Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors determined the levels of N-myc oncogene amplification and RNA expression in three infants with metastatic neuroblastoma. By clinical staging Patients 1 and 2 were Stage IV-S, a disease with limited metastatic potential and generally favorable outcome; Patient 3 was Stage IV. Southern blots of chromosomal DNA showed normal N-myc copy number in the primary tumor of Patient 1, extensive (200-fold) gene amplification in the primary tumor from Patient 2, and intermediate (100-fold) gene amplification in the primary tumor and metastatic lesions from Patient 3. N-myc RNA was expressed in all of the primary and metastatic tumor tissues tested. The level of N-myc RNA expression roughly corresponded to the extent of N-myc gene amplification in Patients 2 and 3 and was overexpressed from a single N-myc gene copy in Patient 1. N-myc gene amplification and RNA expression levels were approximately the same in the primary and metastatic lesions for each of the patients tested. The two patients with N-myc gene amplification had a poor outcome, but the patient with normal N-myc gene copy number had no evidence of disease. Despite the clinical picture in Patient 2 of Stage IV-S neuroblastoma, the pattern of N-myc amplification and expression more closely resembled that of Patient 3 (Stage IV neuroblastoma) than that of Patient 1 (bona fide Stage IV-S neuroblastoma).
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PMID:N-myc oncogene expression and amplification in metastatic lesions of stage IV-S neuroblastoma. 169 6

A permanent cell line established from a xenograft of neuroblastoma which occurred in a 5-year-old girl was investigated for its morphological and biological characteristics. The cultured cells were tumorigenic in nude mice. Microscopically, each tumor consisted of small round to polygonal cells with irregular nuclei and prominent nucleoli, corresponding to the features of the primary and xenografted tumor cells. Electron microscopic examination revealed that both the transplanted tumor cells and the cultured cells contained scanty microtubules and dense-core neurosecretory granules. Chromosome analysis of this cell line showed monosomy for chromosomes 1, 10, 19 and X, and structural rearrangements involving chromosomes 8, 17 and 20, in addition to numerous double minutes. The N-myc oncogene was found to be amplified 40- to 80-fold in the transplanted and cultured tumor cells, as well as in the primary tumor cells. In situ hybridization with a digoxigenin-labeled uridine-triphosphate N-myc RNA probe detected abundant mRNA in the tumor cells. This neuroblastoma line may become a valuable in vitro experimental model system for studies aimed at better characterization of neuroblastoma.
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PMID:Morphological and cytogenetic characterization and N-myc oncogene analysis of a newly established neuroblastoma cell line. 175 17

Neuroblastomas are malignant childhood neoplasms that arise from derivatives of the neural crest. We report the characterization of a new neuroblastoma cell line, designated NBL-W, derived from the primary tumor of a patient with stage IVS disease (S. L. Cohn, C. V. Herst, H. S. Maurer, and S. T. Rosen, J. Clin. Oncol., 5: 1441-1444, 1987) according to the criteria of Evans [A. E. Evans, G. J. D'Angio, and J. Randolf, Cancer (Phila.), 27: 374-378, 1971]. Neurite-bearing (N) and substrate-adherent (S) cell lines have been subcloned from the parent line. N and S cells can interconvert, and both cell types label with the neural crest cell surface marker antibody, HNK-1. Cells in the subcloned lines and in the parent line have been shown by Southern blot analysis to contain approximately 100 copies of the N-myc gene. Cytogenetic analysis shows a homogeneously staining region present on chromosome 19. Although these subclones are of identical genotype, the S cells express lower amounts of N-myc mRNA and protein as compared to the N cells. N cells express several neuronal proteins including the neurotransmitter-processing enzymes tyrosine hydroxylase and dopamine beta-hydroxylase, the neuronal intermediate filament proteins peripherin and NF66/alpha-internexin, and the neural cell adhesion molecule. S cells generally lack neuronal markers but express the mesenchymal intermediate filament protein vimentin, and a small subset of the S cells express glial fibrillary acidic protein. Some S cells were labeled weakly with neural cell adhesion molecule antibody; others were negative. S cells did not express the glial marker S-100 or a melanocyte marker, tyrosinase. Thus, S cells express the neural crest marker HNK-1 but do not express a set of antigens characteristic of any known cell type derived from the neural crest. These results are consistent with the suggestion that differential N-myc expression may be involved in the interconversion of N and S cells but indicate that the S cell phenotype need not represent a highly differentiated neural crest derivative.
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PMID:Differential expression of N-myc in phenotypically distinct subclones of a human neuroblastoma cell line. 193 96

