Anti-Angiogenesis Drug Discovery and Development


by

Atta-ur-Rahman, Choudhary Iqbal

DOI: 10.2174/97816080516251110101
eISBN: 978-1-60805-162-5, 2011
ISBN: 978-1-60805-648-4
ISSN: 2210-268X

  
  




The inhibition of angiogenesis is an effective mechanism of slowing down tumor growth and malignancies. The process of induction or pr...[view complete introduction]
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Table of Contents

Preface , Pp. i-iii (3)

Atta-ur-Rahman and M. Iqbal Choudhary

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Contributors , Pp. iv-vi (3)

Atta-ur-Rahman and M. Iqbal Choudhary

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Antiangiogenic Treatment of Hematological Tumors , Pp. 1-11 (11)

Domenico Ribatti, Vito Longo and Angelo Vacca

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Multiligands/Rage Axis: An Emerging Actor in Tumour Angiogenesis , Pp. 12-33 (22)

Armando Rojas, Hector Figueroa, Ileana Gonzalez, Jacqueline Romero and Miguel Morales

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Ginsenoside Rg3 and Rh2: The Anti-Cancer and Anti- Angiogenic Saponins from Ginseng , Pp. 34-57 (24)

Patrick Y.K. Yue, Y. Huang and Ricky N.S. Wong

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Antiangiogenic Therapy for Cardiovascular Diseases , Pp. 58-69 (12)

Mustafa Sacar and Yalın Tolga Yaylali

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Role of Phosphoinositide 3-Kinases and Angiogenesis in Cardiovascular Diseases , Pp. 70-85 (16)

Cinzia Perrino, Giovanni Esposito, Giuseppe Gargiulo, Gianluigi Pironti, Gabriele G. Schiattarella and Massimo Chiariello

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Redox Regulation of Angiogenesis: NADPH Oxidase as a Drug Target , Pp. 86-115 (30)

Elsa C. Chan, Hitesh Peshavariya, Srinivasa Raju Datla, Gregory J. Dusting and Fan Jiang

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Thymidine Phosphorylase Inhibitors , Pp. 116-147 (32)

Radim Nencka

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Neurological Complications of Antiangiogenic Therapy , Pp. 148-170 (23)

Jose Tarcisio Feitosa Vieira da Silva, Italo Gustavo Lima Monteiro, Carlos Tairo Diogenes Holanda and Francisco de Assis Aquino Gondim

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Autoimmunity and Angiogenesis , Pp. 171-186 (16)

A. Mirshafiey and R. Boghozian

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Author Index to Volume 1 , Pp. 187

Atta-ur-Rahman and M. Iqbal Choudhary

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Preface

Angiogenesis, a normal physiological process of new blood vessel formation, is involved in pathological conditions such as tumor growth metastatic retinopathy, etc. Poor vascularization or abnormally high vasculature are both targets of active pharmaceutical research in recent years. The inhibition of angiogenesis is an effective mechanism of slowing down tumor growth and malignancies. The process of induction or pro-angiogenesis is highly desirable for the treatment of cardiovascular diseases, wound healing disorders, etc. Efforts to understand the molecular basis, both for inhibition and induction, have yielded fascinating results. Despite the importance of this complex cascade of biochemical events only a few monographs are found in the international literature. The book entitled “Anti-angiogenesis Drug Discovery and Development” is an excellent compilation of well-written reviews on various aspects of the anti-angiogenesis process. These reviews have been contributed by leading practitioners in the field and highlight the major developments in this exciting field in the last two decades.

The first review by Ribatti et al. deals with the treatment of hematological malignancies, such as leukemia, lymphoma, myelodysplastic syndrome, etc. The review lists a number of chemotherapeutic agents which have been clinically tested and found to be effective. This well-written and well-referenced review also discusses the molecular basis of these new therapeutic agents.

