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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The literature on chemical induction and natural occurrence of neurogenic tumors in mice and some unpublished data from our laboratories are reviewed. Neurogenic tumors are a minor component of the total tumorigenic response of mice to alkylating agents such as ENU and MNU. In comparison with rats, a given dose of ENU induces a much lower incidence of neurogenic tumors in mice, and the mean latency is much longer than in rats. Although most neurogenic tumors induced by ENU in mice by either transplacental or direct postnatal exposure are of glial or Schwann cell origin, as in rats, and occur most frequently in the cerebrum or cranial nerves, respectively, medulloblastomas of the cerebellum also occur in treated mice. Transplacental and neonatal exposure to ENU were much more effective in inducing neurogenic tumors than treatment later in life. Ependymomas were not seen in mice, although they are common in ENU-treated rats. Neuroblastoma of the adrenal medulla, a common human pediatric tumor, has not been induced to either species, but it does occur spontaneously in mice. The induction by ENU of medulloblastomas demonstrates that this rodent equivalent of an embryonal tumor of the human nervous system can result from exposure to exogenous chemical agents.
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PMID:Transplacental and neonatal induction of neurogenic tumors in mice: comparison with related species and with human pediatric neoplasms. 38 62

We have examined the hypothesis that nonhematopoietic malignancies may contain cells corresponding to those which occur during the differentiation of tissue precursors. Neuroblastoma, an embryonal tumor of the adrenal medulla, was studied because of its well described ability to differentiate both in vivo and in vitro. We examined the expression of four genes during development of the human adrenal medulla: tyrosine hydroxylase, chromagranin A, pG2, and beta-2-microglobulin. The sequential expression of these genes by adrenal neuroblasts marks successive stages during maturation of the chromaffin lineage. We also observed a population of neuroblasts during adrenal medullary development that did not express any of these four genes, suggestive of adrenal medullary cells differentiating along nonchromaffin lineage(s). We then evaluated 27 neuroblastoma cell lines for the expression of these genes and found that 24 expressed chromaffin markers, with 19 of these mimicking the pattern of gene expression found during development. Three cell lines did not express tyrosine hydroxylase, chromogranin A, or pG2, consistent with either a very undifferentiated neural crest cell or maturation along a nonchromaffin lineage. These data indicate that neuroblastoma tumor cells correspond to adrenal neuroblasts arrested during morphogenesis of the adrenal medulla and raise the possibility that malignant transformation of cells at different stages of tissue maturation may contribute to the diversity that characterizes tumors of solid tissues.
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PMID:Human neuroblastoma tumor cell lines correspond to the arrested differentiation of chromaffin adrenal medullary neuroblasts. 198 60

Neuroblastoma is an embryonal tumor that typically arises in cells of the developing adrenal medulla. IGF-II mRNA is expressed at high levels in the adrenal cortex before birth but it is not detectable until after birth in the adrenal medulla. Neuroblastoma cell lines corresponding to early adrenal medullary precursors did not express IGF-II, although all three cell lines we tested were growth stimulated by IGF-II. Cell lines corresponding to more mature adrenal medullary cells expressed IGF-II, and one, SK-N-AS, grows by an IGF-II autocrine mechanism (J. Clin. Invest. 84:829-839) El-Badry, Romanus, Helman, Cooper, Rechler, and Israel. 1989. An examination of human neuroblastoma tumor tissues for IGF-II gene expression using in situ hybridization histochemistry revealed that IGF-II is expressed by tumor cells in only 5 of 21 neuroblastomas, but is detectable in cells of nonmalignant tissues including adrenal cortical cells, stromal fibroblasts, and eosinophils in all 21 tumors. These findings indicate that IGF-II may function as an autocrine growth factor for some neuroblastomas and as a paracrine growth factor for others. They suggest that the growth regulatory pathways utilized by neuroblastoma mimic those used in the precursor cell type from which individual tumors arise.
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PMID:Insulin-like growth factor II-mediated proliferation of human neuroblastoma. 199 49

