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Carcinogens are substances that induce cancer by damaging the genome or through disruption of cellular metabolic processes. Some compounds interact directly with DNA, while others are activated to reactive molecules that can bind with DNA by covalent adducts causing mutations in genes crucial to biological processes. Cigarette smoke is by far the most important and notorious carcinogen. Cigarette smoke contains many carcinogenic substances including polycyclic aromatic hydrocarbons (PAHs), which are known to cause cancer. Nitrites, which are present in many foods, are converted into nitrous acid in the stomach and may then react with amines in food to produce nitrosamines, which are carcinogenic. Aflatoxins produced by Aspergillus flavus are promoter for hepatic cancer. Several cytotoxic drugs are carcinogens especially alkylating agents that interact with DNA. Individuals exposed to certain pesticides may be at risk to the development of certain cancers. Inorganic arsenic exposure has been suggested to be associated with the development of several cancers. Sufficient evidence indicated an association between dioxins and various cancers including soft tissue sarcoma, lymphoma and leukemia. Asbestos has been found to be significantly associated with lung cancer and mesothelioma.

Skin cancer is the most commonly diagnosed malignancy in the United States and worldwide. While melanoma is the deadliest form of skin cancer, non-melanoma skin cancers, which include basal cell carcinoma and squamous cell carcinoma, are responsible for significant morbidity in millions of Americans each year. While numerous attempts have been made to reduce skin cancer risk factors related to ultraviolet radiation exposure, skin cancer incidence continues to rise. Improved understanding of the molecular pathways underlying skin cancer pathogenesis has led to the investigation of new approaches to skin cancer prevention. In particular, the search for ultraviolet radiation associated biomarkers of skin cancer has become a rapidly expanding and promising area of research. Advances in genetic sequencing have facilitated the discovery of novel biomarkers, which have the potential to profoundly improve patient care. Here we will review the molecular genetics of skin cancer and analyze the existing literature of proposed biomarkers for potential use in skin cancer diagnosis and prevention.

Diffuse intrinsic pontine glioma (DIPG) is a leading cause of brain cancer-related death in children. These aggressive high-grade gliomas cannot be effectively treated and are associated with dismal prognosis. Whilst radiation therapy (RT) prolongs survival, it is a palliative therapy, as half of children with DIPG die within 1 year of diagnosis and almost all are dead by 2 years. These statistics have not changed for decades, despite a multitude of clinical trials. No chemotherapeutic regimen has been shown to improve survival, emphasizing the need to find novel and effective treatments. One of the principal reasons for this poor outcome was our limited knowledge of the biology of DIPG’s. Due to their location in brainstem, surgical resection is not feasible and up until recently, even performing a limited biopsy was considered too dangerous. In the last decade, DIPG tumor tissue has become available through autopsies and biopsies. This combined with the genome revolution has resulted in a transformation in our understanding of the underlying biology of this disease. Moreover, viable DIPG cells can now be grown in the laboratory which have allowed development of in-vitro (neurospheres) and in-vivo models (allograft and xenograft). This chapter summarizes recent advances in DIPG and potential novel therapies.

Pollution of indoor and outdoor air has considerably been taken attention abroad as an important environmental problem, and there is sufficient evidence that exposure to outdoor air pollution causes lung cancer and other cancers. Therefore, the current situation of air pollution will be deeply discussed, and a portable environmental gas monitor integrated by a variety of highly sensitive sensors will be developed for rapidly monitoring air pollution, which is able to provide scientific data for environmental pollution control. By this way, human beings are able to be far away from cancer caused by environmental pollution and its suffering.

There has been increased concern surrounding exposure to heavy metals due to the evolving understanding of their role in the development of cancer. This review highlights research related to the impact that heavy metals aluminum, arsenic, beryllium, cadmium, lead, mercury, nickel and radium have on human health. Research was collected through PubMed, and it was compiled to assess the current knowledge of exposure sources, types of cancers induced and therapeutic measures for these metals. Furthermore, it was designed to assist in guiding future research efforts with respect to heavy metals and cancer.

Craniopharyngiomas (CPs) have had a prominent place in neurosurgery due to both the technical difficulty and controversy regarding the optimal treatment of these benign tumors. Harvey Cushing famously described craniopharyngiomas in 1936 as “the most forbidding of the intracranial tumors.” Seventy years later, Rutka still wrote: “There is no other primary brain tumor that evokes more passion, emotion, and as a result, controversy than does the CP.” Craniopharyngiomas comprise 1–2% of all brain tumors and occur in a bimodal distribution, with 40% of cases occurring between age 5–15 years and 60% occurring at ages >55 years. The differential diagnosis for craniopharyngioma can include a variety of entities, including pituitary macroadenoma, metastasis, Rathke’s cleft cyst, colloid cyst, glioma, meningioma, germinoma, abscess, sarcoid, or aneurysm. Imaging characteristics usually include a solid cystic lesion, speckled with calcifications in 50–80% of craniopharyngiomas (especially pediatric patients), as well a presentation with hypopituitarism and diabetes insipidus, which influence clinical thinking toward establishing this diagnosis.

