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)

Three peptides corresponding respectively to two Epstein-Barr viral epitopes and to the c-erbB-2 oncogene product were synthesized with the aim of developing an immunoenzymatic assay. Preliminary experiments indicated that the efficiency of the assay was profoundly affected by the nature of the solid phase for each peptide. In order to optimize the assay the three peptides were covalently coupled to functionalized polystyrene microplates which were used to immobilize both haptens and nucleic acids in a previous study. The results obtained indicate that the use of the carboxylated surfaces permits the linking strategy to be adapted to each peptide. Moreover, high sensitivities (5 x 10(-10)-1 x 10(-13) M) were obtained using amounts of the peptides much lower than those used in the standard system.
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PMID:Grafting peptides onto polystyrene microplates for ELISA. 754 Jun 41

The purpose of this study was to characterize the clinical and histological features of intraoral squamous cell carcinoma in men who were seropositive for the human immunodeficiency virus and to evaluate viral cofactors (human papillomavirus, herpes simplex virus, Epstein-Barr virus), proliferative index (proliferating cell nuclear antigen), a factor associated with invasion (cathepsin D), and mutated tumor suppressor gene and proto-oncogene products (mutated p53, c-erbB-2). Four men who were seropositive for the human immunodeficiency virus and had acquired immunodeficiency syndrome presented with painful oral lesions of variable duration. Oral cancer risk factors included heavy tobacco use (four of four), heavy alcohol use (three of four), and previous radiotherapy (one of four). The lesions consisted of ulcers (two of four), a fungating mass (one of four), and papillary erythroplakia (one of four). Incisional biopsy specimens were obtained. High-stringency in situ hybridization was performed with DNA probes to the human papillomavirus (types 6/11; 16/18; 31/33/35) and Epstein-Barr virus: Immunocytochemical studies for the herpes simplex virus, proliferating cell nuclear antigen, cathepsin D, mutated p53, and c-erbB-2 were performed. Two lesions were moderately differentiated squamous cell carcinoma, one lesion was a basaloid squamous cell carcinoma, and one was carcinoma in situ. Stage of disease at diagnosis was II (one of four), III (two of four), and IV (one of four). Three cases were positive for the human papillomavirus, one case was positive for Epstein-Barr virus, and three cases were positive for the herpes simplex virus. C-erbB-2 was focally positive in one case, and mutated p53 was positive in a separate case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraoral squamous cell carcinoma in human immunodeficiency virus infection. A clinicopathologic study. 755 63

The c-erbB-2 tyrosine kinase is often overexpressed in human breast cancer, but correlations of receptor expression with tumour behaviour have proven elusive in patients without metastases at diagnosis. To address the possibility that receptor function may be more informative than expression, we previously developed function-specific c-erbB-2 antibodies using synthetic tyrosine-phosphorylated peptide immunogens (Epstein et al., Proc. Natl. Acad. Sci. USA 1992; 89: 10435-10439). Here the converse approach has been taken to determine the functional status of c-erbB-2 receptors detected by antibodies to dephosphorylated (dep) autophosphorylation sequences. In contrast to antiphosphopeptide (apt) antibodies, dep antibodies to the Tyr1248 autophosphorylation site exhibited preferential, but not exclusive, binding to tyrosine-dephosphorylated c-erbB-2. Consistent with this, catalytically active and inactive receptors could not be clearly distinguished by in vitro autophosphorylation experiments in which c-erbB-2 was immunoprecipitated using a monoclonal Tyr1248 dep antibody. A dep antiserum recognizing autophosphorylation sites N-terminal to Tyr1248 exclusively recognized tyrosine-dephosphorylated c-erbB-2 following antibody preabsorption with homologous phosphopeptides. Although indirect, these data are consistent with a model of sequential c-erbB-2 autophosphorylation in which Tyr1248 is the final residue modified. Moreover, since many studies of c-erbB-2 expression have used antibodies to dephosphorylated autophosphorylation sites, these results caution against automatically equating such receptor immunoreactivity with in vivo function or clinical significance.
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PMID:Preferential detection of catalytically inactive c-erbB-2 by antibodies to unphosphorylated peptides mimicking receptor tyrosine autophosphorylation sites. 762 46

