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https://www.readbyqxmd.com/read/28430630/estrogen-and-androgen-converting-enzymes-17%C3%AE-hydroxysteroid-dehydrogenase-and-their-involvement-in-cancer-with-a-special-focus-on-17%C3%AE-hydroxysteroid-dehydrogenase-type-1-2-and-breast-cancer
#1
REVIEW
Erik Hilborn, Olle Stål, Agneta Jansson
Sex steroid hormones such as estrogens and androgens are involved in the development and differentiation of the breast tissue. The activity and concentration of sex steroids is determined by the availability from the circulation, and on local conversion. This conversion is primarily mediated by aromatase, steroid sulfatase, and 17β-hydroxysteroid dehydrogenases. In postmenopausal women, this is the primary source of estrogens in the breast. Up to 70-80% of all breast cancers express the estrogen receptor-α, responsible for promoting the growth of the tissue...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429243/slco1b1-polymorphisms-and-plasma-estrone-conjugates-in-postmenopausal-women-with-er-%C3%A2-breast-cancer-genome-wide-association-studies-of-the-estrone-pathway
#2
Tanda M Dudenkov, James N Ingle, Aman U Buzdar, Mark E Robson, Michiaki Kubo, Irada Ibrahim-Zada, Anthony Batzler, Gregory D Jenkins, Tracy L Pietrzak, Erin E Carlson, Poulami Barman, Matthew P Goetz, Donald W Northfelt, Alvaro Moreno-Aspita, Clark V Williard, Krishna R Kalari, Yusuke Nakamura, Liewei Wang, Richard M Weinshilboum
BACKGROUND: Estrone (E1), the major circulating estrogen in postmenopausal women, promotes estrogen-receptor positive (ER+) breast tumor growth and proliferation. Two major reactions contribute to E1 plasma concentrations, aromatase (CYP19A1) catalyzed E1 synthesis from androstenedione and steroid sulfatase (STS) catalyzed hydrolysis of estrone conjugates (E1Cs). E1Cs have been associated with breast cancer risk and may contribute to tumor progression since STS is expressed in breast cancer where its activity exceeds that of aromatase...
April 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28428354/multiplex-tandem-mass-spectrometry-enzymatic-activity-assay-for-newborn-screening-of-the-mucopolysaccharidoses-and-type-2-neuronal-ceroid-lipofuscinosis
#3
Yang Liu, Fan Yi, Arun Babu Kumar, Naveen Kumar Chennamaneni, Xinying Hong, C Ronald Scott, Michael H Gelb, Frantisek Turecek
BACKGROUND: We expanded the use of tandem mass spectrometry combined with liquid chromatography (LC-MS/MS) for multiplex newborn screening of seven lysosomal enzymes in dried blood spots (DBS). The new assays are for enzymes responsible for the mucopolysaccharidoses (MPS-I, -II, -IIIB, -IVA, -VI, and -VII) and type 2 neuronal ceroid lipofuscinosis (LINCL). METHODS: New substrates were prepared and char-acterized for tripeptidyl peptidase 1 (TPP1), α-N-acetylglucosaminidase (NAGLU), and lysosomal β-glucuronidase (GUSB)...
April 20, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28406629/first-dual-inhibitors-of-steroid-sulfatase-sts-and-17%C3%AE-hydroxysteroid-dehydrogenase-type-1-17%C3%AE-hsd1-designed-multiple-ligands-as-novel-potential-therapeutics-for-estrogen-dependent-diseases
#4
Mohamed Salah, Ahmed Saad Abdelsamie, Martin Frotscher
STS and 17β-HSD1 are attractive targets for the treatment of estrogen-dependent diseases like endometriosis and breast cancer. The simultaneous inhibition of both enzymes appears more promising than blockage of either protein alone. We describe a designed multiple target approach resulting in highly potent dual inhibitors. The most interesting compound 9 showed nanomolar IC50s for both proteins, membrane permeability and no interference with estrogen receptors. It efficiently reversed E1S- and E1-induced T47D cell proliferation...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28401457/comparative-studies-of-vertebrate-iduronate-2-sulfatase-ids-genes-and-proteins-evolution-of-a-mammalian-x-linked-gene
#5
REVIEW
Roger S Holmes
IDS is responsible for the lysosomal degradation of heparan sulfate and dermatan sulfate and linked to an X-linked lysosomal storage disease, mucopolysaccharidosis 2 (MPS2), resulting in neurological damage and early death. Comparative IDS amino acid sequences and structures and IDS gene locations were examined using data from several vertebrate genome projects. Vertebrate IDS sequences shared 60-99% identities with each other. Human IDS showed 47% sequence identity with fruit fly (Drosophila melanogaster) IDS...
