Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Naltrexone, an opioid antagonist, had an inhibitory effect on the growth of murine S20Y neuroblastoma in BALB/c nude mice. Daily injections of 0.1 mg naltrexone/kg, which invoked a receptor blockade for 6-8 hours/day, resulted in 31-92% delay in latency time prior to tumor expression and a 27-49% increase in mean survival time; the magnitude of antitumor response was governed by tumor burden. Inoculation of neuroblastoma (10(6)-2.5 X 10(4) cells) resulted in measurable tumors in 10-13 days and mean survival times of 30-34 days. Immunoreactive beta-endorphin was detected in tumor tissue (39.7 pg/mg protein). Receptor binding assays revealed specific saturable binding of ligands related to delta- and kappa-binding sites, but not for the mu-binding site. These results demonstrate that opioid antagonist modulation of neuro-oncogenesis is not dependent on the integrity of T-cell-mediated immunity and suggest the feasibility of utilizing the nude mouse model in exploring the role of endogenous opioids in human cancers.
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PMID:Modulation of murine neuroblastoma in nude mice by opioid antagonists. 302 1

The role of endogenous opioid systems (endogenous opioids and opioid receptors) in human cancer was explored using an opioid antagonist paradigm and neuroblastoma cells (SK-N-MC) transplanted into nude mice. Mice inoculated with 2.5 X 10(6) neuroblastoma cells received daily injections of either 0.1 or 10 mg/kg naltrexone (=0.1 and 10 NTX groups) which blocked the opioid receptor for 6-8 hr/day or the entire 24 hr/day, respectively, or sterile water. The latency for appearance of a measurable tumor (5 mm diameter) in the 0.1 NTX group was 27% longer than controls (11 days), and the first death in this group occurred 33% later than controls (day 27). Mice inoculated with tumor cells in the 10 NTX group had an acceleration (18%) in the latency of tumor appearance and, 2 weeks after cell inoculation, 70% of the mice in this group had tumors, in contrast to 10% of the controls. At the termination of the experiment (day 45), only 33% of the 10 NTX group were alive, in contrast to 90% of the controls. Receptor binding assays using DAGO, DADLE, or EKC revealed specific saturable binding only for DADLE and EKC. NTX administration resulted in a 148-186% increase in density for both binding sites, but no changes in binding affinity. Measures of opioid levels showed that tumor tissue levels of both beta-endorphin and methionine-enkephalin were elevated 2.5 to 6.5 fold from control values in both NTX groups, whereas plasma beta-endorphin was subnormal by 4 to 6 fold. These results indicate that endogenous opioid systems regulate human neuro-oncogenesis, with opioids being active inhibitors of growth. Opioid antagonists up-regulate receptors and increase tissue levels of endogenous opioids and, under conditions in which the opioid antagonist is short-acting (e.g., 0.1 NTX), can have an exaggerated antitumor effect during the interval when the antagonist is no longer present.
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PMID:Modulation of human neuroblastoma transplanted into nude mice by endogenous opioid systems. 304 Nov 43

It is clear that there are at least two classes of cancer-related genes. The more characterized of these are the oncogenes, whose activation appears to play a major role in human neoplasia. There are now two families of oncogenes, the myc and ras families, whose cooperation seems capable of transforming normal cells in culture to tumorigenic cells. As such, they appear to form complementation groups with immortalizing and transforming properties, respectively. Moreover, the oncogenes can be subclassified as tyrosine kinases or kinase related, GTP binding proteins, growth factors or growth factor receptors or nuclear proteins. More than 20 viral oncogenes have been identified, for which more than 30 proto-oncogenes or pseudogenes exist in the human genome. Many of these have been cloned, characterized to some extent, and mapped to particular chromosomes or regions of chromosomes. Further, more than 20 additional putative oncogenes or transforming genes have been identified by tumor DNA transfection studies or at sites of integration or translocation for which no viral transforming gene cognates exist. Oncogenes can be activated by increased or unregulated expression, increased copy number (duplication, amplification), or somatic mutation resulting in a protein with increased oncogenic potential. Examples of all of these mechanisms can be found in several specific human cancers or leukemias. The cytogenetic correlate of enhanced expression is a translocation between two chromosomes at specific breakpoints with no net loss of genetic material (e.g., increased c-myc expression resulting from the 8;14 translocation in Burkitt's lymphoma). The phenomenon of increased gene copy number can sometimes be visualized as trisomy or tetrasomy for a particular chromosome but more dramatically as the development of extrachromosomal DMs or as chromosomally integrated HSRs (e.g., the N-myc gene amplification seen in neuroblastoma). Finally, certain somatic mutations can be associated with translocations (e.g., the bcr/abl fusion product created as a result of the 9;22 translocation in chronic myelogenous leukemia), but they are more commonly submicroscopic (as characterized by point mutations in the ras gene family). Evidence is accumulating for a second class of cancer-related genes whose absence or inactivation is associated with tumorigenesis. These genes are associated at the cytogenetic level with chromosomal deletions, in which the breakpoints may be variable, but specific, common regions are consistently deleted.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The involvement of oncogenes and suppressor genes in human neoplasia. 331 93

