Methods of cancer diagnosis, therapy, and prognosis Volume 2, General methods and overviews, lung carcinoma and prostate carcinoma

PART I GENERAL METHODS AND OVERVIEWS 1.1. METABOLIC TRANSFORMATIONS OF MALIGNANT CELLS (AN OVERVIEW) Leslie C. Costello and Renty B. Franklin INTRODUCTION DEFINING A MALIGNANT CELL: A PARASITIC EXISTENCE THE IN SITU ENVIRONMENT OF THE MALIGNANT CELL DICTATES ITS METABOLISM TUMOR CELL PROLIFERATION: METABOLIC PATHWAYS FOR ITS ACHIEVEMENT COUPLING OF GLYCOLYSIS VIA CITRATE TO DE NOVO LIPOGENESIS/CHOLESTEROGENESIS OPERATION OF THE KREBS CYCLE IN TUMOR CELLS GLUTAMINOLYSIS AS AN ALTERNATE OR ADDITIONAL PATHWAY IN TUMOR CELLS OPERATION OF THE KREBS CYCLE IN TUMOR CELLS APPLICATION OF MOLECULAR GENETICS AND PROTEOMICS TO TUMOR CELL INTERMEDIARY METABOLISM ACKNOWLEDGEMENT REFERENCES 1.2. IMAGING TO DETECT RECURRENT CANCER S.J. Gwyther INTRODUCTION LUNG CANCER BREAST CANCER COLORECTAL CANCER LYMPHOMAS PANCREATIC CANCER PROSTATE CANCER GYNECOLOGICAL CANCERS Ovarian Cancer Endometrial Cancer Cervical Cancer HEAD AND NECK CANCERS THYROID CANCER RENAL AND BLADDER TUMORS PRIMARY INTRACRANIAL TUMORS CONCLUSIONS REFERENCES 1.3. TUMOR GENE THERAPY: MAGNETIC RESONANCE IMAGING AND MAGNETIC RESONANCE SPECTROSCOPY Mikko I. Kettunen and Olli H.J. Grohn INTRODUCTION TUMOR GENE THERAPY MAGNETIC RESONANCE IMAGING Endogenous Magnetic Resonance Imaging Contrast Exogenous Contrast Agents MAGNETIC RESONANCE SPECTROSCOPY DETECTION OF TRANSGENE DELIVERY AND EXPRESSION USING MAGNETIC RESONANCE IMAGING AND SPECTROSCOPY DETECTION OF GENE THERAPY RESPONSE USING MAGNETIC RESONANCE IMAGING AND SPECTROSCOPY Volumetric Imaging Endogenous Contrasts Sodium Magnetic Resonance Imaging Molecular Imaging Magnetic Resonance Spectroscopy of Metabolic Alterations SUMMARY REFERENCES 1.4. ASSESSMENT OF GENE TRANSFER: MAGNETIC RESONANCE IMAGING AND 18F-FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY Annette Altman and Uwe Haberkorn INTRODUCTION MOLECULAR IMAGING MODALITIES FOR GENE EXPRESSION MOLECULAR IMAGING OF SUICIDE GENE TRANSFER AND THERAPEUTIC EFFECTS MOLECULAR IMAGING SUBSTRATE UPTAKE AFTER SUICIDE GENE TRANSDUCTION NONINVASIVE IMAGING OF REPORTER GENE TRANSFER REFERENCES 1.5. ROLE OF MUTATIONS IN TP53 IN CANCER (AN OVERVIEW) Franck Toledo INTRODUCTION IMPACT OF TP53 MUTATIONS ON P53 TRANSACTIVATION CAPACITY OTHER EFFECTS OF TP53 MUTATIONS TP53 MUTATIONS AND THE ETIOLOGY OF HUMAN CANCERS PROGNOSTIC AND PREDICTIVE VALUE OF TP53 MUTATIONS CORRECTION OF P53 PATHWAY IN TUMORS FUTURE PERSPECTIVES REFERENCES 1.6. PERSONALIZED CANCER MEDICINE (AN OVERVIEW) Sarah J. Welsh and Garth Powis INTRODUCTION WHY IS PERSONALIZED MEDICINE IMPORTANT IN CANCER? TO WHAT EXTENT IS CANCER MEDICINE ALREADY PERSONALIZED? FUTURE OF PERSONALIZED MEDICINE IN CANCER CHALLENGES FOR ACHIEVING PERSONALIZED MEDICINE REFERENCES 1.7. RADIATION DOSES TO PATIENTS USING COMPUTED RADIOGRAPHY, DIRECT DIGITAL RADIOGRAPHY, AND SCREEN-FILM RADIOGRAPHY Gaetano Compagnone INTRODUCTION