Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
antibody selection for cancer target validation of fsh-receptor in immunohistochemical settings.the follicle-stimulating hormone (fsh)-receptor (fshr) has been reported to be an attractive target for antibody therapy in human cancer. however, divergent immunohistochemical (ihc) findings have been reported for fshr expression in tumor tissues, which could be due to the specificity of the antibodies used.201731548530
comparison of cell-based versus cell-free mammalian systems for the production of a recombinant human bone morphogenic growth factor.the human bone morphogenetic protein-2 (hbmp2) is a glycoprotein, which induces de novo bone formation. here, recombinant production in stably transfected chinese hamster ovary (cho) cells is compared to transient expression in human embryo kidney (hek) cells and cell-free synthesis in cho cell lysates containing microsomal structures as sites of post-translational processing. in case of the stably transfected cells, growth rates and viabilities were similar to those of the parent cells, while e ...201732624737
assessment of genotoxic effects of pendimethalin in chinese hamster over cells by the single cell gel electrophoresis (comet) assay.pendimethalin (n-(1-ethylpropyl)-3,4-dimethyl-2,6-dinitrobenzeneamine) is a dinitroaniline herbicide compound which selectively controls weeds. it is a cell division and growth inhibitor. it descends plants in a short time after seedling. it is a soil and water pollutant due to the widespread use of formulations in turkey and around the world. pendimethalin is manufactured in and imported by turkey. pendimethalin is a slightly toxic compound that is classified in toxicity class 3 by the united s ...201732454612
assessment of cytotoxicity profiles of different phytochemicals: comparison of neutral red and mtt assays in different cells in different time periods.phenolic compounds exhibit several health protective properties. galangin, curcumin, pycnogenol, puerarin and ursolic acid are commonly used plant phenolics in folk medicine. the aim of our study was to evaluate the difference between neutral red uptake (nru) and mtt assays using different plant phenolics (galangin, curcumin, pycnogenol, puerarin and ursolic acid) in healthy and cancer cells in different time periods.201732454600
effect of adenovirus infection on transgene expression under the adenoviral mlp/tpl and the cmvie promoter/enhancer in cho cells.the adenovirus major late promoter (mlp) and its translational regulator - the tripartite leader (tpl) sequence - can actively drive efficient gene expression during adenoviral infection. however, both elements have not been widely tested in transgene expression outside of the adenovirus genome context. in this study, we tested whether the combination of mlp and tpl would enhance transgene expression beyond that of the most widely used promoter in transgene expression in mammalian cells, the cyt ...201730647657
producing defucosylated antibodies with enhanced in vitro antibody-dependent cellular cytotoxicity via fut8 knockout cho-s cells.to engineer a host cell line that produces defucosylated mabs with superior antibody-dependent cellular cytotoxicity, we disrupted α-1, 6 fucosyltransferase (fut8) gene in cho-s (cho is chinese hamster ovary) cells by clustered regularly interspaced short palindromic repeats-crispr associated nuclease 9. the gene knockout cell line was evaluated for growth, stability, and product quality. the growth profile of fut8 gene knockout cho-s (fut8-/-) cells was comparable with wild type cho-s cells. fu ...201732624826
impact of cell lysis on the description of cell growth and death in cell culture.the primary task of process development is a process design that guarantees product quality and maximizes product quantity. one part of the process development is the identification of critical process parameters. especially in cell culture processes, unwanted cell damage as critical process parameter is still challenging in stirred tank reactors and needs therefore to be considered. nevertheless, this topic and its effects on process performance are currently not well discussed and not verified ...201732624789
overexpression of grp78 enhances survival of cho cells in response to serum deprivation and oxidative stress.chinese hamster ovary (cho) cells are regarded as one of the most commonly used mammalian hosts, which decreases the productivity due to loss in culture viability. overexpressing antiapoptosis genes in cho cells was developed as a means of limiting cell death upon exposure to environmental insults. glucose-regulated protein 78 (grp78) is traditionally regarded as a major er chaperone that participates in protein folding and other cell processes. it is also a potent antiapoptotic protein and play ...201732624757
laccase-mediated enhancement of the antioxidant activity of propolis and poplar bud exudates.the treatment of propolis and poplar bud exudates with laccase from trametes versicolor and 2,2,6,6-tetramethyl-1-piperidinyloxy free radical increased the antioxidant activity, as evaluated by the 2,2'-diphenyl picrylhydrazyl (dpph)- and t-butyl-ooh-induced dna breakage comet assay analyses. the effect was highest for shorter reaction times. propolis showed the highest antioxidant activity in the dpph test, whereas poplar bud exudates were more active in reducing the t-butyl-ooh-induced lesions ...201730023668
antioxidant and cancer chemopreventive activities of cistus and pomegranate polyphenols.polyphenol rich extracts obtained from cistus herb (cistus incanus l.) and pomegranate peel (punica granatum l.) exhibited significant antioxidant activity in v79 cell culture (chinese hamster lung fibroblasts) -cistus extract reduced intracellular content of reactive oxygen species (ros) by 30-40% and pomegranate extract by 29-36%. in human breast (mcf-7) and colon (lovo) cancer cell lines cistus and pomegranate extracts decreased cancer cell growth both in drug-sensitive cells by 15-30% and in ...201729624275
conditions of prooxidant activity of cistus and pomegranate polyphenols in v79 cell cultures.polyphenol rich extracts obtained from cistus herb (cistus incanus l.) and pomegranate peels (punica granatunm l.) added at high concentrations (25-100 pg/ml) to v79 (chinese hamster lung fibroblast) cell cultures, markedly increased intracellular level of ros (reactive oxygen species). also in cells exposed to the exogenous oxidant - h₂0₂, [100 μm, 30 min., 37'c] intracellular ros level was augmented, although to a lower extent than in resting cells not exposed to h₂0₂. additionally, cistus and ...201729624273
pm2.5 obtained from urban areas in beijing induces apoptosis by activating nuclear factor-kappa b.particulate matter (pm), which has adverse effects on citizen health, is a major air pollutant in beijing city. pm2.5 is an indicator of pm in urban areas and can cause serious damage to human health. many epidemiological studies have shown that nuclear factor-kappa b (nf-κb) is involved in pm2.5-induced cell injury, but the exact mechanisms are not well understood.201729502513
