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https://www.readbyqxmd.com/read/29035165/development-of-highly-sensitive-cell-based-akt-kinase-elisa-for-monitoring-pi3k-beta-activity-and-compound-efficacy
#1
Mahesh Yanamandra, Labanyamoy Kole, Archana Giri, Sayan Mitra
Phosphatidylinositol-3 kinase pathway regulates multiple cellular function involving cell survival, growth, motility proliferation, apoptosis, and adhesion. These are deregulated in various diseases like cancer, atherosclerosis, and inflammation. PI3Ks phosphorylate phosphatidylinositol 4,5 biphosphate (PIP2) yielding phosphatidylinositol 3, 4, 5 triphosphate (PIP3) that in turn activates AKT kinase (serine/threonine kinase) which is the central enzyme in regulation of metabolic functions. Due to their implications in disease pathophysiology, PI3K/AKT inhibitors became attractive targets for pharmaceutical industries...
October 16, 2017: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/29030599/genome-wide-meta-analysis-associates-hla-dqa1-drb1-and-lpa-and-lifestyle-factors-with-human-longevity
#2
Peter K Joshi, Nicola Pirastu, Katherine A Kentistou, Krista Fischer, Edith Hofer, Katharina E Schraut, David W Clark, Teresa Nutile, Catriona L K Barnes, Paul R H J Timmers, Xia Shen, Ilaria Gandin, Aaron F McDaid, Thomas Folkmann Hansen, Scott D Gordon, Franco Giulianini, Thibaud S Boutin, Abdel Abdellaoui, Wei Zhao, Carolina Medina-Gomez, Traci M Bartz, Stella Trompet, Leslie A Lange, Laura Raffield, Ashley van der Spek, Tessel E Galesloot, Petroula Proitsi, Lisa R Yanek, Lawrence F Bielak, Antony Payton, Federico Murgia, Maria Pina Concas, Ginevra Biino, Salman M Tajuddin, Ilkka Seppälä, Najaf Amin, Eric Boerwinkle, Anders D Børglum, Archie Campbell, Ellen W Demerath, Ilja Demuth, Jessica D Faul, Ian Ford, Alessandro Gialluisi, Martin Gögele, MariaElisa Graff, Aroon Hingorani, Jouke-Jan Hottenga, David M Hougaard, Mikko A Hurme, M Arfan Ikram, Marja Jylhä, Diana Kuh, Lannie Ligthart, Christina M Lill, Ulman Lindenberger, Thomas Lumley, Reedik Mägi, Pedro Marques-Vidal, Sarah E Medland, Lili Milani, Reka Nagy, William E R Ollier, Patricia A Peyser, Peter P Pramstaller, Paul M Ridker, Fernando Rivadeneira, Daniela Ruggiero, Yasaman Saba, Reinhold Schmidt, Helena Schmidt, P Eline Slagboom, Blair H Smith, Jennifer A Smith, Nona Sotoodehnia, Elisabeth Steinhagen-Thiessen, Frank J A van Rooij, André L Verbeek, Sita H Vermeulen, Peter Vollenweider, Yunpeng Wang, Thomas Werge, John B Whitfield, Alan B Zonderman, Terho Lehtimäki, Michele K Evans, Mario Pirastu, Christian Fuchsberger, Lars Bertram, Neil Pendleton, Sharon L R Kardia, Marina Ciullo, Diane M Becker, Andrew Wong, Bruce M Psaty, Cornelia M van Duijn, James G Wilson, J Wouter Jukema, Lambertus Kiemeney, André G Uitterlinden, Nora Franceschini, Kari E North, David R Weir, Andres Metspalu, Dorret I Boomsma, Caroline Hayward, Daniel Chasman, Nicholas G Martin, Naveed Sattar, Harry Campbell, Tōnu Esko, Zoltán Kutalik, James F Wilson
Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28971574/aberrant-lipid-metabolism-in-cancer-cells-the-role-of-oncolipid-activated-signaling
#3
REVIEW
Upasana Ray, Sib Sankar Roy
Metabolic activities of malignant cells are extremely different from their non-transformed equivalents, which establishes metabolic reprogramming as an important hallmark of every transformed cell. Precisely, the current arena of research in this field aims to understand the regulatory effect of oncogenic signaling on metabolic rewiring in transformed cells in order to exploit this information for therapeutic benefits. Alterations in lipid metabolism serve as one of the main aspects of metabolic rewiring of the transformed cells...
