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https://www.readbyqxmd.com/read/28638737/selective-activation-of-anti-cd73-mechanisms-in-control-of-primary-tumors-and-metastases
#1
Dipti Vijayan, Deborah S Barkauskas, Kimberley Stannard, Erin Sult, Rebecca Buonpane, Kazuyoshi Takeda, Michele W L Teng, Kris Sachsenmeier, Carl Hay, Mark J Smyth
The emerging role for CD73 in driving cancer growth and metastasis has presented opportunities to develop anti-CD73 monoclonal antibodies (mAbs) in the treatment of human cancers. Blockade of CD73 by antagonistic CD73 mAbs ameliorates tumor growth and metastasis via the inhibition of enzymatic and non-enzymatic CD73 pathways. In this study, we investigated whether Fc-receptor cross-linking represented a non-redundant mechanism by which anti-CD73 mAbs exert potent suppression of solid tumors and metastases. We engineered four anti-CD73 mAbs, each different in their ability to modulate CD73 enzymatic function and bind Fc receptors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28634336/lc-ms-ms-quantification-of-sulfotransferases-is-better-than-conventional-immunogenic-methods-in-determining-human-liver-sult-activities-implication-in-precision-medicine
#2
Cong Xie, Tong-Meng Yan, Jia-Mei Chen, Xiao-Yan Li, Juan Zou, Li-Jun Zhu, Lin-Lin Lu, Ying Wang, Fu-Yuan Zhou, Zhong-Qiu Liu, Ming Hu
This study aims to determine whether enzyme activities are correlated with protein amounts and mRNA expression levels of five major human sulfotransferase (SULT) enzymes in 10 matched pericarcinomatous and hepatocellular carcinoma liver samples. The MRM UHPLC-MS/MS method, Western blot and RT-PCR were used along with SULT activity measurement using probe substrates. The LC-MS/MS method was specific for all five tested SULTs, whereas Western blot was specific for only two isoforms. The activities of SULT1A1, SULT1B1, SULT1E1 and SULT2A1 in 9 of 10 samples showed a significant decrease in tumor tissues relative to matched pericarcinomatous tissues, whereas the activities of SULT1A3 in 7 of 10 samples increased...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630292/tetrahydrobiopterin-regulates-monoamine-neurotransmitter-sulfonation
#3
Ian Cook, Ting Wang, Thomas S Leyh
Monoamine neurotransmitters are among the hundreds of signaling small molecules whose target interactions are switched "on" and "off" via transfer of the sulfuryl-moiety (-SO3) from PAPS (3'-phosphoadenosine 5'-phosphosulfate) to the hydroxyls and amines of their scaffolds. These transfer reactions are catalyzed by a small family of broad-specificity enzymes-the human cytosolic sulfotransferases (SULTs). The first structure of a SULT allosteric-binding site (that of SULT1A1) has recently come to light. The site is conserved among SULT1 family members and is promiscuous-it binds catechins, a naturally occurring family of flavanols...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28601433/characterization-of-xenobiotic-metabolizing-enzymes-of-a-reconstructed-human-epidermal-model-from-adult-hair-follicles
#4
Daniel Bacqueville, Carine Jacques, Laure Duprat, Emilien L Jamin, Beatrice Guiraud, Elisabeth Perdu, Sandrine Bessou-Touya, Daniel Zalko, Hélène Duplan
In this study, a comprehensive characterization of xenobiotic metabolizing enzymes (XMEs) based on gene expression and enzyme functionality was made in a reconstructed skin epidermal model derived from the outer root sheath (ORS) of hair follicles (ORS-RHE). The ORS-RHE model XME gene profile was consistent with native human skin. Cytochromes P450 (CYPs) consistently reported to be detected in native human skin were also present at the gene level in the ORS-RHE model. The highest Phase I XME gene expression levels were observed for alcohol/aldehyde dehydrogenases and (carboxyl) esterases...
