Publications

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a robust transfection reagent for the transfection of cho and hek293 cells and production of recombinant proteins and lentiviral particles - ptg1.bioproduction of recombinant proteins (r-proteins) and recombinant lentiviral particles (r-lentiviral particles) requires robust transfections consisting of efficient protocols that are easy to implement, with good reproducibility for a maximum production of proteins and lentiviral particles in a short time with low cytotoxicity. this study evaluates the capacity of histidinylated polyethyleneimine i (ptg1) to facilitate robust dna transfection, with low cytotoxicity, of chinese hamster ovary (c ...201425215936
effect of peptone feeding on transient gene expression process in cho dg44.transient gene expression (tge) gained popularity over the last decade as a rapid method for the production of milligram to gram quantities of recombinant proteins for preclinical studies in biophama industry. thereby, the optimization of the tge technique for chinese hamster ovary (cho) as the dominant host for the production of biotherapeutics is of great interest to reach the values for human embryo kidney-293 (hek-293) cells in terms of transfection efficiencies and production titers. tge ef ...201425215178
enhanced cellular uptake of antisecretory peptide af-16 through proteoglycan binding.peptide af-16, which includes the active site of antisecretory factor protein, has antisecretory and anti-inflammatory properties, making it a potent drug candidate for treatment of secretory and inflammatory diseases such as diarrhea, inflammatory bowel diseases, and intracranial hypertension. despite remarkable physiological effects and great pharmaceutical need for drug discovery, very little is yet understood about af-16 mechanism of action. in order to address interaction mechanisms, we inv ...201425289567
interaction of β-cyclodextrin with nile red in a single live cho cell: an initiative towards developing a prospective strategy for the excretion of adsorbed drugs from the cell membrane.a successful endeavour has been made to develop a prospective strategy to oust the drug molecules adsorbed on the cell membranes by simply using the non-toxic β-cyclodextrin (β-cd). for this purpose, fluorescent probes of different geometries and charge characteristics, namely phenosafranin (psf) and nile red (nr), were exploited for the in vitro studies using different lipids as model membranes. considering the success of the in vitro study, the present work is extended to a live chinese hamste ...201425274028
accurate comparison of antibody expression levels by reproducible transgene targeting in engineered recombination-competent cho cells.over the years, chinese hamster ovary (cho) cells have emerged as the major host for expressing biotherapeutic proteins. traditional methods to generate high-producer cell lines rely on random integration(s) of the gene of interest but have thereby left the identification of bottlenecks as a challenging task. for comparison of different producer cell lines derived from various transfections, a system that provides control over transgene expression behavior is highly needed. this motivated us to ...201425158835
comparison of the biological effects of (18)f at different intracellular levels.we herein examined the biological effects of cells treated with (18)f labeled drugs for positron emission tomography (pet). the relationship between the intracellular distribution of (18)f and levels of damaged dna has yet to be clarified in detail. we used culture cells (chinese hamster ovary cells) treated with two types of (18)f labeled drugs, fluorodeoxyglucose (fdg) and fluorine ion (hf). fdg efficiently accumulated in cells, whereas hf did not. to examine the induction of dna double strand ...201425301551
acute toxicity and genotoxicity study of fermented traditional herb formula guibi-tang.guibi-tang (guipi-tang in chinese and kihi-to in japanese) is a multi-herb traditional medicine commonly prescribed to treat psychoneurosis in east asia. although this medicine has been widely used, there is little available information on the safety and toxicity of guibi-tang, especially on the fermented one.201425218323
functional bioassays for immune monitoring of high-risk neuroblastoma patients treated with ch14.18/cho anti-gd2 antibody.effective treatment of high-risk neuroblastoma (nb) remains a major challenge in pediatric oncology. human/mouse chimeric monoclonal anti-gd2 antibody (mab) ch14.18 is emerging as a treatment option to improve outcome. after establishing a production process in chinese hamster ovary (cho) cells, ch14.18/cho was made available in europe for clinical trials. here, we describe validated functional bioassays for the purpose of immune monitoring of these trials and demonstrate gd2-specific immune eff ...201425226154
peptides derived from central turn motifs within integrin αiib and αv cytoplasmic tails inhibit integrin activation.we previously found that peptides derived from the full length of integrin αiib and αv cytoplasmic tails inhibited their parent integrin activation, respectively. here we showed that the cell-permeable peptides corresponding to the conserved central turn motif within αiib and αv cytoplasmic tails, myr-krnrppleed (αiib peptide) and myr-krvrppqeeq (αv peptide), similarly inhibited both αiib and αv integrin activation. pre-treatment with αiib or αv peptides inhibited mn(2+)-activated αiibβ3 binding ...201425290158
mutations of rat surfactant protein a have distinct effects on its glycosylation, secretion, aggregation and degradation.surfactant protein a (sp-a) plays critical roles in the innate immune system and surfactant homeostasis of the lung. mutations in sp-a2 of the carbohydrate recognition domain (crd) impair its glycosylation and are associated with pulmonary fibrosis in humans. we aim to examine how mutations in sp-a that impair its glycosylation affect its biological properties and lead to disease.201425242514
[expression of neural cell adhesion molecule and modification of its n-glycan in ldld-14 cells].neural cell adhesion molecule (ncam) is a glycoprotein expressing on the surface of neurons, glial cells, bone cells and natural killer cells. ncam plays an important role in the process of cell - cell adhesion and cell migration, and is also a model protein to study polysialic acid. in this paper, ncam gene from mouse mammary gland cells (nmumg) was cloned into eukaryotic expression vectors pcdna3.1(+) and transfected into mutant chinese hamster ovary cells ldld-14. the stable transfection over ...201425212013
structural basis of drugs that increase cardiac inward rectifier kir2.1 currents.we hypothesize that some drugs, besides flecainide, increase the inward rectifier current (ik1) generated by kir2.1 homotetramers (ikir2.1) and thus, exhibit pro- and/or antiarrhythmic effects particularly at the ventricular level. to test this hypothesis, we analysed the effects of propafenone, atenolol, dronedarone, and timolol on kir2.x channels.201425205296
[construction of controlled expression system of class b g-protein coupled receptor pac1].pac1 is the neuropeptide pituitary adenylate cyclase activating polypeptide (pacap) preferring receptor, which belongs to class b g protein-coupled receptors (gpcr) family. pac1 mediates the most effects of pacap as neurotransmitter, neuroregulator and neuroprotectant, while its high expression has close relationship with some physiological and pathological processes such as nerve-injury and tumor. to further understand the function of pac1, a cell line that expressed inducible pac1 was construc ...201425195253