Indirect immunofluorescence analysis of sera from breast carcinoma patients whose tumors were characterized for overexpression of the c-erbB-2 oncoprotein (p185HER2) and for lympho-plasma cell infiltration, revealed no circulating antibodies specifically directed against the p185HER2 molecule in the 20 samples tested, whereas supernatants of B-cell clones, derived from Epstein-Barr virus-transformed peripheral blood lymphocytes from 10 of these patients, contained such antibodies in 6 of the 7 c-erbB-2- and lympho-plasma cell infiltration-positive cases. The antibodies contained in two of the positive supernatants immunoprecipitated a M(r) 185,000 molecule from oncoprotein-positive cell extracts that was identified as the oncoprotein in sequential immunoprecipitation experiments with anti-p185HER2 monoclonal antibodies. No cells producing antibodies with a similar reactivity were obtained from Epstein-Barr virus-transformed peripheral blood lymphocytes from breast carcinoma patients with p185HER2-negative tumors or from healthy donors. These data prove the existence of an antibody response specifically directed against the p185HER2 oncoprotein in breast carcinoma patients that may represent an important effector mechanism in the control of c-erbB-2-overexpressing tumors.
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PMID:Antibody response against the c-erbB-2 oncoprotein in breast carcinoma patients. 790 96

The c-erbB-2 receptor tyrosine kinase is often overexpressed in human tumors, but the functional implications of this phenotype remain unclear. We previously used phosphorylation-specific antibodies to define major differences in c-erbB-2 tyrosine kinase activity between overexpressing human tumor cell lines (Epstein, R. J., Druker, B. J., Roberts, T. M., and Stiles, C. D. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 10435-10439). Here we extend this approach to define the relationship between c-erbB-2 tyrosine phosphorylation and protein kinase C (PKC)-dependent transmodulation. Phosphorylation-specific antibodies to the juxtamembrane PKC site Thr686 recognize tyrosine-dephosphorylated wild-type c-erbB-2 following G8/DHFR 3T3 cell treatment with PKC agonists. B104-1-1 cells transformed by activated c-erbB-2 express a subset of tyrosine-phosphorylated receptors that are homologously phosphorylated on Thr686, indicating that Thr686 phosphorylation alone is insufficient to abrogate receptor tyrosine phosphorylation. Similarly, the c-erbB-2-overexpressing human cancer cell lines SK-Ov-3 and BT-474 express constitutively Thr686-phosphorylated receptors. SK-Ov-3 cells express predominantly kinase-inactive c-erbB-2 that is heavily Thr686-phosphorylated, indicating that Thr686 phosphorylation in this line is heterologous in origin. In contrast, BT-474 cells express constitutively autophosphorylated c-erbB-2 despite Thr686 phosphorylation. These results indicate that Thr686 phosphorylation does not directly abolish c-erbB-2 activity and suggest that such phosphorylation reflects constitutive PKC activity induced by either receptor-activating mutations or heterologous growth factors. The latter possibility suggests in turn that c-erbB-2 interacts in an as yet undefined way with heterologous growth factor receptors in human tumor cells.
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PMID:Human cancer cells exhibit protein kinase C-dependent c-erbB-2 transmodulation that correlates with phosphatase sensitivity and kinase activity. 870 75

Twenty percent of breast cancer adenocarcinomas overexpress the oncogene c-erb-2 that is recognized by the humanized anti-Her2/neu monoclonal antibody Herceptin. Results from clinical studies suggest that antibody-dependent cellular cytotoxicity (ADCC) is involved in the clinical response of Herceptin-treated patients. The purpose of the current study was to evaluate the possibility of amplifying in vitro the CD3-/CD16+ natural killer (NK) cell subset that mediates ADCC from breast cancer patients after chemotherapy. Peripheral blood mononuclear cells from six breast cancer patients taken 2 months after chemotherapy completion were co-cultured with an autologous irradiated Epstein-Barr virus-transformed B-lymphoblastoid cell line (LCL) in the presence of interleukin-2 (IL-2) for 4-6 weeks. These LCL + IL2 activated cultures (ACs) were tested for ADCC potential, and their CD3/CD16 NK proportion was quantified. Among the ACs, the proportion of CD3-/CD16+ NK cells increased up to 64% over the first 2 weeks of culture and the ACs continued to expand for 1 month thereafter. Control and patient ACs displayed ADCC activity (tested in the presence of Rituximab against the autologous LCL to take into account any possible effect of inhibitory NK receptors) as well as against the MCF-7(Her2/neu) breast cancer cell line in the presence of Herceptin. This ADCC activity was maintained during the entire culture period. In conclusion, chemotherapy in breast cancer patients does not obviate the possibility of amplifying in vitro the NK cell subset that mediates ADCC. Consequently, adoptive transfer of lymphocytes mediating ADCC can be considered using this protocol to test its benefit in patients under Herceptin treatment.
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PMID:Long-term preservation of antibody-dependent cellular cytotoxicity (ADCC) of natural killer cells amplified in vitro from the peripheral blood of breast cancer patients after chemotherapy. 1636