October 3, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28939644/role-of-lysophosphatidic-acid-and-its-receptors-in-the-kidney
#4
Frank Park, Duane Miller
Lysophosphatidic acid (LPA) is a bioactive phospholipid, which can exert diverse biological effects in various diseased states of the kidney by activating at least 6 cognate G-protein coupled receptors and its complex network of heterotrimeric G-proteins. In many models of acute and chronic kidney injury, pathological elevations in LPA promotes abnormal changes in renal tubular epithelial cell architecture by activating apoptotic signaling, recruit immune cells to the site of injury, and stimulate pro-fibrotic signaling by increasing gene transcription...
September 22, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28938552/novel-pleiotropic-effects-of-bioactive-phospholipids-in-human-lung-cancer-metastasis
#5
Gabriela Schneider, Zachariah Payne Sellers, Kamila Bujko, Sham S Kakar, Magda Kucia, Mariusz Z Ratajczak
We previously proposed that one of the unwanted side effects of chemotherapy and radiotherapy is the increase in several peptide- and non-peptide based chemoattractants in damaged tissues, leading to induction of a prometastatic microenvironment for remaining cancer cells. Herein, we turned out our attention to a potential role of bioactive phospholipids (BphsLs), such as sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), lysophosphatidylcholine (LPC), and lysophosphatidic acid (LPA) in lung cancer (LC) metastasis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28910191/lysophosphatidic-acid-is-a-biomarker-for-peritoneal-carcinomatosis-of-gastric-cancer-and-correlates-with-poor-prognosis
#6
Ruolan Zeng, Bin Li, Junhui Huang, Meizuo Zhong, Li Li, Chaojun Duan, Shan Zeng, Jin Huang, Wei Liu, Jingchen Lu, Youhong Tang, Lingming Zhou, Yiping Liu, Jianhuang Li, Zhengxi He, Quan Wang, Youyi Dai
BACKGROUND: Peritoneal carcinomatosis (PC) is an important cause of morbidity and mortality among patients with gastric cancer. Thus, it is important to identify an ideal biomarker for PC. METHODS: Plasma and ascites samples were collected from gastric cancer patients with PC and a control group. Lysophosphatidic acid (LPA) levels were tested and analyzed. RESULTS: The plasma LPA levels of gastric cancer patients with PC were significantly higher than those in gastric cancer patients after radical resection (p = 0...
September 14, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28865867/a-longitudinal-study-of-promis-pediatric-symptom-clusters-in-children-undergoing-chemotherapy
#7
Jichuan Wang, Shana Jacobs, Darren A Dewalt, Emily Stern, Heather Gross, Pamela S Hinds
CONTEXT: Children in treatment for cancer experience multiple, troubling and interrelated symptoms. Analyzing the interrelatedness of symptoms and how that changes during treatment could yield clinically relevant patient profiles to guide patient care. OBJECTIVES: The aims were to identify a) pediatric profiles with respect to PROMIS symptom measures, b) changes in profile status throughout a chemotherapy cycle, and c) if a baseline single-item fatigue measure could significantly predict symptom profile status and its changes...
