Telomerases, telomeres, and cancer /
[edited by] Guido Krupp, Reza Parwaresch.
Georgetown, TX : Landes Bioscience/ ; New York : Kluwer Academic/Plenum, c2002.
421 p. : ill. ; 24 cm.
More Details
Georgetown, TX : Landes Bioscience/ ; New York : Kluwer Academic/Plenum, c2002.
catalogue key
Includes bibliographical references and index.
A Look Inside
About the Author
Author Affiliation
Guido Krupp: artus GmbH Nobistor Hamburg, Germany Reza Parwaresch: Christian-Albrechts-University Kiel, Germany
This item was reviewed in:
SciTech Book News, September 2003
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Main Description
This volume provides broad insights to the most recent discoveries in telomere biology, with current applications in tumor diagnostics and future potentials in therapy. Special features of diverse organisms are presented, with ciliates, the "telomerase discoverer organisms"; yeasts, the "molecular genetisists' toy for eukaryotes"; including plants and insects as well. 28 chapters were written by a group of leading research scientists, working in the telomere/telomerase fields today. This book will be a core reference for any physician, scientist or "educated reader" with an interest in the exciting developments in this research field.
Table of Contents
Telomerases, Telomeres and Cancerp. 1
Telomerase Activity and Cancerp. 2
The Significance of Quantitative Evaluation of Telomerase Activity and hTERT mRNA Expression in Colorectal Cancersp. 3
Introductionp. 3
Telomerase and Colorectal Cancerp. 3
Quantification of Telomerase Activity in Cancerp. 4
Telomerase Activity and hTERT Expression in Colon Cancerp. 4
Conclusionsp. 5
Experimental Proceduresp. 9
The Role of Telomerase De-Regulation in Keratinocyte Immortality and the Progression of Human Head and Neck Cancerp. 13
Introductionp. 13
The Immortalisation of Neoplastic Human Keratinocytesp. 15
Genetic Evidence for the Inactivation of M1 Senescence in OPLs and SCC-HN: the Role of p16[superscript INK4A] and p53p. 17
The Role of M2 Crisis in the Suppression of Human Squamous Neoplasiap. 17
The Genetics of SCC-HN Progression In Vivo: Do They Reflect the Acquisition of Immortality In Vitro?p. 19
Conclusions and Further Questionsp. 20
Telomerase in Mesothelioma: Diagnostic and Therapeutic Applicationsp. 24
Introductionp. 24
Telomerase Activity in Malignant Mesotheliomap. 25
Gene Expression Profile of Components of Telomerase in Mesotheliomap. 30
Detection of Telomerase at the Cellular Levelp. 31
hTERC Anti-Sense Inhibition of Telomerase-Function in Mesothelioma Cell Linesp. 34
Conclusionsp. 35
Future Perspectivesp. 37
Telomerase Activity in Mesenchymal Tumorsp. 41
Introductionp. 41
Results of Telomerase Activity Analyses in Selected Tumor Entitiesp. 41
Telomerase Activity and the Phenomenon of Telomeric Associationp. 44
Summaryp. 45
Telomerase Activity in Neuroblastomas: A New Molecular Marker for Treatment Stratification and Prognostic Groupingp. 47
Introduction: Clinical Aspects and Molecular Biology of Neuroblastomap. 47
Telomerase and Telomeresp. 47
What is the Role of Telomerase in Neuroblastomas?p. 48
Conclusions: Telomerase Activity as New Molecular Marker for Treatment Stratification and Prognostic Groupingp. 53
Telomerase and Radiosensitivity of Human Tumorsp. 60
Introductionp. 60
Telomerase in Cell Proliferation and Developmentp. 61
Telomerase Activity and Ionizing Radiosensitivityp. 70
Telomere Dysfunction and Ionizing Radiation Sensitivityp. 73
Amplification of hTERT, the Telomerase Reverse Transcriptase Gene in Human Cancersp. 79
Introductionp. 79
FISH Analysis Reveals hTERT Gene Amplification in Cell Lines and Tumorsp. 80
Conclusionsp. 81
Telomerase Activity as a Marker of Tumor Cell Survival to Evaluate Sensitivity of Neoplastic Cells to Cancer Treatmentp. 84
Introductionp. 84
The In Vitro Chemosensitivity Assays and the Possible Role of R-TRAPp. 85
Experimental Approachesp. 87
The In Vitro R-TRAP Assay for Antitumor Cell-Mediated or Antibody-Mediated Cytotoxicityp. 95
Acknowledgmentsp. 96
Telomerase-based Approaches for Cancer Therapiesp. 99
PNA and Oligonucleotide Inhibitors of Human Telomerasep. 100