discovery of potent 2,4-difluoro-linker poly(adp-ribose) polymerase 1 inhibitors with enhanced water solubility and in vivo anticancer efficacy.poly (adp-ribose) polymerase 1 (parp1) is overexpressed in a variety of cancers, especially in breast and ovarian cancers; tumor cells that are deficient in breast cancer gene 1/2 (brca1/2) are highly sensitive to parp1 inhibition. in this study, we identified a series of 2,4-difluorophenyl-linker analogs (15-55) derived from olaparib as novel parp1 inhibitors. four potent analogs 17, 43, 47, and 50 (ic50=2.2-4.4 nmol/l) effectively inhibited the proliferation of chinese hamster lung fibroblast ...201728770827
over-expression of a codon optimized yeast cytosolic pyruvate carboxylase (pyc2) in cho cells for an augmented lactate metabolism.monoclonal antibodies are the most demanding biotherapeutic drugs now a days used for the cure of various critical illnesses. chinese hamster ovary (cho) cells are one of the main hosts used for the large scale production of these antibodies. however, the cell line and production processes are the key factors to determine the cost and affordability of these antibodies. the metabolic waste lactic acid and ammonium are accumulated during a cell culture process and adversely affects productivity as ...201728769797
in vitro genotoxicity of asbestos substitutes induced by coupled stimulation of dissolved high-valence ions and oxide radicals.the wide use of asbestos and its substitutes has given rise to studies on their possible harmful effects on human health and environment. however, their toxic effects remain unclear. the present study was aimed to disclose the coupled effects of dissolved high-valence ions and oxide radicals using the in vitro cytotoxicity and genotoxicity of chrysotile (ca), nano-sio2 (ns), ceramic fiber (cf), glass fiber (gf), and rock wool (rw) on chinese hamster lung cells v79. all samples induced cell morta ...201728766145
structural basis and genotype-phenotype correlations of insr mutations causing severe insulin resistance.the insulin receptor (insr) gene was analyzed in four patients with severe insulin resistance, revealing five novel mutations and a deletion that removed exon 2. a patient with donohue syndrome (ds) had a novel p.v657f mutation in the second fibronectin type iii domain (fniii-2), which contains the α-β cleavage site and part of the insulin-binding site. the mutant insr was expressed in chinese hamster ovary cells, revealing that it reduced insulin proreceptor processing and impaired activation o ...201728765322
metabolic engineering of cho cells for the development of a robust protein production platform.chinese hamster ovary (cho) cells are the most preferred mammalian host used for the bio-pharmaceutical production. a major challenge in metabolic engineering is to balance the flux of the tuned heterogonous metabolic pathway and achieve efficient metabolic response in a mammalian cellular system. pyruvate carboxylase is an important network element for the cytoplasmic and mitochondrial metabolic pathway and efficiently contributes in enhancing the energy metabolism. the lactate accumulation in ...201728763459
hinge-deficient igg1 fc fusion: application to human lactoferrin.fusion of therapeutic proteins with the antibody fc domain is a strategy widely applied to increase protein half-life in plasma. in our previous study, we generated a recombinant human lactoferrin (hlf)-immunoglobulin g1 fc fusion protein (hlf-hinge-ch2-ch3) with improved stability, biological activity, and pharmacokinetics ( shiga , y. et al. eur j pharm sci. , 2015 , 67 , 136 - -143 ). however, the fc domain in fusion proteins can potentially induce antibody-dependent and complement-dependent ...201728763236
ursolic acid activates the tgr5 receptor to enhance glp-1 secretion in type 1-like diabetic rats.endogenous takeda g-protein-coupled receptor 5 (tgr5), g-protein-coupled bile acid receptor 1 (gpbar1), regulates glucose metabolism. in animals, tgr5 activation by a chemical agonist may increase incretin secretion and reduce the blood sugar level. recently, betulinic acid has been suggested to activate tgr5. ursolic acid is a well-known pentacyclic triterpenoid that is similar to betulinic acid. it is of special interest to determine the potential effect of ursolic acid on tgr5. therefore, we ...201728756460
glycosylation flux analysis reveals dynamic changes of intracellular glycosylation flux distribution in chinese hamster ovary fed-batch cultures.n-linked glycosylation of proteins has both functional and structural significance. importantly, the glycan structure of a therapeutic protein influences its efficacy, pharmacokinetics, pharmacodynamics and immunogenicity. in this work, we developed glycosylation flux analysis (gfa) for predicting intracellular production and consumption rates (fluxes) of glycoforms, and applied this analysis to cho fed-batch immunoglobulin g (igg) production using two different media compositions, with and with ...201728754360
sensitization of asic3 by proteinase-activated receptor 2 signaling contributes to acidosis-induced nociception.tissue acidosis and inflammatory mediators play critical roles in pain. pro-inflammatory agents trypsin and tryptase cleave and activate proteinase-activated receptor 2 (par2) expressed on sensory nerves, which is involved in peripheral mechanisms of inflammation and pain. extracellular acidosis activates acid-sensing ion channel 3 (asic3) to trigger pain sensation. here, we show that a functional interaction of par2 and asic3 could contribute to acidosis-induced nociception.201728754162
microfluidic cell retention device for perfusion of mammalian suspension culture.continuous production of biologics, a growing trend in the biopharmaceutical industry, requires a reliable and efficient cell retention device that also maintains cell viability. current filtration methods, such as tangential flow filtration using hollow-fiber membranes, suffer from membrane fouling, leading to significant reliability and productivity issues such as low cell viability, product retention, and an increased contamination risk associated with filter replacement. we introduce a novel ...201728751635
calcineurin dysregulation underlies spinal cord injury-induced k+ channel dysfunction in drg neurons.dysfunction of the fast-inactivating kv3.4 potassium current in dorsal root ganglion (drg) neurons contributes to the hyperexcitability associated with persistent pain induced by spinal cord injury (sci). however, the underlying mechanism is not known. in light of our previous work demonstrating modulation of the kv3.4 channel by phosphorylation, we investigated the role of the phosphatase calcineurin (can) using electrophysiological, molecular, and imaging approaches in adult female sprague daw ...201728751455
bilayered nanoparticles with sequential release of vegf gene and paclitaxel for restenosis inhibition in atherosclerosis.complete reendothelialization followed by inhibition of smooth muscle cell (smc) proliferation is considered as an effective therapeutic option to prevent restenosis. we have designed poly(lactide-co-glycolide)-loaded bilayered nanoparticles (nps) with the ability to sequentially release vascular endothelial growth factor (vegf)-encoding plasmids from the outer layer and paclitaxel (ptx) from the core to promote endothelial regeneration as well as prevent restenosis. comparing with conventional ...201728748694