the tarantula toxin jingzhaotoxin-xi (κ-theraphotoxin-cj1a) regulates the activation and inactivation of the voltage-gated sodium channel nav1.5.specific peptide toxins interact with voltage-gated sodium channels by regulating the activation or inactivation of targeted channels. however, few toxins possessing dual effects have been identified. in the present study, we showed that jingzhaotoxin-xi/κ-theraphotoxin-cj1a (jztx-xi), a 34-residue peptide from the venom of the chinese spider chilobrachys jingzhao, inhibits the sodium conductance (ic50 = 124 ± 26 nm) and slows the fast inactivation (ec50 = 1.18 ± 0.2 μm) of nav1.5 expressed in c ...201425240294
dimerisation of the drosophila odorant coreceptor orco.odorant receptors (ors) detect volatile molecules and transform this external information into an intracellular signal. insect ors are heteromers composed of two seven transmembrane proteins, an odor-specific orx and a coreceptor (orco) protein. these ors form ligand gated cation channels that conduct also calcium. the sensitivity of the ors is regulated by intracellular signaling cascades. heterologously expressed orco proteins form also non-selective cation channels that cannot be activated by ...201425221476
differential complement activation pathways promote c3b deposition on native and acetylated ldl thereby inducing lipoprotein binding to the complement receptor 1.lipoproteins can induce complement activation resulting in opsonization and binding of these complexes to complement receptors. we investigated the binding of opsonized native ldl and acetylated ldl (acldl) to the complement receptor 1 (cr1). binding of complement factors c3b, igm, c1q, mannose-binding lectin (mbl), and properdin to ldl and acldl were investigated by elisa. subsequent binding of opsonized ldl and acldl to cr1 on cr1-transfected chinese hamster ovarian cells (cho-cr1) was tested ...201425349208
lqt1 mutations in kcnq1 c-terminus assembly domain suppress iks using different mechanisms.long qt syndrome 1 (lqt1) mutations in kcnq1 that decrease cardiac iks (slowly activating delayed rectifier k(+) current) underlie ventricular arrhythmias and sudden death. lqt1 mutations may suppress iks by preventing kcnq1 assembly, disrupting surface trafficking, or inhibiting gating. we investigated mechanisms underlying how three lqt1 mutations in kcnq1 c-terminus assembly domain (r555h/g589d/l619m) decrease iks in heterologous cells and cardiomyocytes.201425344363
[expression, purification and functional identification of human psmp recombinant protein in chinese hamster ovary cells].to construct a new human chemotactic cytokine psmp eukaryotic expression vector to express psmp in chinese hamster ovary (cho) cells and to obtain the purified recombinant psmp protein for its functional mechanism study.201425331384
peptone supplementation of culture medium has variable effects on the productivity of cho cells.the optimization of cell culture conditions for growth and productivity of recombinant chinese hamster ovary (cho) cells is a critical step in biopharmaceutical manufacturing. in the present study, the effects of the timing and amount of peptone feeding of a recombinant cho cell line grown in a basal medium in serum-free suspension culture were determined for eight peptones of different origin (plant and casein). the amino acid content and the average molecular weight of the peptones chosen were ...201425317401
measurement and control of host cell proteins (hcps) in cho cell bioprocesses.chinese hamster ovary (cho) cells are widely used for the production of biotherapeutic recombinant proteins for a range of molecules including monoclonal antibodies and fc-fusion proteins. regulatory requirements for the final product include the removal of host cell proteins (hcps) to acceptable amounts (<100ppm). recent research has begun to unravel the extent to which upstream process conditions and subsequent product recovery and purification processes impact upon the hcp profile. a number o ...201425032907
progesterone receptor membrane component 1 is a functional part of the glucagon-like peptide-1 (glp-1) receptor complex in pancreatic β cells.glucagon-like peptide-1 (glp-1) is an incretin hormone that regulates glucose homeostasis. because of their direct stimulation of insulin secretion from pancreatic β cells, glp-1 receptor (glp-1r) agonists are now important therapeutic options for the treatment of type 2 diabetes. to better understand the mechanisms that control the insulinotropic actions of glp-1, affinity purification and mass spectrometry (ap-ms) were employed to uncover potential proteins that functionally interact with the ...201425044020
niemann-pick c1 affects the gene delivery efficacy of degradable polymeric nanoparticles.despite intensive research effort, the rational design of improved nanoparticulate drug carriers remains challenging, in part due to a limited understanding of the determinants of nanoparticle entry and transport in target cells. recent studies have shown that niemann-pick c1 (npc1), the lysosome membrane protein that mediates trafficking of cholesterol in cells, is involved in the endosomal escape and subsequent infection caused by filoviruses, and that its absence promotes the retention and ef ...201425010491
phenylboronic acid as a multi-modal ligand for the capture of monoclonal antibodies: development and optimization of a washing step.in this work, phenylboronic acid (pba) was thoroughly investigated as a synthetic ligand for the purification of an immunoglobulin g (igg) from a clarified cell supernatant from chinese hamster ovary (cho) cell cultures. in particular, the study was focused on the development of a washing step and in the optimization of the elution step using a serum containing supernatant. from the different conditions tested, best recoveries - 99% - and purifications - protein purity of 81% and a purification ...201424947887
[construction and specificity of porcine bmp15 gene reporter vector].the aim of this study is to identify the express specificity of bone morphogenetic protein 15 (bmp15) in porcine. the pbmp15-egfp reporter vector was constructed from the 2.2 kb fragment of porcine bmp15 promoter to trace the differentiation process of stem cells into oocyte-like cells. we used porcine ovary and chinese hamster ovary cell line (cho), mouse myoblast cell line (c2c12) and porcine amniotic fluid stem cell (pafsc) to investigate the expression and regulation of this gene via rt-pcr, ...201424941742
comparative in vitro toxicity of nitrosamines and nitramines associated with amine-based carbon capture and storage.amine-based co2 capture is a prime contender for the first full-scale implementation of co2 capture at fossil fuel-fired power plants postcombustion. however, the formation of potentially carcinogenic n-nitrosamines and n-nitramines from reactions of flue gas nox with the amines presents a potential risk for contaminating airsheds and drinking water supplies. setting regulatory emission limits is hampered by the dearth of toxicity information for the n-nitramines. this study employed quantitativ ...201424940705
evaluation of toxicity of calophyllum brasiliense stem bark extract by in vivo and in vitro assays.calophyllum brasiliense camb., clusiaceae, is commonly known as "guanandi" and its stem bark is used in brazilian traditional medicine to treat rheumatism, vein problems, hemorrhoids and gastric ulcers. the aim of this study was to evaluate the toxicity of hexane extract of calophyllum brasiliense stem bark (hecb) using in vitro and in vivo experimental models.201424933219