June 7, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28597227/a-hemoglobin-adduct-as-a-biomarker-for-the-internal-exposure-to-the-rodent-carcinogen-furfuryl-alcohol
#5
Benjamin Sachse, Jan Hielscher, Alfonso Lampen, Klaus Abraham, Bernhard H Monien
Furfuryl alcohol is a common food contaminant, which is formed by acid- and heat-catalyzed degradation of fructose and glucose. Its carcinogenic effect in rodents originates most likely from sulfotransferase (SULT)-catalyzed conversion into the mutagenic sulfate ester 2-sulfoxymethylfuran. In this study, a protein adduct biomarker was sought for the medium-term internal exposure to furfuryl alcohol. A UPLC-MS/MS screening showed that the adduct N-((furan-2-yl)methyl)-Val (FFA-Val) at the N-terminus of hemoglobin is a valid target analyte...
June 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28554218/implications-of-sulfotransferase-activity-in-interindividual-variability-in-drug-response-clinical-perspective-on-current-knowledge
#6
Natalia Marto, Judit Morello, Emilia C Monteiro, Sofia A Pereira
The interindividual variability in drug response is a major issue in clinical practice and in drug development. Sulfoconjugation is an important Phase II reaction catalyzed by cytosolic sulfotransferases (SULTs), playing a major role in homeostatic functions, xenobiotic detoxification, and carcinogen bioactivation. SULT display wide interindividual variability, explained only partially by genetic variation, suggesting that other non-genetic, epigenetic, and environmental influences could be major determinants of variability in SULT activity...
June 20, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28552400/celecoxib-affects-estrogen-sulfonation-catalyzed-by-several-human-hepatic-sulfotransferases-but-does-not-stimulate-17-sulfonation-in-rat-liver
#7
Sriram Ambadapadi, Peter L Wang, Sergiu P Palii, Margaret O James
Celecoxib is known to alter the preferred position of SULT2A1-catalyzed sulfonation of 17β-estradiol (17β-E2) and other estrogens from the 3- to the 17-position. Understanding the effects of celecoxib on estrogen sulfonation is of interest in the context of the investigational use of celecoxib to treat breast cancer. This study examined the effects on celecoxib on cytosolic sulfotransferases in human and rat liver and on SULT enzymes known to be expressed in liver. Celecoxib's effects on the sulfonation of several steroids catalyzed by human liver cytosol were similar but not identical to those observed previously for SULT2A1...
May 24, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28541672/impacts-of-unregulated-novel-brominated-flame-retardants-on-human-liver-thyroid-deiodination-and-sulfotransferation
#8
Tristan A Smythe, Craig M Butt, Heather M Stapleton, Kerri Pleskach, Geemitha Ratnayake, Chae Yoon Song, Nicole Riddell, Alex Konstantinov, Gregg T Tomy
The inhibitory effects of five novel brominated flame retardants, 1,2-bis(2,4,5-tribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP), and β-tetrabromoethylcyclohexane (β-TBECH), on thyroid hormone deiodinase (DIO) and sulfotransferase (SULT) activity were investigated using human in vitro liver microsomal and cytosolic bioassays. Enzymatic activity was measured by incubating active human liver subcellular fractions with thyroid hormones (T4 and rT3 separately) and measuring changes in thyroid hormone (T4, T3, rT3, and 3,3'-T2) concentrations...
June 7, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28540728/sulfonation-disposition-of-acacetin-in-vitro-and-in-vivo
#9
Qisong Zhang, Lijun Zhu, Xia Gong, Yanjiao Ruan, Jia Yu, Huangyu Jiang, Ying Wang, XiaoXiao Qi, Linlin Lu, Zhongqiu Liu
Acacetin, an important component of acacia honey, exerts extensive therapeutic effects on many cancers. However, the sulfonation disposition of acacetin has rarely been reported. Therefore, this study aimed to investigate the sulfonation disposition of acacetin systematically. The results showed that acacetin-7-sulfate was the main metabolite mediated primarily by sulfotransferases (SULT) 1A1. Dog liver S9 presented the highest formation rate of acacetin-7-sulfate. Compared with that in wild-type Friend Virus B (FVB) mice, plasma exposure of acacetin-7-sulfate decreased significantly in multidrug resistance protein 1 knockout (Mrp1(-/-)) mice vut increased clearly in breast cancer resistance protein knockout (Bcrp(-/-)) mice...
