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)

High-molecular-weight DNAs from 43 human primary tumor tissues were examined by Southern blot hybridization for possible rearrangement and/or amplification of the following protooncogenes: the c-myc, c-erbB-1, N-myc, c-mos and c-fos genes. In an adenosquamous cell carcinoma of the stomach, the c-myc and c-erbB-1 genes were found to be simultaneously amplified 5- and 30-fold, respectively. Cooperative expression of the amplified c-myc and c-erbB-1 genes might be involved in the genesis or progression of the gastric cancer.
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PMID:DNA amplification of the c-myc and c-erbB-1 genes in a human stomach cancer. 310 22

Our previous work has shown that 26 of 38 cases (68.4%) of primary adenocarcinoma of the colon exhibited significantly elevated levels of c-myc RNA compared to normal colonic mucosa (M. D. Erisman, P. G. Rothberg, R. E. Diehl, C. C. Morse, J. M. Spandorfer, and S. M. Astrin. Mol. Cell. Biol., 5: 1969-1976, 1985; P. G. Rothberg, J. M. Spandorfer, M. D. Erisman, R. N. Staroscik, H. F. Sears, R. O. Petersen, and S. M. Astrin. Br. J. Cancer, 52: 629-632, 1985). In this study, we have compared those levels of expression to the clinical profiles of the affected individuals in an effort to define useful correlates, especially with regard to recurrence of disease and patient survival. Log-rank comparisons of recurrence curves for the entire patient population, for those patients with low levels of c-myc RNA in resected tumor tissue, and for those patients with significantly elevated levels of RNA show no statistically significant differences. Similarly, no statistically significant difference was observed between the high- and low-myc RNA groups with respect to their survival during the postoperative period of observation (median, 25 months). Consequently, the levels of c-myc gene expression observed in primary tumor tissue did not help to define those individuals at higher or lower risk for recurrence of disease and did not point to the likelihood of increased or decreased survival in individuals undergoing surgery for adenocarcinoma of the colon.
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PMID:Noncorrelation of the expression of the c-myc oncogene in colorectal carcinoma with recurrence of disease or patient survival. 334 13

We have examined the level of the c-myc transcript in 6 esophageal, 16 gastric, 19 colorectal and 1 anal cancer tissue samples; these included four lymph nodes and six hepatic metastases obtained surgically. The esophageal cancer tissues were without an increase of the c-myc transcript, some of the gastric cancer samples showed a two to three fold increase and most of the colorectal and the one anal cancer samples showed a two to ten fold increase when compared with a normal mucosal layer. Therefore, the level of the c-myc transcript in human gastrointestinal malignancies shows organ dependency. Local, lymphatic, and hepatic metastases showed little difference in the level of c-myc mRNA from that of the primary tumor.
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PMID:Expression of the c-myc gene in human gastrointestinal malignancies. 361 99

A human pancreatic cancer cell line, PSN-1, was established from pancreatic adenocarcinoma tissue that had been stored for 1.5 years at -80 degrees C without any special treatment. The stored tissues were first transplanted into nude mice, and from the xenograft, the PSN-1 cell line was established. The original primary tumor and two metastatic lymph nodes were previously found to have 50-fold amplification of c-myc and also 3- to 6-fold amplification of activated c-Ki-ras with a point mutation from GGT to CGT at codon 12. PSN-1 cells are unique in that amplifications of both c-myc and activated c-Ki-ras are present in the same degree as the original tumors. These cells were also found to contain increased amounts of c-myc and c-Ki-ras transcripts.
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PMID:Establishment of a human pancreatic adenocarcinoma cell line (PSN-1) with amplifications of both c-myc and activated c-Ki-ras by a point mutation. 377 42

Primary diffuse infiltrative cancer of the large bowel shows poor prognosis. A human rectal cancer cell line, designated as SRM, was established from the metastatic lymph node of a 35-year-old female patient. SRM cells have been cultured with RPMI-1640 medium supplemented with 10% fetal calf serum and grew as monolayers, showing a tendency to pile up. The doubling time of this cell line was 23.0 hours, and the modal number of chromosomes was 64 at passage 14. The cells produced CA19-9 and TPA in the spent medium and formed tumors in nude mice, the histology of which was similar to that of the primary tumor. CA19-9 in the cytoplasma of the transplanted tumor cells was demonstrated by the ABC method and the c-myc oncogene was amplified in the transplanted tumor in nude mice.
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PMID:[Establishment and characterization of a human rectal cancer cell line, SRM from primary diffuse infiltrating type cancer]. 834 49

