Cecconi / D'Amelio Apoptosome

An up-and-coming therapeutical tool
1. Auflage 2009
ISBN: 978-90-481-3415-1
Verlag: Springer Netherlands
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 322 Seiten

"Apoptosome" is the first book that presents a concise synthesis of recent developments in the understanding of how the activation of the cell death cascade is handled by a cytosolic signalling platform known as the apoptosome.

The book also discusses how insights into the regulation of apoptosome may be exploited for designing new drugs aimed at interfere with a plethora of pathogenetic processes involved in human diseases.

The authors emphasize novel translational approaches that are rapidly moving from the laboratory bench top to the patient's bedside for the future treatment of diseases associated with apoptosis.

This book will be a valuable resource for researchers investigating the role of apoptosome-dependent cell death in cancer and other diseases, for researchers investigating the molecular mechanism of chemotherapeutic agents and drug-resistance and for physicians using chemotherapeutic agents. Additionally, this book will be an important educational source for PhD students and MD students specializing in molecular and cell biology, and to anybody interested in science, medicine, as well as in recent developments of the ideas and concepts of the molecular biology of programmed cell death.

Autoren/Hrsg.

Cecconi, Francesco

D'Amelio, Marcello

Inhaltsverzeichnis

1;Cecconi_Frontmatter.pdf;1
1.1;Anchor 1;4
1.2;Anchor 2;6
2;Cecconi_Ch01.pdf;9
2.1;Chapter 1;9
2.1.1;Physiological and Pathological Role of Apoptosis;9
2.1.1.1;1.1 Introduction;9
2.1.1.2;1.2 The Apoptotic Pathways;10
2.1.1.2.1;1.2.1 The Extrinsic Pathway;11
2.1.1.2.2;1.2.2 The Intrinsic Pathway;11
2.1.1.3;1.3 Apoptosis in Development;13
2.1.1.3.1;1.3.1 Apaf1 Knockout;14
2.1.1.3.2;1.3.2 Caspase-9 Knockout;14
2.1.1.3.3;1.3.3 Caspase-3 Knockout;15
2.1.1.3.4;1.3.4 Cytochrome c Knockout and Knockin;15
2.1.1.3.5;1.3.5 Bax Knockout;16
2.1.1.3.6;1.3.6 Bcl-2 Knockout;17
2.1.1.3.7;1.3.7 Bcl-X Knockout;17
2.1.1.4;1.4 Apoptosis in Disease: A Life or Death Decision;18
2.1.1.4.1;1.4.1 Too Little Apoptosis;19
2.1.1.4.1.1;1.4.1.1 Neoplastic Diseases;19
2.1.1.4.1.2;1.4.1.2 Autoimmune Diseases;20
2.1.1.4.1.3;1.4.1.3 Virus Infections;21
2.1.1.4.2;1.4.2 Too Much Apoptosis;22
2.1.1.4.2.1;1.4.2.1 Neurodegenerative Diseases;22
2.1.1.4.2.2;1.4.2.2 Tissue Damage;24
2.1.1.4.2.3;1.4.2.3 HIV-1 Infection;25
2.1.2;References;26
3;Cecconi_Ch02.pdf;35
3.1;Chapter 2;35
3.1.1;Apoptosome Structure and Regulation;35
3.1.1.1;2.1 Introduction;35
3.1.1.2;2.2 The Apoptosome;36
3.1.1.2.1;2.2.1 Apaf 1;36
3.1.1.2.2;2.2.2 Apoptosome Assembly;38
3.1.1.2.3;2.2.3 Apoptosome Structure;39
3.1.1.2.4;2.2.4 Cytochrome c;40
3.1.1.2.5;2.2.5 Apoptosome Dependent Caspase-9 Activation;41
3.1.1.2.6;2.2.6 IAPs as Modulators of the Apoptosome;41
3.1.1.3;2.3 The Apoptosome in Evolution;42