Background: Topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) as precursors of protoporphyrin IX (PPIX) have been used in skin cancer treatment and other skin diseases. To establish new topical PDT, protocols are necessary first to conduct studies in vivo using animal skin models. The goal of this study is to evaluate the robust correlation between porcine and human skin models in vivo by optical methods to confirm the suitability of porcine skin models to predict drug behavior in the human skin on topical PDT protocols. Methods: The study was performed in vivo using porcine and human skin models. In human skin, ALA and MAL cream mixture samples were applied to the inner arm in a circular area of 1 cm2. In porcine skin, the cream was applied on the back in an area of 4 cm2, over which an occlusive dressing was placed. PPIX production was monitored for up to 5 h using widefield fluorescence imaging and fluorescence spectroscopy techniques. Results: Human skin models showed similar behavior to porcine skin models, which indicates high similarity between both models and confirms that porcine skin is an adequate model to establish new clinical PDT protocols in human volunteers.

Glioblastoma (also called glioblastoma multiforme – GBM) is a primary brain neoplasm, representing about 55% of all gliomas. It is a very aggressive and infiltrative tumor. Glioblastoma is usually highly malignant, with more than 90% 5-year mortality and a median survival of about 14.6 months. Compared to other cancers, the survival rate has not greatly changed over time and no current treatment is curative for this disease. Because the tumor has a heterogeneous cell population containing several types of cells, the treatment for GBM is one of the most challenging in clinical oncology. This chapter will discuss the current approaches in glioblastoma treatment, including resection techniques, chemotherapy and radiation therapy.

The commonest saying goes as “cancer has no answer,” we have really come a long way in that aspect. From being able to detect and diagnose the disease early, effective treatment modalities, improvement in therapeutic outcome and even effective palliative measures. The research focus emphasized upon detecting preventable risk factors. Tobacco a Global culprit is often discussed as the most important risk factor for cancer. Modern day life and with its so-called stress measures are the ones often been blamed without a concrete scientific evidences. Psychological makeup of a person, emotional stress and cellular phones are intricately associated with a modern lifestyle. In this chapter we would be focusing upon the causal relationship between these factors and malignancy with available scientific literature. At the end we would present possible measures to avoid them and any future research areas to be looked upon.

This chapter presents an overview of possibilities for the therapy of melanoma, current knowledge and future direction. Skin cancer is one of the most frequent types of cancers. Melanoma is much less common than basal cell and squamous cell skin cancers, but it is far more dangerous. Detailed knowledge of melanoma at the molecular level allows to develop new treatment alternatives and to design effective new drugs. There are two approaches in therapy of melanoma in the present based on immunotherapy and targeted therapy or their combination. Immunotherapy includes immune checkpoint blockades, whereas targeted therapy is represented by protein kinase inhibitors, such as BRAF inhibitors, MEK inhibitors, and NRAS inhibitors. Detailed knowledge of protein structure and the understanding of its role in key signaling pathways in melanoma development lead to the designation of new protein kinase inhibitors in targeted therapy.

Gliomas develop genetic traits to rapidly form aggressive phenotypes. Hence, management of gliomas is complicated and difficult. Besides genetic aberrations such as oncogenic copy number variation and mutations, alternative mRNA splicing triggers prooncogenic episodes in many cancers. In gliomas, we found alternative splicing at the KCNMA transcription process. KCNMA1 encodes the pore forming α-subunit of large-conductance calcium-activated voltage-sensitive potassium (BKCa) channels. These channels play critical role in glioma invasion and proliferation. We identified a novel KCNMA1 mRNA splice variant with a deletion of 108 base pairs (KCNMA1v) mostly overexpressed in high grade gliomas. We found that KCNMA1 alternative pre-mRNA splicing enhanced glioma growth, progression and diffusion. The role of KCNMA1 and its splicing as a critical posttranscriptional regulator of BKCa channel expression is presented in this chapter. Our research implies that high grade gliomas express KCNMA1v and BKCa channel isoform to accelerate growth and transformation to glioblastoma multiforme (GBM). We demonstrated that tumors hardly develop in mice injected with KCNMA1v transfected cell line expressing short-hairpin RNA (shRNA) compared to mice injected with KCNMA1v transected glioma cells. We conclude that targeting the KCNMA1 variants may be a clinically beneficial strategy to prevent or at least slow down glioma transformation to GBM.

Glioblastoma is the most aggressive brain tumor. Gene therapies, such as cytokine-based, suicide gene, and oncolytic virus therapies, are different types of treatments from chemotherapy such as using temozolomide as a standard treatment. However, overall survival was not prolonged in some clinical trials because of the low efficiency of gene transduction and viral infection. Neural stem cells (NSCs) have tumor trophic migratory capacity and can be cellular delivery vehicles of cytokines, suicide genes, and oncolytic virus. NSCs can be differentiated from embryonic stem cells. In addition, mesenchymal stem cells can be another cellular delivery vehicle. Recently, induced pluripotent stem cells (iPSCs) have been established. iPSCs are multipotent; hence, they can efficiently differentiate to NSCs and can possibly overcome ethical and practical issues in clinical application. In this study, current topics about stem cell therapy for malignant glioma are reviewed.

A vestibular schwannoma (VS) is a benign tumor that arises from the neurilemmal sheath of the vestibular nerve. VSs make up to 6–8% of all intracranial tumors and 70–80% of all cerebellopontine angle tumors. Three therapeutic options are currently considered for VS: expectant treatment, microsurgical resection, and radiosurgery. No class I evidence exists to support one treatment over the others, and some clinical aspects are usually taken into consideration in the decision-making process. Very few comparative studies published so far have addressed the clinical aspects supporting any one treatment modality. The pathology, diagnosis and treatment of VS are discussed in this chapter. Moreover, we aim in this chapter to discuss the results of the most recent clinical studies performed on different treatment strategies for VS. In addition, the results of the comparative studies between microsurgical and radiosurgical treatments for VS are discussed.

