PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “neuroblastoma”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1976

Sensitisation of neuroblastoma patients and related and unrelated contacts to neuroblastoma extracts.

Sensitisation to neuroblastoma extracts was tested by the leucocyte migration inhibition technique in 8 neuroblastoma patients, 22 relatives, and 49 unrelated contacts. All three groups showed a high frequency of positive reactions compared with 61 controls having no exposure to neuroblastoma. The frequency of sensitisation could be related to closeness of contact, but the nature of the sensitising material and its mode of transmission are unknown. Virus studies by the sensitive techniques of tumour virology are suggested. The absence of case clustering and the low familial incidence of neuroblastoma indicate that simple exposure to the tumour is not a major oncogenic factor.

Age Factors↗
PubMed1979

Endocytosis of cholera toxin in GERL-like structures of murine neuroblastoma cells pretreated with GM1 ganglioside. Cholera toxin internalization into Neuroblastoma GERL.

Cholera toxin (CT), covalently attached to horseradish peroxidase (HRP), is a specific cytochemical marker for GM1 ganglioside (GM1) and retains the ability of the native toxin to raise levels of cyclic AMP in avian erythrocytes. Using a cytochemical stain for HRP, we found that 9% of control cultured murine neuroblastoma cells bound cholera toxin-horseradish peroxidase conjugates (CT-HRP) on their surfaces after incubations for 1 h at 4 degrees C. Exogenous GM1, the natural receptor of CT, becomes associated in the culture medium with the plasma membranes of these cells so that 96% of cells are stained. Cells preincubated with GM1 at 4 degrees C were exposed to CT-HRP for 1 h at 4 degrees C. After washing, cells were incubated at 37 degrees C for 30 min-24 h. Endocytosis of CT-HRP occurred within 30 min and CT-HRP remained, throughout the 24-h period, in tubules, vesicles, and cisternae often found near the Golgi apparatus; this aggregate of peroxidase-positive elements probably corresponds to Golgi apparatus-endoplasmic reticulum-lysosomes (GERL) of neurons. In metaphase cells, CT-HRP was observed in aggregates of vesicles and tubules clustered near the centriole. Conjugates of HRP with subunit B, the GM1 binding component of CT, were internalized by cells pretreated with GM1 as was CT-HRP. The 9% of neuroblastoma cells binding CT-HRP in the absence of exogenous GM1 internalized the ligand in a manner indistinguishable from that of the treated cells. These findings indicate that, in neuroblastoma cells, a system of vesicles, tubules, and cisternae, analogous to GERL of neurons, is the primary recipient of adsorptive endocytosis of CT bound to endogenous or exogenously introduced GM1.

Animals↗
PubMed1979

[Neuroblastoma sympathicum problem: our own experiences with 10 neuroblastoma patients].

Special problems of neuroblastoma sympathicum are being demonstrated by means of 10 cases. Although in the past 20 years therapy ahs been improved considerably, the 2-year survival rate in 35--40% was hardly increased. Three children are specially presented: case I with myoclonus encephalopathy, case II with spontaneous regression and case III, where therapy was carried through by radical surgery. Various possible causes of myoclonus encephalopathy are being discussed and, regarding prognosis, assessed favourably. Several samples of excision should be required, since the tumor substance varies histologically. It is further reported about immunological phenomena. We point out especially that, if a tumor is manifested in a child under one year of age, the prospect is very good. The tumor should be excised by radical surgery, and, if vital structures are included, a resection en bloc might be necessary, with re-implantation of important blood vessels. Favourable factors with regard to prognosis are being counted up. Therapy should be carried out individually, depending on a low risk or high risk case.

Child, Preschool↗
PubMed2026

Third-generation whole-genome sequencing reveals the role of CNTNAP2 as a tumor suppressor gene in high-risk neuroblastomas.

