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)

Diagnosis- and/or prognosis-related alterations of (proto) oncogenes may be detected in neuroblastoma (N-myc), carcinoma of breast and ovary (HER2/neu), NHL (c-myc, bcl-2), CML (c-abl/bcr), and some other neoplasias. A wide variety of methods for the detection of gene alterations can be applied. The methods of detection have to be chosen according to the expected mechanisms of oncogene activation, the availability of adequately prepared tissue, and the technical standard of the laboratory. The sensitivity, specificity, and quantitation of morphological techniques (immunohistochemistry and in situ hybridization) is restricted and their results have to be interpreted most carefully. Whenever possible, at least two different techniques should be used, preferably on two different levels, i.e. RNA/DNA and protein. Furthermore, the combination of morphological and non morphological methods should be aspired.
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PMID:[Oncogenes and oncogene products--possibilities and significance of their detection]. 170 8

The neu gene in rat neuro/glioblastoma was found to be activated by a single point mutation in the DNA sequence encoding the transmembrane region of the neu-encoded p185 protein. The human homologue of the rat neu gene, termed c-erbB-2 or HER-2, can also be activated in vitro by a similar mutation in the corresponding region. Although the human neu gene was shown to be amplified/overexpressed in a large portion of human breast and ovarian cancer, no reports indicate that the human neu gene is activated by a point mutation in human tumor. To study the possible point mutation of neu gene in human tumors, we characterized the genomic structure in the transmembrane region of human neu gene, which in turn allowed us to determine DNA sequence in this region directly following DNA amplification by polymerase chain reaction. We analyzed 7 tumor cell lines (2 breast cancer, 1 neuroblastoma, 1 rhabdomyosarcoma, and 3 glioma) and 11 tumor tissue samples (8 breast and 3 ovarian cancers). No mutation was found in the transmembrane region of human neu gene. Our results suggest that unlike the rat neuro/glioblastoma, the single point mutation in the transmembrane region of the human neu gene is a rare event in human tumors. In this study, we developed a technique for direct DNA sequencing of the transmembrane region of the human neu gene. This technique makes it possible to screen a large number of tumor samples.
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PMID:Direct sequencing analysis of transmembrane region of human Neu gene by polymerase chain reaction. 220 83

To determine whether the amplification of the proto-neu oncogene (also called c-erbB-2) plays a role in tumorigenicity, we previously generated an NIH 3T3 transfectant (DHFR/G-8) that carried the amplified proto-neu gene. The DHFR/G-8 cells exhibited normal morphology. Their growth curve was similar to that of NIH 3T3 cells but was different from that of the B104-1 cell, and NIH 3T3 transfectant that carries the activated neu oncogene. When injected into nude mice, B104-1 cells produced tumors within 2 weeks, whereas the DHFR/G-8 cells did not produce tumors until 3 months after injection, and the NIH 3T3 cells did not produce any tumors even after 3 months. The tumors produced by the injection of the DHFR/G-8 cells were excised and grown in culture. The cells derived from the tumors were of transformed morphology and highly tumorigenic. The DNAs from the tumor cells were transfected into NIH 3T3 cells. The transfection resulted in foci on the NIH 3T3 monolayer. Southern analysis indicated that the foci derived from the transfection contained the neu gene. Using oligonucleotides as probes, the neu gene in the foci was found to carry a single-point mutation identical to the one previously found in the rat neuroblastoma and glioblastoma induced by the ethylnitrosourea. We conclude that the DNA region encoding the transmembrane domain of neu is a hot spot for converting the proto-neu gene into an activated oncogene and that amplification of the proto-neu gene facilitates mutation of the hot spot.
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PMID:Amplification of the proto-neu oncogene facilitates oncogenic activation by a single point mutation. 256 34

Exposure of neu-oncogene-transformed NIH 3T3 cells to monoclonal antibodies reactive with the neu gene product, p185, results in the rapid and reversible loss of both cell-surface and total cellular p185. Although not directly cytotoxic, monoclonal anti-p185 antibody treatment causes neu-transformed NIH 3T3 cells to revert to a nontransformed phenotype, as determined by anchorage-independent growth. Isotype matched control antibodies of an unrelated specificity do not affect p185 levels or colony formation in soft agar by neu-transformed NIH 3T3 cells. Soft agar colony formation by NIH 3T3 cells transformed by ras oncogenes is not affected by anti-p185 antibody treatment. Anchorage-independent growth of cells from the ethylnitrosourea-induced rat neuroblastoma line in which neu was originally detected by DNA transfection is also inhibited in the presence of anti-p185 monoclonal antibodies. Collectively, these results suggest that p185 is required to maintain transformation induced by the neu oncogene.
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PMID:Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. 286 Sep 72

Various kinds of lesions exist which should be discriminate from malignant or premalignant or borderline lesions. If there were a morphologic technical procedure on detection of malignant transformation of the cells at the initiation stage, before the lesion would develop a definitely identical with malignant lesion, such method must be most highly applicable for pathologists. DNA diagnosis has realized a warning of diagnosis of certain diseases or genetical maldevelopment prior to develop their clinical manifestation. Gene analysis has introduced in ++phragmatical screening test for certain diseases such as diabetes mellitus, thalassemia, T-cell leukemia or lymphoma, neuroblastoma, muscular dystrophy of Duchenne or Becker type, Ph' chromosome and so on. Immunohistochemical technology has provided an intracellular oncogene detection in some neoplastic malignancies such as n-myc in neuroblastoma. Amplification of c-erb B2 (also referred as neu and HER-2/neu) has indicated a higher malignant mammary carcinoma with poor-prognosis, even their size small and early stage. Oncogene analysis is expected to be available sperimposing on pathological morphology.
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PMID:[Detection of early stage cancer: pathological aspect with special reference to differential diagnosis]. 317 85

