate for the treatment of acute myeloid leukemia. | few treatment options are available for acute myeloid leukemia (aml) patients. dcll9718a is an antibody-drug conjugate that targets c-type lectin-like molecule-1 (cll-1). this receptor is prevalent on monocytes, neutrophils, and aml blast cells, and unlike cd33, is not expressed on hematopoietic stem cells, thus providing possible hematopoietic recovery. dcll9718a comprises an anti-cll-1 igg1 antibody (mcll0517a) linked to a pyrrolobenzodiazepine (pbd) dimer payload, via a cleavable disulfide-la ... | 2019 | 30183491 |
| coagulation biomarkers in healthy male cynomolgus macaque monkeys (macaca fascicularis). | we designed this study to define reference values of the cynomolgus monkey coagulation system, as the normal range of values has not been established. measurement of coagulation function was determined by testing plasma samples from 30 healthy male cynomolgus monkeys. prothrombin time (pt), pt activity, pt international normalized ratio (inr), activated prothrombin time (aptt), antithrombin iii activity, factor ii, v, vii, viii, ix, x, xi, and xii, protein c activity, protein s activity, and d-d ... | 2019 | 30183120 |
| persistent marburg virus infection in the testes of nonhuman primate survivors. | sexual transmission of filoviruses was first reported in 1968 after an outbreak of marburg virus (marv) disease and recently caused flare-ups of ebola virus disease in the 2013-2016 outbreak. how filoviruses establish testicular persistence and are shed in semen remain unknown. we discovered that persistent marv infection of seminiferous tubules, an immune-privileged site that harbors sperm production, is a relatively common event in crab-eating macaques that survived infection after antiviral t ... | 2018 | 30173956 |
| oocyte retrieval after heterotopic transplantation of ovarian tissue cryopreserved by closed vitrification protocol. | a device for closed vitrification was designed to reduce the risk of contamination and investigated on its efficacy for ovarian function recovery after cryopreservation and heterotopic transplantation. | 2018 | 30173352 |
| effects of gs-9876, a novel spleen tyrosine kinase inhibitor, on platelet function and systemic hemostasis. | spleen tyrosine kinase (syk) mediates signal transduction in multiple hematopoietic cells, including platelets. syk signals downstream of immunoreceptors and syk inhibition may ameliorate disease pathology in multiple autoimmune disorders; however, the impact of syk inhibition in platelets and its potential relevance to bleeding is not fully understood. these studies evaluated the effect of an oral syk inhibitor, gs-9876, on platelets in vitro and in vivo, and the impact of gs-9876 plus non-ster ... | 2018 | 30172129 |
| genetic variants of glutathione s-transferase gstt1 and gstt2 in cynomolgus macaques: identification of gstt substrates and functionally relevant alleles. | glutathione s-transferase (gst) is a family of important drug-metabolizing enzymes, conjugating endogenous and exogenous compounds. genetic polymorphisms result in the inter-individual variability of gst activity in humans. especially, human gstt1 and gstt2 null alleles are associated with toxicity and various cancers derived from chemicals. cynomolgus macaque, a nonhuman primate species widely used in drug metabolism studies, has molecular and enzymatic similarities of gsts to the human ortholo ... | 2018 | 30169019 |
| ontogenetic changes to muscle architectural properties within the jaw-adductor musculature of macaca fascicularis. | changes to soft- and hard-tissue components of the masticatory complex during development can impact functional performance by altering muscle excursion potential, maximum muscle forces, and the efficiency of force transfer to specific bitepoints. within macaca fascicularis, older individuals exploit larger, more mechanically resistant food items and more frequently utilize wide-gape jaw postures. we therefore predict that key architectural and biomechanical variables will scale during ontogeny ... | 2018 | 30168867 |
| nonhuman primate model of persistent erectile and urinary dysfunction following radical prostatectomy: feasibility of minimally invasive therapy. | persistent urinary incontinence (ui) and/or erectile dysfunction (ed) occur in 30-50% of post-radical prostatectomy patients regardless of nerve sparing approaches. identification of potential treatment options for these patients will require testing in an animal model that develops these chronic conditions. the objective was to characterize a nonhuman primate (nhp) model of persistent post-prostatectomy ed and ui and then test the feasibility of periurethral injection of the chemokine cxcl-12. | 2018 | 30168617 |
| dna-based determination of ancestry in cynomolgus macaques (macaca fascicularis). | interest in the genetic composition of cynomolgus macaques (macaca fascicularis) has increased due to the rising demand for nhp models in human biomedical research. significant genetic differences among regional populations of cynomolgus macaques can confound interpretations of research results because they do not solely reflect differences in experimental treatment effects. therefore, the common origin of cynomolgus macaques used as research subjects should be verified by using region-specific ... | 2018 | 30165920 |
| comparison of cellular localisation of the ca2+ -binding proteins calbindin, calretinin and parvalbumin in the retina of four different macaca species. | ca2+ -binding proteins are differentially expressed in the nervous system; their functional role often remains unclear. this immunohistochemical study aimed at characterising and comparing the expression pattern of the ca2+ -binding proteins calbindin (calb), calretinin (calr) and parvalbumin (parv) in the retina of four species of macaque monkeys: macaca fascicularis (cynomolgus macaque), m. mulatta (rhesus macaque), m. thibetana (tibetan macaque) and m. fuscata (japanese macaque). calb was fou ... | 2018 | 30155916 |
| renal ischemia-reperfusion injury in a diabetic monkey model and therapeutic testing of human bone marrow-derived mesenchymal stem cells. | clinically, acute kidney injury (aki) episodes in diabetes mellitus (dm) patients are associated with a cumulative risk of developing end-stage renal disease. in this study, we asked whether the severity of aki induced by renal ischemia-reperfusion injury (iri) is more prominent in dm than in non-dm control using a cynomolgus monkey (macaca fascicularis) model. we also investigated whether human bone marrow-derived mesenchymal stem cells (hbm-mscs) infused via the renal artery could ameliorate r ... | 2018 | 30155487 |