Squamous cell carcinoma (SCC) is the second most frequent non-melanoma skin cancer (NMSC) and carries with it a significant psychosocial and economic burden for both patients and health-care systems. Known risk factors for SCC include chronic ultraviolet (UV) exposure, chronic wounds and inflammation, exposure to certain chemicals and immunosuppression. The considerable risk of SCC recurrence and metastasis has driven the need for the discovery of new molecules that could explain the initiation and biological behavior of this type of NMSC. In this respect, proteomic research techniques have rapidly evolved and adapted in order to connect missing links and single out distinctive skin cancer biosignatures. Proteomic analysis of normal, dysplastic, and malignant keratinocytes appears to be promising in respect to SCC biomarker discovery, with the potential to aid in risk assessment, early detection, disease progression and development of novel targeted therapeutic agents. Identifying changes in the keratinocyte proteome pattern from normal to inflammatory and malignant cells will lead to the discovery of novel SCC biomarkers that could represent valuable tools for patient screening, diagnosis, management and follow-up.

Trigeminal schwannomas (TS) are rare entities occurring in various trigeminal nerve locations and present a peak incidence between the fourth and fifth decades of life, being more common in women. Patients usually present with symptoms of trigeminal nerve dysfunction. Depending on the tumor’s topography, various approaches might be used to obtain its gross total resection. Trigeminal schwannoma’s classification, nuances of the approaches, pathology, postoperative care, and outcomes are revised as follows. In conclusion, anatomical knowledge and the disease’s comprehension are essential when dealing with such lesions, and despite their rarity, we must be obstinately committed to the surgical technique and devoted to the patient’s functional postoperative outcome.

This chapter offers literary review of most frequently observed brain tumors in childhood. It offers basics of epidemiology, clinical presentation and diagnostics of most often occurring types of tumors according to new WHO classification of brain tumors from 2016 and emphasizes molecular biological characteristics and role of altered genes and genetic pathways in brain tumor etiology, classification and treatment. This review not only concentrates on gliomas, medulloblastomas and ependymomas, but also offers characterization of other less frequently observed lesions. Each tumor characteristics also contains basics of therapeutical possibilities of these lesions with focus on targeted and individually designed therapy according to molecular and genetic alterations found in tumor tissue sample.

Melanomas, which originate from melanocytic cells, mainly develop in the skin but can also arise at other body sites. The disease accounts for approximately 90% of deaths related to cutaneous tumors with late stage metastatic melanoma having a very poor prognosis of 6–9 month median survival for untreated patients. Research in the last decades resulted in ground-breaking discoveries of melanoma genetics and biology. High frequency mutations in genes like BRAF, NRAS and KIT, which lead to hyper-activation of the MAPK signaling pathway, drive melanoma progression. Targeting the MAPK signaling pathway has successfully been translated into effective therapies that significantly improve patient survival. Despite the unquestionable importance of such genetic events, the involvement of epigenetic alterations for melanoma development, and resistance to aforementioned therapies is becoming increasingly apparent. In this chapter, epigenetic alterations commonly found in melanoma are introduced, with a focus on histone and DNA modifications and their relevance for melanoma development, progression and therapy response. Detailed knowledge about this emerging aspect of melanoma research will help to understand the plastic nature of melanoma and set the foundation for novel treatment strategies that target aberrant gene regulation on genetic and epigenetic levels.

Melanoma is the most aggressive and serious type of skin cancer. Known for being highly malignant and metastatic, melanoma typically has low survival rates. Prognosis can be improved with an early diagnosis and a good monitoring of the disease. However, current melanoma biomarkers display severe limitations, making them inadequate for early detection of the malignancy. Therefore, it is of urgent matter for us to characterize and establish novel biomarkers with a direct application to daily clinics in order to accurately detect early american joint committee on cancer (AJCC) stages in melanoma patients, efficiently monitor the disease progression, and reliably predict the response to therapies, survival, and likely future recurrence. Long non-coding RNAs (lncRNAs) are a promising biomarker and regulator of tumor progression for many cancers. They are secreted into the bloodstream inside exosomes by a wide range of malignant cells and several of them have actually been validated as promising circulating molecular signatures of other cancer types, but not melanoma. However, in recent years there has been much research into lncRNA melanoma biomarkers, and many of them have been characterized as potentially clinically relevant.

Melanoma treatment depends largely on the clinical stage of the disease. The preferred treatment is surgical resection of the disease. The surgical margins depend on the depth of the disease. Sentinel lymph node biopsy is generally advised for all lesions greater than 1 mm depth. Complete lymphadenopathy of surrounding lymph nodes is recommended in the presence of nodal disease. There are some controversies surrounding the timing and benefit of complete lymphadenopathy in clinically occult disease. There is evidence to support the role of adjuvant therapies in the form of immunotherapy in regionally advanced disease, and there has been a significant improvement in medical therapies for advanced melanoma. BRAF inhibitors have become mainstay treatment for patients with a BRAF mutation. Immunotherapy is another cornerstone of therapy for advanced melanoma. There is ongoing research to define the optimal therapeutic regimen. Future guidelines will likely incorporate this recent research. Chemotherapy has been relegated to second-line therapy in melanoma.

