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)

The neu oncogene encodes a 185-kDa transmembrane glycoprotein tumor antigen, termed p185. We have recently described a monoclonal antibody reactive with a cell surface domain of the p185 molecule. In vivo treatment with this anti-p185 monoclonal antibody was able to significantly inhibit the tumorigenic growth of neu-transformed NIH 3T3 cells implanted into nude mice. Such treatment had no effect on the tumorigenic growth of Ha-ras-transformed NIH 3T3 cells. Furthermore, anti-p185 antibody treatment was able to inhibit the growth of the rat neuroblastoma cells from which the neu oncogene was initially isolated. These results demonstrate that a monoclonal antibody reactive with the extracellular domain of an oncogene-encoded protein can exert a significant antitumor effect; such antibodies may prove useful in the therapy of certain malignancies.
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PMID:Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen. 346 78

Protein products of the ras family of oncogenes were immunoprecipitated by an anti-p21 monoclonal antibody, separated by two-dimensional gel electrophoresis and subsequently detected by western immunoblot analysis using the same anti-p21 monoclonal antibody as a probe. Using this method, a 21 kDa oncogene protein (p21) was detected and characterized in cell lines containing Harvey (Ha), Kirsten (Ki), neuroblastoma (N), or cellular (proto) ras genes. The ras gene products from all cell types occurred with multiple forms differing in size, charge or in both parameters. Transforming ras oncogene proteins occurred in easily identifiable groups that were different from each other in molecular weight and charge, were distinctive for each ras gene type and were different from cellular ras equivalents. Similar, but not identical, family groups occurred in different cell types containing the same oncogene. The reproducible occurrence of unpredicted p21 forms suggests that previously unreported post-translational processing steps may be associated with the synthesis of certain oncogene products. This immunoprecipitation/two-dimensional gel/western blot technique is a simple method for the identification and characterization of p21 gene products.
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PMID:Analysis of ras oncogene products by two-dimensional gel electrophoresis: evidence for protein families with distinctive molecular forms. 348 4

The ras gene family of rodents and humans is highly conserved and consists of several distinct genes, i.e., rodent Harvey and Kirsten, and human Harvey, Kirsten and neuroblastoma. This gene family mediates transformation via (1) a point-mutation resulting in the change of one amino acid in the 21 kDA ras gene product (p21) or (2) increased expression of ras p21. Group-specific, type-selective and interspecies indirect binding liquid competition radioimmunoassays (RIAs), capable of providing truly quantitative analyses of the 21 ras oncogene and proto-oncogene products, have been developed. Using purified recombinant ras p21 from Escherichia coli expressing the full-length T24 mutant human Harvey-ras gene protein product as a standard in these RIAs, we have defined the absolute numbers of pg, fM and molecules of ras p21 in: (1) E. coli expressing the point-mutated or proto-ras p21 and (2) mammalian cell lines of human and murine origin. Two of the RIAs developed can be termed group-specific in that they have the ability to detect the point-mutated and proto forms of all 3 human ras genes (Harvey, Kirsten, and neuroblastoma), while the third RIA is type-selective, since it detects an antigenic determinant located primarily on the Harvey ras p21. All 3 RIAs are interspecies-specific since they are able to detect ras p21 in rodent as well as human cells. The adaptability of the RIAs to various assay conditions and ease of methodology make these immunoassays applicable to the study of several parameters associated with ras p21 expression. These assays, used in conjunction with specific cDNA probes to identify specific ras proto-oncogenes or point-mutated oncogenes being expressed, now provide truly quantitative analysis of ras p21 in mammalian cells to further the study of the association between ras p21 expression and transformation.
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PMID:Development of quantitative liquid competition radioimmunoassays for the ras oncogene and proto-oncogene p21 products. 348 81

Several distinct and high-conserved genes comprise the ras gene family of rodents and humans, i.e., rodent Harvey and Kirsten, and human Harvey, Kirsten and neuroblastoma. Transformation, either by a point-mutation resulting in a change in one amino acid of the 21 kDa ras gene product (p21), or by increased expression of ras p21, has been demonstrated to be mediated by members of this gene family. We report here the development of direct binding liquid competition radioimmunoassays for the detection and quantitation of the ras oncogene and proto-oncogene products. Using these radioimmunoassays and ras p21 purified from Escherichia coli containing the full-length T24 mutant human Harvey ras gene protein product as a standard, we have defined the actual amount of ras p21 per micrograms of total cellular protein, or per cell, in various ras transformed and 'normal' mammalian cell lines. One of the radioimmunoassays developed is group-specific, since the antigenic determinant recognized is shared by both the point-mutated and proto-forms of Harvey, Kirsten and neuroblastoma members of the ras gene family, while the second may be termed type-selective, since it recognizes an antigenic determinant localized primarily on the Harvey ras p21. Both radioimmunoassays are interspecies, since they detect a ras p21 antigenic determinant common to cells of human and rodent origin. These studies thus describe the first means for defining absolute values of any oncogene or proto-oncogene protein product. The assays described, when used in combination with specific c-DNA probes to define specific ras proto-oncogenes or point-mutated oncogenes being expressed, will now permit truly quantitative analyses of ras p21 expression in experimental cell culture systems, animal models and human biopsy material.
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PMID:Absolute values of ras p21 defined by direct binding liquid competition radioimmunoassays. 381