| impact of ring size and drug loading on the pharmacokinetics of a combination dapivirine-darunavir vaginal ring in cynomolgus macaques. | this work investigates the impact of vaginal ring size and drug loading on the in vitro release, safety, ease of fit, and pharmacokinetics in cynomolgus macaques of matrix-type silicone elastomer vaginal rings containing a combination of the non-nucleoside reverse transcriptase inhibitor dapivirine and the protease inhibitor darunavir. drug-free and drug-loaded vaginal rings having three different geometries were manufactured by reaction injection molding. in vitro drug release was assessed usin ... | 2018 | 30153490 |
| mucosal antibody responses to vaccines targeting siv protease cleavage sites or full-length gag and env proteins in mauritian cynomolgus macaques. | hiv mutates rapidly and infects cd4+ t cells, especially when they are activated. a vaccine targeting conserved, essential viral elements while limiting cd4+ t cell activation could be effective. learning from natural immunity observed in a group of highly hiv-1 exposed seronegative kenyan female sex workers, we are testing a novel candidate hiv vaccine targeting the 12 viral protease cleavage sites (pcss) (the pcs vaccine), in comparison with a vaccine targeting full-length gag and env (the gag ... | 2018 | 30153293 |
| [sequencing and phylogenetic tree construction of 18s ribosomal dna from five species of plasmodium from yunnan border between china and myanmar and other areas]. | to analyze sequence variation and construct phylogenetic tree based on 18s ribosomal dna among five species of plasmodium in yunnan border between china and myanmar and other areas. | 2016 | 30141590 |
| vaccine-mediated induction of an ebolavirus cross-species antibody binding to conserved epitopes on the glycoprotein heptad repeat 2/membrane-proximal external junction. | the membrane-proximal external regions (mper) of the human immunodeficiency virus envelope glycoprotein (gp) generate broadly reactive antibody responses and are the focus of vaccine development efforts. the conservation of amino acids within filovirus gp heptad repeat region (hr)2/mper suggests that it may also represent a target for a pan-filovirus vaccine. we immunized a cynomolgus macaque against ebola virus (ebov) using a deoxyribonucleic acid/adenovirus 5 prime/boost strategy, sequenced me ... | 2018 | 30137549 |
| establishment of a macaca fascicularis gut microbiome gene catalog and comparison with the human, pig, and mouse gut microbiomes. | macaca fascicularis, the cynomolgus macaque, is a widely used model in biomedical research and drug development as its genetics and physiology are close to those of humans. detailed information on the cynomolgus macaque gut microbiota, the functional interplay between the gut microbiota and host physiology, and possible similarities to humans and other mammalians is very limited. the aim of this study was to construct the first cynomolgus macaque gut microbial gene catalog and compare this catal ... | 2018 | 30137359 |
| sirt6 deficiency results in developmental retardation in cynomolgus monkeys. | sirt6 acts as a longevity protein in rodents1,2. however, its biological function in primates remains largely unknown. here we generate a sirt6-null cynomolgus monkey (macaca fascicularis) model using a crispr-cas9-based approach. sirt6-deficient monkeys die hours after birth and exhibit severe prenatal developmental retardation. sirt6 loss delays neuronal differentiation by transcriptionally activating the long non-coding rna h19 (a developmental repressor), and we were able to recapitulate thi ... | 2018 | 30135584 |
| two vaccines for staphylococcus aureus induce a b-cell-mediated immune response. | staphylococcus aureus causes severe disease in humans for which no licensed vaccine exists. a novel s. aureus vaccine (sa4ag) is in development, targeting the capsular polysaccharides (cps) and two virulence-associated surface proteins. vaccine-elicited antibody responses to cps are efficacious against serious infection by other encapsulated bacteria. studies of natural s. aureus infection have also shown a role for th17 and/or th1 responses in protection. single-antigen vaccines, including cps, ... | 2018 | 30135219 |
| intrathecal delivery of human esc-derived mesenchymal stem cell spheres promotes recovery of a primate multiple sclerosis model. | nonhuman primate experimental autoimmune encephalomyelitis (eae) is a valuable model for multiple sclerosis, an inflammatory demyelinating disease in the central nervous system (cns). human embryonic stem cell-derived mesenchymal stem cells (emsc) are effective in treating murine eae. yet, it remains unknown whether the emsc efficacy is translatable to humans. here we induced a primate eae model in cynomolgus monkeys and delivered emsc in spheres (emscsp) to preserve the cell viability during lo ... | 2018 | 30131877 |
| generation and characterization of a high affinity anti-human fcrn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma igg concentration. | rozanolixizumab (ucb7665), a humanized high-affinity anti-human neonatal fc receptor (fcrn) monoclonal antibody (igg4p), has been developed to reduce pathogenic igg in autoimmune and alloimmune diseases. we document the antibody isolation and compare rozanolixizumab with the same variable region expressed in various mono-, bi- and trivalent formats. we report activity data for rozanolixizumab and the different molecular formats in human cells, fcrn-transgenic mice, and cynomolgus monkeys. rozano ... | 2018 | 30130439 |
| detection of complement activators in immune attack eyes after ips-derived retinal pigment epithelial cell transplantation. | to determine whether human induced pluripotent stem (ips) cell-derived retinal pigment epithelial (rpe) cells (ips-rpe) can express complement factors. | 2018 | 30128491 |
| metagenomic comparison of the rectal microbiota between rhesus macaques (macaca mulatta) and cynomolgus macaques (macaca fascicularis). | rhesus macaques (macaca mulatta) and cynomolgus macaques (macaca fascicularis) are frequently used in establishing animal models for human diseases. to determine the differences in gut microbiota between these species, rectal swabs from 20 rhesus macaques and 21 cynomolgus macaques were collected, and the microbial composition was examined by deep sequencing of the 16s rrna gene. we found that the rectal microbiota of cynomolgus macaques exhibited significantly higher alpha diversity than that o ... | 2019 | 30127329 |
| komodo dragon predation on crab-eating macaques at the rinca island's visitor centre, indonesia. | we investigated the proportion of crab-eating macaques in the diet of komodo dragons and quantified the spatial habitat use between the species as a proxy for predation threat and in relation to prey availability due to ecotourism. in 2013, in loh buaya valley of rinca island, komodo national park, we conducted macroscopic identification of hairs, claws, dentition and osteological remains of consumed prey. for habitat use, we quantified the use of vertical strata by macaques through focal animal ... | 2018 | 30114686 |