This chapter examines a number of different aspects of renal cancer. Firstly, an introduction into the numerous forms of renal cancers is provided, focusing on renal cell carcinomas their causes and the different treatment options currently available. This chapter also takes a look at renal cancer from a toxicological point of view. Due to the crucial role of the kidneys in blood filtration, this allows them to become susceptible to the exposure and accumulation of potentially carcinogenic chemicals. For this reason, renal carcinogens are looked at in detail focusing on the varying mechanisms of genotoxic renal carcinogens such as aristolochic acid and potassium bromate, and their non-genotoxic renal carcinogens counterparts including ochratoxin A and chlorothalonil. This chapter also examines the different methods currently used to detect a compound’s carcinogenic potential, including the in vitro Ames test and animal based carcinogenicity screening methods.

Cutaneous malignant melanoma (CMM), which is ranked as the 8th most common cancers in the US, makes 4–7% of skin cancers but it causes approximately 80% of skin cancer deaths. CMM is characterized by insidious and fast progression, heterogenic evolution, and significant resistance to numerous therapeutic strategies. CMM is the result of the uncontrolled proliferation of melanocytes, the cells which reside in the basal layer of the epidermis. The most efficient therapy is the surgical removal if the lesion is in an early stage. For metastatic melanomas, there are different strategies, extremely rarely leading to total cure. Tyrosinase-related protein-2 (TRP2) or L-Dopachrome tautomerase (L-DCT) is a member of Tyrosinase-related protein family known for many years for its enzymatic activity in the distal steps of melanogenesis. The modern DCT image is focusing more on processes and mechanisms related to cell development and response to environmental and therapeutic stressors in normal and transformed cell phenotypes. This chapter provides an extended, updated biological status of TRP2/L-DCT encompassing the structural and functional particularities within melanoma molecularity, in the attempt to get new insights into the complex mechanisms of this neoplasm and raise the interest for DCT unexplored yet potential in melanoma diagnosis/prognosis and therapy.

More than 90 years have passed since Baily and Cushing first introduced a histogenetic classification for tumours of the cranial nervous system (CNS). More recently, our knowledge of the genetic and molecular basis of tumorigenesis has caused a major paradigm shift towards defining tumours genetically, thus allowing greater diagnostic accuracy and prognostication to better guide tumour management. Correspondingly, successes in integrated management and improved survival rates have shifted attention towards overall quality of life studies, where psychosocial sequelae and adjustment implications are of particular interest to mental health professionals. To date, research relevant to this field has focused on the identification of neuropsychiatric symptoms at manifestation of illness. Such studies indicate that mood, cognition and psychosocial functioning are important factors in early diagnosis, mediating health outcomes, especially following radical and risk-adapted anti-neoplastic treatment. In addition to psychological burden, the neuropsychiatric aspects of childhood CNS tumours, including posterior fossa syndrome and cerebellar cognitive affective syndrome, are increasingly recognised as crucial causes of poor outcomes. The chapter ahead will initially address the shifting landscape of neuro-oncology, and then provide an overview of the neuropsychiatric aspects of CNS tumours in childhood, highlighting the underlying neurobiological and pathogenic mechanisms, whenever possible.

Among the pediatric brain tumors, medulloblastoma (MB) is the most common solid variety and entirely occur in the posterior fossa with tendency to seed into CSF spaces. Despite innovations in technological developments and understanding of tumor biology, modern imaging facilities, advances in surgical practices, and newer chemotherapeutic and radiation techniques, this malignant type of tumor continues to be a formidable entity. Even though, the outcome in terms of survival rate is better than any time before, the overall result is still disappointing. With advances in management strategy, chances of survival with good quality of life have been amplified, where newer targeted therapies and rehabilitation plays an immense role. While the adverse effects of surgery and adjuvant therapies are still on play, researchers are trying ceaselessly to minimize those to give maximum wellbeing to these unfortunate children.

Google-Books-ID: g4RIDwAAQBAJ; International audience; Rho GTPases control many aspects of cell physiology. This includes polarity, endo/exocytosis, adhesion, motility, transcriptional activation, cell cycle progression or apoptosis. In view of such pleiotropic activities, Rho-controlled signaling has proven to be of medical relevance, especially in tumorigenesis, disease-associated bone remodeling and infectiology.This book is divided into three parts. Part 1 gives an evolutionary perspective of the Rho family, its atypical members, and an overview of how Rho activity is regulated. Part 2 addresses two important aspects of multicellularity controlled by Rho-dependent pathways, namely, cell-cell interactions and mechanotransduction. It also describes how post-translational modifications control Rho activity and how this is exploited by pathogenic bacteria. Part 3 explores several examples of the variety of pathophysiological processes controlled by Rho signaling, and gives a successful example of translational research, from the inhibition of Rho activation to the development of new molecules against osteoporosis.This updated review on the biology of Rho GTPases is an essential read for molecular and cell biologists. It is also an invaluable guide to post-graduate and medical students who wish to deepen their knowledge in cell biology.

One of the most feared consequences of cancer is the possibility of severe and uncontrolled pain in patients with advanced cancer. Patients with head and neck cancer (HNC) have the highest prevalence of pain among patients with cancer,and it is often one of the major reasons for seeking care. A subspecialty approach that incorporates anatomical and technical knowledge to alleviate pain through minimally invasive procedures is relatively recent. The purpose of this chapter is to present different interventional techniques which are used for the treatment of pain in HNC patients when drug treatment is unsuccessful.