3.1.1.3.1;2.3.1 Caenorhabditis elegans;43
3.1.1.3.2;2.3.2 Drosophila Melanogaster;44
3.1.2;References;45
4;Cecconi_Ch03.pdf;48
4.1;Chapter 3;48
4.1.1;Chemical Regulation of the Apoptosome: New Alternative Treatments for Cancer;48
4.1.1.1;3.1 Introduction;49
4.1.1.2;3.2 The Intrinsic Cell Death Pathway an Evolutionary Conserved Pathway?;52
4.1.1.3;3.3 Cytochrome c a Protein Signalling Molecule for Apoptosome Formation;53
4.1.1.4;3.4 Cytochrome c Unlocks Apaf-1 to Initiate Apoptosome Formation;57
4.1.1.5;3.5 Apoptosome Formation Requires Adenine Nucleotides;60
4.1.1.6;3.6 The Apoptosome Recruits Caspase-9 to Form a Caspase-Processing Complex;61
4.1.1.7;3.7 Physiological and Chemical Regulation of Apoptosome Formation;64
4.1.1.8;3.8 Physiological and Chemical Regulation of Apoptosome Dependent Caspase Activation;68
4.1.1.9;3.9 Aberrant Apaf-1 Levels and Apoptosome Formation in Cancer;70
4.1.1.10;3.10 The Apoptosome a Good Target for New Alternative Treatments for Cancer Therapy?;73
4.1.2;References;74
5;Cecconi_Ch04.pdf;82
5.1;Chapter 4;82
5.1.1;Molecules That Bind a Central Protein Component of the Apoptosome, Apaf-1, and Modulate Its Activity;82
5.1.1.1;4.1 Introduction;82
5.1.1.2;4.2 Protein-Dependent Regulation of Apaf-1;83
5.1.1.2.1;4.2.1 Apo-cytochrome c;84
5.1.1.2.2;4.2.2 Interactions with Bcl-2 Family Members;84
5.1.1.2.3;4.2.3 Apaf-1 and Heat Shock Proteins Interactions;84
5.1.1.2.4;4.2.4 Apaf-1 Interactions with Proteins Implicated in Cell Cycle;85
5.1.1.2.5;4.2.5 Proteins Implicated in Ischemic Processes Able to Interact with Apaf-1;86
5.1.1.2.6;4.2.6 Apaf-1 Interactions with Phosphatases and Kinases;86
5.1.1.2.7;4.2.7 HCA66 – Apaf-1 Interaction;87
5.1.1.3;4.3 Transcriptional Regulation of Apaf-1;87
5.1.1.4;4.4 Chemical Regulation of Apaf-1;89
5.1.1.4.1;4.4.1 Apaf-1 Inhibitors;89
5.1.1.4.1.1;4.4.1.1 Diarylurea Compounds;89
5.1.1.4.1.2;4.4.1.2 Peptoid Inhibitors;91
5.1.1.4.1.3;4.4.1.3 Taurine;94
5.1.1.4.1.4;4.4.1.4 Intracellular Concentration of Potassium and Calcium;94
5.1.1.4.1.5;4.4.1.5 Nitric Oxide Donors;95
5.1.1.4.1.6;4.4.1.6 dATP/ATP;95
5.1.1.4.2;4.4.2 Apaf-1 Activators;95
5.1.1.4.2.1;4.4.2.1 Wells’ Activator;96
5.1.1.4.2.2;4.4.2.2 Deoxyadenosine Analogs;97
5.1.1.4.2.3;4.4.2.3 PETCM;97
5.1.1.5;4.5 Conclusion;97
5.1.2;References;98
6;Cecconi_Ch05.pdf;102
6.1;Chapter 5;102
6.1.1;Regulation of Cell Death and Survival by RNA Interference – The Roles of miRNA and siRNA;102
6.1.1.1;5.1 Introduction;102
6.1.1.2;5.2 Regulation of Gene Expression by RNAi;103
6.1.1.2.1;5.2.1 Mechanism: from miRNA to siRNA;103
6.1.1.2.2;5.2.2 siRNA Design;105
6.1.1.2.3;5.2.3 Delivery of siRNA or shRNA;106
6.1.1.2.4;5.2.4 Off-Target Effects;108
6.1.1.3;5.3 RNAi As a Tool in Apoptosis Research and Its Therapeutic Implications;108
6.1.1.3.1;5.3.1 Developmental Apoptotic Cell Death: Lessons from Worms and Flies;109
6.1.1.3.2;5.3.2 Cancer;110
6.1.1.3.3;5.3.3 Neurodegenerative Diseases;112
