Publications

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kir2.1 and k2p1 channels reconstitute two levels of resting membrane potential in cardiomyocytes.outward and inward background currents across the cell membrane balance, determining resting membrane potential. inward rectifier k+ channel subfamily 2 (kir2) channels primarily maintain the resting membrane potential of cardiomyocytes. human cardiomyocytes exhibit two levels of resting membrane potential at subphysiological extracellular k+ concentrations or pathological hypokalaemia, however, the underlying mechanism is unclear. in the present study, we show that human cardiomyocytes derived ...201728543529
the ik1/kir2.1 channel agonist zacopride prevents and cures acute ischemic arrhythmias in the rat.arrhythmogenesis in acute myocardial infarction (mi) is associated with depolarization of resting membraine potential (rmp) and decrease of inward rectifier potassium current (ik1) in cardiomyocytes. however, clinical anti-arrhythmic agents that primarily act on rmp by enhancing the ik1 channel are not currently available. we hypothesized that zacopride, a selective and moderate agonist of the ik1/kir2.1 channels, prevents and cures acute ischemic arrhythmias. to test this viewpoint, adult sprag ...201728542320
low-density lipoprotein receptor-related protein-1 (lrp1) c4408r mutant promotes amyloid precursor protein (app) α-cleavage in vitro.previous studies have demonstrated that the low-density lipoprotein receptor-related protein-1 (lrp1) plays conflicting roles in alzheimer's disease (ad) pathogenesis, clearing β-amyloid (aβ) from the brain while also enhancing app endocytosis and resultant amyloidogenic processing. we have recently discovered that co-expression of mutant lrp1 c-terminal domain (lrp1-ct c4408r) with swedish mutant amyloid precursor protein (appswe) in chinese hamster ovary (cho) cells decreases aβ production, wh ...201728612181
differential killing and radio-modifying effects of iodoacetate in mammalian normal and cancer cells.to explore possible applications of iodoacetate (ia), a glycolytic inhibitor, in cancer treatment, we screened its cytotoxicity and radioprotective/sensitizing efficacy in three different mammalian cell lines; a549 (human lung carcinoma), mcf7 (human mammary cancer), a non-cancerous cho (chinese hamster ovary) cells and human lymphocytes. experiments were carried out using ia concentrations ranging from 0.01 to 2.5 µg/ml, with or without 60coγ-radiation. in the outcomes, ia was found to exhibit ...201728612110
a new fully human recombinant fsh (follitropin epsilon): two phase i randomized placebo and comparator-controlled pharmacokinetic and pharmacodynamic trials.what are the differences and similarities of pharmacokinetic (pk) and pharmacodynamic (pd) characteristics of the novel recombinant human fsh follitropin epsilon expressed in the human cell line glycoexpress compared with a chinese hamster ovary (cho) derived compound and a urinary derived product?201728591833
distinct cellular phenotype linked to defective dna interstrand crosslink repair and homologous recombination.repair of dna interstrand crosslinks (icls) predominantly involves the fanconi anemia (fa) pathway and homologous recombination (hr). the hr repair system eliminates dna double strand breaks (dsbs) that emerge during icls removal. the current study presents a novel cell line, cl‑v8b, representing a new complementation group of chinese hamster cell mutants hypersensitive to dna crosslinking factors. cl‑v8b exhibits increased sensitivity to various dna‑damaging agents, including compounds leading ...201728627616
rapid protein production from stable cho cell pools using plasmid vector and the cumate gene-switch.to rapidly produce large amounts of recombinant proteins, the generation of stable chinese hamster ovary (cho) cell pools represents a useful alternative to large-scale transient gene expression (tge). we have developed a cell line (chobri/rcta) allowing the inducible expression of recombinant proteins, based on the cumate gene switch. after the identification of optimal plasmid dna topology (supercoiled vs linearized plasmid) for peipro™ mediated transfection and of optimal conditions for methi ...201728625678
characterization of a novel modification of a cho-produced mab: evidence for the presence of tyrosine sulfation.herein we describe the investigation of a chinese hamster ovary (cho)-expressed human mab molecule found partially modified by a +80 da adduct. this mass difference, suggestive of a single sulfation or phosphorylation addition, was observed by mass analysis of the intact and reduced molecule by mass spectrometry (ms). the modification was located on tyrosine 31 (y31) of the light chain in the complementarity-determining region 1 by liquid chromatography (lc)-ms peptide mapping and electron trans ...201728590151
the β4 subunit of the voltage-gated calcium channel (cacnb4) regulates the rate of cell proliferation in chinese hamster ovary cells.the β subunits of voltage-gated calcium channel (vgcc) are cytosolic proteins that interact with the vgcc pore -forming subunit and participate in the trafficking of the channel to the cell membrane and in ion influx regulation. β subunits also exert functions independently of their binding to vgcc by translocation to the cell nucleus including the control of gene expression. mutations of the neuronal cacnb4 (β4) subunit are linked to human neuropsychiatric disorders including epilepsy and intel ...201728587927
variability among tsh measurements can be reduced by combining a glycoengineered calibrator to epitope-defined immunoassays.measuring protein markers with variable glycosylation, such as thyroid-stimulating hormone (tsh), with high accuracy is not an easy task. despite highly sensitive third-generation tests, discrepancies among tsh assays still remain unsolved and are the focus of important standardization efforts. earlier work from our group showed that a lack of similarity in epitope expression between standards and samples may account for discordant hormone measurements. in this study, we aimed at producing a gly ...201728611942
cellular response to exponentially increasing and decreasing dose rates: implications for treatment planning in targeted radionuclide therapy.the treatment of cancer using targeted radionuclide therapy is of interest to nuclear medicine and radiation oncology because of its potential for killing tumor cells while minimizing dose-limiting toxicities to normal tissue. the ionizing radiations emitted by radiopharmaceuticals deliver radiation absorbed doses over protracted periods of time with continuously varying dose rates. as targeted radionuclide therapy becomes a more prominent part of cancer therapy, accurate models for estimating t ...201728541775
genetic analysis of heterogeneous sub-clones in recombinant chinese hamster ovary cells.chinese hamster ovary (cho) cells have been widely used for production of recombinant proteins and therapeutic antibodies. however, owing to the instability and heterogeneity of cho cells, the development of stable and high-expression recombinant cho cell lines is often time-consuming. to investigate the mechanisms associated with heterogeneity in protein productivity, we performed transcriptome analysis on the subclones derived from a stable parental cho clone. two high-expression subclones and ...201728540426