The ultrastructure of neuroblastoma was examined using unstained sections so that ferritin particles could be identified by the electron density of their iron cores. Ferritin and hemosiderin were found in ten of 11 neuroblastomas that were examined when the patients first presented. The study was therefore expanded to an additional group of children, including some diagnosed by noninvasive procedures and given chemotherapy before the excision of their tumors. In this second group 12 of 20 specimens contained ferritin and hemosiderin in variable amounts. In both groups there was a tendency for patients with advanced disease to have increased amounts of iron compounds in the tumor tissue (Stage III and particularly Stage IV). Most Stage IV patients also had elevated serum ferritin levels. However, based on the available heterogenous material, no absolute relationship could be established between age, disease stage, tumoral storage iron, and the level of serum ferritin. The presence of ferritin in neuroblastoma may be linked to the elevated serum ferritin levels and may be implicated in tumorigenesis.
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PMID:Neuroblastomas contain iron-rich ferritin. 336 71

The phenomenon of familial neuroblastoma is discussed in the context of case reports describing disseminated neuroblastoma in two of three half-brothers who share a common unaffected mother and who each have a different father. This family's cytogenetics proved to be unremarkable; also, the mother's peripheral blood DNA did not show tumorigenic capacities in transfection-nude mice experiments. An analysis of reported cases permits an updated examination of the clinical features of this entity and defines the limits of genetic counseling of families of all neuroblastoma patients. Multiple primaries are a hallmark of familial neuroblastoma. Most diagnoses are made in the first 18 months of life and at ages that fall within 12 months of the age of diagnosis of the other affected family member. Difficulties in determining the incidence and penetrance of an inherited susceptibility to neuroblastoma derive from undiagnosed tumors that have undergone regression or spontaneous maturation to benign ganglioneuroma, as well as from early deaths or long-term treatment complications that preclude reproduction and multigenerational pedigrees. Nevertheless, the risk of neuroblastoma in siblings or offspring of the large majority of persons with neuroblastoma appears to be less than 6%. Recent observations concerning chromosomal aberrations and oncogenes in embryonal malignancies are presented in an integrated model of tumorigenesis that corresponds to clinical experience.
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PMID:Familial neuroblastoma. Case reports, literature review, and etiologic considerations. 395 26

Although rarely reported, neuroblastoma in monozygotic siblings merits attention because study of its features may aid in elucidating mechanisms of tumorigenesis. We describe disseminated neuroblastoma in one of monozygotic triplets, including both documentation of monozygosity and long-term follow-up of the unaffected co-twins. Information from reports of monozygotic twins concordant and discordant for neuroblastoma reinforces the hypothesis that hereditary factors may be predominant in neuroblastoma diagnosed in infants, whereas nonheritable random mutational genetic events may be more important in neuroblastoma diagnosed after infancy.
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PMID:Monozygotic siblings discordant for neuroblastoma: etiologic implications. 404 Sep 63

Amplified cellular genes in mammalian cells frequently manifest themselves as double minute chromosomes (DMs) and homogeneously staining regions of chromosomes (HSRs). With few exceptions both karyotypic abnormalities appear to be confined to tumour cells. All vertebrates possess a set of cellular genes homologous to the transforming genes of RNA tumour viruses, and there is circumstantial evidence that these cellular oncogenes are involved in tumorigenesis. We have recently shown that DMs and HSRs in cells of the mouse adrenocortical tumour Y1 and an HSR in the human colon carcinoma COLO320 contain amplified copies of the cellular oncogenes c-Ki-ras and c-myc, respectively. Both DMs and HSRs are found with remarkable frequency in cells of human neuroblastomas. We show here that a DNA domain detectable by partial homology to the myc oncogene is amplified up to 140-fold in cell lines derived from different human neuroblastomas and in a neuroblastoma tumour, but not in other tumour cells showing cytological evidence for gene amplification. By in situ hybridization we found that HSRs are the chromosomal sites of the amplified DNA. The frequency with which this amplification appears in cells from neuroblastomas and its apparent specificity raise the possibility that one or more of the genes contained within the amplified domain contribute to tumorigenesis.
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PMID:Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. 688 61

