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in vitro and in vivo pharmacological profile of the selective β3-adrenoceptor agonist mirabegron in rats.to investigate the pharmacological properties of mirabegron in in vitro and in vivo, the effects on camp accumulation in chinese hamster ovary (cho) cells expressing rat β-adrenoceptors, the relaxant activity in isolated rat bladder smooth muscle, and the voiding effects in cerebral infarcted rats were evaluated. mirabegron increased camp accumulation with ec(50) value and intrinsic activity of 19 nmol/l and 1.0, respectively, in cho cells expressing rat β(3)-adrenoceptors. the ec(50) values and ...201323239087
autocrine endocannabinoid signaling through cb1 receptors potentiates ox1 orexin receptor signaling.it has been proposed that ox(1) orexin receptors and cb(1) cannabinoid receptors can form heteromeric complexes, which affect the trafficking of ox(1) receptors and potentiate ox(1) receptor signaling to extracellular signal-regulated kinase (erk). we have recently shown that ox(1) receptor activity releases high levels of the endocannabinoid 2-arachidonoyl glycerol (2-ag), suggesting an alternative route for ox(1)-cb(1) receptor interaction in signaling, for instance, in retrograde synaptic tra ...201323233488
continuous purification of antibodies from cell culture supernatant with aqueous two-phase systems: from concept to process.an aqueous two-phase extraction (atpe) process based on a peg/phosphate system was developed for the capture of human immunoglobulin g and successfully applied to a chinese hamster ovary and a per.c6® cell supernatant. a continuous atpe process incorporating three different steps (extraction, back-extraction, and washing) was set up and validated in a pump mixer-settler battery. most of the higher molecular weight cell supernatant impurities were removed during the extraction step, while most of ...201323229953
combined exposure to 3-chloro-4-dichloromethyl-5-hydroxy-2(5h)-furanone and microsytin-lr increases genotoxicity in chinese hamster ovary cells through oxidative stress.the disinfection byproducts 3-chloro-4-dichloromethyl-5-hydroxy-2(5h)-furanone (mx) and microcystins-lr (mc-lr), which are common contaminants in drinking water, often occur together in water sources in areas with high gastrointestinal tract cancer risks. while often studied alone, combination effects of these compounds are unknown. here, we examine combined genotoxic responses to mixtures of mx and mc-lr using the ames test, a cytokinesis-block micronuclei assay, and the comet assay with analys ...201323286199
effect of cholesterol depletion on the pore dilation of trpv1.the trpv1 ion channel is expressed in nociceptors, where pharmacological modulation of its function may offer a means of alleviating pain and neurogenic inflammation processes in the human body. the aim of this study was to investigate the effects of cholesterol depletion of the cell on ion-permeability of the trpv1 ion channel. the ion-permeability properties of trpv1 were assessed using whole-cell patch-clamp and yo-pro uptake rate studies on a chinese hamster ovary (cho) cell line expressing ...201323279936
pharmacological characterization of gsk573719 (umeclidinium): a novel, long-acting, inhaled antagonist of the muscarinic cholinergic receptors for treatment of pulmonary diseases.activation of muscarinic subtype 3 (m3) muscarinic cholinergic receptors (machrs) increases airway tone, whereas its blockade improves lung function and quality of life in patients with pulmonary diseases. the present study evaluated the pharmacological properties of a novel machr antagonist, gsk573719 (4-[hydroxy(diphenyl)methyl]-1-{2-[(phenylmethyl)oxy]ethyl}-1-azoniabicyclo[2.2.2]octane; umeclidinium). the affinity (ki) of gsk573719 for the cloned human m1-m5 machrs ranged from 0.05 to 0.16 n ...201323435542
modified pamam dendrimer with 4-carbomethoxypyrrolidone surface groups reveals negligible toxicity against three rodent cell-lines.modification of the surface groups of dendrimers is one of the methods to improve their biocompatibility. this article presents results of experiments related to the toxicity of a modified polyamidoamine (pamam) dendrimer of the fourth generation with 4-carbomethoxypyrrolidone surface groups (pamam-pyrrolidone dendrimer). the cytotoxic activity of the dendrimer was tested on chinese hamster fibroblasts (b14), embryonic mouse hippocampal cells (mhippoe-18) and rat liver derived cells (brl-3a). th ...201323434674
relationship of cellular topoisomerase iiα inhibition to cytotoxicity and published genotoxicity of fluoroquinolone antibiotics in v79 cells.fluoroquinolone (fq) antibiotics are bacteriocidal through inhibition of the bacterial gyrase and at sufficient concentrations in vitro, they can inhibit the homologous eukaryotic topoisomerase (topo) ii enzyme. fq exert a variety of genotoxic effects in mammalian systems through mechanisms not yet established, but which are postulated to involve inhibition of topo ii enzymes. to assess the relationship of inhibition of cell nuclear topo ii to cytotoxicity and reported genotoxicity, two fq, clin ...201323340199
solvation dynamics of biological water in a single live cell under a confocal microscope.time-resolved confocal microscopy has been applied to study the cytoplasm and nucleus region of a single live chinese hamster ovary (cho) cell. to select the cytoplasm and the nucleus region, two different fluorescent probes are used. a hydrophobic fluorescent dye, dcm, localizes preferentially in the cytoplasm region of a cho cell. a dna binding dye, dapi, is found to be inside the nucleus of the cell. the locations of the probes are clearly seen in the image. emission maxima of the dyes (dcm i ...201323336846
cell surface-fluorescence immunosorbent assay for real-time detection of hybridomas with efficient antibody secretion at the single-cell level.for establishing cells that secrete antibodies most efficiently (e.g., hybridomas, cho (chinese hamster ovary) cells), the screening and subsequent breeding of promising cells have been performed at the single-colony level, which requires several weeks to propagate a substantial number of cells by forming colonies from single cells for evaluation by the conventional assays. however, this screening process lacks high-throughput performance in time and colony numbers. therefore, development of nov ...201323297690
particulate matter promotes in vitro receptor-recognizable low-density lipoprotein oxidation and dysfunction of lipid receptors.particulate matter may promote cardiovascular disease, possibly as a consequence of its oxidative potential. studies using susceptible animals indicate that particulate matter aggravates atherosclerosis by increasing lipid/macrophage content in plaques. macrophage lipid uptake requires oxidized low-density lipoprotein and scavenger receptors; same receptors are involved in particulate matter uptake. we studied in vitro particulate matter potential to oxidize low-density lipoproteins and subseque ...201323297186
a comparison of the signalling properties of two tyramine receptors from drosophila.in invertebrates, the phenolamines, tyramine and octopamine, mediate many functional roles usually associated with the catecholamines, noradrenaline and adrenaline, in vertebrates. the α- and β-adrenergic classes of insect octopamine receptor are better activated by octopamine than tyramine. similarly, the tyramine 1 subgroup of receptors (or octopamine/tyramine receptors) are better activated by tyramine than octopamine. however, recently, a new tyramine 2 subgroup of receptors was identified, ...201323356740