June 21, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28536265/structural-and-enzymatic-insights-into-species-specific-resistance-to-schistosome-parasite-drug-therapy
#10
Alexander B Taylor, Kenneth M Roberts, Xiaohang Cao, Nathaniel E Clark, Stephen P Holloway, Enrica Donati, Chiara M Polcaro, Livia Pica-Mattoccia, Reid S Tarpley, Stanton F McHardy, Donato Cioli, Philip T LoVerde, Paul F Fitzpatrick, P John Hart
The antischistosomal pro-drug oxamniquine is activated by a sulfotransferase (SULT) in the human parasite Schistosoma mansoni Of the three main human blood fluke species, only S. mansoni is sensitive to oxamniquine therapy despite the presence of SULT orthologs in S. haematobium and S. japonicum The reason for this species-specific drug action has remained a mystery for decades. Here we present the crystal structures of S. haematobium and S. japonicum SULTs, including S. haematobium SULT in complex with oxamniquine...
May 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28482697/biotransformation-enzyme-activities-and-phase-i-metabolites-analysis-in-litopenaeus-vannamei-following-intramuscular-administration-of-t-2-toxin
#11
Yijia Deng, Yaling Wang, Lijun Sun, Pengli Lu, Rundong Wang, Lin Ye, Defeng Xu, Riying Ye, Ying Liu, Siyuan Bi, Ravi Gooneratne
T-2 toxin (T-2) is a type-A trichothecene produced by Fusarium that causes toxicity to animals. T-2 contamination of grain-based aquatic feed is a concern for the industries related to edible aquatic crustacean species such as the shrimp industry because it can lead to serious food safety issues. T-2, its metabolites, and selected phase I (EROD, CarE) and phase II (GST, UGT, SULT) detoxification enzymes in hemolymph and tissues were monitored at 0, 5, 10 15, 30, 45, and 60 min following T-2 intramuscular administration (3 mg/kg bw) in shrimp (Litopenaeus vannamei)...
May 8, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28454052/a-multi-biomarker-approach-in-scallop-chlamys-farreri-to-assess-the-impact-of-contaminants-in-qingdao-coastal-area-of-china
#12
Ruiming Guo, Luqing Pan, Rongwang Ji
A multi-biomarker approach was carried out to classify the environmental quality and the adverse effects of contaminants on scallop Chlamys farreri. The scallops were collected from three sampling stations in Qingdao coastal area of China in March, May, August and October of 2015. A suite of environmental factors and biomarkers, including temperature, salinity, pH, the concentrations of polycyclic aromatic hydrocarbons (PAHs), tetrabromobisphenol A (TBBPA) and metals (Cr, Mn, Cu, Zn, Cd, Pb, As) in seawater and soft tissue, mRNA expression of aryl hydrocarbon receptor (AhR) and P-glycoprotein (P-gp), 7-ethoxyresorufin O-deethylase (EROD), glutathione-S-transferase (GST), uridine-diphosphate-glucuronyl-transferase (UGT), sulfotransferase (SULT), metallothionein (MT), Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation (LPO) and protein carbonyl (PC) contents and DNA strand breaks, were measured in the gill and digestive gland...
