Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro cultivated cells of 28 colorectal cancers were analyzed for chromosomal abnormalities that might signal amplification of DNA, either as double minutes (DMs) or homogeneously staining chromosomal regions (HSRs). Cells derived from 18 tumors showed DMs in 10 to 100% of all metaphases examined. Surveys that employed a panel of available oncogene probes failed to detect amplification of a known cellular oncogene with the exception of three cases where the ERBB2 gene was amplified. In one of these three cases neither DMs nor HSRs were detectable. Our studies show that from 28 lines established in culture, 19 (68%) show amplification of DNA, and indicate that DNA amplification is a frequent genetic alteration in colorectal cancers in addition to other genetic changes. Amplification is correlated with high Dukes stage, but not with histological grade. The identity of the amplified DNA remains to be established for most cases.
Genes Chromosomes Cancer 1990 May
PMID:Cytogenetics and DNA amplification in colorectal cancers. 198 Jun 7

Molecular mechanism of development and progression of gastric cancer which could be a base of molecular diagnosis was described. Amplification and point mutation of oncogenes are less common in gastric carcinomas, even though it is valuable for diagnosis. Amplification of ERBB2 seems to be an indicator for metastatic ability of gastric carcinoma. Overexpression of EGF/receptor system is a biologic marker for high malignancy. Diagnostic significance for scirrhous gastric carcinomas is found in over-expression of TGF beta, IGF and PDGF. Loss of heterozygosity on chromosomes 5q and 17p frequently occurs commonly in well differentiated type gastric cancer. More accumulation of molecular alterations in the development and progression of gastric cancer should make the molecular diagnosis more valuable in clinical field.
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PMID:[Molecular diagnosis of gastric cancer]. 198 3

Many malignancies exhibit distinct patterns of metastasis that appear to be mediated by receptor/ligand-like interactions between tumor cells and organ-specific vascular endothelium. In order to study endothelial cell surface molecules involved in the binding of metastatic cells, we developed a perfusion method to isolate outside-out membrane vesicles from the lumenal surface of rat lung microvascular endothelium. Lungs were perfused in situ for 4 h at 37 degrees C with a solution of 100 mM formaldehyde, 2 mM dithiothreitol in phosphate-buffered saline to induce endothelial cell vesiculation. Radioiodinated rat lung endothelial cell membrane vesicles bound lung-metastatic tumor cells (B16F10, R323OAC-MET) in significantly higher numbers than their low or nonmetastatic counterparts (B16F0, R323OAC-LR). In contrast, leg endothelial membrane vesicle showed no binding preference for either cell line. Neuraminidase treatment of vesicles abolished specificity of adhesion of lung-derived vesicles to lung metastatic tumor cells. These results demonstrate that in situ perfusion is an appropriate technique to obtain pure endothelial cell membrane vesicles containing functionally active adhesion molecules. The preferential binding of lung-derived endothelial cell membrane vesicles by lung metastatic tumor cells is evidence of the importance of endothelial cell adhesion molecules in the formation of metastases.
Cancer Res 1991 Jan 01
PMID:Endothelial cell membrane vesicles in the study of organ preference of metastasis. 198

To establish an objective basis for therapeutic decisions and follow-up programs in patients with follicular thyroid cancer, the authors developed a prognostic scoring system. The prognostic impact of nine clinical, histologic, and therapeutic parameters was quantified retrospectively based on a multivariate analysis covering 149 patients. The relative relapse risk in follicular thyroid cancer (RR) was 6.8-fold increased in the presence of a moderate when compared with a high degree of histologic tumor differentiation. The RR rose with increasing age of the patient at time of tumor diagnosis by a factor of 1.8 per 20 years. The RR was reduced by a factor of 4.3 after the performance of a neck dissection and by a factor of 2.3 after percutaneous radiation therapy of the neck. The relative mortality risk in follicular thyroid cancer (RM) rose in the absence of a tumor capsule by a factor of 10, in the presence of a moderate compared with a high degree of histologic tumor differentiation by a factor of 5.9, in the presence of distant metastases by a factor of 3.2, and with increasing age of the patient at the time of tumor diagnosis by a factor of 2.2 per 20 years. From these data prognostic indices denoting the individual risk for tumor relapse (IRR index) and tumor mortality (IMR index) were calculated. The indices categorize patients into low-risk, medium-risk, or high-risk groups with regard to tumor relapse and tumor-related death. Consequently, the IRR and IMR indices contribute to select patients with follicular thyroid cancer who need an aggressive form of treatment and an intensive follow-up program. The indices may also be used for risk stratification in prospective therapy trials.
Cancer 1991 Apr 01
PMID:Prognostic indices for tumor relapse and tumor mortality in follicular thyroid carcinoma. 200 4