Neuroblastoma is a predominantly pediatric cancer, arising from the primordial neural crest cells that form the sympathetic nervous system. The prognosis for patients with neuroblastoma can vary from uniform survival in low risk patients to fatality in patients with high risk disease. This chapter gives a brief overview of the epidemiology, genetics, clinical presentation, diagnosis, and discussion of the various staging systems and risk classifications of neuroblastoma. We also briefly describe our understanding of the conventional and novel treatment modalities available and their effects on the current prognosis of patients with neuroblastoma. The purpose of this chapter is to serve as a brief overview of the clinical aspects of neuroblastoma, to serve as a foundation of knowledge for scientists aspiring to develop new therapeutic modalities for this dreadful pediatric disease.

Neuroblastoma (NB) is one of the major challenges of pediatric oncology with a 5‐year survival rate of less than 40% despite intense therapy. The aggressiveness of the disease has been recently correlated to the degree of myeloid cells infiltrating the tumor. Together with the tumor cells and immunosuppressive cytokines (e.g., IL‐10 and TGF‐β), these cells hamper the generation of an efficient antitumor immune response and, therefore, favor tumor growth and metastasis. Novel therapeutic approaches are designed to target immune cells instead of cancer cells. To improve their efficacy, recent cancer immunotherapy strategies have focused on the depletion, blockade, or reprogramming of these tolerogenic immune effectors. Therefore, the principal clinical challenge is currently to identify therapeutic strategies which could overcome the primary and secondary resistances to these cancer immunotherapies. In this review, we discuss the dialogue of immune microenvironment of neuroblastoma and the immunotherapeutic strategies to cure neuroblastoma.

Neuroblastoma is a notably malignant cancer originates from neuroblastoma stem cells during embryogenesis. It can originate from any region of the peripheral nervous system. Neuroblastoma is a heterogeneous cancer. The cells responsible for heterogeneous structure are neuroblastoma stem cells that initiate the cancer and generate into all the cancer cells and have self‐renewal property. Although some specific surface markers and genetic patterns of neuroblastoma stem cell were determined, all mechanisms have not been illuminated yet. Mutations that are specific to neuroblastoma development, risk group, and disease‐stage are identified. However, epigenetic dysregulations also play major roles in the development of neuroblastoma. Patients gradually develop resistance to conventional chemotherapy or relapse occurs after treatment. New therapy approaches have been developed, either as alternatives to conventional chemotherapy, or in combination with it, in order to overcome the handicaps. Targeted therapies, those directly affecting the cancer cell or the cancer stem cell and having a minimal effect on healthy cells, constitute these approaches. Since neuroblastoma is highly heterogeneous both genetically and epigenetically, the data obtained from molecular mechanisms will greatly contribute to the survival of patients.

Head and neck cancer (HNC) is referred to the cancers of aerodigestive tract covering number of structures viz, oral and nasal cavity, paranasal sinuses, lips, salivary glands, oropharynx, hypopharynx, pharynx, larynx, and local lymph nodes. It is the sixth most common cancer in the world. MicroRNAs (miRNAs) are small single‐stranded noncoding RNAs (ncRNAs) of about 19–25 nucleotides. These miRNAs have been reported to influence number of biological activities, i.e., gene regulation, differentiation, organ formation, cell death, cell proliferation, and stress responses. The first ever study involving miRNAs in HNC was published in 2005. Since then, association between dysregulation of miRNAs and head and neck tumorigenesis has been documented by a number of researchers. This chapter has covered a comprehensive state of the art literature review of the recent studies about the role of miRNAs in HNC including oral squamous cell carcinoma (OSCC) and human nasopharyngeal carcinoma. Despite significant improvement in multimodal treatment, the prognosis of advanced HNC is quite poor. Recent studies are promising regarding the potential role of miRNAs as prognostic indicators. Recently, some miRNAs have been discovered as important diagnostic biomarkers. In fact, miRNAs are found circulated stably in different body fluids, i.e., urine, blood, saliva, as well as in breath. Hence, these miRNAs can be assessed easily with noninvasive methods. miRNAs are the key therapeutic targets in addition to their prognostic and diagnostic value. Use of synthetically designed “miRNAs sponges,” miR mimics (agomiRs), miR antagonists (“antagomiRs”), and miR inhibitors (antimiRNAs oligonucleotides) is an innovative strategy to modulate oncogenic and tumor‐suppressive pathways. Our understanding of miRNAs involvement in HNC is in its infancy. The discovery of miRNAs heralds a complete new paradigm in the understanding of exact molecular pathways involved in HNC development. More detailed studies are required for better understanding and therapeutic targets to treat HNC.

Neuroblastoma is an embryonal extracranial solid tumor originating from undifferentiated neural crest cell and it is the most common among children. Neuroblastoma is highly heterogeneous, and on these bases different outcomes are observed across the subtypes. Its clinical impact (~13% of all pediatric cancer mortality) has made this aggressive malignancy the focus of a considerable translational research effort. New insights into tumor biology are leading to the development of novel therapeutic approaches, which include small-molecule inhibitors as well as epigenetic approaches, noncoding-RNA, and cell-based immunologic therapies. Recently, chromatin immunoprecipitation with high-throughput sequencing and RNA-sequencing studies have demonstrated that epigenetic changes contribute to the aggressive pathophysiology of pediatric neuroblastoma disease. Epigenetic abnormalities are feature of human cancer cells and the epigenetic alterations may be the key toward tumorigenesis. In particular, the increase of deacetylation has been involved in epigenetically mediated tumor-suppressor gene silencing. In addition, several studies evaluated the 5-methylcytosine (5 mC) distribution patterns, which distinguish cancer cells from normal cells, and how CpG methylation contributes to the oncogenic phenotype.