6.1.1.3.4;5.3.4 Viral Infections;115
6.1.1.3.5;5.3.5 Ischemic Cell Death;117
6.1.1.4;5.4 Outlook;118
6.1.2;References;119
7;Cecconi_Ch06.pdf;125
7.1;Chapter 6;125
7.1.1;Beneficial Role of Taurine Against Myocardial Apoptosis During Ischemic Injury;125
7.1.1.1;6.1 Introduction;125
7.1.1.2;6.2 Role of Anti-apoptotic Effect of Taurine Against Myocardial Ischemia;127
7.1.1.2.1;6.2.1 Effect of Taurine on Myocardial Ischemic Injury;127
7.1.1.2.2;6.2.2 Effect of Taurine on Myocardial Ischemia/Reperfusion Injury;127
7.1.1.2.3;6.2.3 Taurine and Calcium Paradox;129
7.1.1.3;6.3 Signaling Pathway Involved in the Anti-apoptotic Effect of Taurine in the Ischemic Myocardium;129
7.1.1.3.1;6.3.1 Mitochondria-Mediated Signaling Pathway;129
7.1.1.3.2;6.3.2 caspase-8-Mediated Apoptotic Pathway;130
7.1.1.3.3;6.3.3 Akt/Protein Kinase B;131
7.1.1.3.4;6.3.4 Protein kinase C isoforms;131
7.1.1.4;6.4 Potential Actions Related to Anti-apoptotic Effect of Taurine;132
7.1.1.4.1;6.4.1 Oxidative Stress and Calcium Overload;132
7.1.1.4.2;6.4.2 Osmotic Stress;133
7.1.1.5;6.5 Conclusion;134
7.1.2;Cited articles;136
8;Cecconi_Ch07.pdf;142
8.1;Chapter 7;142
8.1.1;BAG3 Protein: Role in Some Neoplastic Cell Types and Identification as a Candidate Target for Therapy;142
8.1.1.1;7.1 Introduction;142
8.1.1.2;7.2 BAG3 Protein and bag3 Gene;143
8.1.1.3;7.3 Functional Activity of BAG3;144
8.1.1.4;7.4 Conclusions;147
8.1.2;References;148
9;Cecconi_Ch08.pdf;152
9.1;Chapter 8;152
9.1.1;Targeting Survivin in Cancer Therapy: Pre-clinical Studies;152
9.1.1.1;8.1 Introduction;153
9.1.1.2;8.2 Survivin Structure and Function;154
9.1.1.2.1;8.2.1 The Structure of Survivin;154
9.1.1.2.2;8.2.2 Functional Roles of Survivin;154
9.1.1.2.3;8.2.3 Survivin Splice Variants;156
9.1.1.3;8.3 Survivin Expression in Normal and Tumor Tissues;156
9.1.1.4;8.4 Current Understanding of the Role of Survivin in Treatment Resistance;157
9.1.1.4.1;8.4.1 Survivin as a Chemoresistance Factor;157
9.1.1.4.2;8.4.2 Survivin as a Radioresistance Factor;158
9.1.1.5;8.5 Therapeutic Targeting of Survivin;158
9.1.1.5.1;8.5.1 Molecular Antagonists;159
9.1.1.5.1.1;8.5.1.1 Antisense Oligonucleotides;159
9.1.1.5.1.2;8.5.1.2 Ribozymes;160
9.1.1.5.1.3;8.5.1.3 Small Interfering RNAs;161
9.1.1.5.2;8.5.2 Small Molecules;162
9.1.1.5.2.1;8.5.2.1 Cyclin-Dependent Kinase (CDK) Inhibitors;162
9.1.1.5.2.2;8.5.2.2 Hsp90 Inhibitors;162
9.1.1.5.2.3;8.5.2.3 YM155;163
9.1.1.5.2.4;8.5.2.4 Terameprocol;163
9.1.1.5.3;8.5.3 Adenoviral Expression of Dominant-Negative Mutants of Survivin;164
9.1.1.5.4;8.5.4 Survivin-Based Immunotherapy;164
9.1.1.6;8.6 Conclusions and Future Directions;165
9.1.2;References;166
10;Cecconi_Ch09.pdf;174
10.1;Chapter 9;174
10.1.1;Hsp70 and Hsp27: Emerging Targets in Cancer Therapy;174
10.1.1.1;9.1 Introduction;175
10.1.1.2;9.2 Cytoprotective Functions of Hsp70 and Hsp27;176
10.1.1.2.1;9.2.1 Hsp70 and Hsp27 Are Molecular Chaperones;176
