Table Of ContentShaker A. Mousa
Paul J. Davis
Angiogenesis
Modulations in
Health and Disease
Practical Applications of Pro- and
Anti-angiogenesis Targets
Angiogenesis Modulations in Health and Disease
Shaker A. Mousa (cid:129) Paul J. Davis
Editors
Angiogenesis Modulations
in Health and Disease
Practical Applications
of Pro- and Anti-angiogenesis Targets
Editors
Shaker A. Mousa Paul J. Davis
The Pharmaceutical Research Institute at The Pharmaceutical Research Institute at
Albany College of Pharmacy and Health Albany College of Pharmacy and Health
Sciences Sciences
Rensselaer , NY , USA Rensselaer , NY , USA
ISBN 978-94-007-6466-8 ISBN 978-94-007-6467-5 (eBook)
DOI 10.1007/978-94-007-6467-5
Springer Dordrecht Heidelberg New York London
Library of Congress Control Number: 2013936733
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Contents
Introduction .................................................................................................... ix
1 Angiogenesis Assays: An Appraisal of Current Techniques .............. 1
Shaker A. Mousa and Paul J. Davis
Part I Pro-angiogenesis Targets and Clinical Implications
2 Survey of Pro-angiogenesis Strategies .................................................. 15
Shaker A. Mousa
3 Angiogenesis Modulation by Arachidonic Acid-derived Lipids:
Positive and Negative Regulators of Angiogenesis .............................. 19
Robert C. Block , Murat Yalcin , Mathangi Srinivasan ,
Steve Georas , and Shaker A. Mousa
4 Pro-angiogenic Activity of Thyroid Hormone Analogues:
Mechanisms, Physiology and Clinical Prospects ................................. 29
Paul J. Davis , Faith B. Davis , Hung-Yun Lin , Mary K. Luidens ,
and Shaker A. Mousa
5 Actions of Steroids and Peptide Hormones on Angiogenesis ............. 47
Paul J. Davis , Shaker A. Mousa , Faith B. Davis ,
and Hung-Yun Lin
6 Role of Non-neuronal Nicotinic Acetylcholine Receptors
in Angiogenesis Modulation .................................................................. 55
Shaker A. Mousa , Hugo R. Arias , and Paul J. Davis
7 Catecholamine Neurotransmitters: An Angiogenic Switch
in the Tumor Microenvironment .......................................................... 77
Sujit Basu and Partha Sarathi Dasgupta
8 Impact of Nanotechnology on Therapeutic Angiogenesis .................. 87
Dhruba J. Bharali and Shaker A. Mousa
vv
vi Contents
Part II Anti-angiogenesis Targets and Clinical Applications
9 Survey of Anti-angiogenesis Strategies ................................................ 95
Shaker A. Mousa
10 Tetraiodothyroacetic Acid (Tetrac), Nanotetrac
and Anti-angiogenesis ............................................................................ 107
Paul J. Davis , Faith B. Davis , Mary K. Luidens , Hung-Yun Lin ,
and Shaker A. Mousa
11 Integrin Antagonists and Angiogenesis ................................................ 119
Shaker A. Mousa and Paul J. Davis
12 Anti-angiogenesis Therapy as an Adjunct
to Chemotherapy in Oncology .............................................................. 143
Shaker A. Mousa and Laila H. Anwar
13 Anti-VEGF Strategies in Ocular Angiogenesis-mediated
Disorders, with Special Emphasis on Age-related
Macular Degeneration ........................................................................... 157
Shaker A. Mousa
14 Application of Nanotechnology to Prevent Tumor
Angiogenesis for Therapeutic Benefi t .................................................. 173
Dhruba J. Bharali and Shaker A. Mousa
15 Biomarkers of Response and Resistance
to Anti-angiogenic Treatment ............................................................... 181
Dan G. Duda
16 Speculations on New Directions in Which Angiogenesis
May Proceed ........................................................................................... 199
Shaker A. Mousa and Paul J. Davis
Index ................................................................................................................ 205
Contributors
Laila H. Anwar Albany College of Pharmacy and Health Sciences , Albany , NY ,
USA
Hugo R. Arias Department of Medical Education, College of Medicine , California
North State University , Elk Grove , CA , USA
Sujit Basu Department of Pathology and Arthur G. James Comprehensive Cancer
Center , Ohio State University , Columbus , OH , USA
Dhruba J. Bharali The Pharmaceutical Research Institute at Albany College of