One hundred eighteen children with metastatic (Childrens Cancer Study Group [CCSG] stage IV), extensive regional (stage III), or stage II neuroblastoma with N-myc amplification received an intensive chemotherapeutic regimen of cis-platinum, etoposide, doxorubicin, and cyclophosphamide combined with persistent aggressive attempts at complete primary tumor resection. Fourteen patients were unevaluable and 42 left the study to be placed on bone marrow transplant protocols. The remaining 62 children were evaluated in detail. Complete excision was eventually accomplished in 39 patients (63%), 23 of whom are disease-free survivors after 8 to 47 months (median, 20 months). Twenty-three patients underwent partial excision or biopsy of their lesion and only 6 are alive without evidence of disease (P = .0011). Timing of surgery or site of tumor did not influence surgical outcome. N-myc oncogene expression could not predict which lesions would be completely resectable. Surgical complications occurred 21% of the time but the impact on the clinical course and chemotherapy administration was minimal. The ipsilateral kidney was removed with the tumor in 18 cases, 14 of which were during complete resection. Twelve of these children are disease-free survivors. With new intensive chemotherapy capable of eliciting an effective response from primary and metastatic neuroblastoma, aggressive surgical approaches for complete tumor resection are warranted and can be expected to improve patient outcome.
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PMID:Aggressive surgery combined with intensive chemotherapy improves survival in poor-risk neuroblastoma. 150 Oct 51

We detected a rearrangement in the N-myc gene region in a neuroblastoma from a 9-month-old girl. In this case, the N-myc gene was amplified 50-fold in the primary tumor, the lymph node metastasis, and the hepatic metastasis. The rearrangement was detected only in the primary tumor and the lymph node metastasis, whereas N-myc RNA and protein expression were detected only in the primary tumor and the hepatic metastasis. Both the rearranged N-myc gene and the normal N-myc gene were amplified 25-fold, and the rearrangement occurred 723 nucleotides downstream from the 3' end of exon 3. The cell line (NH-6) derived from the primary tumor showed N-myc gene amplification without this rearrangement. These results suggest the following: (a) the primary tumor had a least two clones; (b) the rearrangement interrupted N-myc gene expression; and (c) oncogenesis preceded N-myc gene amplification.
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PMID:Neuroblastoma with DNA amplification and rearrangement in the N-myc gene region. 200 81

A neuroblastic-like cell line (NUB-20) was derived from a case of histopathologically diagnosed metastatic neuroblastoma. The metastatic tumor and nude mouse heterotransplant resembled neuroblastoma by histological criteria, in contrast to the primary tumor, which was differentially classified as Ewing's sarcoma. However, the cell line demonstrated a unique phenotype in culture with respect to morphology, immunohistochemical markers, and sensitivity to a battery of differentiation modulators. These characteristics, together with the presence of a chromosomal translocation (11;22),(q24;q12) and amplification with enhanced expression of the c-myc protooncogene rather than N-myc, established this tumor as neuroepithelioma. Neuroepithelioma is a tumor type distinct from, but related to, neuroblastoma in its development from the neural crest lineage. These results emphasize the growing importance of cytogenetic and molecular markers in the classification and characterization of human tumors.
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PMID:Importance of phenotypic and molecular characterization for identification of a neuroepithelioma tumor cell line, NUB-20. 215 99

One hundred forty-two foci of small cell lung carcinoma (SCLC) from 47 patients were examined for amplification of myc family oncogenes (c-myc, N-myc, and L-myc), by dot blot hybridization using formalin-fixed and paraffin-embedded materials which were resected surgically or obtained at autopsy. Some selected patients were also examined by in situ hybridization. Amplification of myc family genes was detected in 11 patients (23.4%) (c-myc in one, N-myc in five, and L-myc in five). Two of the 11 patients (one with N-myc and one with L-myc) had heterogenously amplified clones. In the patient with N-myc amplification, amplification was detected in metastatic tumors in the pancreas, lung, and pleura, but not in the liver and lymph node metastases. In the primary tumor, areas with and without N-myc amplification were seen. In the patient with L-myc amplification, although amplification was not detected in the surgically resected primary lesion, mediastinal lymph node metastatic lesions obtained at autopsy showed L-myc gene amplification. These two cases, together with previously reported evidence, suggest that myc gene amplification plays an important role in malignant progression, rather than development, of SCLC. In Stage III and IV groups, patients with over ten-fold myc gene amplification were suggested to survive for a shorter time than patients without such amplification (P = 0.06).
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PMID:Heterogenous amplification of myc family oncogenes in small cell lung carcinoma. 217 44