Class I major histocompatibility complex (MHC) antigen expression in neuroblastoma may play a role in the oncogenicity of this embryonal tumor of childhood. Since N-myc amplification in neuroblastoma tumors is associated with rapid tumor progression (33) and N-myc decreases Class I MHC antigen expression in rat neuroblastoma cells (21), we quantitated levels of N-myc mRNA and Class I MHC cell surface antigens in a panel of 24 human neuroblastoma cell lines. We found that N-myc expression is not invariably associated with low levels of beta 2-microglobulin (B2M) and Class I MHC antigen expression. As we considered that Class I MHC antigens may be regulated in association with the differentiation stage of the neuroblastoma tumor, we examined the expression of B2M during development of the human adrenal medulla, the tissue of origin of most neuroblastomas. We found that B2M is a marker of differentiated adrenal medullary cells, expressed late during the third trimester of development. Moreover, using morphological and immunological criteria, we found that B2M is expressed in differentiated tumor cells. These data suggest that the expression of B2M in neuroblastoma is associated with the stage of differentiation of the tumor cell and not N-myc expression. Furthermore, these findings suggest that neuroblastomas may correspond to the arrested differentiation of adrenal neuroblasts at different stages of development.
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PMID:Beta 2-microglobulin expression in human embryonal neuroblastoma reflects its developmental regulation. 218

We constructed a human pheochromocytoma cDNA library and used differential hybridization to human pheochromocytoma and human neuroblastoma cDNA probes to isolate genes that are highly expressed in the adrenal medullary neuroendocrine tumor, pheochromocytoma, but not in the more immature embryonal tumor of adrenal medulla, neuroblastoma. Two cDNA clones, pG8 and pG2, were more highly expressed in normal and neoplastic chromaffin tissue than they are in neuroblastoma. Furthermore, they are expressed in a remarkably limited number of other human tumors or normal tissues. pG8 is highly expressed in medullary thyroid carcinoma, another tumor of neural crest origin, which can occur in association with pheochromocytoma in the multiple endocrine neoplasia type II syndrome. pG2 is highly expressed in the adrenal cortex, an endocrine gland thought to be embryologically unrelated to the neural crest-derived adrenal medulla. The expression of both pG8 and pG2 can be induced in human neuroblastoma cells with dexamethasone, suggesting a mechanism by which glucocorticoids may influence development of a neuroendocrine phenotype.
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PMID:Molecular markers of neuroendocrine development and evidence of environmental regulation. 347 Jul 97

This report documents, in seven infants younger than 2 years of age, a previously unrecognized association of a renal embryonal neoplasm (malignant rhabdoid tumor in six patients and a Wilms' tumor in one) with an embryonal primary tumor originating in the central nervous system. The neuroepithelial tumors included three cerebellar medulloblastomas, one pineoblastoma, one primitive neuroepithelial tumor (probably cerebral neuroblastoma), one malignant subependymal giant cell astrocytoma, and one cerebellar medulloepithelioma with divergent glial and neuronal differentiation. There is no evidence that this association is based on the selective neoplastic transformation of embryonal cells of similar histogenetic or cytogenetic origin. The relationship between these dissimilar, embryologically unrelated tumors remains enigmatic.
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PMID:The association of embryonal tumors originating in the kidney and in the brain. A report of seven cases. 609 60

H19 and insulin-like growth factor II (IGF2) are among a few genes which have been confirmed to be imprinted in normal human embryonal tissues. This results in monoallelic expression of maternal H19 and paternal IGF2. Loss of imprinting of these genes producing biallelic expression has been observed in Wilm's tumor and embryonal rhabdomyosarcoma, suggesting that an epigenetic change of DNA, in addition to a genetic change in oncogene(s) and/or tumor suppressor gene(s), may be involved in the development of these childhood cancers. Neuroblastoma, which is an embryonal tumor originating from neural crest-derived cells, occasionally occurs in individuals with the Beckwith-Wiedemann syndrome; Wilm's tumor and embryonal rhabdomyosarcoma occur even more frequently in the Beckwith-Wiedemann syndrome; and paternal uniparental disomy of H19 and IGF2 loci (chromosome 11p15) is present in the Beckwith-Wiedemann syndrome. Furthermore, neuroblastoma cell lines express IGF2, and autocrine/paracrine effects of IGF2 have been demonstrated in these cells. Thus, we examined for imprinting of both H19 and IGF2 in primary untreated neuroblastomas using the RsaI and ApaI polymorphisms within these genes, respectively. Seven of 15 tumors were informative for H19 and for IGF2, and all of these cases showed monoallelic expression of both of these genes. These results indicate that loss of imprinting of H19 and IGF2 does not occur in neuroblastomas.
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PMID:Maintenance of normal imprinting of H19 and IGF2 genes in neuroblastoma. 761 76