EGFR gene transcription in rat embryo and adult tissues were analysed by RNA Northern and Dot hybridization using 2.4 Kb human EGFR cDNA pE 7 as probe. In Northern hybridization (Fig. 1), the normal rat liver RNA showed a major 5.6 Kb RNA band which was a common EGFR mRNA present in human normal and cancer cells. For the comparison of EGFR gene transcription in embryo of different stages and different tissues, the density scanning data of dot hybridization signals are shown as bars in accompanying figures. The results indicated that the highest level of EGFR transcription was seen in rat embryo at 10th to 12th day during neonatal development (Fig. 2 and Fig. 3). In adult rat tissues, EGFR gene was commonly expressed with some variation in different tissues, for example, much more expressed in kidney than in liver, heart, brain and spleen, and moderately expressed in testis and lung (Fig. 4). The EGFR gene transcription could be induced in liver by hepatectomy. Fig. 5 showed the increase of EGFR gene transcripts at the 2-8 th hour of liver regeneration and the decrease after the 8th hour, even reaching a value lower than that of normal liver after the 24th hour. The results suggest that EGFR gene transcripts are commonly present in a wide range of normal tissues and may be involved in the control of proliferation and differentiation in embryo and adult tissues.
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PMID:[Analysis of EGFR gene transcription in rat embryo and adult tissues]. 203 13

The presence of gene amplification was determined in 66 fresh head-and-neck SCC specimens using a battery of 9 different probes. Amplification of at least one gene was found in 12 samples (18%), of which 7 were amplified at multiple loci (58%). We observed amplifications for EGFR (10% of samples) and c-myc (9%), as well as co-amplification of bcl-1/int-2 (7%). No amplifications were demonstrated for c-Ha-ras-1, TGF alpha, c-mos, c-erbB-2, or c-erbA-2. The incidence of proto-oncogene amplification in head-and-neck SCC patients is comparable to that reported for other solid tumours. There was no statistically significant difference in survival between patients with or without gene amplification. However, the presence of multiple amplifications in several patients with advanced primary tumours suggests that the accumulation of genetic changes may correlate more closely with tumour size than with inherent biologic aggression.
Int J Cancer 1991 Jun 19
PMID:Analysis of gene amplification in head-and-neck squamous-cell carcinoma. 204 98

The TPR-MET oncogenic rearrangement was originally observed in an in vitro transformed human osteosarcoma cell line. Recently, we detected the expression of this rearrangement at very low levels in several cell lines derived from human tumors of nonhematopoietic origin using a highly sensitive method based on polymerase chain reaction amplification of the transcript. We report here the results of analysis of TPR-MET expression in cell lines derived from human gastric tumors and 22 biopsy samples of human gastric mucosa showing cancer or precursor lesions. The rearranged RNA was expressed in all four cell lines as well as in biopsy samples from 12 of the 22 patients. Overexpression of TPR-MET RNA in superficial gastritis lesions with hyperplasia of glandular neck cells suggests the possible involvement of this oncogene at an early stage of gastric tumorigenesis. Analysis of gastric biopsy samples for RAS gene mutations showed base substitutions occurring in the codon 12 region of Ki- and Ha-RAS genes in four cases, including two precursor lesions.
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PMID:The TPR-MET oncogenic rearrangement is present and expressed in human gastric carcinoma and precursor lesions. 205 72