May 2017: 3 Biotech
https://www.readbyqxmd.com/read/28391878/autosomal-dominant-familial-dysbetalipoproteinemia-a-pathophysiological-framework-and-practical-approach-to-diagnosis-and-therapy
#6
REVIEW
Charlotte Koopal, A David Marais, Jan Westerink, Frank L J Visseren
Familial dysbetalipoproteinemia (FD) is a genetic disorder of lipoprotein metabolism associated with an increased risk for premature cardiovascular disease. In about 10% of the cases, FD is caused by autosomal dominant mutations in the apolipoprotein E gene (APOE). This review article provides a pathophysiological framework for autosomal dominant FD (ADFD) and discusses diagnostic challenges and therapeutic options. The clinical presentation and diagnostic work-up of ADFD are illustrated by two cases: a male with premature coronary artery disease and a p...
January 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28362416/a-straightforward-method-for-glucosinolate-extraction-and-analysis-with-high-pressure-liquid-chromatography-hplc
#7
Katharina Grosser, Nicole M van Dam
Glucosinolates are a well-studied and highly diverse class of natural plant compounds. They play important roles in plant resistance, rapeseed oil quality, food flavoring, and human health. The biological activity of glucosinolates is released upon tissue damage, when they are mixed with the enzyme myrosinase. This results in the formation of pungent and toxic breakdown products, such as isothiocyanates and nitriles. Currently, more than 130 structurally different glucosinolates have been identified. The chemical structure of the glucosinolate is an important determinant of the product that is formed, which in turn determines its biological activity...
March 15, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28348236/optical-visualization-and-quantification-of-enzyme-activity-using-dynamic-droplet-lenses
#8
Lauren D Zarzar, Julia A Kalow, Xinping He, Joseph J Walish, Timothy M Swager
In this paper, we describe an approach to measuring enzyme activity based on the reconfiguration of complex emulsions. Changes in the morphology of these complex emulsions, driven by enzyme-responsive surfactants, modulate the transmission of light through a sample. Through this method we demonstrate how simple photodetector measurements may be used to monitor enzyme kinetics. This approach is validated by quantitative measurements of enzyme activity for three different classes of enzymes (amylase, lipase, and sulfatase), relying on two distinct mechanisms for coupling droplet morphology to enzyme activity (host-guest interactions with uncaging and molecular cleavage)...
March 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28334757/perturbations-in-cell-signaling-elicit-early-cardiac-defects-in-mucopolysaccharidosis-type-ii
#9
Roberto Costa, Andrea Urbani, Marika Salvalaio, Stefania Bellesso, Domenico Cieri, Ilaria Zancan, Mirella Filocamo, Paolo Bonaldo, Ildiko Szabò, Rosella Tomanin, Enrico Moro
Morphogens release and activity can be negatively affected by an impaired glycosaminoglycans (GAGs) turnover and proteoglycans assembly in the extracellular matrix, leading to altered tissue morphogenesis. In this work, we show that loss of Iduronate-2-sulfatase (IDS) activity, affecting GAGs catabolism and responsible for a life-threatening valvulopathy in mucopolysaccharidosis type II (MPSII), triggers early Sonic Hedgehog (Shh) and Wnt/β-catenin signaling defects, leading to aberrant heart development and atrioventricular valve formation in a zebrafish model...
