Download Book

Total Page:16

File Type:pdf, Size:1020Kb

Download Book Advances in Experimental Medicine and Biology 1311 Anne Le Editor The Heterogeneity of Cancer Metabolism Second Edition Advances in Experimental Medicine and Biology Volume 1311 Series Editors Wim E. Crusio, Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS and University of Bordeaux, Pessac Cedex, France Haidong Dong, Departments of Urology and Immunology, Mayo Clinic, Rochester, MN, USA Heinfried H. Radeke, Institute of Pharmacology & Toxicology, Clinic of the Goethe University Frankfurt Main, Frankfurt am Main, Hessen, Germany Nima Rezaei, Research Center for Immunodefciencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran Junjie Xiao, Cardiac Regeneration and Ageing Lab, Institute of Cardiovascular Science, School of Life Science, Shanghai University, Shanghai, China Advances in Experimental Medicine and Biology provides a platform for scientifc contributions in the main disciplines of the biomedicine and the life sciences. Tis series publishes thematic volumes on contemporary research in the areas of microbiology, immunology, neurosciences, biochemistry, biomedical engineering, genetics, physiology, and cancer research. Covering emerging topics and techniques in basic and clinical science, it brings together clinicians and researchers from various felds. Advances in Experimental Medicine and Biology has been publishing exceptional works in the feld for over 40 years, and is indexed in SCOPUS, Medline (PubMed), Journal Citation Reports/Science Edition, Science Citation Index Expanded (SciSearch, Web of Science), EMBASE, BIOSIS, Reaxys, EMBiology, the Chemical Abstracts Service (CAS), and Pathway Studio. 2019 Impact Factor: 2.450 5 Year Impact Factor: 2.324 More information about this series at http://www.springer.com/series/5584 Anne Le Editor The Heterogeneity of Cancer Metabolism Second Edition Editor Anne Le Department of Pathology and Oncology Johns Hopkins University School of Medicine Baltimore, MD, USA Department of Chemical and Biomolecular Engineering, Johns Hopkins University Whiting School of Engineering, Baltimore, MD, USA This book is an open access publication. ISSN 0065-2598 ISSN 2214-8019 (electronic) Advances in Experimental Medicine and Biology ISBN 978-3-030-65767-3 ISBN 978-3-030-65768-0 (eBook) https://doi.org/10.1007/978-3-030-65768-0 © The Editor(s) (if applicable) and The Author(s) 2021 Open Access This book is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made. The images or other third party material in this book are included in the book’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the book’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifc statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland This book is dedicated to my colleague and mentor, Dr. Arthur J. L. Cooper. Foreword According to the Center for Disease Control (CDC) in 2018, there were 599,274 cancer deaths in the USA; 283,721 were among females and 315,553 were among males (out of an estimated total US population of 328 million in 2018) [1]. Worldwide in 2020 there were an estimated 10.1 million new cases of cancer in males and 5.5 million cancer-related deaths; in females estimated new cases were 9.2 million and 4.4. million deaths [2]. Lung cancer is cur- rently the leading cause of all cancer deaths (25.1% of all cases), but for females breast cancer is currently the leading cause of cancer deaths (15.5%) [2]. According to an April 4th, 2020 report of the International Agency for Research on Cancer (IARC), cancer is now the most common form of death worldwide ahead of heart disease. The report suggests that many cancers can be prevented, and better diagnoses and treatment could improve outcomes [3]. The World Health Organization (WHO) warns that if current trends con- tinue, the world will see a greater than 100% increase in annual cancer deaths over the next 40 years – from about 9–10 million deaths in 2020 to about 19 million deaths in 2060 [4]. The greatest increase (81%) in new cases will occur in low- and middle-income countries, where survival rates are currently lowest. This is double (40%) the new cancer cases that are expected in high- income countries [4]. The report outlines several steps to save millions of lives worldwide, including (1) controlling tobacco use (currently responsible for 