cell type-dependent induction of dna damage by 1800 mhz radiofrequency electromagnetic fields does not result in significant cellular dysfunctions.although iarc clarifies radiofrequency electromagnetic fields (rf-emf) as possible human carcinogen, the debate on its health impact continues due to the inconsistent results. genotoxic effect has been considered as a golden standard to determine if an environmental factor is a carcinogen, but the currently available data for rf-emf remain controversial. as an environmental stimulus, the effect of rf-emf on cellular dna may be subtle. therefore, more sensitive method and systematic research stra ...201323355902
a new integrated lab-on-a-chip system for fast dynamic study of mammalian cells under physiological conditions in bioreactor.for the quantitative analysis of cellular metabolism and its dynamics it is essential to achieve rapid sampling, fast quenching of metabolism and the removal of extracellular metabolites. common manual sample preparation methods and protocols for cells are time-consuming and often lead to the loss of physiological conditions. in this work, we present a microchip-bioreactor setup which provides an integrated and rapid sample preparation of mammalian cells. the lab-on-a-chip system consists of fiv ...201324709705
role for phospholipid flippase complex of atp8a1 and cdc50a proteins in cell migration.type iv p-type atpases (p4-atpases) and cdc50 family proteins form a putative phospholipid flippase complex that mediates the translocation of aminophospholipids such as phosphatidylserine (ps) and phosphatidylethanolamine (pe) from the outer to inner leaflets of the plasma membrane. in chinese hamster ovary (cho) cells, at least eight members of p4-atpases were identified, but only a single cdc50 family protein, cdc50a, was expressed. we demonstrated that cdc50a associated with and recruited p4 ...201323269685
clinicopathological and functional significance of xrcc1 expression in ovarian cancer.x-ray repair cross-complementing gene 1 (xrcc1) is essential for dna base excision repair, single strand break repair and nucleotide excision repair. we investigated clinicopathological and functional significance of xrcc1 expression in ovarian cancers. xrcc1 protein expression was evaluated in 195 consecutive human ovarian cancers and correlated with clinicopathological variables and survival outcomes. functional preclinical studies were conducted in a panel of xrcc1 deficient and proficient ch ...201323225521
an engineered fibrinogen variant aαq328,366p does not polymerise normally, but retains the ability to form α cross-links.a fibrin clot is stabilised through the formation of factor xiiia-catalysed intermolecular ε-lysyl-γ-glutamyl covalent cross-links between α chains to form α polymers and between γ chains to form γ dimers. in a previous study we characterised fibrinogen seoul ii, a heterozygous dysfibrinogen in which a cross-linking acceptor site in aα chain, gln328, was replaced with pro (aαq328p). following on the previous study, we investigated whether the alteration of gln residues aα328 and aα366 affects fi ...201323224113
overproduction of recombinant human mannose-binding lectin (mbl) in chinese hamster ovary cells.mannose-binding lectin (mbl) is an important serum protein that functions in the innate immune system and has been considered to have therapeutic potential in mbl replacement therapies for patients with deficient or low levels of mbl. in this study, we established a chinese hamster ovary (cho) cell line that overexpresses the recombinant human mbl (rhmbl) protein. in an 11-day batch culture process using a 30-l bioreactor (20-l working volume) and serum-free medium, these cells could produce ove ...201323201283
parkinson's disease-associated human p5b-atpase atp13a2 increases spermidine uptake.p-type ion pumps are membrane transporters that have been classified into five subfamilies termed p1-p5. the ion transported by the p5-atpases is not known. five genes, atp13a (atpase type 13a) 1-atp13a5, that belong to the p5-atpase group have been identified in humans. mutations of the human gene atp13a2 underlie a form of pd (parkinson's disease). previous studies have suggested a relation between polyamines and p5b-atpases. we have recently shown that the cytotoxicity induced by the polyamin ...201323205587
cell uptake and cytotoxicity of a novel cyclometalated iridium(iii) complex and its octaarginine peptide conjugate.the synthesis and characterisation of iridium(iii) bis(2-(2,4-difluorophenyl)pyridinato-n, c2')-2(4-carboxylphenyl)imidazo[4,5-f][1,10]phenanthroline perchlorate, [ir(dfpp)(2)(piccooh)](+) and its octaarginine conjugate [ir(dfpp)(2)(picconh-arg(8))](9+) are reported. both complex and conjugate exhibit intense and long-lived luminescence, which is o(2) and ph sensitive. conjugation to the polyarginine peptide renders the complex very water soluble. the uptake of the parent iridium(iii) complex an ...201323201851
dual role of dextran sulfate 5000 da as anti-apoptotic and pro-autophagy agent.dextran sulfate 5,000 da (ds), a sulfated polysaccharide, has been used in recombinant mammalian cell cultures to prevent cell aggregation, thereby increasing cell viability. previous studies using chinese hamster ovary (cho) suspension cultures had shown that low concentrations of ds are related to an inhibition of apoptosis. in this study, ds was used on anchorage-dependent cho cells producing erythropoietin (epo), in order to investigate the effect of this molecule on anti-apoptotic and pro-s ...201323180219
pulmonary delivery of an aerosolized recombinant human butyrylcholinesterase pretreatment protects against aerosolized paraoxon in macaques.butyrylcholinesterase (bche) is the leading pretreatment candidate against exposure to organophosphates (ops), which pose an ever increasing public and military health. since respiratory failure is the primary cause of death following acute op poisoning, an inhaled bche therapeutic could prove highly efficacious in preventing acute toxicity as well as the associated delayed neuropathy. to address this, studies have been performed in mice and macaques using chinese hamster ovary cells (cho)-deriv ...201323178380
increased susceptibility to delayed genetic effects of low dose x-irradiation in dna repair deficient cells.to examine whether the levels of micronuclei induction, as a marker for genomic instability in the progeny of x-irradiated cells, correlates with dna repair function.201323176200
intraoperative hyperthermic chemotherapy perfusion for malignant pleural mesothelioma: an in vitro evaluation.hyperthermic chemotherapy perfusion has been used in the treatment of both pleural and peritoneal mesothelioma without an extensive basic science foundation. clinical data are limited with no prospective randomized trials to support the use of this potentially toxic therapy. we sought to generate basic scientific support for this clinical practice and to define the optimal conditions for use in future clinical trials.201323174177
cyp3a4 overexpression enhances the cytotoxicity of the antitumor triazoloacridinone derivative c-1305 in cho cells.to examine how the higher expression level of cyp3a4 isoenzyme influenced the cytotoxicity of the antitumor triazoloacridinone derivative c-1305 in chinese hamster ovary (cho) cells.201323160340
