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)

Overexpression of the nuclear phosphoprotein p53 has been detected in many different transformed human cell lines and primary adult tumors. Elevated steady-state levels of p53 appear to be the result of an increase in the stability of the protein and, in adult cancers, high levels of the protein are associated with mutation of the p53 gene. In this study, overexpression of p53 was detected in 4 out of 5 human neuroblastoma-derived cell lines. The protein expressed by each of these four lines had a significantly prolonged half-life relative to the p53 protein in immortalized rodent fibroblasts and normal bovine adrenal medullary cells. However, no mutations were detected in the highly conserved regions of the p53 gene in these four neuroblastoma lines and the protein being expressed was not recognized by the mutant-specific anti-p53 monoclonal antibody, PAb 240. Upon retinoic acid-induced differentiation of the LA-N-5 neuroblastoma cell line, the level of p53 protein declined, as did the level of p53 mRNA, but the half-life of the protein remained unchanged. The high level of protein observed in the undifferentiated cell lines appears to result from expression of a stable wild-type p53 protein and increased transcription. In contrast, p53 protein was undetectable in two neuroepithelioma-derived cell lines; the p53 gene in one of these lines contained a nonsense mutation, while the other transcribed truncated p53 mRNA.
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PMID:Expression of p53 in human neuroblastoma- and neuroepithelioma-derived cell lines. 174 Nov 60

A definite association between the transcription of N-myc oncogene and proliferation-related genes, histone H3, c-myc and p53, was found in a set of 12 primary untreated neuroblastomas and a metastasis of one of these at relapse. Molecular analysis allowed us to discriminate between actually proliferating and non-proliferating tumors, and suggested a link between N-myc and proliferation. Flow cytometric analysis of DNA distribution was less reliable for assessing tumor proliferative activity. Our data also seem to indicate a down-regulation of c-myc by N-myc in human neuroblastoma.
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PMID:Transcription of N-myc and proliferation-related genes is linked in human neuroblastoma. 200 53

The common malignancies apparently develop by a stepwise accumulation of gene alterations including oncogenes and suppressor genes. Point mutation or deletion might be an early event for carcinogenesis and tumor progression, while amplification of several oncogenes occur as a late event. Amplification of some oncogenes apparently relate with patient prognosis, i.e. erbB2 for breast, ovarian and gastric carcinomas, HST-1/INT-2 for esophageal and breast carcinomas, and N-myc for neuroblastoma. Although amplification of erbB1 is less common, its expression indicate poorer prognosis in patients with esophageal, gastric and bladder carcinomas. Combination analysis of the gene amplification and other gene alterations, such as p53 gene might provide more useful clinical informations for the postoperative management and prognosis of cancer patients.
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PMID:[Oncogene and patient prognosis]. 205 66

The evidence for human tumor suppressor genes is reviewed. Initial evidence was provided by somatic cell hybridization, where somatic cell hybrids derived from the fusion of malignant and normal parental cells were found to be transformed but nontumorigenic. Tumorigenic segregants appeared at later intervals and were associated with the loss of specific normal chromosomes. Evidence for loss of tumor suppressor genes in many human malignancies was provided by a combination of cytogenetic and restriction fragment length polymorphism analyses. Functional analyses, using monochromosome transfer from normal cells into cancer cells, have confirmed the existence of suppressor genes and their critical role in control of tumor formation. Recently, the tumor suppressor gene Rb-1 has been cloned and also shown to have tumor-suppressing properties. Most recently, a candidate tumor suppressor gene on chromosome 17 (p53) has been implicated in colorectal carcinomas and other human malignancies. It is of interest to note that this gene was originally described as an oncogene. The biological mechanism of tumor suppression has been linked to the induction of differentiation in both somatic cell hybrids and osteosarcoma cells transfected with the normal Rb-1 gene. However, recent studies with monochromosome transfer into neuroblastoma cells indicates that differentiation may be dissociated from tumor suppression. Tumor suppressor genes do not act directly as negative regulators of conventional "dominantly-acting" oncogenes and therefore cannot be considered as anti-oncogenes in the sense of directly interacting with and regulating the expression of such oncogenes as ras and myc. However, it is speculated that they may negatively regulate an, as yet undiscovered, family of oncogenes which would not be dominantly expressed.
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PMID:The evidence for human tumor suppressor genes. 257 36

LA-N-5 human neuroblastoma cells were found to express high levels of an Mr 53,000 cellular tumor antigen (p53), a protein that has been implicated as playing a fundamental role in the control of cell division and differentiation processes in a variety of tumor systems. When LA-N-5 cells are treated with retinoic acid, they undergo growth and morphological, biochemical, and electrophysiological changes that are characteristic of neuronal maturation and a reduction of the malignant phenotype. We find that these retinoic acid-induced changes are accompanied by a marked decrease in the levels of p53 and p53 mRNA. In our study, p53 levels decreased in concert with both morphological differentiation and with inhibition of cellular proliferation in vitro. These results suggest that p53 levels are intimately related to an undifferentiated phenotype in neuroblastoma cells and support studies which relate p53 levels to the malignant phenotype in other tumor systems.
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PMID:Modulation of Mr 53,000 protein with induction of differentiation of human neuroblastoma cells. 328 Jan 24