August 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28441724/multiple-udp-glucuronosyltransferase-and-sulfotransferase-enzymes-are-responsible-for-the-metabolism-of-verproside-in-human-liver-preparations
#13
Ju-Hyun Kim, Deok-Kyu Hwang, Ju-Yeon Moon, Yongnam Lee, Ji Seok Yoo, Dae Hee Shin, Hye Suk Lee
Verproside, an active iridoid glycoside component of Veronica species, such as Pseudolysimachion rotundum var. subintegrum and Veronica anagallis-aquatica, possesses anti-asthma, anti-inflammatory, anti-nociceptive, antioxidant, and cytostatic activities. Verproside is metabolized into nine metabolites in human hepatocytes: verproside glucuronides (M1, M2) via glucuronidation, verproside sulfate (M3) via sulfation, picroside II (M4) and isovanilloylcatalpol (M5) via O-methylation, M4 glucuronide (M6) and M4 sulfate (M8) via further glucuronidation and sulfation of M4, and M5 glucuronide (M7) and M5 sulfate (M9) via further glucuronidation and sulfation of M5...
April 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28411281/long-term-stability-of-cryopreserved-human-hepatocytes-evaluation-of-phase-i-and-ii-drug-metabolizing-enzyme-activities-and-cyp3a4-5-induction-for-more-than-a-decade
#14
Miyako Sudo, Mitsuhiro Nishihara, Junzo Takahashi, Satoru Asahi
We evaluated the long-term stability of hepatocytes stored in the vapor phase of liquid nitrogen for their viability, cytochrome P450 (CYP) 1A2 activity, CYP3A4/5 activity, uridine diphosphate-glucuronosyl transferase (UGT) activity, sulfotransferase (SULT) activity, and CYP3A4/5 induction during 14 years of preservation. No substantial degradation of viability, CYP1A2 activity, UGT activity, or CYP3A4/5 induction was observed. CYP3A4/5 activity showed a slight decrease after 7 years of storage, and SULT activity gradually decreased during storage, although substantial activities remained even after 14 years...
July 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28396528/human-enterocytes-as-an-in-vitro-model-for-the-evaluation-of-intestinal-drug-metabolism-characterization-of-drug-metabolizing-enzyme-activities-of-cryopreserved-human-enterocytes-from-twenty-four-donors
#15
Ming-Chih David Ho, Nick Ring, Kirsten Amaral, Utkarsh Doshi, Albert Li
We report here successful isolation and cryopreservation of enterocytes from human small intestine. The enterocytes were isolated by enzyme digestion of the intestinal lumen followed by partial purification via differential centrifugation. The enterocytes were cryopreserved directly after isolation without culturing to maximize retention of in vivo drug metabolizing enzyme activities. Post-thaw viability of the cryopreserved enterocytes was consistently over 80% based on trypan blue exclusion. Cryopreserved enterocytes pooled from 8 donors (4 male and 4 female) were evaluated for their metabolism of 14 pathway-selective substrates: CYP1A2 (phenacetin hydroxylation), CYP2A6 (coumarin 7-hydroxylation), CYP2B6 (bupropion hydroxylation), CYP2C8 (paclitaxel 6α-hydroxylation), CYP2C9 (diclofenac 4-hydroxylation), CYP2C19 (s-mephenytoin 4-hydroxylation), CYP2D6 (dextromethorphan hydroxylation), CYP2E1 (chlorzoxazone 6-hydroxylation), CYP3A4 (midazolam 1'-hydroxylation and testosterone 6β-hydroxylation), CYP2J2 (astemizole O-demethylation), UDP-glucuronosyltransferase (UGT; 7-hydroxycoumarin glucuronidation), sulfotransferase (SULT; 7-hydroxycoumarin sulfation), and carboxylesterase 2 (CES2; irinotecan hydrolysis) activities...