August 30, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28854359/lysophosphatidic-acid-receptor-4-activation-augments-drug-delivery-in-tumors-by-tightening-endothelial-cell-cell-contact
#8
Kazuhiro Takara, Daisuke Eino, Koji Ando, Daisuke Yasuda, Hisamichi Naito, Yohei Tsukada, Tomohiro Iba, Taku Wakabayashi, Fumitaka Muramatsu, Hiroyasu Kidoya, Shigetomo Fukuhara, Naoki Mochizuki, Satoshi Ishii, Haruhiko Kishima, Nobuyuki Takakura
Vascular normalization in tumors may improve drug delivery and anti-tumor immunity. Angiogenesis inhibitors induce hypoxia, which may facilitate malignant progression; therefore, we investigated other methods to promote vascular maturation. Here, we show that lysophosphatidic acid (LPA) enhances blood flow by promoting fine vascular networks, thereby improving vascular permeability and suppressing tumor growth when combined with anti-cancer drug treatment. Six different G protein-coupled receptors have been identified as LPA receptors (LPA1-6)...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28792932/structural-insights-into-ligand-recognition-by-the-lysophosphatidic-acid-receptor-lpa6
#9
Reiya Taniguchi, Asuka Inoue, Misa Sayama, Akiharu Uwamizu, Keitaro Yamashita, Kunio Hirata, Masahito Yoshida, Yoshiki Tanaka, Hideaki E Kato, Yoshiko Nakada-Nakura, Yuko Otani, Tomohiro Nishizawa, Takayuki Doi, Tomohiko Ohwada, Ryuichiro Ishitani, Junken Aoki, Osamu Nureki
Lysophosphatidic acid (LPA) is a bioactive lipid composed of a phosphate group, a glycerol backbone, and a single acyl chain that varies in length and saturation. LPA activates six class A G-protein-coupled receptors to provoke various cellular reactions. Because LPA signalling has been implicated in cancer and fibrosis, the LPA receptors are regarded as promising drug targets. The six LPA receptors are subdivided into the endothelial differentiation gene (EDG) family (LPA1-LPA3) and the phylogenetically distant non-EDG family (LPA4-LPA6)...
August 17, 2017: Nature
https://www.readbyqxmd.com/read/28782946/synergistic-tailoring-of-electrostatic-and-hydrophobic-interactions-for-rapid-and-specific-recognition-of-lysophosphatidic-acid-an-early-stage-ovarian-cancer-biomarker
#10
Ying Wang, Hanwen Pei, Yan Jia, Jianhua Liu, Zelun Li, Kelong Ai, Zhongyuan Lu, Lehui Lu
Early detection of ovarian cancer, the most lethal type of gynecologic cancer, can dramatically improve the efficacy of available treatment strategies. However, few screening tools exist for rapidly and effectively diagnosing ovarian cancer in early stages. Here, we present a facile "lock-key" strategy, based on rapid, specific detection of plasma lysophosphatidic acid (LPA, an early stage biomarker) with polydiacetylenes (PDAs)-based probe, for the early diagnosis of ovarian cancer. This strategy relies on specifically inserting LPA "key" into the PDAs "lock" through the synergistic electrostatic and hydrophobic interactions between them, leading to conformation transition of the PDA backbone with a concomitant blue-to-red color change...
August 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28743508/design-synthesis-docking-and-biological-evaluation-of-4-phenyl-thiazole-derivatives-as-autotaxin-atx-inhibitors
#11
Anand Balupuri, Dae-Yon Lee, Myeong Hwi Lee, Sangeun Chae, Eunmi Jung, Yunki Kim, Jeonghee Ryu, Nam Sook Kang
The autotaxin-lysophophatidic acid (ATX-LPA) signaling pathway is involved in several human diseases such as cancer, autoimmune diseases, inflammatory diseases neurodegenerative diseases and fibrotic diseases. Herein, a series of 4-phenyl-thiazole based compounds was designed and synthesized. Compounds were evaluated for their ATX inhibitory activity using FS-3 and human plasma assays. In the FS-3 assay, compounds 20 and 21 significantly inhibited the ATX at low nanomolar level (IC50=2.99 and 2.19nM, respectively)...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28735625/free-fatty-acid-receptor-ffar-agonists-inhibit-proliferation-of-human-ovarian-cancer-cells
#12
Mandi M Hopkins, Kathryn E Meier
Many cellular actions of omega-3 fatty acids are mediated by two G protein-coupled receptors, FFA1 and FFA4, free fatty acid receptor (FFAR) family members that are activated by these dietary constituents. FFAR agonists inhibit proliferation of human prostate and breast cancer cells. Since omega-3 fatty acids can inhibit ovarian cancer cell growth, the current study tested the potential role of FFARs in the response. OVCAR3 and SKOV3 human ovarian cancer cell lines express mRNA for FFA1; FFA4 mRNA was detected at low levels in SKOV3 but not OVCAR3...
