Mass Spectrometry in Cancer Research

by Roboz; John

• ISBN13: 9780849301674
• ISBN10: 084930167X
• Format: Hardcover
• Copyright: 2002-03-25
• Publisher: CRC Press

Summary

Cancer research is becoming multidisciplinary. The complex structural and therapeutic problems require synergistic approaches employing an assortment of biochemical manipulations, chromatographic or electrophoretic separations, sequencing strategies, and … more and more mass spectrometry.Mass Spectrometry in Cancer Research provides a broad examination of current strategies and techniques and their application to the study of:(i) occupational and environmental carcinogens;(ii) antineoplastic and chemopreventive agents;(iii) pertinent proteins, lipids, nucleic acids and glycoconjugates. Also included are a chapter on instrumentation and methodologies for biologists and physicians and a brief review of the relevant concepts of cancer biology and medicine for mass spectrometrists.This book is intended for: mass spectrometrists in research or those providing core services; researchers in biological, medical, pharmaceutical or environmental sciences; physicians in academic medicine; and academic/industrial research managers.

Author Biography

John Roboz is a Professor in the Department of Medicine (Division of Medical Oncology) of the Mount Sinai School of Medicine, New York

Table of Contents

About the Author	xiii
Foreword	xv
Mass Spectrometry: An Oncologist's Viewpoint	xvii
Preface	xix
Acknowledgments	xxi
Terminology and Abbreviations	1	(544)
Overview and Scope of Applications	5	(18)
The Essentials	5	(2)
Functions and Types of Instrument Components	7	(8)
Sample Introduction Systems	7	(2)
Ion Sources	9	(3)
Mass Analyzers	12	(2)
Ion Detectors	14	(1)
Vacuum Systems	15	(1)
Data Systems	15	(1)
Measures of Performance	15	(2)
Resolution and Resolving Power	15	(1)
Mass Range	16	(1)
Mass Accuracy	16	(1)
Scan Speed	16	(1)
Specificity Sensitivity and Limit of Detection	17	(1)
Information from Mass Spectra and Scope of Applications	17	(6)
Instrumentation and Techniques of Mass Spectrometry	23	(58)
Ion Sources	23	(13)
Electron Ionization	23	(1)
Chemical Ionization	24	(1)
Atmospheric Pressure Chemical Ionization	25	(1)
Electrospray Ionization	26	(3)
Nano-Electrospray	29	(1)
Microfabricated Silicone Chip-Based Electrospray Ion Sources	29	(1)
Multiplexed Electrospray	29	(1)
Fast Atom and Ion Bombardment	30	(1)
Matrix-Assisted Laser Desorption Ionization	31	(2)
Surface-Enhanced Laser Desorption Ionization (SELDI)	33	(1)
Photoionization	33	(1)
Direct Laser Desorption Ionization	33	(1)
Resonance-Enhanced Multiphoton Ionization	33	(1)
Inductively Coupled Plasma	34	(1)
Miscellaneous Ionization Techniques	34	(1)
Secondary Ion Mass Spectrometry	34	(1)
Field Ionization and Field Desorption	34	(1)
Californium-252 Plasma Desorption	35	(1)
Glow Discharge	35	(1)
Spark Source	35	(1)
Thermal Ionization	36	(1)
Mass Analyzers	36	(13)
Time-of-Flight Analyzers	36	(2)
Orthogonal Acceleration TOF	38	(1)
Reflectrons (Ion Mirrors)	38	(1)
Delayed Extraction	39	(1)
Quadrupole Analyzers	39	(2)
Quadrupoles as Ion Guides	41	(1)
Hexapoles	41	(1)
Quadrupole Ion Traps	41	(1)
Magnetic Analyzers	42	(1)