parallel labeling experiments with [1,2-(13)c]glucose and [u-(13)c]glutamine provide new insights into cho cell metabolism.we applied a parallel labeling strategy using two isotopic tracers, [1,2-(13)c]glucose and [u-(13)c]glutamine, to determine metabolic fluxes in chinese hamster ovary (cho) cells. cho cells were grown in parallel cultures over a period of six days with glucose and glutamine feeding. on days 2 and 5, isotopic tracers were introduced and (13)c-labeling of intracellular metabolites was measured by gas chromatography-mass spectrometry (gc-ms). metabolites in glycolysis pathway reached isotopic steady ...201323111062
process model comparison and transferability across bioreactor scales and modes of operation for a mammalian cell bioprocess.a monod kinetic model, logistic equation model, and statistical regression model were developed for a chinese hamster ovary cell bioprocess operated under three different modes of operation (batch, bolus fed-batch, and continuous fed-batch) and grown on two different bioreactor scales (3 l bench-top and 15 l pilot-scale). the monod kinetic model was developed for all modes of operation under study and predicted cell density, glucose glutamine, lactate, and ammonia concentrations well for the bio ...201323143896
investigation of alginate-ε-poly-l-lysine microcapsules for cell microencapsulation.cell microencapsulation is a promising approach for cell implantation, cell-based gene therapy, and large-scale cell culture. the well-studied α-ap (alginate-α-poly-l-lysine) microcapsules have been restricted to large-scale cell-culture and clinical applications because of high costs and cytotoxic effects in some cases. this study used ε-poly-l-lysine (ε-pll), a high-biocompatible and low-cost food additives produced by fermentation, to prepare ε-ap (alginate-ε-pll) microcapsules with various t ...201323065714
equine cytochrome p450 2b6--genomic identification, expression and functional characterization with ketamine.ketamine is an anesthetic and analgesic regularly used in veterinary patients. as ketamine is almost always administered in combination with other drugs, interactions between ketamine and other drugs bear the risk of either adverse effects or diminished efficacy. since cytochrome p450 enzymes (cyps) play a pivotal role in the phase i metabolism of the majority of all marketed drugs, drug-drug interactions often occur at the active site of these enzymes. cyps have been thoroughly examined in huma ...201323142468
eliminating tyrosine sequence variants in cho cell lines producing recombinant monoclonal antibodies.amino acid sequence variants are defined as unintended amino acid sequence changes that contribute to product variation with potential impact to product safety, immunogenicity, and efficacy. therefore, it is important to understand the propensity for sequence variant (sv) formation during the production of recombinant proteins for therapeutic use. during the development of clinical therapeutic products, several monoclonal antibodies (mabs) produced from chinese hamster ovary (cho) cells exhibite ...201323108857
p.d1690n nav1.5 rescues p.g1748d mutation gating defects in a compound heterozygous brugada syndrome patient.we identified 2 compound heterozygous mutations (p.d1690n and p.g1748d) in the scn5a gene encoding cardiac na(+) channels (nav1.5) in a proband diagnosed with brugada syndrome type 1. furthermore, in the allele encoding the p.d1690n mutation, the p.h558r polymorphism was also detected.201323085483
multiple mechanisms of ligand interaction with the human organic cation transporter, oct2.oct2 is the entry step for organic cation (oc) secretion by renal proximal tubules. although many drugs inhibit oct2 activity, neither the mechanistic basis of their inhibition nor their transport status is generally known. using representatives of several structural classes of oct2-inhibitory ligands described recently (kido y, matsson p, giacomini km. j med chem 54: 4548-4558, 2011), we determined the kinetic basis of their inhibition of 1-methyl-4-phenylpyridinium (mpp) transport into chinese ...201323034939
selective transport of long-chain fatty acids by fat/cd36 in skeletal muscle of broilers.fatty acid translocase (fat/cd36) is a membrane receptor that facilitates long-chain fatty acid uptake. to investigate its role in the regulation of long-chain fatty acid composition in muscle tissue, we studied and compared fat/cd36 gene expression in muscle tissues of commercial broiler chickens and chinese local silky fowls. the results from gas chromatography-mass spectrometry analysis of muscle samples demonstrated that chinese local silky fowls had significantly higher (p < 0.05) proportio ...201323031491
characterisation of the post-translational modifications of a novel, human cell line-derived recombinant human factor viii.host cell lines used for recombinant protein expression differ in their ability to perform post-translational modifications (ptms). the currently available recombinant human fviii (rhfviii) products are produced in mammalian, non-human cell lines. for rhfviii, glycosylation and sulfation are vital for functionality and von willebrand factor (vwf)-binding affinity. here we present the characterisation of the ptms of a novel, human cell line-derived recombinant human fviii (human-cl rhfviii). rhfv ...201323058466
exploration of bac versus plasmid expression vectors in recombinant cho cells.vector engineering approaches are commonly used to increase recombinant protein production in mammalian cells, and among various concepts, bacterial artificial chromosomes (bac) have been proposed to serve as open chromatin regions to omit chromosome positional effects. for proof of concept, we developed stable recombinant chinese hamster ovary (cho) cell lines using different expression vector systems: the plasmid vectors contained the identical expression cassette as the bac constructs. two an ...201323081777
hyperthermia inhibits homologous recombination repair and sensitizes cells to ionizing radiation in a time- and temperature-dependent manner.hyperthermia has long been known as a radio-sensitizing agent that displays anti-tumor effects, and has been developed as a therapeutic application. the mechanisms of hyperthermia-induced radio-sensitization are highly associated with inhibition of dna repair. our investigations aimed to show how hyperthermia inactivate homologous recombination repair in the process of sensitizing cells to ionizing radiation by using a series of dna repair deficient chinese hamster cells. significant differences ...201323254360
evaluation of the cytotoxicity of cigarette smoke total particulate matter using three in vitro assays and two types of cells.in vitro cytotoxicity assays can be used to evaluate potential toxicological effects of tobacco products. total particulate matter (tpm) from mainstream cigarette smoke trapped by a cambridge filter is used widely for biological evaluation of smoke. this study compared neutral red uptake (nru), lactate dehydrogenase (ldh) activity and wst-1 assays for assessing the cytotoxicity of tpm, and evaluated the sensitivity of chinese hamster ovary (cho) cells and human lung adenocarcinoma epithelial cel ...201323193988