short-term cooling increases serum triglycerides and small high-density lipoprotein levels in humans.cold exposure and β3-adrenergic receptor agonism, which both activate brown adipose tissue, markedly influence lipoprotein metabolism by enhancing lipoprotein lipase-mediated catabolism of triglyceride-rich lipoproteins and increasing plasma high-density lipoprotein (hdl) levels and functionality in mice. however, the effect of short-term cooling on human lipid and lipoprotein metabolism remained largely elusive.201728625343
[the establishment and identification of stable cho cell line with canine transferrin receptor expression].to construct eukaryotic expressing recombinant vector of canine transferrin receptor gene (tfr ), then to transfect chinese hamster ovary (cho) cells with the vector for establishment of stable expression of tfr in cho cell line.201728612559
physicochemical and biological characterization of sustained isopropyl unoprostone-release device made of poly(ethyleneglycol) dimethacrylates.transscleral drug delivery is becoming increasingly popular to manage posterior eye diseases. to evaluate the clinical application of a transscleral, sustained, unoprostone (uno)-release device (urd) constructed of photopolymerized tri(ethyleneglycol) dimethacrylate and poly(ethyleneglycol) dimethacrylate, we evaluated physicochemical and biological properties of this device. the urd consists of a drug-impermeable reservoir and a semi-permeable cover. the in vitro release rate of uno from the ur ...201728534288
contribution of muscarinic receptors to in vitro and in vivo effects of ruscus extract.the objectives of this study were to evaluate, in vitro and in vivo, the contribution of muscarinic receptors to the effects of ruscus extract. ruscus extract was tested in competition binding experiments at recombinant human muscarinic receptors, heterologous expressed in chinese hamster ovary (cho) cells and in cellular assays measuring ca2+ liberation and activator protein-1 (ap-1) reporter gene activation. the impact of muscarinic blockade on prolonged treatment outcome was evaluated using t ...201728529172
identification of fc gamma receptor glycoforms that produce differential binding kinetics for rituximab.fc gamma receptors (fcγr) bind the fc region of antibodies and therefore play a prominent role in antibody-dependent cell-based immune responses such as adcc, cdc and adcp. the immune effector cell activity is directly linked to a productive molecular engagement of fcγrs where both the protein and glycan moiety of antibody and receptor can affect the interaction and in the present study we focus on the role of the fcγr glycans in this interaction. we provide a complete description of the glycan ...201728576848
orexin receptor agonist yan 7874 is a weak agonist of orexin/hypocretin receptors and shows orexin receptor-independent cytotoxicity.two promising lead structures of small molecular orexin receptor agonist have been reported, but without detailed analyses of the pharmacological properties. one of them, 1-(3,4-dichlorophenyl)-2-[2-imino-3-(4-methylbenzyl)-2,3-dihydro-1h-benzo[d]imidazol-1-yl]ethan-1-ol (yan 7874), is commercially available, and we set out to analyze its properties. as test system we utilized human ox1 and ox2 orexin receptor-expressing chinese hamster ovary (cho) k1 cells as well as control cho-k1 and neuro-2a ...201728575023
myeloma-derived light chain paired with a diagnostic monoclonal antibody hinders immunoassay performance.monoclonal antibodies are widely used as the capture and detection reagents in diagnostic immunoassays. in the past, myeloma fusion partners expressing endogenous heavy and/or light chains were often used to generate hybridoma cell lines. as a result, mixed populations of antibodies were produced that can cause inaccurate test results, poor antibody stability, and significant lot-to-lot variability. we describe one such scenario where the p3u1 (p3x63ag8u.1) myeloma fusion partner was used in the ...201728557609
co-overexpression of mgat1 and mgat4 in cho cells for production of highly sialylated albumin-erythropoietin.terminal sialic acids on n-glycan of recombinant human erythropoietin are very important for in vivo half-life, as this glycoprotein has three n-glycosylation sites. n-acetylglucosaminyltransferases i, ii, iv, and v (i.e. mgat1, mgat2, mgat4, and mgat5) catalyze the formation of a glycan antennary structure. these enzymes display different reaction kinetics for a common substrate and generally show low expression in chinese hamster ovary (cho) cells. therefore, genetic control of mgat expression ...201728554385
mammalian systems biotechnology reveals global cellular adaptations in a recombinant cho cell line.effective development of host cells for therapeutic protein production is hampered by the poor characterization of cellular transfection. here, we employed a multi-omics-based systems biotechnology approach to elucidate the genotypic and phenotypic differences between a wild-type and recombinant antibody-producing chinese hamster ovary (cho) cell line. at the genomic level, we observed extensive rearrangements in specific targeted loci linked to transgene integration sites. transcriptional re-wi ...201728544881
cellular evaluation of diselenonicotinamide (dsna) as a radioprotector against cell death and dna damage.diselenonicotinamide (dsna), a synthetic organoselenium compound, was evaluated for its radioprotective effect in cellular models. a clonogenic assay in chinese hamster ovary (cho) cells and an apoptosis assay in murine splenic lymphocytes indicated that pre-treatment with dsna at a concentration of 25 μm significantly protected them from radiation-induced cell death. upon irradiation (1-12 gy), dose-response studies were carried out under similar treatment conditions, and its dose modification ...201728503683
labeling glycans on living cells by a chemoenzymatic glycoengineering approach.structural glycobiology has traditionally been a challenging field due to a limited set of tools available to investigate the diverse and complex glycan molecules. however, we cannot ignore that glycans play critical roles in health as well as in disease, and are present in more than 50% of all proteins and on over 80% of all surface proteins. chemoenzymatic glycoengineering (cge) methods are a powerful set of tools to synthesize complex glycans, but the full potential of these methods have not ...201728500031
characterization of host cell proteins (hcps) in cho cell bioprocesses.host cell protein content during bioprocessing of biotherapeutic proteins generated from cultured chinese hamster ovary (cho) cells is typically measured using immunological and gel-based methods. estimation of hcp concentration is usually undertaken using enzyme-linked immunosorbent assays (elisa), while estimation of hcp clearance/presence can be achieved by comparing 2d-page images of samples and by undertaking western blotting of 2d-page analyzed samples. here, we describe the analyses of hc ...201728493135
the ef-1α promoter maintains high-level transgene expression from episomal vectors in transfected cho-k1 cells.in our previous study, we demonstrated that episomal vectors based on the characteristic sequence of matrix attachment regions (mars) and containing the cytomegalovirus (cmv) promoter allow transgenes to be maintained episomally in chinese hamster ovary (cho) cells. however, the transgene expression was unstable and the number of copies was low. in this study, we focused on enhancers, various promoters and promoter variants that could improve the transgene expression stability, expression magnit ...201728557288