RADIATION QUANTITIES USED IN PATIENT DOSIMETRY CONVENTIONAL SCREEN-FILM SYSTEMS PATIENT DOSE AND IMAGE QUALITY WITH CONVENTIONAL SCREEN-FILM SYSTEMS COMPUTED RADIOGRAPHY PATIENT DOSE AND IMAGE QUALITY WITH COMPUTED RADIOGRAPHY DIRECT DIGITAL RADIOGRAPHY PATIENT DOSE AND QUALITY WITH DIRECT DIGITAL RADIOGRAPHY CONCLUSIONS REFERENCES 1.8. CANCER VACCINES AND IMMUNE MONITORING (AN OVERVIEW) Zsuzsanna Tabi and Stephen Man INTRODUCTION PROPHYLACTIC CANCER VACCINES Vaccines to Prevent HPV Infection and Cervical Cancer Vaccines to Prevent Hepatitis B Infection and Liver Cancer Vaccines to Prevent Hepatitis C Infection and Liver cancer Other Viruses Associated with Cancer THERAPEUTIC CANCER VACCINES Dendritic Cell Vaccines Adoptive T Cell Transfer (ATC) Peptide- and Protein-based Vaccines Recombinant Viral Vector-vaccines Non-specific Immune Stimulants -- Immune Response Modifiers Combination of Cancer Vaccines with Chemo- and Radiotherapy MONITORING IMMUNE RESPONSES Proliferation Assays Cytotoxicity Assays Cytokine Secretion Assays Tetramers Standardization Summary CONCLUSION AND OUTLOOK 1.9. NEW INSIGHTS INTO THE ROLE OF INFECTION, IMMUNITY, AND APOPTOSIS IN THE GENESIS OF CANCER STEM CELLS Peter Grandics INTRODUCTION EXTERIOR CELL SURFACE LAYER ACTIVATION OF COAGULATION INFECTION AND INFLAMMATION INFECTION, AUTOIMMUNITY, AND CANCER DEFECTIVE APOPTOSIS DISCUSSION AND THERAPEUTIC IMPLICATIONS SUMMARY REFERENCES 1.10. SUCCESSFUL CANCER TREATMENT: ERADICATION OF CANCER STEM CELLS David Dingli and Jorge M. Pacheco INTRODUCTION TISSUE ORGANIZATION AND STEM CELLS EVIDENCE FOR CANCER STEM CELLS ORIGIN OF CANCER STEM CELLS STOCHASTIC DYNAMICS OF CANCER STEM CELLS MARKERS OF CANCER STEM CELLS TREATING CANCER STEM CELLS Problems with targeting Cancer Stem Cells Overcoming Drug Resistance Evidence for effective Anticancer Stem Cell Therapy The Future REFERENCES 1.11. OVEREXPOSURE OF PATIENTS TO IONIZING RADIATION (AN OVERVIEW) Philip Clewer INTRODUCTION JUSTIFICATION AND OPTIMIZATION UNINTENDED EXPOSURES OVEREXPOSURE IN RADIOLOGY OVEREXPOSURE IN NUCLEAR MEDICINE OVEREXPOSURE IN RADIOTHERAPY AT WHAT LEVEL SHOULD WE BE CONCERNED REGARDING OVEREXPOSURES? REFERENCES PART II LUNG CANCER 2.1. LUNG CARCINOMA M.A. Hayat INTRODUCTION REFERENCES 2.2. EXTRA-PULMONARY SMALL CELL CANCER: DIAGNOSIS, TREATMENT, AND PROGNOSIS Rabia K. Shahid, Kamal Haider, Amer Sami, Imran Ahmed, Florence Arnold, Sunil Yadav, Kristie Harding, David Popkin, and Shahid Ahmed INTRODUCTION EPIDEMIOLOGY PATHOLOGY CLINICAL FEATURES DIFFERENTIAL DIAGNOSIS STAGING MANAGEMENT PROGNOSIS GENITOURINARY TRACT GYNECOLOGICAL SITES GASTROINTESTINAL TRACT HEAD AND NECK REGION BREAST UNKNOWN PRIMARY REFERENCES 2.3. MAGNETIC RESONANCE IMAGING OF THE LUNG: AUTOMATED SEGMENTATION METHOD William F. Sensakovic and Samuel G. Armato III INTRODUCTION THORACIC MAGNETIC RESONANCE IMAGING AND ACQUISITION ARTIFACTS AUTOMATED SEGMENTATION METHODS Thresholding, Shape Descriptors, and Morphological Operators Model-Based