Genomic amplification of the oncogene N-myc is associated with rapid tumor progression and poor prognosis in patients with neuroblastoma (NB). However, 40% of NBs which lack N-myc amplification are also clinically aggressive. Factors other than N-myc copy number must therefore play a role in determining tumor progression in these NBs. We have established an unusual human NB cell line (NBL-S) from the primary tumor of a patient with rapidly progressive disease which lacks N-myc amplification. The doubling time in vitro (48 h) and the time from injection of 2 x 10(7) cells to detectable tumors in nude mice (46 days) in similar to NB cell lines with amplified N-myc. However, karyotype analysis reveals no evidence of double minutes (DMs), homogeneously staining regions (HSRs), or chromosome 1p deletions, features commonly seen in NB cell lines. The cells have the cell surface phenotype typical of N-myc amplified NB (HLA-A,B,C negative and HSAN 1.2 positive), and similar to other NB cell lines, N-myc RNA and protein are expressed. Interestingly, the half-life of the N-myc protein in NBL-S is prolonged (approximately 100 min) compared to the short N-myc protein half-life previously described in N-myc amplified NB cell lines (approximately 30 min). Because N-myc protein is thought to have a regulatory role, prolongation of the half-life of this protein may be an important factor in the regulation of growth in NBs which lack N-myc amplification and rapidly progress.
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PMID:Prolonged N-myc protein half-life in a neuroblastoma cell line lacking N-myc amplification. 228 1

The expression of myc-related genes (c-myc, N-myc, and L-myc) in small cell lung cancer (SCLC) was studied by RNA-RNA tissue in situ hybridization. The tissues investigated included cytospins of ten cell lines derived from patients with SCLC, four corresponding nude mouse xenografts from cell lines, and metastatic tumor tissue obtained by surgical biopsy and at autopsy. The probes were prepared as 35S labeled complementary RNA. The expression of each gene was demonstrated specifically by autoradiography in the cytoplasm of the neoplastic cell samples. The average levels of oncogene expression in each specimen corroborated previous data obtained by Northern blot assays. In addition, heterogeneity in gene expression from cell to cell in each sample was noted. This study represents the first attempt to demonstrate oncogene expression in lung cancer cell lines and tissues in situ, and confirms that the expression of these myc related genes can be seen in the primary tumor. The technique of RNA-RNA tissue in situ hybridization has great potential in answering fundamental questions of tumor cell heterogeneity and progression in SCLC. It should be useful in both prospective and retrospective studies.
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PMID:A study of myc-related gene expression in small cell lung cancer by in situ hybridization. 245 19

We have determined the prevalence of amplification of c-myc, N-myc, L-myc, H-ras, Ki-ras, and N-ras oncogenes in 23 cases of squamous cell carcinoma of the oral cavity, using Southern hybridization analysis of DNA extracted from the primary tumor tissues. Nick-translated oncogene probes and oncogene inserts labeled to high specific activities were used. We observed a 5- to 10-fold amplification of one or more of c-myc, N-myc, Ki-ras and N-ras oncogenes in 56% of the tumor tissue samples, with these oncogenes not being amplified in the peripheral blood cells of the same patients. L-myc and H-ras were not amplified in any of our samples. The oncogene amplifications seemed to be associated with advanced stages of squamous cell carcinomas, with the ras and myc family oncogenes being amplified in stages 3 and 4. Hybridization with N-myc detected an additional 2.3 kb EcoRI fragment, along with the normal 2.1 kb fragment. Our data also demonstrated amplification of multiple oncogenes in the same tumor tissue sample. About 60% of the samples with amplified oncogenes showed simultaneous amplification of 2 or more oncogenes. The results showing different oncogene amplifications in similar tumors, as well as multiple oncogene amplifications in the same tumor, suggest that these oncogenes may be alternatively or simultaneously activated in oral carcinogenesis.
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PMID:Oncogene amplification in squamous cell carcinoma of the oral cavity. 250 19


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