Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The subject of this retrospective study was to evaluate the potential benefit of the c-erbB-2 oncogene amplification and expression in 27 complete hydatidiform moles as well as in 9 cases of persistent gestational trophoblastic disease defined by elevated serum beta-human choriongonadotropin. The persistent cases were histopathologically classified as 5 complete hydatidiform moles, 3 invasive moles and 1 choriocarcinoma. In addition, we determined the DNA content and the karyotype of the sex chromosomes. The data were correlated with the histopathologic characteristics of gestational trophoblastic diseases. Cases with c-erbB-2 amplification and expression in combination with DNA hyperploidy showed higher proliferation and a more aggressive behavior (2 complete hydatidiform moles with lung and liver metastases, 2 invasive moles and 1 choriocarcinoma). XY karyotype was evident in the choriocarcinoma and in two complete hydatidiform moles with advanced stage and DNA hyperploidy.
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PMID:C-erbB-2 amplification and expression in gestational trophoblastic disease correlates with DNA content and karyotype. 944 75

The Kirsten-ras (onco)gene codes for a GTP-binding membrane protein that is involved in signal transduction. Activated ras triggers a cascade of protein-phosphorylations that ultimately lead to cell proliferation. Ras-mutations are the main cause for adenocarcinomas of the pancreas besides some mutations in the tumor suppressor gene p53 and the c-erbB-2 oncogene. The site of ras mutations in pancreatic cancer is restricted to codon 12 that normally encodes a glycine. For analysis of codon-12 mutations, DNA is extracted from cells in pancreatic fluid and amplified by PCR. Because most of these cells originate from normal tissue with only a few tumor cells in the fluid, "enrichment PCR" must be utilized: In a first round of the PCR, ras sequences from all cells are amplified. By utilizing an appropriate restriction enzyme, wild-type sequences can be digested and the remaining fragments containing mutated sequences be amplified again. An artificial restriction site must be introduced by the 5'primer (...GGA CCT GGT...) for an enzyme (BstNI) (5'CC!WGG 3') to differentiate between wild-type sequence (...GGA GCT GGT...) (during amplification, the G is replaced by a C) and mutated sequences (_...GGA GCT (GTT), (CGT), (CCT), etc.). The necessary manipulations pose a considerable risk for contamination for the second round of the PCR procedure. Therefore, we considered whether it would be feasible to perform the restriction digest simultaneously with the first PCR reaction, and avoiding the second round altogether. The results of our experiments demonstrate that one tumor cell in 1000 normal cells can be determined readily, paralleling the results with the original two step-assay. The restriction enzyme used to enrich mutated sequences is stable long enough to be included into the PCR procedure. By this, wild-type sequence amplicons are digested while they are formed and mutated sequences can be enriched selectively.
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PMID:Restriction digest PCR (RD-PCR) for the analysis of gene mutations. Application to Ki-ras. 980 67

In this study the expression of epidermal growth factor receptor (EGFR) and c-erbB-2, c-erbB-3 and c-erbB-4 oncogenes were investigated in gestational trophoblastic diseases and normal first trimester placenta. Furthermore, the possibility that macrophage (IL-1 alpha, IL-1 beta, TNF) and lymphocyte (IL-2, gamma-IFN, GM-CSF) cytokines effects are mediated by changes in EGFR expression were studied. Paraffin sections of 16 cases of partial mole, 25 cases of complete mole, 10 cases of gestational choriocarcinoma and 11 cases of therapeutic abortion were studied immunohistochemically for EGFR, c-erbB-2, c-erbB-3 and c-erbB-4 proteins. The presence of EGFR mRNA was studied using in situ hybridization. JEG-3 human choriocarcinoma cells were incubated with varying concentrations of interleukin 1-alpha, interleukin 1-beta, interleukin 2, gamma-interferon, granulocyte-macrophage colony stimulating factor and tumor necrosis factor-alpha, and the expression of EGFR was measured by radioimmunoassay using a murine monoclonal antibody with specificity for EGFR. Staining for EGFR was detected immunohistochemically in all cell type in gestational trophoblastic diseases and normal placenta. The levels of expression of EGFR in choriocarcinoma and syncytiotrophoblasts and cytotrophoblasts in complete mole were significantly greater than those in syncytiotrophoblasts and cytotrophoblasts in both normal placenta and partial mole (p < 0.01, p < 0.01). The immunoreactivity of c-erbB-2 was significantly stronger in choriocarcinoma and extravillous trophoblast in complete mole than that in extravillous trophoblast in partial mole and normal placenta (p < 0.02, p < 0.01, respectively). Strong immunostaining for EGFR (p = 0.02) and c-erbB-3 (p < 0.01) in extravillous trophoblasts of complete mole was found to be significantly correlated with the development of persistent postmolar gestational trophoblastic tumor. Macrophage-derived cytokines IL-1 alpha, IL-1 beta and TNF significantly suppressed cell growth; this was associated with a significant increase in EGFR expression. The lymphocyte (IL-2, gamma-IFN, GM-CSF) cytokines had no significant effect on either EGFR expression or cell growth. These findings support the concept that cytokines may act as paracrine mediators of autocrine processes involved in choriocarcinoma cell growth regulation by modulating growth factor receptor expression. The EGFR-related family of oncogenes may be important in the pathogenesis and prognosis of gestational trophoblastic diseases.
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PMID:[The c-erbB-related oncoproteins in normal placenta and in gestational trophoblastic diseases (in vitro study)]. 1142 88

