Advances in

CANCERRESEARCH

Volume 94

George F. Vande Woude

George Klein

Contributors to Volume 94 ix

Molecular Mechanisms in GliomagenesisEsther Hulleman and Kristian Heli n

I. Classification of Gliomas 2

II. Cell Cycle Control 3

III. Signal Transduction 7IV. Molecular Mechanisms of GBM Formation 1 3

V. Future Directions 16References 1 8

Activation of AKT Kinases in Cancer : Implications fo rTherapeutic TargetingAlfonso Bellacosa, C . Chandra Kumar, Antonio Di Cristofano ,

and Joseph Robert Test a

I. Introduction 3 0II. Historical Perspective 32

III. Structure of AKTs 3 3IV. AKT Activation During Signal Transduction 3 4

V. Crystal Structure of AKT Kinases 36VI. Substrates of AKT Mediating its Cellular Functions 3 8

VII. AKT Alterations in Human Cancers 4 4VIII. Alterations of Other Components of the PI3KIAKT Pathway in Huma n

Cancers 54IX. In Vivo Models of AKT Activation 5 7

X. Implications of AKT Pathway Activation for Therapeutic Targeting 6 1

XI. Conclusions 7 1References 72

Mitochondria as Functional Targets of ProteinsCoded by Human Tumor VirusesDonna M . D'Agostino, Paolo Bernardi, Luigi Chieco-Bianchi ,and Vincenzo Ciminal e

I. Introduction 8 8II. Mitochondrial Proteins Coded by Human Tumor Viruses 10 0

III. Concluding Remarks 12 4References 125

Apoptotic Pathways and Therapy Resistanc ein Human Malignancies

Kristina Viktorsson, Rolf Lewensohn, and Boris Zhivotovsky

I. Introduction 14 4II. Signaling Pathways that Lead to Apoptosis i n

Mammalian Cells 144III. Modulators of Apoptotic Signaling 15 6IV. Apoptosis Resistance and its Involvement in Impede d

Therapy Responses 16 4V. Reactivation of Apoptotic Signaling as an Approach i n

Anticancer Therapy 17 1VI. Concluding Remarks 179

References 180

Endostatin Signaling and Regulation of Endothelia lCell-Matrix Interaction sSara A . Wickström, Kari Alitalo, and Jorma Keski-Oj a

I. Introduction 19 8II. Basement Membranes 199

III. Basement Membrane-Derived Inhibitors of Angiogenesis 20 2IV Characterization and Structural Features of Endostatin 20 4V. Biological Roles of Endostatin 20 5

VI. Effects of Endostatin on Tumor Growth 20 7VII. Cell Surface Receptors for Endostatin 20 7

VIII. Regulation of Cell Migration, Adhesion, and Acti nCytoskeleton by Endostatin 21 1

IX. Regulation of Pericellular Proteolysis by Endostatin 21 5X. Other Mechanisms of Endostatin Action 21 7

XI. Endostatin in Cancer Therapy 21 9XII. Conclusions and Perspective 22 0

References 221

A Calcium-Based Theory of Carcinogenesis

Lionel F. Jaffe

I. The Epigenetic Initiation of Cancer 23 2II. Classes of Epigenetic Theories of Carcinogenesis 236III. The Calcium Dependence of Epigenesis 23 71V Calcium and Carcinogenesis 23 9V. Proposed Tests of Calcium-Based Theories of Cancer Initiatio n

with Aequorinated Mice 25 2VI. Calzium Uber Alles 25 3

References 25 3

Index 265