Advances in Cancer Research, Vol. 108

171 Pages·2010·1.062 MB·English

by  George F. Vande Woude (ed.), George Klein (ed.)

Advances in
CANCER
RESEARCH
Volume 108
Thispageintentionallyleftblank
Advances in
CANCER
RESEARCH
Volume 108
Edited by
George F. Vande Woude
VanAndelResearchInstitute
GrandRapids
Michigan,USA
George Klein
MicrobiologyandTumorBiologyCenter
KarolinskaInstitute
Stockholm,Sweden
AMSTERDAM • BOSTON (cid:129) HEIDELBERG (cid:129) LONDON
NEW YORK (cid:129) OXFORD (cid:129) PARIS (cid:129) SAN DIEGO
SAN FRANCISCO (cid:129) SINGAPORE (cid:129) SYDNEY (cid:129) TOKYO
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Contents
ContributorstoVolume108 vii
Insights into the Evolution of Lymphomas Induced by
Epstein–Barr Virus
DavidVereideandBillSugden
I. EBVanditsExtensivePresenceinLymphomas 2
II. TumorCellsDifferinTheirDependenceonEBV 6
III. AModelforEBV-InducedLymphomagenesis 9
IV. Conclusion 14
References 15
Recent Advances in the Research of Hepatitis B Virus-Related
Hepatocellular Carcinoma:Epidemiologic and Molecular
Biological Aspects
Jia-HorngKao,Pei-JerChen,andDing-ShinnChen
I. Introduction 22
II. FactorsAssociatedwithHCCDevelopmentinPatients
withChronicHBVInfection 26
III. ViralFactorsinHBV-RelatedHCC 27
IV. NonviralFactorsinHBV-RelatedHCC 44
V. PrimaryPreventionofHBV-RelatedHCC 45
VI. MolecularCarcinogenesisofHBV-RelatedHCC 46
VII. GeneticVariationsandHCC:VirusandHostPerspectives 50
VIII. Conclusions 60
References 61
v
vi Contents
The ATM–Chk2 and ATR–Chk1 Pathways in DNA Damage
Signalingand Cancer
JoanneSmith,LyeMunTho,NaihanXu,andDavidA.Gillespie
I. Introduction 74
II. ActivationoftheATM–Chk2andATR–Chk1DNAPathways 75
III. CheckpointFunctionsoftheATM–Chk2andATR–Chk1Pathways 79
IV. TheThreeRsofDamageSignaling:Resection,Recombination,andRepair 84
V. ATM–Chk2andATR–Chk1PathwayAlterationsinCancer 87
VI. Exploiting Homologous Recombinational Repair (HRR) Defects for Cancer
Therapy 92
VII. DNADamageSignalingasaBarriertoTumorigenesis 95
VIII. CheckpointSuppressionasaTherapeuticPrinciple 97
IX. FuturePerspectives 102
References 104
microRNAs in Cancer: From Bench to Bedside
MariaAngelicaCortez,CristinaIvan,PengZhou,XueWu,MirceaIvan,
andGeorgeAdrianCalin
I. Introduction 114
II. AlterationsofmiRNAExpressioninCancer 115
III. CausesofmiRNAExpressionVariations 117
IV. PathwaysInvolvingmiRNAAlterations 126
V. ClinicalApplications 136
VI. ConcludingRemarks 143
References 144
Index 159
Contributors
Numbersinparenthesesindicatethepagesonwhichtheauthors’contributionsbegin.
George Adrian Calin, Department of Experimental Therapeutics and
The RNA Interference and non-codingRNA Center, The University of
Texas MD Anderson CancerCenter,Houston,Texas, USA (113)
Ding-Shinn Chen, Department of Internal Medicine, Graduate Institute of
ClinicalMedicine,HepatitisResearchCenter,NationalTaiwanUniversity
College of Medicine and National Taiwan University Hospital, Taipei,
Taiwan(21)
Pei-Jer Chen, Department of Internal Medicine, Graduate Institute of
Clinical Medicine, Hepatitis Research Center and Department of
Medical Research, National Taiwan University College of Medicine and
National Taiwan University Hospital,Taipei, Taiwan (21)
Maria Angelica Cortez, Department of Experimental Therapeutics and
The RNA Interference and non-codingRNA Center, The University of
Texas MD Anderson CancerCenter,Houston,Texas, USA (113)
DavidA.Gillespie,BeatsonInstituteforCancerResearch,GarscubeEstate
and Faculty of Medicine,University ofGlasgow,Glasgow,UK (73)
Cristina Ivan, Department of Experimental Therapeutics and The RNA