modulation of the plasma kallikrein-kinin system proteins performed by heparan sulfate proteoglycans.human plasma kallikrein-kinin system proteins are related to inflammation through bradykinin. in the proximity of its target cells, high molecular weight kininogen (h-kininogen) is the substrate of plasma kallikrein, which releases bradykinin from h-kininogen. heparan sulfate proteoglycans (hspgs) play a critical role in either recruiting kinin precursors from the plasma, or in the assembly of kallikrein-kinin system components on the cell surface. furthermore, hspgs mediate the endocytosis and ...201728744223
sumoylation determines the voltage required to activate cardiac iks channels.iks channels open in response to depolarization of the membrane voltage during the cardiac action potential, passing potassium ions outward to repolarize ventricular myocytes and end each beat. here, we show that the voltage required to activate iks channels depends on their covalent modification by small ubiquitin-like modifier (sumo) proteins. iks channels are comprised of four kcnq1 pore-forming subunits, two kcne1 accessory subunits, and up to four sumos, one on lys424 of each kcnq1 subunit. ...201728743749
activation of liver x receptor inhibits oct2-mediated organic cation transport in renal proximal tubular cells.liver x receptor (lxr) is transcriptional factor that plays an important role in the regulation of energy metabolism such as cholesterol, lipid, and glucose metabolism as well as membrane transporters and channels. using both in vitro and in vivo models, lxr regulation of the expression and function of renal organic cation transporter 2 (oct2) was observed. synthetic lxr agonist (gw3965) and endogenous lxr agonist (22r-hydroxycholesterol) significantly reduced the uptake of 3h-mpp+, a prototypic ...201728741179
pmab-52: specific and sensitive monoclonal antibody against cat podoplanin for immunohistochemistry.podoplanin (pdpn) is expressed in several normal tissues, such as lymphatic endothelial cells, podocytes of renal glomerulus, and type i alveolar cells of lung. pdpn activates platelet aggregation by binding to c-type lectin-like receptor-2 (clec-2) on platelet. although monoclonal antibodies (mabs) against human pdpn, mouse pdpn, rat pdpn, rabbit pdpn, dog pdpn, and bovine pdpn have been established, anticat pdpn (cpdpn) mabs have not been developed. in this study, we immunized mice with chines ...201728737447
comparative proteomic analysis of three chinese hamster ovary (cho) host cells.chinese hamster ovary (cho) cells have been widely used to express heterologous genes and produce therapeutic proteins in biopharmaceutical industry. different cho host cells have distinct cell growth rates and protein expression characteristics. in this study, the expression of about 1,307 host proteins in three sublines, i.e. cho k1, cho s and cho/dihydrofolate reductase (dhfr)- , were investigated and compared using proteomic analysis. the proteins involved in cell growth, glycolysis, tricarb ...201728736500
preselection of recombinant gene integration sites enabling high transcription rates in cho cells using alternate start codons and recombinase mediated cassette exchange.site-specific recombinase mediated cassette exchange (rmce) enables the transfer of the gene of interest (goi) into pre-selected genomic locations with defined expression properties. for the generation of recombinant production cell lines, this has the advantage that screening for high transcription rates at the genome integration site would be required only once, with the possibility to reuse the selected site for new products. here, we describe a strategy that aims at the selection of transcri ...201728734047
aryl- and alkyl-phosphorus-containing flame retardants induced mitochondrial impairment and cell death in chinese hamster ovary (cho-k1) cells.phosphorus-containing flame retardants (pfrs) are increasingly in demand worldwide as replacements for brominated flame retardants (bfrs), but insufficient available toxicological information on pfrs makes assessing their health risks challenging. mitochondria are important targets of various environmental pollutants, and mitochondrial dysfunction may lead to many common diseases. in the present study, mitochondria impairment-related endpoints were measured by a high content screening (hcs) assa ...201728732339
computational modelling of genome-scale metabolic networks and its application to cho cell cultures.genome-scale metabolic models (gems) have become increasingly important in recent years. currently, gems are the most accurate in silico representation of the genotype-phenotype link. they allow us to study complex networks from the systems perspective. their application may drastically reduce the amount of experimental and clinical work, improve diagnostic tools and increase our understanding of complex biological phenomena. gems have also demonstrated high potential for the optimisation of bio ...201728732234
development of a fluorescent reporter system for monitoring er stress in chinese hamster ovary cells and its application for therapeutic protein production.mammalian cell expression systems have become a workhorse for the production of biotherapeutic proteins. as such, there is an ever increasing demand for higher productivity from these expression platforms to reduce manufacturing costs. while great advances have been made in the optimization of culture conditions and cell line selection to improve productivity, protein mis-folding remains a common limitation to high levels of production of therapeutic proteins. accumulation of mis- and unfolded p ...201728832690
role of the oatp transporter family and a benzbromarone-sensitiveefflux transporter in the hepatocellular disposition of vincristine.vincristine is known to interfere with oatp-mediated uptake of other compounds, hinting that vincristine itself could be a substrate of oatp transporters. the present study therefore aimed to investigate the role of oatp transporters in the hepatocellular disposition of vincristine.201728828541
in vitro genotoxicity of airborne ni-np in air-liquid interface.studies using advanced toxicological methods enabling in vitro conditions that are more realistic are currently needed for understanding the risks of pulmonary exposure to airborne nanoparticles. owing to the carcinogenicity of certain nickel compounds, the increased production of nickel nanoparticles (ni-nps) raises occupational safety concerns. the aim of this study was to investigate the genotoxicity of airborne ni-nps using a recently developed air-liquid interface exposure system. the wild- ...201728815640
