Cellular senescence : implications for cancer therapy / Razmik Mirzayans and David Murray.

Format:

Book

Author/Creator:

Mirzayans, Razmik.

Contributor:

Murray, David, Ph. D.

Language:

English

Subjects (All):

Cells--Aging.

Cells.

Cancer--Treatment.

Cancer.

Physical Description:

113 p. : ill. (some col.)

Edition:

1st ed.

Place of Publication:

New York : Nova Biomedical Books, c2009.

Language Note:

English

Summary:

Normal human cells have a limited life span when grown in culture. Aging cells enter a state of permanent growth arrest called replicative senescence, which is regulated by multiple signal transduction pathways involving p53 and other cancer-associated proteins. Senescent cells exhibit flattened and enlarged morphology, retain cell membrane integrity, remain metabolically active, but cease to divide when explanted in culture. Exposure of young (early passage) human cells to genotoxic agents such as ionizing radiation and cancer therapeutic drugs can also trigger a state of permanent growth arrest. One mechanism of stress-induced growth arrest is similar to replicative senescence and is commonly termed accelerated or premature senescence. Whereas some normal human cell types (e.g., skin fibroblasts) lose their clonogenic potential in response to genotoxic stress primarily through the process of premature senescence, it has been generally assumed that cancer-derived cells die through necrosis or programmed cell death (apoptosis) but do not exhibit premature senescence following exposure to genotoxic agents. Recently, however, it has become evident that exposure of human solid tumor-derived cells to genotoxic agents can trigger not only premature senescence, but also growth arrest by an ill-defined process leading to the development of multinucleated/polyploid cells. Here the author provides evidence reinforcing the notion that ionizing radiation-triggered premature senescence in cancer cells is generally dependent on the wild-type p53 function, and that the development of giant cells is a response of p53-deficient cells, presumably reflecting their failure to engage the premature senescence program.

Contents:

Intro

CELLULAR SENESCENCE: IMPLICATIONS FOR CANCER THERAPY

CONTENTS

PREFACE

Chapter 1 INTRODUCTION

Chapter 2 TELOMERASE-BASED SENESCENCE

Chapter 3 STRESS-TRIGGERED PREMATURE SENESCENCE

Chapter 4 FEATURES OF PREMATURE SENESCENCE

CELL MORPHOLOGY

SENESCENCE-ASSOCIATED β-GALACTOSIDASE EXPRESSION

SUSTAINED P21 UP-REGULATION

INHIBITION OF CELL GROWTH

NUCLEAR ACCUMULATION OF ACTIN

STRESS-ASSOCIATED NUCLEAR FOCI

Chapter 5 DIFFERENT MODES OF GROWTH ARREST ARE TRIGGERED BY GENOTOXIC STRESS

Chapter 6 CLASSIFICATION OF CDK INHIBITORS

Chapter 7 ROLES OF P21, P53 AND P16 IN SENESCENCE

Chapter 8 REGULATION OF P21WAF1 TRANSCRIPT AND P21 PROTEIN LEVELS

Chapter 9 MODE OF ACTION OF P21

Chapter 10 P53 SIGNALING AND CELLULAR RESPONSE TO DNA-DAMAGING AGENTS

IONIZING RADIATION-TRIGGERED RESPONSES

UV-TRIGGERED RESPONSES

APOPTOTIC THRESHOLD IN CANCER CELLS EXPOSED TO DNA-DAMAGING AGENTS

WHAT FACTORS MIGHT CONTRIBUTE TO THE APOPTOTIC THRESHOLD?

Chapter 11 CELL-TO-CELL COMMUNICATION TRIGGERED BY DNA-DAMAGING AGENTS

ROS-ASSOCIATED BYSTANDER EFFECT OF RADIATION

P53-MEDIATED BYSTANDER EFFECT OF RADIATION

DIFFUSIBLE "AT-CORRECTING" FACTORS

Chapter 12 MODULATING SENESCENCE IN THE CONTEXT OF CANCER THERAPY

PROS AND CONS OF ACTIVATING SENESCENCE IN CANCER CELLS

ASSAYS FOR PRECLINICAL TESTING OF ANTICANCER AGENTS

Chapter 13 AGING, SENESCENCE, AND "HORMESIS"

Chapter 14 HUMAN GENETIC DISORDERS ASSOCIATED WITH GENOMIC INSTABILITY AND CANCER PREDISPOSITION

WERNER SYNDROME

HUTCHINSON-GILFORD'S PROGERIA SYNDROME

BLOOM SYNDROME

ROTHMUND-THOMPSON SYNDROME

COCKAYNE SYNDROME

XERODERMA PIGMENTOSUM

FANCONI ANEMIA

ATAXIA TELANGIECTASIA

LI-FRAUMENI SYNDROME.

Chapter 15 BIOLOGICAL CONSEQUENCES OF THE FAILURE OF CELLS TO UNDERGO SENESCENCE/APOPTOSIS FOLLOWING GENOTOXIC STRESS: BASIS FOR THE EMERGENCE OF HIGHLY METASTATIC AND THERAPY-RESISTANT DISEASE?

CONCLUSION

ACKNOWLEDGMENTS

REFERENCES

INDEX

Blank Page.

Notes:

Bibliographic Level Mode of Issuance: Monograph

Includes bibliographical references (p. [75]-100) and index.

Description based on print version record and CIP data provided by publisher.

ISBN:

1-61728-173-5

OCLC:

923662897