Rajas et al. have reviewed an important linkage between the receptors for advanced Glycation Endproducts (RAGE) and angiogenesis cascade. It has been reported that RAGE engagement promotes many changes in tumor and host cells and leads to the formation of new blood vessels. The review further discusses the pharmacological approaches to inhibit RAGE ligands as well as inhibitors of AGE formation in order to down regulate the angiogenic process. Yue et al. have contributed a review on potential anti-angiogenic and anti-cancer effects of ginsenosides. These compounds are steroidal saponins obtained from a famous medicinal plant Panax ginseng. Two of these ginsenosides (Rg3 and Rh2) were found to inhibit cancer growth, most probably by inhibiting new vessel formation. These exciting discoveries in in vitro and in vivo models deserve further studies to understand their mechanism of action at molecular levels, as well as to assess their safety profile.

Sacar and Yaylali in their review describe the role of neo-vascularization in intra-plaque hemorrhage and progression of atherosclerosis. While discussing the role of various factors in the complex cascade of angiogenesis, the authors describe various points for intervention to block angiogenesis. The objective of these intervention is to block and inhibit intralesion angiogenesis and thickening of neointima. The use of various drugs and invasive interventions have been described to achieve this objective.

The role of phosphoinositide 3-kinases (PI 3K) in angiogenesis has been reviewed by Perrino et al. The inhibition of PI 3K suppresses angiogenesis and tumor growth as established through a number of animal studies. Thus the regulation of PI 3K to modulate the angiogenic process holds great promise for the future.

Chan et al. review the studies on the complex process of angiogenesis with reference to its redox regulation by NADPH oxidase. It has been unambiguously established that NADPH oxidase, the only enzyme system dedicated to generate ROS (Reactive Oxygen Species), serves as intracellular signal amplifier for multiple receptor tyrosinase kinase mediated pathways involved in angiogenesis. Thus the inhibition of NADPH oxidase enzyme activity is an attractive new target for antiangiogenic therapies. However achieving specific inhibition of different isoforms of NADPH oxidase still remains an unmet challenge.

Nencka describes the important role of thymidine phosphorylase (TP) as a pro-angiogenic factor. TP inhibitors are known to interfere with the catalytic action of the enzyme, including TP-mediated angiogenesis. This review extensively discusses the potential of TP inhibitors in clinical management of angiogenesis in various diseases.

Silva Jr. et al. in their well written review article describe the neurological complications, including central and peripheral neurotoxicity, of antiangiogenic chemotherapy. The knowledge of such side effects of antiangiogenic drugs is not only important for physicians prescribing the drugs, but it is also equally important in the designing and development of new antiangiogenic agents.

Last but not the least, Mirshafey and Boghozian present an equally important aspect of angiogenesis, its correlation with autoimmunity and chronic inflammation. They built the argument that interventions, such as the use of anti-inflammatory drugs in autoimmune diseases, also inhibit the angiogenic mediator production.

The feast of these reader-friendly reviews on topics of great scientific importance and health relevance, makes this book an excellent reading, both for the novice as well as for the subject expert. We are grateful to all the contributors for their useful and scholarly written review articles. We are also thankful to the staff members of the Bentham Science Publishers, specially Mr. Mahmood Alam (Director), Ms. Taqdees Malik (Editorial Assistant) and Ms. Sadaf Idrees Khan (Composer) for their diligent and tireless efforts to bring this excellent treatise in print in a timely manner.