In recent years cellular homologues of many viral oncogenes have been identified. As these genes are partially homologous to viral oncogenes and are activated in some tumour cell lines they are termed "proto-oncogenes". In tumour cell lines proto-oncogenes are activated by either quantitative or qualitative changes in gene structure: activation of these genes was originally thought to be a necessary primary event in carcinogenesis, but activated cellular oncogenes, unlike viral oncogenes, do not transform normal cells in culture. In experimental models cooperation between two oncogenes can induce transformation of early passage cells, and this has become the basis of an hypothesis for multistep carcinogenesis. Proto-oncogene products also show sequence homology to various components in the mitogenic pathway (growth factors, growth factor receptors, signal transducing proteins and nuclear proteins), and it has been postulated that they may cause deregulation of the various components of this pathway. In human tumours single or multiple oncogene activation occurs. The pattern of oncogene activation in common solid malignancies is not consistent within any one class of tumour, nor is it uniform between classes, with three exceptions. In neuroblastoma, breast cancer, and perhaps in lung cancer there is relatively consistent activation of N-myc, neu, and c-myc/N-myc, respectively. Amplification of these genes generally correlates with poor prognosis. The introduction of methods for the direct study of oncogene transcription and their products will undoubtedly broaden our vision of cancer biology in man and, hopefully, add diagnostic and prognostic precision to tumour typing.
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PMID:Cellular oncogenes in neoplasia. 331 99

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

We used antisense RNA to inhibit the expression of oncogene neu and investigated the effects of diminished neu expression on the phenotypes of B104 cells containing activated oncogene neu. Antisense MT-neu and pSV-neo plasmids were cotransfected into neuroblastoma B104 cells. Southern analysis showed the integration of anti-neu DNA into B104 cells. The expression of neu was inhibited up to 90% as quantitated by immunoprecipitation. The growth rate and the potential to differentiate in these transfectants were not affected as compared to the parental cell lines. The ability to grow in soft agar was inhibited more than 90% in these transfectants. Our results indicated that antisense-RNA against a specific oncogene can decrease the tumorigenicity of tumor cells but may not be able to revert it to normal cells completely.
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PMID:Partial reversion of transformed phenotype of B104 cancer cells by antisense nucleic acids. 809 70

The neu proto-oncogene encodes a plasma membrane protein belonging to the epidermal growth factor receptor family. The cell line B104, derived from BDIX rat neuroblastoma, carries a point mutation in neu, and forms a tumor when injected into these rats. The human homologue of the neu oncogene (here called HER2) is overexpressed in certain types of cancer. Rats were immunized with HER2 protein (HER2) to investigate a possible cross-reaction between the homologous proteins which could protect them against subsequent inoculation with B104. Specific antibody in the serum was measured by cell-based enzyme-linked immunoabsorbent assay and fluorescence immunocytochemistry, and delayed-type hypersensitivity by an ear assay. Sera from animals immunized with the HER2 extracellular domain (HER2-ECD) reacted with both HER2- and neu-expressing cells. In the ear assay, a significant cellular response to both HER-ECD (P < 0.05) and neu protein (P < 0.001) was observed in HER2-ECD-immunized rats. However, the growth of B104 tumors in rats was not affected by preimmunization with HER2-ECD. The results indicate that an autoreactive immune response to neu was induced by immunization with HER2-ECD, but was too weak to affect the growth of the neu-bearing tumor.
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PMID:Humoral and cellular responses raised against the human HER2 oncoprotein are cross-reactive with the homologous product of the new proto-oncogene, but do not protect rats against B104 tumors expressing mutated neu. 864 Aug 46

The multimodular glycoprotein tenascin-C is transiently expressed, predominantly by glial cells, during the development of the central and peripheral nervous systems. This extracellular matrix glycoprotein is involved in the control of cell adhesion, neuron migration and neurite outgrowth. Distinct functional properties for neuronal cell types have been attributed to separate tenascin-C domains using antibody perturbation studies and in vitro experiments on tenascin-C fragments. In order to study potential roles of tenascin-C for glial cell biology, a library of recombinant tenascin-C domains was used in a bioassay in vitro. Embryonic day 14 astrocytes, various astroglial-derived cell lines (C6, A7 and Neu7) and oligodendroglial-derived cell types (Oli-neu and G26-20) were examined in an adhesion assay and compared to the neuroblastoma cell line N2A. A binding site for most cell types, except for A7 and N2A, could be assigned to the first three fibronectin type III domains. Repulsive properties could be mapped to three different sites the epidermal growth factor-like repeats, fibronectin type III repeats 4 and 5 and to the alternatively spliced region of the molecule. The responses to these repulsive sites varied according to the cell type. These data are consistent with the interpretation that different cell types express distinct sets of tenascin-C receptors which might regulate cellular responses via distinct second messenger pathways.
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PMID:Glial cell interactions with tenascin-C: adhesion and repulsion to different tenascin-C domains is cell type related. 884 7


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