25% of all cancer deaths), (2) vaccinating against hepatitis B to prevent liver cancer, (3) eliminating cervical cancer by vaccinating against HPV, (4) improving screening and treatment, and (5) implementing high-impact can- cer management interventions that bring value for money, and ensure access to palliative care, including pain relief. The report notes that in highincome countries there has been a marked decline (by approximately 20%) in prema- ture deaths due to cancer between the years 2000 and 2015. This is presum- ably due to outstanding research into cancer causes and the development of improved treatments. On the other hand, the report notes that the situation is much less promising in low-income countries where the reduction in cancer mortality during this period was only 5%. Much of this discrepancy is due to inadequate methods for diagnosis and treatment in lowincome countries ver- sus high-income countries [4]. What can be done to improve the diagnoses of cancer and the survival rate, especially in low-income countries? Obviously, early diagnosis and improved diagnostic accuracy are vitally important and I will return to this point later. President Richard Nixon in his January 1971 State of the Union Address to vii viii Foreword the Nation declared war on cancer signing the National Cancer Act into law. This act gave the National Cancer Institute (NCI) unique autonomy within the National Institutes of Health (NIH) with special budgetary authority in the fght against cancer [5]. Many years later, President Barack Obama, hav- ing lost his mother to ovarian cancer, picked up the cause and called for an aggressive war on the disease. In his fnal State of the Union message in 2016 President Obama tasked his vice president—Joe Biden—to spearhead an ini- tiative to cure cancer: “Last year, Vice President Biden said that with a new moonshot, America can cure cancer,” Obama said, noting that Biden had worked with Congress to add resources for the NIH. Obama stated in part “For the loved ones we’ve all lost, for the family, we can still save, let’s make America the country that cures cancer once and for all” [6]. There is no ques- tion of the enormous contributions of the NIH (and many other government- sponsored and private funding agencies in the USA and worldwide) that have helped biomedical researchers understand how cancers arise and how to develop appropriate treatments. The physics of what was required to land a man on the moon was well understood in 1969 (the year of the frst successful moon landing). However, no such unique understanding pertains to cancer. We now know that every type of cancer is different and can arise from a mul- titude of disparate inherited or acquired mutations, and that even within a single type of cancer, individual cancer cells may have varying mutational and phenotypic profles. These considerations pose enormous challenges for the early diagnosis of many cancers and for appropriate interventions to pre- vent cancer metastases. What options are available to minimize the risk of cancer? Obvious life- style changes that can help minimize the risk of cancer include eschewing smoking, maintaining a healthy diet, maintaining a recommended body-mass index, exercising regularly, avoiding excessive sunlight, acquiring appropri- ate vaccinations, and avoiding risky lifestyles [7]. Regular health checkups, including screening for colon, breast, and skin cancers, can help detect can- cers at an early enough stage to improve treatment outcomes, especially among those with increased risk. But what sorts of treatments are available once a patient has been diagnosed with cancer? The American Cancer Society lists seven possible treatment options, namely, surgery, chemotherapy, radia- tion therapy, targeted therapy, immunotherapy, stem cell or bone marrow transplant, and hormone therapy [8]. The NCI provides a similar list of treat- ment options, but also includes a category entitled precision medicine [9]. Targeted therapy and precision medicine are relatively new concepts regard- ing cancer treatment options. Targeted therapy is aimed at the changes in cancer cells that help them grow, divide, and spread [9]. On the other hand, precision medicine helps doctors select treatments that are most likely to help patients based on genetic or other characteristics of their disease [9].