10.1.1.2.2;9.2.2 Hsp27 and Hsp70 Interfere with the Action of Key Apoptotic Proteins;178
10.1.1.2.2.1;9.2.2.1 Hsps, Cell Signalling and Apoptosis;178
10.1.1.2.2.2;9.2.2.2 Hsp70;180
10.1.1.2.2.2.1;Hsp70 and Mitochondrial Dependent Apoptosis;180
10.1.1.2.2.2.2;Hsp70 and the Extrinsic Death Receptor Pathway;181
10.1.1.2.2.2.3;Hsp70 and Alternatives, Caspase-Independent, Apoptosis-Like pathways;182
10.1.1.2.2.2.4;In Conclusion, Hsp70 Can Be Considered as the Quintessential Inhibitor of Apoptosis;183
10.1.1.2.2.3;9.2.2.3 Hsp27;184
10.1.1.3;9.3 Hsps and Cancer;186
10.1.1.3.1;9.3.1 Hsp70: Tumorigenicity and Cancer Cell Resistance;186
10.1.1.3.2;9.3.2 The Inhibition of Hsp70 in Cancer Therapy;187
10.1.1.3.3;9.3.3 Hsp27, Tumorigenicity and Cancer Cell Resistance;188
10.1.1.3.4;9.3.4 The Inhibition of Hsp27 in Cancer Therapy;189
10.1.1.4;9.4 Anti-Cancer Therapeutical Approaches Based on Extracellular Hsps;190
10.1.1.4.1;9.4.1 Extracellular Hsps Have an Immunological Function;190
10.1.1.4.2;9.4.2 Immuno-therapeutical Approaches Based on Hsps;193
10.1.1.5;9.5 Concluding Remarks;194
10.1.2;References;195
11;Cecconi_Ch10.pdf;208
11.1;Chapter 10;208
11.1.1;Role of the RNA-Binding Protein HuR in Apoptosis and Apoptosome Function;208
11.1.1.1;10.1 Introduction;209
11.1.1.2;10.2 Post-transcriptional Regulation of Gene Expression;210
11.1.1.3;10.3 HuR;210
11.1.1.3.1;10.3.1 HuR and the Stress Response;211
11.1.1.3.2;10.3.2 HuR and Apoptosis;211
11.1.1.4;10.4 Anti-apoptotic HuR Target mRNAs;213
11.1.1.4.1;10.4.1 Prothymosin a;213
11.1.1.4.2;10.4.2 SIRT1;213
11.1.1.4.3;10.4.3 Bcl-2, Mcl-1;214
11.1.1.4.4;10.4.4 p21;214
11.1.1.4.5;10.4.5 COX-2;215
11.1.1.4.6;10.4.6 HIF-1a;215
11.1.1.4.7;10.4.7 Cyclins;215
11.1.1.4.8;10.4.8 MKP-1;216
11.1.1.5;10.5 Pro-Apoptotic HuR Target mRNAs;216
11.1.1.5.1;10.5.1 p53;216
11.1.1.5.2;10.5.2 c-myc;217
11.1.1.5.3;10.5.3 p27;217
11.1.1.5.4;10.5.4 Cytochrome c;218
11.1.1.6;10.6 Anti-Apoptotic HuR Protein Partners;218
11.1.1.6.1;10.6.1 SETa;218
11.1.1.7;10.7 Pro-apoptotic HuR Protein Partners;219
11.1.1.7.1;10.7.1 PP32/PHAPI;219
11.1.1.8;10.8 Perspective: HuR as a Master Modulator of Apoptosome Function;220
11.1.2;References;221
12;Cecconi_Ch11.pdf;226
12.1;Chapter 11;226
12.1.1;Acetylcholinesterase as a Pharmacological Target in Cancer Research;226
12.1.1.1;11.1 Introduction;226
12.1.1.2;11.2 Regulation of Acetylcholinesterase Gene Expression;227
12.1.1.3;11.3 Alternative Splicing Variants of Acetylcholinesterase Distribution;227
12.1.1.4;11.4 Cholinergic Function of Acertylcholinesterase;228
12.1.1.5;11.5 Non-cholinergic Function of Acertylcholinesterase;228
12.1.1.6;11.6 Targeting Acertylcholinesterase to Treat Neurodegeneration;229
12.1.1.7;11.7 Role of Acertylcholinesterase in Apoptosis;230
12.1.1.7.1;11.7.1 Involvement of Acetylcholinesterase in Differentiation and Proliferation;230
12.1.1.7.2;11.7.2 Involvement of Acetylcholinesterase in Apoptosis;230