February 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334745/disease-correction-by-aav-mediated-gene-therapy-in-a-new-mouse-model-of-mucopolysaccharidosis-type-iiid
#10
Carles Roca, Sandra Motas, Sara Marcó, Albert Ribera, Víctor Sánchez, Xavier Sánchez, Joan Bertolin, Xavier León, Jennifer Pérez, Miguel Garcia, Pilar Villacampa, Jesús Ruberte, Anna Pujol, Virginia Haurigot, Fatima Bosch
Gene therapy is a promising therapeutic alternative for Lysosomal Storage Disorders (LSD), as it is not necessary to correct the genetic defect in all cells of an organ to achieve therapeutically significant levels of enzyme in body fluids, from which non-transduced cells can uptake the protein correcting their enzymatic deficiency. Animal models are instrumental in the development of new treatments for LSD. Here we report the generation of the first mouse model of the LSD Muccopolysaccharidosis Type IIID (MPSIIID), also known as Sanfilippo syndrome type D...
April 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334528/why-prodrugs-and-propesticides-succeed
#11
John E Casida
What are the advantages of bioactivation in optimizing drugs and pesticides? Why are there so many prodrugs and propesticides? These questions are examined here by considering compounds selected on the basis of economic value or market success. The 100 major drugs and 90 major pesticides are divided into ones acting directly and those definitely or possibly requiring bioactivation. Established or candidate prodrugs accounted for 19% of the total drug sales with corresponding values of 20, 37 and 17% for proinsecticides, proherbicides and profungicides...
March 23, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28326039/estrone-sulfate-transport-and-steroid-sulfatase-activity-in-colorectal-cancer-implications-for-hormone-replacement-therapy
#12
Lorna C Gilligan, Ali Gondal, Vivien Tang, Maryam T Hussain, Anastasia Arvaniti, Anne-Marie Hewitt, Paul A Foster
Hormone replacement therapy (HRT) affects the incidence and potential progression of colorectal cancer (CRC). As HRT primarily consists of estrone sulfate (E1S), understanding whether this conjugated estrogen is transported and metabolized in CRC will define its potential effect in this malignancy. Here, we show that a panel of CRC cell lines (Colo205, Caco2, HCT116, HT-29) have steroid sulfatase (STS) activity, and thus can hydrolyze E1S. STS activity is significantly higher in CRC cell lysate, suggesting the importance of E1S transport in intracellular STS substrate availability...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28320104/sulfatase-2-promotes-the-growth-and-metastasis-of-colorectal-cancer-by-activating-akt-and-erk1-2-pathways
#13
Youmao Tao, Tao Han, Tao Zhang, Caixia Sun
The molecular mechanisms underlying the growth and metastasis of colorectal cancer (CRC) remain largely unknown. Sulfatase-2 (SULF2) was found to play critical roles in human cancers. Recent study reported that SULF1/2 overexpression resulted in increased viability and proliferation, and augmented cell migration in CRC cells. However, the expression of SULF2 and its underlying molecular mechanisms in CRC remain unknown. In this study, we found that the expressions of SULF2 in CRC tissues and cell lines were significantly increased compared to control groups...
March 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28315670/sulfatase-activity-assay-using-an-activity-based-probe-by-generation-of-n-methyl-isoindole-under-reducing-conditions
#14
Hey Young Yoon, Jong-In Hong
Sulfatases catalyze the hydrolysis of sulfate esters that are present in a range of biomolecules. This is an important step in several biological processes such as cellular degradation, hormone regulation, and cell signaling. We have developed a new activity-based sulfatase probe (probe 1) that generates a fluorescent N-methylisoindole upon hydrolysis by sulfatase. Because of the autoxidation of N-methylisoindole, the sulfatase activity was also tested under reducing conditions, containing either glutathione (GSH) or tris(2-carboxyethyl)phosphine (TCEP), exhibiting little change in kinetic parameters compared to non-reducing conditions...
March 16, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28302098/in-vivo-confocal-microscopy-of-pre-descemet-corneal-dystrophy-associated-with-x-linked-ichthyosis-a-case-report
#15
Hui Shi, Xiao-Feng Qi, Tao-Tao Liu, Qian Hao, Xiao-Hong Li, Ling-Ling Liang, Yi-Miao Wang, Zhi-Hua Cui
BACKGROUND: Pre-Descemet corneal dystrophy (PDCD) is characterized by the presence of numerous, tiny, polymorphic opacities immediately anterior to Descemet membrane, which is a rare form of corneal stromal dystrophy and hard to be diagnosed. In vivo confocal microscopy (IVCM) is a useful tool to examine the minimal lesions of the cornea at the cellular level. In this article, we report a rare case of PDCD associated with X-linked ichthyosis and evaluate IVCM findings. CASE PRESENTATION: We present a 34-year-old male Chinese patient with PDCD associated with X-linked ichthyosis...