targeting xrcc1 deficiency in breast cancer for personalized therapy.xrcc1 is a key component of dna base excision repair, single strand break repair, and backup nonhomologous end-joining pathway. xrcc1 (x-ray repair cross-complementing gene 1) deficiency promotes genomic instability, increases cancer risk, and may have clinical application in breast cancer. we investigated xrcc1 expression in early breast cancers (n = 1,297) and validated in an independent cohort of estrogen receptor (er)-α-negative breast cancers (n = 281). preclinically, we evaluated xrcc1-def ...201323253910
identification of the integrin β3 l718p mutation in a pedigree with autosomal dominant thrombocytopenia with anisocytosis.αiibβ3 integrin mutations that result in the complete loss of expression of this molecule on the platelet surface cause glanzmann thrombasthenia. this is usually autosomal recessive, while other mutations are known to cause dominantly inherited macrothrombocytopenia (although such cases are rare). here, we report a 4-generation pedigree including 10 individuals affected by dominantly inherited thrombocytopenia with anisocytosis. six individuals, whose detailed clinical and laboratory data were a ...201323253071
interstitial telomeric sequences are not preferentially involved in the chromosome damage induced by the methylating compound streptozotocin in chinese hamster cells.the effect of the methylating compound streptozotocin (stz) on interstitial telomeric sequences (itss) was investigated in chinese hamster ovary (cho) cells by using peptide nucleic acid-fluorescence in situ hybridization with a pantelomeric probe. cells were exposed to increasing concentrations of stz, and chromosomal aberrations were analyzed at the first mitosis after treatment. the frequency of chromosomal aberrations directly involving itss increased in stz-treated cells by a factor of 2.6 ...201323192999
pharmacokinetics and brain uptake in the rhesus monkey of a fusion protein of arylsulfatase a and a monoclonal antibody against the human insulin receptor.metachromatic leukodystrophy (mld) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase a (asa). it is not possible to treat the brain in mld with recombinant asa, because the enzyme does not cross the blood-brain barrier (bbb). in the present investigation, a bbb-penetrating igg-asa fusion protein is engineered and expressed, where the asa monomer is fused to the carboxyl terminus of each heavy chain of an engineered monocl ...201323192358
identification and quantitation of vesivirus 2117 particles in bioreactor fluids from infected chinese hamster ovary cell cultures.the prevention of adventitious agent contamination is a top priority throughout the entire biopharmaceutical production process. for example, although viral contamination of cell banks or cell cultures is rare, it can result in serious consequences (e.g., shutdown and decontamination of manufacturing facilities). to ensure virus free production, numerous in vivo and in vitro adventitious agent assays and biophysical characterizations such as electron microscopy are conducted on cell banks, raw m ...201323184768
effects of synthetic a3 adenosine receptor agonists on cell proliferation and viability are receptor independent at micromolar concentrations.the question as to whether a3 adenosine receptor (a3ar) agonists, n (6)-(3-iodobenzyl)-adenosine-5'-n- methyluronamide (ib-meca) and 2-chloro-n (6)-(3-iodobenzyl)-adenosine-5'-n-methyluronamide (cl-ib-meca), could exert cytotoxic effects at high concentrations with or without the involvement of a3ar has been a controversial issue for a long time. the initial findings suggesting that a3ar plays a crucial role in the induction of cell death upon treatment with micromolar concentrations of ib-meca ...201323184730
uncoupling of m1 muscarinic receptor/g-protein interaction by amyloid β(1-42).the overproduction of β-amyloid (aβ) fragments in transgenic appswe/ps1de9 mice results in formation of amyloid deposits in the cerebral cortex and hippocampus starting around four months of age and leading to cognitive impairment much later. we have previously found an age and transgene-dependent weakening of muscarinic receptor-mediated transmission that was not present in young (6-10-week-old) animals but preceded both amyloid deposits and cognitive deficits. now we investigated immediate and ...201323206502
affinity chromatographic purification of human immunoglobulin a from chinese hamster ovary cell culture supernatant.hexamer peptide ligand hwrgwv, initially screened from a solid phase combinatorial peptide library for immunoglobulins g (igg) purification, is shown to also have potential for immunoglobulin a (iga) purification. the determined dissociation constants for higa on hwrgwv resins at three different peptide densities from 0.11 to 0.55 meq/g fall in the range of 10(-6) -10(-7) m, which are somewhat lower than those for higg. although relatively low dynamic binding capacity (dbc) in the range of 9.2-1 ...201323125152
a simple eccentric stirred tank mini-bioreactor: mixing characterization and mammalian cell culture experiments.in industrial practice, stirred tank bioreactors are the most common mammalian cell culture platform. however, research and screening protocols at the laboratory scale (i.e., 5-100 ml) rely primarily on petri dishes, culture bottles, or erlenmeyer flasks. there is a clear need for simple-easy to assemble, easy to use, easy to clean-cell culture mini-bioreactors for lab-scale and/or screening applications. here, we study the mixing performance and culture adequacy of a 30 ml eccentric stirred tan ...201323124589
optimized signal peptides for the development of high expressing cho cell lines.recombinant biotherapeutic proteins such as monoclonal antibodies are mostly produced in chinese hamster ovary (cho) cells and pharmaceutical companies are interested in an appropriate platform technology for the development of large-scale production processes. a major aim of our study was therefore to improve the secretion efficiency of a recombinant biotherapeutic antibody by optimizing signal peptides. reporter molecules such as gaussia and vargula luciferase or secreted alkaline phosphatase ...201323124363
interaction of ssr161421, a novel specific adenosine a(3) receptor antagonist with adenosine a(3) receptor agonists both in vitro and in vivo.a novel adenosine a(3) receptor antagonist (ssr161421) was characterized by both receptor binding assays and pharmacological tests. binding studies on cloned human adenosine receptors showed that ssr161421 has high affinity for adenosine ha(3) receptors (k(i)=0.37 nm) with at least 1000-fold selectivity compared to ha(1), ha(2a) and ha(2b) receptors. the receptor antagonist nature of ssr161421 was determined in a functional study on chinese hamster ovarian cells (cho) cells expressing human aden ...201323219789
cell-surface glycosaminoglycans inhibit intranuclear uptake but promote post-nuclear processes of polyamidoamine dendrimer-pdna transfection.interaction of cell-surface glycosaminoglycans (gags) with non-viral vectors seems to be an important factor which modifies the intracellular destination of the gene complexes. intracellular kinetics of polyamidoamine (pamam) dendrimer as a non-viral vector in cellular uptake, intranuclear delivery and transgene expression of plasmid dna with regard to the cell-surface gags has not been investigated until now.201323131796