the glucagon-like peptide-1 receptor in the ventromedial hypothalamus reduces short-term food intake in male mice by regulating nutrient sensor activity.pharmacological activation of the glucagon-like peptide-1 receptor (glp-1r) in the ventromedial hypothalamus (vmh) reduces food intake. here, we assessed whether suppression of food intake by glp-1r agonists (glp-1ra) in this region is dependent on amp-activated protein kinase (ampk) and mammalian target of rapamycin (mtor). we found that pharmacological inhibition of glycolysis, and thus activation of ampk, in the vmh attenuates the anorectic effect of the glp-1r agonist exendin-4 (ex4), indica ...201728811293
rapid characterization of the cho platform cell line and identification of pseudo attp sites for phic31 integrase.the chinese hamster ovary (cho) cell lines, applicable to post-translational modifications, are preferred systems for biopharmaceutical protein production. in this study, by using the jump-in™ ti™ technology which employs phic31 and r4 bacteriophage recombinases, a platform cho-k1 cell line containing a r4-attp site was generated. here, a combination of quantitative fluorescent-polymerase chain reaction (qf-pcr) and semi-random, two-step pcr (st-pcr), was performed to feature the platform cell c ...201728802644
dna methylation in cho cells.chinese hamster ovary (cho) cells account for the production of the majority of biopharmaceutical molecules - however, the molecular basis for their versatile properties is not entirely understood yet and the underlying cellular processes need to be characterized in detail. one such process that is supposed to contribute significantly to cho cell phenotype is methylation of dna at cytosine residues. dna methylation was shown to be involved in several central biological processes in humans and to ...201728801067
fluorescent polymer nanoparticles for cell barcoding in vitro and in vivo.fluorescent polymer nanoparticles for long-term labeling and tracking of living cells with any desired color code are developed. they are built from biodegradable poly(lactic-co-glycolic acid) polymer loaded with cyanine dyes (dio, dii, and did) with the help of bulky fluorinated counterions, which minimize aggregation-caused quenching. at the single particle level, these particles are ≈20-fold brighter than quantum dots of similar color. due to their identical 40 nm size and surface properties, ...201728791769
internalization of rat fsh and lh/cg receptors by rec-ecg in cho-k1 cells.equine chorionic gonadotropin (ecg) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (fsh) and luteinizing hormone (lh) in other species. previous studies from this laboratory had demonstrated that recombinant ecg (rec-ecg) from chinese hamster ovary (cho-k1) cells exhibited both fsh- and lh-like activity in rat granulosa and leydig cells. in this study, we analyzed receptor internalization through rec-ecgs, wild type ecg (ecgβ/α) and mutant ecg ...201728791335
alteration of the pi3k/akt signaling pathway by swainsonine affects 17β-estradiol secretion in ovary cells.the ingestion of locoweed that contains the toxic indolizidine alkaloid swainsonine (sw) disrupts ovarian function, accompanied by delayed estrus, increased estrous cycle length, delayed conception, and abortion.201728780483
adoption of the q transcriptional system for regulating gene expression in stem cells.the field of mammalian synthetic biology seeks to engineer enabling technologies to create novel approaches for programming cells to probe, perturb, and regulate gene expression with unprecedented precision. to accomplish this, new genetic parts continue to be identified that can be used to build novel genetic circuits to re-engineer cells to perform specific functions. here, we establish a new transcription-based genetic circuit that combines genes from the quinic acid sensing metabolism of neo ...201728776984
cho cell cytotoxicity and genotoxicity analyses of disinfection by-products: an updated review.the disinfection of drinking water is an important public health service that generates high quality, safe and palatable tap water. the disinfection of drinking water to reduce waterborne disease was an outstanding public health achievement of the 20th century. an unintended consequence is the reaction of disinfectants with natural organic matter, anthropogenic contaminants and bromide/iodide to form disinfection by-products (dbps). a large number of dbps are cytotoxic, neurotoxic, mutagenic, ge ...201728774627
zebrafish embryo toxicity of 15 chlorinated, brominated, and iodinated disinfection by-products.disinfection to protect human health occurs at drinking water and wastewater facilities through application of non-selective oxidants including chlorine. oxidants also transform organic material and form disinfection by-products (dbps), many of which are halogenated and cyto- and genotoxic. only a handful of assays have been used to compare dbp toxicity, and researchers are unsure which dbp(s) drive the increased cancer risk associated with drinking chlorinated water. the most extensive data set ...201728774621
investigation of nuclear enzyme topoisomerase as a putative molecular target of monohaloacetonitrile disinfection by-products.disinfection by-products occur widely as the unintended effect of water disinfection and are associated with toxicity and adverse human health effects. yet the molecular mechanisms of their toxicity are not well understood. to investigate the molecular basis of hyperploidy induction by monohaloacetonitriles, the interaction of monohaloacetonitriles with topoisomerase ii in chinese hamster ovary cells was examined. we showed a concentration-dependent inhibition of dna decatenation activity of top ...201728774614
characterization of a cathepsin d protease from cho cell-free medium and mitigation of its impact on the stability of a recombinant therapeutic protein.during purification process development of a recombinant therapeutic protein, an endoproteolytic activity endogenous to the chinese hamster ovary (cho) cells and leading to degradation at particular hydrophobic amino acid residues (e.g., phe and trp) was observed when processing at acidic ph. the presence of residual levels of protease activity in purified protein batches affected the inherent activity of the product when stored as a solution. to develop a robust purification strategy to minimiz ...201728726323
polymer-mediated flocculation of transient cho cultures as a simple, high throughput method to facilitate antibody discovery.most biopharmaceutical drugs, especially monoclonal antibodies (mabs), bispecific antibodies (bsabs) and fc-fusion proteins, are expressed using chinese hamster ovary (cho) cell lines. cho cells typically yield high product titers and high product quality. unfortunately, cho cell lines also generate high molecular weight (hmw) aggregates of the desired product during cell culture along with cho host cell protein (hcp) and cho dna. these immunogenic species, co-purified during protein a purificat ...201728722325
