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https://www.readbyqxmd.com/read/28795252/ipet-study-an-flt-pet-window-study-to-assess-the-activity-of-the-steroid-sulfatase-inhibitor-irosustat-in-early-breast-cancer
#1
Carlo Palmieri, Richard Szydlo, Marie Miller, Laura Barker, Neva H Patel, Hironobu Sasano, Tara Barwick, Henry Tam, Dimitri Hadjiminas, Jasmin Lee, Abeer Shaaban, Hanna Nicholas, R Charles Coombes, Laura M Kenny
BACKGROUND: Steroid sulfatase (STS) is involved in oestrogen biosynthesis and irosustat is a first generation, irreversible steroid sulfatase inhibitor. A pre-surgical window-of-opportunity study with irosustat was undertaken in estrogen receptor-positive (ER+) breast cancer to assess the effect of irosustat on tumour cell proliferation as measured by 3'-deoxy-3'-[18F] fluorothymidine uptake measured by PET scanning (FLT-PET) and Ki67. METHODS: Postmenopausal women with untreated ER+ early breast cancer were recruited, and imaged with FLT-PET at baseline and after at least 2 weeks treatment with irosustat, 40 mg once daily orally...
August 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28783562/simultaneous-determination-of-paeonilactone-a-and-paeonilactone-b-in-rat-plasma-after-oral-administration-of-albiflorin-by-uplc-tof-ms-following-picolinoyl-derivatization
#2
Zhigang Wang, Shuhan Tang, Masao Hattori, Hailong Zhang, Xiuhong Wu
A new highly sensitive analytical method was developed to investigate the in vivo metabolism of albiflorin, one of the most principal components in traditional Chinese medicine. After hydrolyzation with sulfatase, the main metabolites paeonilactone A and paeonilactone B of paeoniflorin in rat plasma were successfully detected for the first time by liquid chromatography mass spectrometry following picolinoyl derivatization. Borneol was used as the internal standard compound to quantify paeonilactone A and paeonilactone B in rat plasma...
July 29, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28743544/sodium-dependent-organic-anion-transporter-slc10a6-knockout-mice-show-normal-spermatogenesis-and-reproduction-but-elevated-serum-levels-for-cholesterol-sulfate
#3
Katharina Bakhaus, Josefine Bennien, Daniela Fietz, Alberto Sánchez-Guijo, Michaela Hartmann, Rosanna Serafini, Charles C Love, Andrei Golovko, Stefan A Wudy, Martin Bergmann, Joachim Geyer
The sodium-dependent organic anion transporter SOAT (gene name SLC10A6 in man and Slc10a6 in mice) is a plasma membrane transporter for sulfated steroids, which is highly expressed in germ cells of the testis. SOAT can transport biologically inactive sulfated steroids into specific target cells, where they can be reactivated by the steroid sulfatase (STS) to biologically active, unconjugated steroids known to regulate spermatogenesis. Significantly reduced SOAT mRNA expression was previously found in different forms of impaired spermatogenesis in man...
July 22, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28724898/improvement-in-the-production-of-the-human-recombinant-enzyme-n-acetylgalactosamine-6-sulfatase-rhgalns-in-escherichia-coli-using-synthetic-biology-approaches
#4
Luis H Reyes, Carolina Cardona, Luisa Pimentel, Alexander Rodríguez-López, Carlos J Alméciga-Díaz
Previously, we demonstrated production of an active recombinant human N-acetylgalactosamine-6-sulfatase (rhGALNS) enzyme in Escherichia coli as a potential therapeutic alternative for mucopolysaccharidosis IVA. However, most of the rhGALNS produced was present as protein aggregates. Here, several methods were investigated to improve production and activity of rhGALNS. These methods involved the use of physiologically-regulated promoters and alternatives to improve protein folding including global stress responses (osmotic shock), overexpression of native chaperones, and enhancement of cytoplasmic disulfide bond formation...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720494/the-eukaryotic-enzyme-bds1-is-an-alkyl-but-not-an-aryl-sulfohydrolase
#5
Grace L Waddell, Caroline R Gilmer, Nicholas G Taylor, John Randolf S Reveral, Marcello Forconi, Jennifer L Fox
