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)

One hundred and nine primary breast cancers were analyzed to assess the presence of the HER-2/neu gene product (p185), the oestrogen (ER) and the progesterone (PR) receptors, and the total cathepsin D status. An enzyme-linked immunosorbent assay (ELISA kit, Oncogene Science Inc.) was used for the evaluation of p185 in pellets obtained after a 100,000 x g centrifugation, ER and PR were measured by enzyme immunoassay (EIA kit, Abbott Laboratories), and the total cathepsin D content was evaluated by immunoradiometric assay (IRMA kit, CIS Biointernational). We showed that the ELISA kit is feasible to quantify the p185 present in breast cancer cell membranes, and that the detector antibody recognises a protein of apprroximatly M(r) 185,000. The detected antigen was inversely related to both ER and PR, but it did not correlate to total cathepsin D. No significant differences were found in the expression of p185, ER, PR, cathepsin D between infiltrating ductal carcinomas without special features (NOS) and non-ductal (non-NOS) carcinomas. Nevertheless, in NOS carcinomas, a trend was observed in the p185 levels expressed by the tumours with different histological grades, in that p185 concentration was higher in the poorly differentiated grade 3 with respect to grade 2 and grade 1.
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PMID:Enzyme-linked immunosorbent assay of HER-2/neu gene product (p185) in breast cancer: its correlation with sex steroid receptors, cathepsin D and histologic grades. 790 96

ErB-2 protein levels in breast cancer tissue extracts were determined by an enzyme immuno assay (ErbB-2 EIA "Nichirei") using anti-c-erbB-2 monoclonal antibodies, and compared with the c-erbB-2 gene amplification detected by dot blot hybridization or differential PCR, and with the overexpression detected by immunostaining. The positivities of c-erbB-2 gene amplification and overexpression in breast cancer tissues were 25.0% (14/56) and 39.3% (46/117), respectively. The cut-off values of the Erb B-2 protein in tissue extract by EIA were set at 18.0 ng/mg-protein for gene amplification and 10.4 ng/mg-protein for overexpression, respectively, from the data of breast cancer tissues which were negative for c-erbB-2 gene. The accuracy of the ErbB-2 protein levels in tissue extract with c-erbB-2 gene amplification and overexpression were 90.6% and 79.2% using these cut-off values respectively. The result of c-erbB-2 gene amplification, overexpression, and ErbB-2 protein levels were significantly correlated with negative estrogen receptor (ER) and progesterone receptor (PgR) status in tissue cytosol fraction. These results indicate that measurement of ErbB-2 protein in tissue extract is useful to estimate the c-erbB-2 gene amplification and/or overexpression in breast cancer tissues.
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PMID:[Clinical evaluation of ErbB-2 protein in tissue extract using an enzyme immuno assay (ErbB-2 EIA "Nichirei")]. 791 82

The HER-2/neu (also known as c-erbB-2) oncogene is the second member of the epidermal growth factor receptor family. It is overexpressed in many different types of human cancers, including breast, ovarian, lung, gastric, and oral cancers. Overexpression of HER-2/neu in breast cancer has been associated with poor overall survival and has been shown preclinically to enhance malignancy and the metastatic phenotypes. Although discrepancies exist between different studies, HER-2/ neu overexpression seems to induce chemoresistance in certain experimental conditions. Many studies have convincingly shown that repression of HER-2/neu suppresses the malignant phenotypes of HER-2/neu-overexpressing cancer cells. These findings strongly suggest that HER-2/neu may serve as an excellent target for developing anticancer agents specific for HER-2/neu-overexpressing cancer cells. HER-2/neu-encoded p185 protein is a receptor tyrosine kinase that can be associated with multiple signal transduction pathways. However, it is not yet clear how a specific signal pathway may correspond to a specific biological response. This report reviews basic information on signal transduction of HER-2/neu receptor tyrosine kinase and summarizes our approaches to targeting HER-2/neu-overexpressing cancer cells. The HER-2/neu promoter was targeted using cationic liposomes or an adenovirus vector to deliver the adenovirus-5 EIA gene products and a nontransformed mutant of the SV40 large T antigen into the tumor-bearing mice. This resulted in suppression of the tumor growth and prolongation of survival. For repressing the function of HER-2/neu we used emodin, a tyrosine kinase inhibitor. This agent can inhibit the tyrosine kinase activity of HER-2/neu and preferentially block the growth of the HER-2/neu-overexpressing human breast cancer cells in tissue culture as well as in nude mice.
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PMID:Basic science of HER-2/neu: a review. 1048 94

HER-2/neu-overexpressing breast cancer cells are more resistant to the chemotherapeutic agent paclitaxel (Taxol) than low-HER-2/neu-expressing breast cancer cells, and the adenoviral type 5 EIA can down-regulate HER-2/neu overexpression. Therefore, in this study, we asked (a) whether EIA might sensitize response to paclitaxel in human HER-2/neu-overexpressing ovarian cancer cells, and, if so, what is the mechanism responsible; and (b) whether this enhanced chemosensitivity would translate into a therapeutic effect in an ovarian cancer xenograft model. Consequently, we demonstrated that: (a) adenovirus type 5 E1A could enhance the sensitivity of paclitaxel in paclitaxel-resistant HER-2/neu-overexpressing human ovarian cancer cells in vitro by inducing apoptosis, (b) this induction was heavily dependent on activation of the caspase-3 pathway, and (c) nude mice bearing i.p. HER-2/neu-overexpressing human ovarian cancer cells and treated with both paclitaxel and E1A gene therapy survived significantly longer than did mice treated only with paclitaxel or E1A gene therapy. Thus, we concluded that the E1A gene enhanced both the in vitro and in vivo sensitivity of paclitaxel in paclitaxel-resistant HER-2/ neu-overexpressing ovarian cancer SKOV3.ipl cells. Because a Phase I clinical trial using E1A gene targeted to HER-2/neu down-regulation has recently been completed, the current study also provided a scientific basis to further develop a novel therapy that combines paclitaxel and E1A gene therapy and its testing in a Phase II trial.
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PMID:E1A-mediated paclitaxel sensitization in HER-2/neu-overexpressing ovarian cancer SKOV3.ip1 through apoptosis involving the caspase-3 pathway. 1065 56