inhibitory modulation of human estrogen receptor α and β activities by dicyclohexyl phthalate in human breast cancer cell lines.phthalate esters (paes) are man-made compounds that are used widely in industry, and the ubiquitous exposure of humans to paes has been reported. although some paes have been suggested to function as xenoestrogens in in vitro systems, such as human estrogen receptors (ers) expressed in chinese hamster ovary (cho)-k1 cells, few studies have attempted to elucidate whether paes affect human erα/erβ-mediated signaling in human breast cancer cells (i.e., combination between human ers and human cells) ...201728717100
a short synthetic chimeric sequence harboring matrix attachment region/psar2 increases transgene expression in chinese hamster ovary cells.a chimeric dna fragment containing an interferon-beta matrix attachment region (mar) and an immunoglobulin mar (psar2) was synthesized. psar2 was cloned into the upstream or downstream region of an enhanced green fluorescent protein (egfp) expression cassette in a eukaryotic vector, which was then transfected into cho cells. the results showed that psar2 did not effectively increase transgene expression when it was cloned into the upstream region of the egfp expression cassette. however, when in ...201728715274
on-line prediction of the glucose concentration of cho cell cultivations by nir and raman spectroscopy: comparative scalability test with a shake flask model system.in this study, near-infrared (nir) and raman spectroscopy were compared in parallel to predict the glucose concentration of chinese hamster ovary cell cultivations. a shake flask model system was used to quickly generate spectra similar to bioreactor cultivations therefore accelerating the development of a working model prior to actual cultivations. automated variable selection and several pre-processing methods were tested iteratively during model development using spectra from six shake flask ...201728711673
quantitative intracellular flux modeling and applications in biotherapeutic development and production using cho cell cultures.chinese hamster ovary (cho) cells have been widely used for producing many recombinant therapeutic proteins. constraint-based modeling, such as flux balance analysis (fba) and metabolic flux analysis (mfa), has been developing rapidly for the quantification of intracellular metabolic flux distribution at a systematic level. such methods would produce detailed maps of flows through metabolic networks, which contribute significantly to better understanding of metabolism in cells. although these ap ...201728710856
toxicity of wastewater with elevated bromide and iodide after chlorination, chloramination, or ozonation disinfection.water reuse is receiving unprecedented attention as many areas around the globe attempt to better-manage their fresh water resources. wastewaters in coastal regions may contain elevated levels of bromide (br-) and iodide (i-) from seawater intrusion or high mineral content in the source waters. disinfection of such wastewater is essential to prevent the spread of pathogens; however, little is known about the toxicity of the treated wastewater. in this study, we evaluated the genotoxicity to chin ...201728691804
assessing and resolving model misspecifications in metabolic flux analysis.metabolic flux analysis (mfa) is an indispensable tool in metabolic engineering. the simplest variant of mfa relies on an overdetermined stoichiometric model of the cell's metabolism under the pseudo-steady state assumption to evaluate the intracellular flux distribution. despite its long history, the issue of model error in overdetermined mfa, particularly misspecifications of the stoichiometric matrix, has not received much attention. we evaluated the performance of statistical tests from line ...201728952528
metabolic characterization of a cho cell size increase phase in fed-batch cultures.normally, the growth profile of a cho cell fed-batch process can be divided into two main phases based on changes in cell concentration, being an exponential growth phase and a stationary (non-growth) phase. in this study, an additional phase is observed during which the cell division comes to a halt but the cell growth continues in the form of an increase in cell size. the cell size increase (si) phase occurs between the exponential proliferation phase (also called the number increase or ni pha ...201728951949
13c metabolic flux analysis identifies limitations to increasing specific productivity in fed-batch and perfusion.industrial cell culture requires substantial energy to generate protein. the protein generated is not only the product of interest (igg in this case), but also the protein associated with biomass. here, 13c-metabolic flux analysis (13c-mfa) was utilized to compare the stationary phase of a fed-batch process to a perfusion process producing the same product by the same clone. the fed-batch process achieved significantly higher specific productivity, approximately 60% greater than the perfusion pr ...201728951188
multimodal chromatography for purification of biotherapeutics - a review.process chromatography forms the core of purification of biotherapeutics. the unparalleled selectivity that it offers over other alternatives combined with the considerable robustness and scalability make it the unit operation of choice in downstream processing. it is typical to have three to five chromatography steps in a purification process for a biotherapeutic. generally, these steps offer different modes of separation such as ion-exchange, reversed phase, size exclusion, and hydrophobic int ...201729065828
development of bioassay system for evaluation of materials for personal protective equipment (ppe) against toxic effects of ionizing radiations.health effects caused by ionizing radiations raise considerable concern among general public and radiation workers. to estimate ability of personal protective equipment (ppe) materials that reduce toxic effects of ionizing radiations, we developed an experimental bioassay system using chinese hamster v79 cells. the system developed here distinguished the biological effectiveness of x-ray that was significantly affected by elements composed of shielding materials. survival of the cells exposed to ...201729021414
duodenal cytochrome b (cybrd1) ferric reductase functional studies in cells.dietary non-heme ferric iron is reduced by the ferric reductase enzyme, duodenal cytochrome b (dcytb), before absorption by the divalent metal transporter 1 (dmt1). a single nucleotide polymorphism (snp rs10455 mutant) that is located in the last exon of the dcytb gene was reported in c282y haemochromatosis hfe subjects. the present work therefore investigated the phenotype of this mutant dcytb in chinese hamster ovary (cho) cells. these cultured cells were transfected with either wild type (wt) ...201728937159
cell-free synthesis of functional antibodies using a coupled in vitro transcription-translation system based on cho cell lysates.antibodies are indispensable tools for basic research as well as diagnostic and therapeutic applications. consequently, the development of alternative manufacturing strategies which circumvent the hurdles connected to conventional antibody production technologies is of enormous interest. to address this issue, we demonstrate the synthesis of complex antibody formats, in particular immunoglobulin g (igg) and single-chain variable fragment fc fusion (scfv-fc), in a microsome-containing cell-free s ...201728931913