relocalization of kit d816v to cell surface after dasatinib treatment: potential clinical implications.systemic mastocytosis (sm) is a heterogeneous disease that displays variable aggressivity. adults with sm frequently have a d816v mutation in the tyrosine kinase (tk) receptor gene kit. we previously reported that, in a chinese hamster ovarian cell model expressing exogenous kit variants, constitutive activating kit mutations induced intracellular mislocalization of kit reversed by inhibition of kit tk activity. hence, we hypothesized that inhibition of kit kinase activity by the tk inhibitor da ...201323127495
efficient recombinant protein production and secretion from nuclear transgenes in chlamydomonas reinhardtii.microalgae are diverse photosynthetic microbes which offer the potential for production of a number of high value products (hvp) such as pigments, oils, and bio-active compounds. fast growth rates, ease of photo-autotrophic cultivation, unique metabolic properties and continuing progress in algal transgenics have raised interest in the use of microalgae systems for recombinant protein (rp) production. this work demonstrates the development of an advanced rp production and secretion system for th ...201323099045
gene polymorphisms predict toxicity to neoadjuvant therapy in patients with rectal cancer.toxicity from neoadjuvant chemoradiation therapy (nt) increases morbidity and limits therapeutic efficacy in patients with rectal cancer. the objective of this study was to determine whether specific polymorphisms in genes associated with rectal cancer response to nt were correlated with nt-related toxicity.201323096768
involvement of gangliosides in the process of cbp/pag phosphorylation by lyn in developing cerebellar growth cones.the association of gangliosides with specific proteins in the central nervous system was examined by coimmunoprecipitation with an anti-ganglioside antibody. the monoclonal antibody to the ganglioside gd3 (r24) immunoprecipitated the csk (c-terminal src kinase)-binding protein (cbp). sucrose density gradient analysis showed that cbp of rat cerebellum was detected in detergent-resistant membrane (drm) raft fractions. r24 treatment of the rat primary cerebellar cultures induced lyn activation and ...201323035659
a comparative analysis of radiobiological models for cell surviving fractions at high doses.for many years the linear-quadratic (lq) model has been widely used to describe the effects of total dose and dose per fraction at low-to-intermediate doses in conventional fractionated radiotherapy. recent advances in stereotactic radiosurgery (srs) and stereotactic radiotherapy (srt) have increased the interest in finding a reliable cell survival model, which will be accurate at high doses, as well. different models have been proposed for improving descriptions of high dose survival responses, ...201323098282
pex5p stabilizes pex14p: a study using a newly isolated pex5 cho cell mutant, zpeg101.pex5p [pts (peroxisome-targeting signal) type 1 receptor] plays an essential role in peroxisomal matrix protein import. in the present study, we isolated a novel pex5-deficient cho (chinese-hamster ovary) cell mutant, termed zpeg101, showing typical peroxisomal import defects of both pts1 and pts2 proteins. zpeg101 is distinct from other known pex5 cho mutants in its pex5p expression. an undetectable level of pex5p in zpeg101 results in unstable pex14p, which is due to inefficient translocation ...201323009329
detection of the cytotoxicity of water-insoluble fraction of cigarette smoke by direct exposure to cultured cells at an air-liquid interface.for the biological evaluation of cigarette smoke in vitro, the particulate phase (pp) and the gas vapor phase (gvp) of mainstream smoke have usually been collected individually and exposed to biological material such as cultured cells. using this traditional method, the gvp is collected by bubbling in an aqueous solution such as phosphate-buffered saline (pbs). in such a way the water-insoluble gvp fraction is excluded from the gvp, meaning that the toxic potential of the water-insoluble gvp fra ...201322999638
a kinetic-metabolic model based on cell energetic state: study of cho cell behavior under na-butyrate stimulation.a kinetic-metabolic model approach describing and simulating chinese hamster ovary (cho) cell behavior is presented. the model includes glycolysis, pentose phosphate pathway, tca cycle, respiratory chain, redox state and energetic metabolism. growth kinetic is defined as a function of the major precursors for the synthesis of cell building blocks. michaelis-menten type kinetic is used for metabolic intermediates as well as for regulatory functions from energy shuttles (atp/adp) and cofactors (na ...201322976819
n-glycan analysis of human α1-antitrypsin produced in chinese hamster ovary cells.human alpha-1-antitrypsin (α1at) is a glycoprotein with protease inhibitor activity protecting tissues from degradation. patients with inherited α1at deficiency are treated with native α1at (nat) purified from human plasma. in the present study, recombinant α1at (rat) was produced in chinese hamster ovary (cho) cells and their glycosylation patterns, inhibitory activity and in vivo half-life were compared with those of nat. a peptide mapping analysis employing a deglycosylation reaction confirme ...201323065139
channel sialic acids limit herg channel activity during the ventricular action potential.activity of human ether-a-go-go-related gene (herg) 1 voltage-gated k(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface n-glycosylation modified herg channel function. voltage-dependent herg channel gating and activity were evaluated as expressed in a set of chinese hamster ovary (cho) cell lines under conditions of full g ...201323139156
pkcδ-mediated phosphorylation of bag3 at ser187 site induces epithelial-mesenchymal transition and enhances invasiveness in thyroid cancer fro cells.protein kinase c delta (pkcδ) is a serine (ser)/threonine kinase, which regulates numerous cellular processes, including proliferation, differentiation, migration and apoptosis. in the current study, chinese hamster ovary cells were transfected with either a constitutively activated pkcδ or a dominant negative pkcδ, phosphoprotein enrichment, two-dimensional difference gel electrophoresis and mass spectrometry was combined to globally identified candidates of pkcδ cascade. we found that bcl-2 as ...201323108398
high-throughput screening of drug-binding dynamics to herg improves early drug safety assessment.the use of computational models to predict drug-induced changes in the action potential (ap) is a promising approach to reduce drug safety attrition but requires a better representation of more complex drug-target interactions to improve the quantitative prediction. the blockade of the human ether-a-go-go-related gene (herg) channel is a major concern for qt prolongation and torsade de pointes risk. we aim to develop quantitative in-silico ap predictions based on a new electrophysiological proto ...201323103500
application of aurintricarboxylic acid for the adherence of mouse p19 neurons and primary hippocampal neurons to noncoated surface in serum-free culture.dissociated primary neuron culture has been the most widely used model systems for neuroscience research. most of these primary neurons are cultured on adhesion matrix-coated surface to provide a proper environment for cell anchorage under serum-free conditions. in this study, we provide an alternative technique to promote the adhesions of these neurons using aurintricarboxylic acid (ata), a nonpeptide compound, without surface manipulations. we first demonstrated that ata could promote chinese ...201323011767