July 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28732508/lysophosphatidic-acid-plasma-concentrations-in-healthy-subjects-circadian-rhythm-and-associations-with-demographic-anthropometric-and-biochemical-parameters
#13
Anna Michalczyk, Marta Budkowska, Barbara Dołęgowska, Dariusz Chlubek, Krzysztof Safranow
BACKGROUND: Lysophosphatidic acid (LPA) is a bioactive lipid with a wide biological activity. Previous studies have shown its potential usefulness as a diagnostic marker for ovarian cancer. The aim of the study was to investigate which factors may influence plasma LPA concentrations in healthy subjects and to propose reference values. METHODS: The study group consisted of 100 healthy subjects. From all of them the blood samples were taken at 7 a.m. (fasting state)...
July 21, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28731719/discovery-structure-activity-relationship-and-binding-mode-of-an-imidazo-1-2-a-pyridine-series-of-autotaxin-inhibitors
#14
Agnès Joncour, Nicolas Desroy, Christopher Housseman, Xavier Bock, Natacha Bienvenu, Laëtitia Cherel, Virginie Labeguere, Christophe Peixoto, Denis Annoot, Luce Lepissier, Jörg Heiermann, Willem Jan Hengeveld, Gregor Pilzak, Alain Monjardet, Emanuelle Wakselman, Veronique Roncoroni, Sandrine Le Tallec, René Galien, Christelle David, Nele Vandervoort, Thierry Christophe, Katja Conrath, Mia Jans, Alexandre Wohlkonig, Sameh Soror, Jan Steyaert, Robert Touitou, Damien Fleury, Lionel Vercheval, Patrick Mollat, Nicolas Triballeau, Ellen van der Aar, Reginald Brys, Bertrand Heckmann
Autotaxin (ATX) is a secreted enzyme playing a major role in the production of lysophosphatidic acid (LPA) in blood through hydrolysis of lysophosphatidyl choline (LPC). The ATX-LPA signaling axis arouses a high interest in the drug discovery industry as it has been implicated in several diseases including cancer, fibrotic diseases, and inflammation, among others. An imidazo[1,2-a]pyridine series of ATX inhibitors was identified out of a high-throughput screening (HTS). A cocrystal structure with one of these compounds and ATX revealed a novel binding mode with occupancy of the hydrophobic pocket and channel of ATX but no interaction with zinc ions of the catalytic site...
September 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28716620/distinct-physical-function-profiles-in-older-adults-receiving-cancer-chemotherapy
#15
Christine Miaskowski, Melisa L Wong, Bruce A Cooper, Judy Mastick, Steven M Paul, Katherine Possin, Michael Steinman, Janine Cataldo, Laura B Dunn, Christine Ritchie
CONTEXT: Although physical function is an important patient outcome, little is known about changes in physical function in older adults receiving chemotherapy (CTX). OBJECTIVES: Identify subgroups of older patients based on changes in their level of physical function; determine which demographic and clinical characteristics were associated with subgroup membership; and determine if these subgroups differed on quality-of-life (QOL) outcomes. METHODS: Latent profile analysis was used to identify groups of older oncology patients (n = 363) with distinct physical function profiles...