The eukaryotic enzyme Bds1 in Saccharomyces cerevisiae is a metallo-β-lactamase-related enzyme evolutionarily originating from bacterial horizontal gene transfer that serves an unknown biological role. Previously, Bds1 was reported to be an alkyl and aryl sulfatase. However, we demonstrate here that Bds1 acts on primary alkyl sulfates (of 6-12 carbon atoms) but not the aryl sulfates p-nitrophenyl sulfate and p-nitrocatechol sulfate. The apparent catalytic rate constant for hydrolysis of the substrate 1-hexyl sulfate by Bds1 is over 100 times lower than that of the reaction catalyzed by its bacterial homolog SdsA1...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28711911/human-steroid-sulfatase-induces-wnt-%C3%AE-catenin-signaling-and-epithelial-mesenchymal-transition-by-upregulating-twist1-and-hif-1%C3%AE-in-human-prostate-and-cervical-cancer-cells
#6
Sangyun Shin, Hee-Jung Im, Yeo-Jung Kwon, Dong-Jin Ye, Hyoung-Seok Baek, Donghak Kim, Hyung-Kyoon Choi, Young-Jin Chun
Steroid sulfatase (STS) catalyzes the hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) to their unconjugated biologically active forms. Although STS is considered a therapeutic target for estrogen-dependent diseases, the cellular functions of STS remain unclear. We found that STS induces Wnt/β-catenin s Delete ignaling in PC-3 and HeLa cells. STS increases levels of β-catenin, phospho-β-catenin, and phospho-GSK3β. Enhanced translocation of β-catenin to the nucleus by STS might activate transcription of target genes such as cyclin D1, c-myc, and MMP-7...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28710970/validation-of-a-probe-for-assessing-deconjugation-of-glucuronide-and-sulfate-phase-ii-metabolites-assayed-through-lc-ms-ms-in-biological-matrices
#7
Claire Grignon, Antoine Dupuis, Marion Albouy-Llaty, Maxime Condylis, Laurence Barrier, Pascal Carato, Bertrand Brunet, Virginie Migeot, Nicolas Venisse
LC-MS/MS has been proposed in various areas such as Therapeutic Drug Monitoring (TDM), Human Biomonitoring (HBM), disease diagnosis, clinical toxicology and doping control to identify and quantify chemical parents and their metabolites in biological matrices. To determine the total content of a xenobiotic (unconjugated+conjugated forms), an enzymatic hydrolysis step is required. Most studies in the literature have not controlled the effectiveness of the deconjugation process because no method has been described for that purpose...
July 10, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28710204/bio-plex-immunoassay-measuring-the-quantity-of-lysosomal-n-acetylgalactosamine-6-sulfatase-protein-in-dried-blood-spots-for-the-screening-of-mucopolysaccharidosis-iva-in-newborn-a-pilot-study
#8
Chih-Kuang Chuang, Hsiang-Yu Lin, Tuan-Jen Wang, Sung-Fa Huang, Shuan-Pei Lin
OBJECTIVE: Mucopolysaccharidosis (MPS) IVA (Morquio syndrome A) is an autosomal-recessive lysosomal storage disorder caused by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS) resulting in excessive lysosomal storage of keratan sulfate. Treatments for MPS IVA have recently become available with optimal outcomes associated with early diagnosis and treatment which can be achieved by newborn screening. DESIGN: Newborn screening programme for MPS IVA pilot study...
July 13, 2017: BMJ Open
https://www.readbyqxmd.com/read/28710038/steroid-sulfatase-and-filaggrin-mutations-in-a-boy-with-severe-ichthyosis-elevated-serum-ige-level-and-moyamoya-syndrome
#9
Qian Zhang, Nuo Si, Yaping Liu, Dong Zhang, Rong Wang, Yan Zhang, Shuo Wang, Xingju Liu, Xiaofeng Deng, Yonggang Ma, Peicong Ge, Jizong Zhao, Xue Zhang
X-linked ichthyosis (XLI) is a relatively common, recessive condition caused by mutations in the steroid sulfatase (STS) gene. Common loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and predispose individuals to atopic eczema. We report a case of a 6-year-old boy who presented with unusually severe XLI, an increased serum immunoglobulin E level (2120IU/ml) and moyamoya angiopathy. Whole-exome sequencing identified a gross deletion encompassing the STS in Xp22.31 and the p.K4022X FLG mutation...
