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Lysyl oxidase-like 2

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https://www.readbyqxmd.com/read/28220932/a-phase-2-study-of-simtuzumab-in-patients-with-primary-post-polycythaemia-vera-or-post-essential-thrombocythaemia-myelofibrosis
#1
Srdan Verstovsek, Michael R Savona, Ruben A Mesa, Hua Dong, Julia D Maltzman, Shringi Sharma, Jeffrey Silverman, Stephen T Oh, Jason Gotlib
Simtuzumab, a monoclonal antibody inhibitor of extracellular matrix enzyme lysyl oxidase-like-2, showed preclinical promise and was well tolerated in clinical studies. A phase 2, open-label study of simtuzumab was conducted in patients with primary myelofibrosis (MF), post-polycythaemia vera MF and post-essential thrombocythaemia MF. Fifty-four patients were randomized to receive simtuzumab alone (200 or 700 mg [n = 12 each group]) or simtuzumab (200 or 700 mg) with ruxolitinib (n = 15 each group) for 24 weeks...
February 21, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28203099/a-new-dermocosmetic-containing-retinaldehyde-delta-tocopherol-glucoside-and-glycylglycine-oleamide-for-managing-naturally-aged-skin-results-from-in-vitro-to-clinical-studies
#2
Céline Rouvrais, Daniel Bacqueville, Patrick Bogdanowicz, Marie-José Haure, Laure Duprat, Christine Coutanceau, Nathalie Castex-Rizzi, Hélène Duplan, Valérie Mengeaud, Sandrine Bessou-Touya
INTRODUCTION: Natural aging of skin tissues, the addition of the cumulative action of the time and radiation exposure result in skin atrophy, wrinkles and degeneration of the extracellular matrix (ECM). The aim of the study was to investigate the beneficial effect of a combination containing retinaldehyde (RAL), delta-tocopherol glucoside (delta-TC) and glycylglycine ole-amide (GGO) and of a dermocosmetic containing the combination. MATERIALS AND METHODS: The protective effect of the combination was assessed through in vitro gene expression of ultraviolet (UV)-irradiated fibroblasts...
2017: Clinical, Cosmetic and Investigational Dermatology
https://www.readbyqxmd.com/read/28199967/pre-clinical-evaluation-of-small-molecule-loxl2-inhibitors-in-breast-cancer
#3
Joan Chang, Morghan C Lucas, Lidia E Leonte, Marc Garcia-Montolio, Lukram Babloo Singh, Alison D Findlay, Mandar Deodhar, Jonathan S Foot, Wolfgang Jarolimek, Paul Timpson, Janine T Erler, Thomas R Cox
Lysyl Oxidase-like 2 (LOXL2), a member of the lysyl oxidase family of amine oxidases is known to be important in normal tissue development and homeostasis, as well as the onset and progression of solid tumors. Here we tested the anti-tumor properties of two generations of novel small molecule LOXL2 inhibitor in the MDA-MB-231 human model of breast cancer. We confirmed a functional role for LOXL2 activity in the progression of primary breast cancer. Inhibition of LOXL2 activity inhibited the growth of primary tumors and reduced primary tumor angiogenesis...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28196225/blood-vessel-basement-membrane-alterations-in-human-retinal-microaneurysms-during-aging
#4
Mariana López-Luppo, Victor Nacher, David Ramos, Joana Catita, Marc Navarro, Ana Carretero, Alfonso Rodriguez-Baeza, Luísa Mendes-Jorge, Jesús Ruberte
Purpose: Microaneurysms, considered a hallmark of retinal vascular disease, are present in aged retinas. Here, the basement membrane of human retinal microaneurysms has been analyzed during aging. Methods: Retinas were obtained from 17 nondiabetic donors. Whole mount retinas and paraffin sections were marked immunohistochemically with antibodies against the main components of the blood basement membrane. Trypsin digestion and transmission electron microscopy also were performed...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28112368/loxl3-sv2-a-novel-variant-of-human-lysyl-oxidase-like-3-loxl3-functions-as-an-amine-oxidase
#5
Chankyu Jeong, Youngho Kim
Human lysyl oxidase-like 3 (LOXL3) functions as a copper-dependent amine oxidase toward collagen and elastin. The LOXL3 protein contains four scavenger receptor cysteine-rich (SRCR) domains in the N-terminus in addition to the C-terminal characteristic domains of the lysyl oxidase (LOX) family, such as a copper-binding domain, a cytokine receptor‑like domain and residues for the lysyl-tyrosyl quinone cofactor. Using BLASTN searches, we identified a novel variant of LOXL3 (termed LOXL3-sv2), which lacked the sequences corresponding to exons 4 and 5 of LOXL3...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28087451/in-depth-comparative-analysis-of-the-chicken-eggshell-membrane-proteome
#6
Tamer A E Ahmed, Henri-Pierre Suso, Maxwell T Hincke
: The avian eggshell membrane (ESM) is stabilized by extensive cross-linkages, making the identification of its protein constituents technically challenging. Herein, we applied various extraction/solubilization conditions followed by proteomic analysis to characterize the protein constituents of ESM derived from the unfertilized chicken eggs. The egg white and eggshell proteomes (including previous published work) were determined and compared to ESM to identify proteins that are relatively or highly specific to ESM...
