Abstract:
:Tumor-targeted Salmonella VNP20009 preferentially replicate within tumor tissue and partially suppress tumor growth in murine tumor models. These Salmonella have the ability to locally induce apoptosis when they are in direct contact with cancer cells but they lack significant bystander killing, which may correlate with their overall lack of antitumor activity in human clinical studies. In order to compensate for this deficiency without enhancing overall toxicity, we engineered the bacteria to express epidermal growth factor receptor (EGFR)-targeted cytotoxic proteins that are released into the extracellular milieu. In this study, we demonstrate the ability of the Salmonella strain VNP20009 to produce three different forms of the Pseudomonas exotoxin A (ToxA) chimeric with a tumor growth factor alpha (TGFα) which results in its producing culture supernatants that are cytotoxic and induce apoptosis in EGFR positive cancer cells as measured by the tetrazolium dye reduction, and Rhodamine 123 and JC-10 mitochondrial depolarization assays. In addition, exchange of the ToxA REDLK endoplasmic reticulum retention signal for KDEL and co-expression of the ColE3 lysis protein resulted in an overall increased cytotoxicity compared to the wild type toxin. This approach has the potential to significantly enhance the antitumor activity of VNP20009 while maintaining its previously established safety profile. Biotechnol. Bioeng. 2016;113: 2698-2711. © 2016 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals, Inc.
journal_name
Biotechnol Bioengjournal_title
Biotechnology and bioengineeringauthors
Quintero D,Carrafa J,Vincent L,Bermudes Ddoi
10.1002/bit.26026subject
Has Abstractpub_date
2016-12-01 00:00:00pages
2698-2711issue
12eissn
0006-3592issn
1097-0290journal_volume
113pub_type
杂志文章abstract::Centrifugal adsorption technology (CAT) is a new compact, countercurrent technology for efficient adsorption from large liquid streams by using adsorbent particles in the micrometer range. CAT seems particularly suited for the recovery of macromolecules at low concentrations, because the small particle dimensions lead...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.10121
更新日期:2002-05-05 00:00:00
abstract::The kinetics and mechanism of Fe(III) reduction to Fe(II) were studied in pure batch cultures of Pseudomonas sp. 200. The rate of iron reduction has been mechanistically related to aqueous phase iron speciation. In the absence of microbial activity the iron reduction rate was negligible. Initial rates of microbial iro...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260281110
更新日期:1986-11-01 00:00:00
abstract::Aryl-alcohol oxidase (AAO) plays a fundamental role in the fungal ligninolytic secretome, acting as a supplier of H2 O2 . Despite its highly selective mechanism of action, the presence of this flavooxidase in different biotechnological settings has hitherto been hampered by the lack of appropriate heterologous express...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.26585
更新日期:2018-07-01 00:00:00
abstract::Effective enzyme-mediated viscosity reduction, disaggregation, or "liquefaction," is required to overcome the rheological challenges resulting from the fibrous, hygroscopic nature of lignocellulosic biomass, particularly at the high solids loadings that will be required for an economically viable process. However, the...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.26381
更新日期:2017-11-01 00:00:00
abstract::Microparticle-enhanced cultivation (MPEC) was applied as a novel method for improved biomass and product formation during cultivation of filamentous microorganisms. Exemplarily, chloroperoxidase (CPO) formation by Caldariomyces fumago was analyzed in the presence and absence of microparticles of different size. Partic...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.21713
更新日期:2008-02-15 00:00:00
abstract::PHA, a naturally occurring biopolymer produced by a wide range of microorganisms, is known for its applications as bioplastic. In recent years the use of agro-industrial wastewater as substrate for PHA production by bacterial enrichments has attracted considerable research attention. Crude glycerol as generated during...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.24991
更新日期:2013-12-01 00:00:00
abstract::The fermentation kinetics of methane production from whey permeate in a packed bed immobilized cell bioreactor at mesophilic temperatures and pHs around neutral was studied. Propionate and acetate were the only two major organic intermediates found in the methanogenic fermentation of lactose. Based on this finding, a ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260370412
更新日期:1991-02-20 00:00:00