differential effect of manool--a diterpene from salvia officinalis, on genotoxicity induced by methyl methanesulfonate in v79 and hepg2 cells.salvia officinalis (sage) is a perennial woody subshrub native to the mediterranean region that is commonly used as a condiment and as an anti-inflammatory, antioxidant and antimicrobial agent due to its biological activities. manool is the most abundant micro-metabolite found in salvia officinalis essential oils and extracts. we therefore decided to evaluate the cytotoxic, genotoxic and antigenotoxic potential of manool in chinese hamster lung fibroblasts (v79) and human hepatoma cells (hepg2). ...201425007786
recombinant γt305a fibrinogen indicates severely impaired fibrin polymerization due to the aberrant function of hole 'a' and calcium binding sites.we examined a 6-month-old girl with inherited fibrinogen abnormality and no history of bleeding or thrombosis. routine coagulation screening tests showed a markedly low level of plasma fibrinogen determined by functional measurement and also a low level by antigenic measurement (functional/antigenic ratio=0.295), suggesting hypodysfibrinogenemia.201424968960
nanoscale protein diffusion by sted-based pair correlation analysis.we describe for the first time the combination between cross-pair correlation function analysis (pair correlation analysis or pcf) and stimulated emission depletion (sted) to obtain diffusion maps at spatial resolution below the optical diffraction limit (super-resolution). our approach was tested in systems characterized by high and low signal to noise ratio, i.e. capsid like particles (clps) bearing several (>100) active fluorescent proteins and monomeric fluorescent proteins transiently expre ...201424967681
vernakalant activates human cardiac k(2p)17.1 background k(+) channels.atrial fibrillation (af) contributes significantly to cardiovascular morbidity and mortality. the growing epidemic is associated with cardiac repolarization abnormalities and requires the development of more effective antiarrhythmic strategies. two-pore-domain k(+) channels stabilize the resting membrane potential and repolarize action potentials. recently discovered k2p17.1 channels are expressed in human atrium and represent potential targets for af therapy. however, cardiac electropharmacolog ...201425108155
in vitro evaluation of cordyceps militaris as a potential radioprotective agent.radiation is an important component of therapy for a wide range of malignant conditions. however, it triggers dna damage and cell death in normal cells and results in adverse side-effects. cordyceps militaris (c. militaris), a traditional medicinal mushroom, produces the bioactive compound, cordycepin (3'-deoxyadenosine) and has multiple pharmacological activities, such as antitumor, antimetastatic, antioxidant and immunomodulatory effects. the present study was undertaken to investigate whether ...201425176413
biologically active constituents from salix viminalis bio-oil and their protective activity against hydrogen peroxide-induced oxidative stress in chinese hamster ovary cells.the protective antioxidative effect of the phenolic extract (pe) isolated from salix viminalis pyrolysis derived bio-oil was shown in vitro on the chinese hamster ovary (cho) cells exposed to hydrogen peroxide (h2o2). cells pretreated with 0.05 μg/ml pe after exposure to different concentrations of h2o2 (300-900 μm) showed up to 25 % higher viability than the unpretreated ones. the antioxidative effect of pe was also observed in a time-dependent manner. the results were confirmed by visual exami ...201425172057
xrcc2 rs3218536 polymorphism decreases the sensitivity of colorectal cancer cells to poly(adp-ribose) polymerase 1 inhibitor.single nucleotide polymorphisms (snps) are associated with the development of certain types of cancer. the present study aimed to investigate the association between x-ray repair complementing defective repair in chinese hamster cells 2 (xrcc2) snps and colorectal cancer (crc) cell sensitivity to the poly(adp-ribose) polymerase (parp) 1 inhibitor olaparib (azd2281). snapshot(®) analysis of xrcc2 snps was performed in five crc cell lines. the azd2281-sensitivities of the crc cells were also analy ...201425120693
mammalian cell-produced therapeutic proteins: heterogeneity derived from protein degradation.therapeutic glycoproteins, for example, antibodies (abs) and fc fusion proteins when produced in mammalian cells, such as chinese hamster ovary (cho) cells generally exhibit heterogeneity. both the oligosaccharide moiety and the protein moiety contribute to this phenomenon. non-enzymatic and enzymatic pathways of protein fragmentation generate heterogeneity in the polypeptide backbone. in the non-enzymatic pathway, physical and chemical events such as light, oxidation, and others can cause the p ...201425118137
glyco-engineering for biopharmaceutical production in moss bioreactors.the production of recombinant biopharmaceuticals (pharmaceutical proteins) is a strongly growing area in the pharmaceutical industry. while most products to date are produced in mammalian cell cultures, namely chinese hamster ovary cells, plant-based production systems gained increasing acceptance over the last years. different plant systems have been established which are suitable for standardization and precise control of cultivation conditions, thus meeting the criteria for pharmaceutical pro ...201425071817
antioxidant potential of sutherlandia frutescens and its protective effects against oxidative stress in various cell cultures.sutherlandia frutescens (l.) r.br. (sf) is a south african plant that is widely used to treat stress, infections, cancer, and chronic diseases, many of which involve oxidative stress. the aim of the study was to quantitatively assess the antioxidant potential of sf extracts in cell-free system as well as in cell lines.201425070435
differential thermodynamic driving force of first- and second-generation antihistamines to determine their binding affinity for human h1 receptors.differential binding sites for first- and second-generation antihistamines were indicated on the basis of the crystal structure of human histamine h1 receptors. in this study, we evaluated differences between the thermodynamic driving forces of first- and second-generation antihistamines for human h1 receptors and their structural determinants. the binding enthalpy and entropy of 20 antihistamines were estimated with the van't hoff equation using their dissociation constants obtained from their ...201425065879
optimal production of a fusion protein consisting of a single-chain variable fragment antibody against a tumor-associated antigen and interleukin-2 in fed-batch culture of pichia pastoris.the aim of the present study was to establish the strategy for producing a single-chain variable fragment (scfv) antibody fused with interleulin-2 (il2) by pichia pastoris and to optimize production during fed-batch cultivation in a 5-l fermenter.201425075014
the transcription factor ap-1 regulates monkey 20α-hydroxysteroid dehydrogenase promoter activity in cho cells.monkey 20α-hydroxysteroid dehydrogenase (20α-hsd) is a catabolic enzyme responsible for converting progesterone into biologically inactive 20α-hydroxyprogesterone, thereby playing a key role in the estrous cycle or pregnancy and allowing ovulation and parturition to occur in most mammalian animals. monkey 20α-hsd was highly abundant in ovarian and placental tissues during the pre-ovulation and pre-parturition phase and was primarily localized in the syncytiotrophoblast of the placenta. in this s ...201425073972