development of a 3-step straight-through purification strategy combining membrane adsorbers and resins.the pressures to efficiently produce complex biopharmaceuticals at reduced costs are driving the development of novel techniques, such as in downstream processing with straight-through processing (stp). this method involves directly and sequentially purifying a particular target with minimal holding steps. this work developed and compared six different 3-step stp strategies, combining membrane adsorbers, monoliths, and resins, to purify a large, complex, and labile glycoprotein from chinese hams ...201728556541
modelling and mathematical analysis of the m$_{2}$ receptor-dependent joint signalling and secondary messenger network in cho cells.the muscarinic m$_{2}$ receptor is a prominent member of the gpcr family and strongly involved in heart diseases. recently published experimental work explored the cellular response to iperoxo-induced m$_{2}$ receptor stimulation in chinese hamster ovary (cho) cells. to better understand these responses, we modelled and analysed the muscarinic m$_{2}$ receptor-dependent signalling pathway combined with relevant secondary messenger molecules using mass action. in our literature-based joint signal ...201728505258
polysome profiling of mab producing cho cell lines links translational control of cell proliferation and recombinant mrna loading onto ribosomes with global and recombinant protein synthesis.mrna translation is a key process determining growth, proliferation and duration of a chinese hamster ovary (cho) cell culture and influences recombinant protein synthesis rate. during bioprocessing, cho cells can experience stresses leading to reprogramming of translation and decreased global protein synthesis. here we apply polysome profiling to determine reprogramming and translational capabilities in host and recombinant monoclonal antibody-producing (mab) cho cell lines during batch culture ...201728504349
the 'omics revolution in cho biology: roadmap to improved cho productivity.increased understanding of chinese hamster ovary (cho) cell physiology has been ushered in upon availability of the parental cho-k1 cell line genome. free and openly accessible sequence information has complemented transcriptomic and proteomic studies. the previous decade has also seen an increase in sensitivity and accuracy of proteomic methods due to technology development. in this genomic era, high-throughput screening methods, sophisticated informatic tools, and models continually drive majo ...201728493129
membrane permeabilization of mammalian cells using bursts of high magnetic field pulses.cell membrane permeabilization by pulsed electromagnetic fields (pemf) is a novel contactless method which results in effects similar to conventional electroporation. the non-invasiveness of the methodology, independence from the biological object homogeneity and electrical conductance introduce high flexibility and potential applicability of the pemf in biomedicine, food processing, and biotechnology. the inferior effectiveness of the pemf permeabilization compared to standard electroporation a ...201728462057
improved cho cell line stability and recombinant protein expression during long-term culture.therapeutic proteins require proper folding and posttranslational modifications to be effective and biologically active. chinese hamster ovary (cho) cells are by far the most frequently used host for commercial production of therapeutic proteins. however, an unpredictable decrease in protein productivity during the time required for scale up impairs process yields, time, finance, and regulatory approval for the desired product. therefore, it is important to assess cell lines at stages throughout ...201728493127
safety evaluation of chlorella sorokiniana strain ck-22 based on an in vitro cytotoxicity assay and a 13-week subchronic toxicity trial in rats.the genus chlorella contains unicellular green algae that have been used as food supplements. the purpose of this work was to evaluate the safety of the chlorella sorokiniana strain ck-22 using powdered preparation (ck-22p) both by in vitro and in vivo assays. these included an experiment for cytotoxicity using chinese hamster lung fibroblasts (v79 cells) and a 13-week repeated-dose oral toxicity trial using wistar rats. the cytotoxicity was evaluated by mtt assay of a hot water extract (hw-ex) ...201728522334
the interaction of mc3r and mc4r with mrap2, acth, α-msh and agrp in chickens.the interaction of melanocortin-4 (mc4r) and melanocortin-3 (mc3r) receptors with proopiomelanocortin (pomc)-derived peptides (e.g. α-msh), agouti-related protein (agrp) and melanocortin-2 receptor accessory protein 2 (mrap2) is suggested to play critical roles in energy balance of vertebrates. however, evidence on their interaction in birds remains scarce. our study aims to reveal their interaction in chickens and the results showed that (1) chicken (c-)mc3r and cmc4r expressed in chinese hamst ...201728512117
differential phosphoproteomic analysis of recombinant chinese hamster ovary cells following temperature shift.phosphorylation is one of the most important post-translational modifications, playing a crucial role in regulating many cellular processes, including transcription, cytoskeletal rearrangement, cell proliferation, differentiation, apoptosis, and signal transduction. however, to date, little work has been carried out on the phosphoproteome in cho cells. in this study we have carried out a large scale differential phosphoproteomic analysis of recombinant cho cells following a reduction of culture ...201728509555
investigation of pyrazolo-sulfonamides as putative small molecule oxytocin receptor agonists.the neuropeptide oxytocin has been implicated in multiple central nervous system functions in mammalian species. increased levels have been reported to improve trust, alleviate symptoms related to autism and social phobias, and reduce social anxiety. hoffman-la roche published a patent claiming to have found potent small molecule oxytocin receptor agonists, smaller than the first non-peptide oxytocin agonist reported, way 267,464. we selected two of the more potent compounds from the patent and, ...201728505537
regulation of δ opioid receptor-mediated signaling and antinociception in peripheral sensory neurons by arachidonic acid-dependent 12/15-lipoxygenase metabolites.the function of δ opioid receptors (dor) expressed by peripheral pain-sensing neurons (nociceptors) is regulated by both cyclooxygenase- and lipoxygenase (lox)-dependent arachidonic acid (aa) metabolites. whereas cyclooxygenase metabolites enhance responsiveness, lox metabolites elicit a refractory, nonsignaling state of the dor receptor system for antinociceptive signaling. in this study, using high-performance liquid chromatography-tandem mass spectrometry analyses, we have found that the 12-/ ...201728465374
therapeutic glycoprotein production in mammalian cells.over the last years, the biopharmaceutical industry has significantly turned its biologics production towards mammalian cell expression systems. the presence of glycosylation machineries within these systems, and the fact that monoclonal antibodies represent today the vast majority of new therapeutic candidates, has largely influenced this new direction. recombinant glycoproteins, including monoclonal antibodies, have shown different biological properties based on their glycan profiles. thus, th ...201728465209
filter-aided sample preparation (fasp) for improved proteome analysis of recombinant chinese hamster ovary cells.chinese hamster ovary (cho) cells are the most commonly used mammalian host cell line for biopharmaceutical production because of their ability to correctly fold and posttranslationally modify recombinant proteins that are compatible with human use. proteomics, along with other 'omic platforms, are being used to understand the biology of cho cells with the ultimate aim of enhancing cho cell factories for more efficient production of biopharmaceuticals. in this chapter, we will describe an effici ...201728493131
