Molecular Mechanisms and Their Clinical Application in Malignancies
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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.
Table of Contents
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
Product details
- No. of pages: 292
- Language: English
- Copyright: © Academic Press 1991
- Published: September 28, 1991
- Imprint: Academic Press
- eBook ISBN: 9781483262093
About the Editors
Daniel E. Bergsagel
Tak W. Mak
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