the galnac-type o-glycoproteome of cho cells characterized by the simplecell strategy.the chinese hamster ovary cell (cho) is the major host cell factory for recombinant production of biological therapeutics primarily because of its "human-like" glycosylation features. cho is used for production of several o-glycoprotein therapeutics including erythropoietin, coagulation factors, and chimeric receptor igg1-fc-fusion proteins, however, some o-glycoproteins are not produced efficiently in cho. we have previously shown that the capacity for o-glycosylation of proteins can be one lim ...201425092905
discovery of transcription start sites in the chinese hamster genome by next-generation rna sequencing.chinese hamster ovary (cho) cell lines are one of the major production tools for monoclonal antibodies, recombinant proteins, and therapeutics. although many efforts have significantly improved the availability of sequence information for cho cells in the last years, forthcoming draft genomes still lack the information depth known from the mouse or human genomes. many genes annotated for cho cells and the chinese hamster reference genome still are in silico predictions, only insufficiently verif ...201425086342
subcellular localization and function of mouse radial spoke protein 3 in mammalian cells and central nervous system.radial spoke protein 3 (rsp3) was first identified in chlamydomonas as a component of the radial spoke. the mammalian homologue of the chlamydomonas rsp3 gene is mainly expressed in testis and developing central nervous system (cns). however, the subcellular localization and function of mammalian rsp3 in the developing brain and mammalian cells remain poorly understood. here we show that the mouse rsp3 accumulates at the perinuclear region of chinese hamster ovary (cho) and 293t cells. detailed ...201425079589
effects of glutamine and asparagine on recombinant antibody production using cho-gs cell lines.a unique and nontraditional approach using glutamine and asparagine supplements for cho-glutamine synthetase (gs) cell lines was studied. in our experiments, we found that a decrease in ph and an increase in cell death occurred in production phase of a gs cell line, leading to reduced antibody expression and lower antibody yields. the experimental results and the statistical analysis (anova) indicated that additions of glutamine and asparagine in the basal and feed media were effective to buffer ...201425079388
the fate of internalized α5 integrin is regulated by matrix-capable fibronectin.assembly of fibronectin matrices is associated with integrin receptor turnover and is an important determinant of tissue remodeling. although it is well established that fibronectin is the primary ligand for α5β1 receptor, the relationship between fibronectin matrix assembly and the fate of internalized α5 integrin remains poorly characterized.201425062814
glycosylation-related genes in ns0 cells are insensitive to moderately elevated ammonium concentrations.ns0 and chinese hamster ovary (cho) cell lines are used to produce recombinant proteins for human therapeutics; however, ammonium accumulation can negatively impact cell growth, recombinant protein production, and protein glycosylation. to improve product quality and decrease costs, the relationship between ammonium and protein glycosylation needs to be elucidated. while ammonium has been shown to adversely affect glycosylation-related gene expression in cho cells, ns0 studies have not been perf ...201425062658
a functional high-content mirna screen identifies mir-30 family to boost recombinant protein production in cho cells.the steady improvement of mammalian cell factories for the production of biopharmaceuticals is a key challenge for the biotechnology community. recently, small regulatory micrornas (mirnas) were identified as novel targets for optimizing chinese hamster ovary (cho) production cells as they do not add any translational burden to the cell while being capable of regulating entire physiological pathways. the aim of the present study was to elucidate mirna function in a recombinant cho-seap cell line ...201425061012
effect of lithium chloride on the production and sialylation of fc-fusion protein in chinese hamster ovary cell culture.lithium chloride (licl), which is a specific inhibitor of glycogen synthase kinase-3β, is known to induce cell cycle arrest at the g2/m phase and to regulate apoptosis. to determine the potential of licl as a chemical additive to enhance specific productivity (q p) of recombinant chinese hamster ovary (rcho) cells through cell cycle arrest at g2/m phase, rcho cells producing fc-fusion protein were cultivated in serum-free media with licl concentrations ranging from 0 to 20 mm. the addition of li ...201425132065
competitive mode and site of interaction of ticagrelor at the human platelet p2y12 -receptor.the g-protein-coupled p2y12 -receptor plays a crucial role in platelet aggregation. recently, ticagrelor was licensed as the first perorally active and reversible p2y12 -receptor antagonist.201425186974
reduction in c-terminal amidated species of recombinant monoclonal antibodies by genetic modification of cho cells.during development of recombinant monoclonal antibodies in chinese hamster ovary (cho) cells, c-terminal amidated species are observed. c-terminal amidation is catalysed by peptidylglycine α-amidating monooxygenase (pam), an enzyme known to be expressed in cho cells. the significant variations between clones during clone selection, and the relatively high content of amidated species (up to 15%) in comparison to reference material (4%), led us to develop a cell line with reduced production of c-t ...201425123359
toxicity of drinking water disinfection byproducts: cell cycle alterations induced by the monohaloacetonitriles.haloacetonitriles (hans) are a chemical class of drinking water disinfection byproducts (dbps) that form from reactions between disinfectants and nitrogen-containing precursors, the latter more prevalent in water sources impacted by algae bloom and municipal wastewater effluent discharge. hans, previously demonstrated to be genotoxic, were investigated for their effects on the mammalian cell cycle. treating chinese hamster ovary (cho) cells with monohans followed by the release from the chemical ...201425185076
site-2 protease responds to oxidative stress and regulates oxidative injury in mammalian cells.site-2 protease (s2p) is a membrane-embedded protease that site-specifically cleaves intramembrane transcription factors, a necessary step for their maturation. s2p is well known to regulate cholesterol biosynthesis and endoplasmic reticulum stress in mammalian cells. in this study, we hypothesized that s2p could be responsible for the regulation of cellular oxidative injury under oxidative stress. wild type chinese hamster ovary (wt cho) cells and their mutant m19 cells with defective s2p gene ...201425183265
recombinant antibody color resulting from advanced glycation end product modifications.recombinant antibodies produced in chinese hamster ovary (cho) cells often exhibit a slight yellow-brown color, but the molecular basis for this color has remained elusive. we predicted that the color results from post-translational modifications on the antibody, because colored species were found to coelute with antibody products during size exclusion chromatography. previously, modification by oxidation and advanced glycation end products (ages) had been shown to give rise to colored and fluor ...201425181536
