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Lysyl oxidase like 1

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https://www.readbyqxmd.com/read/28073888/selective-targeting-of-lysyl-oxidase-like-2-loxl2-suppresses-hepatic-fibrosis-progression-and-accelerates-its-reversal
#1
Naoki Ikenaga, Zhen-Wei Peng, Kahini A Vaid, Susan B Liu, Shuhei Yoshida, Deanna Y Sverdlov, Amanda Mikels-Vigdal, Victoria Smith, Detlef Schuppan, Yury V Popov
BACKGROUND/AIMS: We studied the role of lysyl oxidase-like 2 (LOXL2) in collagen crosslinking and hepatic progenitor cell (HPC) differentiation, and the therapeutic efficacy of a LOXL2-blocking monoclonal antibody on liver fibrosis progression/reversal in mice. METHODS: Anti-LOXL2 antibody, control antilysyl oxidase antibody or placebo was administered during thioacetamide (TAA)-induced fibrosis progression or during recovery. Therapeutic efficacy in biliary fibrosis was tested in BALB/c...
January 10, 2017: Gut
https://www.readbyqxmd.com/read/28060764/loxl4-knockdown-enhances-tumor-growth-and-lung-metastasis-through-collagen-dependent-extracellular-matrix-changes-in-triple-negative-breast-cancer
#2
Sul Ki Choi, Hoe Suk Kim, Tiefeng Jin, Woo Kyung Moon
Lysyl oxidase (LOX) family genes catalyze collagen cross-link formation. To determine the effects of lysyl oxidase-like 4 (LOXL4) expression on breast tumor formation and metastasis, we evaluated primary tumor growth and lung metastasis in mice injected with LOXL4-knockdown MDA-MB-231 triple-negative human breast cancer cells. In addition, we analyzed overall survival in breast cancer patients based on LOXL4 expression using a public online database. In the mouse xenograft model, LOXL4 knockdown increased primary tumor growth and lung colonization as well as collagen I and IV, lysine hydroxylase 1 and 2, and prolyl 4-hydroxylase subunit alpha 1 and 2 levels...
2, 2017: Oncotarget
https://www.readbyqxmd.com/read/27939076/efficacy-of-simtuzumab-versus-placebo-in-patients-with-idiopathic-pulmonary-fibrosis-a-randomised-double-blind-controlled-phase-2-trial
#3
Ganesh Raghu, Kevin K Brown, Harold R Collard, Vincent Cottin, Kevin F Gibson, Robert J Kaner, David J Lederer, Fernando J Martinez, Paul W Noble, Jin Woo Song, Athol U Wells, Timothy P M Whelan, Wim Wuyts, Emmanuel Moreau, Scott D Patterson, Victoria Smith, Selina Bayly, Jason W Chien, Qi Gong, Jenny J Zhang, Thomas G O'Riordan
BACKGROUND: Lysyl oxidase-like 2 (LOXL2) catalyses collagen cross-linking and is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the efficacy and safety of simtuzumab, a monoclonal antibody against LOXL2, in patients with IPF. METHODS: In this randomised, double-blind, phase 2 trial, we recruited patients aged 45-85 years with definite IPF diagnosed prior to 3 years of screening from 183 hospitals and respiratory clinics in 14 countries...
January 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/27753755/association-of-lysyl-oxidase-like-1-gene-polymorphism-in-turkish-patients-with-pseudoexfoliation-syndrome-and-pseudoexfoliation-glaucoma
#4
Mahmut Asfuroglu, Busranur Cavdarli, Ozlem G Koz, Ahmet A Yarangumeli, Emine Y Ozdemir
PURPOSE: To investigate the genetic association of lysyl oxidase-like 1 (LOXL1) gene polymorphisms in patients with pseudoexfoliation (PEX) syndrome and PEX glaucoma of Turkish descent. METHODS: Three LOXL1 single nucleotide polymorphisms (SNPs) (rs1048661, rs3825942, and rs2165241) were analyzed in 109 Turkish patients (44 patients with PEX syndrome, 65 patients with PEX glaucoma) and 47 healthy subjects. RESULTS: "A" allele of SNP rs3825942 was underrepresented in control group compared with the glaucoma [odds ratio (OR)=4...
October 6, 2016: Journal of Glaucoma
https://www.readbyqxmd.com/read/27488440/regulation-of-loxl2-and-serpinh1-by-antitumor-microrna-29a-in-lung-cancer-with-idiopathic-pulmonary-fibrosis
#5
Kazuto Kamikawaji, Naohiko Seki, Masaki Watanabe, Hiroko Mataki, Tomohiro Kumamoto, Koichiro Takagi, Keiko Mizuno, Hiromasa Inoue
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that is refractory to treatment and carries a high mortality rate. IPF is frequently associated with lung cancer. Identification of molecular targets involved in both diseases may elucidate novel molecular mechanisms contributing to their pathology. Recent studies of microRNA (miRNA) expression signatures showed that microRNA-29a (miR-29a) was downregulated in IPF and lung cancer. The aim of this study was to investigate the functional significance of miR-29a in lung cancer cells (A549 and EBC-1) and lung fibroblasts (MRC-5) and to identify molecular targets modulated by miR-29a in these cells...