12.1.1.7.3;11.7.3 Alternative Splicing Variants of Acetylcholinesterase Distribution in Cells Undergoing Apoptosis;231
12.1.1.8;11.8 Non-hydrolytic Activity of Acertylcholinesterase in Apoptosis;232
12.1.1.9;11.9 Apoptosome;232
12.1.1.10;11.10 How Dose Acetylcholinesterase Participate in Apoptosome?;233
12.1.1.11;11.11 Modulation of Acetylcholinesterase Activity;234
12.1.1.12;11.12 Conclusion and Future Direction;235
12.1.2;References;236
13;Cecconi_Ch12.pdf;242
13.1;Chapter 12;242
13.1.1;Putative Role of HCA66, A New Apaf-1 Interacting Protein, in the Physiopathology of NF1 Microdeletion Syndrome Patients;242
13.1.1.1;12.1 Introduction;243
13.1.1.2;12.2 HCA66, a Novel Regulator of the Apoptosome;244
13.1.1.2.1;12.2.1 HCA66 Interacts with Apaf-1;244
13.1.1.2.2;12.2.2 A Role for HCA66 in Apoptosis;245
13.1.1.2.3;12.2.3 Haploinsufficiency of HCA66 May Causes Apoptosis Defects in Cell Lines Derived from Patients with NF1 Gene Microdeleti;246
13.1.1.2.3.1;12.2.3.1 General Clinical Features of Neurofibromatosis Type 1;248
13.1.1.2.3.2;12.2.3.2 Genetics and Molecular Mechanisms of Neurofibromatosis Type 1;249
13.1.1.2.3.3;12.2.3.3 Other Modifying Genes Involved in Classical Neurofibromatosis Type I and NF1 Microdeletion Syndrome;250
13.1.1.2.3.4;12.2.3.4 HCA66 and NF1: a Possible Connection;251
13.1.1.2.3.5;12.2.3.5 Conclusion and Future Directions;252
13.1.2;References;252
14;Cecconi_Ch13.pdf;257
14.1;Chapter 13;257
14.1.1;Cristae Remodeling and Mitochondrial Fragmentation: A Checkpoint for Cytochrome c Release and Apoptosis?;257
14.1.1.1;13.1 Introduction;257
14.1.1.2;13.2 Regulation of Mitochondrial Morphology;259
14.1.1.3;13.3 Mitochondrial Fragmentation During Apoptosis;262
14.1.1.4;13.4 The Cristae Remodelling Pathway;263
14.1.1.5;13.5 The Molecular Mechanisms and Consequences of Mitochondrial Fission During Cell Death;264
14.1.1.6;13.6 The Molecular Mechanisms of Cristae Remodeling;266
14.1.1.7;13.7 Can be Cristae Remodeling Targeted in a Proapoptotic Therapy?;268
14.1.1.8;13.8 Conclusions;268
14.1.2;References;269
15;Cecconi_Ch14.pdf;275
15.1;Chapter 14;275
15.1.1;Apoptosome Pharmacological Manipulation: From Current Developments in the Laboratory to Clinical Implications;275
15.1.1.1;14.1 Translational Research: Finding a ‘Common Language’ for Clinicians and Scientists;275
15.1.1.2;14.2 Drug Discovery Process: From Laboratory to Patient;277
15.1.1.2.1;14.2.1 Drug Discovery;278
15.1.1.2.2;14.2.2 Pre-clinical Testing;278
15.1.1.2.3;14.2.3 Clinical Trials;278
15.1.1.2.3.1;14.2.3.1 New Drug Application (NDA);279
15.1.1.3;14.3 Antiapoptotic Drug: The Therapeutic Challenge for Neurodegenerative Diseases;279
15.1.1.3.1;14.3.1 The Role of Mitochondria in Neurodegeneration;280
15.1.2;References;284
16;Cecconi_Ch15.pdf;286
16.1;Chapter 15;286
16.1.1;The Therapeutic Role of Taurine in Ischaemia-Reperfusion Injury;286
16.1.1.1;15.1 Taurine and Ischaemia-Reperfusion Injury;286
16.1.1.2;15.2 Ischaemia-Reperfusion Injury;287