A modification of "reverse chromosome painting" was carried out using genomic DNA from tumor cells as a complex probe for chromosomal in situ suppression hybridization to normal metaphase chromosome spreads. Amplified DNA sequences contained in such probes showed specific signals, revealing the normal chromosome positions from which these sequences were derived. As a model system, genomic DNAs were analyzed from three tumor cell lines with amplification units including the proto-oncogene c-myc. The smallest amplification unit was about 90 kb and was present in 16-24 copies; the largest unit was bigger than 600 kb and was present in 16-32 copies. Specific signals that co-localized with a differently labeled c-myc probe on chromosome band 8q24 were obtained with genomic DNA from each cell line. In further experiments, genomic DNA derived from primary tumor material was used in the case of a male patient with glioblastoma multiforme (GBM). Southern blot analysis using an epidermal growth factor receptor gene (EGFR) probe that maps to 7p13 indicated the amplification of sequences from this gene. Using reverse chromosome painting, signals were found both on band 7p13 and bands 12q13-q15. Notably, the signal on 12q13-q15 was consistently stronger. The weaker 7p13 signal showed co-localization with the major signal of the differently labeled EGFR probe. A minor signal of this probe was seen on 12q13, suggesting cross-hybridization to ERB3 sequences homologous to EGFR. The results indicate co-amplification of sequences from bands 12q13-q15, in addition to sequences from band 7p13. Several oncogenes map to 12q13-q15 providing candidate genes for a tumor-associated proto-oncogene amplification. Although the nature of the amplified sequences needs to be clarified, this experiment demonstrates the potential of reverse chromosome painting with genomic tumor DNA for rapidly mapping the normal chromosomal localization of the DNA from which the amplified sequences were derived. In addition, a weaker staining of chromosomes 10 and X was consistently observed indicating that these chromosomes were present in only one copy in the GBM genome. This rapid approach can be used to analyze cases where no metaphase spreads from the tumor material are available. It does not require any preknowledge of amplified sequences and can be applied to screen large numbers of tumors.
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PMID:Detection of amplified DNA sequences by reverse chromosome painting using genomic tumor DNA as probe. 838 93

Lymphoma represents a major source of morbidity and mortality among AIDS patients. AIDS-associated non-Hodgkin lymphomas (AIDS-NHL) are almost invariably B-cell derived, are classified as high or intermediate grade lymphomas, and display three main histologic types: namely, small non-cleaved cell lymphoma (SNCCL), large cell immunoblastic plasmacytoid lymphoma (LC-IBPL), and large cell lymphoma (LCL). Here we report the in vitro establishment of three new AIDS-NHL cell lines (termed HBL-1, HBL-2, and HBL-3) derived from three AIDS-SNCCL patients differing in primary tumor sites and risk factors for HIV infection. The derivation of the cell lines from the original tumor clones was established by immunophenotypic and molecular genetic analysis. These cell lines display clonal immunoglobulin gene rearrangement, express surface immunoglobulin and B-cell restricted markers, and exhibit a phenotype consistent with SNCCL. Monoclonal Epstein-Barr virus infection was found in only one of the cell lines (HBL-1). Cytogenetic analysis demonstrated the presence of a chromosomal translocation involving the c-myc proto-oncogene and an immunoglobulin locus in all three cell lines. The pattern of genetic lesions detected in HBL-1, HBL-2, and HBL-3 reflects that found in primary AIDS-SNCCL and includes activation of the c-myc oncogene as well as inactivation of the p53 tumor suppressor gene. These cell lines should prove useful in studies of the biological, immunological, and viral factors involved in AIDS-associated lymphomagenesis.
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PMID:In vitro establishment of AIDS-related lymphoma cell lines: phenotypic characterization, oncogene and tumor suppressor gene lesions, and heterogeneity in Epstein-Barr virus infection. 841 24

The role of c-myc in prostatic carcinogenesis is poorly understood. The pathogenetic relationship between high-grade prostatic intraepithelial neoplasia (PIN), prostatic carcinoma, and metastases is not well-defined. We used fluorescence in situ hybridization (FISH) with a region-specific probe for c-myc (band 8q24) and chromosome enumeration probes for chromosomes 7, 8, 10, 12, and Y to evaluate genetic changes in matched PIN (48 foci), localized prostatic carcinoma (71 foci), and lymph node metastases (23 foci) in 25 totally embedded whole-mount stage D1 (T2-3 N1-3 M0) radical prostatectomy and pelvic lymphadenectomy specimens. The c-myc protein expression in these lesions was evaluated by immunohistochemistry. Foci with extra copies of c-myc could be divided into three groups: (a) those with simple gain of a whole chromosome 8 (no increase in c-myc copy number relative to the chromosome 8 centromere), which was identified in 42, 25, and 46% of foci of PIN, carcinoma, and metastases, respectively; (b) those with an intermediate increase in c-myc copy number relative to the chromosome 8 centromere, which was found in 8, 11, and 25% of foci of PIN, carcinoma, and metastases, respectively; and (c) those with substantial amplification of c-myc (large increases in c-myc copy number relative to the chromosome 8 centromere), which was detected in 0, 8, and 21% of foci of PIN, carcinoma, and metastases, respectively. Substantial amplification of c-myc was strongly correlated with increasing cancer nuclear grade and immunohistochemical evidence of c-myc protein overexpression. Numeric chromosomal anomalies were found in 67, 68, and 96% of foci of PIN, carcinoma, and metastases, respectively. The most frequent anomaly in PIN and carcinoma was a gain of chromosome 8, and the presence of this anomaly strongly correlated with Gleason score. Carcinoma foci usually contained more FISH anomalies than paired PIN foci, but three prostates contained one or more PIN foci with more anomalies than carcinoma. Thirteen primary tumor foci exhibited intratumor genetic heterogeneity by FISH. One or more foci of the primary tumor usually shared FISH anomalies with the matched metastases. Our FISH results indicate that: (a) gain of chromosome 8 and amplification of c-myc are potential markers of prostate carcinoma progression; (b) PIN is likely a precursor of carcinoma; (c) intraglandular and intratumoral genetic heterogeneity is relatively common; and (d) usually a single focus of cancer gives rise to metastases.
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PMID:Detection of c-myc oncogene amplification and chromosomal anomalies in metastatic prostatic carcinoma by fluorescence in situ hybridization. 901 85