fcγriia requires lipid rafts, but not co-localization into rafts, for effector function.to determine if receptor localization into lipid rafts, or the lipid rafts themselves, are important for fcγriia effector functions.201322945762
relative biological effects of neutron mixed-beam irradiation for boron neutron capture therapy on cell survival and dna double-strand breaks in cultured mammalian cells.understanding the biological effects of neutron mixed-beam irradiation used for boron neutron capture therapy (bnct) is important in order to improve the efficacy of the therapy and to reduce side effects. in the present study, cell viability and dna double-strand breaks (dna-dsbs) were examined in chinese hamster ovary cells (cho-k1) and their radiosensitive mutant cells (xrs5, ku80-deficient), following neutron mixed-beam irradiation for bnct. cell viability was significantly impaired in the n ...201322966174
flux balance analysis of cho cells before and after a metabolic switch from lactate production to consumption.mammalian cell cultures typically exhibit an energy inefficient phenotype characterized by the consumption of large quantities of glucose and the concomitant production of large quantities of lactate. under certain conditions, mammalian cells can switch to a more energy efficient state during which lactate is consumed. using a metabolic model derived from a mouse genome scale model we performed flux balance analysis of chinese hamster ovary cells before and after a metabolic switch from lactate ...201322991240
dna damage kinetics and apoptosis in ivermectin-treated chinese hamster ovary cells.a comet assay was used to analyze dna damage kinetics in chinese hamster ovary (cho-k1) cells induced by antiparasitic ivermectin (ivm) and the ivm-containing technical formulation ivomec® (ivo; 1% ivm). cells were treated with 50 µg ml(-1) ivm and ivo for 80 min, washed and re-incubated in antiparasiticide-free medium for 0-24 h until assayed using the single-cell gel electrophoresis assay (scge). cell viability remained unchanged up to 3 h of incubation. after 6 h of treatment, cell survival d ...201322961421
c-terminal modification of monoclonal antibody drugs: amidated species as a general product-related substance.twelve therapeutic mabs, comprising 10 igg1s and 2 igg4s, were analyzed by a peptide mapping technique to detect and quantify c-terminal modifications. c-terminal amidated structures were found in 8 out of the 12 mabs. an in vitro study using a commercially available peptidylglycine alpha-amidating monooxygenase (pam) revealed that both igg1 and igg4 can be substrates for pam. this study showed that c-terminal amidation is a general c-terminal modification on the heavy chains of therapeutic mabs ...201323022270
agonist stimulation, talin-1, and kindlin-3 are crucial for α(iib)β(3) activation in a human megakaryoblastic cell line, cmk.platelet integrin α(iib)β(3) activation is regulated by inside-out signaling via agonist stimulation. however, when α(iib)β(3) was exogenously expressed in cell lines such as chinese hamster ovarian cells, physiological agonists hardly induced α(iib)β(3) activation. to overcome this disadvantage, we characterized the functional regulation of endogenously expressed α(iib)β(3) in a megakaryoblastic cell line, cmk, employing an initial velocity assay for pac-1 binding. we firstly demonstrated that ...201323022222
selenium modulates oxidative stress-induced trpm2 cation channel currents in transfected chinese hamster ovary cells.it has been recently reported that the essential antioxidant element selenium has protective effects on cytosolic ca(2+) levels in cell lines. however, the effects of selenium on like transient receptor potential melastatin 2 (trpm2) in response to oxidative stress (h(2) o(2) ) are not well understood. we investigated the effects of selenium on h(2) o(2) -induced trpm2 channel currents in the chinese hamster ovary (cho) cell line using patch-clamp and fura-2 fluorescence imaging techniques.201322905852
cell surface lectin array: parameters affecting cell glycan signature.among the "omics", glycomics is one of the most complex fields and needs complementary strategies of analysis to decipher the "glycan dictionary". as an alternative method, which has developed since the beginning of the 21st century, lectin array technology could generate relevant information related to glycan motifs, accessibility and a number of other valuable insights from molecules (purified and non-purified) or cells. based on a cell line model, this study deals with the key parameters that ...201322899543
assessment of genotoxic effect of maleic acid and edta: a comparative in vitro experimental study.this study aims to evaluate and compare the genotoxic and apoptotic effect of aqueous solutions of ethylenediaminetetraacetic acid (edta) with that of maleic acid (ma) using chinese hamster lung fibroblast (v79) cells growing in vitro.201322893036
cell models for mcardle disease and aminoglycoside-induced read-through of a premature termination codon.mcardle disease results from mutations in the gene encoding muscle glycogen phosphorylase (pygm) protein and the two most common mutations are a premature termination codon (r50x) and a missense mutation (g205s). myoblasts from patients cannot be used to create a cell model of mcardle disease because even normal myoblasts produce little or no pygm protein in cell culture. we therefore created cell models by expressing wild-type or mutant (r50x or g205s) pygm from cdna integrated into the genome ...201322818872
study of the effect of membrane thickness on microcapsule strength, permeability, and cell proliferation.cell microencapsulation is one of the promising strategies for in vitro production of proteins or in vivo delivery of therapeutic products. membrane thickness controls microcapsule strength and permeability, which may in return affect cell growth and metabolism. in this study, the strength, permeability, and encapsulated chinese hamster ovary cell proliferation and metabolism of four groups of microcapsules with different membrane thicknesses were investigated. it was found that increasing membr ...201322968938
pei/dna formation affects transient gene expression in suspension chinese hamster ovary cells via a one-step transfection process.polyethylenimine (pei) has been used widely in transient gene expression studies of mammalian cells. we performed transient gene expression in suspension chinese hamster ovary cells using a one-step transfection procedure in which dna and pei were simultaneously added to a cell culture in suspension without prior pei/dna complex incubation. to further understand the effect of pei/dna formation on the transfection and expression of exogenous gene in shaking state, we investigated the diameter and ...201322782435
advantages of alagln as an additive to cell culture medium: use with anti-cd20 chimeric antibody-producing potelligent™ cho cell lines.l-alanyl-l-glutamine (alagln) is dipeptide that has better solubility and stability than glutamine (gln). in this study, we evaluated the utility of this dipeptide during culture of potelligent™ chinese hamster ovary (cho) cells expressing anti-cd20 chimeric antibody. although alagln in the culture medium lowered the specific growth rate, the mab titer was maximized when gln was completely replaced by alagln in both the basal and feed media. moreover, alagln augmented production of antibody not ...201322695857