16.1.1.3;15.3 Biochemistry of Ischaemia-Reperfusion Injury;287
16.1.1.3.1;15.3.1 Free Radicals;287
16.1.1.3.2;15.3.2 Lipid Peroxidation;289
16.1.1.3.3;15.3.3 Therapeutic Implications;289
16.1.1.4;15.4 Non-Pharmacological Interventions to Attenuate Ischaemia-Reperfusion Injury;290
16.1.1.4.1;15.4.1 Cold;290
16.1.1.4.2;15.4.2 Preservative Solutions;290
16.1.1.4.3;15.4.3 Ischaemic Preconditioning;291
16.1.1.5;15.5 Pharmacological Approaches to Attenuating Ischaemia-Reperfusion Injury;292
16.1.1.5.1;15.5.1 Iron Chelation;292
16.1.1.6;15.6 Superoxide Dismutase and Catalase;292
16.1.1.6.1;15.6.1 Antioxidants Other Than Taurine;294
16.1.1.6.2;15.6.2 Vitamin C (Ascorbic Acid);294
16.1.1.6.3;15.6.3 Vitamin E (Alpha-Tocopherol);295
16.1.1.6.4;15.6.4 Lazaroids;295
16.1.1.6.5;15.6.5 EPC-K1;296
16.1.1.6.6;15.6.6 Transresveratrol;296
16.1.1.7;15.7 Experimental Evidence for a Role for Taurine in Ischaemia-Reperfusion Injury;296
16.1.1.7.1;15.7.1 Cellular Experiments;296
16.1.1.7.2;15.7.2 Taurine and Myocardial Ischaemia-Reperfusion Injury;297
16.1.1.7.3;15.7.3 Isolated Perfused Heart Models;297
16.1.1.7.4;15.7.4 Intact Animals;298
16.1.1.7.5;15.7.5 Taurine and Pulmonary Ischaemia-Reperfusion Injury;298
16.1.1.7.6;15.7.6 Taurine and Hepatic Ischaemia-Reperfusion Injury;298
16.1.1.7.7;15.7.7 Taurine and Renal Ischaemia-Reperfusion Injury;299
16.1.1.7.8;15.7.8 Taurine and Retinal Ischaemia-Reperfusion Injury;299
16.1.1.7.9;15.7.9 Taurine and Cerebral Ischaemia-Reperfusion Injury;299
16.1.1.7.10;15.7.10 Taurine and Gastrointestinal Ischaemia-Reperfusion Injury;300
16.1.1.7.11;15.7.11 Taurine and Testicular Ischaemia-Reperfusion Injury;300
16.1.1.7.12;15.7.12 Taurine and the Distant Consequences of Ischaemia-Reperfusion Injury;300
16.1.1.7.13;15.7.13 Taurine and Skeletal Muscle Ischaemia-Reperfusion Injury;300
16.1.1.8;15.8 Human Studies;301
16.1.1.9;15.9 Future Developments;302
16.1.2;References;302
17;Cecconi_Ch16.pdf;308
17.1;Chapter 16;308
17.1.1;Targeting Survivin in Cancer Therapy: Clinical Considerations;308
17.1.1.1;16.1 Introduction;309
17.1.1.2;16.2 Cancer Biomarker Targeting Survivin;310
17.1.1.2.1;16.2.1 Cancer Diagnostic Marker;310
17.1.1.2.2;16.2.2 Prognostic Marker;310
17.1.1.2.3;16.2.3 Predictor of the Response to Cancer Treatment;311
17.1.1.3;16.3 Cancer Therapeutic Strategies Targeting Survivin;312
17.1.1.3.1;16.3.1 Inhibition of Survivin mRNA and Protein Expression: YM155;313
17.1.1.3.2;16.3.2 Survivin Antisense Oligonucleotides: LY2181308;313
17.1.1.3.3;16.3.3 Destabilizing Survivin Protein;314
17.1.1.3.3.1;16.3.3.1 Terameprocol (EM-1421);314
17.1.1.3.3.2;16.3.3.2 Flavopiridol;315
17.1.1.3.4;16.3.4 Immunotherapy;315
17.1.1.3.4.1;16.3.4.1 Peptide Vaccine;315
17.1.1.3.4.1.1;Survivin Peptide Vaccine;315
17.1.1.3.4.1.2;Survivin-2B, a Splicing Variant of Survivin, Peptide Vaccine;316
17.1.1.3.4.2;16.3.4.2 Dendritic Cell (DC) Vaccine;319
17.1.1.4;16.4 Conclusions;320
17.1.2;References;320
18;Cecconi_Backmatter.pdf;324