BACKGROUND: Neuroblastoma is a common and aggressive pediatric sympathetic nervous system tumor. Genomic structural variants (SVs) contribute substantially to neuroblastoma, yet remain under-characterized in high-risk neuroblastomas. We aimed to elucidate neuroblastoma pathogenesis using third-generation whole-genome sequence high-risk cases to identify driver aberrations and explore potential therapeutic strategies. METHODS: We analyzed third-generation whole-genome sequencing data of 20 high-risk neuroblastoma samples and combined the findings with those obtained from the analysis of clinical samples, in vitro models, and public datasets. RESULTS: The contactin-associated protein-like 2 (CNTNAP2) gene was observed to be frequently aberrated because of structural variants in high-risk neuroblastoma samples. CNTNAP2 expression was significantly correlated with favorable histology and could be used to predict prognosis using clinical samples and neuroblastoma datasets. Overexpression and knockdown experiments and transcriptomic analysis revealed that CNTNAP2 was primarily involved in neuronal differentiation and axon guidance pathways; moreover, CNTNAP2 was required for neuroblastoma differentiation and affected cancer stemness. Immunoprecipitation and mass spectrometry revealed that CNTNAP2 interacted with cytoskeletal proteins like drebrin 1 (DBN1) and myosin-heavy chain 9 (MYH9). CNTNAP2 dynamically reorganises actin and microtubules for DBN1-mediated neuronal differentiation. CNTNAP2 also reduces CTNNB1 transcription and β-catenin pathway activation by inhibiting MYH9 nuclear translocation. CNTNAP2 overexpression in neuroblastoma cell lines resulted in cell cycle arrest, decreased cell proliferation and metastasis. CONCLUSIONS: The recurrent loss of CNTNAP2 in neuroblastoma contributes to an aggressive phenotype by impairing neuronal differentiation and increasing cancer stemness. These findings may serve as a foundation for developing therapeutic strategies to overcome barriers to differentiation.

Humans↗
PubMed2025

m1A methylase TRMT6 promotes neuroblastoma development by demethylating SST mRNA in an m1A/YTHDF2-dependent manner.

BACKGROUND: m1A, a prevalent RNA modification found in various RNA species, has recently been reported to modulate cancer progression. However, its effects on neuroblastoma remain uninvestigated. METHODS: The PCAT database was utilized to analyze the mRNA levels and survival probabilities of m1A regulator genes (TRMT6, TRMT61A, ALKBH1, and ALKBH3) in neuroblastoma patients. Silencing and recovery of TRMT6 were employed to investigate its role in neuroblastoma in vitro and in vivo. m1A-seq and RIP-qPCR were performed to identify and confirm the downstream targets of TRMT6. Additionally, Actinomycin D treatment was administered to assess mRNA stability. RESULTS: m1A transmethylase TRMT6 expression was significantly elevated in high-risk and late-stage neuroblastoma patients. Functionally, TRMT6 promotes the malignancy of neuroblastoma cells in vitro and promotes tumor growth and metastasis in vivo. Mechanistically, TRMT6 reduces SST mRNA levels by inhibiting its stability in an m1A-YTHDF2-dependent manner, thereby promoting the development of neuroblastoma. Furthermore, SST analog octreotide suppresses neuroblastoma cell malignancy, tumor growth, and metastasis. CONCLUSIONS: TRMT6 mediates m1A modification of SST to promote neuroblastoma progression, suggesting that targeting TRMT6 may be a novel potential therapeutic approach for treating neuroblastoma.

Neuroblastoma↗
PubMed1976

Developmental genetics of neuroblastoma.

Case reports of neuroblastoma revealed that some individuals are genetically predisposed and that this genetic predisposition may have other consequences. According to a mutation model, two classes of individuals could acquire neuroblastoma. One (prezygotic) was a rare class that carried a dominant gene imparting high risk of the tumor. The other (postzygotic) comprised all other individuals, each at low risk. The model related tumor incidence to germinal and somatic mutation rates and thereby carried implications for environmental modification of tumorigenesis and demographic variation in incidence. Case reports also revealed associations of neuroblastoma with congenital defects and a susceptibility to second tumors. Analogy with retinoblastoma and Wilms' tumor of the kidney suggested that these associations could result from action of a neuroblastoma gene or from chromosomal aberration. One known dominantly inherited condition, von Recklinghausen's disease, could dispose to neuroblastoma and create some associations. According to the two-mutation model, neuroblastoma may have been a single recessive gene disorder at the level of the cell. The phenomena of aganglionosis, neuroblastoma in situ, maturation of neuroblastoma to ganglioneuroma, and spontaneous regression suggested that such a neuroblastoma gene interfered with normal developmental processes. The specificities of this gene and of those for von Recklinghausen's disease and pheochromocytoma suggested that the functiof a membrane macromolecule.

Carcinoma in Situ↗
PubMed2025

Integration of ALK gene mutations and targeted therapies in pediatric high-risk neuroblastoma: advancements in precision oncology.