Specific constitutional chromosome rearrangements have been described in a small number of individuals with two solid childhood tumors, retinoblastoma and Wilms' tumor. On the basis of these observations, a causal relationship between these chromosome abnormalities and tumorigenesis has been postulated. Though a specific constitutional chromosome abnormality has yet to be reported in association with neuroblastoma, another childhood tumor, we now confirm the involvement of a particular chromosome segment in structural abnormalities in cells from this tumor. Deletions or rearrangements of chromosome 1p were found in preparations from four of six neuroblastomas from individuals with normal constitutional karyotypes and in three of four permanent neuroblastoma cell lines. Structural abnormalities resulting in the loss or rearrangement of material from 1p (with the most frequent break point being 1p32 and with all rearrangements involving the apparent loss or rearrangement of material distal to 1p31, always including 1p34 to 1pter), represent the single most common class of chromosome aberrations in neuroblastoma. This suggests that the distal portion of 1p contains at least one gene involved in the development of neuroblastoma.
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PMID:Abnormalities of chromosome 1p in human neuroblastoma tumors and cell lines. 713 92

We have studied the glycosphingolipid composition in an F-11 neuroblastoma cell line originated from hybridization of a mouse neuroblastoma cell line (N18TG-2) with rat dorsal root ganglion cells. The total lipid-bound glucose of F-11 cells was estimated to be 0.28 micrograms/mg of protein and the total lipid-bound sialic acid was 0.82 micrograms/mg of protein. The major neutral glycosphingolipids were Gb4 (37% of the total neutral glycosphingolipids), Gb3 (15%), LacCer (21%), and GlcCer (15%). The major gangliosides were found to be GM3 (37% of the total gangliosides), GD3 (27%), O-acetylated GD3 (18%), and GD1a (4%), with trace amounts of GD2. The unusually high concentration of O-acetylated GD3 is consistent with its putative role as a tumor marker. Immunocytochemical localization studies of GD3 and O-acetylated GD3, examined by mouse monoclonal antibodies R24 and D1.1, respectively, revealed that the cell bodies and processes were all positively stained. To elucidate the role of O-acetylated GD3 in tumorigenesis, we transfected F-11 cells with the O-acetylesterase gene from influenza C virus. Compared with the original cell line, the transfected cells showed a dramatic increase in the level of GD3 (150% of that in the control cells) and a significant decrease of the concentration of O-acetylated GD3 (27% of control cells). In addition, the transfected F-11 cells exhibited a morphology different from the parental cells with enlarged cell bodies and elongated neurites. We conclude that alteration of ganglioside composition, particularly the expression of GD3 and O-acetylated GD3, may be associated with the morphological changes observed in this cell line.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glycosphingolipid composition of murine neuroblastoma cells: O-acetylesterase gene downregulates the expression of O-acetylated GD3. 754 79

The oncogenic activation by amplification of the MYCN gene is frequently observed in human neuroblastomas and occasionally in other tumours with neuronal qualities. As a consequence of amplification, elevated levels of the mycN protein are expressed. mycN contains a C-terminal basic region (BR) that can bind to DNA, and a helix-loop-helix (HLH)-leucine zipper (Zip) domain, which is responsible for the physical interaction with another HLH-Zip protein, max. This principle structure is conserved among all members of the MYC gene family. The resulting dimers can bind to the DNA sequence CACGTG. The mycN protein, but not max, contains, near the N-terminus, a region conferring the ability to activate the transcription of genes. mycN/max heterodimers probably activate and max/max homodimers repress transcription of, as yet, unidentified target genes. In neuroblastoma cells, where mycN is deregulated, the balanced interaction of BR-HLH-Zip proteins is probably perturbed, and, therefore, genes controlled by mycN might be abnormally expressed and thereby alter normal cell growth with the consequence of tumorigenesis.
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PMID:The mycN/max protein complex in neuroblastoma. Short review. 757 56


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