January 10, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28073888/selective-targeting-of-lysyl-oxidase-like-2-loxl2-suppresses-hepatic-fibrosis-progression-and-accelerates-its-reversal
#7
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
#8
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/28008161/baicalein-inhibits-epithelial-to-mesenchymal-transition-via-downregulation-of-cyr61-and-loxl-2-in-mda-mb231-breast-cancer-cells
#9
Linh Thi Thao Nguyen, Yeon Woo Song, Somi Kim Cho
Epithelial-mesenchymal transition (EMT) is a critical step in the acquisition of the migratory and invasive capabilities associated with metastatic competence. Cysteine-rich protein 61 (CCN1/Cyr61) has been implicated as an important mediator in the proliferation and metastasis of breast cancer. Hence, Cyr61 and associated pathways are attractive targets for therapeutic interventions directed against the EMT. In the present study, we report that baicalein significantly inhibits the expression of Cyr61 and migration and invasion of MDA-MB231 human breast cancer cells...
December 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27997555/exploration-of-serum-proteomic-profiling-and-diagnostic-model-that-differentiate-crohn-s-disease-and-intestinal-tuberculosis
#10
Fenming Zhang, Chengfu Xu, Longgui Ning, Fengling Hu, Guodong Shan, Hongtan Chen, Ming Yang, Wenguo Chen, Jiekai Yu, Guoqiang Xu
AIM: To explore the diagnostic models of Crohn's disease (CD), Intestinal tuberculosis (ITB) and the differential diagnostic model between CD and ITB by analyzing serum proteome profiles. METHODS: Serum proteome profiles from 30 CD patients, 21 ITB patients and 30 healthy controls (HCs) were analyzed by using weak cationic magnetic beads combined with MALDI-TOF-MS technique to detect the differentially expressed proteins of serum samples. Three groups were made and compared accordingly: group of CD patients and HCs, group of ITB patients and HCs, group of CD patients and ITB patients...
2016: PloS One
https://www.readbyqxmd.com/read/27966531/targeting-loxl2-for-cardiac-interstitial-fibrosis-and-heart-failure-treatment
#11
Jin Yang, Konstantinos Savvatis, Jong Seok Kang, Peidong Fan, Hongyan Zhong, Karen Schwartz, Vivian Barry, Amanda Mikels-Vigdal, Serge Karpinski, Dmytro Kornyeyev, Joanne Adamkewicz, Xuhui Feng, Qiong Zhou, Ching Shang, Praveen Kumar, Dillon Phan, Mario Kasner, Begoña López, Javier Diez, Keith C Wright, Roxanne L Kovacs, Peng-Sheng Chen, Thomas Quertermous, Victoria Smith, Lina Yao, Carsten Tschöpe, Ching-Pin Chang
Interstitial fibrosis plays a key role in the development and progression of heart failure. Here, we show that an enzyme that crosslinks collagen-Lysyl oxidase-like 2 (Loxl2)-is essential for interstitial fibrosis and mechanical dysfunction of pathologically stressed hearts. In mice, cardiac stress activates fibroblasts to express and secrete Loxl2 into the interstitium, triggering fibrosis, systolic and diastolic dysfunction of stressed hearts. Antibody-mediated inhibition or genetic disruption of Loxl2 greatly reduces stress-induced cardiac fibrosis and chamber dilatation, improving systolic and diastolic functions...