a bioinformatics pipeline for the identification of cho cell differential gene expression from rna-seq data.in recent years, the publication of genome sequences for the chinese hamster and chinese hamster ovary (cho) cell lines has facilitated study of these biopharmaceutical cell factories with unprecedented resolution. our understanding of the cho cell transcriptome, in particular, has rapidly advanced through the application of next-generation sequencing (ngs) technology to characterize rna expression (rna-seq). in this chapter, we present a computational pipeline for the analysis of cho cell rna-s ...201728493130
z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in colon 26 tumor-bearing mice.cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. there is no therapeutic agent for treatment of this syndrome. we investigated the anti-cachexia effects of z-505 hydrochloride (z-505), a new oral growth hormone secretagogue receptor 1a (ghsr1a) agonist, using a mouse model of cancer cachexia. we performed a calcium flux assay in chinese hamster ovary (cho-k1) cells stably expressing human ghsr1a to quantif ...201728529141
cellular repair of dna-dna cross-links induced by 1,2,3,4-diepoxybutane.xenobiotic-induced interstrand dna-dna cross-links (icl) interfere with transcription and replication and can be converted to toxic dna double strand breaks. in this work, we investigated cellular responses to 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-n7g-bd) cross-links induced by 1,2,3,4-diepoxybutane (deb). high pressure liquid chromatography electrospray ionization tandem mass spectrometry (hplc-esi⁺-ms/ms) assays were used to quantify the formation and repair of bis-n7g-bd cross-links in wild ...201728524082
pharmacokinetic drug evaluation of brodalumab for the treatment of psoriasis.psoriasis is now understood to also be under the driving influence of the il-17/il-23 axis, and the medical breakthrough of novel il-17 inhibitor medications signals a paradigm shift in the way psoriatic patients are managed medically. brodalumab, a fully human chinese hamster ovary cell-derived immunoglobulin g2 (igg2) anti-il-17ra monoclonal antibody, is currently the most-developed treatment that binds to the il-17ra. the authors review and provide updates of efficacy and safety by several st ...201728460549
effects of phenothiazine-structured compounds on app processing in alzheimer's disease cellular model.the excess accumulation of amyloid-β (aβ) peptides derived from the sequential cleavage of amyloid precursor protein (app) by secretases, is one of the toxic key events leading to neuronal loss in alzheimer's disease (ad). studies have shown that cholinergic activity may also be involved in the regulation of app metabolism. in the current study, we have investigated the roles of toluidine blue o (tbo) and thionine (th), newly recognized phenothiazine-derived cholinesterase inhibitors, on the met ...201728457944
delivery of cargo to lysosomes using gneosomes.liposomes have been used to improve the intracellular delivery of a variety of cargos. encapsulation of cargos in liposomes leads to improved plasma half-lives and minimized degradation. here, we present a method for improving the selective delivery of liposomes to the lysosomes using a guanidinylated neomycin (gneo) transporter. the method for synthesizing gneo-lipids, incorporating them into liposomes, and the enhanced lysosomal delivery of encapsulated cargo are presented. gneo-liposomes, ter ...201728456981
glycosylation analysis of therapeutic glycoproteins produced in cho cells.in the last decades, the number of approved therapeutic proteins drugs is increasing exponentially and a large number of new therapeutic entities are progressing through clinical trials, solidifying biologics as the most promising class of pharmaceuticals on the market. several cell lines are available for biopharmaceutical processes but mammalian cells are preferred since they give fewer problems for immunogenicity as they produce human-like post-translational modifications (ptms). glycosylatio ...201728493134
engineer medium and feed for modulating n-glycosylation of recombinant protein production in cho cell culture.chinese hamster ovary (cho) cells have become the primary expression system for the production of complex recombinant proteins due to their long-term success in industrial scale production and generating appropriate protein n-glycans similar to that of humans. control and optimization of protein n-glycosylation is crucial, as the structure of n-glycans can largely influence both biological and physicochemical properties of recombinant proteins. protein n-glycosylation in cho cell culture can be ...201728493133
phosphopeptide enrichment and lc-ms/ms analysis to study the phosphoproteome of recombinant chinese hamster ovary cells.the reversible phosphorylation of proteins on serine, threonine, and tyrosine residues is one of the most important post-translational modifications that regulates many biological processes. the phosphoproteome has not been studied in any great detail in recombinant chinese hamster ovary (cho) cells to date despite phosphorylation playing a crucial role in regulating many molecular and cellular processes relevant to bioprocess phenotypes including, for example, transcription, translation, growth ...201728493132
application of crispr/cas9 genome editing to improve recombinant protein production in cho cells.genome editing has become an increasingly important aspect of chinese hamster ovary (cho ) cell line engineering for improving production of recombinant protein therapeutics. currently, the focus is directed toward expanding the product diversity, controlling and improving product quality and yields. in this chapter, we present our protocol on how to use the genome editing tool clustered regularly interspaced short palindromic repeat (crispr)/crispr-associated protein 9 (cas9) to knockout engine ...201728493126
conditional knockdown of endogenous micrornas in cho cells using tet-on-sandi sponge vectors.micrornas (mirnas) are small, noncoding rnas of about 22 nucleotides in length and have proven to be useful targets for genetic modifications for desirable phenotype in the biotech industry. the use of constitutively expressed "mirna sponge" vectors in which multiple, tandem mirna binding sites containing transcripts are transcriptionally regulated by a constitutive promoter for down regulating the levels of endogenous micrornas in chinese hamster ovary (cho) cells has shown to be more advantage ...201728493125
anti-apoptosis engineering for improved protein production from cho cells.improving the time integral of viable cell concentration by overcoming cell death, namely apoptosis, is one of the widely used strategies for efficient production of therapeutic proteins. by establishing stable cell lines that overexpress anti-apoptotic genes or down-regulate pro-apoptotic genes, the final product yields can be enhanced as cells become more resistance to environmental stresses. from the selection of high-expressing clones to verification of anti-apoptotic activity, the method to ...201728493124
