**Aurora Kinases: New Molecular Targets for the Therapy of Aggressive Thyroid Cancers Aurora Kinases: New Molecular Targets for the Therapy of Aggressive Thyroid Cancers**

Enke Baldini, Chiara Tuccilli, Salvatore Sorrenti, Domenico Mascagni, Stefano Arcieri, Angelo Filippini and Salvatore Ulisse Enke Baldini, Chiara Tuccilli, Salvatore Sorrenti, Domenico Mascagni, Stefano Arcieri, Angelo Filippini and Salvatore Ulisse

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64597

#### **Abstract**

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94 Anti-cancer Drugs - Nature, Synthesis and Cell

Epithelial thyroid carcinomas (TC) account for more than 90% of all endocrine malignancies and represent one of the most frequent cancers in women. They include the well-differentiated TC (DTC), comprising the papillary (PTC) and follicular (FTC) histotypes, the poorly differentiated (PDTC), and the undifferentiated or anaplastic TC (ATC). Both PDTC and ATC are aggressive human neoplasms with a dire prognosis due to the absence of effective therapies, which makes mandatory the identification of novel therapeutic strategies. Intrinsic chromosomal instability (CIN, an increased rate of gain or losses of chromosomes during cell division) is a common feature of solid tumors and represents a major driving force in thyroid cancer progression, thought to be responsible for the acquisition by malignant cells of novel functional capabilities. Different mitotic kinases, whose expression or function has been found altered in human cancer tissues, are major drivers of thyroid tumor aneuploidy. Among these are the three members of the Aurora family (Aurora-A, Aurora-B and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed with promising antitumor effects in preclinical and clinical studies against different human cancers, including TC. Here, we will focus on the Aurora mitotic functions in normal cells; we shall then describe the main implications of their overexpression in the onset of genetic instability and aneuploidy. We will finally describe the consequences of Aurora kinase inhibition on TC cell growth and tumorigenicity.

**Keywords:** thyroid cancers, Aurora kinases, mitosis, therapy, Aurora kinase inhibitors

© 2016 The Author(s). Licensee InTech. This chapter is 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. © 2016 The Author(s). Licensee InTech. This chapter is 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.


**1. Introduction**

The process of the coating deposition is very complex and undoubtedly stochastic [1–7]. Accordingly, the modeling of the coating deposition process is also a complex and many-sided challenge, and in some cases, a probabilistic approach is required to meet this challenge [3–7]. Initially, one of the key tasks for the modeling of the processes under consideration was to predict a thickness of a coating, including a coating deposited on a complex-shape surface. To meet the above challenges, physical and geometric methods were applied, which made it possible to achieve the certain prediction accuracy. In particular, the studies proposed the coating thickness uniformity model [8,9], the cosine analytical and generic computational model [10], and the inverse power law relationship between thickness and source-to-substrate distance was considered [11]. Recent studies also applied true line-of-sight models, based on the inverse square law and also taking into account the effect of shadow masks [12]. In [13], the computational level set method was also applied for tracking topographic change of a surface.

The traditional approaches to the modeling of mass transfer processes, in particular, the coating deposition processes, have significant limitations when described in micro- and mesosystems [14,15]. In connection with the above, the processes are often modeled on micro- nano- and atomic levels, due to the integration of systems with a large number of particles, the motion of which is described, in particular, by equations of molecular dynamics of Newtonian mechanics. A significant problem of these methods is the existing limitation of the maximum number of particles in a system due to the limit of computing power.

Approaches of molecular dynamics are used to model the deposition process [16]. By simulating the interaction of individual atoms, this method makes it possible to predict the morphology, thermal and electronic properties, and also internal stresses of the coating being deposited. When the above method is applied, the forces of interatomic interaction are presented in the form of classical potential forces. The configuration sets obtained in the course of the calculations using the method of molecular dynamics are distributed in accordance with a certain statistical distribution function, for example, a one corresponding to microcanonical distribution. The exact information concerning the trajectories of system particles at large time intervals is not necessary to obtain results of a macroscopic (thermodynamic) nature [17]. The principals of molecular dynamics can be applied to simulate the coating deposition process using dynamic equations and pressure and temperature boundary conditions for substrate and coating surfaces, taking into account the results of the preliminary study of stresses in the coating.

