Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

COVID-19 and Cerebrovascular Diseases

Introduction Coronavirus disease 2019 (COVID-19) is the result of infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Between the start of the outbreak in the last quarter of 2019 and January 25, 2021, there have been 97,831,595 confirmed cases of COVID-19 and 2,120,877 deaths reported to the World Health Organization in 237 countries, areas, and territories. COVID-19 typically affects the respiratory system, resulting in…

Neurological Presentations of COVID-19

Introduction The acute manifestations of SARS-CoV-2 on the nervous system are protean, affecting both the central and peripheral nervous systems ( Table 3.1 ). As detailed in Chapter 2 , SARS-CoV-2 can interact with the nervous system by multiple pathophysiologic mechanisms, including direct viral effects, cytokine-mediated effects, increasing inflammation and/or hypercoagulable states, para- or postinfectious autoimmune effects, and downstream effects from critical illness or treatments. Neurologic…

Neuropathogenesis of SARS-CoV-2 Infection

Disclosure of interests All authors declare they have no conflict of interest. Ethical approval for studies This article does not contain any studies with human and animal participants performed by any of the authors. Introduction The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for causing the novel coronavirus disease 2019 (COVID-19) that became a global concern after it emerged from Wuhan, China in December…

Fears and Hopes

A Novel Virus Sees the Day China awoke on December 31, 2019 to the first public message from the Wuhan Municipal Health Commission alerting its residents of a cluster of 27 cases of viral pneumonia of unknown etiology that had emerged in Wuhan, capital of the Hubei province and home to over 11 million people. The news reached the US Centers for Disease Control and Prevention…

Modulation of Expression of miRNAs for Therapeutic Effects in Human Malignant Neuroblastoma

Acknowledgments This work was supported in part by an award from Soy Health Research Program (SHRP, United Soybean Board, Chesterfield, MO, USA), University of South Carolina School of Medicine Research Development Fund (USC SOM RDF, Columbia, SC, USA), South Carolina Spinal Cord Injury Research Fund (SC SCIRF-2015-I-01, Columbia, SC, USA), and earlier grants (R01 CA91460 and R01 NS057811) from the National Institutes of Health (Bethesda, MD,…

Emerging Evidence for Krüppel-Like Factor 4 (KLF4) as a Tumor Suppressor in Neuroblastoma

Acknowledgments This work was supported in part by an award from Soy Health Research Program (SHRP, United Soybean Board, Chesterfield, MO, USA), University of South Carolina School of Medicine Research Development Fund (USC SOM RDF, Columbia, SC, USA), South Carolina Spinal Cord Injury Research Fund (SC SCIRF-2015-I-01, Columbia, SC, USA), and earlier grants (R01 CA91460 and R01 NS057811) from the National Institutes of Health (Bethesda, MD,…

Current and Future Strategies for Treatment of Relapsed Neuroblastoma

Introduction Despite recent advances in the treatment of high-risk neuroblastoma (HR-NBL), such as the addition of immunotherapy to upfront intensive multimodal therapy , and consequent incremental improvements in outcome, only approximately half of patients will achieve a long-term cure ( Fig. 15.1 ). Approximately 10%–20% of HR-NBL patients, particularly adolescents whose tumors more commonly have loss-of-function mutations in the alpha thalassemia/mental retardation syndrome X-linked ( ATRX )…

Novel Therapeutic Targets in Neuroblastoma

Introduction Neuroblastoma, a tumor of the sympathetic nervous system, is the most common extracranial solid tumor in children. There is broad heterogeneity in the disease course, which can be predicted by clinical staging, tumor histology, and underlying genomic changes. Treatment approaches can vary from observation of spontaneous regression without therapy to extremely intensive, multimodal therapy for the highest risk patients. Low- and intermediate-risk patients generally do well…

Current Challenges in the Management of Neuroblastoma: Noncoding RNA Influences

Introduction The first cases of neuroblastoma (NB) date back to 1864, as described by Rudolf Virchow, where NB and other pediatric abdominal tumors were initially classified as gliomas . Furthermore, between 1925 and 1962, neuroblastoma incidences reached approximately 10% in England and Wales and other European countries . In addition, one of the major mainstay therapies for NB was the administration of elevated doses of vitamin…

Current Pharmacotherapy for Neuroblastoma

Introduction The specifics of treatment of neuroblastoma depend critically on the stage and prognostic features of the tumor, the age of the patient , and, increasingly, the transcriptome of the tumor cells . Children whose neuroblastomas are single, primary tumors without spread to local nodes or contiguous structures, small enough to be completely resected surgically, need no further treatment. Some children with metastatic disease can simply…