combinatorial genome and protein engineering yields monoclonal antibodies with hypergalactosylation from cho cells.one of the key quality attributes of monoclonal antibodies is the glycan pattern and distribution. two terminal galactose residues typically represent a small fraction of the total glycans from antibodies. however, antibodies with defined glycosylation properties including enhanced galactosylation have been shown to exhibit altered properties for these important biomedical modalities. in this study, the disruption of two α-2,3 sialyltransferases (st3gal4 and st3gal6) from chinese hamster ovary ( ...201728926673
methylglyoxal attenuates insulin signaling and downregulates the enzymes involved in cholesterol biosynthesis.methylglyoxal (mg) is a highly reactive dicarbonyl known to be elevated under the hyperglycemic conditions of diabetes and is implicated in the development of diabetic complications. therefore, the current study investigates the role of mg in exacerbating insulin resistance at the insulin signaling level, as well as its effect on the global proteomic level. by using insulin sensitive rat muscle cells (l6) and chinese hamster ovary (cho) cells stably expressing the insulin receptor (ir) and a glu ...201728926063
evaluation of genotoxicity and subchronic toxicity of standardized rose hip extract.rose hip is the fruit of the rose plant, which is widely used in food, cosmetics and as a traditional medicine. therefore, rose hip is considered safe and has a sufficient history of consumption as food. however, few studies have reported on the safety of rose hip extracts in toxicological analyses. thus, to evaluate the safety of rosehip polyphenol mj (rhpmj), an aqueous ethanol extract standardized with the trans-tiliroside content, we performed genotoxicity and 90-day repeated oral dose toxic ...201728920463
adipokinetic hormone receptor gene identification and its role in triacylglycerol mobilization and sexual behavior in the oriental fruit fly (bactrocera dorsalis).energy homeostasis requires continuous compensation for fluctuations in energy expenditure and availability of food resources. in insects, energy mobilization is under control of the adipokinetic hormone (akh) where it is regulating the nutritional status by supporting the mobilization of lipids. in this study, we characterized the gene coding for the akh receptor (akhr) and investigated its function in the oriental fruit fly (bactrocera dorsalis) that is economically one of the most important p ...201728919559
refractive index imaging of cells with variable-angle near-total internal reflection (tir) microscopy.the refractive index in the interior of single cells affects the evanescent field depth in quantitative studies using total internal reflection (tir) fluorescence, but often that index is not well known. we here present method to measure and spatially map the absolute index of refraction in a microscopic sample, by imaging a collimated light beam reflected from the substrate/buffer/cell interference at variable angles of incidence. above the tir critical angle (which is a strong function of refr ...201728918767
high-yield production of "difficult-to-express" proteins in a continuous exchange cell-free system based on cho cell lysates.cell-free protein synthesis (cfps) represents a promising technology for efficient protein production targeting especially so called "difficult-to-express" proteins whose synthesis is challenging in conventional in vivo protein production platforms. chinese hamster ovary (cho) cells are one of the most prominent and safety approved cell lines for industrial protein production. in this study we demonstrated the ability to produce high yields of various protein types including membrane proteins an ...201728916746
costunolide induces micronuclei formation, chromosomal aberrations, cytostasis, and mitochondrial-mediated apoptosis in chinese hamster ovary cells.costunolide (ce) is a sesquiterpene lactone well-known for its antihepatotoxic, antiulcer, and anticancer activities. the present study focused on the evaluation of the cytogenetic toxicity and cellular death-inducing potential of ce in cho cells, an epithelial cell line derived from normal ovary cells of chinese hamster. the cytotoxic effect denoting mtt assay has shown an ic50 value of 7.56 μm ce, where 50% proliferation inhibition occurs. the oxidative stress caused by ce was confirmed based ...201728914393
delayed effects of accelerated heavy ions on the induction of hprt mutations in v79 hamster cells.fundamental research on the harmful effects of ionizing radiation on living cells continues to be of great interest. recently, priority has been given to the study of high-charge and high-energy (hze) ions that comprise a substantial part of the galactic cosmic ray (gcr) spectra that would be encountered during long-term space flights. moreover, predictions of the delayed genetic effects of high linear energy transfer (let) exposure is becoming more important as heavy ion therapy use is increasi ...201728910671
teaching an old drug new tricks: agonism, antagonism, and biased signaling of pilocarpine through m3 muscarinic acetylcholine receptor.pilocarpine is a prototypical drug used to treat glaucoma and dry mouth and is classified as either a full or partial muscarinic agonist. here, we report several unexpected results pertaining to its interaction with muscarinic m3 receptor (m3r). we found that pilocarpine was 1000 times less potent in stimulating mouse-eye pupil constriction than muscarinic agonists oxotremorin-m (oxo-m) or carbachol (cch), although all three ligands have similar kd values for m3r. in contrast to cch or oxo-m, pi ...201728893976
brca2 protects mammalian cells from heat shock.heat shock induces dna double-strand breaks (dsbs) in mammalian cells. mammalian cells are capable of repairing dsbs by utilising the homologous recombination (hr) pathway. breast cancer susceptibility gene 2 (brca2) is known to regulate the hr pathway. here, we investigate the role of brca2 in repairing dna damage induced by heat shock.201728891354
sequential screening by clonepix fl and intracellular staining facilitate isolation of high producer cell lines for monoclonal antibody manufacturing.screening and characterization of cell lines for stable production are critical tasks in identifying suitable recombinant cell lines for the manufacture of protein therapeutics. to aid this essential function we have developed a methodology for the selection of antibody expressing cells using fluorescence based clonepix fl colony isolation and flow cytometry analysis following intracellular staining for immunoglobulin g (igg). our data show that characterization of cells by flow cytometry early ...201728890364