a strategy for fusion expression and preparation of functional glucagon-like peptide-1 (glp-1) analogue by introducing an enterokinase cleavage site.kglp-1, a 31-amino acid glucagon-like peptide-1 (glp-1) analogue, has a great therapeutic potential for anti-diabetes. in this work, a strategy for expression and purification of functional kglp-1 peptide has been established. kglp-1 cdna was fused with glutathione s-transferase (gst), with an enterokinase cleavage site in the fusion junction. the recombinant fusion protein gst-kglp-1 was affinity purified via the gst-tag, and then digested with enterokinase. the resulting gst part as well as th ...201424737080
reduced amino acid specificity of mammalian tyrosyl-trna synthetase is associated with elevated mistranslation of tyr codons.quality control operates at different steps in translation to limit errors to approximately one mistranslated codon per 10,000 codons during mrna-directed protein synthesis. recent studies have suggested that error rates may actually vary considerably during translation under different growth conditions. here we examined the misincorporation of phe at tyr codons during synthesis of a recombinant antibody produced in tyrosine-limited chinese hamster ovary (cho) cells. tyr to phe replacements were ...201424828507
accelerating genome editing in cho cells using crispr cas9 and crispy, a web-based target finding tool.chinese hamster ovary (cho) cells are widely used in the biopharmaceutical industry as a host for the production of complex pharmaceutical proteins. thus genome engineering of cho cells for improved product quality and yield is of great interest. here, we demonstrate for the first time the efficacy of the crispr cas9 technology in cho cells by generating site-specific gene disruptions in cosmc and fut8, both of which encode proteins involved in glycosylation. the tested single guide rnas (sgrnas ...201424827782
calcium influx affects intracellular transport and membrane repair following nanosecond pulsed electric field exposure.the cellular response to subtle membrane damage following exposure to nanosecond pulsed electric fields (nspef) is not well understood. recent work has shown that when cells are exposed to nspef, ion permeable nanopores (<2  nm) are created in the plasma membrane in contrast to larger diameter pores (>2  nm) created by longer micro- and millisecond duration pulses. nanoporation of the plasma membrane by nspef has been shown to cause a transient increase in intracellular calcium concentration wit ...201424825506
chloroquine impairs visual transduction via modulation of acid sensing ion channel 1a.acid-sensing ion channels (asics) are extracellular ph sensors activated by protons, which influence retinal activity and phototransduction. among all asics, asic1a is abundantly expressed in the retina and involved in normal retinal activity. chloroquine, which has been used in the treatment of malaria, rheumatoid arthritis and systemic lupus erythematosus, has been shown to be toxic to the retina. however, the underlying mechanisms remain unclear. in this study, we investigated the role of chl ...201424821433
a tamoxifen derivative, n,n-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine, selectively targets p-glycoprotein-positive multidrug resistant chinese hamster cells.dppe, a tamoxifen derivative with antihistamine activity, was previously shown to potentiate the toxicity of chemotherapeutic drugs. recently, a phase iii clinical study using doxorubicin with dppe demonstrated significant increase in the overall survival of breast cancer patients. in this study we examined the effects of dppe alone on the growth of drug sensitive and p-gp positive cho cell line. our results demonstrate dppe is selectively toxic to p-gp positive cells and the sensitivity to dppe ...201424821111
overexpression of micrornas enhances recombinant protein production in chinese hamster ovary cells.micrornas (mirnas) are short, non-coding rnas that can negatively regulate expression of multiple genes at post-transcriptional levels. using mirnas to target multiple genes and pathways is a promising cell-engineering strategy to increase recombinant protein production in mammalian cells. here, we identified mirs-17, -19b, -20a, and -92a to be differentially expressed between high- and low- monoclonal antibody-producing chinese hamster ovary (cho) cell clones using next-generation sequencing an ...201424819042
novel cationic polyene glycol phospholipids as dna transfer reagents--lack of a structure-activity relationship due to uncontrolled self-assembling processes.cationic glycol phospholipids were synthesized introducing chromophoric, rigid polyenoic c20:5 and c30:9 chains next to saturated flexible alkyl chains of variable lengths c6-20:0. surface properties and liposome formation of the amphiphilic compounds were determined, the properties of liposome/dna complexes (lipoplexes) were established using three formulations (no co-lipid, dope as a co-lipid, or cholesterol as a co-lipid), and the microstructure of the best transfecting compounds inspected us ...201424814958
inhibition of oatp-1b1 and oatp-1b3 by tyrosine kinase inhibitors.the potential of tyrosine kinase inhibitors (tkis) interacting with other therapeutics through hepatic uptake transporter inhibition has not been fully delineated in drug-drug interactions (ddis). this study was designed to estimate the half-maximal inhibitory concentration (ic50) values of five small-molecule tkis (pazopanib, nilotinib, vandetanib, canertinib and erlotinib) interacting with organic anion-transporting polypeptides (oatps): oatp-1b1 and -1b3.201424807167
different pharmacokinetic and pharmacodynamic properties of recombinant follicle-stimulating hormone (rfsh) derived from a human cell line compared with rfsh from a non-human cell line.pharmacokinetic and pharmacodynamic properties of a novel recombinant follicle-stimulating hormone (rfsh) preparation (fe 999049), expressed by a human cell line (per.c6), was compared with an rfsh preparation (follitropin α) expressed by a chinese hamster ovary (cho) cell line in healthy pituitary-suppressed women. following single intravenous administration of 225 iu (steelman-pohley assay), the clearance was lower, 0.31 versus 0.44 l/h, for fe 999049 than for follitropin α. likewise, the appa ...201424800998
transcriptome analyses of cho cells with the next-generation microarray cho41k: development and validation by analysing the influence of the growth stimulating substance igf-1 substitute longr(3.).the increasing importance of chinese hamster ovary (cho) cells for the production of pharmaceutical proteins has awakened the demand to understand the cellular metabolism of these cells. however, satisfactory gene expression studies have yet been impractical due to insufficient coverage of sequences. in this work, previously determined sequence information of cho cells and newly derived data from 454 and illumina sequencing was used to establish the cho41k microarray which contains 41,304 probes ...201424613301