| a method for expansion of t cells from cynomolgus monkey (macaca fascicularis). | t cells have been successfully applied to cancer immunotherapy. however, a challenge is an expansion of t cells from cynomolgus monkey, which is a valuable non-human primate model for t cell therapy transferring to the clinic. here, we compared several strategies to expand cynomolgus monkey t cell and developed an appropriate method. our study demonstrated that 100 ng/ml cd3 mab + 1% pha+ 1000 u/ml il2 therapy significantly expanded peripheral blood cd3+ t cells without compromising t cell pheno ... | 2018 | 30112696 |
| lead concentration in long-tailed macaque (macaca fascicularis) hair in kuala selangor, malaysia. | long-tailed macaque (macaca fascicularis) has the potential to be a good biological indicator for toxic exposure because they have an almost similar physiology and behaviour to humans. the objective of this study is to determine the concentration of lead (pb) in hair samples of long-tailed macaques which were found in and out of the kuala selangor nature park (ksnp) area. the hypothesis is long-tailed macaques that live in the anthropogenic area (outside ksnp) may be exposed to high levels of le ... | 2018 | 30112148 |
| acute-phase cd4+ t cell responses targeting invariant viral regions are associated with control of live attenuated simian immunodeficiency virus. | we manipulated sivmac239δnef, a model of major histocompatibility complex (mhc)-independent viral control, to evaluate characteristics of effective cellular responses mounted by mauritian cynomolgus macaques (mcms) that express the m3 mhc haplotype, which has been associated with poor control of pathogenic simian immunodeficiency virus (siv). we created sivδnef-8x to test the hypothesis that effective siv-specific t cell responses targeting invariant viral regions can emerge in the absence of im ... | 2018 | 30111562 |
| gingival exudatome dynamics implicate inhibition of the alternative complement pathway in the protective action of the c3 inhibitor cp40 in nonhuman primate periodontitis. | periodontitis is a prevalent chronic inflammatory disease associated with dysbiosis. although complement inhibition has been successfully used to treat periodontitis in animal models, studies globally analyzing inflamed tissue proteins to glean insight into possible mechanisms of action are missing. using quantitative shotgun proteomics, we aimed to investigate differences in composition of inflammatory gingival tissue exudate ("gingival crevicular fluid"; gcf), before and after local administra ... | 2018 | 30111112 |
| single-axon tracing of the corticosubthalamic hyperdirect pathway in primates. | individual axons that form the hyperdirect pathway in macaca fascicularis were visualized following microiontophoretic injections of biotinylated dextran amine in layer v of the primary motor cortex (m1). twenty-eight singly labeled axons were reconstructed in 3d from serial sections. the m1 innervation of the subthalamic nucleus (stn) arises essentially from collaterals of long-ranged corticofugal axons en route to lower brainstem regions. typically, after leaving m1, these large caliber axons ... | 2018 | 30109491 |
| development of a synthetic live bacterial therapeutic for the human metabolic disease phenylketonuria. | phenylketonuria (pku) is a genetic disease that is characterized by an inability to metabolize phenylalanine (phe), which can result in neurotoxicity. to provide a potential alternative to a protein-restricted diet, we engineered escherichia coli nissle to express genes encoding phe-metabolizing enzymes in response to anoxic conditions in the mammalian gut. administration of our synthetic strain, synb1618, to the pahenu2/enu2 pku mouse model reduced blood phe concentration by 38% compared with t ... | 2018 | 30102294 |
| nonclinical safety assessment of cfz533, a fc-silent anti-cd40 antibody, in cynomolgus monkeys. | cfz533 is a pathway blocking, nondepleting anti-cd40 antibody that is in clinical development for inhibition of transplant organ rejection and therapy for autoimmune diseases. a 26-week glp toxicity study in sexually mature cynomolgus monkeys was conducted in order to support chronic application of cfz533. cfz533 was subcutaneously administered at doses up to 150 mg/kg/week and was safe and generally well tolerated. cfz533 showed no adverse effects for cardiovascular, respiratory, and neurobehav ... | 2018 | 30099540 |
| a novel highly potent and selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor, inu-101. | 11β-hydroxysteroid dehydrogenase type 1 (11β-hsd1) is a cortisol regenerating enzyme that amplifies tissue glucocorticoid levels, especially in the liver and adipose tissue. knockout mice or a selective inhibitor of 11β-hsd1 improves metabolic syndrome parameters in preclinical models and human clinical trials. here, we evaluated the therapeutic potential of inu-101, a potent and selective oral inhibitor of 11β-hsd1. the in vitro activity of 11β-hsd1 was measured using the homogeneous time-resol ... | 2018 | 30096297 |
| dissociation of lfp power and tuning in the frontal cortex during memory. | working memory, the ability to maintain and manipulate information in the brain, is critical for cognition. during the memory period of spatial memory tasks, neurons in the prefrontal cortex code for memorized locations via persistent, spatially tuned increases in activity. local field potentials (lfps) are understood to reflect summed synaptic activity of local neuron populations and may offer a window into network-level processing. we recorded lfps from areas 8a and 9/46 while two male cynomol ... | 2018 | 30093534 |
| development and characterization of a model for inducing fetal hemoglobin production in cynomolgus macaques (macaca fasicularis). | hydroxyurea induces production of fetal hemoglobin (hbf), a tetramer of α and γ globin proteins and corresponding heme molecules, normally found in less than 1% of adult rbc. increases in circulating hbf are correlated with clinical improvement of patients with hemoglobinopathies, and hydroxyurea, as a daily medication, is the standard treatment for sickle cell anemia. although olive baboons (papio anubis) are considered a key model species for hbf induction, cynomolgus macaques (macaca fasicula ... | 2018 | 30092854 |
| letter to the editor regarding "spontaneous findings in the eyes of cynomolgus monkeys ( macaca fascicularis) of mauritian origin" by woicke et al. ( toxicol pathol 46, 273-282, 2018). | 2018 | 30092740 | |