Interference and non-codingRNA Center, The University of Texas MD
Anderson CancerCenter,Houston, Texas, USA(113)
Mircea Ivan, Department of Medicine, Microbiology and Immunology,
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis,
Indiana,USA (113)
Jia-Horng Kao, Department of Internal Medicine, Graduate Institute of
Clinical Medicine, Hepatitis Research Center and Department of
Medical Research, National Taiwan University College of Medicine and
National Taiwan University Hospital,Taipei, Taiwan (21)
Joanne Smith, Beatson Institute for Cancer Research, Garscube Estate,
Glasgow,UK (73)
Bill Sugden, McArdle Laboratory for Cancer Research, University of
Wisconsin–Madison,Madison, Wisconsin, USA(1)
LyeMunTho,BeatsonInstituteforCancerResearch,GarscubeEstateand
Faculty of Medicine,University ofGlasgow, Glasgow,UK (73)
vii
viii Contributors
David Vereide, McArdle Laboratory for Cancer Research, University of
Wisconsin–Madison,Madison, Wisconsin,USA (1)
XueWu,DepartmentofMedicine,MicrobiologyandImmunology,Indiana
University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana,
USA (113)
Naihan Xu, Beatson Institute for Cancer Research Garscube Estate,
Glasgow, UK (73)
Peng Zhou, Department of Biological Science, Purdue University Calumet,
Hammond, Indiana, USA(113)
Insights into the Evolution
of Lymphomas Induced by
Epstein–Barr Virus
DavidVereideandBillSugden
McArdleLaboratoryforCancerResearch,Universityof
Wisconsin–Madison,Madison,Wisconsin,USA
I. EBVanditsExtensivePresenceinLymphomas
A. EBVIsRetainedinCellsOnlyifItProvidesThemaSelectiveAdvantage
B. SpecificExamplesofEBV-PositiveMalignancies
II. TumorCellsDifferinTheirDependenceonEBV
III. AModelforEBV-InducedLymphomagenesis
A. ImplicationsoftheModel
B. PredictionsfromtheModel
IV. Conclusion
References
Epstein–Barr virus (EBV) encodes a wealth of oncogenic instructions, including
the abilities to drive a resting normal B cell to proliferate and to override apoptotic
stimuli. EBV is found in almost all types of lymphomas at varying frequencies.
However, the particular viral genes expressed differ considerably among tumors.
We have examined the role of EBV in several lymphomas by conditionally evicting
the extrachromosomal viral genome from tumor cells in vitro and have found a
graded dependence on the virus. Tumor cells that express all the known latent viral
genes have been found to depend on the virus to drive proliferation and to block
apoptosis at least in part by repressing the proapoptotic protein Bim. Other tumor
cells, which express fewer viral genes, also depend on the virus to block apoptosis,
but rely on the virus to promote but not to drive proliferation. Lastly, tumor cells
with the fewest viral genes expressed have been found to require EBV to prevent
theinefficient inductionof aBim-independent apoptosis.We presenta model for the
evolutionofEBV-inducedlymphomasinwhichtumorsareinitially“addicted”tothe
virus for almost all oncogenic functions. These tumors are targets for the immune
system because they express multiple immunogenic viral proteins. Therefore, EBV-
induced tumors are under selective pressure to acquire cellular mutations that can
replace viral functions. We posit that the heterogeneity in viral gene expression
among different EBV-associated lymphomas reflects a dynamic process by which
tumors evolve to be less dependent on the virus. #2010ElsevierInc.
AdvancesinCANCERRESEARCH 0065-230X/10$35.00
Copyright2010,ElsevierInc.Allrightsreserved. DOI:10.1016/S0065-230X(10)08004-8
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