**5.4 Palliative chemotherapy for metastasis and relapses NPC**

Palliative chemotherapy is very important and plays role in control of disease and keep patients in good conditions as well as in extending survival of patients with NPC metastases as NPC is very sensitive to chemotherapy cancer. Standard treatment includes chemotherapy with platinum in combination with other drugs such as 5-FU with cisplatin/carboplatin and paclitaxel with gemcitabine. Patients treated for long time with platinum chemotherapy, can achieve a significant response with rates of up to 80% and an average survival rate of 12 to 18 months [77]. There is a significant correlation between higher response rates with a combination therapy regimen than monotherapy, and platinum is a good treatment, but it is not the main criterion or standard treatment. Regardless of the treatment regimen chosen for the first line, the average progression time after 7 to 10 months remains relatively constant [78, 79]; This is related to the development of platinum resistance. The response rates for a triple therapy with paclitaxel/carboplatin/ gemcitabine are impressive and close to 80%. However, the average response time is about 8 months, similar to two drug regimens [80].

#### **5.5 Novel therapies: molecular-targeted agents**

The past 10 years have seen the development of new treatments for NPC and this has been somewhat simultaneous with the development of treatment for other cancers. Little progress has been made in recent years beyond the usual cytotoxic approaches. EGFR-mediated signaling pathways inhibited by the molecular factors that lead to inhibition of cell growth and cell apoptosis which include tyrosine kinase inhibitors, for example gefitinib and monoclonal antibodies [81].

In a number of centers, Ueda and colleagues [82] investigating a combination treatment of carboplatin, paclitaxel and cetuximab in patients with metastatic or recurrent or with repeated platinum-resistant NPC showed good survival benefit, an overall response rate reach to 64 % and a median OS of 29.1 months with follow up for 30 months. The treatment with gefitinib had little response rates in

metastatic and recurrent NPC treated previously with platinum-based chemotherapy. The symptomatic improvement and disease stabilization were observed in some cases [83].

Multikinase inhibitors target tyrosine kinases such as fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR) and drugs such as pazopanib (VEGFR, PDGFR, FGFR, c-KIT), sorafenib (VEGFR, PDGFR, Raf kinases), and sunitinib (PDGFR, VEGFR, C-KIT), have been evaluated in NPC [84, 85].


Preface

Atopic Dermatitis is a common disease characterized by inflamed, itching and dry skin. This relapsing allergic disorder has complex etiology and shows a remarkably high clinical heterogeneity which complicates the diagnosis and clinical management.

This book is divided into 4 sections. The first section (Disease Etiology) describes some of the physiological mechanisms underlying Atopic Dermatitis, including alterations in the immune system and the skin-barrier function. The important role of host-microorganism interactions on the pathophysiology of Atopic Dermatitis is discussed in the second section (Microorganisms in Atopic Dermatitis). An overview of the clinical diagnostic criteria and the disease management protocols commonly used is given in the third section (Diagnosis and Clinical Management). The last section (New Treatments) describes new therapeutic approaches that are not widely used but are currently being studied due to preliminary evidence showing a clinical benefit for Atopic Dermatitis.

As a co-editor, it was my greatest pleasure to work with Dr Jorge Esparza-Gordillo on this book, which handles cutting-edge ideas on atopic dermatitis, provided by ambitious specialists. Every chapter is a real pearl of the subject, and as a clinicianscientist, I was delighted to read the manuscript one by one. I believe clinicians and researchers worldwide will benefit from this book as a unique free online publication.

Thanks to Ms. Bojana Zelenika and Mr. Dejan Grgur of InTech - Open Access Publisher, this book is published with a very quick publication process, and will thus reach the reader with the latest information. Last but not least, I thank my wife Shoko for her enormous support during this project.

> **Itaru Dekio, MD, PhD**  Department of Dermatology, Faculty of Medicine, Shimane University, Izumo, Japan

**Part 1**

**Disease Etiology**

**Part 1**

**Disease Etiology**

**1**

*Japan*

**Flaky Tail Mouse as a Novel Animal Model of**

 **in the Development of Atopic Dermatitis**

*Department of Dermatology, Kyoto University Graduate School of Medicine*

Catharina Sagita Moniaga and Kenji Kabashima

**Atopic Dermatitis: Possible Roles of Filaggrin**

Understanding of human diseases has been enormously expanded by the use of animal models, because they allow for in-depth investigation of pathogenesis and provide invaluable tools for diagnostic and pharmaceutical purposes. Atopic dermatitis (AD) is a chronic, relapsing form of skin inflammation, a disturbance of epidermal-barrier function that culminates in dry skin, pruritus, and IgE-mediated sensitization to food and environmental allergens (Bieber, 2008, Mori, et al., 2010, Tokura, 2010). AD is a common disease with no satisfactory form of therapy; therefore, understanding the mechanism of AD through animal models is an urgent issue to be solved (Jin, et al., 2009, Matsuda, et al., 1997, Shiohara, et al., 2004). The complexity and variability of AD and multiple genetic and environmental factors underlying AD make creating a reproducible, accessible, and relevant

Thus far, a number of mouse models have been developed. These models can be categorized into three groups: (1) models induced by epicutaneous application of sensitizers; (2) transgenic mice that either overexpress or lack selective molecules; and (3) mice that spontaneously develop AD-like skin lesions. These models display many features of human AD, and their studies have resulted in a better understanding of the pathogenesis of AD. They allow for an in-depth dissection of the mediators and cells that are critical for the

Located at the interface between the body and the environment, the epidermis is an elaborate structure that shares few properties with other biological barriers. Key functions include providing physical and biochemical protection (O'Regan &Irvine, 2010), and playing important roles in host defense, inflammation, and regulation of immune responses (Schleimer, et al., 2007). Patients with AD exhibit impaired skin barrier functions and abnormal structure and chemistry of the stratum corneum (SC) (Leung &Bieber, 2003). Alteration of the skin barrier in AD is evidenced by reduction in the water content of the SC and by increased transepidermal water loss (TEWL) (Aioi, et al., 2001). Skin barrier dysfunction has emerged as a critical driving force in the initiation and exacerbation of AD and as "driver" of disease activity (Cork, et al., 2009, Elias, et al., 2008), although it has once

Elias et al. proposed the outside-to-inside pathogenic mechanisms in AD for the following reasons: (1) the extent of the permeability barrier abnormality parallels the severity of the

animal model of AD particularly challenging (Scharschmidt &Segre, 2008).

been noted as a disease of immunological etiology (Leung &Bieber, 2003).

development of allergic responses (Jin, et al., 2009).

**1. Introduction**