INTRODUCTION: Neuroblastoma (NB) is the most common extracranial solid tumor in children. High-risk neuroblastoma remains a therapeutic challenge, with a 5-year survival rate of 60%. The anaplastic lymphoma kinase (ALK) oncogene plays a critical role in the pathogenesis of neuroblastoma, with mutations frequently observed in high-risk cases. In this review we explored the genomic landscape of high-risk neuroblastoma, focusing on ALK mutations and their role in disease progression. We have also discussed the efficacy of ALK-targeted therapies and potential combination strategies to overcome resistance. METHODS: A comprehensive literature search was conducted to collect peer-reviewed publications related to neuroblastoma's biology, classification, and treatment. Articles published between 1980 and 2025 were identified using databases such as PubMed, Scopus, Web of Science, and ClinicalTrials.gov. RESULTS: Neuroblastoma tumorigenesis implicates ALK mutations, particularly at ALK p.R1275Q, ALK p.F1174L, and ALK p.F1245C, with an enrichment in stage 4 tumors and younger patients. Several ALK inhibitors, like crizotinib, ceritinib, lorlatinib, repotrectinib, and alectinib, have shown different levels of success, but resistance to these treatments is still a big challenge. New treatment methods that combine farnesyltransferase inhibitors (FTIs) with ALK tyrosine kinase inhibitors (TKIs) are showing potential in improving how well the treatment works and in stopping the cancer from coming back. CONCLUSION: Precision oncology offers a novel and potentially more effective approach for treating high-risk neuroblastoma. While ALK inhibitors have shown promise, resistance mechanisms necessitate the development of combination therapies and next-generation inhibitors. Future research should focus on optimizing targeted treatment strategies to improve survival outcomes in pediatric patients with ALK-positive neuroblastoma.

ALK inhibitors↗
PubMed1976

Altered enzyme expression in "differentiated" murine neuroblastoma cells.

Out of 17 enzymes studied, only 9 were detectable by starch gel electrophoresis in mouse neuroblastoma cells in culture. Prostaglandin E1 (PGE1) and 4(-3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724), a specific inhibitor of cAMP phosphodiesterase, were used to induce "differentiation". Lactate and 6-phosphogluconate dehydrogenases and adenylate kinase were expressed as single bands in untreated neuroblastoma and induced "differentiated" cells, but the electrophoretic mobility of these enzymes in PGE1-treated cells was slower than that in malignant and R020-1724-treated cells. Three bands of glucose 6-phosphate dehydrogenase were detectable in PGE1-treated cells, whereas the R020-1724-treated cells had two bands and the untreated neuroblastoma cells had only one band. Aldolase was also expressed as a single band; however, the activity of this enzyme was much higher in PGE1-treated cells, whereas the activity was bately detectable for R020-1724-treated and untreated neuroblastoma cells. Some of the enzymes which are present in vivo are absent in vitro. Alkaline phosphatase is present in brain but is absent in neuroblastoma cells in vivo and in vitro. Two bands each of triose phsophate isomerase, fumarase and aldolase are present in brain, but only one band of these enzymes is present in neuroblastoma cells. Although PGE1 and R020-1724 induce many differentiated functions in neuroblastoma cells in a similar manner, PGE1 appears to change characteristically the expression of several enzymes.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed2026

Epigenetic Liquid Biopsy Enables Universal Mutation-Agnostic Molecular Surveillance for High-Risk Neuroblastoma.

PURPOSE: Liquid biopsy monitoring in pediatric solid tumors is limited by low mutational burden and lack of trackable genomic drivers. We sought to develop a mutation-agnostic, methylation-based liquid biopsy framework enabling universal molecular surveillance of high-risk neuroblastoma. EXPERIMENTAL DESIGN: Using whole-genome Oxford Nanopore Technologies sequencing of high-risk neuroblastoma tumors, we compared tumor-derived methylation profiles with a comprehensive atlas of normal human cell types and identified 72 neuroblastoma-specific differentially methylated regions (meNBL) that were reliably detectable in cell-free DNA (cfDNA). Marker robustness and specificity were validated using independent neuroblastoma methylation datasets and assessed against methylation profiles from other cancer types. We established neuroblastoma as a distinct methylation entity within the reference atlas by integrating a panel of 25 meNBLs, enabling quantitative estimation of tumor-derived cfDNA. Assay performance was evaluated across diagnostic, remission, relapse, and healthy control samples and compared with mutation-based and copy number-based approaches. RESULTS: Neuroblastoma-derived cfDNA was consistently detected at diagnosis and relapse but was absent in healthy controls and during confirmed remission. Methylation-based deconvolution demonstrated high specificity, with no detectable background signal in controls, and improved performance relative to copy number-based tumor fraction estimation. Longitudinal profiling enabled early molecular detection of relapse and reliable disease monitoring. CONCLUSIONS: We establish a robust, mutation-independent methylation-based liquid biopsy strategy for neuroblastoma that enables accurate, quantitative disease monitoring across all high-risk patients, including those lacking trackable genomic alterations. This approach supports the clinical translation of methylation-based cfDNA deconvolution as a broadly applicable platform for pediatric precision oncology.