December 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/27396912/methylation-of-loxl1-promoter-by-dnmt3a-in-aged-human-skin-fibroblasts
#6
Léa Moulin, Valérie Cenizo, Alengo Nyamay Antu, Valérie Andre-Frei, Sabine Pain, Pascal Sommer, Romain Debret
Lysyl oxidase-like 1 (LOXL1) is an amino-oxidase involved in maturation of elastic fibres. Its downregulation has been associated with elastic fibres repair loss in ageing aorta, lung, ligament and skin. Several evidences of LOXL1 epigenetic silencing by promoter methylation were reported in cancer and cutis laxa syndrome. We hypothesised that this mechanism could be implicated in skin ageing process, as far as elastic fibres are also concerned. Anti-DNMT3A chromatin immuno-precipitation was conducted with nuclear extracts from skin fibroblasts isolated from young and elderly individuals, and showed a higher level of DNMT3A protein binding to the LOXL1 promoter in older cells concomitantly to the decrease of LOXL1 mRNA expression and the increase of LOXL1 promoter methylation...
July 10, 2016: Rejuvenation Research
https://www.readbyqxmd.com/read/27363654/impact-of-stroma-loxl2-overexpression-on-the-prognosis-of-intrahepatic-cholangiocarcinoma
#7
Damien Bergeat, Alain Fautrel, Bruno Turlin, Aude Merdrignac, Michel Rayar, Karim Boudjema, Cédric Coulouarn, Laurent Sulpice
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis related to early recurrence especially in the remnant liver after surgery. ICC exhibits a dense desmoplastic stroma which plays a pivotal role in ICC aggressiveness. Thus, analyzing gene deregulation in the stroma of ICC may help to identify new prognosis biomarkers and promising therapeutic targets. The aim of this study was to evaluate the clinical relevance of the matrix-remodeling enzyme lysyl oxidase-like 2 (LOXL2) expression in ICC...
June 15, 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27285767/emerging-role-of-loxl2-in-the-promotion-of-pancreas-cancer-metastasis
#8
Joon Seong Park, Ji-Hae Lee, Yun Sun Lee, Jae Keun Kim, Seung Myung Dong, Dong Sup Yoon
Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in cancer. We analyzed the prognostic impact of LOXL2 in pancreatic cancer patients and investigated the role of LOXL2 in pancreatic cancer cell lines. Immunohistochemical analysis was performed in samples from 80 patients and showed LOXL2 expression in 81.2% of patients with pancreatic cancer. Regarding recurrence patterns, LOXL2-positive tumors showed a significantly higher rate of distant recurrence. The 1-year and 3-year disease-free survival rates were 84...
July 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27181406/epithelial-derived-inflammation-disrupts-elastin-assembly-and-alters-saccular-stage-lung-development
#9
John T Benjamin, Riet van der Meer, Amanda M Im, Erin J Plosa, Rinat Zaynagetdinov, Ankita Burman, Madeline E Havrilla, Linda A Gleaves, Vasiliy V Polosukhin, Gail H Deutsch, Hiromi Yanagisawa, Jeffrey M Davidson, Lawrence S Prince, Lisa R Young, Timothy S Blackwell
The highly orchestrated interactions between the epithelium and mesenchyme required for normal lung development can be disrupted by perinatal inflammation in preterm infants, although the mechanisms are incompletely understood. We used transgenic (inhibitory κB kinase β transactivated) mice that conditionally express an activator of the NF-κB pathway in airway epithelium to investigate the impact of epithelial-derived inflammation during lung development. Epithelial NF-κB activation selectively impaired saccular stage lung development, with a phenotype comprising rapidly progressive distal airspace dilation, impaired gas exchange, and perinatal lethality...
July 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/26997634/biological-effect-of-loxl1-coding-variants-associated-with-pseudoexfoliation-syndrome
#10
Shiwani Sharma, Sarah Martin, Matthew J Sykes, Alpana Dave, Alex W Hewitt, Kathryn P Burdon, Maurizio Ronci, Nicolas H Voelcker, Jamie E Craig
Pseudoexfoliation (PEX) syndrome is a systemic disease involving the extracellular matrix. It increases the risk of glaucoma, an irreversible cause of blindness, and susceptibility to heart disease, stroke and hearing loss. Single nucleotide polymorphisms (SNPs) in the LOXL1 (Lysyl oxidase-like 1) gene are the major known genetic risk factor for PEX syndrome. Two coding SNPs, rs1048861 (G > T; Arg141Leu) and rs3825942 (G > A; Gly153Asp), in the LOXL1 gene are strongly associated with the disease risk in multiple populations worldwide...