The cellular tumor antigen p53 was isolated from mouse neuroblastoma cells and was found in a form not complexed to another protein. The p53 in these cells was stable, turning over about every 10 h. Its methionine-labelled tryptic peptides were very similar to those of the p53 isolated from SV40-transformed mouse cells. The labelled protein was purified from neuroblastoma cells by immunoaffinity using specific monoclonal antibodies and was about 80% radiochemically pure. Furthermore, the purified p53 sedimented in sucrose gradients with a sedimentation coefficient of approximately 8S. This correlated with the sedimentation coefficient of p53 prior to purification, showing that the purified protein retained its native size.
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PMID:Immunoaffinity chromatography of a cellular tumor antigen from mouse neuroblastoma cells. 635 54

Knowledge about genetic alterations specific to the metastatic process and chemoresistance in neuroblastoma is progressing steadily. Low or no CD44 expression, increased NM23 expression and specific mutations of the 5' coding regions of NM23 are distinct features of aggressive, metastatic neuroblastoma. MYCN down-regulates Class I HLA antigen expression in many neuroblastoma cell lines and, in turn, may be regulated by a suppressor gene. The MYCN amplified human neuroblastoma cell line, IGR-N-91, established in vitro, metastasises in the nude mouse and has exhibited co-activation of MYCN and PGY1, resulting from direct activation of the oncoprotein on the PGY1 promoter. In this model, the MYCN product activates angiogenesis, the dissemination process and chemoresistance via specific genes (PGY1 and GST3). MYCN, like the BCL-2 and TP53 products, may also play a key role in apoptosis. The implication of these genes in the potential for metastasis and chemoresistance in neuroblastoma is discussed.
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PMID:Genetic alterations associated with metastatic dissemination and chemoresistance in neuroblastoma. 757 68

By subjecting radiosensitive human neuroblastoma IMR 32 cells to a regime of fractionated X-irradiation, a radioresistant variant, XRIMR 32, was obtained. Radiation resistance of XRIMR 32 cells was demonstrated by clonogenic and spheroid regrowth delay assays. The XRIMR 32 cultures were phenotypically unstable, with the resistant phenotype being lost after 3 passages in the absence of radiation-selective pressure, but a monoclonal cell line (clone F) was established that maintained its resistance over 35 passages without irradiation. Flow cytometry showed that exponentially growing IMR 32, XRIMR 32, and clone F cells all had very similar cell cycle distributions. Studies of initial DNA damage and repair, using the technique of neutral filter elution, revealed no differences between these lines. Chromosomal damage, as measured by micronucleus frequency following irradiation, was also seen to be very similar. However, studies of apoptosis following irradiation showed significantly higher levels of apoptosis in IMR 32 cells, compared to the resistant lines. This was true at all time points studied between 6 and 42 h after irradiation. p53 status was examined in the IMR 32 and clone F cells. No mutations were detected in exons 5-8 of the cDNA. Both lines showed increased p53 expression after irradiation. These data are consistent with the evolution of cellular resistance as a possible mechanism for the evolution of cellular radioresistance during protracted radiation regimes. However, the molecular mechanism responsible for the increased radioresistance remains to be discovered.
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PMID:A radioresistant variant derived from a human neuroblastoma cell line is less prone to radiation-induced apoptosis. 758 30

Amplification of the MYCN gene is a well documented genetic alteration of aggressively growing human neuroblastomas. Through cytogenetic studies we have identified neuroblastoma cell lines which, in addition to amplified MYCN, carry amplified DNA not harbouring MYCN. In situ hybridization of biotinylated total genomic DNA to metaphase chromosomes of normal human lymphocytes by reverse genomic hybridization revealed the amplified DNA to be derived from chromosome 12 band q13-14. Subsequent filter analyses showed a 20- to 40-fold amplification of the MDM2 gene, located at 12q13-14, both in three cell lines and in an original tumor, in addition to amplified MYCN. As the apparent consequence of amplification abundant MDM2 protein was present, a part of which was complexed with p53.
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PMID:Non-syntenic amplification of MDM2 and MYCN in human neuroblastoma. 770 Jun 32

Neuroblastoma, a tumor of the sympathetic nervous system, is one of the most common solid malignancies in infants and represents 7% of all cases of childhood cancer outside of the central nervous system. Thirty-five samples of neuroblastoma from 31 patients were obtained from Duke University Medical Center between 1979 and 1991 and studied to determine the relative prognostic value of a number of clinical, histologic, nuclear, and oncogenic features. The features studied were: stage, Shimada classification, DNA ploidy, MIB-1-proliferation index and status for HER-2/neu, p53 and epidermal growth factor receptor (EGFr). Only age (P = .03), HER-2/neu (P = .01), and p53 (P = .02) reached statistical significance as prognostic indicators. The median survival for patients with HER-2/neu expression was 12 months; median survival for patients with no HER-2/neu expression was 138 months. Similarly, the median survival for patients with p53 expression was 12 months; patients with no p53 expression had a median survival was 144 months. The combination of either HER-2/neu or p53 positivity was especially strong as a prognostic indicator (P = .002).
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PMID:Prognostic indicators for neuroblastoma: stage, grade, DNA ploidy, MIB-1-proliferation index, p53, HER-2/neu and EGFr--a survival study. 774 72


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