Abbreviationsp. 100
Introductionp. 100
The "Antisense" Approach to Telomerase Inhibitionp. 101
Oligonucleotide Analogues as Human Telomerase Inhibitorsp. 103
Cell Based Studies and In Vivo Therapyp. 107
Conclusion and Future Perspectivesp. 110
Potential of the Telomerase Catalytic Subunit as a Universal Tumor-Associated Antigen for Cancer Immunotherapyp. 114
Introductionp. 114
Clinical Progress in Tumor Immunityp. 114
Search for Universal Tumor Antigensp. 116
Identification of hTERT as a Widely Expressed Tumor-Associated Antigenp. 116
Prospect of hTERT as a Clinical Target for Immunotherapyp. 118
Conclusionsp. 119
Structure and Function of Telomerases and Telomeresp. 121
Humansp. 122
The Makings of Telomerasesp. 123
Introductionp. 123
The End Replication Problemp. 123
Telomerase RNAp. 125
Telomerase Reverse Transcriptasep. 127
Telomerase-RNA Associated Proteins Involved in Maturation and Stability: La, Sm, Dyskerinp. 128
Chaperone Proteins Promote Telomerase Assemblyp. 129
The Telomerase-Telomere Interaction is Mediated by Est1pp. 129
Multimerization of Telomerasep. 129
Conclusionp. 130
Regulation of Telomerase Activityp. 134
Introductionp. 134
Telomerase Catalytic Subunit (TERT) Gene Expressionp. 135
Alternative Splicing of hTERT RNA Transcriptp. 143
Post Translational Modification: Protein Phosphorylation and Dephosphorylationp. 144
Intra- and Inter-Molecular Interactionsp. 147
Concluding Remarksp. 152
Telomeres and Mechanisms of DNA Double Strand Break Repairp. 160
Introductionp. 160
Mechanisms of DSB Repairp. 160
Telomeres and DSB Repairp. 161
Telomere Maintenance in Mammalian Cells Deficient in NonDSB Repair Pathwaysp. 164
Interaction of Telomeric and DSB Repair Proteinsp. 164
Implicationsp. 165
Roles for hTERT and Telomerase in Cell Differentiation and Apoptosisp. 168
Introductionp. 168
Roles for Telomerase in Cell Proliferation and Differentiationp. 168
Mechanisms of Regulation of Neuronal Differentiation by Telomerasep. 170
Apoptosis in Development, Adult Plasticity and Diseasep. 171
Anti-Apoptotic Actions of Telomerase Activity and TERTp. 172
Molecular Mechanisms Underlying the Anti-Apoptotic Actions of Telomerasep. 174
Possible Clinical Applications of Telomerase Modulationp. 176
Ciliates, Yeasts and other Eukaryotesp. 181
Human, Mouse and Yeast Telomerasep. 182
Introductionp. 182
Telomerase Componentsp. 182
Telomerase Reverse Transcriptasep. 183
Telomerase RNAp. 188
Telomerase-Associated Proteinsp. 192
Mechanism of Telomere Synthesis by Telomerasep. 194
Conclusionsp. 198
The Biology of Telomeres in Hypotrichous Ciliatesp. 205
Introductionp. 205
The Genome of Hypotrichous Ciliatesp. 207
Macronuclear Differentiation in Hypotrichsp. 209
The Telomeres of Hypotrichous Ciliatesp. 212
The Telomerase of Hypotrichsp. 217
In vivo Telomere Interactions and Contribution to Macronuclear Structurep. 217
DNA Primer Extension by Telomerasep. 223
Introductionp. 223
Structure and Assembly of the Telomerase Ribonucleoproteinp. 223
Detailed Analysis of Primer Extension by the Telomerasep. 227
Updated Model for Primer Extension by Telomerasep. 234
Yeast Telomerases: Structure, Mechanisms and Regulationp. 239
Introductionp. 239
Telomerase Componentsp. 239
Biochemistry of Yeast Telomerasep. 247
Regulation of Yeast Telomerasep. 252
Conclusionsp. 254
RAP1 Binding and Length Regulation of Yeast Telomeresp. 259
Domain Structurep. 259
DNA Bindingp. 261
RAP1 Homologuesp. 266
Abundance and Nuclear Localizationp. 268
Functionp. 271
Concluding Remarksp. 277
Linear Plasmids in Yeasts and Filamentous Fungip. 282
Introductionp. 282
Natural Linear Plasmids in Yeastsp. 283
Natural Linear Plasmids in Filamentous Fungip. 284
Artificial Linear Plasmids in Yeastp. 285
Replication Mechanismsp. 286
New Telomere Formation During the Process of Chromatin Diminution in the Parasitic Nematodes Ascaris suum and Parascaris univalensp. 291
Introductionp. 291
Chromatin Diminution Consists of Chromosomal Fragmentation and Elimination of Genetic Material from All Presomatic Cellsp. 292
Breakdown of the Chromosomes During Chromatin Diminution is Preceded by Extensive Structural Changes of the Chromatinp. 292