July 11, 2017: Gene
https://www.readbyqxmd.com/read/28697587/detection-of-bacterial-sulfatase-activity-through-liquid-and-solid-phase-colony-based-assays
#10
Hey Young Yoon, Hyung Jun Kim, Soojin Jang, Jong-In Hong
Bacterial arylsulfatases are crucial to biosynthesis in many microorganisms, as bacteria often utilize aryl sulfates as a source of sulfur. The bacterial sulfatases are associated with pathogenesis and are applied in many areas such as industry and agriculture. We developed an activity-based probe 1 for detection of bacterial sulfatase activity through liquid- and solid-phase colony-based assays. Probe 1 is hydrolyzed by sulfatase to generate fluorescent N-methyl isoindole, which is polymerized to form colored precipitates...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28690541/the-significance-of-the-sulfatase-pathway-for-local-estrogen-formation-in-endometrial-cancer
#11
Maša Sinreih, Tamara Knific, Maja Anko, Neli Hevir, Katja Vouk, Aleš Jerin, Snježana Frković Grazio, Tea Lanišnik Rižner
Endometrial cancer (EC) is the most common estrogen-dependent gynecological malignancy in the developed World. To investigate the local formation of estradiol (E2), we first measured the concentrations of the steroid precursor androstenedione (A-dione) and the most potent estrogen, E2, and we evaluated the metabolism of A-dione, estrone-sulfate (E1-S), and estrone (E1) in cancerous and adjacent control endometrium. Furthermore, we studied expression of the key genes for estradiol formation via the aromatase and sulfatase pathways...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28679314/pre-treatment-of-different-biological-matrices-for-exogenous-testosterone-analysis-a-review
#12
Edna Carolina Pizzato, Marcelo Filonzi, Hemerson Silva da Rosa, André Valle de Bairros
Exogenous testosterone presence has been monitored mainly in urine and blood, however other biological matrices such as hair, nails and saliva samples can be used with successful for in vivo measurement. Chromatographic analysis requires pre-treatment to obtain free testosterone and its metabolites. Among the pre-treatment procedures, digestion, hydrolysis and solvolysis steps are used to reach the analytical purpose. Digestion assay is indicated for hair and nails samples. First, it is recommended decontamination step...
July 5, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28651356/heterologous-expression-in-pichia-pastoris-and-biochemical-characterization-of-the-unmodified-sulfatase-from-fusarium-proliferatum-le1
#13
Svetlana A Korban, Kirill S Bobrov, Maria A Maynskova, Stanislav N Naryzhny, Olga L Vlasova, Elena V Eneyskaya, Anna A Kulmisnkaya
Sulfatases are a family of enzymes (sulfuric ester hydrolases, EC 3.1.6.-) that catalyze the hydrolysis of a wide array of sulfate esters. To date, despite the discovery of many sulfatase genes and the accumulation of data on numerous sulfated molecules, the number of characterized enzymes that are key players in sulfur metabolism remains extremely limited. While mammalian sulfatases are well studied due to their involvement in a wide range of normal and pathological biological processes, lower eukaryotic sulfatases, especially fungal sulfatases, have not been thoroughly investigated at the biochemical and structural level...
June 23, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28650341/two-rheumatoid-arthritis-specific-autoantigens-correlate-microbial-immunity-with-autoimmune-responses-in-joints
#14
Annalisa Pianta, Sheila L Arvikar, Klemen Strle, Elise E Drouin, Qi Wang, Catherine E Costello, Allen C Steere
In rheumatoid arthritis (RA), immunological triggers at mucosal sites, such as the gut microbiota, may promote autoimmunity that affects joints. Here, we used discovery-based proteomics to detect HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. Both GNS and FLNA were highly expressed in synovia. GNS appeared to be citrullinated, and GNS antibody values correlated with anti-citrullinated protein antibody (ACPA) levels...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28649514/early-hematopoietic-stem-cell-transplantation-in-a-patient-with-severe-mucopolysaccharidosis-ii-a-7%C3%A2-years-follow-up
#15
Anneliese L Barth, Tatiana S P C de Magalhães, Ana Beatriz R Reis, Maria Lucia de Oliveira, Fernanda B Scalco, Nicolette C Cavalcanti, Daniel S E Silva, Danielle A Torres, Alessandra A P Costa, Carmem Bonfim, Roberto Giugliani, Juan C Llerena, Dafne D G Horovitz
Mucopolysaccharidosis type II (MPS II - Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency in the enzyme iduronate-2 sulfatase (I2S), leading to the accumulation of the glycosaminoglycans, affecting multiple organs and systems. Enzyme replacement therapy does not cross the blood brain barrier, limiting results in neurological forms of the disease. Another option of treatment for severe MPS, hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for the severe form of MPS type I, since it can preserve neurocognition when performed early in the course of the disease...