Neuroblastoma is considered as the most common extracranial solid tumor occurring during childhood, but takes place rarely after the age of 10 years. The tumors are considered as embryonal tumors that result from the fetal or early postnatal life development and are formed from neural crest-derived cells, and their origination is from the early nerve cells which are called as neuroblasts of sympathetic nervous system. Being heterogeneous in their biological, genetic, and morphological characteristics, tumors which are distinct from other solid tumors due to their biological heterogeneity result in the clinical pattern changes from spontaneous regression to a highly aggressive metastatic disease. Neuroblastoma tumorigenesis is regulated by Myc oncogene, leading to aggressive tumor subset. Many epigenetic factors play crucial role in the disease induction and development, while regulatory effect and outcome result in epigenetic patterns distinguishing neuroectoderm, neural crest, and more mature neural states. Neuroblastoma patients’ clinical management is based on prognostic categories subtracted from studies correlating outcome and clinico-biological variables. Neuroblastoma anatomic boundaries include primarily autonomic nervous system besides other rare locations. Neuroblastoma molecular pathogenesis classifies the tumor according to the different clinical behaviors that are important for the improvement of the patients outcome and overall survival according to the different therapy modalities applied.

It is widely accepted that neuroblastoma origin from Neural Crest Cells (NCC). NCC is a group of embryonic cells located in proximity to neural tube. During the embryonic development they migrate to generate the ganglia of sympathetic nervous system and the adrenal medulla. More than 50% of neuroblastoma masses are detected in the abdomen but the phases of tumorigenesis during the embryonic life are still unknown. Neuroblastoma cells show numerous copy number aberrations (CNAs), both numerical and structural. Several non-random CNAs are detected in clinical stage 4 and associated with tumor aggressiveness. On the contrary, neuroblastoma cells of infants or young patients have several numerical CNAs that are associated with a favorable outcome. MYCN oncogene amplification was one of the first genetic abnormalities observed in neuroblastoma and was found correlated to tumor aggressiveness. About 1% of all neuroblastoma show a hereditable fashion. Nowadays, the ALK gene has been discovered as predisposition gene for neuroblastoma. Moreover, thank to the genome-wide association studies, BARD1, LMO1 and LIN28 genes have been found linked to neuroblastoma predisposition. The two-step and multistep models are not satisfied the genesis of this tumor making the study of neuroblastoma tumorigenesis mandatory. Recently, the role of chromosome instability (CIN) became prominent to explain the neuroblastoma development. Indeed, the chromothripsis was observed in neuroblastoma cells of clinical stage 4, supporting the high genomic instability of these cells. The role of CIN in neuroblastoma is still unclear, but several experimental data suggest that CIN has a pivotal part in the genesis of neuroblastoma.

Neuroblastoma is an embryonal malignancy that originates in the sympathetic nervous system. It is the most common solid tumor in infants and the most frequent extracranial solid tumor in children. Neuroblastoma accounts for 10% of childhood malignancies with 75% occurring in children

In this chapter, we are going to discuss about salivary glands cancers, their clinical manifestations and categories, pathogenesis, diagnosis and treatment. We will go through details in each part in both clinical and surgical aspects based on recently prominent published studies and research in prestigious journals. After a short review on clinical features, epidemiology, pathogenesis, diagnosis and treatment, we will show staging and tumor node metastasis (TNM) classification of major salivary gland tumors and also basic principles of approach to salivary gland cancers. A little will be explained about basic surgical procedures for removal of cancers and benign tumors.

Telomeres are nucleoprotein structures located at the ends of linear chromosomes. In most human adult normal somatic cells, telomeres shorten after each cellular division. This shortening ultimately leads to senescence and/or apoptosis. By contrast, in most cancer cells, telomerase activation compensates this loss and confers to these cells their infinite cell proliferation potential. Neuroblastoma (NBL) is a malignant tumor of the peripheral sympathetic nervous system and the most frequent extracranial solid tumor of childhood. NBLs are remarkably heterogeneous both at the levels of biology, genetic and clinical courses. Indeed, some of NBLs can regress spontaneously or after a mild treatment, while others are in the high-risk category with poor prognosis. The molecular bases underlying this heterogeneity are poorly understood. MYCN (V-Myc Avian Myelocytomatosis Viral Oncogene Neuroblastoma-derived Homolog) amplification, recognized as strongly associated with unfavorable patient outcome, is found in only 40% of the high-risk disease, indicating the involvement of other mechanisms. Recent observations suggest that telomerase expression and telomere dysfunctions may be one critical step in NBL development. This review provides recent insights on telomeres/telomerase regulation in NBL. Because of their involvement in the tumor cell biology, telomere and telomerase are currently at the core of new drug development.