Recommended publications
  • Biochemical and Comparative Transcriptome Analyses Reveal
    biomolecules Article Biochemical and Comparative Transcriptome Analyses Reveal Key Genes Involved in Major Metabolic Regulation Related to Colored Leaf Formation in Osmanthus fragrans ‘Yinbi Shuanghui’ during Development Xuan Chen 1,2, Xiulian Yang 1,3, Jun Xie 2, Wenjie Ding 1,3, Yuli Li 1,3, Yuanzheng Yue 1,3,* and Lianggui Wang 1,3,* 1 Key Laboratory of Landscape Architecture, Jiangsu Province, College of Landscape Architecture, Nanjing Forestry University, No. 159 Longpan Road, Nanjing 210037, China; [email protected] (X.C.); [email protected] (X.Y.); [email protected] (W.D.); [email protected] (Y.L.) 2 College of Fine Arts, Nanjing Normal University of Special Education, No.1 Shennong Road, Nanjing 210038, China; [email protected] 3 Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China * Correspondence: [email protected] (Y.Y.); [email protected] (L.W.); Tel.: +86-138-0900-7625 (L.W.) Received: 25 February 2020; Accepted: 1 April 2020; Published: 4 April 2020 Abstract: Osmanthus fragrans ‘Yinbi Shuanghui’ not only has a beautiful shape and fresh floral fragrance, but also rich leaf colors that change, making the tree useful for landscaping. In order to study the mechanisms of color formation in O. fragrans ‘Yinbi Shuanghui’ leaves, we analyzed the colored and green leaves at different developmental stages in terms of leaf pigment content, cell structure, and transcriptome data. We found that the chlorophyll content in the colored leaves was lower than that of green leaves throughout development. By analyzing the structure of chloroplasts, the colored leaves demonstrated more stromal lamellae and low numbers of granum thylakoid.
    [Show full text]
  • Open Full Page
    Published OnlineFirst February 12, 2018; DOI: 10.1158/0008-5472.CAN-17-2215 Cancer Metabolism and Chemical Biology Research RSK Regulates PFK-2 Activity to Promote Metabolic Rewiring in Melanoma Thibault Houles1, Simon-Pierre Gravel2,Genevieve Lavoie1, Sejeong Shin3, Mathilde Savall1, Antoine Meant 1, Benoit Grondin1, Louis Gaboury1,4, Sang-Oh Yoon3, Julie St-Pierre2, and Philippe P. Roux1,4 Abstract Metabolic reprogramming is a hallmark of cancer that includes glycolytic flux in melanoma cells, suggesting an important role for increased glucose uptake and accelerated aerobic glycolysis. This RSK in BRAF-mediated metabolic rewiring. Consistent with this, phenotypeisrequiredtofulfill anabolic demands associated with expression of a phosphorylation-deficient mutant of PFKFB2 aberrant cell proliferation and is often mediated by oncogenic decreased aerobic glycolysis and reduced the growth of melanoma drivers such as activated BRAF. In this study, we show that the in mice. Together, these results indicate that RSK-mediated phos- MAPK-activated p90 ribosomal S6 kinase (RSK) is necessary to phorylation of PFKFB2 plays a key role in the metabolism and maintain glycolytic metabolism in BRAF-mutated melanoma growth of BRAF-mutated melanomas. cells. RSK directly phosphorylated the regulatory domain of Significance: RSK promotes glycolytic metabolism and the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2), growth of BRAF-mutated melanoma by driving phosphory- an enzyme that catalyzes the synthesis of fructose-2,6-bisphosphate lation of an important glycolytic enzyme. Cancer Res; 78(9); during glycolysis. Inhibition of RSK reduced PFKFB2 activity and 2191–204. Ó2018 AACR. Introduction but recently developed therapies that target components of the MAPK pathway have demonstrated survival advantage in pati- Melanoma is the most aggressive form of skin cancer and arises ents with BRAF-mutated tumors (7).