Magnetic Sector and Electrostatic Analyzers	42	(2)
Fourier Transform Ion-Cyclotron Resonance Analyzers	44	(1)
Tandem Analyzers	45	(1)
Magnetic Analyzers as Components of Tandem Systems	46	(1)
Quadrupole-Time-of-Flight Hybrid Analyzer	47	(1)
Hexapole-TOF Hybrid Analyzer	47	(1)
Accelerator Mass Spectrometry	48	(1)
Ion Current Detectors	49	(3)
Single Point Ion Collectors	50	(1)
Faraday Cup Detectors	50	(1)
Secondary Electron Multipliers	50	(1)
Scintillation Counters	50	(1)
Multipoint (Array) Detectors	51	(1)
Interfaces for Sample Introduction	52	(7)
Gases and Volatile Liquids	53	(1)
Reservoir and Batch Inlets	53	(1)
Membrane Inlets	54	(1)
Static Direct Inlet Probes	54	(1)
Interfaces for Coupling with Gas Chromatographs	54	(1)
Interfaces for Coupling with Liquid Chromatographs	55	(1)
Interfaces for Coupling with Capillary Electrophoresis Systems	56	(2)
High Throughput Inlets and Microfabricated Fluidic Systems	58	(1)
Mass Spectrometry/Mass Spectrometry (MS/MS)	59	(4)
Ion Activation Methods	59	(1)
Metastable Ions	60	(1)
Collision-Induced Dissociation	60	(1)
Electron-Capture Dissociation	60	(1)
Photodissociation and Surface-Induced Dissociation	60	(1)
In-Source Fragmentation	61	(1)
Tandem-in-Space (Transmission) Techniques	61	(1)
Product-Ion Scanning Mode	62	(1)
Precursor Scanning Mode	62	(1)
Constant Neutral Loss Scanning Mode	62	(1)
Selected Reaction Monitoring	62	(1)
Post-Source Decay	62	(1)
Tandem-in-Time (Trapped-Ion) Techniques	63	(1)
Identification and Quantification	63	(6)
Mass Spectral Libraries and Bioinformatics	63	(1)
Accurate Mass Measurement	64	(1)
Selected Ion and Reaction Monitoring	65	(1)
Selected Ion Monitoring	65	(2)
Selected Reaction Monitoring	67	(1)
Stable Isotope Dilution	67	(2)
Resources	69	(12)
Relevant Concepts of Cancer Medicine and Biology	81	(26)
Classification and Epidemiology	81	(4)
Solid Tumors	81	(1)
Hematologic Malignancies	82	(1)
Incidence and Distribution of Cancers	82	(1)
Risk Factors	83	(2)
Cellular Proliferation and Communication	85	(5)
Growth Patterns	85	(1)
Cell Cycle	86	(3)
Cellular Communication and Signal Transduction	89	(1)
Genetic Abnormalities in Cancer	90	(5)
Cancer as a Genetic Disorder of Somatic Cells	90	(1)
Mutation	90	(1)
Oncogenes	91	(3)
Tumor Suppressor Genes	94	(1)
Carcinogenesis Requires an Accumulation of Mutations	94	(1)
Tumor Immunology	95	(3)
Hematopoiesis	95	(1)
Antigens and Antibodies	96	(1)
Types of Immune Response	97	(1)
Diagnosis and Treatment	98	(3)
Clinical Presentation	98	(1)
Diagnostic Work up	98	(2)
Treatment Modalities	100	(1)
Functional Status Complications and Causes of Death	101	(1)
Some Pertinent Experimental Methods	101	(6)
DNA and RNA Analysis	101	(1)
Polymerase Chain Reaction	102	(1)
Determination of Clonality	102	(1)
Cell Cultures	103	(1)
Experimental Mouse Models	104	(1)
Recommended Books	105	(2)
Metabolism and Biomarkers of Carcinogens	107	(94)
Classification, Mechanism of Action and Biomarkers	107	(10)
Classification and Risk Assessment	107	(1)
Risk Assessment	108	(1)
Metabolism Enzymatic Activation and Mechanism of Action	109	(1)
Absorption Distribution and Storage	109	(2)
Key Steps in Chemical Carcinogenesis	111	(1)
Functions of Phase I and II Enzymes	112	(1)