May 2016: Experimental Eye Research
https://www.readbyqxmd.com/read/26855560/lysyl-oxidase-like-1-polymorphisms-in-a-southwestern-greek-cataract-population-with-pseudoexfoliation-syndrome
#11
Alexios A Panoutsopoulos, Vassiliki S Gartaganis, Marios P Giannakopoulos, Panos D Goumas, Evangelos D Anastassiou, Sotirios P Gartaganis
PURPOSE: The aim of this study was to determine the possible association of rs1048661 and rs3825942 single nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene of cataract patients from southwestern Greece with pseudoexfoliation (PEX) syndrome. PATIENTS AND METHODS: Ninety-three patients with PEX syndrome and 74 without PEX syndrome were recruited with the principal diagnosis being cataract. LOXL1 SNPs, rs1048661 and rs3825942, were genotyped by using polymerase chain reaction...
2016: Clinical Ophthalmology
https://www.readbyqxmd.com/read/26829347/vaginal-expression-of-loxl1-in-premenopausal-and-postmenopausal-women-with-pelvic-organ-prolapse
#12
Nathan Kow, Beri Ridgeway, Mei Kuang, Robert S Butler, Margot S Damaser
OBJECTIVES: This study aimed to compare cellular expression of lysyl oxidase-like 1 (LOXL1), a key enzyme in elastin metabolism, of premenopausal women with pelvic organ prolapse (POP) compared with premenopausal controls without POP and postmenopausal women with POP. In addition, we examined whether variation of LOXL1 expression was dependent on biopsy site. METHODS: A standardized protocol was utilized to obtain vaginal biopsies from 30 women (10 premenopausal POP, 10 postmenopausal POP, and 10 premenopausal non-POP)...
July 2016: Female Pelvic Medicine & Reconstructive Surgery
https://www.readbyqxmd.com/read/26804196/inhibition-of-lysyl-oxidase-and-lysyl-oxidase-like-enzymes-has-tumour-promoting-and-tumour-suppressing-roles-in-experimental-prostate-cancer
#13
Maria Nilsson, Hanibal Adamo, Anders Bergh, Sofia Halin Bergström
Lysyl oxidase (LOX) and LOX-like (LOXL) enzymes are key players in extracellular matrix deposition and maturation. LOX promote tumour progression and metastasis, but it may also have tumour-inhibitory effects. Here we show that orthotopic implantation of rat prostate AT-1 tumour cells increased LOX and LOXLs mRNA expressions in the tumour and in the surrounding non-malignant prostate tissue. Inhibition of LOX enzymes, using Beta-aminopropionitrile (BAPN), initiated before implantation of AT-1 cells, reduced tumour growth...
January 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/26758070/loxl1-gene-analysis-in-turkish-patients-with-exfoliation-glaucoma
#14
Suzan Guven Yilmaz, Melis Palamar, Huseyin Onay, Orhan Ilim, Ayca Aykut, Feristah Ferda Ozkinay, Ayse Yagci
The purpose of this study is to evaluate whole lysyl oxidase like 1 (LOXL1) gene by sequence analysis in Turkish patients with exfoliation glaucoma (XFG). A total of 48 (35 male, 13 female) patients with XFG were enrolled. Besides routine ophthalmological examination, peripapillary retinal nerve fibre layer (RNFL) analysis with optic coherence tomography was performed. Blood samples of 2 ml with EDTA were obtained and sent to Medical Genetics Department, Molecular Genetics Laboratory for LOXL1 polymorphism (PCR and agarose gel imaging) analysis...
October 2016: International Ophthalmology
https://www.readbyqxmd.com/read/26648185/exfoliation-syndrome-assembling-the-puzzle-pieces
#15
Louis R Pasquale, Terete Borrás, John H Fingert, Janey L Wiggs, Robert Ritch
PURPOSE: To summarize various topics and the cutting edge approaches to refine XFS pathogenesis that were discussed at the 21st annual Glaucoma Foundation Think Tank meeting in New York City, Sept. 19-20, 2014. METHODS: The highlights of three categories of talks on cutting edge research in the field were summarized. RESULTS: Exfoliation syndrome (XFS) is a systemic disorder with a substantial ocular burden, including high rates of cataract, cataract surgery complications, glaucoma and retinal vein occlusion...