March 16, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/28293481/a-genetic-variant-within-sts-previously-associated-with-inattention-in-boys-with-attention-deficit-hyperactivity-disorder-is-associated-with-enhanced-cognition-in-healthy-adult-males
#16
Trevor Humby, Amelia Fisher, Christopher Allen, Meghann Reynolds, Annette Hartman, Ina Giegling, Dan Rujescu, William Davies
INTRODUCTION: The enzyme steroid sulfatase (STS) converts sulfated steroids to their non-sulfated forms. Deficiency for this enzyme is associated with inattention but preserved response control. The polymorphism rs17268988 within the X-linked STS gene is associated with inattentive, but not other, symptoms in boys with attention deficit hyperactivity disorder (ADHD). METHODS: We initially tested whether rs17268988 genotype was associated with attention, response control, and underlying aspects of cognition, using questionnaires and neuropsychological tasks, in two independent cohorts of healthy adult males...
March 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28284963/a-structural-appraisal-of-sterol-carrier-protein-2
#17
REVIEW
Noelia I Burgardt, Alejo R Gianotti, Raúl G Ferreyra, Mario R Ermácora
Sterol Carrier Protein 2 (SCP2) has been associated with lipid binding and transfer activities. However, genomic, proteomic, and structural studies revealed that it is an ubiquitous domain of complex proteins with a variety functions in all forms of life. High-resolution structures of representative SCP2 domains are available, encouraging a comprehensive review of the structural basis for its success. Most SCP2 domains pertain to three major families and are frequently found as stand-alone or at the C-termini of lipid related peroxisomal enzymes, acetyltransferases causing bacterial resistance, and bacterial environmentally important sulfatases...
March 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28274582/estrogen-receptor-agonists-antagonists-in-breast-cancer-therapy-a-critical-review
#18
REVIEW
A Jameera Begam, S Jubie, M J Nanjan
Estrogens display intriguing tissue selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer. There are also strong evidences to show that both endogenous and exogenous estrogens are involved in the pathogenesis of breast cancer. Tamoxifen has been the only drug of choice for more than 30years to treat patients with estrogen related (ER) positive breast tumors. There is a need therefore, for identifying newer, potential and novel candidates for breast cancer...
February 23, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28273623/changes-in-enzymatic-activities-in-metal-contaminated-and-reclaimed-lands-in-northern-ontario-canada
#19
Ramya Narendrula-Kotha, Kabwe K Nkongolo
Metal and sulfur dioxide (SO2) contaminations in Northern Ontario (Canada), especially in the Greater Sudbury Region (GSR) caused by mining activities have resulted in severe environmental degradations. A long term restoration program has led to significant landscape changes and healthy ecosystems. The objective of this study was to assess variation in enzymatic activities and soil respiration in metal contaminated and reclaimed ecosystems. Soil analysis revealed that respiration rates were higher in metal contaminated limed soils (65ppm) compared to adjacent unlimed areas (35ppm)...
March 5, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28257906/comparative-and-evolutionary-studies-of-mammalian-arylsulfatase-and-sterylsulfatase-genes-and-proteins-encoded-on-the-x-chromosome
#20
Roger S Holmes
At least 19 sulfatase genes have been reported on the human genome, including four arylsulfatase (ARS) genes (ARSD; ARSE; ARSF; ARSH) and a sterylsulfatase (STS) gene located together on the X-chromosome. Bioinformatic analyses of mammalian genomes were undertaken using known human STS and ARS amino acid sequences to study the evolution of these genes and proteins encoded on eutherian and marsupial genomes. Several domain regions and key residues were conserved including signal peptides, active site residues, metal (Ca(2+)) and substrate binding sequences, transmembranes and N-glycosylation sites...
February 24, 2017: Computational Biology and Chemistry
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