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)

It is now possible to detect low copy numbers of messenger ribonucleic acid (mRNA) while retaining good histologic morphology for the determination of specific gene expression in diseased tissues. This technology will allow the pathologist to provide important prognostic information about tumors (expression of oncogenes and growth factors), to identify the subclones within the tumor which may be most likely to metastasize (expression of adhesion molecules and proteases) and to identify etiologic genetic aberrations (viral insertions). A technique for in-situ hybridization to mRNA has been developed for use in formalin fixed paraffin embedded tissues which is suitable for a hospital histology laboratory. Optimal conditions for the procedure were determined by using a biotinylated poly (d)T oligonucleotide probe. Results were dependent on the tissue type, fixation time, condition of the tissue prior to fixation, and degree of digestion before hybridization. The temperature and conditions of hybridization were optimized so that the poly d(T) control probe and the longer test probe could be run simultaneously. Streptavidin and avidin alkaline phosphatase detection systems were tested using levamisole to minimize background staining, and a biotin blocking agent to reduce reaction to renal tubular biotin. Increasing the temperature of stringency washes did not significantly improve the specificity but had a markedly detrimental effect on tissue morphology. The mRNA appears to remain stable within routinely fixed surgical material over long periods of time allowing for large retrospective studies. A review of c-erbB-2 expression in 16 human breast lesions was carried out comparing mRNA in-situ hybridization to immunoperoxidase and cytosolic methods. By direct localization of both message and antigen, it was possible to demonstrate focal positivity that cytosolic methods did not detect. Aberrant translation was noted in one case, and c-erbB-2 expression in non-malignant breast was detected in two cases.
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PMID:mRNA in-situ hybridization using biotinylated oligonucleotide probes: implications for the diagnostic laboratory. 752 37

Bispecific monoclonal antibodies (BsmAb) with specificity for tumor Ag and effector cell trigger molecules have been shown to redirect the cytotoxicity of several peripheral blood mononuclear cell populations against relevant tumor. The BsmAb, 2B1, binds to the extracellular domain of the c-erbB-2 gene product of the HER2/neu proto-oncogene and to CD16. In this report, the binding and cytotoxic characteristics of 2B1 are presented. Maximal saturation binding of 2B1 to PBL and c-erbB-2 expressing SK-OV-3 cells occurred in the 1 microgram/ml concentration range. However, substantial lysis potentiation was observed at 1000-fold lower BsmAb concentrations. Optimal tumor lysis was obtained when the BsmAb, PBL, and target cells were continuously coincubated. When PBL were franked with 2B1, washed, and added to labeled targets, substantially less lysis was observed. These results suggest that the best way to therapeutically exploit the cytotoxic attributes of 2B1 may be to obtain continuous BsmAb exposure to tumor. Approaches based on franking of this BsmAb to PBL may not be warranted.
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PMID:Binding and cytotoxicity characteristics of the bispecific murine monoclonal antibody 2B1. 810 70

ERBB family receptor tyrosine kinases are overexpressed in a significant subset of breast cancers. One of these receptors, HER2/neu, or ErbB-2, is the target for a new rational therapeutic antibody, Herceptin. Other inhibitors that target this receptor, and another family member, the epidermal growth factor (EGF) receptor, are moving into clinical trials. Both of these receptors are sometimes overexpressed in breast cancer, and still subject to regulation by hormones and other physiological regulators. Optimal use of therapeutics targeting these receptors will require consideration of the several modes of regulation of these receptors and their interactions with steroid receptors.
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PMID:Tyrosine kinase signalling in breast cancer: ErbB family receptor tyrosine kinases. 1125 Jul 7

Clinical studies have confirmed epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) used in lung cancer patients with EGFR mutations can obtain a better result, but still part of the patients with poor efficacy. EGFR mutation is highly related to female, nonsmoking and adenocarcinoma. Thus, we hypothesize that estrogen and circulating HER-2/neu protein might influence the efficacy of EGFR-TKIs in EGFR mutant patients with non-small cell lung cancer. HER-2/neu expression level of 357 eligible patients in its peripheral serum was determined using ELISA. The median progression-free survival (PFS) in five groups (premenopausal group, perimenopause group, peri to postmenopausal group, postmenopausal group and control group) was statistically difference (P = 0.025). Premenopausal group could predict the efficacy of EGFR-TKI (HR = 2.45, 95% CI = 1.42-4.23, P = 0.001). No statistical significance was found in median overall survival (OS) among five groups. Optimal diagnostic cut off value of HER-2/neu was set at 47.5 ng/ml, with P = 0.0607. As the cutoff value to 47.5 ng/ml division, concentrations and menopausal status was of no significant difference (P = 0.874). PFS of the group below 47.5 ng/ml was significantly longer than that of the group over 47.5 ng/ml (P = 0.000). HER-2/neu concentration was positively correlated with optimal efficacy (P = 0.042). HER-2/neu concentration over than 47.5 ng/ml was a risk factor of EGFR-TKI prognosis. Premenopausal status is an independent predictor of EGFR-TKI curative effect and circulating HER-2/neu protein is an independent prognostic factor in patients with advanced NSCLC.
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PMID:Impact of menopausal status and HER-2/neu protein on efficacy of EGFR-TKI in EGFR mutant patients with non-small cell lung cancer. 3021 Jun 20