In situ subcellular localization of epitope-tagged human and rabbit carboxylesterases

Potter, Philip M.; Wolverton, Judith S.; Morton, Christopher L.; Whipple, David O.; Danks, Mary K.

doi:10.1002/(sici)1097-0320(19980701)32:3<223::aid-cyto9>3.0.co;2-k

Cited by 14 publications

(7 citation statements)

References 19 publications

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“…Human liver CE (CES1, hCE1) demonstrates little variability in expression in liver microsomes, and primarily metabolizes small, planar substrates (e.g., Tamiflu, Ritalin, Plavix; [12]). It is a 60kDa protein that requires processing within the ER for enzymatic activity [18, 19]. Using molecular approaches, hCE1 has been engineered to be secreted and this has allowed large scale purification and the determination of the x-ray crystal structure of the protein (Figure 4; [4–7, 20]).…”

Section: Human Carboxylesterasesmentioning

confidence: 99%

Carboxylesterases: General detoxifying enzymes

Hatfield

Umans

Hyatt

et al. 2016

Chemico-Biological Interactions

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137

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Carboxylesterases (CE) are members of the esterase family of enzymes, and as their name suggests, they are responsible for the hydrolysis of carboxylesters into the corresponding alcohol and carboxylic acid. To date, no endogenous CE substrates have been identified and as such, these proteins are thought to act as a mechanism to detoxify ester-containing xenobiotics. As a consequence, they are expressed in tissues that might be exposed to such agents (lung and gut epithelia, liver, kidney, etc.). CEs demonstrate very broad substrate specificities and can hydrolyze compounds as diverse as cocaine, oseltamivir (Tamiflu), permethrin and irinotecan. In addition, these enzymes are irreversibly inhibited by organophosphates such as Sarin and Tabun. In this overview, we will compare and contrast the two human enzymes that have been characterized, and evaluate the biology of the interaction of these proteins with organophosphates (principally nerve agents).

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Section: Human Carboxylesterasesmentioning

confidence: 99%

Carboxylesterases: General detoxifying enzymes

Hatfield

Umans

Hyatt

et al. 2016

Chemico-Biological Interactions

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137

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“…We also reported efficacy following treatment with HB1.F3.C1 cells expressing IFN-h and an interim analysis (6-month survival) following treatment with HB1.F3.C1 cells expressing a secreted form of a rabbit carboxylesterase (rCE) in combination with CPT-11 (2,(7)(8)(9)(10). We now report the long-term efficacy for the latter approach and also document that plasma carboxylesterase activities are unchanged and SN-38 levels are within levels tolerated by pediatric patients (11)(12)(13) at doses of CPT-11 that produced 1-year disease-free survival of 90% of mice.…”

Section: Introductionmentioning

confidence: 99%

Tumor-Targeted Enzyme/Prodrug Therapy Mediates Long-term Disease-Free Survival of Mice Bearing Disseminated Neuroblastoma

et al. 2007

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Neural stem cells and progenitor cells migrate selectively to tumor loci in vivo. We exploited the tumor-tropic properties of HB1.F3.C1 cells, an immortalized cell line derived from human fetal telencephalon, to deliver the cDNA encoding a secreted form of rabbit carboxylesterase (rCE) to disseminated neuroblastoma tumors in mice. This enzyme activates the prodrug CPT-11 more efficiently than do human enzymes. Mice bearing multiple tumors were treated with rCE-expressing HB1.F3.C1 cells and schedules of administration of CPT-11 that produced levels of active drug (SN-38) tolerated by patients. Both HB1.F3.C1 cells and CPT-11 were given i.v. None of the untreated mice and 30% of mice that received only CPT-11 survived long term. In contrast, 90% of mice treated with rCE-expressing HB1.F3.C1 cells and 15 mg/kg CPT-11 survived for 1 year without detectable tumors. Plasma carboxylesterase activity and SN-38 levels in mice receiving both rCE-expressing HB1.F3.C1 cells (HB1.F3.C1/AdCMVrCE) and CPT-11 were comparable with those in mice receiving CPT-11 only. These data support the hypothesis that the antitumor effect of the described neural stem/progenitor cell-directed enzyme prodrug therapy (NDEPT) is mediated by production of high concentrations of active drug selectively at tumor sites, thereby maximizing the antitumor effect of CPT-11. NDEPT approaches merit further investigation as effective, targeted therapy for metastatic tumors. We propose that the described approach may have greatest use for eradicating minimum residual disease. [Cancer Res 2007;67(1):22-5]

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“…1). Carboxylesterases are a family of serine-dependent esterases involved in the metabolism of endogenous lipids and drugs by hydrolyzing ester groups of drugs and toxins [34][35][36][37]. Xu et al [38] reported that human carboxylesterase 2 is commonly expressed in tumor tissue and is correlated with activation of irinotecan chemotherapy for solid tumors.…”

Section: Immunity and Defensementioning

confidence: 99%

Gene expression profiling in streptozotocin-induced diabetic rat liver in response to fungal polysaccharide treatment

Hwang

Kim

Baek

et al. 2009

Korean J. Chem. Eng.

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We established the gene expression profiling in streptozotocin (STZ)-induced diabetic rat liver in response to hypoglycemic fungal polysaccharides (EPS), using oligonucleotide microarray analysis. Differentially regulated genes showing higher fold change than 2 were identified and categorized through hierarchical clustering analysis. Among the 835 genes analyzed, 244 were up-regulated, while 321 were down-regulated after diabetes induction. Interestingly, many gene expressions altered after STZ-treatment mimicked a normal rat liver by EPS therapy. Most of these genes included genes involving cell structure and motility, immunity and defense, lipid, fatty acid and steroid metabolism, protein metabolism and modification, and signal transduction. More importantly, we found a total of 36 genes that showed significant fold changes in their expression that have not previously been examined in the context of diabetes. To validate the microarray results, we further confirmed the gene expression patterns by RT-PCR using four genes of interest (carboxylesterase 2, stearoyl-coenzyme A desaturase 1, insulin-like growth factor 1, and insulin-like growth factor binding protein 2). Taken together, EPS acted as a potent regulator of gene expression for a wide variety of genes in diabetic rat liver.

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In situ subcellular localization of epitope-tagged human and rabbit carboxylesterases

Cited by 14 publications

References 19 publications

Carboxylesterases: General detoxifying enzymes

Carboxylesterases: General detoxifying enzymes

Tumor-Targeted Enzyme/Prodrug Therapy Mediates Long-term Disease-Free Survival of Mice Bearing Disseminated Neuroblastoma

Gene expression profiling in streptozotocin-induced diabetic rat liver in response to fungal polysaccharide treatment

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