Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathological and cytogenetic features of an extrarenal malignant rhabdoid tumor (MRT) arising from the paravertebral region in an infant were investigated. The patient died 4 months after diagnosis, due to aggressive tumor progression. The tumor was composed of medium-sized round cells with cytoplasm containing eosinophilic inclusions, which ultrastructurally were composed of densely packed whorled intermediate filaments. Flow-cytometric analysis of the tumor cells revealed a diploid pattern. Amplification of the N-myc oncogene was not identified. Immunohistologically, the inclusion bodies showed a positive reaction with antiserum against vimentin. The tumor cells were not reactive with antiserum against epithelial membrane antigen, anti-keratin (polyclonal) or cytokeratin (monoclonal, CK1), but did react with 5H10, an antiserum established from human sarcomatous Wilms' tumor. This case is discussed with reference to the literature on extrarenal MRT, placing stress on the histogenesis of this tumor.
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PMID:Cytogenetic characteristics of a malignant rhabdoid tumor arising from the paravertebral region. A case report. 150 7

DNA sequences of specific human papillomavirus (HPV) types are found integrated in the cell genome in most invasive genital carcinomas. We have determined the chromosomal localization of integrated HPV type 16 (HPV-16) or HPV-18 genomes in genital cancers by in situ hybridization experiments. In three cancers, HPV sequences were localized in chromosome band 8q24.1, in which the c-myc gene is mapped, and in one cancer HPV sequences were localized in chromosome band 2p24, which contains the N-myc gene. In three of the four cases, the proto-oncogene located near integrated viral sequences was found to be structurally altered and/or overexpressed. These data indicate that HPV genomes are preferentially integrated near myc genes in invasive genital cancers and support the hypothesis that integration plays a part in tumor progression via an activation of cellular oncogenes.
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PMID:Integration of papillomavirus DNA near myc genes in genital carcinomas and its consequences for proto-oncogene expression. 164 48

Thirty-four patients of an Italian population affected by neuroblastoma (NB) were evaluated at diagnosis for multidrug resistance gene (MDR1) and N-myc oncogene amplification. No patients showed MDR1 amplification, while extra copies of the N-myc gene were found in 9 out of 34 patients (26%). N-myc amplification was correlated (p = 0.008) with a shorter progression-free survival. RNA was purified from fresh tumor biopsies and analysed in 29 NB samples. MDR1 gene expression was found to be increased in 5 out of 29 tumor samples at onset (17%) and in 1 out of 3 at relapse, but none of them expressed both MDR1 and N-myc genes simultaneously. No correlation was found between MDR1 or N-myc genes expression and tumor progression. MDR1 mRNA transcription may occur spontaneously after onset, suggesting that certain NB tumors could be resistant to antineoplastic drugs at onset. All 5 patients showing MDR1 mRNA transcription achieved complete or partial clinical remission after polychemotherapy. This was presumably due to inclusion in the therapeutic protocol of a high dose of Cisplatin, a drug not susceptible to the effects of the MDR1 gene product. Our findings show that cells which actively transcribe for the MDR1 gene are present in several untreated NB patients. No gene amplification was detected and probably the MDR1 gene expression is regulated at the transcriptional level.
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PMID:Expression of multiple drug resistance gene, MDR1, and N-myc oncogene in an Italian population of human neuroblastoma patients. 197 10

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

DNA ploidy and N-myc genomic content were analyzed in a series of stage IVS neuroblastomas by flow cytometry and Southern blot hybridization, respectively. Of the 12 stage IVS neuroblastomas studied, nine were aneuploid (DNA index [DI] greater than 1), two were diploid (DI = 1), and one was not assessable for DNA content due to insufficient tumor material. N-myc gene amplification was present in two of 12 tumors. None of the aneuploid tumors exhibited N-myc amplification. Among the aneuploid neuroblastomas, the DIs were between 1.27 and 1.60, ie, in the near-triploid range. The follow-up from diagnosis ranged from 1 to 41 months (mean, 20 months). The nine neuroblastomas with near-triploid DNA content were free of disease at the end of the follow-up period. In contrast, a rapid and fatal tumor progression was observed for the three neuroblastomas with N-myc amplification and/or diploidy. Although involving only a limited series, these results strongly suggest that the combined analysis of DNA ploidy and N-myc genomic content could predict clinical outcome in stage IVS neuroblastoma and should help to identify patients for whom a more aggressive therapy is required.
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PMID:N-myc genomic content and DNA ploidy in stage IVS neuroblastoma. 207 40