Head and neck irradiation is the standard treatment of advanced oral/oropharyngeal cancer. The treatment has severe side effects such as mucositis, xerostomia, irradiation caries, trismus, and osteoradionecrosis. Side effects can lead to treatment discontinuation, infection, increased drug consumption, and increased duration of hospital admission and can have negative impact on the quality of life and overall survival. Furthermore, some of them (mucositis and xerostomia) affect almost every (>90%) patient. Since nearly two‐thirds of oral/oropharyngeal cancers are diagnosed in advanced stage, one might conclude that the great majority of patients will be affected. However, these side effects can be prevented or at least reduced by proper oral/dental care. Therefore, every patient planned for head and neck irradiation should undergo dental evaluation before beginning of the treatment.

Rapidly increasing trend of thyroid cancer incidence has turned this disease into a global concern. An estimated number of 64,300 new cases of thyroid cancer occurred in men and women in 2016, which represents 3.8% of all new cancer cases of USA (https://seer.cancer.gov/statfacts/html/thyro.html). Thus, there is a high possibility for every physician to encounter a case of thyroid cancer during his/her professional lifetime. In this chapter, we clarified epidemiology, different categories, and new approaches toward diagnosis and management of thyroid cancer.

Medullary thyroid carcinoma is a hormone-producing malignant tumor that synthesizes calcitonin. MTC can be sporadic or familial. It has a malignant behavior. Our chapter has 3 parts: 1.Updates on the diagnosis of MTC -in this part we review the clinical findings in MTC: isolated thyroid nodule, palpable cervical lymph nodes and systemic manifestations. Fine needle aspiration, serum calcitonin, computed tomography (CT) and fludeoxyglucose - positron emission tomograpyh (FDG-PET) are summarized. Biomarkers with prognostic value are be described in detail: plasma calcitonin, carcino-embryonic antigen, germ-line RET mutation and matrix metalloproteinase. 2. Updates on the management and treatment of MTC -we discuss the surgical treatment, radiation therapy, systemic therapy with angiogenesis inhibitors and transcatheter arterial embolization to prevent extension of the tumor. Based on the characteristics of MTC a new approach using gene therapy has been developed to obtain complete remission of the carcinoma. 3. We describe a typical case of MTC from the oncology department, with cervical lymph nodes and a thyroid nodule. Immunohistochemistry staining showed calcitonin in the tumor cells. Thyroid ultrasound with fine needle aspiration biopsy confirmed the MTC. CT images of the cervical lymph nodes and thyroid nodule as well as microscopy images are presented. Chemotherapy with Dacarbazine was initiated with favorable outcome.

The prosthetic rehabilitation of the maxillectomy defect is important to restore oral functions and facial contours as well as to improve patients’ health-related quality of life (HRQOL). This literature review aims to assess the HRQOL of maxillectomy patients rehabilitated with obturator prostheses and their determinants as well as to identify the most commonly used HRQOL measures. A literature search has been performed using PubMed, EMBASE, and Google Scholar to identify studies published before October 10, 2016. Twenty-three studies were identified. Most studies are cross-sectional. The most frequently used HRQOL measures were the Obturator Functioning Scale and the University of Washington Quality of Life scale version 4. Studies showed that postoperative radiation therapy, residual dentition, obturator functioning, impairment of ingestion, speech, appearance, the extent of therapy, and pain were important factors affecting patients’ HRQOL. This review provides valuable information for clinicians and researchers in determining patients’ needs, selecting HRQOL measure, planning future studies, as well as planning and developing comprehensive prosthetic rehabilitation programs. Well-designed clinical, multicenter, longitudinal studies with a larger sample are needed to evaluate the impacts of different reconstruction and retention methods as well as several determinants including sociodemographic, clinical, and psychological on patients’ HRQOL.

Introductory Chapter: Be Careful! It Can Be Cancer

Head and neck cancer (HNC) is one of the most prevalent human malignancies, affecting different anatomic sites of the upper aerodigestive tract (UADT) such as the oral cavity, larynx, and naso-, oro-, and hypopharynx. HNC develops through the accumulation of multiple genetic and epigenetic alterations in a multistep process. In this issue, the aim is to describe epigenetic mechanisms behind HNC. The main mechanisms evaluated are DNA methylation, posttranslational histone modification, and noncoding RNAs.

The main modifications that characterize cancer are represented by alterations in oncogenes, tumor-suppressor genes, and non-coding RNA genes. Most of these alterations are somatic and the process is a multistep one. Tumors often arise from an initial transformed cell, and after subsequent genetic alterations different cytogenetically clones lead to tumor heterogeneity.

Malignant melanoma is the sixth most commonly diagnosed cancer in developed countries. Like in many cancers, survival rates are closely associated with the time of melanoma detection. Regrettably, most cases of melanoma are caught at diffuse state and methods used in clinical practice and experimental trials are not effective. Thus, there is a great interest in discovering biomarkers that could be used for screening those with melanoma, as prognostic and prediction factors as well as new potential targets for melanoma treatment. For this purpose, many groups have examined alteration in the structure and expression of carbohydrate part of glycoconjugates to identify changes that occur with melanoma. The observed changes include increased β1,6 branching correlating with higher abundance of polylactosamine extension, increased sialylation accompanied by differences in the position of sialic acid residues, increased fucosylation, higher levels of T and Tn antigens as well as changes in the expression of ganglioside structures. As a consequence of glycan modification, the loosened matrix adhesion, increased motility, higher invasive potential and metastasis formation have been observed. Growth and migration of melanoma cells have been also found to be stimulated by advanced glycation end products. Biomarker discovery is a multi-step process and the recent glycomic data on melanoma are mostly related to the discovery phase, as the first one leading to validation and standardisation steps.