| effects of unilateral electroacupuncture on bilateral proprioception in a unilateral anterior cruciate ligament injury model. | background anterior cruciate ligament (acl) injury can cause knee proprioception degeneration, on which the electroacupuncture (ea) treatment has a definite effect. however, it is still not clear whether conducting ea intervention on the injured side can promote bilateral proprioception recovery. material and methods we randomly selected 6 of 9 normal cynomolgus monkeys to develop unilateral acl injury models via arthroscopy. all knees were divided into 5 groups: the normal control (nc) group, i ... | 2018 | 30082677 |
| dosikit, a new immunoassay for fast radiation biodosimetry of hair and blood samples. | dosikit is a field radiation biodosimetry immunoassay for fast triage of individuals exposed to external total-body or partial-body irradiation (tbi or pbi). assay proof-of-concept based on γ-h2ax analysis of human blood samples has been previously described as a promising tool for rapid assessment of tbi. here, we report on the performance of the assay for pbi based on an analysis of hair follicles irradiated with a 137cs gamma-ray source, at doses ranging from 0 to 20 gy and dose rates ranging ... | 2018 | 30074847 |
| mycobacterium tuberculosis erdman infection of cynomolgus macaques of chinese origin. | nearly one-third of the population worldwide is estimated to have latent tuberculosis infection (ltbi), which represents a vast reservoir for a constant source of tuberculosis (tb) transmission. it has been suggested that cynomolgus macaques are less susceptible to mycobacterium tuberculosis (m.tb) infection than rhesus macaques, we examined m.tb infection of chinese cynomolgus macaques. | 2018 | 30069358 |
| characterization of [11c]pxt012253 as a pet radioligand for mglu4 allosteric modulators in nonhuman primates. | modulation of presynaptic metabotropic glutamate receptor 4 (mglu4) by an allosteric ligand has been proposed as a promising therapeutic target in parkinson's disease and levodopa-induced dyskinesia. a positron emission tomography (pet) ligand for an allosteric site of mglu4 may provide evidence that a clinical drug candidate reaches and binds the target. a carbon-11-labeled pet radioligand binding an allosteric site of mglu4, [11c]pxt012253, has been recently developed. here, we describe the de ... | 2019 | 30066121 |
| an adapted isotope dilution 1h-13c heteronuclear single-quantum correlation (id-hsqc) for rapid and accurate quantification of endogenous and exogenous plasma glucose. | a wide variety of methods, such as enzymatic methods, lc-ms, and lc-ms/ms, are currently available for the concentration determination of plasma glucose in studies of diabetes, obesity, exercise, etc. however, these methods rarely discriminate endogenous and exogenous glucose in plasma. a novel nmr strategy for discriminative quantification of the endogenous and exogenous glucose in plasma has been developed using an adapted isotope dilution 1h-13c heteronuclear single-quantum correlation (id-hs ... | 2018 | 30054692 |
| non-clinical evaluation of jr-051 as a biosimilar to agalsidase beta for the treatment of fabry disease. | fabry disease (fd) is an x-linked lysosomal storage disease. it is caused by deficiency of the enzyme α-galactosidase a (α-gal a), which leads to excessive deposition of neutral glycosphingolipids, especially globotriaosylceramide (gl-3), in cells throughout the body. progressive accumulation of gl-3 causes life-threatening complications in several tissues and organs, including the vasculature, heart, and kidney. currently available enzyme replacement therapy for fd employs recombinant α-gal a i ... | 2018 | 30054149 |
| humanized anti-sialyl-tn antibodies for the treatment of ovarian carcinoma. | the expression of sialyl-tn (stn) in tumors is associated with metastatic disease, poor prognosis, and reduced overall survival. stn is expressed on ovarian cancer biomarkers including ca-125 (muc16) and muc1, and elevated serum levels of stn in ovarian cancer patients correlate with lower five-year survival rates. in the current study, we humanized novel anti-stn antibodies and demonstrated the retention of nanomolar (nm) target affinity while maintaining stn antigen selectivity. stn antibodies ... | 2018 | 30052649 |
| discovery of risdiplam, a selective survival of motor neuron-2 ( smn2) gene splicing modifier for the treatment of spinal muscular atrophy (sma). | sma is an inherited disease that leads to loss of motor function and ambulation and a reduced life expectancy. we have been working to develop orally administrated, systemically distributed small molecules to increase levels of functional smn protein. compound 2 was the first smn2 splicing modifier tested in clinical trials in healthy volunteers and sma patients. it was safe and well tolerated and increased smn protein levels up to 2-fold in patients. nevertheless, its development was stopped as ... | 2018 | 30044619 |
| immunogenicity of adenovirus-vector vaccine targeting hepatitis b virus: non-clinical safety assessment in non-human primates. | a new promising therapeutic approach has emerged for patients chronically infected by the hepatitis b virus (hbv) with the development of a non-replicative adenovirus vector vaccine candidate (ad-hbv). the vaccine encodes a fusion protein composed of a truncated hbv core protein, mutated polymerase protein, and two envelope domains. in this study, we assessed the immunogenicity of ad-hbv administered to cynomolgus monkeys during a non-clinical safety assessment. | 2018 | 30041659 |
| predicting response to sepantronium bromide (ym155), a survivin suppressant, by pet imaging with [11c]ym155. | sepantronium bromide (ym155) is a survivin suppressant that induces apoptosis in tumor cells. although ym155 induces tumor regression in various tumor types in vivo, phase i and ii studies demonstrated responding and non-responding patient populations. we investigated 11c-labeled ym155 ([11c]ym155) used as a positron emission tomography (pet) tracer to assess whether tumor uptake of [11c]ym155 correlated with its anti-tumor effect, thereby allowing identification of patients who would respond to ... | 2019 | 30041149 |
| neonatal fc receptor antagonist efgartigimod safely and sustainably reduces iggs in humans. | intravenous ig (ivig), plasma exchange, and immunoadsorption are frequently used in the management of severe autoimmune diseases mediated by pathogenic igg autoantibodies. these approaches modulating igg levels can, however, be associated with some severe adverse reactions and a substantial burden to patients. targeting the neonatal fc receptor (fcrn) presents an innovative and potentially more effective, safer, and more convenient alternative for clearing pathogenic iggs. | 2018 | 30040076 |