    [Show full text]
  • Localization of Heparanase in Esophageal Cancer Cells: Respective Roles in Prognosis and Differentiation
    Laboratory Investigation (2004) 84, 1289–1304 & 2004 USCAP, Inc All rights reserved 0023-6837/04 $30.00 www.laboratoryinvestigation.org Localization of heparanase in esophageal cancer cells: respective roles in prognosis and differentiation Takaomi Ohkawa1, Yoshio Naomoto1, Munenori Takaoka1, Tetsuji Nobuhisa1, Kazuhiro Noma1, Takayuki Motoki1, Toshihiro Murata1, Hirokazu Uetsuka1, Masahiko Kobayashi1, Yasuhiro Shirakawa1, Tomoki Yamatsuji1, Nagahide Matsubara1, Junji Matsuoka1, Minoru Haisa1, Mehmet Gunduz2, Hidetsugu Tsujigiwa2, Hitoshi Nagatsuka2, Masao Hosokawa3, Motowo Nakajima4 and Noriaki Tanaka1 1Department of Gastroenterological Surgery, Transplant, and Surgical Oncology; 2Department of Oral Pathology and Medicine, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan; 3Keiyukai Sapporo Hospital, Sapporo, Japan and 4Tsukuba Research Institute, Novartis Pharma KK Tsukuba, Japan In this study, we examined the distribution of heparanase protein in 75 esophageal squamous cell carcinomas by immunohistochemistry and analyzed the relationship between heparanase expression and clinicopatho- logical characteristics. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Heparanase expression correlated significantly with depth of tumor invasion, lymph node metastasis, tumor node metastasis (TNM) stage and lymphatic
    [Show full text]
  • Ultrasensitive Small Molecule Fluorogenic Probe for Human Heparanase
    bioRxiv preprint doi: https://doi.org/10.1101/2020.03.26.008730; this version posted March 29, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Ultrasensitive small molecule fluorogenic probe for human heparanase Jun Liu1, 2, Kelton A. Schleyer1, 2, Tyrel L. Bryan2, Changjian Xie2, Gustavo Seabra1, Yongmei Xu3, Arjun Kafle2, Chao Cui1, 2, Ying Wang2, Kunlun Yin2, Benjamin Fetrow2, Paul K. P. Henderson2, Peter Z. Fatland2, Jian Liu3, Chenglong Li1, Hua Guo2, and Lina Cui1, 2, * 1Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA (Current) 2Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM 87131, USA 3Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA *Correspondence should be addressed to L.C. E-mail: [email protected] Abstract Heparanase is a critical enzyme involved in the remodeling of the extracellular matrix (ECM), and its elevated expression has been linked with diseases such as cancer and inflammation. The detection of heparanase enzymatic activity holds tremendous value in the study of the cellular microenvironment, and search of molecular therapeutics targeting heparanase, however, assays developed for this enzyme so far have suffered prohibitive drawbacks. Here we present an ultrasensitive fluorogenic small-molecule probe for heparanase enzymatic activity. The probe exhibits a 756-fold fluorescence turn-on response in the presence of human heparanase, allowing one-step detection of heparanase activity in real-time with a picomolar detection limit.
    [Show full text]
  • Heparanase Is Required for Activation and Function of Macrophages
    Heparanase is required for activation and function of macrophages Lilach Gutter-Kapona, Dror Alishekevitzb, Yuval Shakedb, Jin-Ping Lic, Ami Aronheimd, Neta Ilana, and Israel Vlodavskya,1 aCancer and Vascular Biology Research Center, Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel; bDepartment of Cell Biology and Cancer Science, Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel; cDepartment of Medical Biochemistry and Microbiology, University of Uppsala, SE-751 05 Uppsala, Sweden; and dDepartment of Molecular Genetics, the Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel Edited by Joseph Schlessinger, Yale University School of Medicine, New Haven, CT, and approved October 17, 2016 (received for review July 13, 2016) The emerging role of heparanase in tumor initiation, growth, The carcinoma microenvironment includes nontransformed metastasis, and chemoresistance is well recognized and is encouraging epithelial cells, fibroblasts, endothelial cells, and infiltrated immune the development of heparanase inhibitors as anticancer drugs. Unlike cells. Endothelial cells lining blood and lymph vessels are major the function of heparanase in cancer cells, very little attention has component of the tumor microenvironment, and antiangiogenesis been given to heparanase contributed by cells composing the tumor therapy, targeting vascular endothelial growth factor (VEGF) or microenvironment. Here we used a genetic approach and examined its receptor (VEGFR2), is implemented clinically (15). In addi- the behavior and function of macrophages isolated from wild-type tion, recent research has revealed the critical roles of inflam- (WT) and heparanase-knockout (Hpa-KO) mice. Hpa-KO macrophages matory responses in different stages of tumor development and express lower levels of cytokines (e.g., TNFα,IL1-β) and exhibit lower metastasis (16).