functional heterogeneity and heritability in cho cell populations.in this study, we address the hypothesis that it is possible to exploit genetic/functional variation in parental chinese hamster ovary (cho) cell populations to isolate clonal derivatives that exhibit superior, heritable attributes for biomanufacturing--new parental cell lines which are inherently more "fit for purpose." one-hundred and ninety-nine chok1sv clones were isolated from a donor chok1sv parental population by limiting dilution cloning and microplate image analysis, followed by primary ...201322833427
pergolide block of the cloned kv1.5 potassium channels.pergolide mesylate, an ergot-derivative dopamine receptor agonist, is prescribed for the management of patients with parkinson's disease. pergolide caused vasoconstriction in a pulmonary artery. kv1.5 channel is highly expressed in pulmonary arterial smooth muscle cells, where it plays an important role as a determinant of vascular tone. in the present study, we investigated the effects of pergolide on kv1.5 stably expressed in chinese hamster ovary cells using the whole-cell patch-clamp techniq ...201322763615
deletion of scavenger receptor a gene in mice resulted in protection from septic shock and modulation of tlr4 signaling in isolated peritoneal macrophages.scavenger receptor a (sra), also known as macrophage scavenger receptor 1 (msr1), is a surface glycoprotein preferentially present in macrophages that plays a primary role in innate immunity. previous studies have shown that sra is a modifier gene for the response to bacterial lps in mice at the level of il-10 production, in particular. in the present study, we found that sra(-/-) mice are more resistant to septic shock induced by cecal ligation and puncture than wild-type c57bl/6 j (b6) mice. i ...201322751446
mass spectrometric characterization of amyloid-β species in the 7pa2 cell model of alzheimer's disease.the chinese hamster ovary cell line 7pa2, stably transfected with the 751 amino acid isoform of amyloid-β protein precursor (aβpp) containing the val → phe mutation at residue 717, is one of the most used models to study the biochemistry and toxicity of secreted amyloid-β (aβ) peptides, particularly aβ oligomers, which are considered to be of relevance to the pathogenesis of alzheimer's disease. here, we present a detailed immunochemical and mass spectrometric characterization of primary structu ...201322886024
effects of geissoschizine methyl ether, an indole alkaloid in uncaria hook, a constituent of yokukansan, on human recombinant serotonin 7 receptor.effects of seven alkaloids, geissoschizine methyl ether (gm), hirsutine, hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine and isocorynoxeine, in uncaria hook, a constituent of the kampo medicine yokukansan, on serotonin(7) (5-ht(7)) receptor were investigated using chinese hamster ovary (cho) cell membranes and human embryonic kidney 293 (hek293) cells stably expressing the human recombinant 5-ht(7) receptor. a competitive binding assay using cho membranes showed that gm (ic(50) = 0. ...201322968712
host cell protein quantification by fourier transform mid infrared spectroscopy (ft-mir).process development in up- and downstream processing requires enhanced, non-time-consuming, and non-expensive monitoring techniques to track product purity, for example, the level of endotoxins, viral particles, and host cell proteins (hcps). currently, hcp amounts are measured by laborious and expensive hcp-enzyme-linked immunosorbent assay (elisa) assays best suited for measuring hcp amounts in the low concentration regime. the measurement of higher hcp amounts using this method requires dilut ...201322811255
controlled release of nutrients to mammalian cells cultured in shake flasks.though cell culture-based protein production processes are rarely carried out under batch mode of operation, cell line and initial process development operations are usually carried out in batch mode due to simplicity of operation in widely used scale down platforms like shake flasks. nutrient feeding, if performed, is achieved by bolus addition of concentrated feed solution at different intervals, which leads to large transient increases in nutrient concentrations. one negative consequence is i ...201322002953
high-throughput analysis of intraclonal variability of glycoprotein sialylation.development of recombinant chinese hamster ovary (cho) cells producing therapeutic proteins requires analyzing the quality, such as sialic acid content, of proteins produced by many cell clones. in order to perform these analyses, high-throughput methods are required. conventional methods for quantifying sialic acid, however, require protein purification, which is time consuming and cannot be used for high-throughput analysis. here we used a high-throughput method (htm) that we recently develope ...201322065488
a mechanistic study on the effect of dexamethasone in moderating cell death in chinese hamster ovary cell cultures.dexamethasone (dex) was previously shown (jing et al., biotechnol bioeng. 2010;107:488-496) to play a dual role in increasing sialylation of recombinant glycoproteins produced by chinese hamster ovary (cho) cells. dex addition increased sialic acid levels of a recombinant fusion protein through increased expression of α2,3-sialyltransferase and β1,4-galactosyltransferase, but also decreased the sialidase-mediated, extracellular degradation of sialic acid through slowing cell death at the end of ...201322140034
effect of hydrocortisone on the production and glycosylation of an fc-fusion protein in cho cell cultures.glucocorticoids are known to modulate various cellular functions such as cell proliferation, metabolism, glycosylation, and secretion of many proteins. we tested the effect of hydrocortisone (hc) on cell growth, viability, metabolism, protein production, and glycosylation of an fc-protein expressing chinese hamster ovary (cho) cell culture. hc extended cell viability but impaired cell growth. the inhibitory effect on cell growth was dose-dependent and decreased when the glucocorticoid addition w ...201322535835
glucocorticoid receptor-mediated reduction of igg-fusion protein aggregation in chinese hamster ovary cells.formation of high molecular weight (hmw) species is a common issue encountered during manufacture of protein therapeutics. with advanced purification techniques, efficient removal of protein aggregates is no longer a challenging task, but it is important to minimize protein aggregation level at the culture stage to reduce the downstream burden and improve overall process yield. in this regard, our recent effort on medium optimization has led us to unexpectedly discover that glucocorticoids can s ...201320549677
influence of catechins on bystander responses in cho cells induced by alpha-particle irradiation.in this work, we studied alpha-particle induced and medium-mediated bystander effects in chinese hamster ovary (cho) cells through micronucleus (mn) assay. we showed that signal transduction from irradiated cells to bystander cells occur within a short time after irradiation. we then studied the effects of ros (reactive oxygen species)-scavenging catechins in the medium before irradiation. we observed decreases in the percentage of bystander cells with mn formation and thus proved the protection ...201319892559