Humans↗
PubMed1977

Chromosomal aberrations in human neuroblastomas.

Six human neuroblastomas were analyzed by Giemsa and fluorescence banding techniques to identify chromosomal aberrations. Two neuroblastomas were primary tumors from untreated children, and four were well lines established from human neuroblastomas. Five of the six tumors studied were diploid or near diploid; one was near tetraploid. A 1p- was found in three of the neuroblastomas examined. The 1p-was present in both primary tumors, and in one it was the only abnormality detected. This deletion was also found in the cells of an established line, in addition to other abnormalities. Giant markers of different origins were found in the four cell lines, and no double-minute chromosomes were found in the primaries or the cell lines studied. Thus, a 1p-deletion was the most consistent abnormality found in the six human neuroblastomas examined in this study. We attempt to correlate this finding with Knudson's hypothesis on the origin of childhood cancer. Additional studies of primary tumors should clarify whether this specific chromosomal abnormality is related to the the acquisition of malignant behavior in human neuroblastomas.

Cell Line↗
PubMed1975

Effect of neurotransmitters, Guanosine triphosphate, and divalent ions on the regulation of adenylate cyclase activity in malignant and adenosine cyclic 3':5'-monophosphate-induced "differentiated" neuroblastoma cells.

The effect of acetylcholine, 3,4-dihydroxyphenylethylamine, prostaglandin (PGE1), guanosine triphosphate (GTP), and divalent ions on adenylate cyclase activity in homogenates of ""differentiated" and malignant mouse neuroblastoma cells was studied. The sensitivity of adenylate cyclase to acetylcholine and 3,4-dihydroxyphenylethylamine markedly increased in adenosine cyclic 3:5-monophosphate-induced differentiated neuroblastoma cells. Although 3,4-dihydroxyphenylethylamine stimulated adenylate cyclase activity in malignant neuroblastoma cells, it failed to do so in X-irradiation induced differentiated cells. PGE1 and GTP stimulated adenylate cyclase activity in malignant and adenosine cyclic 3:5-monophosphate induced differentiated neuroblastoma cells to about the same level. GTP protentiated the PGE1 effect in differentiated concentrations of magnesium and manganese inhibited adenylate cyclase activity; this effect was more pronounced in differentiated cells than in malignant cells. Calcium stimulated adenylate cyclase activity in malignant and differentiated cells to about the same level. There was no significant difference in the values of Km and Vmax of neuroblastoma cells. This study shows that the sensitivity of adenylate cyclase to neurotransmitters and divalent ions (magnesium and manganese) and the sensitivity of PGE1 stimulated enzyme activity to GTP increase in adenosine cyclic 3:5-monophosphate-induced differentiated neuroblastoma cells. Therefore, we suggest that the reverse may be true during malignant transformation of nerve cells.

Acetylcholine↗
PubMed1979

Glycogen in neuroblastomas. A light- and electron-microscopic study of 40 cases.

A light- and electron-microscopic review of 40 cases diagnosed at Children's Hospital of Pittsburgh as ganglioneuroblastoma, neuroblastoma, or small round cell tumor-probably neuroblastoma disclosed four cases that contained abundant glycogen. Two were unquestionable neuroblastomas by electron microscopy; one was primary in the adrenal gland, the other in the mediastinum. In the third case, a paraspinal tumor, the light-microscopic appearance was suggestive or neuroblastoma, but no catecholamine granules or neural processes were demonstrated in the material available for electron microscopy. The fourth case was an undifferentiated malignant tumor in the pectoralis muscle of a 12-year-old girl. By electron microscopy, neural processes were demonstrated and the tumor was classified as peripheral neuroblastoma. Of the remaining 36 cases, electron microscopy readily indicated a diagnosis of neuroblastoma or glangioneuroblastoma in 35 of them. In the other case, the tissue had been fixed in formalin and only a few catecholamine granules were found after an extensive search.

Adolescent↗
PubMed1978

[Biochemical studies on familial neuroblastoma].