Melanoma is the deadliest form of skin cancer. The disease is driven by molecular alterations in oncogenic signaling pathways, such as mitogen‐activated protein kinase (MAPK) and phosphatidylinositol 3‐kinase (PI3K). Activating mutations in oncogenes, such as BRAF and NRAS, and inactivating mutations in tumor suppressors genes, such as PTEN, promote this disease by altering cellular processes involved in growth, survival, and migration. Therapies targeting critical nodes in these pathways have demonstrated efficacy in clinical trials, but their therapeutic potential has been limited by the rapid onset of drug resistance. Durable therapeutic responses have also been observed in patients receiving immunotherapy. However, this activity appears to be confined to a subset of patients, and combinations with targeted therapies have raised safety concerns. Accumulating evidence strongly suggests that the pathogenesis of melanoma is also shaped by the aberrant activity of epigenetic factors that regulate gene expression through the modification of DNA and chromatin. This chapter provides a comprehensive review of the epigenetic alterations in melanoma and highlights the roles played by specific chromatin regulators during disease progression. We also discuss the clinical utility of both first and second generation epigenetic therapies in the melanoma setting, placing emphasis on the potential to overcome resistance to targeted therapies and to serve as priming agents for immunotherapies.

Over the past decade, leukemia exists and frequently occurs in adults. Radiation exposure, hereditary syndromes, smoking, age, and many other unknown factors are generally the major risk factors for leukemia. Acute myeloid leukemia (AML) is a hematological malignancy that is dispersed from its beginning and may be perceived as a prototype of metastatic cancer, yet leukemia is considered a highly malignant neoplasms responsible for a large number of cancer-related deaths. In addition, to uninhibited proliferation, leukemic cells dispense early from the bone marrow into the peripheral blood, followed by an infiltration of various organs such as lymph nodes, liver, spleen, lungs, intestinal tract, skin, or mucous membranes. Several studies are concerned with the critical role of angiogenesis in the development and growth of solid tumors and hematological malignancies. Moreover, angiogenic mediators created by AML cells act through external or internal autocrine loops, thereby directly indorsing cell survival, spread, and disease development. In recent years, many researchers focus on angiopioetins (Ang), an innovative family of angiogenic mediators, which have shown to be vital regulators of angiogenesis and vascular stability. Ang-1 and its antagonist Ang-2 act via the receptor tyrosine kinase sTie 2, which is expressed in endothelial cells (ECs) of the vasculature and in subset of hematopoietic stem cells. Binding of Ang-1 causes phosphorylation of sTie2 and ensures the integrity of the vasculature by stimulating interactions between ECs and endothelial support cells. This chapter reviews the incidence, mortality, pathogenesis, and diagnostic procedures of AML. As well as aims at evaluating serum levels of endostatin, MMP- 9, and uPAR in acute myeloid leukemia patients before chemotherapy and after achieving complete remission. At the same time, the chapter also assesses the pretreatment levels of plasma Ang-1, Ang-2, and sTie2, and the calculated ratio of Ang2/sTie2 receptor in a cohort of AML patients also studies their impact on the AML patients' overall survival.

Diffuse intrinsic pontine glioma (DIPG) is a tumor of the brainstem, specifically in the pons, accounting for 10–20% of all of central nervous system (CNS) tumors in children. Unfortunately, DIPG is the leading cause of death in children with CNS cancers. Clinical interventions trying to effectively treat children with DIPG have failed despite 40 years of clinical trials. The critical location of these tumors eliminates extensive surgical resection as an option. Radiation therapy (RT) is the standard of care, and although it improves the clinical symptoms of most patients, the results are temporary, with tumor progression typically occurring months post radiation. Given the dismal prognosis associated with this disease and the challenge to find chemotherapeutic agents, especially molecularly targeted drugs that improve the survival of the patients, there is a strong incentive to move new treatments forward into clinical trials. The more effective treatment would potentially involve combinatory therapeutic regimens with new epigenetic drugs that can offer synergistic benefits and potentially increase therapeutic efficacy. The increasing knowledge of genomic, epigenomic, and proteomic characteristics of DIPG is opening doors to new therapeutic avenues and provides hope and promise for this devastating childhood cancer.

The current research in oncology is focused on genetics and molecular oncology in order to obtain better understanding of the etiology of tumor disease. Detailed knowledge of oncogenesis mechanisms could lead to invention of effective therapeutic tools against cancer. Under healthy conditions, cell cycle is regulated by oncogenes and tumor suppressor genes, which should be in strict balance. Genesis of tumor is a consequence of the accumulation of genetic alterations, which help the cell to escape normal cellular regulatory mechanisms and destruction by immune system. Glioblastoma (GBM) is a highly malignant primary brain tumor occurring mostly in population of adults. Patients suffering from GBM have very poor prognosis. Despite development in radiology methods promising earlier diagnosis and development of clinical and radiation oncology with newer treatment regimes, the effect of therapy remains limited and prognosis of patients has not improved as expected. Target of GBM research are genes involved in response to oxidative stress and DNA damage, genes regulating cell cycle, genes determining immune response, growth factors, and others. Genetic alterations are studied in connection to their possible relationship to susceptibility of brain tissue for tumor formation, to sensitivity of brain tissue for various environmental etiology factors, to effect of anticancer treatment or resistance of tumor tissue to therapy, to overall survival, and progression-free interval.