Segmentation Parametric Active Contours Neural Network/Active Contour Combination REFERENCES 2.4. PERIPHERAL LUNG LESIONS: DIAGNOSIS USING TRANSCUTANEOUS CONTRAST-ENHANCED SONOGRAPHY Christian Gorg and Angelique Holland INTRODUCTION PATHOPHYSIOLOGIC BASICS OF PULMONARY VASCULARITY GENERAL CONSIDERATIONS OF CONTRAST-ENHANCED SONOGRAPHY CLINICAL DATA OF CONTRAST-ENHANCED SONOGRAPHY Pleurisy Pulmonary Embolism Pleural-Based Pulmonary Nodules Pneumonia Atelectasis Primary Lung Tumors REFERENCES 2.5. SMALL PULMONARY NODULES: DETECTION USING MULTIDETECTOR-ROW COMPUTED TOMOGRAPHY Marco Das THE PULMONARY NODULE DIFFERENTIAL DIAGNOSIS OF PULMONARY NODULES MULTIDETECTOR-ROW COMPUTED TOMOGRAPHY FOR PULMONARY NODULES Technique Low-dose Computed Tomography Contrast-Enhanced Computed Tomography Dynamic Computed Tomography DIAGNOSTIC WORKUP Detection of Pulmonary Nodules Nodule Density Nodule Size Nodule Growth Recommended Workup Algorithms LUNG CANCER SCREENING ADVANCED DIAGNOSIS OF PULMONARY NODULES Computer-Aided Detection Computer-Aided Volumetry REFERENCES 2.6. SECONDARY PRIMARY CANCER FOLLOWING CHEMORADIATION FOR NON-SMALL CELL LUNG CANCER Nagio Takigawa and Katsuyuki Kiura INTRODUCTION RESULTS DISCUSSION REFERENCES 2.7. ADVANCED NON-SMALL CELL LUNG CANCER: SECOND- LINE TREATMENT WITH DOCETAXEL Cesare Gridelli and Paolo Maione INTRODUCTION SECOND-LINE TREATMENT DOCETAXEL VERSUS BEST SUPPORTIVE CARE IN THE SECOND-LINE TREATMENT DOCETAXEL VERSUS OTHER CHEMOTHERAPEUTIC AGENTS IN THE SECOND-LINE TREATMENT Docetaxel given every 3 weeks compared with weekly schedule DOCETAXEL VERSUS TARGETED THERAPIES IN THE SECOND-LINE TREATMENT ONGOING STUDIES ON DOCETAXEL REFERENCES 2.8. NON-SMALL CELL LUNG CANCER WITH BRAIN METASTASES: PLATINUM-BASED CHEMOTHERAPY Fabrizio Nelli and Luca Moscetti EPIDEMIOLOGY PROGNOSIS AND TREATMENT OPTIONS SHIFTING THE PARADIGM OF THE BLOOD-BRAIN BARRIER PLATINUM-BASED CHEMOTHERAPY: PHASE II TRIALS PLATINUM-BASED CHEMOTHERAPY: PHASE III TRIALS REFERENCES 2.9. NON-SMALL CELL LUNG CARCINOMA: EGFR GENE MUTATIONS AND RESPONSE TO GEFITINIB Armando Bartolazzi INTRODUCTION EPIDERMAL GROWTH FACTOR RECEPTOR AND DOWNSTREAM SIGNALING EPIDERMAL GROWTH FACTOR RECEPTOR MOLECULAR TARGETED THERAPY FOR NON-SMALL CELL LUNG CARCINOMAS EPIDERMAL GROWTH FACTOR RECEPTOR MUTATIONS AND THEIR CLINICAL RELEVANCE ONCOGENE ADDICTION AND GEFITINIB RESPONSE NON-SMALL CELL LUNG CARCINOMA SENSITIVITY TO EPIDERMAL GROWTH FACTOR RECEPTOR TARGETED THERAPY, AND MECHANISMS OF RESISTANCE. IRREVERSIBLE EPIDERMAL GROWTH FACTOR INHIBITORS AND COMBINATORIAL APPROACHES WITH OTHER TARGETED THERAPIES FUTURE ADVANCES REFERENCES 2.10. ADVANCED NON-SMALL CELL LUNG CARCINOMA: ACQUIRED RESISTANCE TO GEFITINIB Katsuyuki Kiura, Nagio Takigawa, and Yoshihiko Segawa INTRODUCTION DISCOVERY OF SOMATIC EPIDERMAL GROWTH FACTOR RECEPTOR- TYROSINE KINASE MUTATIONS RESISTANCE TO GEFITINIB Primary Resistance Acquired Resistance OVERCOMING ACQUIRED RESISTANCE TO GEFITINIB REFERRENCES 2.11. PROGNOSTIC