Chromatin Diminution Involves Chromosomal Breakage and New Telomere Formation Occurring Within Specific Chromosomal Regions (CBRs)p. 293
Somatic Telomeres May be Formed by a Specialized Telomerase Activityp. 295
The A. Suum Telomerase Activity is Developmentally Regulatedp. 296
Chromosome Breakage and New Telomere Addition May Occur During the S-phase Preceding the Diminution Mitosesp. 296
Chromatin Diminution May Act as a "Gene Throw Away" Approach to Gene Silencingp. 297
Telomerase Activity in Sponges (Porifera), the Closest Related Taxa of the Hypothetical Ancestral Animal the Urmetazoap. 300
Introduction: Urmetazoa - Hypothetical Ancestor of Metazoap. 300
Primmorphs: Model System to Study the Differentiation State of Sponge Cellsp. 302
Telomerase Activity in Tissue from S. domuncula and G. cydoniump. 302
Telomerase Activity in Dissociated Sponge Cellsp. 303
Telomerase Activity in Primmorphs of S. domunculap. 304
Control of Cell Homeostasis in Sponges: Apoptosisp. 305
Telomerase Activity in S. domuncula in Response to Apoptotic Stimulip. 308
Conclusionsp. 309
Structure and Maintenance of Chromosome Ends in Plantsp. 314
Introductionp. 314
DNA Sequences Constituting Plant Telomeresp. 315
Subdomain Structure of Chromosome Terminip. 316
Stable Telomere Maintenance in Plantsp. 319
Nuclear Localization of Plant Telomeresp. 326
Maintaining Telomeres without Telomerasep. 333
Telomeres without Telomerase in Saccharomyces cerevisiaep. 334
Introductionp. 334
Telomere Erosion When Telomerase Function is Lostp. 335
Two Types of 'Survivors' in the Absence of Telomerasep. 338
Survival in the Absence of Telomerase Requires Homologous Recombinationp. 339
The Survival Pathways Have Other Genetic Requirementsp. 340
Mechanisms of ALTp. 341
RAD52 Independent Mechanisms?p. 343
Unanswered Questions and Future Directionsp. 344
Recombinational Telomere Elongation in the Yeast Kluyveromyces lactisp. 347
Introductionp. 347
Telomere Structure in K. lactisp. 347
Deleting Telomerase Causes Progressive Telomere Shortening and Cell Senescencep. 348
Senescence Caused by terl Deletions is Due to Shortened Telomeres, Not Absence of Telomerasep. 349
Post-Senescence Survivors Emerge with Restored Growth Ratesp. 350
Survivors Contain Telomeres that were Elongated through Recombinationp. 350
Survivor Telomeres and Growth Phenotypes are Unstablep. 351
Regions Near Short Telomeres are Subject to High Rates of Recombinationp. 353
Mismatch Repair Influences the Rate of Survivor Emergencep. 353
Common Telomeric Patterns Are Present in Elongated Telomeres within a Given Survivorp. 354
Models for Recombinational Telomere Elongationp. 355
Circles with Telomeric Repeats Can Very Effectively Promote Telomere Elongationp. 355
The 'Roll and Spread' Model of Recombinational Telomere Elongationp. 356
Can Circles Promote Telomere Elongation in Other Organisms?p. 356
Telomere Maintenance in Human Cell Lines and Tumors without Telomerasep. 359
Introductionp. 359
Evidence for the Existence of ALT in Cell Lines in vitro Immortalized Cell Linesp. 359
Further Evidence that Telomerase is not Involved in the ALT Mechanismp. 360
ALT in Human Tumors and Tumor-Derived Cell Linesp. 362
ALT-Associated PML Bodies (APBs)p. 364
Evidence for the Involvement of Recombination in ALTp. 365
Coexistence of ALT and Telomerasep. 366
Repression of ALTp. 368
Perspectivesp. 370
Non-Classical Telomere Structuresp. 375
Telomeres in Drosophila and Other Insectsp. 376
Introductionp. 376
Telomere Elongation: Mechanisms in Insectsp. 376
Retrotransposition in Drosophila melanogasterp. 378
Chromosome Capping in Drosophilap. 384
Telomeric Silencing and TASp. 386
Conclusionsp. 390
Mitochondrial Telomeres: Alternative Solutions to the End-Replication Problemp. 396
Introductionp. 396
Linear Mitochondrial Genomes: More Than an Evolutionary Oddityp. 396
The Concept of Mitochondrial Telomeresp. 399
Variability of Mitochondrial Telomeric Structuresp. 399
Mitochondrial Telomeric Proteinsp. 402
Mitochondrial Telomeric Minicirclesp. 403
Evolutionary Considerationsp. 407
Medical Implicationsp. 410
Indexp. 418
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