Molecular Mechanisms and Their Clinical Application in Malignancies

1st Edition - September 28, 1991
Editors: Daniel E. Bergsagel, Tak W. Mak
Language: English
eBook ISBN:
9 7 8 - 1 - 4 8 3 2 - 6 2 0 9 - 3

Molecular Mechanisms and their Clinical Application in Malignancies is a collection of manuscripts presented at the 12th Annual Bristol-Myers Squibb Symposium on Cancer Research,… Read more

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Molecular Mechanisms and their Clinical Application in Malignancies is a collection of manuscripts presented at the 12th Annual Bristol-Myers Squibb Symposium on Cancer Research, held in Toronto, Canada on September 26-27, 1989. This symposium reviews the current understanding of the mechanisms of malignant transformation and the application of several technologies to the diagnosis, evaluation, and treatment of malignancies. This book is divided into 14 chapters. The opening chapters deal with the genetic basis of neoplasia and the molecular biology of oncogenes, the regulation of transcription, and the rearrangement of T- and B-cell genes during development and in malignancies. The subsequent chapters focus on the genetic abnormalities detected in specific tumors, such as retinoblastoma, colorectal carcinoma, and lung cancer. These chapters also examine the retinoid and thyroid hormone receptors. Other chapters explore the genetic basis of the cellular response to therapy, drug resistance, cachectin-tumor necrosis factor in the biology of disease, acute myelogenous leukemia, and the stages in tumor progression. The final chapters look into the application of molecular biology to clinical treatment in the form of receptor specific intoxication on tumor cells, the molecular genetic analysis of the phakomycoses, and the structural design of antitumor compounds. This book will prove useful to oncologists, molecular biologists, clinicians, and researchers.

Contributors

Editor's Foreword

Foreword

Preface

1 Molecular Genetic Analysis of the Phakomatoses

I. Introduction

II. von Recklinghausen’s Neurofibromatosis

III. Bilateral Acoustic Neurofibromatosis

IV. von Hippel-Lindau Disease

V. Summary

References

2 P-Glycoprotein and Resistance to Anticancer Drugs

I. Introduction

II. Molecular Studies of P-Glycoprotein and MDR

III. Drug Resistance in P388 Tumors

IV. Immunohistochemical Detection of P-Glycoprotein

V. P-Glycoprotein Expression in Childhood Soft-Tissue Sarcoma

VI. Concluding Remarks

References

3 Interactions between Regulators and Chemotherapy Affecting the Blast Cells of Acute Myeloblastic Leukemia

I. Introduction

II. The Clonal Hemopathies

III. Blast Cells in Culture

IV. Lineage Infidelity

V. Myelopoietic Growth Factors

VI. Myelopoietic Growth Factors and Blast Cells

VII. Growth Factors and Chemosensitivity

VIII. Nuclear Receptors

IX. Retinoic Acid, Blast Self-Renewal, and Chemosensitivity

X. Conclusion

References

4 Molecular Pathogenesis of Lung Cancer

I. Introduction

II. Abnormalities in Dominant Oncogenes

III. Abnormalities in Recessive Oncogenes

IV. Several Mechanisms of Tumor Promotion in the Pathogenesis of Lung Cancer

V. Conclusions

References

5 Receptor-Specific Intoxication of Tumor Cells: Design, Construction, and Properties of Microbial Toxin—Growth Factor Fusion Proteins

I. Introduction

II. Diphtheria Toxin Structure and Mode of Action

III. Genetic Construction of Diphtheria Toxin-Related Polypeptide Hormone Fusion Proteins

IV. Conclusion

References

6 Regulation of Transcription

I. Introduction

II. Regulation of Initiation of Transcription

References

7 Cachectin—TNF in the Biology of Disease

I. Introduction

II. Biosynthesis of Cachectin-TNF

III. Cachectin—TNF as a Mediator of Septic Shock

IV. Anticachectin—TNF Antibodies in Septic Shock

V. Cachectin—TNF as a Mediator of Cachexia

VI. Cachectin—TNF in Inflammation, Edema Formation, and Tissue Remodeling

VII. Cachectin—TNF Serum Levels versus Paracrine (Local) Effects

References

8 Molecular Biology of Oncogenes

I. Introduction

II. Proto-Oncogenes

III. Protein-Tyrosine Kinases

IV. Proto-Oncogenes That Encode Nuclear Proteins

V. Conclusion

References

9 Genetics of Colorectal Cancer

I. Introduction

II. Genetics of Adenomatous Polyposis Coli

III. Chromosome 5 Marker Allele Loss in Colorectal Carcinomas

IV. Other Genetic Changes in Colorectal Carcinomas

V. Discussion

References

10 Stages of Tumor Progression: Loss of Genetic Heterozygosity

I. Introduction

II. Model for Loss of Genetic Information in Cancer Predisposition and Progression

III. Associated Cancers: Common Predisposition but Mixed Progression?

IV. Conclusions

References

11 Retinoid and Thyroid Hormone Receptors

I. Introduction

II. Results

III. Discussion

References

12 Retinoblastoma Gene: Mutations, Expression, and Putative Function

I. Retinoblastoma: The Knudson Hypothesis

II. Tests of the Knudson Hypothesis

III. Lessons and Conclusions from the Analysis of Mutations

IV. A Model for the Possible Role(s) of the RB1 Gene Product in Normal Cells

References

13 Structural Design in Antitumor Compounds

I. Introduction

II. Early Studies of Carcinogenesis

III. High-Affinity Receptor Protein Kinase C

IV. Computer Modeling of the Tumor-Promoter Pharmacophore

V. Design of PKC Activators

VI. Bryostatin Agonist Activity

VII. Conclusion

References

14 T-Cell Receptor Genes in Malignant Disease

I. Introduction

II. Genes of the T-Cell Antigen Receptors

III. Thymic Selection of T Cells

IV. T-Cell Receptor and Immunoglobulin Gene Rearrangements in Lymphoproliferative Disorders

V. Chromosomal Translocations Involving TcR Genes

VI. T-Cell Responses in Disease Situations

References

Index