vector fragmentation: characterizing vector integrity in transfected clones by southern blotting.the chinese hamster ovary production cell line development process using methotrexate (mtx) amplification is well studied and commonly used for biopharmaceutical processes. however, successful mtx amplification varies from clone to clone and suggested reasons include vector fragmentation during the transfection process and genomic rearrangement of the chinese hamster ovary chromosomes. here, we elucidated the vector integration patterns of 40 transfected single-cell clones by southern blotting a ...201319847885
modeling kinetics of a large-scale fed-batch cho cell culture by markov chain monte carlo method.markov chain monte carlo (mcmc) method was applied to model kinetics of a fed-batch chinese hamster ovary cell culture process in 5,000-l bioreactors. the kinetic model consists of six differential equations, which describe dynamics of viable cell density and concentrations of glucose, glutamine, ammonia, lactate, and the antibody fusion protein b1 (b1). the kinetic model has 18 parameters, six of which were calculated from the cell culture data, whereas the other 12 were estimated from a traini ...201319834967
fluorinert, an oxygen carrier, improves cell culture performance in deep square 96-well plates by facilitating oxygen transfer.in bioprocess development, the 96-well plate format has been widely used for high-throughput screening of production cell line or culture conditions. however, suspension cell cultures in conventional 96-well plates often fail to reach high cell density under normal agitation presumably due to constraints in oxygen transfer. although more vigorous agitation can improve gas transfer in 96-well plate format, it often requires specialized instruments. in this report, we employed fluorinert, a biolog ...201321954223
estimating cell specific oxygen uptake and carbon dioxide production rates for mammalian cells in perfusion culture.we present robust methods for online estimation of cell specific oxygen uptake and carbon dioxide production rates (q(o2) and q(co2), respectively) during perfusion cultivation of mammalian cells. perfusion system gas and liquid phase mass balance expressions for oxygen and carbon dioxide were used to estimate q(o2), q(co2) and the respiratory quotient (rq) for chinese hamster ovary (cho) cells in perfusion culture over 12 steady states with varying dissolved oxygen (do), ph, and temperature set ...201321626724
increase in efficiency of media utilization for recombinant protein production in chinese hamster ovary culture through dilution.animal cells are extensively used for the large-scale production of recombinant proteins. processes and genetically engineered cell lines have been developed to enhance longevity of the culture and increase protein productivity. in this study, we tested the effect of diluting a culture of chinese hamster ovary (cho) cells with phosphate-buffered saline (pbs) on cell growth and efficiency of media utilization. an immunoglobulin g-expressing cho cell line was cultured in cd cho media followed by d ...201321446956
effect of chemical chaperone addition on production and aggregation of recombinant flag-tagged comp-angiopoietin 1 in chinese hamster ovary cells.to investigate the effect of chemical chaperones on the production and aggregation of flag-tagged cartilage oligomeric matrix protein-angiopoietin1 (fca1) in recombinant chinese hamster ovary (cho) cells, cho cells were cultivated in serum-free media with various chemical chaperones, 1 mm 4-phenylbutyrate (4-pba), 200 mm proline, 3% glycerol, 2% dimethyl sulfoxide (dmso), and without chemical chaperone as control. the addition of chemical chaperones enhanced fca1 production and specific fca1 pro ...201321425253
effects of fullerenol c60(oh)24 on the frequency of micronuclei and chromosome aberrations in cho-k1 cells.poly-hydroxylated c(60) fullerenols (c(60)(oh)(n)) have attracted much attention in biomedical research, due to a variety of biological activities. however, the studies investigating the genotoxic effects of fullerenols are still insufficient. the aim of the present study was to analyze the genotoxic and antigenotoxic potential of fullerenol c(60)(oh)(24). the investigation was carried out with mitomycin c (mmc)-treated and control chinese hamster ovary cells (cho-k1), using the chromosome aberr ...201319733687
thymol, a naturally occurring monocyclic dietary phenolic compound protects chinese hamster lung fibroblasts from radiation-induced cytotoxicity.the effect of thymol (toh), a dietary compound was investigated for its ability to protect against radiation-induced cytotoxicity in chinese hamster lung fibroblast (v79) cells growing in vitro. treatment of v79 cells with 25 microg/ml of toh prior to 10 gy gamma radiation resulted increase in the cell viability than that of radiation alone as evaluated by mtt assay. similarly, there was a significant increase in the surviving fraction observed with 25 microg/ml of toh administered 1h prior to g ...201319815091
mcl-1 overexpression leads to higher viabilities and increased production of humanized monoclonal antibody in chinese hamster ovary cells.bioreactor stresses, including nutrient deprivation, shear stress, and byproduct accumulation can cause apoptosis, leading to lower recombinant protein yields and increased costs in downstream processing. although cell engineering strategies utilizing the overexpression of antiapoptotic bcl-2 family proteins such as bcl-2 and bcl-x(l) potently inhibit apoptosis, no studies have examined the use of the bcl-2 family protein, mcl-1, in commercial mammalian cell culture processes. here, we overexpre ...201319551877
effect of constitutively active ras overexpression on cell growth in recombinant chinese hamster ovary cells.constitutively active ras (ca-ras) is known to enhance cell growth through the induction of various signaling cascades including the phosphoinositide 3-kinase (pi3k)/akt and mitogen-activated protein kinase (mapk)/erk signaling pathways, although the cellular response is highly dependent on the cell type. to evaluate the effect of ca-ras overexpression on cell growth in recombinant chinese hamster ovary (rcho) cells, an erythropoietin (epo)-producing rcho cell line with regulated ca-ras overexpr ...201321438179
effects of lithium deficiency in some insulin-sensitive tissues of diabetic chinese hamsters.in this work, we report the effect of low-dose lithium carbonate on blood glucose levels and tissue lithium content in hereditary spontaneous diabetic chinese hamsters (hsdchs). hepatic lithium levels are significantly lower in diabetic hamsters when compared to healthy controls: 2.05 +/- 0.26 and 3.04 +/- 0.11 micrograms/g, respectively. the same trend was observed in kidney and muscle: 18.26 +/- 0.24 vs 20.23 +/- 1.10 micrograms/g and 4.66 +/- 0.17 vs 5.95 +/- 0.67 micrograms/g, respectively. ...20139363324
chromosome studies on bone marrow from chinese hamsters treated with benzodiazepine tranquillizers and cyclophosphamide. 20135801080
effect of 5-bromodeoxyuridine on the male meiosis in chinese hamsters (cricetus griseus). 20135708070
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