Methods of cancer diagnosis, therapy and prognosis : General overviews, head and neck cancer and thyroid cancer / Vol. 7

PART I. GENERAL METHODS AND OVERVIEWS Diagnosis 1. ROLE OF RNA INTERFERENCE IN UNDERSTANDING THE MOLECULAR BASIS OF CANCER; Jeffrey P. MacKeigan and Alex Gaither MECHANISM OF RNA INTERFERENCE RNA INTERFERENCE AS A CELL BASED SCREENING TOOL RNA INTERFERENCE TO UNDERSTAND COMPOUND MECHANISM OF ACTION COMPOUND SENSITIZATION, COMBINATION STRATEGIES AND SYNTHETIC LETHAL RNA INTERFERENCE SCREENS PROBLEMS ASSOCIATED WITH RNA INTERFERENCE BASED APPROACHES REFERENCES 2. CANCER BIOMARKERS (AN OVERVIEW); William C.S. Cho INTRODUCTION EMERGING TECHNOLOGIES FOR CANCER BIOMARKER DISCOVERY DNA Microarray Serial Analysis of Gene Expression MicroRNA Microarray Two Dimensional Polyacrylamide Gel Electrophoresis Free Flow Electrophoresis Capillary Electrophoresis Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Liquid Chromatography Coupled with Tandem Mass Spectrometry Linear Ion Trap Quadrupole-Orbitrap Imaging Mass Spectrometry Isotope-Coded Affinity Tags Multiple Reaction Monitoring Absolute Quantification of Proteins Protein Microarray Tissue Array Bioinformatics CURRENTLY USED CANCER BIOMARKERS BIOMARKERS FOR THE DIAGNOSIS OF CANCERS Genomic-based Biomarkers in Cancer Transcriptomic-based Biomarkers in Cancer Proteomic-based Biomarkers in Cancer BIOMARKERS FOR THE TREATMENT AND PROGRESSION OF CANCERS Genomic-based Biomarkers in Cancer Transcriptomic-based Biomarkers in Cancer Proteomic-based Biomarkers in Cancer BIOMARKERS FOR THE PROGNOSIS OF CANCERS Genomic-based Biomarkers in Cancer Transcriptomic-based Biomarkers in Cancer Proteomic-based Biomarkers in Cancer CHALLENGES AND PERSPECTIVES REFERENCES TUMOR ANGIOGENESIS IN CANCERS: EXPRESSION OF CD105 MARKER; Osamu Tokunaga, Rahmawati Minhajat, and Daisuke Mori INTRODUCTION MORPHOLOGICAL FEATURES OF TUMOR ANGIOGENESIS DETECTION OF THE ENDOTHELIUM IMMUNOHISTOLOGY Antigenecity Retrieval Immunohistology SIMULTANEOUS MASS AND COMPARATIVE STUDY: TISSUE ARRAY SPECIFIC MARKERS FOR VASCULAR ENDOTHELIUM IN TUMORS Angiogenesis CD105/ENDOGLIN ENDOTHELIAL MARKER SPECIFIC FOR NEWLY FORMED BLOOD VESSELS CD105 AND VASCULOGENESIS ORGAN SPECIFICITY OF CD105 POSITIVE TUMOR ANGIOGENESIS APPLICATION OF CD105 FOR ANTI-ANGIOGENIC CANCER THERAPY REFERENCES 4. SPINDLE CELL ONCOCYTOMA OF THE ADENOHYPOPHYSIS: INTEGRATED CLINICOPATHOLOGIC DIAGNOSIS BY IMAGING, HISTOLOGY, AND IMMUNOHISTOCHEMISTRY; Istvan Vajtai and Rahel Sahli INTRODUCTION CLINICAL PRESENTATION IMAGING ASPECTS HISTOLOGY AND IMMUNOPHENOTYPE DIFFERENTIAL DIAGNOSIS THERAPEUTIC AND PROGNOSTIC IMPLICATIONS DISCUSSION AND PERSPECTIVES REFERENCES 5. DISSEMINATED CARCINOMA OF UNKNOWN PRIMARY SITE: DETECTION WITH F-FLUORODEOXYGLUCOSE- POSITRON EMISSION TOMOGRAPHY; Pascal Seve and John R. Mackey INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES 6. UNKNOWN LYMPHADENOPATHY: DIAGNOSIS USING AN ENDOSCOPIC ULTRASOUND-GUIDED FINE-NEEDLE ASPIRATION; Ichiro Yasuda INTRODUCTION APPLICATION EQUIPMENT PROCEDURE DIAGNOSTIC YIELD REFERENCES Therapy 7. PRETARGETED RADIOIMMUNOTHERAPY IN CANCER: AN OVERVIEW; Stefano Papi, Chiara Maria Grana, Mirco Bartolomei, Laura Ravasi, Marta Cremonesi, Mahila Ferrari, Luigi Martano, Lucia Garaboldi, Marco Chinol, and Giovanni Paganelli INTRODUCTION THERAPEUTIC RADIOISOTOPES LIMITATIONS OF CLASSICAL RADIOIMMUNOTHERAPY IN SOLID TUMORS PRETARGETING APPROACH AVIDIN-BIOTIN SYSTEM Avidin-Biotin Pretargeting in Glioma OTHER DEVELOPMENTS CONCLUSION REFERENCES 8. CHEMOTHERAPY-INDUCED NEUROTOXICITY; Sussana B. Park and Mathew C. Kiernan INTRODUCTION CLINICAL PRESENTATIONS OF NEUROTOXICITY INCIDENCE OF NEUROTOXICITY PATHOPHYSIOLOGY OF NEUROTOXICITY CLINICAL EVALUATION AND ASSESSMENT NEUROPHYSIOLOGICAL ASSESSMENT CHARACTERISTICS OF NEUROTOXIC CHEMOTHERAPIES Taxanes Cisplatin Vincea alkaloids Other Neurotoxic Chemotherapies OXALIPLATIN-INDUCED NEUROTOXICITY Pathophysiological Mechanisms of Oxaliplatin Assessment of Oxaliplatin-Induced Neurotoxicity Nerve Excitability Studies in Oxaliplatin Neuropathy Future Directions and Neuroprotections REFERENCES 9. MULTIDRUG RESISTANCE; Ernesto Yague and Selina Raguz INFLUENCE OF PHARMACOLOGICAL AND PHYSIOLOGICAL FACTORS MOLECULAR MECHANISMS OF RESISTANCE TO TRADITIONAL CHEMOTHERAPY Intracellular Drug Activation Detoxifying Systems DNA Repair Cell Death Regulation Membrane Proteins CELLULAR MODELS TO STUDY DRUG RESISTANCE Leukemic K562 Cells as a Model to Study Multi-Drug Resistance ANIMAL MODELS TO STUDY DRUG RESISTANCE CANCER STEM CELLS AND DRUG RESISTANCE DRUG RESISTANCE IN THE CLINIC REVERSAL OF DRUG RESISTANCE IN THE CLINICAL SETTING REFERENCES 10. ROLE OF ANTIBODIES IN CANCER TREATMENT: AN OVERVIEW; Huguette Albrecht INTRODUCTION STRUCTURE OF AN ANTIBODY RECOMBINANT ANTIBODIES Chimeric and Humanized Monoclonal Antibodies Antibody Fragments Antibody Fragments Combinatorial Libraries PHARMACOKINETICS OF ANTIBODIES TUMOR ANTIGENS MANUFACTURING OF ANTIBODIES MECHANISMS OF ACTION OF THERAPEUTIC MONOCLONAL ANTIBODIES TOXICITIES ASSOCIATED WITH THERAPEUTIC MONOCLONAL ANTIBODIES THERAPEUTIC MONOCLONAL ANTIBODIES CURRENTLY LICENSED Anti-CD20 Monoclonal Antibodies Anti-CD33 Monoclonal Antibody Anti-CD52 Monoclonal Antibody Anti-HER-2 Monoclonal Antibody Anti-EGFR Monoclonal Antibodies Anti-VEGF Monoclonal Antibody THERAPEUTIC MONOCLONAL ANTIBODIES AND ANTIBODY TARGETED THERAPEUTICS UNDER INVESTIGATION Clinical Evaluation Preclinical Evaluation REFERENCES 11. INCORPORATING PHARMACOGENOMICS INTO CANCER THERAPY; Wooin Lee and Craig Lockhart INTRODUCTION CURRENT USE OF PHARMACOGENOMICS IN CLINICAL ONCOLOGY Thiopurine Methyltransferase (TPMT) UDP-Glucuronosyltransferase 1A1 (UGT1A1) Other Pharmacogenomic Markers in Clinical Investigation Drug-metabolizing Enzymes Transporter Proteins Drug Target, Pathway Genes DNA Repair Genes METHODOLOGY Genotyping Assays Different Approaches in Pharmacogenomics IMPLEMENTATION OF PHARMACOGENOMICS IN DRUG DISCOVERY AND DEVELOPMENT FUTURE DIRECTIONS REFERENCES 12. CANCER STEM CELLS: AN OVERVIEW; Eiichi Morii and Katsuyuki Aozasa INTRODUCTION CANCER STEM CELLS: CONCEPT ISOLATION OF CANCER STEM CELLS ORIGIN OF CANCER STEM CELLS EPIGENETICS AND CANCER STEM CELLS FUTURE PERSPECTIVES REFERENCES 13. TRANSLATING IN VITRO CELL LINES RESULT INTO CLINICAL PRACTICE; Jai Prakash Mehta, Lorraine O'Driscoll, Niall Barron, Martin Clynes and Padraig Doolan INTRODUCTION HOW CELL LINES ARE GENERATED TYPES OF CELL CULTURE SELECTION BIAS SELECTION PRESSURE CELL LINE PREFERENCE AND AVAILABILITY CROSS-CONTAMINATION MICROBIAL CONTAMINATION HANDLING ERRORS NEW INSIGHT: MICROARRAY GENE-EXRESSION PROFILING OF TUMOURS AND CELL LINES REFERENCES Prognosis 14. CLASSIFICATION OF CANCER STAGE USING PATIENT'S IMMUNE SYSTEM; Patrizia Pellegrini, Ida Contasta, Anna Maria Berghella, Tiziana Del Beato and Domenico Adorno INTRODUCTION CLASSIFICATION SYSTEM FOR CANCER STAGE TH1/TH2/TH3/TH17 CYTOKINE PHYSIOLOGICAL NETWORK IN PERIPHERAL BLOOD SAMPLES TH1/TH2/TH3/TH17 CYTOKINE NETWORK: IMMUNE SYSTEM METHOD TO STUDY THE TH1/TH2/TH3/HT17 CYTOKINE NETWORK PHYSIOLOGICAL EVALUATION OF THE IMMUNE SYSTEM IMMUNOLOGICAL PARAMETERS FOR STAGE CLASSIFICATION DISEASE STAGE INDICES IN COLORECTAL CANCER REFERENCES 15. LATE RELAPSE OF GERM CELL MALIGNANCIES: INCIDENCE, MANAGEMENT AND PROGNOSIS; Jan Oldenburg and Sophie D. Fossa INTRODUCTION INCIDENCE SEMINOMA CLINICAL STAGE I SEMINOMA CLINICAL STAGE > I NONSEMINOMA CLINICAL STAGE I NONSEMINOMA CLINICAL STAGE > I DETECTION AND DIFFERENTIAL DIAGNOSIS TREATMENT AND SURVIVAL Seminoma Nonseminoma REFERENCES PART II. HEAD AND NECK CANCER 16. HEAD AND NECK SQUAMOUS CELL CARCINOMA: THERAPY WITH FUSARIC ACID/PACLITAXEL; Brendan C. Stack, Jr., Brett Clarke, Joshua McElderry, Yeumeng Dai, and Jian-Hui Ye INTRODUCTION A NEW CLASS OF AGENTS FOR HEAD AND NECK CANCER Head and Neck Squamous Cell Carcinoma Fusaric Acid Picolinic Acid A NEW TARGET IN THE HEAD AND NECK CANCER CELL Zinc Finger Proteins Metallopanstimulin Metallopanstimulin-1 EVIDENCE FOR FUSARIC ACID AS A NEW HEAD AND NECK CANCER THERAPY Docetaxol Carboplatin Vascular Endothelial Growth Factor Squamous Cell Carcinoma Tarceva Terminal Nick End Label REFERENCES 17. EARLY STAGE ORAL SQUAMOUS CELL CARCINOMA: USE OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3 AS A RISK FACTOR FOR POOR DIAGNOSIS; Neelam.G. Shah and T.I. Trivedi INTRODUCTION SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION ACTIVATION OF STAT SIGNALING STAT3 PHYSIOLOGICAL