In a retrospective study of 488 women with primary breast cancer, after a median follow-up of 10 years, we sought interactions between disease-free survival (DFS) and overall survival (OS) and tumor antigen levels of two components of the plasminogen system, urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1, and the transmembrane growth factor receptor c-erbB-2. We used ELISAs (American Diagnostica, Greenwich, CT, USA) to quantify uPA and PAI-1 antigen levels in cytosols, and a double monoclonal antibody-based assay (EIA) (Ciba Corning Diagnostics, Alameda, CA, USA) to quantify c-erbB-2 in membrane extracts of the same tissues. Weak positive correlations were found between uPA and c-erbB-2 (r(s) = 0.146; p = 0.001) and between PAI-1 and c-erbB-2 (r(s) = 0.154; p < 0.001). In the overall population, using univariate analyses, c-erbB-2 overexpression and high uPA and PAI-1 antigen levels (> 300 IU/mg, > 1.40 ng/mg and > 5.53 ng/mg, respectively) were significantly associated with shorter DFS (p = 0.003, p < 0.001 and p < 0.001, respectively) and OS (p < 0.001 in all cases). Using multivariate analyses, PAI-1, node status and tumor size were independent predictors of DFS and c-erbB-2 was retained in the model only for OS. In the node-negative subgroup, PAI-1 was the strongest significant survival predictor both for OS (p = 0.003; HR 2.52) and DFS (p < 0.001; HR 2.39). This study shows that in primary breast cancer c-erbB-2 offers no additional prognostic information when uPA and/or PAI-1 are candidates in the multivariate analyses.
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PMID:Limited prognostic value of c-erbB-2 compared to uPA and PAI-1 in primary breast carcinoma. 1453 92

The assessment of ERa, PgR and HER2 status is routinely performed today to determine the endocrine responsiveness of breast cancer samples. Such determination is usually accomplished by means of immunohistochemistry and in case of HER2 amplification by means of fluorescent in situ hybridization (FISH). The analysis of these markers can be improved by simultaneous measurements using quantitative real-time PCR (Qrt-PCR). In this study we compared Qrt-PCR results for the assessment of mRNA levels of ERa, PgR, and the members of the human epidermal growth factor receptor family, HER1, HER2, HER3 and HER4. The results were obtained in two independent laboratories using two different methods, SYBR Green I and TaqMan probes, and different primers. By linear regression we demonstrated a good concordance for all six markers. The quantitative mRNA expression levels of ERa, PgR and HER2 also strongly correlated with the respective quantitative protein expression levels prospectively detected by EIA in both laboratories. In addition, HER2 mRNA expression levels correlated well with gene amplification detected by FISH in the same biopsies. Our results indicate that both Qrt-PCR methods were robust and sensitive tools for routine diagnostics and consistent with standard methodologies. The developed simultaneous assessment of several biomarkers is fast and labor effective and allows optimization of the clinical decision-making process in breast cancer tissue and/or core biopsies.
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PMID:Simultaneous quantitative detection of relevant biomarkers in breast cancer by quantitative real-time PCR. 1671 11

Employing CLIA and EIA methods simultaneously, we determined serum HER-2/neu levels a total of 92 times in 51 patients with metastatic breast cancer(MBC)and 3 patients with non-recurrent breast cancer, and compared the levels measured by both methods with the level of IHC-staining for HER-2 and the clinical course. Among 20 patients with IHC HER-2/3+ MBC (including FISH+MBC), 14(70%)showed high levels by the CLIA method (>cut-off value of 15.2 ng/mL), whereas only 4(20%)revealed high levels by the EIA method(>cut-off value of 6.5 ng/mL). None of the patients with CR or non-recurrent breast cancer exhibited high levels by either method. Some IHC HER-2(-) patients also frequently showed high levels by the CLIA method. The EIA method not only revealed low-level sensitivity, but also was subject to interference(abnormally low levels)due to trastuzumab administration. The results obtained by the CLIA method were in agreement with the clinical course. In 93 MBC patients(except CR patients)whose serum HER-2 levels were determined by the CLIA method, the initial HER-2 levels were compared with the CEA and CA15-3 levels. Of the 32 IHC HER-2/3+ patients, 25, 13, and 12 were noted to have high serum levels of HER-2, CEA, and CA15-3, respectively. These results indicate that the serum HER-2 level as assessed by the CLIA method is the most sensitive marker of HER-2-positive MBC.
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PMID:[Serum HER-2 determination using a centauer HER-2/neu kit (CLIA method) in metastatic breast cancer]. 1946 Nov 77