abstract::Hairy roots have the potential to produce a variety of valuable small and large molecules. The mist reactor is a gas phase bioreactor that has shown promise for low-cost culture of hairy roots. Using a newer, disposable culture bag, mist reactor performance was studied with two species, Artemisia annua L. and Arachis ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.22892
更新日期:2010-12-01 00:00:00
abstract::The effects ensuing from the interaction between membrane-bound sarcosine dehydrogenase and the surrounding lipids as well as the effects of membrane fluidity were described in this study. A 25-fold activation was observed upon the reconstitution of the enzyme in bilayers of SUVs made of DMPC. The considerable decreas...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260370904
更新日期:1991-04-15 00:00:00
abstract::The C-terminal lysine variation is commonly observed in biopharmaceutical monoclonal antibodies. This modification can be important since it is found to be sensitive to the production process. The methods commonly used to probe this charge variation, including IEF, cIEF, ion-exchange chromatography, and LC-MS, were ev...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.21855
更新日期:2008-08-15 00:00:00
abstract::We originally investigated the suitability of chitosan scaffolds loaded with bone morphogenetic protein 6 (BMP-6) in both stationary and dynamic conditions for cartilage tissue engineering. In the first part of the present study, ATDC5 murine chondrogenic cells were seeded in chitosan and BMP-6 loaded chitosan scaffol...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.22426
更新日期:2009-10-15 00:00:00
abstract::This research focused on how the extent and type of primary solid-liquid separation can affect the performance of guard filtration and chromatography, in this instance hydrophobic interaction chromatography. The system used in the study was yeast (Saccharomyces cerevisiae) with the target molecule being an intracellul...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.21823
更新日期:2008-08-01 00:00:00
abstract::Constitutive activation of Wnt signaling plays an important role in colorectal and liver tumorigenesis. Cell-based assays using synthetic TCF/LEF (T-cell factor/lymphoid enhancer factor) reporters, as readouts of β-catenin/TCF-dependent transcriptional activity, have contributed greatly to the discovery of small molec...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.26394
更新日期:2017-12-01 00:00:00
abstract::In order to evaluate the sensitivity of hepatocellular cultures to variations in both substrate stiffness and bioactive ligand presentation, hepatocytes were cultured on differentially compliant polyacrylamide gel discs functionalized with varying amounts of the ECM ligand, fibronectin (FN). Subconfluent cell cultures...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.20328
更新日期:2005-02-05 00:00:00
abstract::Mathematical models to describe transcription (Arnold et al. (2001); Biotech Bioeng 72:548-561) and translation (Mehra et al. (2003); Biotech Bioeng 84:822-841) in bacteria are modified in order to improve reaction kinetics and to include the number of polymerase molecules that are active on the DNA, as well as to inc...
journal_title:Biotechnology and bioengineering
pub_type: 评论,信件
doi:10.1002/bit.21065
更新日期:2007-03-01 00:00:00
abstract::The rate of celluose degradation, limited due to the inhibition by cellobiose, can be increased by the hydrolysis of cellobiose to glucose using immobilized beta-glucosidase. Production of beta-glucosidase in four yeasts was studied and a maximum activity of 1.22 IU/mg cells was obtained in cells of Pichia etchellsii ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260260408
更新日期:1984-04-01 00:00:00
abstract::trans-4-Hydroxy- l-proline (Hyp) is an abundant component of mammalian collagen and functions as a chiral synthon for the syntheses of anti-inflammatory drugs in the pharmaceutical industry. Proline 4-hydroxylase (P4H) can catalyze the conversion of l-proline to Hyp; however, it is still challenging for the fermentati...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.26818
更新日期:2019-01-01 00:00:00
abstract::A continuous viral inactivation (CVI) chamber has been designed to operate with acceptable residence time distribution (RTD) characteristics. However, altering the CVI's geometry and operation to accommodate the scale was not obvious. In this work, we elucidate the influence of Dean vortices and leverage the transitio...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.27223
更新日期:2020-03-01 00:00:00
abstract::Intracellular events that take place during influenza virus replication in animal cells are well understood qualitatively. However, to better understand the complex interaction of the virus with its host cell and to quantitatively analyze the use of cellular resources for virion formation or the overall dynamic for th...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章,评审
