**Author details**

Yasumitsu Nishimura, Megumi Maeda, Naoko Kumagai-Takei, Hidenori Matsuzaki, Suni Lee and Takemi Otsuki *Department of Hygiene, Kawasaki Medical School, Japan* 

Megumi Maeda *Division of Bioscience, Department of Biofunctional Chemistry, Graduate School of Natural Science and Technology, Okayama University, Japan* 

Kazuya Fukuoka and Takashi Nakano *Department of Respiratory Medicine, Hyogo College of Medicine, Japan* 

Takumi Kishimoto *Okayama Rosai Hospital, Japan* 

#### **5. References**

44 Malignant Mesothelioma

malignant mesothelioma.

**Acknowledgment** 

KENKYU JOSEI-2).

**Author details** 

Megumi Maeda

Takumi Kishimoto

*Okayama Rosai Hospital, Japan* 

Yasumitsu Nishimura, Megumi Maeda,

*and Technology, Okayama University, Japan* 

Kazuya Fukuoka and Takashi Nakano

*Department of Hygiene, Kawasaki Medical School, Japan* 

Naoko Kumagai-Takei, Hidenori Matsuzaki, Suni Lee and Takemi Otsuki

*Department of Respiratory Medicine, Hyogo College of Medicine, Japan* 

*Division of Bioscience, Department of Biofunctional Chemistry, Graduate School of Natural Science* 

mesothelioma. These findings suggest that those characteristic functional alterations of NK and Th cells shown in patients with malignant mesothelioma might be caused by inhaled and accumulated asbestos in the body. Furthermore, they also suggest the possibility that decreases in NKp46 on NK cells and CXCR3 on Th cells might contribute to early diagnosis of malignant mesothelioma as markers to monitor asbestos-related immune suppression. Today, the diagnosis of malignant mesothelioma is dependent on X-ray and CT image analyses, as well as pathohistological analysis, but these procedures involve several problems such as difficulty in obtaining a consistent diagnosis and a risk of radiation exposure or invasiveness. In contrast, the drawing of blood necessary for analysis of immunological markers is safe and easy, and can be performed frequently during a year. Therefore, imaging and pathohistological analyses of malignant mesothelioma combined with immunological analysis for expression of NKp46 and CXCR3 might provide more valuable information for people who are exposed to asbestos and worry about the development of malignant mesothelioma. Further studies regarding the immunological effect of asbestos exposure will contribute to the effective diagnosis and therapy of

We thank Dr. Y. Yodoi for generously providing YT-Al cells, and Ms. Tamayo Hatayama, Satomi Hatada, Yoshiko Yamashita, Minako Kato, Tomoko Sueishi, Keiko Kimura, Misao Kuroki, Naomi Miyahara, and Shoko Yamamoto for their technical help. This study was supported by Special Coordination Funds for Promoting Science and Technology (H18-1-3- 3-1), JSPS KAKENHI Grants (19790431, 18390186, 19659153, 19790411, 20890270, 20390178 and 22700933), The Takeda Science Foundation (Tokutei Kenkyu Josei I, 2008), Kawasaki Medical School Project Grants (18-209T, 19-407M, 19-603T, 19-205Y, 19-506, and 20-210O), and The Kawasaki Foundation for Medical Science and Medical Welfare (KYOIKU


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**Chapter 3** 

© 2012 Albonici et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2012 Albonici et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Role of Inflammation and Angiogenic Growth** 

Malignant mesothelioma (MM) is a highly aggressive tumor which arises from the mesothelial cell lining of the serosal surfaces, most cases (>90%) being of pleural origin (Attanoos & Gibbs, 1997; Robinson & Lake, 2005). The pathogenesis of MM has been mainly associated with previous asbestos exposure (Berman & Crump, 2008), with a latency period of up to 40 years, although other agents such as Simian virus 40 (SV40) or genetic susceptibility factors have been linked to the development of this tumor (Carbone et al., 2002; Pisick & Salgia, 2005). Indeed, human mesothelial cells are highly susceptible to SV40 mediated transformation *in vitro* and SV40 DNA sequences and large T antigen (Tag) have been detected in human MM cells (Bocchetta et al., 2000; Carbone et al., 2012; Gazdar et al.,

MM is largely unresponsive to conventional chemotherapy or radiotherapy and, despite its low metastatic efficiency, it is highly invasive to surrounding tissues so that its extensive growth leads to the failure of the organs underlying the serosal membranes (Astoul, 1999). In fact, the primary cause of fatality in MM is related to the propensity of the tumor cells to invade locally, even though MM metastasis are more common after surgery and, at the autopsy, metastatic diffusion is observed in 50% of patients (Astoul, 1999). At present, the

The mesothelium is not just a passive protective surface, but a highly dynamic membrane (Mutsaers, 2004). It consists of a single layer of elongated, flattened, squamous-like cells of mesodermal origin, characterized by dual epithelial/mesenchymal features. Cuboidal mesothelial cells can also be found at various locations in physiological conditions. Further, mesothelial cells can adopt a cuboidal morphology, which reflects a metabolically activated state, after injury or stimulation of the serosal surface (Mutsaers, 2004). Indeed, mesothelial cells are sentinel cells that can sense and respond to a variety of signals within their

median survival from diagnosis of MM is less than two years (Palumbo et al., 2008).

**Factors in Malignant Mesothelioma** 

Loredana Albonici, Camilla Palumbo and Vittorio Manzari

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/47951

**1. Introduction** 

2003).