Role of Stemness Factors in Neuroblastoma: Neuroblastoma Stem Cells, Tumor Microenvironment, and Chemoresistance

Cancer Stem Cells The cancer stem cell (CSC) paradigm is the idea that subpopulations of cancer cells exist within a tumor that has capabilities similar to a normal stem cell: self-renewal, multipotency, proliferation, and tumor maintenance . This concept that tumors may develop from stem cells is not a new one. The embryonal rest theory from the early 19th century stated that embryonic tissues persisting in…

Advances in the Surgical Treatment of Neuroblastoma

Introduction The initial diagnosis of neuroblastoma requires close collaboration among the surgical oncologist, pediatric oncologist, and pathologist, especially in the assessment of MYCN amplification, histopathology, and DNA index (ploidy) . The surgeon has a vital role in neuroblastoma management. Specifically, the surgeon must acquire an adequate tumor sample for both histopathology and molecular biological studies, while being meticulous during surgical resection of the primary tumor in…

Immunotherapy for Neuroblastoma

Acknowledgments We thank Joe Olechnowicz for editorial assistance. Introduction Standard care for patients with high-risk neuroblastoma (NB) currently consists of aggressive multimodal therapy including high-dose chemotherapy, surgery, and radiotherapy . Immunotherapy utilizes mechanisms of action that are not cross-reactive with other antitumor modalities, and is thus, an attractive therapeutic option, particularly to eradicate minimal residual disease. Moreover, in the young children typically afflicted with NB, chemotherapy…

Molecular Imaging in Neuroblastoma

Disclosure No funding received from any organization for this study. The authors declare that there is no conflict of interest. Neuroblastoma tumors are usually detected in a symptomatic child. Sometimes, it may be noticed incidentally. If child is symptomatic and presents with an abdominal mass, the first investigation should be ultrasonography (USG). The tumor is heterogeneous, and most of the time USG will show calcification in it.…

Energy Metabolism and Metabolic Targeting of Neuroblastoma

Acknowledgments This work was supported by Austrian Research Promotion Agency (822782/THERAPEP) and the Children's Cancer Foundation Salzburg. Introduction Most cancer cells reprogram their metabolism and pathways of nutrient acquisition to ensure high levels of energy supply and biomass production, while maintaining specific metabolic reduction-oxidation (redox) states, for achieving high proliferation. Mitochondria are the cell organelles involved in aerobic respiration, many essential metabolic and catabolic pathways, calcium…

Autophagy and Novel Therapeutic Strategies in Neuroblastoma

Acknowledgments This work is founded by The Italian Neuroblastoma Foundation “Fondazione Italiana per la Lotta al Neuroblastoma”. The authors would like to thank Carlo Zanon for his critical revision of the chapter. Introduction From the previous chapters, we have learned that the neuroblastomas show heterogeneous clinical and biological features. Patients with localized tumor usually respond very well to the therapy, and infants show a better response…

Targeting Angiogenesis in Neuroblastoma

Acknowledgments This work is dedicated to the memory of Dr. Vito Pistoia, a leading expert in this field. You’re Reading a Preview Become a Clinical Tree membership for Full access and enjoy Unlimited articles Become membership If you are a member. Log in here

GD2-Targeted Immunotherapy of Neuroblastoma

Introduction Cancer immunotherapy has been hailed as a potential “game changer” in the treatment of cancer. However, the number of antigen targets proven effective remains limited and is restricted to protein antigens, with the exception of Dinutuximab, a chimeric antibody directed against GD2, which was approved for the treatment of neuroblastoma, thereby widening the net of potential pharmaceutical targets. Altered glycosylation on glycoproteins and glycolipids is…

Neuroblastoma: Molecular Mechanisms and Therapeutic Interventions

Introduction Major strides have been made in targeted cancer therapy over the past decades due to better understanding of underlying cancer biology, identification of cancer vulnerabilities, and integration of multiple therapy approaches . These advances have led to the development of small-molecule inhibitors and monoclonal antibodies that target dysregulated pathways and malfunctioning or overexpressed molecules. For example, imatinib mesylate, the ABL tyrosine kinase inhibitor, has been…

Role of Genetic and Epigenetic Alterations in Pathogenesis of Neuroblastoma

Introduction Neuroblastoma is a sympathetic nervous system malignant tumor, which is derived from the neural crest cells and constitutes 7%–11% of the total number of childhood malignant tumors, taking fourth place in the structure of cancer morbidity after acute leukemia, central nervous system tumors, and malignant lymphomas. The incidence of neuroblastoma constitutes 0.85–1.1 cases per 100000 children under 15 years . The disease age distribution is…