doi:10.1002/bit.20096
更新日期:2004-10-05 00:00:00
abstract::In vivo mesenchymal stem cell (MSC) survival is relevant to therapeutic applications requiring engraftment and potentially to nonengraftment applications as well. MSCs are a mixture of progenitors at different stages of cellular aging, but the contribution of this heterogeneity to the survival of MSC implants is unkno...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.27195
更新日期:2020-01-01 00:00:00
abstract::An 11-L helical ribbon impeller (HRI) bioreactor was tested for the culture of Spodoptera frugiperda (Sf-9) cells. This impeller and surface baffling ensured homogeneous mixing and high oxygen transfer through surface aeration and surface-induced babble generation. Serum-supplemented and serum-free cultures, using TNM...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260380607
更新日期:1991-09-01 00:00:00
abstract::Currently in America the biofuel ethanol is primarily being produced by the dry grind technique to obtain the starch contained in the corn grains and subsequently subjected to fermentation. This so-called 1st generation technology has two setbacks; first the lingering debate whether its life cycle contributes to a red...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.21881
更新日期:2008-09-01 00:00:00
abstract::Gluconic acid and sorbitol were simultaneously produced from glucose and Jerusalem artichoke using a glucose-fructose oxidoreductase of Zymomonas mobilis and inulinase. Inulinase was immobilized on chitin by cross-linking with glutaraldehyde. Cells of Z. mobilis permeabilized with toluene were coimmobilized with chiti...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260390312
更新日期:1992-02-05 00:00:00
abstract::Cost-effective production of biopharmaceuticals on a large scale can be carried out by perfusion cultures of mammalian cells. One problem with this mode of operation for submerged free-cell cultures is the requirement for an efficient cell separation device located in the effluent stream. The present work investigates...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0290(19970505)54:3<239::AID-BIT
更新日期:1997-05-05 00:00:00
abstract::Gene deletion strategies using flux balance analysis (FBA) have improved the growth-coupled production of various compounds. However, the productivities were often below the expectation because the cells failed to adapt to these genetic perturbations. Here, we demonstrate the productivity of the succinate of the desig...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.26568
更新日期:2018-06-01 00:00:00
abstract::Feasibility of elemental sulfur reduction by Desulfovibrio desulfuricans in anaerobic conditions in a stirred reactor was studied. Hydrogen was used as energy source, whereas the carbonated species were bicarbonate and yeast extract. Attention was paid to reactor engineering aspects, biofilm formation on the sulfur su...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.21457
更新日期:2007-10-15 00:00:00
abstract::A modified simulation procedure based on a statistical approach was investigated. The procedure predicts the time course of fed-batch culture for glutamic acid production by a temperature-sensitive strain of Brevibacterium flavum. The statistical approach requires only a data base of state points obtained in experimen...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260330208
更新日期:1989-01-10 00:00:00
abstract::Corynebacterium hydrocarboclastus KY 8835 grew in the acetate medium and accumulated 28mM Corynecins which was the highest production yield among the processes using various carbon sources. Selective production of Corynecin I (over 90% of all Corynecins), which had been desired for increase of the product yield, was a...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260190705
更新日期:1977-07-01 00:00:00
abstract::Kluyveromyces marxianus UCD (FST) 55-82 cells were immobilized in Na alginate beads and used in a packed-bed bioreactor system for the continuous production of ethanol from the extract of Jerusalem artichoke tubers. Volumetric ethanol productivities of 104 and 80 g ethanol/ L/h were obtained at 80 and 92% sugar utiliz...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260240703
更新日期:1982-07-01 00:00:00
abstract::MicroRNAs are small non-coding RNAs that play a critical role in post-transcriptional control of gene expression. Recent publications of genomic sequencing data from the Chinese Hamster (CGR) and Chinese hamster ovary (CHO) cells provide new tools for the discovery of novel miRNAs in this important production system. ...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.25539
更新日期:2015-07-01 00:00:00