Pharmacy and Health Sciences , Rensselaer , NY , USA
Robert C. Block Department of Public Health Sciences, Division of Cardiology,
Department of Medicine , University of Rochester School of Medicine and Dentistry ,
Rochester , NY , USA
Partha Sarathi Dasgupta Signal Transduction and Biogenic Amines Department ,
Chittaranjan National Cancer Institute , Kolkata , India
Faith B. Davis The Pharmaceutical Research Institute at Albany College of
Pharmacy and Health Sciences , Rensselaer , NY , USA
Paul J. Davis The Pharmaceutical Research Institute at Albany College of Pharmacy
and Health Sciences , Rensselaer , NY , USA
Department of Medicine , Albany Medical Center , Albany , NY , USA
Dan G. Duda Steele Laboratory for Tumor Biology, Department of Radiation
Oncology , Massachusetts General Hospital, Harvard Medical School , Boston , MA ,
USA
Steve Georas Division of Pulmonary and Critical Care Medicine, Department
of Medicine , University of Rochester School of Medicine and Dentistry ,
Rochester , NY , USA
vviiii
viii Contributors
Hung-Yun Lin Institute of Cancer Biology and Drug Discovery , Taipei Medical
University , Taipei , Taiwan
Mary K. Luidens Department of Medicine , Albany Medical College , Albany , NY ,
USA
Shaker A. Mousa The Pharmaceutical Research Institute at Albany College of
Pharmacy and Health Sciences , Rensselaer , NY , USA
Mathangi Srinivasan The Pharmaceutical Research Institute at Albany College
of Pharmacy and Health Sciences , Rensselaer , NY , USA
Murat Yalcin Veterinary Medicine Faculty, Department of Physiology , Uludag
University , Gorukle, Bursa , Turkey
The Pharmaceutical Research Institute at Albany College of Pharmacy and Health
Sciences , Rensselaer , NY , USA
Introduction
Our intent in this textbook is to facilitate development of agents with clinical potential
for modulating new blood vessel formation. We provide overviews of strategies in
pro- and anti-angiogenesis, discuss certain classical and a number of recently
emphasized targets in angiogenesis—such as several integrins—and we review the
actions of classes of agents only recently appreciated to stimulate or inhibit angio-
genesis. Discussed here is the impact of novel nanotechnology-based formulations
of blood vessel-targeted drugs on the actions of these agents. We also review the
assets and certain limitations of assays for angiogenesis and cover the challenging
subject of biomarkers of new blood vessel formation. Finally, we speculate about
new directions in which modulation of angiogenesis may proceed. We did not
intend to provide an extensive overview of history and discovery in physiological
and pathologic angiogenesis, but rather we present the current strategies in the mod-
ulation of angiogenesis in health and diseases.
The feasibility of clinically important modulation of angiogenesis is a legacy of
Dr. Judah Folkman’s [1]. The concept moved through the three requisite phases of
a newly appreciated truth that Schopenhauer described, namely, dismissal, then
strenuous opposition and, fi nally, the declaration that the new truth was self-evident
from the start. The motivation to identify steps in angiogenesis that could be manip-
ulated was initially driven in Folkman and others by the desire to interrupt the vas-
cularization of cancers. Potential anti-angiogenesis agents have emerged in concert
with vascular growth factor discovery and the uncovering of steps in the molecular
bases of growth factor action. A model case is that of vascular endothelial growth
factor (VEGF), where antibodies or a trap have targeted VEGF, itself, and other
agents have been directed at the VEGF receptor or at the kinases associated with the
receptor. Vascular growth factors in addition to VEGF are of course now known to
exist. Thus, it is not surprising that clinical effectiveness is variable from one type
of cancer to another of a single anti-angiogenesis agent that targets a single apparent
point of vulnerability in the mechanism of action of a single vascular growth factor.
The concept of combining several anti-angiogenesis agents that target individual
vascular growth factors—VEGF, basic fi broblast growth factor (bFGF) and epidermal
growth factor (EGF)—in one therapeutic modality is attractive and, so far, impractical.
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