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)

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.
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PMID:Developmental genetics of neuroblastoma. 18 2

All known tumor types have been reported in the neonate. A numerical listing and discussion are beyond the scope of this review. Wells and Fraumeni give some insight into common congenital malignant neoplasms. Table 2 lists the percentage of neonatal deaths caused by type-specific cancers. Retinoblastoma is probably the most common malignant tumor in the neonate. About seven per cent of these tumors have been apparent at birth. This tumor is not discussed in either article because it is not lethal until muypes in neonatal and pediatric patients. Some congenital malformations in the in the neonate are recognized as being frankly benign (cysts), potentially malignant (teratomas), and frankly malignant (neuroblastoma). A high percentage of teratomas are benign in the newborn period. Leukemia in the newborn appears to be more aggressive yet neuroblastoma has a better prognosis. More studies are needed to help us define why the neonate does better with some tumors and worse with others. Surface cell markers on neonatal leukemia, B and T cell function studies, and other immunologic surveillance studies are needed. Study of neonatal oncology may add to our knowledge of carcinogenesis and oncogenesis in the future.
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PMID:Neonatal oncology. 19 75

Single subcutaneous inoculation of human adenovirus type 12 (Ad.12), 0.05-0.1 ml of 10(8.0) TCID50 HEK cells/0.1 ml, was made on the back of 0-day-old hamsters. In 21 of 25 hamsters (84.0%), multiple solid tumors developed close to the inoculation site within 3 months. No control hamsters developed tumors. Tumor histopathology revealed the characteristic Homer Wright rosettes of neuroblastoma. Ad. 12-specific tumor antigens were demonstrable in both the primary and the cultured tumor cells by the immunofluorescein technique. Histochemical demonstration of cholinesterase and NADH oxidoreductase gave rise to a predominantly positive intracytoplasmic granule within the tumor cells. Electron microscopy showed remarkably uniform cell morphology: small, undifferentiated neuroblastic cells with poorly developed intracytoplasmic organelles; many possessed characteristic solitary cilia in a 9 + 0 tubules pattern. Intercellular junctions were poorly developed. Search for an incipient tumor cell aggregate by means of immunofluorescein T-antigen detection was carried out through a 240-h period following Ad. 12 inoculation. A sequential study in parallel with electron microscopic examination of the normal subcutaneous tissue proved that neuroblastic cells closely associated with the muscle spindle anlage could preferentially become the most sensitive target for Ad. 12 tumorigenesis.
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PMID:Cell origin of human adenovirus type 12-induced subcutaneous tumor in Syrian hamsters. 44 84

The c-Myc protein is a potential activator of transcription, with the ability to bind in a heterodimer form with Max to DNA sequences containing the core hexanucleotide sequence CAC(G/A)TG. These properties are shared with L-Myc, a homologous oncoprotein expressed in small cell lung carcinoma cells; with N-Myc, expressed in neuroblastoma cells; and with avian v-Myc, the c-Myc homolog expressed by a chicken retrovirus. The c-Myc, and probably v-Myc, proteins also have nonspecific DNA binding function, which may improve the kinetics of specific DNA binding. Curiously, this domain appears not to be conserved in L-Myc or N-Myc [22]. The data that have accumulated to date are consistent with a model in which a c-Myc/Max heterodimer positively regulates the transcription of growth-related genes, with Max homodimer functioning as a negative regulator of the same genes (Fig. 4) [55]. Max is expressed constitutively at low levels, whereas c-Myc is expressed at low levels in quiescent cells, but high levels of c-Myc are induced by mitogenic stimulation [56]. Thus, in proliferating cells c-Myc/Max heterodimers might bind to the regulatory elements of growth-related genes, where the c-Myc TAD might stimulate transcription. Conversely, in quiescent cells with little c-Myc present, Max homodimers might predominate. They might bind to exactly the same regulatory elements, but due to the apparent absence of a TAD in Max [36], transcription might be repressed. Validation of this model will require the demonstration of clear regulation of a physiological promoter of a growth-related gene by c-Myc/Max. Although it is widely believed that Myc proteins function as transcriptional activators, this hypothesis has only been conclusively supported recently [57, 58]. A theory that c-Myc plays a role in DNA replication is not as well substantiated at this point. It is even possible that Myc might be involved in both transcription and replication. Although the function of these fascinating proteins has been enigmatic for a decade, the rate of progress in our understanding of Myc function is accelerating. Such progress will undoubtedly lead to a deeper appreciation of this protein, which lies at the crossroads of cellular proliferation and oncogenesis.
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PMID:DNA binding by the Myc oncoproteins. 136 64

Insulin-like growth factors (IGF-I and IGF-II) are mitogenic polypeptides that play an important role in normal growth and development. IGF-II has been shown to stimulate the growth of neuroblastoma tumors in an autocrine and paracrine fashion. Critical in determining the role of IGF-II in tumorigenesis is the necessity to delineate factors affecting the transcription of IGF-II in normal and tumor tissues. To date such factors are poorly characterized. In this study we find that retinoic acid (RA), a naturally occurring morphogen, that has been shown to be indispensable in the development of the chick limb bud, stimulates an increase in IGF-II messenger RNA (mRNA) in the Lan-1-15N neuroblastoma cell line. This increase in IGF-II is coincident with RA mediated inhibition of DNA synthesis. An increase in the steady state levels of IGF-II mRNA is detectable within 2 h of RA treatment and maximal by 24 h. In RA-treated Lan-1-15N cells, IGF-II mRNA levels are regulated at the level of new gene transcription and result in an increase in IGF-II protein in the culture supernatant. These studies suggest one mechanism affecting the production of IGF-II in vivo may be mediated by RA and detail a model system by which transcriptional regulation of IGF-II mRNA can be analyzed.
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PMID:Retinoic acid regulates insulin-like growth factor II expression in a neuroblastoma cell line. 137 6