| development of a human papillomavirus type 6/11 vaccine candidate for the prevention of condyloma acuminatum. | condyloma acuminatum (ca) represents a significant human papillomavirus (hpv) disease burden worldwide, resulting in substantial healthcare costs and loss of life quality in both genders. to address this problem, we tried to develop a bivalent hpv6/11 virus-like particle (vlp) vaccine targeting ca. hpv6/11 vlps were generated in hansenula polymorpha, and a disassembly and reassembly (d/r) treatment was further conducted to improve the stability and monodispersity of the vlps. the hpv6/11 vlps we ... | 2018 | 30037483 |
| discovery of am-6226: a potent and orally bioavailable gpr40 full agonist that displays efficacy in nonhuman primates. | gpr40 (ffa1) is a g-protein-coupled receptor, primarily expressed in pancreatic islets and enteroendocrine l-cells, and, when activated, elicits increased insulin secretion only in the presence of elevated glucose levels. we recently reported the discovery of am-1638 (2), a full agonist of gpr40. herein, we present further structure-activity relationships progressing from am-1638 (2) to am-6226 (14) that possesses a profile acceptable for dosing cynomolgus monkeys. the gpr40 full agonist am-6226 ... | 2018 | 30034614 |
| first molecular identification of strongyloides fuelleborni in long-tailed macaques in thailand and lao people's democratic republic reveals considerable genetic diversity. | strongyloides fuelleborni is a soil-transmitted nematode parasite of non-human primates. the worm is prevalent also in human populations in africa and south-east asia. in this study, we amplified and sequenced a portion of the 18s ribosomal rna gene (rrna) and of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of strongyloides adult males recovered from faecal samples from long-tailed macaques (macaca fascicularis) in thailand and lao pdr. the prevalence in thailand was 31.1% (55/17 ... | 2019 | 30027858 |
| surgical removal of internal limiting membrane and layering of aav vector on the retina under air enhances gene transfection in a nonhuman primate. | to determine if the surgical removal of the internal limiting membrane (ilm) in nonhuman primates (nhps) will result in safe and effective transfection of adeno-associated viral (aav2) vectors using green fluorescent protein (gfp) as a reporter. | 2018 | 30025098 |
| serotonin concentration enhancers at clinically relevant doses reduce [11c]az10419369 binding to the 5-ht1b receptors in the nonhuman primate brain. | the serotonin (5-ht) system plays an important role in the pathophysiology and treatment of several major psychiatric disorders. currently, no suitable positron emission tomography (pet) imaging paradigm is available to assess 5-ht release in the living human brain. [11c]az10419369 binds to 5-ht1b receptors and is one of the most 5-ht-sensitive radioligands available. this study applied 5-ht concentration enhancers which can be safely studied in humans, and examined their effect on [11c]az104193 ... | 2018 | 30013068 |
| artificial liver and renal support system for cynomolgus monkeys with surgery-induced acute renal failure: a preclinical study. | renal dysfunction is one of the most common complications of liver cirrhosis and is associated with increased morbidity and mortality. however, no available technology can simultaneously support liver and renal function in these patients. the aim of this study was to evaluate the safety and efficacy of an artificial liver and renal support system in cynomolgus monkeys with surgery-induced arf. the arf model was established by ligature of bilateral renal arteries in eight cynomolgus monkeys, whic ... | 2018 | 29992160 |
| effects of a novel selective ep2 receptor agonist, omidenepag isopropyl, on aqueous humor dynamics in laser-induced ocular hypertensive monkeys. | to investigate the mechanism of the intraocular pressure (iop)-lowering effect of a novel selective prostaglandin e2 receptor 2 (ep2) receptor agonist, omidenepag isopropyl (omdi). | 2018 | 29989843 |
| a bridging immunogenicity assay for monoclonal antibody: case study with shr-1222. | shr-1222 is a humanized monoclonal antibody targeted to soluble sclerostin. to support the preclinical study of shr-1222 in cynomolgus monkeys, a method for the detection of anti-drug antibodies is required. | 2018 | 29987936 |
| effects of treatment delay on efficacy of tecovirimat following lethal aerosol monkeypox virus challenge in cynomolgus macaques. | tecovirimat (st-246) is being developed as an antiviral therapeutic for smallpox for use in the event of an accidental or intentional release. the last reported case of smallpox was 1978 but the potential for use of variola virus for biowarfare has renewed interest in smallpox antiviral therapeutics. | 2018 | 29982575 |
| a cynomolgus monkey model of carotid atherosclerosis induced by puncturing and scratching of the carotid artery combined with a high-fat diet. | cardio-cerebrovascular disease is one of the three major causes of mortality in humans and constitutes a major socioeconomic burden. carotid atherosclerosis (cas) is a very common lesion of the arterial walls, which leads to narrowing of the arteries, in some cases occluding them entirely, increasing the risk of cardiovascular events. the aim of the present study was to evaluate a cynomolgus monkey model of carotid atherosclerosis (cas) induced by puncturing and scratching combined with a high-f ... | 2018 | 29977359 |
| vaccination with the conserved caveolin-1 binding motif in human immunodeficiency virus type 1 glycoprotein gp41 delays the onset of viral infection and provides partial protection in simian/human immunodeficiency virus-challenged cynomolgus macaques. | we have previously reported that the cbd1 peptide (sleqiwnnmtwmqwdk), corresponding to the consensus caveolin-1 binding domain in human immunodeficiency virus type 1 (hiv-1) envelope glycoprotein gp41, elicits peptide-specific antibodies. here, we have investigated the cellular immune response and the protective efficacy against a simian/human immunodeficiency virus (shiv162p3) challenge. in addition to the cbd1 peptide, peptides overlapping the caveolin-binding-motif (cbm) (622iwnnmtwmqw631 or ... | 2018 | 29976675 |
| basic research on uterus transplantation in nonhuman primates in japan. | uterus transplantation (utx) is now a potential option for women with uterine factor infertility to have a child. however, utx is still in an experimental stage and basic animal studies including in nonhuman primates are needed for accumulation of data that will provide important information for establishment of utx in humans. herein, we summarized our experiences using cynomolgus macaques, with the goal of promoting further development of utx studies in nonhuman primates. our basic studies usin ... | 2018 | 29974599 |
