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Clinics in Perinatology Mar 2021Neuroblastoma accounts for approximately 8% of all pediatric cancers, with 5% diagnosed during the neonatal period. Despite the disproportionate contribution of... (Review)
Review
Neuroblastoma accounts for approximately 8% of all pediatric cancers, with 5% diagnosed during the neonatal period. Despite the disproportionate contribution of neuroblastoma to childhood cancer deaths, neonatal neuroblastoma has a favorable prognosis, often with little or no therapy required. Therefore, minimizing therapy and mitigating complications/toxicities are emphasized, including using a watch-and-wait approach for patients at low risk for disease progression/relapse. However, stage MS neuroblastoma exhibits a unique pattern of disseminated disease, can be challenging to manage, and may require early intervention with systemic chemotherapy. In this review, the epidemiology, treatment options, and anticipated outcomes for neonatal neuroblastoma are discussed.
Topics: Child; Humans; Infant; Neoplasm Staging; Neuroblastoma; Prognosis
PubMed: 33583499
DOI: 10.1016/j.clp.2020.11.006 -
JCO Clinical Cancer Informatics Jan 2021Prognosis of high-risk neuroblastoma (HRNB) remains poor despite multimodal therapies. Better prediction of survival could help to refine patient stratification and...
Prognosis of high-risk neuroblastoma (HRNB) remains poor despite multimodal therapies. Better prediction of survival could help to refine patient stratification and better tailor treatments. We established a mechanistic model of metastasis in HRNB relying on two processes: growth and dissemination relying on two patient-specific parameters: the dissemination rate μ and the minimal visible lesion size S. This model was calibrated using diagnosis values of primary tumor size, lactate dehydrogenase circulating levels, and the meta-iodobenzylguanidine International Society for Paediatric Oncology European (SIOPEN) score from nuclear imaging, using data from 49 metastatic patients. It was able to describe the data of total tumor mass (lactate dehydrogenase, R > 0.99) and number of visible metastases (SIOPEN, R = 0.96). A prediction model of overall survival (OS) was then developed using Cox regression. Clinical variables alone were not able to generate a model with sufficient OS prognosis ability ( = .507). The parameter μ was found to be independent of the clinical variables and positively associated with OS ( = .0739 in multivariable analysis). Critically, addition of this computational biomarker significantly improved prediction of OS with a concordance index increasing from 0.675 (95% CI, 0.663 to 0.688) to 0.733 (95% CI, 0.722 to 0.744, < .0001), resulting in significant OS prognosis ability ( = .0422).
Topics: Child; Humans; Models, Theoretical; Neuroblastoma; Prognosis
PubMed: 33439729
DOI: 10.1200/CCI.20.00092 -
Biomaterials Science Mar 2021Metastasis is a complex and multifactorial process highly dependent on the interaction between disseminated tumor cells and the pre-metastatic niche. The metastatic...
Metastasis is a complex and multifactorial process highly dependent on the interaction between disseminated tumor cells and the pre-metastatic niche. The metastatic sites detected in the bone of patients affected by neuroblastoma (NB), a malignancy of the developing sympathetic nervous system, are particularly aggressive. To improve our current knowledge of metastatic tumor cell biology and improve treatment success, appropriate in vitro and in vivo models that more closely resemble the native metastatic niche are needed. In this study, the impact of the geometry of synthetic β-tricalcium-phosphate (β-TCP) structures on the interaction of NB tumor cells with the stromal component has been examined. The tumor microenvironment is dynamically shaped by the stroma, which sustains the growth of NB cells inside the metastatic niche. The 3D growth conditions are a determining factor for the cell proliferation rate in β-TCP. With respect to planar counterparts, channeled 3D β-TCP structures stimulate more interleukin-6 and Fibronectin production and define Connexin 43 distribution inside the cells. Together, these results highlight how the biomechanical properties of the 3D microenvironment enable tumor cells to form spheroid-shaped arrangements. This, in turn, facilitates their pro-migratory and pro-invasive patterns and mimics the in vivo situation by translating realistic mechanobiological cues to the metastatic NB.