Methodologies for Biomarkers	113	(1)
DNA Adducts	113	(3)
Hemoglobin Adducts	116	(1)
Occupational Carcinogens	117	(20)
Aromatic Hydrocarbons	117	(1)
Benzene	117	(5)
Risk Assessment of Polycyclic Aromatic Hydrocarbons in Coke Workers	122	(3)
Gasoline and Diesel Exhaust	125	(1)
Aromatic Amines	125	(1)
Benzidine	125	(2)
Miscellaneous	127	(1)
Plastic Monomers	128	(1)
Acrylonitrile	128	(1)
Ethylene and Propylene Oxides	129	(2)
Vinyl Chloride	131	(1)
Butadiene	132	(1)
Styrene and Styrene Oxide	133	(1)
Exposure by Health Care Personnel to Cytotoxic Drugs	134	(3)
Environmental Carcinogens	137	(42)
Tobacco	137	(1)
Quantification of Nicotine and Its Metabolites	137	(5)
Benzene and Polycyclic Aromatic Hydrocarbons	142	(1)
4-Aminobiphenyl	143	(3)
Tobacco-Specific N-Nitrosamines	146	(6)
Air	152	(1)
Gasoline and Diesel Fuels	152	(3)
Polycyclic Aromatic Hydrocarbons	155	(1)
Monitoring Miscellaneous Complex Mixtures	156	(2)
Food	158	(1)
Aflatoxins	158	(3)
Heterocyclic Aromatic Amines	161	(7)
Nitrosamines	168	(2)
Polycyclic Aromatic Hydrocarbons	170	(1)
Dioxins and Pesticides	170	(1)
Water and Soil	171	(1)
Membrane Inlet Mass Spectrometry	171	(1)
Carcinogen Identification in Well Water by High-Resolution MS	172	(1)
Vinyl Chloride Monomer in Drinking Water	173	(1)
Phenolic Xenoestrogens in Water	174	(1)
Mutagenic Heterocyclic Amines in the Danube River	174	(1)
Polycyclic Aromatic Hydrocarbons in Soils	174	(2)
Composted Municipal Sludge and Compost-Amended Soil	176	(1)
Helicobacter Pylori	176	(1)
Elements	177	(1)
Arsenic	177	(1)
Selenium	178	(1)
Chromium	179	(1)
DNA Damage by Radiation and Oxidation	179	(22)
References	180	(21)
Mechanism of Action and Metabolism of Antineoplastic and Chemopreventive Agents	201	(160)
Cytotoxic Therapy	201	(70)
Basic Principles	201	(1)
Cell Kill Hypothesis Classification and Mechanisms of Action	201	(3)
Toxicity Resistance and Combination Chemotherapy	204	(2)
Drug Discovery and Development Clinical Trials	206	(5)
Alkylating Agents	211	(1)
Mechanism of Action	211	(1)
Nitrogen Mustards	211	(13)
Alkyl Sulfonates	224	(3)
Nitrosoureas	227	(1)
Nonclassic Alkylating Agents	228	(1)
Platinum Compounds	229	(8)
Topoisomerase Inhibitors	237	(1)
Topoisomerase I Inhibitors	238	(5)
Topoisomerase II Inhibitors	243	(11)
Antimicrotubule Agents	254	(1)
Microtubules and Tubulins	254	(2)
Vinca Alkaloids	256	(2)
Taxanes	258	(5)
Miscellaneous	263	(2)
Antimetabolites	265	(1)
Purine and Pyrimidine Analogs	265	(3)
Antifolates	268	(3)
Opportunistic Fungal Infections	271	(1)
Endocrine Therapy	271	(18)
Mechanism of Action	271	(1)
Aromatase Inhibitors	271	(2)
Structure and Function	273	(1)
Nonsteroidal Inhibitors	273	(2)
Steroidal Inhibitors	275	(2)
Aromatase Inhibitory Activity of Androgens	277	(1)
Antiestrogens	278	(1)
Tamoxifen	278	(10)
Toremifene	288	(1)
Targeted Drug Delivery and Therapy	289	(16)
Drugs Conjugated to Proteins Antibodies or Lipids	289	(1)
Angiogenesis Inhibitors	290	(9)
Antisense Oligonucleotides	299	(2)
Ras Oncoprotein Inhibitors	301	(1)
Antibody-Directed Enzyme Prodrug Therapy	302	(1)
Miscellaneous Strategies for Targeting	302	(1)
Photodynamic Therapy	302	(2)
Differentiating Agents	304	(1)
Arsenic Trioxide	304	(1)
Nutritional and Chemical Prevention	305	(56)