| cynomolgus monkeys (macaca fascicularis) as an experimental infection model for human group a rotavirus. | group a rotaviruses (rva) are one of the most common causes of severe acute gastroenteritis in infants worldwide. rotaviruses spread from person to person, mainly by faecal⁻oral transmission. almost all unvaccinated children may become infected with rva in the first two years of life. the establishment of an experimental monkey model with rva is important to evaluate new therapeutic approaches. in this study, we demonstrated viral shedding and viraemia in juvenile⁻adult macaca fascicularis orall ... | 2018 | 29973483 |
| dynamics of immune responses during experimental mycobacterium kansasii infection of cynomolgus monkeys (macaca fascicularis). | to profile the dynamic changes of immune responses for m. kansasii infection, 3 cynomolgus monkeys were experimentally infected with m. kansasii by intratracheal inhalation of 1 × 106 cfu bacteria per monkey. every 2 to 4 weeks, tuberculin skin testings (tsts) were performed and blood samples were collected for immunoassay. multiple cytokines in a single sample were measured by luminex xmap technologies. igm and iga were detected by double-antibody sandwich elisa. igg against ppd and 11 m. tuber ... | 2018 | 29967568 |
| 2,4-diaminoquinazolines as dual toll-like receptor (tlr) 7/8 modulators for the treatment of hepatitis b virus. | a novel series of 2,4-diaminoquinazolines was identified as potent dual toll-like receptor (tlr) 7 and 8 agonists with reduced off-target activity. the stereochemistry of the amino alcohol was found to influence the tlr7/8 selectivity with the ( r) isomer resulting in selective tlr8 agonism. lead optimization toward a dual agonist afforded ( s)-3-((2-amino-8-fluoroquinazolin-4-yl)amino)hexanol 31 as a potent analog, being structurally different from previously described dual agonists ( mcgowan j ... | 2018 | 29965759 |
| selection and investigation of a primate model of spontaneous degenerative knee osteoarthritis, the cynomolgus monkey (macaca fascicularis). | background the aim of this study was to identify a primate model of degenerative knee osteoarthritis (koa) that may be more relevant for research studies on degenerative koa in humans. material and methods sixteen specific-pathogen-free (spf) male cynomolgus monkeys (macaca fascicularis) were divided into group a (n=8), an old group (22.0-25.3 years of age), and group b (n=8), a young group (3.0-5.2 years of age). for each primate, the behavior was observed, knee circumference was measured, knee ... | 2018 | 29961076 |
| an anti-cll-1 antibody-drug conjugate for the treatment of acute myeloid leukemia. | the treatment of acute myeloid leukemia (aml) has not significantly changed in 40 years. cytarabine- and anthracycline-based chemotherapy induction regimens (7 + 3) remain the standard of care, and most patients have poor long-term survival. the reapproval of mylotarg, an anti-cd33-calicheamicin antibody-drug conjugate (adc), has demonstrated adcs as a clinically validated option to enhance the effectiveness of induction therapy. we are interested in developing a next-generation adc for aml to i ... | 2019 | 29959143 |
| pedicled instep flap and tibial nerve reconstruction in a cynomolgus monkey [macaca fascicularis]. | a male cynomolgus monkey experienced extensive soft tissue trauma to the right caudal calf area. some weeks after complete healing of the original wounds, the monkey developed a chronic pressure sore on plantar surface of the heel of its right foot. a loss of sensitivity in the sole of the foot was hypothesized. the skin defect was closed by a medial sensate pedicled instep flap followed by counter transplantation of a full thickness graft from the interdigital webspace. the integrity of the tib ... | 2016 | 29955415 |
| extending human igg half-life using structure-guided design. | engineering of antibodies for improved pharmacokinetics through enhanced binding to the neonatal fc receptor (fcrn) has been demonstrated in transgenic mice, non-human primates and humans. traditionally, such approaches have largely relied on random mutagenesis and display formats, which fail to address related critical attributes of the antibody, such as effector functions or biophysical stability. we have developed a structure- and network-based framework to interrogate the engagement of igg w ... | 2018 | 29947573 |
| early-drug development in the era of immuno-oncology: are we ready to face the challenges? | the classical development of drugs has progressively faded away, and we are currently in an era of seamless drug-development, where first-in-human trials include unusually big expansion cohorts in the search for early signs of activity and rapid regulatory approval. the fierce competition between different pharmaceutical companies and the hype for immune combinations obliges us to question the current way in which we are evaluating these drugs. in this review, we discuss critical issues and cave ... | 2018 | 29945232 |
| molecular and functional characterization of udp-glucuronosyltransferase 1a in cynomolgus macaques. | udp-glucuronosyltransferases (ugts) are drug-metabolizing enzymes essential for the metabolism of endogenous substrates and xenobiotics. molecular characteristics of ugts have been extensively investigated in humans, but in cynomolgus macaques, a non-human primate species widely used in drug metabolism studies, remain to be investigated. in this study, 12 ugt1a cdnas (ugt1a1, 1a2, 1a4a, 1a4b, 1a5a, 1a5b, 1a5c, 1a6, 1a7, 1a8, 1a9, and 1a10) were isolated and characterized in cynomolgus macaques. ... | 2018 | 29944869 |
| the brain-penetrant clinical atm inhibitor azd1390 radiosensitizes and improves survival of preclinical brain tumor models. | poor survival rates of patients with tumors arising from or disseminating into the brain are attributed to an inability to excise all tumor tissue (if operable), a lack of blood-brain barrier (bbb) penetration of chemotherapies/targeted agents, and an intrinsic tumor radio-/chemo-resistance. ataxia-telangiectasia mutated (atm) protein orchestrates the cellular dna damage response (ddr) to cytotoxic dna double-strand breaks induced by ionizing radiation (ir). atm genetic ablation or pharmacologic ... | 2018 | 29938225 |
| farletuzumab, a monoclonal antibody directed against folate receptor alpha, shows no evidence of teratogenicity in cynomolgus monkeys. | farletuzumab is a humanized monoclonal antibody targeting human folate receptor alpha, which is being developed as an anti-cancer drug. a non-human primate reproductive study was conducted to evaluate whether it could cause any embryonic or fetal abnormalities. farletuzumab was administered intravenously to pregnant cynomolgus monkeys (n = 16/group) at doses of 0 or 67.5 mg/kg once weekly during gestation day (gd) 20 through 97. c-section was performed on gd100 ± 2, and fetuses were evaluated fo ... | 2018 | 29928988 |