Topics: Cell Line, Tumor; Cues; Humans; Neuroblastoma; Printing, Three-Dimensional; Tumor Microenvironment
PubMed: 33428699
DOI: 10.1039/d0bm00921k -
Head and Neck Pathology Sep 2021Neuroblastoma is the most common extracranial solid cancer of infancy, occurring mainly in the adrenal gland, with high metastatic potential. However, involvement of the... (Review)
Review
Neuroblastoma is the most common extracranial solid cancer of infancy, occurring mainly in the adrenal gland, with high metastatic potential. However, involvement of the head and neck region is rare. Here, we present two cases of metastatic neuroblastoma of childhood, in which a mandibular swelling was the first sign of disseminated disease. Case 1 describes a 4-year-old boy with a 2-week history of painful swelling in the left mandibular region, body soreness and weakness. Panoramic radiography and computed tomography showed a destructive lesion in the left mandibular ramus. Case 2 describes a 3-year-old boy with a 1-month history of swelling in the right mandibular area. Panoramic radiograph and cone-beam computed tomography showed a destructive lesion in the right body and ramus of the mandible, displacing tooth germs, with the destruction of vestibular and lingual bone cortices. In both cases, microscopic analyses revealed a diffuse proliferation of small, round, and blue cells with hyperchromatic nuclei and scant cytoplasm. While Case 1 was more undifferentiated, Case 2 presented eosinophilic areas suggestive of neuropil. A large immunohistochemical panel was performed, showing expression of neural markers such as CD56, neuron-specific enolase (in Case 2), chromogranin, and synaptophysin. Both lesions presented a high proliferation index (Ki67 > 70% and 80%, respectively). Positron emission tomography-computed tomography revealed ipsilateral adrenal primary lesions in both cases, with multiple bone metastatic lesions. Besides the mandible, multiple sites of the axial and appendicular skeleton were affected. Treatment consisted of induction chemotherapy, adrenalectomy, consolidation chemoradiotherapy, and post-consolidation therapy.
Topics: Adrenal Gland Neoplasms; Child, Preschool; Humans; Male; Mandibular Neoplasms; Neuroblastoma
PubMed: 33394374
DOI: 10.1007/s12105-020-01277-2 -
Journal of Dentistry For Children... Sep 2020Neuroblastoma is a malignant embryonal tumor derived from the neural crest cells of the sympathetic nervous system. Curative therapy is challenging, especially because...
Neuroblastoma is a malignant embryonal tumor derived from the neural crest cells of the sympathetic nervous system. Curative therapy is challenging, especially because early-stage diagnosis in toddlers is difficult. Successful treatment of high-risk neuroblastoma is only achieved in approximately half of the cases and requires an immediate interdisciplinary approach. We present a 34-month-old toddler with swelling of the left side of the face of three days duration and a mandibular mass of unknown duration, which was diagnosed as a metastasis of a neuroblastoma. He also had metastases in the kidney, long bones and skull. Despite the poor prognosis in cases of disseminated skeletal involvement and N-myc amplification, the young patient remained free of recurrence during a follow-up period of 36 months after multidisciplinary treatment. The purpose of this case report is to increase awareness of the clinical features of neuroblastoma among pediatric dentists to support early-stage diagnosis and highlight interdisciplinary management.
Topics: Child, Preschool; Humans; Infant; Male; Neuroblastoma; Prognosis
PubMed: 33349301
DOI: No ID Found -
Frontiers in Cell and Developmental... 2020Neuroblastoma (NB) is a neural crest-derived tumor, which develops before birth or in early childhood, with metastatic dissemination typically preceding diagnosis....