ROLE OF STAT 3 STAT3 IN ONCOGENESIS STAT3 IN ORAL SQUAMOUS CELL CARCINOMA ENZYME MOBILITY SHIFT ASSAY COMPETITION MOBILITY SHIFT ASSAY SUPER SHIFT ASSAY DNA BINDING AFFINITY PURIFICATION IN SITU HYBRIDIZATION IMMUNOBLOTTING IMMUNOHISTOCHEMICAL LOCALIZATION REVERSE TRANSCRIPTION-POLYMERASE CHAIN REACTION REFERENCES 18. SALIVARY GLAND TUMORS: PREOPERATIVE TISSUE CHARACTERIZATION WITH APPARENT DIFFUSION COEFFICIENT MAPPING; Takashi Nakamura, Misa Sumi, and Marc Van Cauteren INTRODUCTION DIFFUSION-WEIGHTED IMAGING Measurement of Diffusion-Weighted Imaging Clinical Use of Diffusion-Weighted Imaging SALIVARY GLAND TUMORS 2D Apparent Diffusion Coefficient Color Mapping of Mapping Salivary Gland Tumors Apparent Diffusion Coefficients of Healthy Major Salivary Glands| Apparent Diffusion Coefficients of Benign Salivary Gland Tumors Apparent Diffusion Coefficients of Malignant Salivary Gland Tumors TISSUE CHARACTERIZATION WITH APPARENT DIFFUSION COEFFICIENT MAPPING APPLICATION OF APPARENT DIFFUSION COEFFICIENT MAPPING TO THE DIAGNOSIS OF MALIGNANT LESIONS HIGH-RESOLUTION IMAGING USING A SURFACE COLI REFERENCES 19. ROLE OF HUMAN PAPILLOMA VIRUS IN TONSILLAR CANCER; Eva Munck-Wikland, Lalle Hammarstedt, and Hanna Dahlstrand INTRODUCTION TONSILLAR CANCER HUMAN PAPILLOMAVIRUS (HPV) EPIDEMIOLOGY EVIDENCE OF HPV ROLE IN CARCINOGENESIS SEXUAL BEHAVIOUR AND OROPHARYNGEAL CANCER HPV AND PROGNOSIS IN TONSILLAR CANCER IMPACT OF VIRAL LOAD ON PROGNOSIS P16 INK4A -- A SURROGATE MARKER FOR HPV 16 HPV IN OTHER OROPHARYNGEAL CANCER FUTURE PERSPECTIVES METHODS OF HPV DETECTION AND GENOTYPING Polymerase Chain Reaction (PCR) Hybrid Capture DNA In Situ Hybridization (ISH) HPV Genotyping HPV mRNA Amplification and Detection HPV Serology HPV DNA Load REFERENCES 20. QUANTITATIVE REVERSE TRANSCRIPTION-POLYMERASE CHAIN REACTION BASED ASSESSMENT OF THE CANDIDATE BIOMARKERS FOR TONGUE CANCER METASTASIS; Xiaofeng Zhou, Tianwei Yu, and David T. Wong INTRODUCTION QUANTITATIVE POLYMERASE CHAIN REACTION QPCR Chemistries Taqman Probes Molecular Beacons Self fluorescing amplicons SYBR Green Quantification of Results Standard Curve Method Comparative CT Method ORAL TONGUE CANCER Oral Tongue Squamous Cell Carcinoma (OTSCC), A Major Subset of Oral Cancer Metastasis -- A Major Clinical Problem of Oral Cancer THE QPCR BASED EVALUATION OF CANDIDATE TONGUE CANCER METASTASIS MARKERS Cancer Biomarkers Quantitative PCR Based Detection of Metastasis Markers in Tongue Cancer Cortactin (CTTN) Matrix Metalloprotinase (MMP9) Quantification and Statistical Evaluation of the Markers FUTURE DEVELOPMENTS REFERENCES 21. NASOPHARYNGEAL CARCINOMA (RETROPHARYNGEAL LYMPH NODE METASTASIS): SPREAD PATTERN, PROGNOSIS AND STAGING; Li Li and Li-Zhi Liu INTRODUCTION MATERIALS AND METHODS Patient Characteristics Imaging Protocol and Criteria for RLN Metastasis