presenilin-1 influences processing of the acetylcholinesterase membrane anchor prima.presenilin-1 (ps1) is the catalytic component of the γ-secretase complex. in this study, we explore if ps1 participates in the processing of the cholinergic acetylcholinesterase (ache). the major ache variant expressed in the brain is a tetramer (g(4)) bound to a proline-rich membrane anchor (prima). overexpression of the transmembrane prima protein in chinese hamster ovary cells expressing ache and treated with the γ-secretase inhibitor n-[n-(3,5-difluorophenacetyl)-l-alanyl]-s-phenylglycine t- ...201424612677
efficient production and purification of extracellular domain of human fgfr-fc fusion proteins from chinese hamster ovary cells.the family of fibroblast growth factor receptors (fgfrs) plays an important role in cell growth, survival, differentiation and angiogenesis. the three immunoglobulin-like extracellular domains of fgfr (d1, d2, and d3) are critical for ligand binding and specificity towards fibroblast growth factor and heparan sulfate. fibroblast growth factor receptors are overexpressed in a wide variety of tumors, such as breast, bladder, and prostate cancer, and therefore they are attractive targets for differ ...201424727156
optimization of heterologous protein production in chinese hamster ovary cells under overexpression of spliced form of human x-box binding protein.the optimization of protein production is a complex and challenging problem in biotechnology. different techniques for transcription, translation engineering and the optimization of cell culture conditions have been used to improve protein secretion, but there remain many open problems involving post-translational modifications of the secreted protein and cell line stability.201424725707
effect of glutamine substitution by tca cycle intermediates on the production and sialylation of fc-fusion protein in chinese hamster ovary cell culture.in an effort to reduce the accumulation of ammonia in culture medium, three different tca cycle intermediates, (alpha-ketoglutarate (α-kg), citric acid and succinic acid) along with glutamic acid for a comparison, were examined as a substitute for glutamine with rcho cell line producing a fc-fusion glycoprotein. among them, α-kg showed the best production performance. when cells were cultivated with 4 mm α-kg, the final ammonia concentration did not exceed 3 mm, which is less than one fourth of ...201424721212
ultrasound driven assembly of lignin into microcapsules for storage and delivery of hydrophobic molecules.oil-filled microcapsules of kraft lignin were synthesized by first creating an oil in water emulsion followed by a high-intensity, ultrasound-assisted cross-linking of lignin at the water/oil interface. the rationale behind our approach is based on promoting documented lignin hydrophobic interactions within the oil phase, followed by locking the resulting spherical microsystems by covalent cross-linking using a high intensity ultrasound treatment. as further evidence in support of our rationale, ...201424720505
synthesis, spectral characterization, and antiproliferative studies of mixed ligand titanium complexes of adamantylamine.titanium complexes have been synthesized by the reaction between titanium tetrachloride (ticl4), respective bidentate ligand [4,4' -dimethoxy-2,2' -bipyridine (bpome), 6,6'-dimethyl-2,2'-bipyridine (dpme), 1,2-diaminocyclohexane (dach), 1,10-phenanthroline (phen), and benzoylacetone (bzac)], and adamantylamine (ada) in 1 : 2 : 2 molar ratios, respectively. the structure of synthesized complexes was confirmed using elemental analysis, ftir, uv-visible, (1)h nmr, and mass spectrometry techniques. ...201424715822
influence of the phase effect on gradient-based and statistics-based focus measures in bright field microscopy.autofocusing is essential to high throughput microscopy and live cell imaging and requires reliable focus measures. phase objects such as separated single chinese hamster ovary cells are almost invisible at the optical focus position in bright field microscopy images. because of the phase effect, defocused images of phase objects have more contrast. in this paper, we show that widely used focus measures exhibit an untypical behaviour for such images. in the case of homogeneous cells, that is, wh ...201424611652
a novel luminescence-based method for the detection of functionally active antibodies to muscarinic acetylcholine receptors of the m3 type (machr3) in patients' sera.in different bioassays, functional antibodies reacting with the human muscarinic acetylcholine receptor m3(machr3) have been detected in sera from patients with sjögren's syndrome (ss), and there is strong evidence that those antibodies may have pathogenetic relevance. however, depending on the method of detection, their prevalence varied. furthermore, those bioassays are difficult to standardize. we report on the development and optimization of a novel test system based on a luminometric method ...201424628494
the brca2 gene is a potential molecular target during 5-fluorouracil therapy in human oral cancer cells.5-fluorouracil (5-fu) is widely used in clinical cancer therapy. it is commonly used either alone or in combination with other drugs and/or radiation for head and neck, and other types of cancers. 5-fu induces dna double-strand breaks (dsbs). inhibition of the repair of 5-fu-induced dsbs may improve the therapeutic response in many tumors to this anticancer agent. the aim of the present study was to further our understanding of the pathways which are involved in the repair of 5-fu-induced dsbs. ...201424627042
disruption of the actin cortex contributes to susceptibility of mammalian cells to nanosecond pulsed electric fields.nanosecond pulsed electric fields (nspefs) perturb membranes of cultured mammalian cells in a dose-dependent manner with different types of cells exhibiting characteristic survivability. adherent cells appear more robust than non-adherent cells during whole-cell exposure. we hypothesize that cellular elasticity based upon the actin cytoskeleton is a contributing parameter, and the alteration of a cell's actin cortex will significantly affect viability upon nspef exposure. chinese hamster ovary ( ...201424619788
cell compatible arginine containing cationic polymer: one-pot synthesis and preliminary biological assessment.synthetic cationic polymers are of interest as both nonviral vectors for intracellular gene delivery and antimicrobial agents. for both applications synthetic polymers containing guanidine groups are of special interest since such kind of organic compounds/polymers show a high transfection potential along with antibacterial activity. it is important that the delocalization of the positive charge of the cationic group in guanidine significantly decreases the toxicity compared to the ammonium func ...201424619618
occurrence and subcellular distribution of the nadphx repair system in mammals.hydration of nad(p)h to nad(p)hx, which inhibits several dehydrogenases, is corrected by an atp-dependent dehydratase and an epimerase recently identified as the products of the vertebrate carkd (carbohydrate kinase domain) and aibp (apolipoprotein ai-binding protein) genes respectively. the purpose of the present study was to assess the presence of these enzymes in mammalian tissues and determine their subcellular localization. the carkd gene encodes proteins with a predicted mitochondrial prop ...201424611804
