Tài liệu Research on melanoma – a glimpse into current directions and future trends Edited by Mandi Murph

RESEARCH ON MELANOMA – A GLIMPSE INTO CURRENT DIRECTIONS AND FUTURE TRENDS
Edited by Mandi Murph

Contents
Preface IX


Part 1 Epigenetics 1
Chapter 1 Predictive Capacity and Functional
Significance of MicroRNA in Human Melanoma 3
Xiaobo Li and Yaguang Xi
Chapter 2 Epigenetic Changes in Melanoma and
the Development of Epigenetic Therapy for Melanoma 19
Duc P. Do and Syed A.A. Rizvi
Chapter 3 Genetic, Epigenetic and Molecular Changes in Melanoma:
A New Paradigm for Biological Classification 35
Stefania Staibano, Massimo Mascolo, Maria Siano,
Gennaro Ilardi and Gaetano De Rosa


Part 2 Therapeutics 69
Chapter 4 A Bromophosphonate Analogue
of Lysophosphatidic Acid Surpasses Dacarbazine
in Reducing Cell Proliferation and Viability
of MeWo Melanoma Cells 71
Duy Nguyen, Oanh Nguyen, Honglu Zhang,
Glenn D. Prestwich and Mandi M. Murph
Chapter 5 Low-Anticoagulant Heparins in the
Treatment of Metastasis 81
Narayanam V. Rao, Glenn D. Prestwich,
John R. Hoidal and Thomas P. Kennedy
Chapter 6 Novel Antifolates as Produgs for the
Treatment of Melanoma 101
Jose Neptuno Rodriguez-Lopez, Luis Sanchez-del-Campo,
Magali Saez-Ayala, Maria F. Montenegro and
Juan Cabezas-Herrera
Chapter 7 The Potential of Triterpenoids in
the Treatment of Melanoma 125
J. Sarek, M. Kvasnica, M. Vlk, M. Urban,
P. Dzubak and M. Hajduch


Part 3 Molecular Signaling 159
Chapter 8 New Molecular Targets for
the Systemic Therapy of Melanoma 161
Kausar Begam Riaz Ahmed and Michael A. Davies
Chapter 9 BRAF V600E Mutated Gene Variant
as a Circulating Molecular Marker
in Metastatic Melanoma Patients 181
Viviana Vallacchi, Licia Rivoltini and Monica Rodolfo
Chapter 10 Ultraviolet Light as a Modulator
of Melanoma Development 197
Graeme Walker and Elke Hacker
Chapter 11 Dual Roles of the Melanoma CAM (MelCAM/METCAM)
in Malignant Progression of Melanoma 229
Guang-Jer Wu
Chapter 12 Dual Function of Wnts in Human
Cutaneous Melanoma 243
Ksenia Kulikova, Alexey Kibardin, Nikolay Gnuchev,
Georgii Georgiev and Sergey Larin
Chapter 13 A POU3F2-MITF-SHC4 Axis in Phenotype
Switching of Melanoma Cells 269
Thomas Strub, Dominique Kobi,
Dana Koludrovic and Irwin Davidson
Chapter 14 The Role of Cellular Differentiation
and Cell Fate in Malignant Melanoma 287
Paul Kuzel and Andy J. Chien


Part 4 Tumor Progression and the Microenvironment 309
Chapter 15 Role of Angiogenesis and Microenvironment
in Melanoma Progression 311
Roberto Ria, Antonia Reale and Angelo Vacca
Chapter 16 Stromal Microenvironment
Alterations in Malignant Melanoma 335
Svetlana Brychtova, Michala Bezdekova, Jaroslav Hirnak,
Eva Sedlakova, Martin Tichy and Tomas Brychta
Contents VII
Chapter 17 Current Insight Into the Metastatic Process
and Melanoma Cell Dissemination 361
Isabelle Bourgault-Villada, Michelle Hong, Karen Khoo,
Muly Tham, Benjamin Toh,Lu-En Wai and Jean-Pierre Abastado
Chapter 18 Increased Resistance of Vasculogenic Mimicry-Forming
Uveal Melanoma Cells against Cytotoxic Agents in
Three-Dimensional Cultures 377
Klara Valyi-Nagy, Andras Voros, Eva Gagyi and Tibor Valyi-Nagy
Chapter 19 The Role of Adhesion Receptors in Melanoma
Metastasis and Therapeutic Intervention Thereof 393
Michael Alexander and Gerd Bendas

Preface
This is an exciting time for the field of melanoma research. So far in 2011 the FDA has
approved two new immunotherapies against this malignancy and is likely to vote on a
targeted therapeutic soon. The clinical trials evaluating BRAF inhibitors are being
discussed at major symposia and appearing in popular news media. There hasn’t been
this much activity on melanoma therapeutics since 1998. For researchers it is particularly
exciting to see years of studying aberrant molecular mechanisms in the laboratory
translate into the clinic. The goal of scientists who tirelessly study mechanisms of disease
is this – to contribute to developing lifesaving interventions. Now is the time when this
dream is coming to fruition. Although the ability to cure every melanoma patient may
still be elusive, exploiting melanoma’s molecular weaknesses and observing dramatic
effects provides hope and confidence to researchers that it can be done.
Thus, this book on melanoma research provides a glimpse of many diverse scientific
aspects that are currently underway in melanoma research laboratories around the
world. Although the topics are different they all have the same goals, to develop better
understandings of malignancy and treatment methods. The sections of this book are
organized to reflect emerging trends in research, starting with epigenetics. The role of
epigenetics is under investigation in melanoma as well as other types of cancers. There
is much progress to be made in this complex area to help explain the etiology of
disease, a topic that patients always ask when attempting to pinpoint the source of
their cancer. In addition, a subsequent section contains work discussing emerging,
promising and much‐needed therapeutics. Although newer drugs have an enhanced
ability for treatment, they also suffer from chemoresistance development, a huge
clinical problem among other cancer types. Thus, there is still much work to be done in
the area of melanoma therapeutics.
In the section on Molecular Signaling, the manuscripts cover a broad range of areas.
The classical pathways are discussed, including BRAF, along with some emerging
proteins that are likely highly relevant to melanoma. This theme is continued with the
final section on Tumor Progression and the Microenvironment. Manuscripts organized
in this section are focused on angiogenesis, the tumor microenvironment and
metastasis. All of these reflect clinical problems in need of additional research,
whereby contributions aimed towards melanoma are likely to be translatable to
numerous cancer types.
This book would not have been possible without the help of several wonderful people.
These include Ana Pantar, Petra Nenadic, Juliet Eneh and Molly Altman. I would also
like to thank my spouse, Gary Rollie, who has always been incredibly supportive of
my career and dealt with me this past year as I worked on this project. I think he knew
when I said, “This will only take a few more minutes”, that it wasn’t true, but he
patiently understood that at some point I would finish.
Sincerely,
Mandi Murph, Ph.D.
Assistant Professor Department of Pharmaceutical and
Biomedical Sciences University of Georgia College of Pharmacy
Athens, GA,
USA