Much debate exists on factors predicting the development of persistent gestational trophoblastic disease (pGTD). Diagnosis is still limited by following persistently elevated or rising postevacutation beta-human chorionic gonadotropin (beta-hCG) titers. The aim of the present work was to evaluate the hypothesis that the presence of c-erbB-2 oncogene amplification and expression, in combination with parameters such as DNA-content and karyotype of the sex chromosomes, confer an increased risk of developing pGTD. Clinicopathological characteristics were evaluated in 36 cases of gestational trophoblastic diseases (GTD) and analyzed for c-erbB-2 amplification and protein p185 expression using differential polymerase chain reaction (DPCR) and immunohistochemical (IHC) techniques. The DNA-content was determined by image analysis on Feulgen stained nuclear cell preparations and karyotyping for XY chromosomes was performed by fluorescence in situ hybridization (FISH). The data was correlated with histopathological characteristics of GTD. Seventy-five percent (n = 27) of the examined cases showed spontaneous regression after evacuation, including 2 patients who received additional chemotherapy. Twenty-five percent (n = 9) resulted in a persistent or metastatic disease. The median time between antecedent pregnancy and GTD was 45.4 months. Complete remission was achieved in all patients with pGTD after administration of chemotherapeutic agents or adjuvant surgical procedures. Cases with cerbB-2 amplification and expression in combination with DNA hyperploidy showed higher proliferation and more aggressive behavior (2 complete hydatidiform moles with lung and liver metastases, 2 invasive moles and 1 choriocarcinoma). XY karyotype was evident in the choriocarcinoma and in 2 complete hydatidiform moles with advanced stage and DNA hyperploidy. From these results we conclude that c-erbB-2 amplification and/or protein expression in combination with DNA-content show a significant correlation with the proliferative and aggressive potential of GTD, suggesting their combined use as a possible marker for pGTD.
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PMID:Clinicopathologic profile of gestational trophoblastic disease. 1265 8

A real-time PCR technique with automated computerized analysis (TaqMan ) was tested to detect K-ras mutations in 66 patients suffering from NSCLC. This technology is characterized by high reproducibility of data and a time-saving analysis procedure. In 11% (7/66) of the tumour specimens and 2% (1/58) of adjacent tumour-free lung specimens a K-ras codon 12 mutation was detected. In adenocarcinomas containing > or =40% tumour cells, however, K-ras mutations were seen in 25% of the cases. The point mutations detected in tumours were GGT right curved arrow TGT in five cases and GGT right curved arrow GTT in two cases. As compared with immunohistochemical parameters, the K-ras mutated group was characterized by a c-erbB-2 negativity (p=0.04) and a smaller number of c-erbB-3 (p=0.02) positive cases. EGFR, bcl-2, p53, Ki-67 and p120 expression did not differ significantly. Determination of the K-ras point mutations by automated TaqMan PCR in NSCLC tumour specimens is feasable and highly specific. Due to its high throughput capacity this method represents a valuable tool for routine screening.
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PMID:Automated real-time PCR to determine K-ras codon 12 mutations in non-small cell lung cancer: comparison with immunohistochemistry and clinico-pathological features. 1296 94