and Other Cervical Lymph Nodes Treatment Follow-up and Statistical Analysis RESULTS Spread Pattern of RLN Metastasis Based on MRI Data Incidence and Distribution of RLNs Demonstrated by MRI Relationship between Metastatic RLNs and Tumor Involvement Prognosis and Staging of RLN Metastasis Demonstrated by CT Prognosis Hazard Consistency and Hazard Discrimination Comparing Staging Categories of RLN Metastasis DISCUSSION Imaging Criteria for Metastatic RLNs Incidence of RLNs Metastasis Spread Patterns of RLNs Metastasis Prognostic Significance and Staging of RLNs Metastasis 22. RETINOBLASTOMA: DIAGNOSIS, TREATMENT, AND PROGNOSIS; Aubin Balmer, Francis Munier, and Leonidas Zografos INTRODUCTION DIAGNOSIS Epidemiology Genetics Semeiology Clinical Features Clinical Investigation Classification Differential Diagnosis TREATMENT Treatment Methods Future Advances PROGNOSIS REFERENCES PART III. THYROID CARCINOMA Diagnosis 23. MOLECULAR GENETICS OF THYROID CANCER; Deanne King, Donald Bodenner, and Brendan C. Stack, Jr. INTRODUCTION PAPILLARY THYROID CARCINOMAS RET Oncogenes RAS Oncogene BRAF Gene APC Gene FOLLICULAR CARCINOMA RAS Oncogene PAX8/PPAR PTEN MEDULLARY CARCINOMA RET Oncogene ANAPLASTIC CARCINOMA P53 Mutations MRP-1 MOLECULAR PROFILING FINE NEEDLE ASPIRATION REPORT REFERENCES 24. THYROID CANCER: IDENTIFICATION OF GENE EXPRESSION MARKERS FOR DIAGNOSIS; Obi L. Griffith, Adrienne Melck, Steven J.M. Jones, and Sam M. Wiseman INTRODUCTION GENE EXPRESSION TECHNOLOGIES CDNA Microarrays Oligonucleotide Arrays Serial Analysis of Gene Expression Future Tag-Sequence Methods EXPERIMENTAL ISSUES Array Design Sample Preparation Replicates DATA ANALYSIS ISSUES Quality Assessment Normalization and Background Correction Probe/Tag Mapping Differential Expression Analysis Expression Profiling Software and Databases VALIDATION METHODS CLUSTERING AND CLASSIFICATION ANALYSIS Cancer Diagnosis Using Tumor Gene Expression Signatures Defining New Molecular Subtypes with Gene Expression Data Developing Biomarkers or Panels from Microarray Class Predictors EXPRESSION PROFILING STUDIES IN THYROID CANCER CROSS-PLATFORM INTEGRATION AND META-ANALYSIS MOLECULAR MARKERS FOR THYROID CANCER REFERENCES 25. PAPILLARY THYROID CARCINOMA: USE OF HBME1 AND CK19 AS DIAGNOSTIC MARKERS; Michel R. Nasr and Sanjay Mukhopadhyay INTRODUCTION PROTOCOL MATERIALS METHODS INTERPRETATION OF STAINING HBME1 IN PAPILLARY THYROID CARCINOMA AND BENIGN THYRIOD LESIONS CK19 IN PAPILLARY THYROID CARCINOMA AND BENIGN THYROID LESIONS CONCLUSION REFERENCES 26. PAPILLARY THYROID CARCINOMA: DETECTION OF COPY GAIN OF PLATELET DERIVED GROWTH FACTOR B USING ARRAY COMPARATIVE GENOMIC HYBRIDIZATION IN COMBINATION WITH LASER CAPTURE MICRODISSECTION; Stephen P. Finn, John J. O'Leary, and Orla M. Sheils INTRODUCTION COMPARATIVE GENOMIC HYBRIDIZATION METHODOLOGY Tumors