large-scale transient transfection of chinese hamster ovary cells in suspension.we describe a one-liter transfection of suspension-adapted chinese hamster ovary (cho-dg44) cells using polyethyleneimine (pei) for dna delivery. the method involves transfection at a high cell density (5 × 106 cells/ml) by direct addition of plasmid dna (pdna) and pei to the culture and subsequent incubation at 31 °c with agitation by orbital shaking. we also describe an alternative method in which 90% of the pdna is replaced by nonspecific (filler) dna, and the production phase is performed at ...201728493122
identification of indothiazinone as a natural antiplatelet agent.cardiovascular disease, which is caused by unregulated platelet aggregation, is one of the main causes of deaths worldwide. many studies have focused on natural products with antiplatelet effects as a safe alternative therapy to prevent the disease. in this context, an in-house chemical library was screened to find natural products capable of inhibiting the interaction between platelet integrin αiibβ3 and fibrinogen, which is an essential step in platelet aggregation. on the basis of the screeni ...201728432753
novel high-throughput cell-based hybridoma screening methodology using the celigo image cytometer.hybridoma screening is a critical step for antibody discovery, which necessitates prompt identification of potential clones from hundreds to thousands of hybridoma cultures against the desired immunogen. technical issues associated with elisa- and flow cytometry-based screening limit accuracy and diminish high-throughput capability, increasing time and cost. conventional elisa screening with coated antigen is also impractical for difficult-to-express hydrophobic membrane antigens or multi-chain ...201728414024
overexpression of the regulatory subunit of glutamate-cysteine ligase enhances monoclonal antibody production in cho cells.for decades, chinese hamster ovary (cho) cells have been the preferred host for therapeutic monoclonal antibody (mab) production; however, increasing mab titer by rational engineering remains a challenge. our previous proteomic analysis in cho cells suggested that a higher content of glutathione (gsh) might be related to higher productivity. gsh is an important antioxidant, cell detoxifier, and is required to ensure the formation of native disulfide bonds in proteins. to investigate the involvem ...201728436007
investigation of triamterene as an inhibitor of the tgr5 receptor: identification in cells and animals.g-protein-coupled bile acid receptor 1 (gpbar1, also known as tgr5) has been shown to participate in glucose homeostasis. in animal models, a tgr5 agonist increases incretin secretion to reduce hyperglycemia. many agonists have been developed for clinical use. however, the effects of tgr5 blockade have not been studied extensively, with the exception of studies using tgr5 knockout mice. therefore, we investigated the potential effect of triamterene on tgr5.201728435224
ryanodine and ip3 receptor-mediated calcium signaling play a pivotal role in neurological infrared laser modulation.pulsed infrared (ir) laser energy has been shown to modulate neurological activity through both stimulation and inhibition of action potentials. while the mechanism(s) behind this phenomenon is (are) not completely understood, certain hypotheses suggest that the rise in temperature from ir exposure could activate temperature- or pressure-sensitive ion channels or create pores in the cellular outer membrane, allowing an influx of typically plasma-membrane-impermeant ions. studies using fluorescen ...201728413806
modulation and modeling of monoclonal antibody n-linked glycosylation in mammalian cell perfusion reactors.mammalian cell perfusion cultures are gaining renewed interest as an alternative to traditional fed-batch processes for the production of therapeutic proteins, such as monoclonal antibodies (mab). the steady state operation at high viable cell density allows the continuous delivery of antibody product with increased space-time yield and reduced in-process variability of critical product quality attributes (cqa). in particular, the production of a confined mab n-linked glycosylation pattern has t ...201728409838
improving pertuzumab production by gene optimization and proper signal peptide selection.using proper signal peptide and codon optimization are important factors that must be considered when designing the vector to increase protein expression in chinese hamster ovary (cho) cells. the aim of the present study is to investigate how to enhance pertuzumab production through heavy and light chain coding gene optimization and proper signal peptide selection. first, cho-k1 cells were transiently transfected with whole-antibody-gene-optimized, variable-regions-optimized and non-optimized co ...201728476488
the palmitoylation of the n-terminal extracellular cys37 mediates the nuclear translocation of vpac1 contributing to its anti-apoptotic activity.vpac1 is class b g protein-coupled receptors (gpcr) shared by pituitary adenylate cyclase activating polypeptide (pacap) and vasoactive intestinal peptide (vip). the first cysteine (cys37) in the n-terminal extracellular domain of mature vpac1 is a free cys not involved in the formation of conserved intramolecular disulfide bonds. in order to investigate the biological role of this cys37 in vpac1, the wild-type vpac1 and cys37/ala mutant (vpac1-c37/a) were expressed stably as fusion proteins wit ...201728473666
a comparative genomic hybridization approach to study gene copy number variations among chinese hamster cell lines.chinese hamster ovary (cho) cells are aneuploid in nature. the genome of recombinant protein producing cho cell lines continuously undergoes changes in its structure and organization. we analyzed nine cell lines, including parental cell lines, using a comparative genomic hybridization (cgh) array focused on gene-containing regions. the comparison of cgh with copy-number estimates from sequencing data showed good correlation. hierarchical clustering of the gene copy number variation data from cgh ...201728409824
glycoengineering of cho cells to improve product quality.chinese hamster ovary (cho) cells represent the predominant platform in biopharmaceutical industry for the production of recombinant biotherapeutic proteins, especially glycoproteins. these glycoproteins include oligosaccharide or glycan attachments that represent one of the principal components dictating product quality. especially important are the n-glycan attachments present on many recombinant glycoproteins of commercial interest. furthermore, altering the glycan composition can be used to ...201728493121
cation and voltage dependence of lidocaine inhibition of the hyperpolarization-activated cyclic nucleotide-gated hcn1 channel.lidocaine is known to inhibit the hyperpolarization-activated mixed cation current (ih) in cardiac myocytes and neurons, as well in cells transfected with cloned hyperpolarization-activated cyclic nucleotide-gated (hcn) channels. however, the molecular mechanism of ih inhibition by this drug has been limitedly explored. here, we show that inhibition of ih by lidocaine, recorded from chinese hamster ovary (cho) cells expressing the hcn1 channel, reached a steady state within one minute and was re ...201728455536
comparative pharmacology of a new recombinant fsh expressed by a human cell line.recombinant fsh proteins are important therapeutic agents for the treatment of infertility, including follitropin alfa expressed in chinese hamster ovary (cho) cells and, more recently, follitropin delta expressed in the human cell line per.c6. these recombinant fsh proteins have distinct glycosylation, and have distinct pharmacokinetic and pharmacodynamic profiles in women. comparative experiments demonstrated that follitropin delta and follitropin alfa displayed the same in vitro potency at th ...201728450423