September 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28643276/a-rapid-two-step-iduronate-2-sulfatatse-enzymatic-activity-assay-for-mpsii-pharmacokinetic-assessment
#16
Mitra Azadeh, Luying Pan, Yongchang Qiu, Ruben Boado
Clinical studies involving enzyme replacement therapies (ERTs) have increasingly utilized enzymatic activity assays to monitor efficacy and biofunction of the drug; as a result, these assays have become an important part of pharmacokinetic (PK) and pharmacodynamic assessments in ERT trials. This paper presents a two-step enzymatic activity assay for iduronate-2-sulfatase (I2S) (EC 3.1.6.13) which we have optimized to fit in 1 day and to complete in less than 6 h. The rapid assay presented here is a significant improvement over the original two-step method with run time of 24 h which spanned 2 days...
June 23, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28630303/how-members-of-the-human-gut-microbiota-overcome-the-sulfation-problem-posed-by-glycosaminoglycans
#17
Alan Cartmell, Elisabeth C Lowe, Arnaud Baslé, Susan J Firbank, Didier A Ndeh, Heath Murray, Nicolas Terrapon, Vincent Lombard, Bernard Henrissat, Jeremy E Turnbull, Mirjam Czjzek, Harry J Gilbert, David N Bolam
The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron, a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases and sulfatases that mediate degradation...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28612226/iris-study-a-phase-ii-study-of-the-steroid-sulfatase-inhibitor-irosustat-when-added-to-an-aromatase-inhibitor-in-er-positive-breast-cancer-patients
#18
Carlo Palmieri, Rob C Stein, Xinxue Liu, Emma Hudson, Hanna Nicholas, Hironobu Sasano, Fouzia Guestini, Chris Holcombe, Sophie Barrett, Laura Kenny, Sadie Reed, Adrian Lim, Larry Hayward, Sacha Howell, R Charles Coombes
PURPOSE: Irosustat is a first-generation, orally active, irreversible steroid sulfatase inhibitor. We performed a multicentre, open label phase II trial of the addition of Irosustat to a first-line aromatase inhibitor (AI) in patients with advanced BC to evaluate the safety of the combination and to test the hypothesis that the addition of Irosustat to AI may further suppress estradiol levels and result in clinical benefit. EXPERIMENTAL DESIGN: Postmenopausal women with ER-positive locally advanced or metastatic breast cancer who had derived clinical benefit from a first-line AI and who subsequently progressed were enrolled...
September 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28593992/insights-into-hunter-syndrome-from-the-structure-of-iduronate-2-sulfatase
#19
Mykhaylo Demydchuk, Chris H Hill, Aiwu Zhou, Gábor Bunkóczi, Penelope E Stein, Denis Marchesan, Janet E Deane, Randy J Read
Hunter syndrome is a rare but devastating childhood disease caused by mutations in the IDS gene encoding iduronate-2-sulfatase, a crucial enzyme in the lysosomal degradation pathway of dermatan sulfate and heparan sulfate. These complex glycosaminoglycans have important roles in cell adhesion, growth, proliferation and repair, and their degradation and recycling in the lysosome is essential for cellular maintenance. A variety of disease-causing mutations have been identified throughout the IDS gene. However, understanding the molecular basis of the disease has been impaired by the lack of structural data...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28588698/clinical-significance-of-the-estrogen-modifying-enzymes-steroid-sulfatase-and-estrogen-sulfotransferase-in-epithelial-ovarian-cancer
#20
Felicitas Mungenast, Stefanie Aust, Ignace Vergote, Adriaan Vanderstichele, Jalid Sehouli, Elena Braicu, Sven Mahner, Dan Cacsire Castillo-Tong, Robert Zeillinger, Theresia Thalhammer
17β-estradiol (E2) can contribute to the progression of epithelial ovarian cancer (EOC). Although the majority of patients with EOC are postmenopausal woman, when de novo estrogen production in the ovary has ceased, ovarian cancer cells remain exposed to estrogens synthesized locally in the cancer cells from inactive sulfonated steroid hormone precursors-such as estrone sulfate taken up from the circulation via the sulfatase pathway. An abundance of the estrogen-modifying enzymes, including estrogen-activating steroid sulfatase (STS) and estrogen-inactivating estrogen-sulfotransferase (SULT1E1), is important for providing active estrogen to EOC cells...
June 2017: Oncology Letters
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