Open Access Medical Books

MALIGNANT MESOTHELIOMA

MALIGNANT MESOTHELIOMA
Edited by Carmen Belli and Santosh Anand .

Malignant mesothelioma (MM) is a highly invasive tumor arising from the mesothelial 
cells of serosal surfaces. It shows an extremely poor progression and is diagnosed 
mostly in locally advanced or metastatic stage, thus drastically limiting its treatment 
options. Past asbestos exposure has been shown to be the most important predictor of 
MM, although other environmental and genetic factors like Simian Virus-40 (SV-40) 
infection and genetic predisposition might also play important roles.
This book brings together the knowledge of experts in the filed of malignant 
mesothelioma who provide their invaluable insights into this deadly disease from 
different perspectives.
The book starts with a tour de force account of MM epidemiology in South Africa (SA) 
by scholars who have spent major part of their professional careers working in this 
field. In a gripping tell-a-tale, they recall how South Africa benefitted financially from 
the exploitation of its asbestos mineral reserves, but at a huge cost of human lives due 
to asbestos related diseases, including MM and lung cancer. South Africa plays a 
historically important role in our understanding of epidemiology of MM, thanks 
mainly to the seminal work by Dr. J. C. Wagner who showed definitive link between 
asbestos exposure and mesothelioma. In this chapter, the authors give a detailed 
account of the cases of mesothelioma in South Africa meticulously linking them to 
different forms of asbestos exposure (both occupational and non-occupational). They 
further dissect the carcinogenic potentials of the most common asbestos fibers mined 
in SA. There are many important lessons to be learnt from this SA experience, aptly 
summarized at the end of this chapter.
In the next chapter, Yasumitsu Nishimura et al. describe in detail the anti-tumor 
immunity and immunological alterations in MM, a hitherto neglected but nevertheless 
important aspect of MM-geneis. The authors show that exposure to asbestos might 
cause a suppressive effect on anti-tumor immunity in addition to the tumorigenic 
effect on mesothelial cells. This 'immunological' insight could not have come at a better 
time as only recently it is shown that blockade of PD-1, an inhibitory receptor 
expressed by T cells, gives promising therapeutic results in patients of many advanced 
cancers (Suzanne L. Topalian et al., and Julie R. Brahmer et al.; NEJM, 2012).
In the following chapter, Loredana Albonici and colleagues describe the roles of 
inflammation and angiogenic growth factors in MM. Angiogenesis plays a key role in 
the growth of any tumor as shown by the seminal work of Judah Folkman in 1971.
Here the authors go beyond this basic fact by showing that asbestos driven 
inflammation plays an important role in MM and that there is a cross-talk between 
inflammation and angiogenesis in the genesis and progression of MM. They describe 
how mesothelial cells work as sentinels sensing a variety of signals and stimuli, 
including asbestos fibers. In response, the mesothelial cells can release a host of 
chemokines, cytokines and reactive oxygen and nitrogen species, thus triggering
chronic inflammatory reactions potentially leading to MM. The authors show in great 
details the roles of various transcription factors like NF-kB, AP-1 and NFAT in this 
process. Furthermore, they also explore the roles of various angiogenic growth factors, 
many of which could be potential targets for therapy.
The penultimate chapter by Rossella Galati links the inflammation in MM to upregulation 
of the inducible cyclooxygenase-2 (COX-2), leading to an increase in its 
product prostaglandin-E2 (PGE-2), which in turn is associated with increased risk of 
cancers. The author describes the complex interaction between COX-2, EGFR and 
Aromatase (CYP19A1), which has the potential to open new therapeutics in MM.
The last chapter by Giulia Pasello and Adolfo Favaretto describes neoadjuvant 
chemotherapy in malignant pleural mesothelioma (MPM). In this deadly malignancy 
that is refractory to almost all treatments, the possibility to pursue novel and rational 
strategies is extremely exciting. The chapter begins with the rationale of neoadjuvant 
therapy, followed by the current path to neoadjuvant chemotherapy in MPM. It 
culminates in an extensive review of various neoadjuvant chemotherapeutic regimens 
and strategies in MPM.
We would like to thank all the contributing authors for making this book possible. Our 
special thanks goes to publishing process managers Ms. Sandra Bakic, Ms. Martina 
Blecic and Mr. Vedran Greblo for their continuous help during the entire process. We 
would like to dedicate this book to the readers in the hope that they will find it useful 
in the ultimate quest for the cure of malignant mesothelioma.

Carmen Belli and Santosh Anand
San Raffaele Hospital, and San Raffaele Scientific Institute, Milan,
Italy

CONTENTS :
Chapter 1 Mineralogy and Malignant Mesothelioma: 
The South African Experience 1
James I. Phillips, David Rees, Jill Murray and John C.A. Davies

Chapter 2 Effect of Asbestos on Anti-Tumor Immunity and Immunological Alteration in Patients
with Malignant Mesothelioma 31
Yasumitsu Nishimura, Megumi Maeda, Naoko Kumagai-Takei, Hidenori Matsuzaki, Suni Lee, Kazuya Fukuoka, Takashi Nakano, Takumi Kishimoto and Takemi Otsuki

Chapter 3 Role of Inflammation and Angiogenic Growth Factors 
in Malignant Mesothelioma 49
Loredana Albonici, Camilla Palumbo and Vittorio Manzari

Chapter 4 The Role of Cyclooxygenase-2, Epidermal Growth Factor 
Receptor and Aromatase in Malignant Mesothelioma 79
Rossella Galati

Chapter 5 Neoadjuvant Chemotherapy in Malignant Pleural Mesothelioma 93
Giulia Pasello and Adolfo Favaretto .


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