ppp1r15a-mediated dephosphorylation of eif2α is unaffected by sephin1 or guanabenz.dephosphorylation of translation initiation factor 2 (eif2α) terminates signalling in the mammalian integrated stress response (isr) and has emerged as a promising target for modifying the course of protein misfolding diseases. the [(o-chlorobenzylidene)amino]guanidines (guanabenz and sephin1) have been proposed to exert protective effects against misfolding by interfering with eif2α-p dephosphorylation through selective disruption of a pp1-ppp1r15a holophosphatase complex. surprisingly, they pr ...201728447936
characterization of four latin american families confirms previous findings and reveals novel features of acid-labile subunit deficiency.acid-labile subunit deficiency (aclsd), caused by inactivating mutations in both igfals gene alleles, is characterized by marked reduction in igf-i and igfbp-3 levels associated with mild growth retardation. the aim of this study was to expand the known phenotype and genetic characteristics of aclsd by reporting data from four index cases and their families.201728445628
induction of micronuclei and cell cycle arrest by some tri- and tetrachlorobiphenyls in mammalian cells deficient in xenobiotic-metabolizing enzymes.polychlorinated biphenyls (pcbs) are persistent organic pollutants with continued public health concerns. the lower chlorinated biphenyls are supposed to be mutagenic following metabolic activation. however, in a preliminary study, we recently observed induction of micronuclei by several pcbs in a subclone of chinese hamster v79 cell line, v79-mz, which is deficient in xenobiotic-metabolizing enzyme activities. in this study, metabolism-free genotoxicity of pcbs was investigated, using 10 tri- a ...201728444994
model-based analysis of n-glycosylation in chinese hamster ovary cells.the chinese hamster ovary (cho) cell is the gold standard for manufacturing of glycosylated recombinant proteins for production of biotherapeutics. the similarity of its glycosylation patterns to the human versions enable the products of this cell line favorable pharmacokinetic properties and lower likelihood of causing immunogenic responses. because glycan structures are the product of the concerted action of intracellular enzymes, it is difficult to predict a priori how the effects of genetic ...201728486471
xe991 and linopirdine are state-dependent inhibitors for kv7/kcnq channels that favor activated single subunits.m-channel inhibitors, especially xe991, are being used increasingly in animal experiments; however, insufficient characterization of xe991 at times confounds the interpretation of results when using this compound. here, we demonstrate that xe991 and linopirdine are state-dependent inhibitors that favor the activated-subunit of neuronal kv7/kcnq channels. we performed patch-clamp experiments on homomeric kv7.2 or heteromeric kv7.2/3 channels expressed in chinese hamster ovary cells to characteriz ...201728483800
preparative separation of monoclonal antibody aggregates by cation-exchange laterally-fed membrane chromatography.cation exchange (cex) chromatography is widely used for large-scale separation of monoclonal antibody (mab) aggregates. the aggregates bind more strongly to cex media and hence elute after the monomeric mab in a salt gradient. however, monomer-aggregate resolution that is typically obtained is poor, which results in low product recovery. in the current study we address this challenge through the use of cation-exchange laterally-fed membrane chromatography (lfmc). three different lfmc devices, ea ...201728477519
enhancing protein production yield from chinese hamster ovary cells by crispr interference.chinese hamster ovary (cho) cells are an important host for biopharmaceutical production. generation of stable cho cells typically requires cointegration of dhfr and a foreign gene into chromosomes and subsequent methotrexate (mtx) selection for coamplification of dhfr and foreign gene. crispr interference (crispri) is an emerging system that effectively suppresses gene transcription through the coordination of dcas9 protein and guide rna (grna). however, crispri has yet to be exploited in cho c ...201728418635
identification and control of novel growth inhibitors in fed-batch cultures of chinese hamster ovary cells.chinese hamster ovary (cho) cells in culture are known to consume large amounts of nutrients and divert most of them toward byproducts, some of which, including lactate and ammonia, are known to be toxic in nature. glucose limitation strategies can successfully control lactate accumulation in fed-batch cultures yielding higher peak cell densities and titers. interestingly, even in such optimized cultures, cell growth slows and eventually stops, indicating the emergence of other factors that nega ...201728409820
generation of peroxisome-deficient somatic animal cell mutants.cell mutants with a genetic defect affecting various cellular phenotypes are widely utilized as a powerful tool in genetic, biochemical, and cell biological research. more than a dozen complementation groups of animal somatic mutant cells defective in peroxisome biogenesis have been successfully isolated in chinese hamster ovary (cho) cells and used as a model system reflecting fatal human severe genetic disorders named peroxisome biogenesis disorders (pbd). isolation and characterization of per ...201728409474
azithromycin causes a novel proarrhythmic syndrome.the widely used macrolide antibiotic azithromycin increases risk of cardiovascular and sudden cardiac death, although the underlying mechanisms are unclear. case reports, including the one we document here, demonstrate that azithromycin can cause rapid, polymorphic ventricular tachycardia in the absence of qt prolongation, indicating a novel proarrhythmic syndrome. we investigated the electrophysiological effects of azithromycin in vivo and in vitro using mice, cardiomyocytes, and human ion chan ...201728408648
quantitative electron-microscopic studies of langerhans islets in normoglycemic chinese hamsters of a diabetic strain.on the basis of previous studies of the retina and the pituitary, normoglycemic chinese hamsters from a diabetic strain were divided into two groups, depending on the thickness of their capillary basement membrane and on the number of somatotrophs. both values were significantly lower in group i than in group ii. quantitative electron microscopy of the islets of langerhans showed in group ii a tendency to a volume increase for a-cells, to a decrease for d- and b-cells. also the number of b-granu ...2017362782
eel kisspeptins: identification, functional activity, and inhibition on both pituitary lh and gnrh receptor expression.the european eel (anguilla anguilla) presents a blockade of sexual maturation at a prepubertal stage due to a deficient production of gonadotropins. we previously initiated, in the eel, the investigation of the kisspeptin system, one of the major gatekeepers of puberty in mammals, and we predicted the sequence of twokissgenes. in the present study, we cloned and sequencedkiss1andkiss2cdnas from the eel brain. the tissue distributions ofkiss1andkiss2transcripts, as investigated by quantitative re ...201729375473