The c-myc gene product is known to be involved in the regulation of cell proliferation and differentiation. Altered c-myc gene expression is a common event in a variety of tumors. This study was designed to investigate c-myc overexpression in transitional cell carcinoma (TCC). The first part was designed to investigate the frequency of c-myc overexpression in relation to tumor stage and tumor grade. A second set of experiments was directed at the mechanisms underlying c-myc overexpression in TCC. A total of 185 paraffin-embedded urothelial tissue specimens were investigated immunohistochemically for c-myc overexpression. A single case of overexpression (6%) was observed in normal urothelial tissue (n = 16). c-myc overexpression was also infrequent in carcinoma in situ (TIS) (7/39 = 18%). In contrast, papillary urothelial tumors (n = 65) yielded c-myc overexpression in 38 cases (58%). Investigation of infiltrating bladder tumors revealed c-myc overexpression in 56% of T1 tumors and 59% of muscle-infiltrating tumors. The staining pattern in multifocal tumors was heterogeneous in 10 of 18 cases. Similarly, only 12 of 28 patients with tumor recurrences showed the same c-myc staining pattern in the primary tumor and in tumor recurrences. c-myc overexpression did not correlate with tumor grade or tumor progression. Nevertheless, the high frequency of c-myc overexpression in urothelial carcinoma suggests an important role for this protein in urothelial carcinoma. Therefore, the mechanism underlying c-myc overexpression was further investigated in six bladder carcinoma cell lines. Southern blot experiments under standardized conditions showed no significant gene amplification. The comparison of c-myc mRNA expression to that of histone H3 as a measure of cell proliferation revealed a moderate correlation (r = 0.45) in the six cell lines examined. These data suggest that in accord with its established role as a cell cycle competence factor, c-myc may be necessary but not sufficient for the induction of proliferation in urothelial carcinoma.
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PMID:c-myc in bladder cancer. Clinical findings and analysis of mechanism. 907 56

The ether lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3; Edelfosine) has been shown to be a rapid inducer of apoptosis in human leukemic cells and has been considered as a promising drug in cancer treatment. Here we have found that ET-18-OCH3 induced apoptosis not only in human tumor cell lines but also in primary tumor cell cultures from cancer patients. Human leukemic cells were highly sensitive to ET-18-OCH3, whereas normal cells remained unaffected. Among the distinct modifications of the ET-18-OCH3 molecule assayed, we found that substitutions in positions sn-2 and sn-3 of the glycerol backbone resulted in a complete loss of its capacity to induce apoptosis, highlighting the importance of the molecular structure of ET-18-OCH3 in its apoptotic effect. Induction of apoptosis by ET-18-OCH3 was very well correlated with the uptake of this ether lipid. ET-18-OCH3-resistant 3T3 fibroblasts became sensitive and incorporated significant amounts of the ether lipid following transformation with the SV40 virus. ET-18-OCH3-induced apoptosis as well as ET-18-OCH3 uptake were not mediated through binding of the ether lipid to the platelet-activating factor receptor. Overexpression of bcl-2 or bcl-xL by gene transfer in the human erythroleukemic HEL cells abrogated apoptosis induced by ET-18-OCH3. ET-18-OCH3 did not affect the expression of bcl-2, bcl-xL, or bax in HEL and HL-60 human leukemic cells but induced expression of c-myc, an important effector of apoptosis in several systems. Thus, ET-18-OCH3 behaves as a potent and highly selective antitumor drug able to induce an apoptotic pathway of cell death in tumor cells but not in nonmalignant cells.
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PMID:Selective induction of apoptosis in cancer cells by the ether lipid ET-18-OCH3 (Edelfosine): molecular structure requirements, cellular uptake, and protection by Bcl-2 and Bcl-X(L). 910 20


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