Small cell lung cancer (SCLC) tumor progression can involve partial or complete conversion to a more treatment-resistant non-small cell (NSCLC) phenotype. In a cell culture model of this phenomenon, we have previously demonstrated that insertion of the viral Harvey ras gene (v-Ha-ras) into SCLC cell lines with amplification and overexpression of the c-myc gene induced many NSCLC phenotypic features. We now report that the v-Ha-ras gene can also induce morphologic, biochemical, and growth characteristics consistent with the NSCLC phenotype in an N-myc amplified SCLC cell line, NCI-H249. We show that v-Ha-ras has novel effects on these cells, abrogating an SCLC-specific growth requirement for gastrin-releasing peptide, and inducing mRNA expression of three NSCLC-associated growth factors and receptors, platelet-derived growth factor B chain, transforming growth factor-alpha (TGF-alpha), and epidermal growth factor receptor (EGF-R). TGF-alpha secretion and EGF-R also appear, consistent with the induction of an autocrine loop previously shown to be growth stimulatory for NSCLC in culture. These data suggest that N-myc and v-Ha-ras represent functional classes of genes that may complement each other in bringing about the phenotypic alterations seen during SCLC tumor progression, and suggest that such alterations might include the appearance of growth factors and receptors of potential importance for the growth of the tumor and its surrounding stroma.
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PMID:v-rasH induces non-small cell phenotype, with associated growth factors and receptors, in a small cell lung cancer cell line. 216 28

Amplification is one mechanism for activation of oncogenes and results in an excess of DNA template, which can lead to overproduction of oncogene-specific RNA and protein. Amplification of oncogenes has been observed in different tumor tissues. In certain cases amplification and overexpression of particular oncogenes have been correlated with tumor progression and clinical behavior. The best example is neuroblastoma in which the N-myc oncogene frequently is found to be amplified. Over 1,000 patients with breast cancer have been studied for amplification of the c-erbB-2 oncogene until now. The evidence from the studies that amplification of c-erbB-2 is correlated with poor prognosis is in our opinion not convincing. More and more investigations about oncogenes and disease prognosis will take place rather at the protein level than at the DNA level.
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PMID:Amplification of oncogenes and disease prognosis. 218 30

Class I major histocompatibility complex (MHC) antigen expression in neuroblastoma may play a role in the oncogenicity of this embryonal tumor of childhood. Since N-myc amplification in neuroblastoma tumors is associated with rapid tumor progression (33) and N-myc decreases Class I MHC antigen expression in rat neuroblastoma cells (21), we quantitated levels of N-myc mRNA and Class I MHC cell surface antigens in a panel of 24 human neuroblastoma cell lines. We found that N-myc expression is not invariably associated with low levels of beta 2-microglobulin (B2M) and Class I MHC antigen expression. As we considered that Class I MHC antigens may be regulated in association with the differentiation stage of the neuroblastoma tumor, we examined the expression of B2M during development of the human adrenal medulla, the tissue of origin of most neuroblastomas. We found that B2M is a marker of differentiated adrenal medullary cells, expressed late during the third trimester of development. Moreover, using morphological and immunological criteria, we found that B2M is expressed in differentiated tumor cells. These data suggest that the expression of B2M in neuroblastoma is associated with the stage of differentiation of the tumor cell and not N-myc expression. Furthermore, these findings suggest that neuroblastomas may correspond to the arrested differentiation of adrenal neuroblasts at different stages of development.
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PMID:Beta 2-microglobulin expression in human embryonal neuroblastoma reflects its developmental regulation. 218

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

Amplification of the N-myc oncogene is detected in about 30% of untreated neuroblastomas. Amplification is associated with advanced stages of disease and rapid tumor progression. However, it was not known if the N-myc copy number was homogeneous in tumor tissue of an individual patient, or if it changed with time in vivo. Therefore, we have made 66 observations on multiple simultaneous or consecutive tumor samples from 60 patients with neuroblastoma. (a) Simultaneous samples were obtained from different areas of 31 tumor masses from 30 patients: a similar N-myc copy number (1-2, 3-10, or greater than 10) was found in all samples from each patient. (b) Simultaneous samples were obtained from different anatomical sites in ten patients. No difference in N-myc copy number was seen. (c) Finally, 25 patients had two or more tumor samples obtained over time. Thirteen patients had a single copy of N-myc in all samples, and 12 had consistent levels of amplification in all samples. Two of the latter cases had single copy of N-myc in a second-look surgery sample, but no tumor was evident histologically. This study demonstrates that the N-myc copy number in human neuroblastomas is usually consistent within a tumor, not only at different tumor sites, but also at different times in vivo. Overall, these findings suggest that N-myc amplification is an intrinsic biological property of a subset of neuroblastomas, and if amplification is going to occur, it is generally present at the time of diagnosis.
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PMID:Consistent N-myc copy number in simultaneous or consecutive neuroblastoma samples from sixty individual patients. 244 May 61


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