    [Show full text]
  • Trevigen Price List 2008 International.Indd
    BASEMENT MEMBRANE EXTRACT PRODUCTS AND SPECIALTY PROTEINS • CELL INVASION ASSAYS • DIRECTED IN VIVO ANGIOGENESIS ASSAYS • COMETASSAYTM • TREVIGEN PAR/PARP/PARG • PRODUCT FOCUS and price list 2008-2009MAY 2008 TACSTM IN SITU APOPTOSIS DETECTION KITS • 1.800.TREVIGEN • www.trevigen.com 2008 TREVIGEN PRODUCT FOCUS AND PRICE LIST Product Overviews BME Tools for 3D Culture Assays TACS™ Basement Membrane Extract Products and 3D Culture Cell Proliferation Assay (96 well) .......10 In Situ Apoptosis Detection Kits .....................18-23 Specialty Proteins ............................................2-5 3D Culture Cell Harvesting Kit ............................11 Annexin DIVAA™ PAR/PARP/PARG For monitoring apoptosis via flow cytometry ...24-25 Directed in vivo Angiogenesis Assays .................6-7 Kits, Reagents, Antibodies, and Enzymes .......12-14 Oxidative Stress Kits Cell Invasion/Migration Assays CometAssay™ ..................................................................26-27 Kits, Reagents, and Plates ................................8-9 Kits, Reagents, and Slides ............................15-17 Trevigen Product International Cell Assays ......................................25 Price List ..........................................28-38 Distributors ..............................39-40 Ordering Information • Please use product names and catalog numbers when ordering. Conditions Trevigen products are sold for Research Use Only. • Please provide your name, purchase order number, shipping address, billing address, and telephone number
    [Show full text]
  • Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) Beyond SMARCA4 Mutations: a Comprehensive Genomic Analysis
    cells Article Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) beyond SMARCA4 Mutations: A Comprehensive Genomic Analysis Aurélie Auguste 1,Félix Blanc-Durand 2 , Marc Deloger 3 , Audrey Le Formal 1, Rohan Bareja 4,5, David C. Wilkes 4 , Catherine Richon 6,Béatrice Brunn 2, Olivier Caron 6, Mojgan Devouassoux-Shisheboran 7,Sébastien Gouy 2, Philippe Morice 2, Enrica Bentivegna 2, Andrea Sboner 4,5,8, Olivier Elemento 4,8, Mark A. Rubin 9 , Patricia Pautier 2, Catherine Genestie 10, Joanna Cyrta 4,9,11 and Alexandra Leary 1,2,* 1 Medical Oncologist, Gynecology Unit, Lead Translational Research Team, INSERM U981, Gustave Roussy, 94805 Villejuif, France; [email protected] (A.A.); [email protected] (A.L.F.) 2 Gynecological Unit, Department of Medicine, Gustave Roussy, 94805 Villejuif, France; [email protected] (F.B.-D.); [email protected] (B.B.); [email protected] (S.G.); [email protected] (P.M.); [email protected] (E.B.); [email protected] (P.P.) 3 Bioinformatics Core Facility, Gustave Roussy Cancer Center, UMS CNRS 3655/INSERM 23 AMMICA, 94805 Villejuif, France; [email protected] 4 Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY 10001, USA; [email protected] (R.B.); [email protected] (D.C.W.); [email protected] (A.S.); [email protected] (O.E.); [email protected] (J.C.) 5 Institute for Computational Biomedicine, Weill Cornell
    [Show full text]
  • TITLE PAGE Oxidative Stress and Response to Thymidylate Synthase
    Downloaded from molpharm.aspetjournals.org at ASPET Journals on October 2, 2021 -Targeted -Targeted 1 , University of of , University SC K.W.B., South Columbia, (U.O., Carolina, This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted. The final version may differ from this version. This article has not been copyedited and formatted.