Objectives and Classifications	305	(2)
Phytoestrogens	307	(1)
Multicomponent Analysis in Food	308	(4)
Multicomponent Analysis in Body Fluids	312	(4)
Metabolism and Antineoplastic Effects	316	(5)
Flavan-3-ols (Catechins)	321	(1)
Tea	321	(1)
Wine	321	(1)
Terpenes and Ginsenosides	322	(1)
Metabolism of d-Limonene	322	(3)
Ginsenosides	325	(1)
Carotenoids	325	(2)
Sulfur-Containing Compounds	327	(1)
Isothiocyanates	327	(2)
Garlic	329	(1)
Oltipraz and N-acetylcysteine	330	(1)
Retinoids, Vitamins, and Selenium	331	(1)
Retinoids	331	(1)
Vitamin E	332	(1)
Selenium	333	(1)
References	333	(28)
Strategies Techniques and Applications in Cancer Biochemistry and Biology	361	(184)
Proteins and Peptides	361	(99)
Proteome Technology	361	(1)
Proteomics and Strategies of Proteome Analysis	361	(4)
Protein Isolation Digestion and Delivery into the Ion Source Instrumentation	365	(4)
Sequencing by Edman Degradation	369	(1)
Mass Spectrometric Peptide Mapping	370	(1)
Peptide Ladder Sequencing	371	(1)
Sequencing by Tandem Mass Spectrometry	372	(5)
Protein Identification by Database Searches	377	(4)
Mass Measurement of Intact Proteins	381	(2)
Quantification	383	(2)
Posttranslational Modifications	385	(2)
Phosphorylation	387	(8)
Selected Other Posttranslational Modifications	395	(3)
Miscellaneous Proteins	398	(1)
Enzymes	398	(4)
Antigens	402	(1)
Non-Glycosylated Cytokines	403	(4)
Tumor-Associated Proteins	407	(1)
Tumor Proteomics	407	(2)
Hematologic Malignancies	409	(9)
Gynecologic Malignancies	418	(6)
Genitourinary Malignancies	424	(4)
Gastrointestinal Malignancies	428	(6)
Other Cancers	434	(3)
Peptides and Class I Major Histocompatibility Complexes	437	(1)
Class I MHC Molecules	437	(3)
Strategies and Techniques	440	(2)
Peptide Antigens in Malignancies	442	(7)
Noncovalent Interactions and Protein Folding	449	(1)
Protein-Ligand Interactions	449	(1)
Protein-Protein Interactions	450	(3)
Protein-DNA Interactions	453	(2)
Protein Conformation and Folding	455	(5)
Lipids	460	(12)
Ceramides	462	(6)
Eicosanoids	468	(2)
Lysophospholipids	470	(1)
Platelet-Activating Factor	471	(1)
Oligonucleotides and Nucleic Acids	472	(14)
Mass Spectra	472	(1)
Nomenclature of Fragmentation	472	(1)
Electrospray Ionization	473	(1)
MALDI-TOFMS	474	(1)
High-Resolution MALDI-FTICRMS	474	(1)
Analysis of Large Nucleic Acids	475	(1)
Techniques and Strategies	475	(1)
Polymerase Chain Reaction	475	(1)
Differential Sequencing	476	(1)
Mass Spectrometric Methods for Genotyping	476	(4)
Detection of Mutation	480	(1)
DNA Sequencing and Genetic Diagnosis	480	(1)
Sequencing Exons of the p53 Gene	480	(1)
Identifying Microsatellite Alleles	481	(1)
Familial Adenomatous Polyposis	482	(1)
Multiple Endocrine Neoplasia Type 2A	483	(2)
Breast Cancer Susceptibility Gene BRCA1	485	(1)
Carbohydrates and Glycoconjugates	486	(59)
Carbohydrates	486	(1)
Nomenclature and Techniques for Collision-Induced Dissociation	486	(2)
Sialic Acids	488	(1)
Polysaccharides and Glycosaminoglycans	488	(1)
Glycosylation	489	(2)
Glycoproteins	491	(1)
Mucins	492	(7)
Antigens	499	(4)
Miscellaneous Glycoproteins	503	(6)
Glycolipids (Gangliosides) in Various Malignancies	509	(9)
Recommended Books	518	(1)
References	518	(27)
Index	545