We present cytogenetic and molecular genetic analyses of two cases of alveolar rhabdomyosarcoma. The characteristic translocation between chromosomes 2 and 13, t(2;13)(q35;q14), has been identified in both cases. Using cell lines derived from these tumor specimens, we have performed Southern blot analysis to investigate the possibility of rearrangement of 14 candidate genes mapping to the relevant regions of 2q and 13q. These candidate genes can be divided into 5 groups: signal transduction proteins (RB1, inhibin alpha, FLT1, and HOX4B), muscle-specific products [myosin light chain, desmin, and nicotinic cholinergic receptor subunits gamma and delta (CHRNG and CHRND)], extracellular matrix proteins (collagen type VI alpha 3 chain, elastin, and fibronectin), transformation-associated products (intestinal alkaline phosphatase and L-plastin), and other genes (esterase D). Conventional gel electrophoresis followed by Southern blot analysis indicated no evidence of rearrangement within or near these genes except for a rearrangement in the CHRNG-CHRND locus, which occurred only in a subpopulation of the late recurrence tumor cells of one patient. In addition, we employed pulsed-field gel electrophoresis-Southern blot analysis to demonstrate the absence of detectable rearrangements within a larger region around each of these genes.
Genes Chromosomes Cancer 1991 Mar
PMID:Molecular and cytogenetic analysis of chromosomal arms 2q and 13q in alveolar rhabdomyosarcoma. 206 13

Human esophageal and gastric carcinomas express multi-autocrine growth factors and hormones including epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and beta, platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) and sex hormones. Overexpression of EGF, TGF-alpha and EGF receptor (EGFR) by tumor cells is closely correlated with the tumor invasion and patient prognosis. This is substantiated by the facts that EGF and TGF-alpha act as autocrine growth factors and then induce the expression of mRNAs for multi-growth factors and their receptors (EGF, TGF-alpha, EGFR, ERBB2, PDGF). Moreover, they stimulate the expression of metalloproteinase genes suggesting that EGF and TGF-alpha successively evoke cascade phenomena which are most convenient for tumor progression, invasion and metastasis. On the other hand, multiple oncogene alterations take place in the process of tumor progression. HST-1 and INT-2 genes which is a member of fibroblast growth factor gene family, are amplified in approximately 50% of primary tumors and all the metastatic tumors of esophageal carcinomas. The amplification of ERBB2 gene in metastatic gastric carcinomas is detected more frequently than in primary carcinomas. Overexpression of multi-growth factor-receptor systems might lead to genetical alterations. Scirrhous gastric carcinoma has vast fibrous stroma with rapid and extensive growth and exhibits high malignancy. Its fibrous stroma may account for synchronous overexpression of EGF, TGF-alpha, PDGF, IGF and TGF-beta by tumor cells. Most of well differentiated adenocarcinomas show overexpression of p 185ERBB2 and coexpression of p 185ERBB2, and EGFR evidently correlates with high malignancy. In conclusion, the accumulation and interaction of several growth factors produced by tumor cells are necessary for the progression of human esophageal and gastric carcinomas. They may be attributed to genetic changes including activation of oncogenes, inactivation and deletion of anti-oncogenes and transcriptional regulatory sequences.
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PMID:Growth factors in progression of human esophageal and gastric carcinomas. 209 74

We studied 41 patients with myelodysplastic syndromes or acute myeloid leukemia to assess the presence of point mutations in the human FMS gene (M-CSF receptor). Using the polymerase chain reaction and hybridization of oligonucleotide probes to the amplified sequences, we have detected mutations in eight of 41 patients, at codons 301 and 969. In vitro work has highlighted mutations at these codons as being oncogenic. We now report the detection of potentially activating mutations of the human FMS gene in vivo. The consequence of these mutations in the multistep pathogenesis of myeloid malignancy and their relevance to prognosis remains to be determined.
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PMID:Mutation of the human FMS gene (M-CSF receptor) in myelodysplastic syndromes and acute myeloid leukemia. 214 47


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