September 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28684865/dynamic-relocalization-of-nherf1-mediates-chemotactic-migration-of-ovarian-cancer-cells-toward-lysophosphatidic-acid-stimulation
#16
Yong-Seok Oh, Kyun Heo, Eung-Kyun Kim, Jin-Hyeok Jang, Sun Sik Bae, Jong Bae Park, Yun Hee Kim, Minseok Song, Sang Ryong Kim, Sung Ho Ryu, In-Hoo Kim, Pann-Ghill Suh
NHERF1/EBP50 (Na(+)/H(+) exchanger regulating factor 1; Ezrin-binding phosphoprotein of 50 kDa) organizes stable protein complexes beneath the apical membrane of polar epithelial cells. By contrast, in cancer cells without any fixed polarity, NHERF1 often localizes in the cytoplasm. The regulation of cytoplasmic NHERF1 and its role in cancer progression remain unclear. In this study, we found that, upon lysophosphatidic acid (LPA) stimulation, cytoplasmic NHERF1 rapidly translocated to the plasma membrane, and subsequently to cortical protrusion structures, of ovarian cancer cells...
July 7, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28652252/glycerol-3-phosphate-acyltransferase-1-promotes-tumor-cell-migration-and-poor-survival-in-ovarian-carcinoma
#17
Rosemarie Marchan, Bettina Büttner, Jörg Lambert, Karolina Edlund, Iris Glaeser, Meinolf Blaszkewicz, Gregor Leonhardt, Lisa Marienhoff, Darius Kaszta, Moritz Anft, Carsten Watzl, Katrin Madjar, Marianna Grinberg, Eugen Rempel, Roland Hergenröder, Silvia Selinski, Jörg Rahnenführer, Michaela S Lesjak, Joanna D Stewart, Cristina Cadenas, Jan G Hengstler
Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion, and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-α (CHKA), the enzymes that catabolize the products of EDI3 to determine which downstream pathway is relevant for migration. Our results clearly showed that GPAM influenced cell migration via the signaling lipid lysophosphatidic acid (LPA), linking it with GPAM to cell migration...
June 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28616586/the-autotaxin-lysophosphatidic-acid-pathway-emerges-as-a-therapeutic-target-to-prevent-liver-cancer
#18
Derek J Erstad, Andrew M Tager, Yujin Hoshida, Bryan C Fuchs
Using transcriptome meta-analysis, we recently identified the autotaxin (ATX)-lysophosphatidic acid (LPA) pathway as a regulator of hepatocellular carcinoma (HCC) risk in human cirrhosis patients. Pharmacological targeting of this pathway reduced fibrosis progression and HCC development in animals, identifying ATX-LPA signaling as a novel chemoprevention strategy for cirrhosis and HCC.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28591560/implications-of-the-lysophosphatidic-acid-signaling-axis-in-liver-cancer
#19
REVIEW
Chiara Lopane, Pasquale Agosti, Isabella Gigante, Carlo Sabbà, Antonio Mazzocca
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in western countries. The major risk factors for HCC are hepatitis C or B viruses, alcohol and metabolic disorders. The increasing risk of HCC in patients with metabolic disorders (i.e. obesity, diabetes and non-alcoholic steatohepatitis/NASH) regardless of the presence of liver cirrhosis is becoming relevant. Nevertheless, molecular mechanisms linking these risk factors to liver oncogenesis are unclear. This review focuses on the pathogenic role of the lysophosphatidic acid (LPA) pathway in HCC, highlighting the implications of this bioactive phospholipid in liver cancer biology and metabolism and as potential therapeutic target...
August 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28539367/implications-for-breast-cancer-treatment-from-increased-autotaxin-production-in-adipose-tissue-after-radiotherapy
#20
Guanmin Meng, Xiaoyun Tang, Zelei Yang, Matthew G K Benesch, Alison Marshall, David Murray, Denise G Hemmings, Frank Wuest, Todd P W McMullen, David N Brindley
We have previously established that adipose tissue adjacent to breast tumors becomes inflamed by tumor-derived cytokines. This stimulates autotaxin (ATX) secretion from adipocytes, whereas breast cancer cells produce insignificant ATX. Lysophosphatidate produced by ATX promotes inflammatory cytokine secretion in a vicious inflammatory cycle, which increases tumor growth and metastasis and decreases response to chemotherapy. We hypothesized that damage to adipose tissue during radiotherapy for breast cancer should promote lysophosphatidic acid (LPA) signaling and further inflammatory signaling, which could potentially protect cancer cells from subsequent fractions of radiation therapy...
September 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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