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

Human CD4+ T cells activated with staphylococcal enterotoxin A (SEA) were fractionated by Percoll discontinuous density gradient centrifugation to enrich SEA-reactive CD4+ T cells. The SEA-reactive CD4+ T cells showed significant cytotoxicity, so-called superantigen-dependent cell-mediated cytotoxicity, against SEA-coated class II-positive tumor cells. During lysis of SEA-coated tumor cells, SEA-reactive CD4+ T cells produced high levels of IL-2 and IFN-gamma but not IL-4 in an Ag-specific manner. The skewing of human CD4+ T cells to Th1-type helper/killer T cells was also demonstrated when SEA-reactive CD4+V beta 5.3+ clonal T cells were cultured with SEA, but not with PHA or OKT3 mAb. Interestingly, the generation of SEA-reactive helper/killer T cells was negatively regulated by IL-4, but up-regulated by IL-12. The SEA-reactive CD4+ helper/killer T cells were able to generate from PBMC of tumor patients and could be expanded to 10(9) levels in a 7-day culture. The SEA-reactive CD4+ helper/killer T cells were specifically targeted to c-erbB-2 positive human colon cancer cells using SEA-conjugated-anti-c-erbB-2 mAb. These results initially demonstrated that SEA-activated human CD4+ T cells are a Th1 type of Th cell that has both helper and killer functions which may be useful for adoptive tumor immunotherapy in combination with SEA-conjugated antitumor mAb.
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PMID:Superantigen-induced human CD4+ helper/killer T cell phenomenon. Selective induction of Th1 helper/killer T cells and application to tumor immunotherapy. 783 62

Little is known about the role of the N-linked oligosaccharides in the function of the epidermal growth factor (EGF) receptor (EGF-R). In a human glioma cell line, U373 MG, EGF-Rs contain the bisecting N-linked oligosaccharide sequence recognized by erythroagglutinating phytohemagglutinin lectin from Phaseolus vulgaris (E-PHA). Incubation of E-PHA with cultured U373 MG cells results in inhibition of EGF binding to its receptor and consequently inhibition of EGF-induced autophosphorylation of the receptor. Consistent with the inhibitory effects on the EGF-R, phenotypic events that depend on EGF-R signaling, such as cell spreading and proliferation, were also found to be modified. The effect of this lectin seems to be specific because leukoagglutinating phytohemagglutinin lectin from P. vulgaris (L-PHA), an isolectin of E-PHA, had no effect on EGF-R activity or the biological functions of these cells even though L-PHA was able to bind to the EGF-R. These findings suggest the presence of an important bisecting N-linked oligosaccharide structure in close proximity to the EGF binding site on the receptor. Furthermore, these results suggest the possibility that E-PHA lectin binding may provide an additional approach to blocking EGF-dependent glioma cell growth.
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PMID:Binding of erythroagglutinating phytohemagglutinin lectin from Phaseolus vulgaris to the epidermal growth factor receptor inhibits receptor function in the human glioma cell line, U373 MG. 893 57

The expression of erbB-2 protein (by immunohistochemistry), serum TNF-alpha, soluble TNF-receptor 2 (sTNFR-2, ELISA) concentrations and mitogenic (LPS, ConA, PHA) induced TNF-alpha production of the peripheral blood mononuclear cells (PBMNC) were studied in 91 (UICC Stage 1: 39, Stage 2: 33, Stage 3: 14, Stage 4: 5) patients with carcinoma of the uterine cervix. During a follow-up period of seven years 30 patients died (Stage 4: 5, Stage 3: 12, Stage 2: 11, Stage 1: 2). ErbB-2 protein expression was significantly more frequent in patients with UICC Stages 3-4 (14/19), and in those with fatal outcomes (14/30, p < 0.0001, chi-square test). Serum TNF-alpha (2.70 +/- 0.69 pg/ml) and sTNFR-2 (3.85 +/- 1.05 ng/ml) concentrations were significantly lower in cancer patients (p < 0.0001, Mann-Whitney test) as compared to 64 age-matched control women (TNF-alpha: 4.32 +/- 0.36, TNFR-2: 4.85 +/- 0.82). The mitogenic induced TNF-alpha production of PBMNC was also significantly less with all the three mitogens applied (LPS: 35.24 +/- 8.84, ConA: 26.28 +/- 7.81, PHA: 20.48 +/- 7.04 pg/l million of cells/24 hours, p < 0.0001) as compared to the controls (LPS: 65.33 +/- 8.82, ConA: 51.00 +/- 8.87, PHA: 41.80 +/- 9.01). Serum TNF-alpha, sTNFR-2 concentrations and the mitogenic induced TNF-alpha production of PBMNC was significantly decreased in patients with erbB-2 positivity as compared to those with negativity. In conclusion the expression of the oncoprotein and the lower levels of the members of the TNF system seem to be poor prognostic parameters in patients with carcinoma of the uterine cervix.
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PMID:ErbB-2/HER-2 protein expression, serum tumour necrosis factor-alpha (TFM-alpha) and soluble tumour necrosis factor receptor-2 (TNFR-2) concentrations in human carcinoma of the uterine cervix. 1270 63