According to the two-mutation model of neuroblastoma several investigations were performed in order to find the gene carrier in a family with familial neuroblastoma. The results of these former studies are as follows: 1. Neither chromosomal analyses of the peripheral blood nor the examinations of catecholamines nor of cystathionine in the urine could mark the first step to neuroblastoma. 2. Since cystathioniuria was not only seen in blood-relations but also in relatives by marriage and since vitamin B6 deficiency was revealed, cystathioninuria was interpreted as secondary to vitamin B6 deficiency. In this study the normal values of cystathioninuria and vitamin B6 supply were examined. Furthermore the effect of oral vitamin B6 loading on cystathioninuria and oxaluria in familial neuroblastoma was investigated and the vitamin B6 supply in the neighbours of the family was analysed. The results permitted the following conclusions: 1. In 46 of 58 children and adults cystathioninuria was found in an immeasurable range by column chromatography. Only in 12 persons it could be measured quantitatively. With the exception of 6 explanable elevations no value exceeded 20 mumol/24 hr. These results show that the acceptance of the limiting value of 20 mumol/24 hr for increased cystathioninuria is justified. 2. Vitamine B6 deficiency was found in two of 7 patients. In one child this could be explained by the underlying disease. This finding supports the suggestion that vitamine B6 deficiency can relative frequently observed. 3. The examinations of cystathioninuria and oxaluria before and after loading with vitamine B6 showed different results. Whereas oxaluria decreased after loading cystathioninuria was not surely influenced. 4. The neighbours of the members with familial neuroblastoma showed mostly a reduced vitamine B6 supply. This fact could be an indication of exogenous reason of vitamine B6 deficiency in familial neuroblastoma.

Adult↗
PubMed1977

Morphology, growth, chromosomal pattern and fibrinolytic activity of two new human neuroblastoma cell lines.

Neuroblastoma cell lines LA-N-1 and LA-N-2 were extablished from neuroblastoma cells in the bone marrow and in the primary tumor, respectively, of two children with metastatic neuroblastoma. Morphology, growth in vitro and in athymic nude mice, chromosomal patter, and fibrinolytic activity of these cell lines and of previously extablished human neuroblastoma cell lines IMR-32, SK-N-MC, and SK-N-SH were compared. Most LA-N-1 cells were tear-drop shaped, small cells with processes; they tended to grow in clusters. LA-N-2 was comprised of elongated cells and small round cells, the latter growing in dense clumps on the former. Electron microscopy revealed numerous cytoplasmic dense cores in many LA-N-1 cells but none in LA-N-2 CELLS. During logarithmic growth in vitro, doubling times for LA-N-1, LA-N-2, SK-N-MC, SK-N-SH, and IMR-32 cells were 32,56, 23, 36, and 26 hr, respectively. Cells of all lines formed colonies in soft agar, and, after variable latency periods, LA-N-1, LA-N-2, SK-N-MC, and IMR-32 cells formed tumors in athymic nude mice. The marker chromosome(s) characteristic of each cell line was present in more than 90% of cells of given line. Significant plasminogen-dependent fibrinolytic activity was present in cells of all lines. These studies indicate that LA-N-1 and LA-N-2 cells arose from single but different aberrant progenitor cells and that they have properties of neuroblastoma cells. They also demonstrate that cell lines derived from human neuroblastomas are heterogenous as are the tumors in children.

Animals↗
PubMed1979

Olfactory neuroblastoma (esthesioneuroblastoma): a light and ultrastructural study of two cases.

Olfactory neuroblastoma is a malignant neoplasm with a varied biological behavior. Its clinical course is unpredictable and there is no correlation between its microscopic features and biological behavior. The present study deals with light and ultrastructural characteristics of two cases of olfactory neuroblastoma of the nasal cavity. In one patient, the definitive diagnosis was established on the basis of ultrastructural features of the lesion. The most consistent fine structural findings were the presence of intracytoplasmic densecored neurosecretory granules, "true" and "pseudo-" rosettes, and the neuritic processes emanating from the tumor cells. On the basis of their biochemical, histochemical, and ultrastructural characteristics, olfactory neuroblastomas are similar to neuroblastomas arising from the adrenals or sympathetic nervous system. These findings, therefore, support the hypothesis that olfactory neuroblastomas are most likely of neural crest origin and thus belong to a group of neoplasms collectively known as "apudomas" or neurocristomas. The literature review strongly favors combined surgery and postradiation as the most effective treatment of olfactory neuroblastoma.

Aged↗