The N-myc oncogene has been implicated in the pathogenesis of a number of human tumors, including childhood neuroblastoma and adult small cell lung cancer. We have isolated and characterized complementary DNA clones derived from a transcription unit, N-cym, located on the opposite DNA strand to N-myc, with extensive overlap existing between the 5' ends of the two transcription units. The N-cym gene, which can encode a 109-amino acid protein, is expressed during fetal development, as well as in tumor cell lines containing amplified N-myc loci, where it is expressed at very high levels. Although other examples of overlapping, opposite-strand eukaryotic genes exist, N-myc and N-cym are unique in that they appear to be coregulated in tumor cell lines under basal growth conditions and in response to the differentiating agent retinoic acid. This coregulation suggests that their protein products may be functionally interrelated during normal development and oncogenesis.
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PMID:Isolation and characterization of complementary DNA for N-cym, a gene encoded by the DNA strand opposite to N-myc. 141 2

Male transgenic mice that carry a construct containing 5'-flanking sequences of the gp91-phox gene linked to the early region of the simian virus 40 (SV40) genome reproducibly develop tumors arising from the prostate gland. As gp91-phox is expressed exclusively in terminally differentiating hematopoietic cells of the myelomonocytic lineage, the induction of tumors arising from the prostate gland was unexpected. These lesions appear to be due to a novel transcription signal that was generated during the construction of the transgene. Surprisingly, the histopathological and biochemical properties of the tumor are diagnostic of neuroblastoma rather than of adenocarcinoma of the prostate gland. Tumors produce SV40 T antigen and isoforms of neural cell adhesion molecule characteristic of neuronal cells, and they occur in a testosterone-independent manner. Microscopic examination of prostate glands from young transgenic mice reveals the presence of small lesions arising outside of the prostate gland epithelium, which is consistent with the diagnosis of neuroblastoma and further distinguishes this tumor from prostatic adenocarcinoma. Prostate gland tumors occur in all male animals of susceptible lines carrying the gp91-phox promoter/SV40 early-region transgene. However, variability in the time at which gross tumors appear and the presence of cells expressing T antigen prior to tumorigenesis suggest that somatic events in addition to T-antigen production are required for the development of a malignancy. The extraordinary restriction of the site of tumorigenesis in these animals indicates the presence in the prostate gland of a novel, tissue-specific neuroectodermal cell of origin. These transgenic animals provide a model system for the study of neuroectodermal malignancies.
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PMID:Restriction of neuroblastoma to the prostate gland in transgenic mice. 165 58

We have found a substantial decrease in the level of Na,K-ATPase beta 2-subunit mRNA in xenografts of human renal, lung hepatocellular carcinomas in nude mice as compared with corresponding normal tissues, as well as in the neuroblastoma cell line as compared with the neuron primary cell culture. The level of beta 1 mRNA is decreased in kidney and lung tumor cells, but is unchanged in hepatocellular carcinoma. In the neuroblastoma cell line the level of beta 1 subunit mRNA was found to be higher then in neuron primary cell culture. The level of alpha 1 mRNA in investigated tumors was the same as in normal tissues. These results may give evidence of the involvement of beta 2-subunit in the process of tumorigenesis as was shown for some other adhesion molecules.
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PMID:Tissue-specific expression of Na,K-ATPase beta-subunit. Does beta 2 expression correlate with tumorigenesis? 165 77

Cell adhesion molecules (CAMs) of the immunoglobulin supergene family may play important roles in tumorigenesis and the development of metastatic disease. In a variety of human malignancies, tumor progression has been observed to be associated with changes in CAM expression. An early event in colorectal tumorigenesis appears to be the down regulation of a normally expressed CAM, DCC. Over-expression of a second CAM, carcinoembryonic antigen, is associated with colorectal tumors which have a high risk for metastasis development. Several tumors, including Wilms tumors and neuroblastoma, have been found to express a developmentally regulated form of NCAM which inhibits a variety of cell-cell interactions. Malignant cells not only show aberrations in the expression of their CAMS and thus their normal cell-cell interactions, but establish new adhesive interactions. The development of metastatic potential in cutaneous melanoma is associated with the de novo expression of two CAMs, one of which is ICAM-1, a molecule mediating adhesion between the tumor cells and leukocytes.
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PMID:Cell adhesion molecules of the immunoglobulin supergene family and their role in malignant transformation and progression to metastatic disease. 168 May 75

p34cdc2 is a protein kinase that has an important role in controlling cell cycle progression and may regulate tumor suppressor gene activity. In this work, we show that the arrest of cell growth and induction of differentiation in a tumorigenic neuroblastoma cell line by retinoic acid (RA) is associated with a 75-fold decrease in the level of p34cdc2 protein. The RA induced decrease in p34cdc2 levels does not simply reflect the arrest of cell growth, because p34cdc2 levels are not reduced when neuroblastoma cells are growth arrested by nutrient deprivation. Furthermore, dephosphorylation of the tumor suppressor gene product RB, a substrate for the p34cdc2 kinase activity, is observed only when p34cdc2 levels are decreased in RA treated cells. These studies link regulation of cdc2 level, RB phosphorylation state, and induction of differentiation by RA and suggest that alterations in the cdc2 gene or in genes controlling its regulation contribute to tumorigenesis.
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PMID:Retinoic acid negatively regulates p34cdc2 expression during human neuroblastoma differentiation. 175 5


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