and Cell Lines LASER CAPTURE MICRODISSECTION DNA EXTRACTION ARRAY COMPARATIVE GENOMIC HYBRIDIZATION Labeling Protocol DNASE DIGESTION AND LABELLED PROBE PURIFICATION HYBRIDIZATION PROTOCOL IMAGE ANALYSIS RESULTS DISCUSSION REFERENCES 27. POSITRON EMISSION TOMOGRAPHY IMAGING IN THYROID CARCINOMA; H.H.G. Verbeek, T.T.H. Phan, A.H. Brouwers, K.P. Koopmans, and T.P. Links INTRODUCTION POSITRON EMISSION TOMOGRAPHY COMBINED POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY 18FLUORINE-FLURODEOXYGLUCOSE-POSITRON EMISSION TOMOGRAPHY Mechanism Scan Method Clinical Application Thyroid Nodules Differentiated Thyroid Cancer Follow-Up Medullary Thyroid Cancer 18FLUORINE-DIHYDROXYPHENYLALINE-POSITRON EMISSION TOMOGRAPHY Mechanism Scan Method Clinical Application Medullary Thyroid Cancer 11C-METHIONINE-POSITRON EMISSION TOMOGRAPHY Mechanism Scan Method Clinical Application Differentiated Thyroid Cancer 124IODINE-POSITRON EMISSION TOMOGRAPHY Mechanism Scan Method Clinical Applications Differentiated Thyroid Cancer CONCLUSION REFERENCES Therapy 28. METASTASIZED MEDULLARY THYROID CARCINOMA: DETECTION AND THERAPY USING RADIOLABELED GASTRIN ANALOGS; Martin Gotthardt, Lioe-Fee de Geus-Oei, Thomas M. Behr, and Martin Behe MEDULLARY THYROID CARCINOMA Symptoms Diagnostic Procedures LOCALIZING AND TREATING METASTATIC MEDULLARY THYROID CARCINOMA RADIOPEPTIDE SCANNING VERSUS ANATOMICAL IMAGING MODALITIES RADIOLABELED PEPTIDES MINIGASTRIN FOR DETECTING METASTASIZED MEDULLARY THYROID CARCINOMA Cholecystokinine 2 (CCK2) Receptor Expression Labeling Scanning Protocol Biodistribution of Minigastrin Clinical Studies PEPTIDE RECEPTOR RADIOTHERAPHY OF METASTASIZED MEDULLARY THYROID CARCINOMA WITH GASTRIN ANALOGS FUTURE PERSPECTIVES OF DGlu1-MINIGASTRIN REFERENCES Prognosis 29. MEDULLARY THYROID CARCINOMA: PROGNOSIS BASED ON STAGE OF DISEASE AND AGE; Tracy S. Wang, Julie Ann Sosa, and Sanziana A. Roman INTRODUCTION EPIDEMIOLOGY PATHOLOGY AND PATHOGENESIS OF MEDULLARY THYROID CARCINOMA CLINICAL PRESENTATION Genetic Screening Genotype-Phenotype Correlations PROGNOSTIC FACTORS TREATMENT Treatment of Patients with Clinically Evident MTC Prophylactic Surgery for Patients with ret Protooncogene Mutations Nonsurgical Treatment Modalities SURVEILLANCE REFERENCES 30. OVEREXPRESSION OF THE COMPONENETS OF THE PLASMINOGEN ACTIVATING SYSTEM AS PROGNOSTIC FACTORS IN HUMAN THYROID CARCINOMA; Enke Baldini, Salvatore Ulisse, and Massimino D'Armiento PLASMINOGEN ACTIVATING SYSTEM (PAS) THE PLASMINOGEN ACTIVATING SYSTEM IN PATHOPHYSIOLOGICAL CONDITIONS ROLE OF PLASMINOGEN ACTIVATING SYSTEM IN HUMAN CANCERS CLINICAL SIGNIFICANCE OF THE EXPRESSION OF PLASMINOGEN ACTIVATING SYSTEM COMPONENTS |THE PLASMINOGEN ACTIVATING SYSTEM IN HUMAN THYROID CARCINOMAS METHODS TO EVALUATE EXPRESSION OF PLASMINOGEN ACTIVATING SYSTEM COMPONENTS REFERENCES