insights into the generation of monoclonal antibody acidic charge variants during chinese hamster ovary cell cultures.charge variation is one of the most important heterogeneities during monoclonal antibody (mab) manufacturing and this study presents insights into the generation of acidic charge variants during cell culture processes. since acidic variants generate both intracellularly and extracellularly, main charge fraction collected by weak cation exchange chromatography (wcx) was incubated in harvested cell supernatant (hcs) to simulate and investigate the extracellular process firstly. it is found that th ...201829238873
abin-1 negatively regulates μ-opioid receptor function.the μ-opioid receptor (mor) is a gi/o protein-coupled receptor that mediates analgesic, euphoric, and reward effects. using a bacterial two-hybrid screen, we reported that the carboxyl tail of the rat mor associates with a20-binding inhibitor of nuclear factor κb (abin-1). this interaction was confirmed by direct protein-protein binding and coimmunoprecipitation of mor and abin-1 proteins in cell lysates. saturation binding studies showed that abin-1 had no effect on mor binding. however, the in ...201829237725
haloacetic acid water disinfection byproducts affect pyruvate dehydrogenase activity and disrupt cellular metabolism.the disinfection of drinking water has been a major public health achievement. however, haloacetic acids (haas), generated as byproducts of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic, and teratogenic. previous studies of monohaa-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (gapdh), leading to disruption of cellular metabolism and energy homeostasis. dihaas and trihaas are also prod ...201829261292
development of novel oxazolo[5,4-d]pyrimidines as competitive cb2 neutral antagonists based on scaffold hopping.a series of novel oxazolo[5,4-d]pyrimidines was designed via a scaffold hopping strategy and synthesized through a newly developed approach. all these compounds were evaluated for their biological activity toward cb1/cb2 cannabinoid receptors, their metabolic stability in mice liver microsomes and their cytotoxicity against several cell lines. eight compounds have been identified as cb2 ligands with ki values less than 1 μm. it is noteworthy that 2-(2-chlorophenyl)-5-methyl-7-(4-methylpiperazin- ...201829360044
methods for using small non-coding rnas to improve recombinant protein expression in mammalian cells.the ability to produce recombinant proteins by utilizing different "cell factories" revolutionized the biotherapeutic and pharmaceutical industry. chinese hamster ovary (cho) cells are the dominant industrial producer, especially for antibodies. human embryonic kidney cells (hek), while not being as widely used as cho cells, are used where cho cells are unable to meet the needs for expression, such as growth factors. therefore, improving recombinant protein expression from mammalian cells is a p ...201829315258
using titer and titer normalized to confluence are complementary strategies for obtaining chinese hamster ovary cell lines with high volumetric productivity of etanercept.the selection of clonally-derived chinese hamster ovary (cho) cell lines with the highest production rate of recombinant glycoproteins remains a big challenge during early stages of cell line development. different strategies using either product titer or product titer normalized to cell number are being used to assess suspension-adapted clones when grown statically in microtiter plates. however, no reported study so far has performed a direct head-to-head comparison of these two early reporters ...201829359860
the genotoxicity of an aqueous extract of gyejibokryeong-hwan.gyejibokryeong-hwan (guizhi fuling wan in china), a mixture of five herbal plants, is a well-known treatment for renal diseases including those associated with climacteric syndrome. however, the genotoxicity of gyejibokryeong-hwan has not yet been well established.201829357857
comparative study of the effects of phosphatidylcholine rich in dha and epa on alzheimer's disease and the possible mechanisms in cho-app/ps1 cells and samp8 mice.metabolic stress induced by a high-fat (hf) diet leads to cognitive dysfunction and aging. in the present study, chinese hamster ovary cells stably transfected with amyloid precursor protein (app) and presenilin 1 (ps1) (cho-app/ps1 cells) and samp8 mice fed with an hf diet were used to study the effects of docosahexaenoic acid (dha)-enriched phosphatidylcholine (dha-pc) and eicosapentaenoic acid (epa)-enriched phosphatidylcholine (epa-pc) on alzheimer's disease (ad) and the possible mechanisms ...201829292421
the b cell death function of obinutuzumab-hdel produced in plant (nicotiana benthamiana l.) is equivalent to obinutuzumab produced in cho cells.plants have attracted attention as bio-drug production platforms because of their economical and safety benefits. the preliminary efficacy of zmapp, a cocktail of antibodies produced in n. benthamiana (nicotiana benthamiana l.), suggested plants may serve as a platform for antibody production. however, because the amino acid sequences of the fab fragment are diverse and differences in post-transcriptional processes between animals and plants remain to be elucidated, it is necessary to confirm fu ...201829324849
sirt3 activator honokiol attenuates β-amyloid by modulating amyloidogenic pathway.honokiol (poly-phenolic lignan from magnolia grandiflora) is a sirtuin-3 (sirt3) activator which exhibit antioxidant activity and augment mitochondrial functions in several experimental models. modern evidence suggests the critical role of sirt3 in the progression of several metabolic and neurodegenerative diseases. amyloid beta (aβ), the precursor to extracellular senile plaques, accumulates in the brains of patients with alzheimer's disease (ad) and is related to the development of cognitive i ...201829324783
ecotoxicological potential of the biocides terbutryn, octhilinone and methylisothiazolinone: underestimated risk from biocidal pathways?the use of biocides by industry, agriculture and households increased throughout the last two decades. many new applications with known substances enriched the variety of biocidal pollution sources for the aquatic environment. while agriculture was the major source for a long time, leaching from building facades and preservation of personal care and cleaning products was identified as new sources in the last few years. with the different usage forms of biocidal products the complexity of legisla ...201829306832
multiplexed digital mrna expression analysis profiles system-wide changes in mrna abundance and responsiveness of upr-specific gene expression changes during batch culture of recombinant chinese hamster ovary cells.the unfolded protein response (upr) signalling pathway is viewed as critical for setting the effectiveness of recombinant protein expression in cho cells. in this study, we used nanostring ncounter technology to study expression of a group of genes associated with cellular processes linked to upr activation under er stress and the changing environment of a batch culture. time course induction of er stress, using tunicamycin (tm), showed a group of genes such as chop, trb3, sqstm1, grp78 and herp ...201829323465
development of a chemically defined platform fed-batch culture media for monoclonal antibody-producing cho cell lines with optimized choline content.a chemically defined platform basal medium and feed media were developed using a single chinese hamster ovary (cho) cell line that produces a monoclonal antibody (mab). cell line a, which showed a peak viable cell density of 5.9 × 106 cells/ml and a final mab titer of 0.5 g/l in batch culture, was selected for the platform media development. stoichiometrically balanced feed media were developed using glucose as an indicator of cell metabolism to determine the feed rates of all other nutrients. a ...201829322349