In particular, to model the coating deposition process, the Particle-in-Cell Monte Carlo simulation method [3,4], with both modeling options of simpler 2D [5] and more complex 3D [6–8], requiring advanced computing power, is applied. During the comparison of 2D and 3D models, it was found that the main difference between two-dimensional and three-dimensional options of modeling was consideration of the effect of propagating plasma waves that had a significant influence on the properties of particle transport in discharges limited by a magnetic field. Two-dimensional modeling provides useful qualitative information about the general trends and mechanisms of magnetron discharges, while three-dimensional modeling makes it possible to quantitatively describe the electron transfer and current–voltage characteristics [18]. Based on the results of 2D modeling using the Monte Carlo algorithm, the formation of a coating with feather-like hierarchical structure was demonstrated in [19]. The results of the study focused on the development of a columnar coating structure have proved that the average distance between columns first increases sharply and then stabilizes due to cessation of the growth and regeneration of the structure. The Monte Carlo methods were applied for 2D modeling of the process of micropore formation in a coating, given the stochastic nature of the process [20]. Approaches of computational fluid dynamics were also applied, they give a much rougher description of the process, but at the same time contribute to a noticeable reduction in the amount of calculations, thus making it possible to introduce modeling in the 3D geometry with high-scale detailing [21,22]. A more detailed analysis of various methods for modeling the coating deposition process can be found in [23]. Thus, the most accurate and complete simulation of the deposition process should take into account the stochastic nature of this process and consider the molecular level, because a coating is formed precisely at this level. Several studies [24–26] consider a cluster, hierarchical structure of the coating, deposited through various methods, and the influence of the deposition process parameters on the formation of such structure. However, the influence of the parameters of the nanolayer coating structure on the formation of hierarchical structures in the coating requires an additional study.


**4.1 Physical characteristics of GCs in Ibadan**

This section aims to describe the physical characteristics of GCs in the study areas. In other to achieve this, 10 randomly selected experts from academia and practising firms who are members of Nigeria Institute of Architects and who are conversant with the study areas were selected for the study. The selection requirements for the panel are that such personality must be a design expert and urban planner from academia in addition to professional practice based on their technical know-how and proficiency. These were selected from catalogue of Architect Registration Council of Nigeria (ARCON). These experts comprehensively and objectively measured the subjective physical characteristics of the neighbourhood using ratings from an expert panel from the variables that comprised: the four (4) key elements of physical characteristics which are territoriality, surveillance, milieu and image. These were used as parameters in describing the characteristics of the study areas. This means that the study measured these elements in the areas to be able to describe the characteristics of each area.


**ADVANCEMENTS IN ENERGY STORAGE TECHNOLOGIES**

Edited by **Xiangping Chen** and **Wenping Cao**

#### **Advancements in Energy Storage Technologies**

http://dx.doi.org/10.5772/intechopen.68717 Edited by Xiangping Chen and Wenping Cao

#### **Contributors**

Adio Miliozzi, Raffaele Liberatore, Daniele Nicolini, Elisabetta Veca, Manila Chieruzzi, Tomaso Crescenzi, Luigi Torre, Youngil Kim, Robert J. Harrington, Rached Dhaouadi, Kamyar Khosravi, Yoichi Hori, Sang Jae Kim, Ananthakumar Ramadoss, Balasubramaniam Saravanakumar, Amjad Anvari-Moghaddam, Jeremy Dulout, Corinne Alonso, Bruno Jammes, Josep M. Guerrero, Uroš Stritih, Dragan Stevanovic, Alessandro Serpi, Mario Porru, Alfonso Damiano

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