SIGNIFICANCE OF [18F] - FLUORODEOXYGLUCOSE UPTAKE ON POSITRON EMISSION TOMOGRAPHY IN PATIENTS WITH PATHOLOGICAL STAGE I LUNG ADENOCARCINOMA Hiroaki Nomori INTRODUCTION PATIENTS AND METHODS Positron Emission Tomography Data Analysis Follow-up and Assessment of Tumor Recurrence Statistical Analysis RESULTS Univariate Analysis Multivariate Analysis DISCUSSION REFERENCES 2.12. NON-SMALL CELL LUNG CANCER: PROGNOSIS USING THE TNM STAGING SYSTEM Joachim Pfannschmidt, Heinrich Bulzebruck, and Henndrik Dienemann INTRODUCTION HISTORY OF TNM TNM DESCRIPTORS STAGING PROCEDURES STAGE GROUPING IN NON-SMALL CELL LUNG CANCER Stage IA and IB Stage IIA and IIB Stage IIIA and IIIB Stage IV STAGE REPORTING: FUTURE PERSPECTIVE REFERENCES 2.13. DIFFERENTIATION BETWEEN MALIGNANT AND BENIGN PLEURAL EFFUSIONS: METHYLATION SPECIFIC POLYMERASE CHAIN REACTION ANALYSIS Susana Benlloch, Jose Marcelo Galbis-Caravajal, and Bartomeu Massuti SUMMARY INTRODUCTION MATERIALS AND METHODS Patients Collection and Processing of Pleural Fluid Samples and DNA Extraction Methylation-Specific Polymerase Chain Reaction Statistical Analysis RESULTS DISCUSSION REFERENCES 2.14. PATHOLOGICAL DISTINCTION OF PULMONARY LARGE CELL NEUROENDOCRINE CARCINOMA FROM SMALL- CELL LUNG CARCINOMA USING IMMUNOHISTOCHEMISTRY Kenzo Hiroshima INTRODUCTION SMALL-CELL LUNG CARCINOMA Clinical Presentation Pathologic Features LARGE CELL NEUROENDOCRINE CARCINOMA Clinical Presentation Pathologic Features MORPHOMETRY MOLECULAR BIOLOGY IMMUNOHISTOCHEMISTRY DIFFERENTIAL DIAGNOSIS REFERENCES 2.15. DIFFERENTIATING BETWEEN PLEUROPULMONARY DESMOID TUMORS AND SOLITARY FIBROUS TUMORS: ROLE OF HISTOLOGY AND IMMUNOHISTOCHEMISTRY Dani S. Zander and Loren E. Clarke INTRODUCTION GROSS AND MICROSCOPIC PATHOLOGY Gross Features Microscopic Features IMMUNOHISTOCHEMISTRY Conventional Antibodies ss-catenin and Cyclin D1 REFERENCES 2.16. NON-SMALL CELL LUNG CANCER WITH BRAIN METASTASIS: ROLE OF EPIDERMAL GROWTH FACTOR RECEPTOR GENE MUTATION Edmond S.K. Ma and Chris L.P. Wong INTRODUCTION Histopathological Correlation Epidermal Growth Factor Receptor Gene Mutation Epidermal Growth Factor Receptor Gene Amplification MATERIALS METHODS Tissue Preparation Epidermal Growth Factor Receptor Gene PCR Amplification and Sequencing Analysis Fluorescence In-Situ Hybridization Detection of EGFR Gene Amplification and Loss of Heterozygosity Multiplex Ligation-Dependent Probe Amplification Detection of EGFR Gene Copy Number Changes RESULTS AND DISCUSSION Role of EGFR Gene Mutation in Brain Metastases from NSCLC Molecular Genetic Study of NSCLC with Brain Metastasis Gefitinib Response of Brain Metastases from NSCLC REFERENCES PART III PROSTATE CANCER 3.1. PROSTATE CARCINOMA M.A. Hayat INTRODUCTION Prostate Specific Antigen REFERENCES 3.2. THE ROLE OF INTERMEDIARY METABOLISM AND MOLECULAR GENETICS IN PROSTATE CANCER Renty B. Franklin and Leslie C. Costello INTRODUCTION CITRATE PRODUCTION AND THE HUMAN PROSTATE GLAND CITRATE METABOLISM IN NORMAL