Molecular Mechanisms and Their Clinical Application in Malignancies

Molecular Mechanisms and Their Clinical Application in Malignancies

1st Edition - September 28, 1991

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  • Editors: Daniel E. Bergsagel, Tak W. Mak
  • eBook ISBN: 9781483262093

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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



    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


    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


    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


    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


    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


    6 Regulation of Transcription

    I. Introduction

    II. Regulation of Initiation of Transcription


    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


    8 Molecular Biology of Oncogenes

    I. Introduction

    II. Proto-Oncogenes

    III. Protein-Tyrosine Kinases

    IV. Proto-Oncogenes That Encode Nuclear Proteins

    V. Conclusion


    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


    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


    11 Retinoid and Thyroid Hormone Receptors

    I. Introduction

    II. Results

    III. Discussion


    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


    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


    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



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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