solvation dynamics and intermittent oscillation of cell membrane: live chinese hamster ovary cell.dynamics of the exofacial thiols (i.e., cell surface thiol containing membrane proteins) of a live chinese hamster ovary (cho) cell is probed by time-resolved confocal microscopy. for this purpose, a fluorescent probe, 7-(diethylamino)-3-(4-maleimidophenyl)-4-methylcoumarin (cpm) is covalently attached to the exofacial thiols. the emission maximum of cpm bound exofacial thiols indicates a highly exposed and polar environment. using cpm, we studied solvation dynamics, for the first time, at the m ...201424571625
heat exposure enhances radiosensitivity by depressing dna-pk kinase activity during double strand break repair.from the role of double strand dna dependent protein kinase (dna-pkcs) activity of non-homologous end joining (nhej) repair for dna double strand breaks (dsbs), we aim to define possible associations between thermo-sensitisation and the enzyme activities in x-ray irradiated cells.201424571173
mir-7 inhibits colorectal cancer cell proliferation and induces apoptosis by targeting xrcc2.analysis using publicly available algorithms predicts that x-ray repair complementing defective repair in chinese hamster cells 2 (xrcc2), a key component in the homologous recombination repair pathway, is a potential target of micro-ribonucleic acid-7 (mir-7). some studies have shown that both mir-7 and xrcc2 are associated with cancer development. for this purpose, we searched for the possible relationship between mir-7 and xrcc2 in the development of colorectal cancer (crc).201424570594
apoptosis-inducing activity of hplc fraction from voacanga globosa (blanco) merr. on the human colon carcinoma cell.voacanga globosa (blanco), a plant endemic to the philippines, is traditionally used especially by indigenous people of bataan in the treatment of ulcers, wounds and tumorous growths. this study aimed to provide scientific evidence to therapeutic properties by determining cytotoxic and pro-apoptotic activity of hplc fractions from leaves on hct116 human colon carcinoma and a549 human lung carcinoma cell lines. ethanolic extraction was performed on v globosa leaves followed by hexane and ethyl ac ...201424568467
turoctocog alfa for the treatment of hemophilia a.patients with hemophilia a lack functional coagulation factor viii (fviii), causing excessive spontaneous bleeding episodes and bleeding during trauma or surgery. plasma-derived or synthetic recombinant fviii is used to control bleeding, but currently available treatments are limited because of patient development of fviii inhibitors and cross-contamination of human and animal-derived infectious agents. turoctocog alfa is a recombinant fviii produced in chinese hamster ovary cells that has demon ...201424619589
high-throughput screening platform for engineered nanoparticle-mediated genotoxicity using cometchip technology.the likelihood of intentional and unintentional engineered nanoparticle (enp) exposure has dramatically increased due to the use of nanoenabled products. indeed, enps have been incorporated in many useful products and have enhanced our way of life. however, there are many unanswered questions about the consequences of nanoparticle exposures, in particular, with regard to their potential to damage the genome and thus potentially promote cancer. in this study, we present a high-throughput screenin ...201424617523
poly-γ-glutamic acid enhances the quality of recombant erythropoietin produced by cho cells.the effect of poly-γ-glutamic acid (γpga), which is produced by bacillus sp., on the production of recombinant erythropoietin (repo) by chinese hamster ovary (cho) cells in suspension culture was evaluated. the growth, viability, and productivity of recombinant cho cells were investigated in a chemically defined medium with 50 and 500 kd γpgas at 0.075% or with pluronic f68. cell growth with the two γpgas was lower than that with pluronic f68 but significantly higher than that without any additi ...201426019520
heat-transfer resistance measurement method (htm)-based cell detection at trace levels using a progressive enrichment approach with highly selective cell-binding surface imprints.surface-imprinted polymers allow for specific cell detection based on simultaneous recognition of the cell shape, cell size, and cell membrane functionalities by macromolecular cell imprints. in this study, the specificity of detection and the detection sensitivity for target cells within a pool of non-target cells were analyzed for a cell-specific surface-imprinted polymer combined with a heat-transfer-based read-out technique (htm). a modified chinese hamster ovarian cell line (cho-ldld) was u ...201424606112
promiscuous gating modifiers target the voltage sensor of k(v)7.2, trpv1, and h(v)1 cation channels.some of the fascinating features of voltage-sensing domains (vsds) in voltage-gated cation channels (vgccs) are their modular nature and adaptability. here we examined the vsd sensitivity of different vgccs to 2 structurally related nontoxin gating modifiers, nh17 and nh29, which stabilize k(v)7.2 potassium channels in the closed and open states, respectively. the effects of nh17 and nh29 were examined in chinese hamster ovary cells transfected with transient receptor potential vanilloid 1 (trpv ...201424599966
genotoxic evaluation of titanium dioxide nanoparticles in vivo and in vitro.with the extensive application of titanium dioxide (tio2) nanoparticles (nps) in food industry, there is a rising debate concerning the possible risk associated with exposure to tio2 nps. the purpose of this study is to evaluate the genotoxicity of tio2 nps using in vivo and in vitro test systems. in vivo study, the adult male sprague-dawley rats were exposed to anatase tio2 nps (75 ± 15 nm) through intragastric administration at 0, 10, 50 and 200mg/kg body weight every day for 30 days. the γ-h2 ...201424594277
safety and mutagenicity evaluation of red mold dioscorea fermented from monascus purpureus ntu 568.monascus-fermented products, including red mold rice and red mold dioscorea, have been developed as functional foods with many health benefits. we performed safety and mutagenic evaluations on red mold dioscorea powder (rmdp) fermented from monascus purpureus ntu 568. the results of ames test using salmonella typhimurium strains ta97a, ta98, ta100, ta102, and ta1535 showed that rmdp (⩽5 mg/plate) was not mutagenic. the mammalian chromosomal aberration test showed that the number of chinese hamst ...201424582683
a high throughput screening assay system for the identification of small molecule inhibitors of gsp.mis-sense mutations in the α-subunit of the g-protein, gsα, cause fibrous dysplasia of bone/mccune-albright syndrome. the biochemical outcome of these mutations is constitutively active gsα and increased levels of camp. the aim of this study was to develop an assay system that would allow the identification of small molecule inhibitors specific for the mutant gsα protein, the so-called gsp oncogene. commercially available chinese hamster ovary cells were stably transfected with either wild-type ...201424667240
setting time affects in vitro biological properties of root canal sealers.biocompatibility of root canal sealers is important because of the long-term contact of their eluates and/or degradation products with periapical tissues. the literature still lacks studies about the genotoxic effects of these materials and the influence of setting time on biological properties. the cytotoxicity and genotoxicity of an epoxy resin-based sealer (ah plus), a single methacrylate-based sealer (endorez), and a silicone-based sealer (roekoseal) were assessed.201424666905