effectiveness of aqueous and hydroalcoholic extracts of acanthospermum australe (loefl.) kuntze against diarrhea-inducing bacteria.leaves and roots of acanthospermum australe (asteraceae) have been used in brazilian folk medicine for the treatment of various ailments including diarrhea, skin diseases, blennorrhagia, dyspepsia, parasitic worms and malaria. the aim of study was to characterize the chemical profiles of the aqueous and hydroalcoholic extracts of leaves and roots of a. australe, and to evaluate their antimicrobial activities against diarrhea-inducing bacteria (enterococcus faecalis, shigella dysenteriae and yers ...201829319752
rna-seq highlights high clonal variation in monoclonal antibody producing cho cells.the development of next-generation sequencing technologies has opened new opportunities to better characterize complex eukaryotic cells. chinese hamster ovary (cho) cells play a primary role in therapeutic protein production, with currently five of the top ten blockbuster drugs produced in cho. however, engineering superior cho cells with improved production features has had limited success to date and cell lines are still developed through the generation and screening of large strain pools. her ...201829316330
glycoengineering in cho cells: advances in systems biology.for several decades, glycoprotein biologics have been successfully produced from chinese hamster ovary (cho) cells. the therapeutic efficacy and potency of glycoprotein biologics are often dictated by their post translational modifications, particularly glycosylation, which unlike protein synthesis, is a non-templated process. consequently, both native and recombinant glycoprotein production generate heterogeneous mixtures containing variable amounts of different glycoforms. stability, potency, ...201829316325
design and evaluation of a novel flavonoid-based radioprotective agent utilizing monoglucosyl rutin.in this study, three novel flavonoid composite materials, created by combining an aglycone [quercetin (que), hesperetin (hes) or naringenin (nar)] with monoglucosyl rutin (mgr), were designed to test for improved radioprotectivity compared with that provided by administration of mgr alone. aglycone in the mgr-composite state was highly soluble in water, compared with aglycone alone dissolved in dimethyl sulfoxide or distilled water. the antioxidant activity of the three flavonoid composites was ...201829373678
investigation into the mechanism of homo- and heterodimerization of angiotensin-converting enzyme.angiotensin-converting enzyme (ace) plays a central role in the renin-angiotensin system (ras), which is primarily responsible for blood pressure homeostasis. studies have shown that ace inhibitors yield cardiovascular benefits that cannot be entirely attributed to the inhibition of ace catalytic activity. it is possible that these benefits are due to interactions between ace and ras receptors that mediate the protective arm of the ras, such as the angiotensin-ii receptor type 2 (at2r) and the r ...201829371233
evaluation of reversed-phase nano liquid chromatography conditions by using reversed-phase thin layer chromatography based on hansen solubility parameters for the analysis of amphiphilic glycosylsphingolipid transformations.pulse chase analysis is often used in investigating dynamics of cellular substances. fluorescently labeled lactosyl sphingosine molecule is useful in chasing its transformation, however the analysis of such metabolites in attomole level is of extreme difficult due to the presence of large amount of endogenous amphiphilic molecules such as glycosphingolipids, sphingomyerin, and glycerophospholipids. nano lc suites for analyzing the attomole scale metabolites, therefore removal of endogenous subst ...201829290400
antigenotoxicity properties of copaifera multijuga oleoresin and its chemical marker, the diterpene (-)-copalic acid.in view of the biological activities and growing therapeutic interest in oleoresin obtained from copaifera multijuga, this study aimed to determine the genotoxic and antigenotoxic potential of this oleoresin (cmo) and its chemical marker, diterpene (-)-copalic acid (ca). the micronucleus (mn) assay in v79 cell cultures and the ames test were used for in vitro analyses, as well as mn and comet assays in swiss mice for in vivo analyses. the in vitro genotoxicity/mutagenicity results showed that ei ...201829286884
changes in chromosome counts and patterns in cho cell lines upon generation of recombinant cell lines and subcloning.chinese hamster ovary cells are the number one production system for therapeutic proteins. a pre-requirement for their use in industrial production of biopharmaceuticals is to be clonal, thus originating from a single cell in order to be phenotypically and genomically identical. in the present study it was evaluated whether standard procedures, such as the generation of a recombinant cell line in combination with selection for a specific and stable phenotype (expression of the recombinant produc ...201829328552
substance p as a putative efferent transmitter mediates gabaergic inhibition in mouse taste buds.capsaicin-mediated modulation on taste nerve responses is thought to be produced indirectly by actions of neuropeptides, e.g., calcitonin gene-related peptide (cgrp) and substance p (sp), onto taste cells implying playing a role in taste sensitivity. during processing gustatory information in taste buds, cgrp shapes peripheral taste signals via serotonergic signaling. the underlying assumption has been that sp exerts its effects on taste transmitter secretion in taste buds of mice.201829328505
development of a novel 99m tc-labelled small molecular antagonist for cxcr4 positive tumor imaging.the chemokine receptor 4 (cxcr4) has been an attractive molecular target for tumor imaging, since it is overexpressed in many tumor types and involved in tumor progression and metastasis. the purpose of this study is to examine the cxcr4 targeting properties of 99m tc-labeled amd3465, a small molecule antagonist of cxcr4. 99m tc-amd3465 was prepared in high yield (>95%) and stable in mice serum at least for 4 h. in vitro cell binding experiments were performed with cho (chinese hamster ovary), m ...201829370457
opp labelling enables total protein synthesis quantification in cho production cell lines at the single-cell level.accurate measurement of global and specific protein synthesis rates becomes increasingly important, especially in the context of biotechnological applications such as process modelling or selection of production cell clones. while quantification of total protein translation across whole cell populations is easily achieved, methods that are capable of tracking population dynamics at the single-cell level are still lacking. to address this need, we applied o-propargyl-puromycin (opp) labelling to ...201829369524
enhanced production of anti-pd1 antibody in cho cells through transient co-transfection with anti-apoptotic genes bcl-x l and mcl-1.apoptosis has a negative impact on the cell survival state during cell cultivation. to optimize mammalian cell culture for production of biopharmaceuticals, one of the important approaches is to extend cell life through over-expression of anti-apoptotic genes. here, we reported a cost-effective process to enhance cell survival and production of an antibody through transient co-transfection with anti-apoptotic genes bcl-x l or mcl-1 in chinese hamster ovary (cho) cells with polyethylenimine (pei) ...201829368032
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