PROSTATE EPITHELIAL CELLS M-ACONITASE AND ZINC IN CITRATE PRODUCTION GLUCOSE UTILIZATION FOR NET CITRATE PRODUCTION ASPARTATE AS THE SOURCE OF OXALACETATE FOR CITRATE PRODUCTION THE BIOENERGETICS OF NET CITRATE PRODUCTION THE CITRATE RELATIONSHIP IN PROSTATE CANCER THE GENETIC/METABOLIC CONCEPT OF PROSTATE CANCER ZINC: A TUMOR SUPPRESSOR IN PROSTATE CANCER? ZIP1: A TUMOR SUPPRESSOR GENE IN PROSTATE CANCER? CITRATE METABOLISM AND DE NOVO LIPOGENESIS THE CONCEPT OF "METABOLIC" GENES CLINICAL APPLICATION OF PROSTATE CANCER METABOLISM ACKNOWLEDGEMENT REFERENCES 3.3. ARRAY-BASED COMPARATIVE GENOMIC HYBRIDIZATION IN PROSTATE CANCER: RESEARCH AND CLINICAL APPLICATIONS Franclim R. Ribeiro, Rolf I. Skotheim, Rui Henrique, and Manuel R. Teixeira INTRODUCTION METHODOLOGY Platforms and Techniques Scoring Approaches and Common Pitfalls TECHNICAL LIMITATIONS OF PROSTATE CANCER SAMPLING GENOMIC DATA ON PROSTATE CANCER Genomic Hotspots in Prostate Cancer Recurrent Copy Number Gains and Candidate Oncogenes Recurrent Copy Number Losses and Putative Tumor Suppressor Genes FUSION GENES -- NEWLY DISCOVERED PARTNERS Complementary Technologies CONCLUSIONS AND FUTURE PERSPECTIVES REFERENCES 3.4. PROSTATE CANCER: ROLE OF Vav3 OVEREXPRESSION IN DEVELOPMENT AND PROGRESSION Shan Lu INTRODUCTION MULTIPLE FUNCTIONS OF VAV FAMILY PROTEINS Vav3 is overexpressed in human prostate cancer and stimulates growth of prostate cancer cells Vav3 overexpression enhances androgen receptor transactivation activity potential impact of Vav3 on nongenomic androgen receptor activity Vav3 signaling in prostate cancer role of Vav3 in prostate cancer biology REFERENCES 3.5. PROSTATE CANCER: DETECTION AND MONITORING USING MITOCHONDRIAL MUTATIONS AS A BIOMARKER Gabriel.D. Dakubo, Ryan L. Parr, and John P. Jakupciak INTRODUCTION MITOCHONDRIAL GENETICS MITOCHONDRIAL BIOENERGETICS MITOCHONDRIAL ONCOLOGY UNIQUE PROSTATE EPITHELIAL CELL METABOLISM MITOCHONDRIAL DNA MUTATIONS IN PROSTATE CANCER SAMPLE PREPARATION FOR MITOCHONDRIAL DNA MUTATION ANALYSIS IN PROSTATE CANCER ANALYSIS OF MITOCHONDRIAL DNA POINT MUTATIONS IN PROSTATE CANCER Microarray Resequencing of Mitochondrial DNA Denaturing High-Performance Liquid Chromatography Pyrosequencing Other Emerging Sequencing Technologies REAL TIME POLYMERASE CHAIN REACTION ANALYSIS OF MITOCHONDRIAL DNA IN PROSTATE CANCER QUALITY ASSURANCE ISSUES TO BE CONSIDERED IN MITOCHONDRIAL DNA ANALYSIS REFRENCES 3.6. PROGNOSTIC MARKERS IN PROSTATE CARCINOMA Sonia L. El-Sharkawy, Naglaa F. Abbas, and Nadia G. EL-Hefnawy INTRODUCTION MATERIAL AND METHODS Routine Histopathological Evaluation Immunohistochemistry DNA Content Analysis (Feulgen Staining) AgNORs Scoring of Silver Staining RESULTS AND DISCUSSION REFERENCES 3.7. PROSTATE CANCER: DETECTION OF FREE TUMOR-SPECIFIC DNA IN BLOOD AND BONE MARROW Heidi Schwarzenbach and Klaus Pantel INTRODUCTION Genetics and Epigenetics of prostate tumors Limitations of using tumor tissues for genetic and Epigenetic analyses History