Neuroblastoma (NB) is a neural crest-derived tumor, which develops before birth or in early childhood, with metastatic dissemination typically preceding diagnosis. Tumors are characterized by a highly heterogeneous combination of cellular phenotypes demonstrating varying degrees of differentiation along different lineage pathways, and possessing distinct super-enhancers and core regulatory circuits, thereby leading to highly varied malignant potential and divergent clinical outcomes. Cytoskeletal reorganization is fundamental to cellular transformations, including the processes of cellular differentiation and epithelial to mesenchymal transition (EMT), previously reported by our lab and others to coincide with chemotherapy resistance and enhanced metastatic ability of tumor cells. This study set out to investigate the ability of the neuronal miR-124-3p to reverse the cellular transformation associated with drug resistance development and assess the anti-oncogenic role of this miRNA in models of drug-resistant adrenergic (ADRN) and mesenchymal (MES) neuroblastoma cell lines. Low expression of miR-124-3p in a cohort of neuroblastomas was significantly associated with poor overall and progression-free patient survival. Over-expression of miR-124-3p inhibited cell viability through the promotion of cell cycle arrest and induction of apoptosis in addition to sensitizing drug-resistant cells to chemotherapeutics in a panel of morphologically distinct neuroblastoma cell lines. Finally, we describe miR-124-3p direct targeting and repression of key up-regulated cytoskeletal genes including , and and the reversal of the resistance-associated EMT and enhanced invasive capacity previously reported in our model (SK-N-ASCis24).
PubMed: 33330445
DOI: 10.3389/fcell.2020.559553 -
Pharmaceuticals (Basel, Switzerland) Oct 2020The survival rate among children with relapsed neuroblastomas continues to be poor, and thus new therapeutic approaches identified by reliable preclinical drug testing...
The survival rate among children with relapsed neuroblastomas continues to be poor, and thus new therapeutic approaches identified by reliable preclinical drug testing models are urgently needed. Zebrafish are a powerful vertebrate model in preclinical cancer research. Here, we describe a zebrafish neuroblastoma yolk sac model to evaluate efficacy and toxicity of histone deacetylase (HDAC) inhibitor treatments. Larvae were engrafted with fluorescently labeled, genetically diverse, established cell lines and short-term cultures of patient-derived primary cells. Engrafted tumors progressed locally and disseminated remotely in an intact environment. Combination treatments involving the standard chemotherapy doxorubicin and HDAC inhibitors substantially reduced tumor volume, induced tumor cell death, and inhibited tumor cell dissemination to the tail region. Hence, this model allows for fast, cost-efficient, and reliable in vivo evaluation of toxicity and response of the primary and metastatic tumor sites to drug combinations.
PubMed: 33121173
DOI: 10.3390/ph13110345 -
Virus Research Sep 2020Bovine herpesvirus (BoHV) types 1 and 5 are two closely related alpha-herpesviruses of cattle with neuroinvasive potential. BoHV-5 causes non-suppurative...
Bovine herpesvirus (BoHV) types 1 and 5 are two closely related alpha-herpesviruses of cattle with neuroinvasive potential. BoHV-5 causes non-suppurative meningoencephalitis in calve whereas encephalitis caused by BoHV-1 has been occasionally reported. As an initial step to understand the biology of both BoHV types in neural cells, undifferentiated SH-SY5Y human neuroblastoma cells were infected with BoHV-1 strains Cooper and Los Angeles (LA), BoHV-5 strain 97/613 and A663, a BoHV-5/BoHV-1 natural recombinant. Cytopathic effect (CPE) in these cells was evident earlier for BoHV-5 strain 97/613 and CPE progression was slower for BoHV-1, particularly for Cooper strain. Virus antigen was detected as early as 8 h post-infection (hpi) for all strains, with the exception of BoHV-1 Cooper for which antigen expression was detectable by 24 hpi. All strains released detectable infectious virus in the extracellular medium by 8 hpi, confirming that undifferentiated SH-SY5Y cells are fully permissive to BoHV infection. Significantly different extracellular virus titers among the different strains were detected by 24 hpi, with BoHV-5 97/613 reaching the maximal virus production. The lowest extracellular titer was recorded for BoHV-1 Cooper at all the evaluated time-points. BoHV-1 Cooper, BoHV-1 LA and BoHV-5 97/613 had a steady increase in intracellular virus production. The evaluation of lysis plaques formation revealed that BoHV-5 A663 produced the largest plaques followed by BoHV-5 97/613. Both BoHV-1 strains produced smaller plaques when compared with BoHV-5. Despite a slower replicative cycle, strain A663 is more efficient in cell to cell dissemination. Thus, it is evident that BoHV-5 strains have growth advantages in undifferentiated neural cells compared with BoHV-1. This in vitro model might be useful to analyze the neuropathogenic potential of bovine alphaherpesviruses.