Despite the remarkable amount of clinical and biologic information that has been cumulated on neuroblastoma, particularly in the last two decades, this embryonal tumor of early childhood remains one of the major challenges of pediatric oncology. It is now clear that the term encompasses at least two entities characterized by different features and outcome. The favorable entity includes patients with localized disease, infants and stage IV-s. The unfavorable entity refers to patients older than one year at diagnosis with disseminated disease. However, in both entities exceptions exploiting a clinical course different from expected do occur. Molecular biology is presently suggesting that specific genomic alterations may predict unfavorable events. Patients evaluation should thus include the study of biologic features since they may provide us with strongly predictive clues. In this article the Authors describe the main clinical features of the neoplasia and focus on some of its more peculiar patterns. They also refer on the criteria that the International Neuroblastoma Staging System (INSS) has recently designed regarding diagnosis, evaluation of disease extent, and response to therapy, in order to improve the cooperations and the understanding among the major Cooperative Groups. Finally, the treatment outlines of the main forms of clinical presentations are described.
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PMID:[Neuroblastoma: update on clinical aspects and therapy]. 802 94

Neuroblastoma is an embryonal tumor derived from the sympathetic nervous system. Although all neuroblastomas have a neuronal character, a subset of tumors also show evidence of extra-adrenal neuroendocrine differentiation in discrete cell layers. A characterization of the cells of the developing human sympathetic nervous system was performed, identifying growth-associated protein-43, neuropeptide tyrosine, and Bcl-2 as marker genes for sympathetic neurons. Whereas all neuroblastomas express growth-associated protein-43, neuropeptide tyrosine, and Bcl-2, tumors with differentiating cells with neuroendocrine features expressed these genes only in the morphologically immature, proliferating cells. Thus, with neuroendocrine tumor cell differentiation, neuronal marker gene expression vanished and proliferation ceased and was succeeded by expression of chromogranin A/B and insulin-like growth factor-2, markers of neuroendocrine chromaffin differentiation. These tumors appear to provide examples of spontaneous lineage conversion from a neuronal to a neuroendocrine phenotype.
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PMID:In vivo spontaneous neuronal to neuroendocrine lineage conversion in a subset of neuroblastomas. 900 28

Childhood neuroblastoma, an embryonal neoplasm of sympathetic nervous system progenitors, occurs in a familial form with an autosomal dominant mode of inheritance. Genetic susceptibility to this disorder is thought to arise via a germline mutation affecting a tumor suppressor gene, in accord with the two-hit model established for familial and sporadic retinoblastoma. Surprisingly, the familial neuroblastoma predisposition locus does not map to chromosome band 1p36, a genomic region likely to contain one or more neuroblastoma suppressor genes. We reasoned that inherited point mutations affecting one allele would be unmasked in many cases by somatically acquired deletions of the second allele that included the target gene in the tumor cells from these patients. Thus, to identify chromosomal regions that might contain suppressor genes important in hereditary neuroblastoma, we analyzed six familial tumors by comparative genomic hybridization. Recurrent losses of genetic material were detected on chromosome arms 3p (consensus region, 3p24-pter), 10p (consensus, 10p12-p13), 10q (consensus, 10q25-qter), 16q (consensus, 16q12-q22), and 20q (consensus, 20q13.3-qter), in addition to the regions commonly deleted in sporadic neuroblastomas (1p36 and 11q). These chromosomal sites may harbor novel tumor suppressor genes that could aid in our understanding of the predisposition to and pathogenesis of familial neuroblastoma and potentially sporadic tumors as well.
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PMID:Novel regions of chromosomal loss in familial neuroblastoma by comparative genomic hybridization. 921 99


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