of the detectiNG circulating DNA in blood Elevated levels of cell-free nucleic acids in prostate cancer patients Plasma-based Microsatellite analysIs Plasma-based single nucleotide polymorphism analysIs PCR-based fluorescence microsatellite And SNP technique using Blood and Bone marrow DNA Limitations of the blood-based LOH analysis Technical Considerations of the plasma-based analyses Plasma-based Epigenetic analysIs DNA Methylation Analysis by the Sodium Bisulfite technique REFERENCES 3.8. PROSTATE CARCINOMA: EVALUATION USING TRANSRECTAL SONOGRAPHY Ahmet T. Turgut and Vikram S. Dogra INTRODUCTION PROSTATE CANCER DIAGNOSIS ASSESSMENT OF PROSTATE CANCER USING TRANSRECTAL ULTRASONOGRAPHY Ultrasonography Anatomy Sonographic Anatomy Techniques GRAY SCALE ULTRASOUND COLOR DOPPLER ULTRASOUND POWER DOPPLER ULTRASOUND CONTRAST-ENHANCED ULTRASOUND IMAGING ELASTOGRAPHY TRANSRECTAL ULTRASOUND-GUIDED PROSTATE BIOPSY REPEAT BIOPSIES COMPLICATIONS PAIN OR DISCOMFORT ANESTHESIA THERAPEUTIC APPLICATIONS OF TRANSRECTAL ULTRASOUND FOR PROSTATE CANCER TRANSRECTAL ULTRASOUND TO EVALUATE LOCAL RECURRENCE AFTER REDICAL PROSTATECTOMY REFERENCES 3.9. PROSTATE CANCER: 16ss-(18F) FLUORO-5a-DIHYDROTESTERONE WHOLE-BODY POSITRON EMISSION TOMOGRAPHY Pat Zanzonico INTRODUCTION POTENTIAL ROLE OF ANDROGEN-RECEPTOR IMAGING IN PROSTATE CANCER POSITRON EMISSION TOMOGRAPHY PRECLINICAL STUDIES OF ANDROGEN RECEPTOR RADIOGRAPHS CLINICAL STUDIES OF 16ss -- [18F] FLUORO-5a-DIHYDROTESTERONE RADIATION DOSIMETRY OF 16ss -- [18F] FLUORO-5a- DIHYDROTESTERONE REFERENCES 3.10. EFFECTS OF STANDARD TREATMENTS ON THE IMMUNE RESPONSE TO PROSTATE CANCER Nancy J. Nesslinger, Howard H. Pai, Charles M. Ludgate, and Brad H. Nelson INTRODUCTION METHODOLOGY Western Blotting Assay Materials for Cell Culture Materials for Protein Lysate Preparation and Quantification Materials for Western Blotting Assay Protocol for Cell Culture, Protein Lysate Preparation and Quantification Protocol for Western Blotting SEREX Screening Materials for cDNA Library Construction Materials for SEREX Screening Protocol for cDNA Library Construction Protocol for Pre-clearing Serum Samples Protocol for SEREX Screening Protocol for Analyzing SEREX Antigen Arrays Protocol for Purifying Phage Clones RESULTS AND DISCUSSION REFERENCES 3.11. VINORELBINE, DOXORUBICIN, AND PREDNISONE IN HORMONE REFRACTORY PROSTATE CANCER Samer Kalakish and Frank M. Torti INTRODUCTION ELIGIBILITY TREATMENT PLAN EVALUATION STATISTICAL ANALYSIS RESULTS DISCUSSION REFERENCES 3.12. LOCALLY ADVANCED PROSTATE CANCER- BIOCHEMICAL RECURRENCE AFTER RADIOTHERAPY: USE OF CYCLIC ANDROGEN WITHDRAWAL THERAPY Juanita Crook INTRODUCTION LABORATORY BASIS FOR HUMAN STUDIES MECHANISMS OF PROGRESSION TO ANDROGEN INDENDENCE RATIONALE FOR INTERMITTENT ADMINISTRATION OF ANDROGEN SUPPRESSION IN CLINICAL PRACTICE PHASE II CLINICAL STUDIES PHASE III CLINCAL STUDIES IS THERE AN ACCEPTED STANDARD REGIMEN OF INTERMITTENT ANDROGEN SUPPRESSION SUMMARY AND CONCLUSIONS REFERENCES