| gut microbiome composition in non-human primates consuming a western or mediterranean diet. | the mammalian gastrointestinal tract harbors a highly diverse and dynamic community of bacteria. the array of this gut bacterial community, which functions collectively as a fully unified organ in the host metabolism, varies greatly among different host species and can be shaped by long-term nutritional interventions. non-human primates, our close phylogenetic relatives and ancestors, provide an excellent model for studying diet-microbiome interaction; however, compared to clinical and rodent st ... | 2018 | 29922651 |
| non-human papillomaviruses for gene delivery in vitro and in vivo. | papillomavirus capsids are known to have the ability to package dna plasmids and deliver them both in vitro and in vivo. of all known papillomavirus types, human papillomaviruses (hpvs) are by far the most intensely studied. although hpvs work well as gene transfer vectors, their use is limited as most individuals are exposed to this virus either through a hpv vaccination or natural infection. to circumvent these constraints, we produced pseudovirions (psvs) of ten non-human papillomavirus types ... | 2018 | 29912929 |
| reemergence of reston ebolavirus in cynomolgus monkeys, the philippines, 2015. | in august 2015, a nonhuman primate facility south of manila, the philippines, noted unusual deaths of 6 cynomolgus monkeys (macaca fascicularis), characterized by generalized rashes, inappetence, or sudden death. we identified reston ebolavirus (restv) infection in monkeys by using serologic and molecular assays. we isolated viruses in tissues from infected monkeys and determined viral genome sequences. restv found in the 2015 outbreak is genetically closer to 1 of the 4 restvs that caused the 2 ... | 2018 | 29912712 |
| soft transparent graphene contact lens electrodes for conformal full-cornea recording of electroretinogram. | visual electrophysiology measurements are important for ophthalmic diagnostic testing. electrodes with combined optical transparency and softness are highly desirable, and sometimes indispensable for many ocular electrophysiology measurements. here we report the fabrication of soft graphene contact lens electrodes (graces) with broad-spectrum optical transparency, and their application in conformal, full-cornea recording of electroretinography (erg) from cynomolgus monkeys. the graces give highe ... | 2018 | 29899545 |
| placental and fetal effects of onartuzumab, a met/hgf signaling antagonist, when administered to pregnant cynomolgus monkeys. | onartuzumab is an engineered single arm, monovalent monoclonal antibody that targets the met receptor and prevents hepatocyte growth factor (hgf) signaling. knockout mice have clearly demonstrated that hgf/met signaling is developmentally critical. a pre- and postnatal development study (enhanced design) was conducted in cynomolgus monkeys to evaluate the potential developmental consequences following onartuzumab administration. control or onartuzumab, at loading/maintenance doses of 75/50 mg/kg ... | 2018 | 29893934 |
| naive, captive long-tailed macaques (macaca fascicularis fascicularis) fail to individually and socially learn pound-hammering, a tool-use behaviour. | a subspecies of long-tailed macaques (macaca fascicularis aurea; mfa) has been reported to use stone tools and a specific technique to process nuts in southeast asia, a behaviour known as 'pound-hammering'. the aim of this study was to examine the development of pound-hammering in long-tailed macaques: whether this behavioural form can be individually learnt or whether it has to rely on some forms of social learning. given the absence of mfa from captivity, long-tailed macaques of a highly relat ... | 2018 | 29892375 |
| optimized adeno-associated viral-mediated human factor viii gene therapy in cynomolgus macaques. | hemophilia a is a common hereditary bleeding disorder that is characterized by a deficiency of human blood coagulation factor viii (hfviii). previous studies with adeno-associated viral (aav) vectors identified two liver-specific promoter and enhancer combinations (e03.ttr and e12.a1at) that drove high level expression of a codon-optimized, b-domain-deleted hfviii transgene in a mouse model of the disease. this study further evaluated these enhancer/promoter combinations in cynomolgus macaques u ... | 2018 | 29890905 |
| long-term toxicity, pharmacokinetics and immune effects of a recombinant adenovirus vaccine expressing human papillomavirus 16 e6 and e7 proteins (hpv16 e6e7-ad5 vac) in primates. | this study aimed to: evaluate long-term toxicity and pharmacokinetic parameters; to identify the target organ of toxicity of a recombinant adenovirus vaccine expressing human papillomavirus 16 e6 and e7 proteins (hpv16 e6e7-ad5 vac) in primates; and to determine the specific immune response of this recombinant adenovirus vaccine. | 2018 | 29887967 |
| utility of arterial blood gas, cbc, biochemistry and cardiac hormones as evaluation parameters of cardiovascular disease in nonhuman primates. | cardiovascular disease (cvd) has a tremendous impact on the quality of life of humans. while experimental animals are valuable to medical research as models of human diseases, cardiac systems differ widely across various animal species. thus, we examined a cvd model in cynomolgus monkeys. laboratory primates are precious resources, making it imperative that symptoms of diseases and disorders are detected as early as possible. thus, in this study we comprehensively examined important indicators o ... | 2018 | 29887581 |
| bioanalysis of sulprostone, a prostaglandin e2 analogue and selective ep3 agonist, in monkey plasma by liquid chromatography-tandem mass spectrometry. | sulprostone is a potent prostaglandin e2 (pge2) analogue and one of the first identified selective g-protein-coupled receptor 3 (ep3) agonists. it has been investigated as a potential antiulcer agent and frequently used in the research of ep3 antagonist. to assist pharmacokinetic and pharmacodynamic studies, a rapid and sensitive lc-ms/ms method was developed and qualified for the quantitation of sulprostone in monkey plasma. using electrospray ionization mass spectrometry, an ammonium adduct in ... | 2018 | 29883889 |
| efficacy of an inhaled il-13 antibody fragment in a model of chronic asthma. | il-13 is an important cytokine implicated in the pathogenesis of allergic asthma and is an attractive target for an inhaled therapeutic. | 2018 | 29883204 |