December 14, 2016: Nature Communications
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
#12
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/27860390/increased-lysyl-oxidase-like-2-associates-with-a-poor-prognosis-in-non-small-cell-lung-cancer
#13
Ping Zhan, Xiao-Jing Lv, Ya-Nan Ji, Haiyan Xie, Li-Ke Yu
BACKGROUND: Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family and is associated with invasiveness and metastasis in breast cancer. However, its relevance in non-small cell lung cancer (NSCLC) remained largely unknown. METHODS: LOXL2 protein levels in a cohort of NSCLC and adjacent normal lung tissues were evaluated and analyzed their clinicopathologic and prognostic significance. RESULTS: It was found that cytoplasmic and nuclear LOXL2 levels were higher in lung adenocarcinoma (AD) and squamous cell carcinoma (SCC) tissues than in paired adjacent normal tissues...
November 18, 2016: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/27770022/lysyl-oxidase-like-2-cross-links-collagen-iv-of-glomerular-basement-membrane
#14
Carolina Añazco, Alberto J López-Jiménez, Mohamed Rafi, Lorenzo Vega-Montoto, Ming-Zhi Zhang, Billy G Hudson, Roberto M Vanacore
The 7S dodecamer is recognized as an important structural cross-linking domain of collagen IV networks that provide mechanical stability to basement membranes, a specialized form of extracellular matrix essential for the development and maintenance of tissue architecture. Although the 7S dodecamer is stabilized by covalent cross-linking, the molecular mechanism by which such cross-links are formed has not been revealed. Here, we aimed to identify the enzyme(s) that cross-links the 7S dodecamer and characterize its expression in the kidney glomerulus...
December 9, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27753755/association-of-lysyl-oxidase-like-1-gene-polymorphism-in-turkish-patients-with-pseudoexfoliation-syndrome-and-pseudoexfoliation-glaucoma
#15
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...
February 2017: Journal of Glaucoma
https://www.readbyqxmd.com/read/27735137/lysyl-oxidase-like-2-loxl2-oxidizes-trimethylated-lysine-4-in-histone-h3
#16
Nicolás Herranz, Natàlia Dave, Alba Millanes-Romero, Laura Pascual-Reguant, Lluis Morey, Víctor M Díaz, Víctor Lórenz-Fonfría, Ricardo Gutierrez-Gallego, Celia Jerónimo, Ane Iturbide, Luciano Di Croce, Antonio García de Herreros, Sandra Peiró
: Methylation of histone H3 lysine 4 is linked to active transcription and can be removed by LSD1 or the JmjC domain-containing proteins by amino-oxidation or hydroxylation, respectively. Here we describe that its deamination can be catalyzed by lysyl oxidase-like 2 protein (LOXL2), presenting an unconventional chemical mechanism for H3K4 modification. Infrared spectroscopy and mass spectrometry analyses demonstrated that recombinant LOXL2 specifically deaminates trimethylated H3K4. Moreover, by regulating H3K4me3 deamination, LOXL2 activity is linked with the transcriptional control of the CDH1 gene...
December 2016: FEBS Journal
https://www.readbyqxmd.com/read/27488440/regulation-of-loxl2-and-serpinh1-by-antitumor-microrna-29a-in-lung-cancer-with-idiopathic-pulmonary-fibrosis
#17
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/27430160/the-effect-of-loxl2-in-hepatocellular-carcinoma
#18
Linghong Wu, Yuan Zhang, Ying Zhu, Qingwei Cong, Yan Xiang, Linlin Fu
Lysyl oxidase-like 2 (LOXL2) is key in the hepatocellular carcinoma (HCC) tumor microenvironment and metastatic niche formation. However, its effect on proliferation and clinical parameters in HCC require further elucidation. The present study aimed to investigate LOXL2 expression in HCC from in vitro and clinical aspects. The present study constructed LOXL2‑small interfering RNA with a lentiviral vector, investigated the effect of LOXL2 on proliferation using HCC cell lines via a series of assays, including reverse transcription‑quantitative polymerase chain reaction, cell counting, colony formation, assessment of cell cycle and apoptosis using flow cytometry, MTT and BrdU...
September 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27392148/retraction-notice-to-lysyl-oxidase-like-2-deaminates-lysine-4-in-histone-h3
#19
Nicolás Herranz, Natàlia Dave, Alba Millanes-Romero, Lluis Morey, Víctor M Díaz, Víctor Lórenz-Fonfría, Ricardo Gutierrez-Gallego, Celia Jerónimo, Luciano Di Croce, Antonio García de Herreros, Sandra Peiró
No abstract text is available yet for this article.
July 7, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27363654/impact-of-stroma-loxl2-overexpression-on-the-prognosis-of-intrahepatic-cholangiocarcinoma
#20
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
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