Prof. Dr. Atta-ur-Rahman, FRS
Prof. Dr. M. Iqbal Choudhary
Editors

List of Contributors

Editor(s):
Prof. Dr. Atta-ur-Rahman FRS
University of Karachi
Pakistan


Prof. Dr. Choudhary Iqbal
University of Karachi
Pakistan




Contributor(s):
Domenico Ribatti
Department of Human Anatomy and Histology
University of Bari Medical School
Bari
Italy


Vito Longo
Department of Biomedical Sciences and Human Oncology
Section of Internal Medicine and Clinical Oncology, University of Bari Medical School
Bari
Italy


Angelo Vacca
Department of Biomedical Sciences and Human Oncology
Section of Internal Medicine and Clinical Oncology, University of Bari Medical School
Bari
Italy


Armando Rojas
Medicine Faculty, Catholic University of Maule
Talca
Chile


Héctor Figueroa
Medicine Faculty, Catholic University of Maule
Talca
Chile


Ileana González
Medicine Faculty, Catholic University of Maule
Talca
Chile


Jacqueline Romero
Medicine Faculty, Catholic University of Maule
Talca
Chile


Miguel Morales
ICBM, Medicine Faculty, University of Chile
Santiago
Chile


Patrick Y.K. Yue
Department of Biology
Hong Kong Baptist University
Hong Kong


Y. Huang
Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences and School of Biomedical Sciences
Chinese University of Hong Kong
Hong Kong


Ricky N.S.
Wong Department of Biology
Hong Kong Baptist University
Hong Kong


Mustafa Sacar
Department of Cardiovascular Surgery
Pamukkale University, Faculty of Medicine
Denizli
Turkey


Yalin Tolga Yaylali
Department of Cardiology
Pamukkale University, Faculty of Medicine
Denizli
Turkey


Cinzia Perrino
Division of Cardiology, Department of Clinical Medicine, Cardiovascular and Immunological Sciences
Federico II University
Naples
Italy


Giovanni Esposito
Division of Cardiology, Department of Clinical Medicine, Cardiovascular and Immunological Sciences
Federico II University
Naples
Italy


Giuseppe Gargiulo
Division of Cardiology, Department of Clinical Medicine, Cardiovascular and Immunological Sciences
Federico II University
Naples
Italy


Gianluigi Pironti
Division of Cardiology, Department of Clinical Medicine, Cardiovascular and Immunological Sciences
Federico II University
Naples
Italy


Gabriele G. Schiattarella
Division of Cardiology, Department of Clinical Medicine, Cardiovascular and Immunological Sciences
Federico II University
Naples
Italy


Massimo Chiariello
Division of Cardiology, Department of Clinical Medicine, Cardiovascular and Immunological Sciences
Federico II University
Naples
Italy


Elsa C. Chan O'Brien
Institute, Department of Medicine,
Emory University School of Medicine, Atlanta
Georgia
USA


Hitesh Peshavariya
Emory University School of Medicine, Atlanta
Georgia
USA


Srinivasa Raju Datla
Emory University School of Medicine, Atlanta
Georgia
USA


Gregory J. Dusting
Department of Surgery
Emory University School of Medicine, Atlanta
Northwestern Polytechnical University
Georgia
USA


Fan Jiang Key
Department of Surgery
Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health
Qilu Hospital, Shandong University, Shandong Province
Jinan
China


Radim Nencka
Gilead Sciences and IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic
Centre for New Antivirals and Antineoplastics (IOCB), Flemingovo nám. 2, CZ-166 10, Prague 6
Ghent, B-9000
Czech Republic


José Tarcísio Feitosa Vieira da Silva Júnior
Departamento de Fisiologia e Farmacologia
Universidade Federal do Ceará, Fortaleza
Ceará
Brasil


Ítalo Gustavo Lima Monteiro
Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza
Ceará
Brasil


Carlos Tairo Diógenes Holanda
Hospital Universitário Walter Cantídio, Universidade Federal do Ceará, Fortaleza
Ceará
Brasil


Francisco de Assis Aquino Gondim
Saint Louis University, Saint Louis
Missouri, 63104
USA


A. Mirshafiey
School of Public Health, Tehran University of Medical Sciences
Box 6446
Tehran, 14155
Iran


R. Boghozian
Department of Pathobiology
School of Public Health, Tehran University of Medical Sciences
Box 6446
Tehran, 14155
Iran




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