Preface

Well-differentiated cellular elements, tissues, and organs can originate from the cells of the neural crest. The multipotent differentiation potential of these cell lines is well known, and therefore it is not surprising that the tumors derived from them represent a group of heterogeneous neoplasms. These neoplasms can arise in localizations of the body where cells derived from the neural crest are normally present; however, they can also occur in unusual tissues and locations and in this case, the explanation could be associated with the presence of stem cells that have been shown to be present also in tissues not originating from the neural crest. The classification of tumors derived from neural crest cells has undergone various changes over time. Previously some tumors had been declared of neural crest origin, such as neuroendocrine tumors of the gastrointestinal tract, but a different embryological origin was subsequently demonstrated. Primitive neuroectodermal tumors have always been considered to originate from the cells of the neural crest, but their origin is still unknown today. Pheochromocytoma, paraganglioma and neuroblastoma are the most common neural crest-derived tumors in adults and children, respectively. These neoplasms are associated with significant morbidity and mortality. Although these tumors have different clinical manifestations, courses, and prognoses, their origin can be considered common. Various genetic studies are underway to identify their similarities and differences. Currently being investigated is the role of Stathmin 1 signaling in the pathogenetic mechanism of neuroblastoma and pheochromocytoma, such as the relevance of the PHOX2B gene. Protein is still being studied in the pathogenesis of pheochromocytoma, despite having a fundamental role in the development of precursor cells derived from the neural crest. In this book, we review the current concept of neural crest-cells derived tumors, focusing on pheochromocytoma/paraganglioma and neuroblastoma. In conclusion, I would like to thank everyone who has helped and supported us in this ambitious, long, and demanding job.

**II**

**Chapter 7 99**

Targeting MYC and HDAC8 with a Combination of siRNAs Inhibits Neuroblastoma Cells Proliferation In Vitro and In Vivo Xenograft

Tumor Growth *by Nagindra Prashad*

**Pasquale Cianci**

University of Foggia, Department of Surgery and Traumatology, ASL BAT, Andria, Italy

> **Enrico Restini** "Lorenzo Bonomo" Hospital, ASL BAT, Andria, Italy

**Amit Agrawal** All India Institute of Medical Sciences, India

**1**

Section 1

Introduction

Section 1 Introduction

**3**

**Chapter 1**

Introductory Chapter:

Neural Crest Cell-Derived

Tumors. An Introduction

*Pasquale Cianci, Giandomenico Sinisi and Sabino Capuzzolo*

In the embryonic period, the nervous system originates from a layer of ectodermal cells which is called neuroectoderm. The neuroectoderm extends along the axis of the body to form the neural plate. The latter, turns inward and surrounds itself of neural folds, which then merge together giving life to the neural tube that will develop all the components of the central nervous system and the spinal cord. Finally, from the posterior portion of the neural tube, specialized cells will separate to form the neural crest. Various differentiated cell types, tissues and organs develop from neural crest cells, the mechanisms for this are not well known. However, these cells are multipotent and their subsequent specialization it could be conditioned by the activity of particular genes and by the microenvironment into which they migrate [1]. Hence, neural crest cells have a multipotent differentiation potential. From these cells originate neurons and glial cells, melanocytes, Schwann cells, parafollicular cells of the thyroid, cells of the adrenal medulla, endothelial cells of large vessels and some components of the connective and skeletal tissue of the head [2] (**Figure 1**). Based on these concepts, the tumors that develop from the cells of the neural crest represent a very varied and heterogeneous group of neoplasms, these can affect different body locations where the neural crest cellsderived are normally present. However, neural crest stem cells are also present in some adult tissues that normally do not originate from the neural crest, such as skin and bone marrow [3]. Heterogeneity of tumors originating from neural crest cells is confirmed by the fact that some of them can arise in both peripheral sites or in the central nervous system, while others are specific to the central nervous system or affect only other peripheral locations. Neural crest cell-derived tumors can be grouped into: tumors of peripheral and cranial nerves, melanocytic tumors, peripheral neuroblastic tumors, embryonal tumors of the central nervous system, paraganglioma group, and other tumors of neural crest origin. Most of these are sporadic, some can be hereditary (hereditary paraganglioma-pheochromocytoma syndrome, von Hippel–Lindau disease, neurofibromatosis, schwannomatosis, and multiple neuroendocrine neoplasia (MEN I). Pheochromocytoma/Paraganglyoma

on Pheocromocytoma,

Paraganglyoma and

Neuroblastoma

**1. Introduction**