    [Show full text]
  • Lipid Rafts Activation of a Neutral Sphingomyelinase in T Cells by + and Proliferation of Human CD4 Cholera Toxin B-Subunit Prev
    Cholera Toxin B-Subunit Prevents Activation and Proliferation of Human CD4 + T Cells by Activation of a Neutral Sphingomyelinase in Lipid Rafts This information is current as of October 1, 2021. Alexandre K. Rouquette-Jazdanian, Arnaud Foussat, Laurence Lamy, Claudette Pelassy, Patricia Lagadec, Jean-Philippe Breittmayer and Claude Aussel J Immunol 2005; 175:5637-5648; ; doi: 10.4049/jimmunol.175.9.5637 Downloaded from http://www.jimmunol.org/content/175/9/5637 References This article cites 55 articles, 31 of which you can access for free at: http://www.jimmunol.org/content/175/9/5637.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 1, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Cholera Toxin B-Subunit Prevents Activation and Proliferation of Human CD4؉ T Cells by Activation of a Neutral Sphingomyelinase in Lipid Rafts1 Alexandre K.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Allosteric Regulation
    Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture Chapter 15 Essential Questions • Before this class, ask your self the following questions: Reginald H. Garrett – What are the properties of regulatory enzymes? Enzyygme Regulation Charles M. Grisham • How do you know this enzyme is a regulatory enzyme? – How do regulatory enzymes sense the momentary needfll?ds of cells? ?Դৣ • How signal is delivered ᑣ٫݅ ፐำᆛઠ – Wha t mo lecu lar mec han isms are used to regu la te enzyme activity? http://lms. ls. ntou. edu. tw/course/106 [email protected] 2 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture Outline 15. 1 – What Factors Influence Enzymatic Activity? • Part 1 Factors that influence enzymatic activity 1. The availability of substrates and cofactors! – Zymogen, isozyme and covalent modification! 2. Product accu m ul ates b the rate will dec r ease! • Part 2: The general features of allosteric 3. The amount of enzyme present at any moment – Genetic regulation of enzyme synthesis and decay regulation 4. Regulation of Enzyme activity – The mechanisms of allosteric regulation – Zymogens, isozymes , and modulator proteins may play – Example of a enzyme controlled by both a role allosteric regulation and covalent modification – Enzyme activity can be regulated through covalent modification • Part 3: Special focus on hemoglobin and – Allosteric Regulation myoglbilobin 3 4 Hanjia’s Biochemistry Lecture Hanjia’s Biochemistry Lecture Regulation 1: Zymogen … The proteolytic activation of chymotrypsinogen • Zymogens are inactive
    [Show full text]
  • Building a Metabolic Bridge Between Glycolysis and Sphingolipid Biosynthesis : Implications in Cancer
    University of Louisville ThinkIR: The University of Louisville's Institutional Repository Electronic Theses and Dissertations 8-2014 Building a metabolic bridge between glycolysis and sphingolipid biosynthesis : implications in cancer. Morgan L. Stathem University of Louisville Follow this and additional works at: https://ir.library.louisville.edu/etd Part of the Pharmacy and Pharmaceutical Sciences Commons Recommended Citation Stathem, Morgan L., "Building a metabolic bridge between glycolysis and sphingolipid biosynthesis : implications in cancer." (2014). Electronic Theses and Dissertations. Paper 1374. https://doi.org/10.18297/etd/1374 This Master's Thesis is brought to you for free and open access by ThinkIR: The nivU ersity of Louisville's Institutional Repository. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of ThinkIR: The nivU ersity of Louisville's Institutional Repository. This title appears here courtesy of the author, who has retained all other copyrights. For more information, please contact [email protected]. BUILDING A METABOLIC BRIDGE BETWEEN GLYCOLYSIS AND SPHINGOLIPID BIOSYNTHESIS: IMPLICATIONS IN CANCER By Morgan L. Stathem B.S., University of Georgia, 2010 A Thesis Submitted to the Faculty of the School of Medicine of the University of Louisville In Partial Fulfillment of the Requirements for the Degree of Master of Science Department of Pharmacology and Toxicology University of Louisville Louisville, KY August 2014 BUILDING A METABOLIC BRIDGE BETWEEN GLYCOLYSIS AND SPHINGOLIPID BIOSYNTHESIS: IMPLICATIONS IN CANCER By Morgan L. Stathem B.S., University of Georgia, 2010 Thesis Approved on 08/07/2014 by the following Thesis Committee: __________________________________ Leah Siskind, Ph.D. __________________________________ Levi Beverly, Ph.D.
    [Show full text]