September 2016: Acta Ophthalmologica
https://www.readbyqxmd.com/read/26538021/sex-linked-skeletal-phenotype-of-lysyl-oxidase-like-1-mutant-mice
#16
Loai Alsofi, Eileen Daley, Ian Hornstra, Elise F Morgan, Zachary D Mason, Jesus F Acevedo, R Ann Word, Louis C Gerstenfeld, Philip C Trackman
Lysyl oxidases are required for collagen and elastin cross-linking and extracellular matrix maturation including in bone. The lysyl oxidase family consists of lysyl oxidase (LOX) and 4 isoforms (LOXL1-4). Here we investigate whether deletion of LOXL1, which has been linked primarily to elastin maturation, leads to skeletal abnormalities. Left femurs (n = 8), L5 vertebrae (n = 8), and tibiae (n = 8) were analyzed by micro-computed tomography in 13-week-old wild-type (WT) and LOXL1-/- male and female mice. Right femurs (n = 8) were subjected to immunohistochemistry for LOXL1, and histochemical/histology analyses of osteoclasts and growth plates...
February 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/26465133/estradiol-plays-a-role-in-regulating-the-expression-of-lysyl-oxidase-family-genes-in-mouse-urogenital-tissues-and-human-ishikawa-cells
#17
Wen Zong, Yan Jiang, Jing Zhao, Jian Zhang, Jian-gang Gao
The lysyl oxidase (LOX) family encodes the copper-dependent amine oxidases that play a key role in determining the tensile strength and structural integrity of connective tissues by catalyzing the crosslinking of elastin or collagen. Estrogen may upregulate the expression of LOX and lysyl oxidase-like 1 (LOXL1) in the vagina. The objective of this study was to determine the effect of estrogen on the expression of all LOX family genes in the urogenital tissues of accelerated ovarian aging mice and human Ishikawa cells...
October 2015: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/26338342/mechano-growth-factor-e-regulates-apoptosis-and-inflammatory-responses-in-fibroblast-like-synoviocytes-of-knee-osteoarthritis
#18
Haibin Li, Mingxing Lei, Can Yu, Yonggang Lv, Yang Song, Li Yang
PURPOSES: This study investigated whether mechano growth factor-E (MGF-E) peptide can regulate apoptosis and inflammation responses in fibroblast-like synoviocytes of osteoarthritis (OA). METHODS: A (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay was performed to evaluate cytotoxic effects of exogenous MGF-E peptide on OA fibroblast-like synoviocytes (OA-FLS). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to check messenger RNA (mRNA) expression levels of lysyl oxidase (LOX) family members (LOX) after OA-FLS treatment using MGF-E peptide...
December 2015: International Orthopaedics
https://www.readbyqxmd.com/read/26319397/loxl1-gene-variants-and-their-association-with-pseudoexfoliation-glaucoma-xfg-in-spanish-patients
#19
Lydia Álvarez, Montserrat García, Héctor González-Iglesias, Julio Escribano, Pedro P Rodríguez-Calvo, Luis Fernández-Vega, Miguel Coca-Prados
BACKGROUND: LOXL1 gene is the most important genetic risk factor known so far for pseudoexfoliation glaucoma (XFG). Our purpose was to evaluate the potential association of individual genetic variants of the lysyl oxidase-like 1 (LOXL1) gene and haplotypes with XFG in Spanish patients. METHODS: Blood samples were collected from a total of 105 Spanish patients with XFG and 200 healthy controls. The entire LOXL1 gene along with the promoter, coding and non-coding regions including the 5'- and 3'-untranslated regions, were sequenced using next-generation sequencing in 99 XFG patients...
2015: BMC Medical Genetics
https://www.readbyqxmd.com/read/26307087/genetic-variants-and-cellular-stressors-associated-with-exfoliation-syndrome-modulate-promoter-activity-of-a-lncrna-within-the-loxl1-locus
#20
Michael A Hauser, Inas F Aboobakar, Yutao Liu, Shiroh Miura, Benjamin T Whigham, Pratap Challa, Joshua Wheeler, Andrew Williams, Cecelia Santiago-Turla, Xuejun Qin, Robyn M Rautenbach, Ari Ziskind, Michèle Ramsay, Steffen Uebe, Lingyun Song, Alexias Safi, Eranga N Vithana, Takanori Mizoguchi, Satoko Nakano, Toshiaki Kubota, Ken Hayashi, Shin-ichi Manabe, Shigeyasu Kazama, Yosai Mori, Kazunori Miyata, Nagahisa Yoshimura, Andre Reis, Gregory E Crawford, Francesca Pasutto, Trevor R Carmichael, Susan E I Williams, Mineo Ozaki, Tin Aung, Chiea-Chuen Khor, W Daniel Stamer, Allison E Ashley-Koch, R Rand Allingham
Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly associated with XFS in all studied populations, but a functional role for these variants has not been established. To identify additional candidate functional variants, we sequenced the entire LOXL1 genomic locus (∼40 kb) in 50 indigenous, black South African XFS cases and 50 matched controls...
November 15, 2015: Human Molecular Genetics
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