resveratrol and its major sulfated conjugates are substrates of organic anion transporting polypeptides (oatps): impact on growth of zr-75-1 breast cancer cells.resveratrol is a naturally occurring polyphenolic compound with various pharmacological activities. these effects are observed despite its low bioavailability, which is particularly caused by extensive phase ii metabolism. it is unknown whether resveratrol and its metabolites can accumulate to bioactive levels in organs and tissues through protein-mediated transport mechanisms. because organic anion transporting polypeptides (oatps) mediate the uptake of many clinically important drugs, we inves ...201424996158
translational possibility of [(18) f]mefway to image serotonin 1a receptors in humans: comparison with [(18) f]fcway in rodents.purpose: to compare the cerebral uptake and binding potential of [(18) f]fcway and [(18) f]mefway in the rodent to assess their potential for imaging serotonin 1a (5-ht1a ) receptors. materials and methods: in vitro liver microsomal studies were performed to evaluate the degree of defluorination. dynamic positron emission tomography (pet) studies were then conducted for 2 h with or without an anti-defluorination agent. the regions of interest were the hippocampus and frontal cortex (5-ht1a targe ...201425056144
identification of micrornas specific for high producer cho cell lines using steady-state cultivation.micrornas are short non-coding rnas that play an important role in the regulation of gene expression. hence, micrornas are considered as potential targets for engineering of chinese hamster ovary (cho) cells to improve recombinant protein production. here, we analyzed and compared the microrna expression patterns of high, low, and non-producing recombinant cho cell lines expressing two structurally different model proteins in order to identify micrornas that are involved in heterologous protein ...201425052466
treating cell culture media with uv irradiation against adventitious agents: minimal impact on cho performance.sterility of cell culture media is an important concern in biotherapeutic processing. in large scale biotherapeutic production, a unit contamination of cell culture media can have costly effects. ultraviolet (uv) irradiation is a sterilization method effective against bacteria and viruses while being non-thermal and non-adulterating in its mechanism of action. this makes uv irradiation attractive for use in sterilization of cell culture media. the objective of this study was to evaluate the effe ...201425044686
preparation, characterization, cytotoxicity, and genotoxicity evaluations of thiolated- and s-nitrosated superparamagnetic iron oxide nanoparticles: implications for cancer treatment.iron oxide magnetic nanoparticles have been proposed for an increasing number of biomedical applications, such as drug delivery. to this end, toxicological studies of their potent effects in biological media must be better evaluated. the aim of this study was to synthesize, characterize, and examine the potential in vitro cytotoxicity and genotoxicity of thiolated (sh) and s-nitrosated (s-no) iron oxide superparamagnetic nanoparticles toward healthy and cancer cell lines. fe3o4 nanoparticles wer ...201424949992
enhancement of production of protein biopharmaceuticals by mammalian cell cultures: the metabolomics perspective.the new era of metabolic study is enabling a molecular rationalisation of cellular processes that support high production and quality of recombinant protein in bioprocessing. the completeness of, and confidence in, our understanding of culture metabolism has permitted the development of metabolic models for recombinant cell lines that will facilitate enhancement of bioprocess performance. for chinese hamster ovary (cho) cell lines, key indicators of metabolic events linked to productivity have b ...201424995573
antiproliferative evaluation of isofuranodiene on breast and prostate cancer cell lines.the anticancer activity of isofuranodiene, extracted from smyrnium olusatrum, was evaluated in human breast adenocarcinomas mda-mb 231 and bt 474, and caucasian prostate adenocarcinoma pc 3 cell lines by mts assay. mts assay showed a dose-dependent growth inhibition in the tumor cell lines after isofuranodiene treatment. the best antiproliferative activity of the isofuranodiene was found on pc 3 cells with an ic50 value of 29 μm, which was slightly less than the inhibition against the two breast ...201424967427
engineering and characterization of a humanized antibody targeting tnf-α and rankl.to neutralize the pathological activities of tumor necrosis factor-α (tnf-α) and receptor activator of nf-κb ligand (rankl), we engineered and characterized a humanized 8g12 (h8g12) antibody that targeted tnf-α and rankl. standard molecular biological and complementarity determining region (cdr)-grafting techniques were used to engineer the h8g12 antibody, and enzyme-linked immunosorbent assays (elisas) and western blotting were employed to determine its binding activation and specificity. tnf-α ...201424950406
a framework for the systematic design of fed-batch strategies in mammalian cell culture.a methodology to calculate the required amount of amino acids (a.a.) and glucose in feeds for animal cell culture from monitoring their levels in batch experiments is presented herein. experiments with the designed feeds on an antibody-producing chinese hamster ovary cell line resulted in a 3-fold increase in titer compared to batch culture. adding 40% more nutrients to the same feed further increases the yield to 3.5 higher than in batch culture. our results show that above a certain threshold ...201424975682
recent advances in the understanding of biological implications and modulation methodologies of monoclonal antibody n-linked high mannose glycans.with the prevalence of therapeutic monoclonal antibodies (mabs) in the biopharmaceutical industry, the use of mammalian cell culture systems, particularly chinese hamster ovary (cho) cells, has become the main method for the production of therapeutics. despite their similarity to human cells, one major challenge of mammalian cell based biopharmaceutical production is controlling aberrant glycosylation, especially glycans with five to nine mannose residues-high mannose glycoforms. glycosylation p ...201424975601
a phase 1, randomized study to assess the pharmacokinetic comparability of siltuximab derived from two different cell lines in healthy subjects.siltuximab, a monoclonal antibody (mab) against interleukin (il-6), is under development by janssen research & development, llc. during early clinical development, siltuximab was produced in a murine sp2/0 myeloma cell line. the production cell line was switched to stably transfected chinese hamster ovary (cho) cell line for subsequent clinical development. a two-part, parallel-group, phase 1 study was designed to evaluate the safety and pharmacokinetics (pk) of a single iv administration of sp2 ...201427128840
intracellular generation of ros by 3,5-dimethylaminophenol: persistence, cellular response, and impact of molecular toxicity.epidemiological studies have demonstrated extensive human exposure to the monocyclic aromatic amines, particularly to 3,5-dimethylaniline, and found an association between exposure to these compounds and risk for bladder cancer. little is known about molecular mechanisms that might lead to the observed risk. we previously suggested that the hydroxylated 3,5-dimethylaniline metabolite, 3,5-dimethylaminophenol (3,5-dmap), played a central role in effecting genetic change through the generation of ...201424973092
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