Preparations of DNA isolated from malignant melanoma (Ja heterotransplant), neuroblastoma (L-AN-1 cell line) and breast cancer (SK-BR-3 cell line) induced a high incidence of transformation of recipient NIH 3T3 cells in two consecutive cycles of transfection. Transformed NIH 3T3 cells appeared to be highly tumorigenic in newborn BALB/c mice. The analysis of DNA samples isolated from primary and secondary NIH 3T3 transformants identified Alu-repetitive DNA sequences of human genome as well as additional sequences homologous to ras-family oncogene. Transforming c-Ha-ras I gene was identified for the first time in NIH 3T3 cells transformed by preparations of DNA isolated from human malignant melanoma, neuroblastoma and breast cancer.
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PMID:[Identification of the transforming Ha-ras gene in human melanoma, neuroblastoma and breast cancer cells]. 402 51

DNA from the human neuroblastoma cell line SK-N-SH is capable of inducing foci of transformed NIH 3T3 cells after DNA-mediated gene transfer. Using genetic selection with the Escherichia coli sup F gene, we have isolated human sequences from mouse cells responsible for the oncogenic transformation. These sequences are present in all human DNAs surveyed and no gross rearrangements of these sequences are found in SK-N-SH cells. Although clearly distinct from two other human transforming genes present in bladder, lung, and colon carcinoma cell lines, all three transforming gene sequences may be related members of the ras gene family.
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PMID:Isolation and preliminary characterization of the transforming gene of a human neuroblastoma cell line. 630 Aug 38

A molecular clone containing part of the transforming gene from two human sarcoma cell lines, HT1080 and RD, has been obtained and shown to represent a new member of the human ras gene family. The transforming gene has undergone no major rearrangements and has not been amplified in either sarcoma cell line. The major transcript from the gene is 2,200 nucleotides long and is present at the same levels in both normal fibroblasts and tumour cells. The same gene is also activated in HL60, a promyelocytic leukaemia line and in SK-N-SH, a neuroblastoma line. The gene, N-ras, is located on chromosome 1.
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PMID:Identification of transforming gene in two human sarcoma cell lines as a new member of the ras gene family located on chromosome 1. 630 21

DNAS of some human tumours can transform NIH 3T3 fibroblast cells, thus demonstrating the transforming potential of human ras genes (Hu-rasHa, Hu-rasKi, and Hu-rasN, respectively Harvey, Kirsten and neuroblastoma ras genes). Only a small percentage of a given type of human carcinoma, however, scores positive in this assay system. Activation of ras and subsequent transformation of NIH 3T3 cells are either by a point mutation in the ras gene or enhanced expression of the normal, or proto-onc, ras gene. If the transformation of a given human tumour involves the enhanced expression of the normal or cellular ras gene and the resulting gene product, the tumour DNA would probably score negative in the NIH 3T3 transfection assay. In human colon carcinoma, for example, lesions at position 12 of Hu-rasKi have been found. None of nine colon carcinomas obtained at biopsy, however, contain the ras lesion at this position, using a Hu-rasHa probe; one other colon carcinoma does appear to contain amplified proto-onc ras, and other colon carcinomas do have increased levels of ras RNA. There are at least three explanations for these observations. Either very few colon carcinomas contain point-mutated ras, the lesion in the majority of colon carcinomas is at a position other than 12 or ras activation in many colon carcinomas involves the enhanced expression of either the point-mutated or proto-onc form of a ras gene. We have now used monoclonal antibodies directed against a synthetic peptide reflecting sequences of the human T24 ras gene product to define ras p21 protein expression in a spectrum of colonic disease states. Immunohistochemical analyses of individual cells within tissue sections reveal differences in ras p21 expression in colon carcinomas compared with normal colonic epithelium, benign colon tumours and inflammatory or dysplastic colon lesions. Our data suggest that ras p21 expression is correlated with depth of carcinoma within the bowel wall, and is probably a relatively late event in colon carcinogenesis.
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PMID:Monoclonal antibodies define differential ras gene expression in malignant and benign colonic diseases. 648 68

Three distinct transforming genes present in human tumor cell lines are all related to the viral oncogenes of Harvey and Kirsten murine sarcoma viruses, designated v-H-ras and v-K-ras, respectively. The transforming gene of a bladder carcinoma cell line has been shown to be a human homolog to v-H-ras [Parada, L. F., Tabin, C. J., Shih, C. & Weinberg, R. A. (1982) Nature (London) 297, 474-478; Santos, E., Tronick, S. R., Aaronson, S. A., Pulciani, S. & Barbacid, M. (1982) Nature (London) 298, 343-347]. The transforming gene common to one colon (SK-CO-1) and two lung carcinoma (SK-LU-1 and Calu-1) cell lines is the same human homolog of v-K-ras as is the transforming gene previously identified in a lung carcinoma cell line Lx-1 [Der, C. J., Krontiris, T. G. & Cooper, G. M. (1982) Proc. Natl. Acad. Sci. USA 79, 3637-3640]. The transforming gene of SK-N-SH neuroblastoma cells is weakly homologous to both v-H-ras and v-K-ras. NIH 3T3 cells transformed with the SK-N-SH transforming gene contain increased levels of a protein serologically and structurally related to the protein products of the v-H-ras and v-K-ras genes. Therefore, it represents a third member of the ras gene family, which we have called N-ras. Based on the homology with the v-ras genes, we have established the orientation of transcription and approximate coding regions of the cloned human K-ras and N-ras genes.
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PMID:Three human transforming genes are related to the viral ras oncogenes. 657 64

A family of human transforming genes, previously shown to share homology with the ras family of viral oncogenes, maps to three different human chromosomes. A well-characterized mouse-human hybrid cell panel, combined with Southern blotting, was used in this study. The transforming gene of the T24 bladder carcinoma cell line maps to human chromosome 11. An oncogene isolated from the lung carcinoma cell line SK-Calu-1 maps to human chromosome 12. The third ras-related gene, cloned from SK-N-SH, a neuroblastoma cell line, maps to human chromosome 1.
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PMID:Chromosomal assignment of a family of human oncogenes. 657 47


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