April 10, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28356314/high-throughput-and-reliable-isotope-label-free-approach-for-profiling-24-metabolic-enzymes-in-fvb-mice-and-gender-differences
#16
Jiamei Chen, Lijun Zhu, Xiaoyan Li, Haihui Zheng, Tongmeng Yan, Cong Xie, Sijing Zeng, Jia Yu, Huangyu Jiang, Linlin Lu, Xiaoxiao Qi, Ying Wang, Ming Hu, Zhongqiu Liu
FVB mice are extensively used in transgenic and pharmacokinetic research. In this study, a validated isotope label-free method of using ultrahigh-performance liquid chromatography (UHPLC)-MS/MS was established for quantifying 24 drug-metabolizing enzymes (DMEs) in FVB mice. The DMEs include cytochrome P450 (CYPs/Cyps), UDP-glucuronsyltransferases (UGTs/Ugts), and sulfotransferases (SULTs/Sults), which are the major phase I and II metabolic enzymes responsible for clearing and detoxifying xenobiotic and endogenous substances...
March 29, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28336091/altered-cellular-metabolism-of-hepg2-cells-caused-by-microcystin-lr
#17
Junguo Ma, Yiyi Feng, Siyu Jiang, Xiaoyu Li
This study aimed to evaluate the possible effects of microcystin-LR (MC-LR) exposure on the metabolism and drug resistance of human hepatocellular carcinoma (HepG2) cells. For this purpose, we first conducted an experiment to make sure that MC-LR could penetrate the HepG2 cell membrane effectively. The transcriptional levels of phase I (such as CYP2E1, CYP3A4, and CYP26B1) and phase II (such as EPHX1, SULTs, and GSTM) enzymes and export pump genes (such as MRP1 and MDR1) were altered by MC-LR-exposure for 24 h, indicating that MC-LR treatment may destabilize the metabolism of HepG2 cells...
March 21, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28326452/methyleugenol-dna-adducts-in-human-liver-are-associated-with-sult1a1-copy-number-variations-and-expression-levels
#18
Roman Tremmel, Kristin Herrmann, Wolfram Engst, Walter Meinl, Kathrin Klein, Hansruedi Glatt, Ulrich M Zanger
Methyleugenol is a rodent hepatocarcinogen occurring in many herbs and spices as well as essential oils used for flavoring. Following metabolic activation by cytochromes P450 (CYPs) and sulfotransferases (SULTs), methyleugenol can form DNA adducts. Previously, we showed that DNA adduct formation by methyleugenol in mouse liver is dependent on SULT1A1 expression and that methyleugenol DNA adducts are abundant in human liver specimens. In humans, SULT1A1 activity is affected by genetic polymorphisms, including single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs)...
March 22, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28303724/non-alcoholic-fatty-liver-disease-nafld-pathogenesis-classification-and-effect-on-drug-metabolizing-enzymes-and-transporters
#19
Enoch Cobbina, Fatemeh Akhlaghi
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. It is defined by the presence of steatosis in more than 5% of hepatocytes with little or no alcohol consumption. Insulin resistance, the metabolic syndrome or type 2 diabetes and genetic variants of PNPLA3 or TM6SF2 seem to play a role in the pathogenesis of NAFLD. The pathological progression of NAFLD follows tentatively a "three-hit" process namely steatosis, lipotoxicity and inflammation. The presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 has been implicated in the alterations of nuclear factors such as CAR, PXR, PPAR-α in NAFLD...
March 17, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28286122/regioselective-production-of-sulfated-polyphenols-using-human-cytosolic-sulfotransferase-expressing-escherichia-coli-cells
#20
Takehiko Shimohira, Katsuhisa Kurogi, Takuyu Hashiguchi, Ming-Cheh Liu, Masahito Suiko, Yoichi Sakakibara
Dietary polyphenols present in fruits and vegetables have been reported to manifest beneficial health effects on humans. Polyphenol metabolites including their sulfated derivatives have been shown to be biologically active. Primarily due to the difficulty in preparing regiospecific sulfated polyphenols for detailed investigations, the exact functions of sulfated polyphenols, however, remain unclear. The current study aimed to develop a procedure for the regioselective production of sulfated polyphenols using Escherichia coli cells expressing human cytosolic sulfotransferases (SULTs)...
July 2017: Journal of Bioscience and Bioengineering
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