growth rate changes in cho host cells are associated with karyotypic heterogeneity.chinese hamster ovary (cho) cell line instability and clonality issues can affect cell culture phenotypes such as cell growth, productivity, or product quality and remain challenges for biopharmaceutical manufacturing. while there have been efforts for characterizing cell line instability in cho production cell lines, a pre-existing level of cell line instability in cho host cells has not been determined. in this study, cell line instability and chromosomal heterogeneity of the host, cho-duk cel ...201728865132
proteome-wide analysis of n-glycosylation stoichiometry using swath technology.n-glycosylation is a crucial post-translational modification (ptm) and plays essential roles in biological processes. several methods have been developed for the relative quantification of n-glycosylation at the proteome scale. however, the proportion of n-glycosylated forms in a total protein population, or the "n-glycosylation stoichiometry", varies greatly among proteins or cellular states and is frequently missing due to the lack of robust technologies. in the present study, we developed a d ...201728845672
mechanisms of chromosomal aberrations induced by sesamin metabolites in chinese hamster lung cells.sesamin is a major lignan in sesame seeds and oil. we previously demonstrated that sesamin induces chromosomal aberrations (ca) in chinese hamster lung (chl/iu) cells in the presence of a metabolic activation system (s9 mix), although no genotoxicity was detected in vivo. to clarify the mechanism of ca induction by sesamin, we identified its principal active metabolite. a mono-catechol derivative, [2-(3,4-methylenedioxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabi-cyclo[3.3.0]octane (sc-1)], was p ...201728844238
cascading effect in bioprocessing-the impact of mild hypothermia on cho cell behavior and host cell protein composition.a major challenge in downstream purification of monoclonal antibodies (mab) is the removal of host cell proteins (hcps). previous studies have shown that cell culture conditions significantly impact the hcp content at harvest. however, it is currently unclear how process conditions affect physiological changes in the host cell population, and how these changes, in turn, cascade down to change the hcp profile. we examined how temperature downshift (tds) to mild hypothermia affects key upstream pe ...201728843000
leveraging a cho cell line toolkit to accelerate biotherapeutics into the clinic.the biogen upstream platform is capable of delivering equivalent quality material throughout the cell line generation process. this allows us to rapidly deliver high-quality biopharmaceuticals to patients with unmet medical needs. the drive to reduce time-to-market led the cell engineering group to develop an expression system that can enable this strategy. we have developed a clonal chinese hamster ovary (cho) host cell line that can routinely produce consistent antibody material at high titers ...201728842948
e6130, a novel cx3c chemokine receptor 1 (cx3cr1) modulator, attenuates mucosal inflammation and reduces cx3cr1+ leukocyte trafficking in mice with colitis.the chemokine fractalkine (cx3c chemokine ligand 1; cx3cl1) and its receptor cx3cr1 are involved in the pathogenesis of several diseases, including inflammatory bowel diseases such as crohn's disease and ulcerative colitis, rheumatoid arthritis, hepatitis, myositis, multiple sclerosis, renal ischemia, and atherosclerosis. there are no orally available agents that modulate the fractalkine/cx3cr1 axis. [(3s,4r)-1-[2-chloro-6-(trifluoromethyl)benzyl]-3-{[1-(cyclohex-1-en-1-ylmethyl)piperidin-4-yl]c ...201728842393
high yield process for the production of active human α-galactosidase a in cho-k1 cells through lentivirus transgenesis.fabry disease is an x-linked recessive disorder caused by a deficiency in lysosomal α-galactosidase a. currently, two enzyme replacement therapies (ert) are available. however, access to orphan drugs continues to be limited by their high price. selection of adequate high-expression systems still constitutes a challenge for alleviating the cost of treatments. several strategies have been implemented, with varying success, trying to optimize the production process of recombinant human α-galactosid ...201728840666
isotope labeling to determine the dynamics of metabolic response in cho cell perfusion bioreactors using maldi-tof-ms.the steady-state operation of chinese hamster ovary (cho) cells in perfusion bioreactors requires the equilibration of reactor dynamics and cell metabolism. accordingly, in this work we investigate the transient cellular response to changes in its environment and their interactions with the bioreactor hydrodynamics. this is done in a benchtop perfusion bioreactor using maldi-tof ms through isotope labeling of complex intracellular nucleotides (atp, utp) and nucleotide sugars (udp-hex, udp-hexnac ...201728840654
influence of protein/glycan interaction on site-specific glycan heterogeneity.to study how the interaction between n-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (pdi), a glycoprotein bearing 5 n-glycosylation sites, as a model system and expressed it transiently in a chinese hamster ovary (cho)-s cell line. pdi was produced as both secreted sec-pdi and endoplasmic reticulum-retained glycoprotein (er)-pdi, to study glycan processing by er and golgi resident enzymes. quantitative site-specific gly ...201728679530
generation of induced pluripotent stem cells from chinese hamster embryonic fibroblasts.we derived a stable cell line from chinese hamster embryonic fibroblasts by transduction of four mouse transcription factors (m3o, sox2, klf4, and n-myc) using a lentiviral vector. the cell line possess all the characteristics of an induced pluripotent stem cell (ipsc) line. given that chinese hamster ovary (cho) cells are the predominant host cells used for therapeutic protein production and no pluripotent stem cell line or other normal cell line has been isolated from chinese hamster, this ips ...201728677528
clinicopathological implications to micropapillary bladder urothelial carcinoma of the presence of sialyl lewis x-decorated mucin 1 in stroma-facing membranes.bladder urothelial carcinoma (uc) comprises more than 90% of all bladder cancers. among several uc variants, micropapillary uc (mpuc) is a rare one with high potential for lymphovascular invasion and subsequent lymph node metastasis. histologically, mpuc is characterized by the presence of small papillary carcinoma cell clusters surrounded by lacunar spaces. immunohistochemically, the outer circumference of these clusters, that is, the stroma-facing membrane of carcinoma cells, is reportedly alm ...201728666720
antipodocalyxin antibody chpcmab-47 exerts antitumor activity in mouse xenograft models of colorectal adenocarcinomas.podocalyxin (podxl) is expressed in several cancers, including brain tumors and colorectal cancers. podxl overexpression is an independent predictor of progression, metastasis, and poor outcome. we recently immunized mice with recombinant human podxl, which was produced using ln229 glioblastoma cells, and produced a clone pcmab-47 that could be used for investigating podxl expression by flow cytometry and immunohistochemical analysis. herein, we produced a human-mouse chimeric pcmab-47 (chpcmab- ...201728665782