| simultaneous assessment of transporter-mediated drug-drug interactions using a probe drug cocktail in cynomolgus monkey. | we aim to establish an in vivo preclinical model to enable simultaneous assessment of inhibition potential of an investigational drug on clinically relevant drug transporters, organic anion-transporting polypeptide (oatp)1b, breast cancer resistance protein (bcrp), p-glycoprotein (p-gp), and organic anion transporter (oat)3. pharmacokinetics of substrate cocktail consisting of pitavastatin (oatp1b substrate), rosuvastatin (oatp1b/bcrp/oat3), sulfasalazine (bcrp), and talinolol (p-gp) were obtain ... | 2018 | 29880631 |
| discovery of novel pyrazole-based selective aldosterone synthase (cyp11b2) inhibitors: a new template to coordinate the heme-iron motif of cyp11b2. | it is necessary for aldosterone synthase (cyp11b2) inhibitors to have both high potency and high selectivity over 11β-hydroxylase (cyp11b1), a critical enzyme for cortisol synthesis. previous studies have reported a number of cyp11b2 inhibitors, most of which have an imidazole or pyridine ring to coordinate the heme-iron motif of cyp11b2; however, highly selective inhibitors of human cyp11b2 are still needed. to expand the selectivity in humans, we explored alternative templates and found that p ... | 2018 | 29878770 |
| dosing optimization of ccr4 immunotoxin for improved depletion of ccr4+ treg in nonhuman primates. | recently, we have developed a diphtheria toxin-based recombinant anti-human ccr4 immunotoxin for targeting ccr4+ tumors and tregs. in this study, we further optimized the dosing schedule for improved ccr4+ treg depletion. we have demonstrated that up to a 90% depletion was achieved and the depletion extended to approximately 2 weeks in the peripheral blood and more than 48 days in the lymph node at 25 μg·kg-1 , bid for 8 consecutive days in cynomolgus monkeys. expansion was observed including mo ... | 2018 | 29873181 |
| evidence for sprouting of dopamine and serotonin axons in the pallidum of parkinsonian monkeys. | this light and electron microscopie immunohistochemical quantitative study aimed at determining the state of the dopamine (da) and serotonin (5-ht) innervations of the internal (gpi) and external (gpe) segments of the pallidum in cynomolgus monkeys (macaca fascicularis) rendered parkinsonian by systemic injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp). in contrast to the prominent da denervation of striatum, the gpi in mptp monkeys was found to be markedly enriched in da (th+) a ... | 2018 | 29867377 |
| development of mgd007, a gpa33 x cd3-bispecific dart protein for t-cell immunotherapy of metastatic colorectal cancer. | we have developed mgd007 (anti-glycoprotein a33 x anti-cd3), a dart protein designed to redirect t cells to target gpa33 expressing colon cancer. the gpa33 target was selected on the basis of an antibody-based screen to identify cancer antigens universally expressed in both primary and metastatic colorectal cancer specimens, including putative cancer stem cell populations. mgd007 displays the anticipated-bispecific binding properties and mediates potent lysis of gpa33-positive cancer cell lines, ... | 2018 | 29866746 |
| a novel fully human anti-cd47 antibody as a potential therapy for human neoplasms with good safety. | strategies for targeting cd47 are becoming a hot spot of cancer immunotherapy. however the ubiquitous expression of cd47, especially on the rbc, makes the targeted therapy facing safety risk issues. so, how to balance the safety and efficacy during cd47 inhibition is currently a major question. we had reported an anti-cd47 antibody zf1 with potent anti-tumor effect. in this study, we further developed and assessed a novel fully human anti-cd47 antibody, amms4-g4, derived from zf1 using affinity ... | 2018 | 29864508 |
| pharmacokinetics and pharmacodynamics of the cytolytic anti-cd38 human monoclonal antibody tak-079 in monkey - model assisted preparation for the first in human trial. | we are studying the fully human, igg1λ cytolytic monoclonal antibody tak-079, which binds cd38. cd38 is expressed on plasma and natural killer (nk) cells constitutively and upregulated on subsets of b and t lymphocytes upon activation. tak-079 cross-reacts with cd38 expressed by cynomolgus monkeys and depletes subsets of nk, b, and t cells. therefore, safety and function of tak-079 was evaluated in this species, prior to clinical development, using bioanalytical, and flow cytometry assays. we po ... | 2018 | 29864242 |
| post-exposure protection in mice against sudan virus by a two antibody cocktail. | sudan virus (sudv) and ebola viruses (ebov) are both members of the ebolavirus genus and have been sources of epidemics and outbreaks for several decades. we present here the generation and characterization of cross-reactive antibodies to both sudv and ebov, which were produced in a cell-free system and protective against sudv in mice. a non-human primate, cynomolgus macaque, was immunized with viral-replicon particles expressing the glycoprotein of sudv-boniface (8a). two separate antibody frag ... | 2018 | 29861435 |
| quantitative translational analysis of brain kynurenic acid modulation via irreversible kynurenine aminotransferase ii inhibition. | kynurenic acid (kyna) plays a significant role in maintaining normal brain function, and abnormalities in kyna levels have been associated with various central nervous system disorders. confirmation of its causality in human diseases requires safe and effective modulation of central kyna levels in the clinic. the kynurenine aminotransferases (kat) ii enzyme represents an attractive target for pharmacologic modulation of central kyna levels; however, kat ii and kyna turnover kinetics, which could ... | 2018 | 29853495 |
| the impact of septic stimuli on the systemic inflammatory response and physiologic insult in a preclinical non-human primate model of polytraumatic injury. | established animal trauma models are limited in recapitulating the pathophysiology of human traumatic injury. herein, we characterize the physiologic insult and inflammatory response in two clinically relevant non-human primate (nhp) trauma models. | 2018 | 29849508 |
| relationship between menarche and fertility in long-tailed macaques (macaca fascicularis). | we attempted to elucidate female reproduction in long-tailed macaques (macaca fascicularis). these monkeys have a non-seasonal menstruation cycle, which makes them suitable subjects for studies in a variety fields including medical science and regenerative medicine. we analyzed individual breeding data including time of menarche, start of regular menstruation, and first pregnancy. these three events are related to the maturation of female long-tailed macaques. all research subjects were female l ... | 2018 | 29848903 |