Topics: Animals; Antigens, Viral; Cattle; Cattle Diseases; Cell Line; Herpesvirus 1, Bovine; Herpesvirus 5, Bovine; Humans; Neuroblastoma; Neurons; Viral Load; Virus Replication
PubMed: 32473176
DOI: 10.1016/j.virusres.2020.198037 -
Cancer Medicine Jul 2020Regular off-treatment imaging is often used to assess for recurrence of disease after childhood cancer treatment. It is unclear if this increases survival, or what...
BACKGROUND
Regular off-treatment imaging is often used to assess for recurrence of disease after childhood cancer treatment. It is unclear if this increases survival, or what burden surveillance places on patients, families, or health-care services. This systematic review examines the impact of routine surveillance imaging after treatment of pediatric extracranial solid tumors.
METHODS
Collaborative patient and public involvement informed the design and interpretation of this work. Thirteen electronic databases, conference proceedings, and trial registries were searched alongside reference list checking and forward citation searching from 1990 onwards. Studies were screened and data were extracted by two researchers. Risk of bias was assessed using a modified ROBINS-I tool. Relevant outcomes were overall survival, psychological distress indicators, number of imaging tests, cost-effectiveness, and qualitative data regarding experiences of surveillance programs. PROSPERO (CRD42018103764).
RESULTS
Of 17 727 records identified, 55 studies of 10 207 patients were included. All studies used observational methods. Risk of bias for all except one study was moderate, serious, or critical. Data were too few to conduct meta-analysis; however, narrative synthesis was performed. Surveillance strategies varied, and poorly reported, involving many scans and substantial radiation exposure (eg, neuroblastoma, median 133.5 mSv). For most diseases, surveillance imaging was not associated with increased overall survival, with the probable exception of Wilms tumor. No qualitative or psychological distress data were identified.
CONCLUSIONS
At present, there is insufficient evidence to evaluate the effects of routine surveillance imaging on survival in most pediatric extracranial solid tumors. More high-quality data are required, preferably through randomized controlled trials with well-conducted qualitative elements.
Topics: Diagnostic Imaging; Female; Humans; Male; Neoplasms; Population Surveillance; Survival Analysis
PubMed: 32431088
DOI: 10.1002/cam4.3110 -
Cancer Metastasis Reviews Sep 2020Tumor metastasis comprises a series of coordinated events that culminate in dissemination of cancer cells to distant sites within the body representing the greatest... (Review)
Review
Tumor metastasis comprises a series of coordinated events that culminate in dissemination of cancer cells to distant sites within the body representing the greatest challenge impeding effective therapy of cancer and the leading cause of cancer-associated morbidity. Cancer cells exploit multiple genes and pathways to colonize to distant organs. These pathways are integrated and regulated at different levels by cellular- and extracellular-associated factors. Defining the genes and pathways that govern metastasis can provide new targets for therapeutic intervention. Melanoma differentiation associated gene-9 (mda-9) (also known as Syntenin-1 and SDCBP (Syndecan binding protein)) was identified by subtraction hybridization as a novel gene displaying differential temporal expression during differentiation of melanoma. MDA-9/Syntenin is an established Syndecan binding protein that functions as an adaptor protein. Expression of MDA-9/Syntenin is elevated at an RNA and protein level in a wide-range of cancers including melanoma, glioblastoma, neuroblastoma, and prostate, breast and liver cancer. Expression is increased significantly in metastatic cancer cells as compared with non-metastatic cancer cells or normal cells, which make it an attractive target in treating cancer metastasis. In this review, we focus on the role and regulation of mda-9 in cancer progression and metastasis.
Topics: Animals; Humans; Neoplasm Metastasis; Neoplasms; Syntenins
PubMed: 32410111
DOI: 10.1007/s10555-020-09886-7