acute toxicity and genotoxicity of fermented traditional medicine oyaksungi-san.the traditional medicine oyaksungi-san (oy) has been prescribed in east asia for hundreds of years for the treatment of stroke, paralysis, and ataxia. oy also has therapeutic effects on arthralgia, myalgia, and rheumatoid arthritis, and recent studies have shown its protective effects against apoptosis of hippocampal cells and its anti-inflammatory effects on the peripheral blood cells of patient with cerebral infarction. many studies have explored the use of traditional medicine and herb materi ...201728664144
accumulative scfv-fc antibody gene integration into the hprt chromosomal locus of chinese hamster ovary cells.we have previously developed an accumulative site-specific gene integration system (agis) using cre-recombinase and mutated loxp sites. agis enables repeated transgene integration into a predetermined chromosomal site in mammalian cells. however, the process of establishing cells with multiple integrated copies of the transgene is still time-consuming. in the present study, we describe an improved version of agis that facilitates and accelerates the establishment of high-producer chinese hamster ...201728662917
monoclonal antibodies expression improvement in cho cells by piggybac transposition regarding vectors ratios and design.establishing stable chinese hamster ovary (cho) cells producing monoclonal antibodies (mabs) usually pass through the random integration of vectors to the cell genome, which is sensitive to gene silencing. one approach to overcome this issue is to target a highly transcribed region in the genome. transposons are useful devices to target active parts of genomes, and piggybac (pb) transposon can be considered as a good option. in the present study, three pb transposon donor vectors containing both ...201728662065
a comprehensive model for heat-induced radio-sensitisation.combined radiotherapy (rt) and hyperthermia (ht) treatments may improve treatment outcome by heat induced radio-sensitisation. we propose an empirical cell survival model (alphar model) to describe this multimodality therapy. the model is motivated by the observation that heat induced radio-sensitisation may be explained by a reduction in the dna damage repair capacity of heated cells. we assume that this repair is only possible up to a threshold level above which survival will decrease exponent ...201728641499
impact of the niemann-pick c1 gene mutation on the total cellular glycomics of cho cells.niemann-pick disease type c (npc) is an autosomal recessive lipid storage disorder, and the majority of cases are caused by mutations in the npc1 gene. in this study, we clarified how a single gene mutation in the npc1 gene impacts the cellular glycome by analyzing the total glycomic expression profile of chinese hamster ovary cell mutants defective in the npc1 gene (npc1 ko cho cells). a number of glycomic alterations were identified, including increased expression of lactosylceramide, gm1, gm2 ...201728628327
proteomic analysis of host cell protein dynamics in the supernatant of fc-fusion protein-producing cho dg44 and dukx-b11 cell lines in batch and fed-batch cultures.chinese hamster ovary (cho) cells are the most widely used host cell lines for the commercial production of therapeutic proteins including fc-fusion proteins. during the culture of recombinant cho (rcho) cells, host cell proteins (hcps), secreted from viable cells and released from dead cells, accumulate extracellularly, potentially impairing product quality. in this study, the hcps that accumulated extracellularly in batch and fed-batch cultures of fc-fusion protein-producing rcho cell lines (d ...201728627725
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
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
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
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
danirixin: a reversible and selective antagonist of the cxc chemokine receptor 2.cxc chemokine receptor 2 (cxcr2) is a key receptor in the chemotaxis of neutrophils to sites of inflammation. the studies reported here describe the pharmacological characterization of danirixin, a cxcr2 antagonist in the diaryl urea chemical class. danirixin has high affinity for cxcr2, with a negative log of the 50% inhibitory concentration (pic50) of 7.9 for binding to chinese hamster ovary cell (cho)-expressed human cxcr2, and 78-fold selectivity over binding to cho-expressed cxcr1. danirixi ...201728611093
chomine: an integrated data warehouse for cho systems biology and modeling.the last decade has seen a surge in published genome-scale information for chinese hamster ovary (cho) cells, which are the main production vehicles for therapeutic proteins. while a single access point is available at www.chogenome.org, the primary data is distributed over several databases at different institutions. currently research is frequently hampered by a plethora of gene names and ids that vary between published draft genomes and databases making systems biology analyses cumbersome and ...201728605771
extracellular signal-regulated kinase 5 associates with casein kinase ii to regulate gpib-ix-mediated platelet activation via the pten/pi3k/akt pathway.essentials the mechanisms of extracellular signal-regulated kinase 5 (erk5) in gpib-ix signaling are unclear. function of erk5 in gpib-ix was tested using aggregation, western blotting, and mass spectrometry. the protein interacting with erk5 in human platelets was identified as casein kinase ii (ckii). erk5 associates with ckii to regulate the activation of the pi3k/akt pathway in gpib-ix signaling.201728603902
activation of unfolded protein response pathway is important for valproic acid mediated increase in immunoglobulin g productivity in recombinant chinese hamster ovary cells.process engineering to improve product quality and titers is gaining importance at late-stage cell culture process development. valproic acid, a us food and drug administration-approved histone deacetylase (hdac) inhibitor, has been shown to improve cell culture performance with higher productivities and minimal effect on the product quality. however, the wider physiological impact of valproic acid on recombinant cells has not been investigated till date. in this study, we investigate the role o ...201728601608
investigation of the relative biological effectiveness and uniform isobiological killing effects of irradiation with a clinical carbon sobp beam on dna repair deficient cho cells.spread-out bragg peak (sobp) c ions have been used clinically in charged particle radiation therapy for years. an sobp beam consists of various monoenergetic bragg peaks; however, the biological effect of irradiation with an sobp beam track has not been well-studied. in order to determine the clinically prospective molecular targets, radiosensitivity to the beam track in dna repair deficient cell lines was investigated. a total of four distinct chinese hamster ovary (cho) cell lines, including c ...201728599495
Refresh
firstprev
...251252253254255256257258259260...
nextlast
Displaying items 25201 - 25300 of 26566