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)

Recent studies of erbB-2 expression have shown that the erbB-2 oncoprotein correlated with poor prognosis of patients with breast cancer. Surgical treatment of the bile duct carcinoma is currently unsatisfactory. To evaluate erbB-2 oncoprotein as a marker of prognosis, we analyzed 68 bile duct carcinomas immunohistologically, using monoclonal antibody against erbB-2 oncoprotein, as well as clinicopathological data and outcome. High incidence of expression of erbB-2 oncoprotein was shown in bile duct carcinoma. Positive rates of erbB-2 oncoprotein correlated with stage of bile duct carcinoma. Survival of patients with erbB-2 expression cancer was shorter than those without erbB-2 expression cancer and erbB-2 expression has a prognostic value in bile duct carcinoma.
Nihon Geka Gakkai Zasshi 1992 Sep
PMID:[Evaluation of immunoreactivity to erbB-2 protein as a marker of prognosis in bile duct carcinoma]. 136 58

Monoclonal antibodies to the extracellular domain of the c-erbB-2 oncoprotein (p185) react with routinely processed, paraffin-embedded human tissues, and positive staining with these reagents has been shown to correlate with gene overexpression. To determine whether such antibodies would add prognostic data to the analysis of a pre-defined subset of transitional cell carcinoma (TCC) of the bladder, we studied 20 high-grade (Grade 3) TCCs from patients known to have limited disease (Jewett-Strong stages B1, B2, and C) and for whom at least 3-yr clinical follow-up was available. Data procured from this immunohistochemical analysis were compared with tumoral DNA content (determined by flow cytometry) and conventional clinicopathologic features. Overall, 13 of 20 TCC (65%) were reactive for p185-erbB-2. However, there was no apparent relationship between p185-reactivity and either DNA content, tumor stage or clinical outcome. These results suggest that c-erbB-2 expression may be augmented in localized high-grade TCC but that there is no evidence for the contention that this phenomenon has any effect on the biologic behavior of these neoplasms. The only factor that predicted a more favorable outcome was a relatively low stage at the time of diagnosis.
Mod Pathol 1992 Sep
PMID:c-erbB-2 (HER-2/neu) oncopeptide immunoreactivity in localized, high-grade transitional cell carcinoma of the bladder. 136 64

Alterations in cellular biochemistry which are associated with the development of resistance to cytotoxic peptides, such as tumor necrosis factor (TNF), may also be responsible for changes in the response of cells to cytotoxic agents. Culturing ME-180 cervical carcinoma cells in the presence of escalating concentrations of TNF resulted in the development of an ME-180 cell variant (ME-180R) resistant to TNF but expressing a 3-5-fold increased sensitivity to cisplatin (CDDP) when measured following continuous exposure (low doses) or short-term incubation with CDDP (high doses) and clonogenic analysis. Cellular platinum uptake, efflux, and nuclear platinum content as well as the extent of DNA platination were examined and found to be identical in both ME-180 parental and ME-180R cell lines. Although ME-180R cells showed a relatively higher glutathione content than ME-180 parental cells, the effect of buthionine sulfoximine on the cellular sensitivity to CDDP and glutathione S-transferase activities of both cell lines were almost identical, suggesting that glutathione content or its metabolism did not appear to play a major role in differential CDDP cytotoxicity. Unscheduled DNA synthesis following exposure to CDDP was more inducible in ME-180 parental cells than in CDDP-sensitive ME-180R cells. Alkaline elution studies of cross-linked DNA in CDDP-treated ME-180 cells suggested that accumulation of DNA adducts reached maximal levels 10-15 h after CDDP treatment and was similar in both TNF-resistant and parental cells. Within 24 h after CDDP exposure, the extent of DNA cross-linking was markedly reduced in parental cells but remained elevated in the CDDP-sensitive ME-180R cell line. To examine the proposed regulatory role of phosphorylation in CDDP and TNF-mediated cytotoxicity, epidermal growth factor (EGF) receptor tyrosine kinase activity was measured in both TNF-resistant and parental ME-180 cells. Analysis of cell lysates demonstrated a 3-4-fold higher EGF receptor tyrosine kinase activity in ME-180R cells when compared to the parental population which correlated with increased expression of EGF receptor protein by immunoblot analysis. Based upon colony-forming assays, EGF treatment of ME-180 parental cells resulted in an increased sensitivity to CDDP (similar to ME-180R cells) and 3-fold stimulation of EGF receptor tyrosine kinase activity. Taken together, these results suggest that TNF resistance in ME-180 cervical carcinoma cells correlates with both increased EGF receptor expression and enhanced CDDP cytotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
Cancer Res 1992 Sep 01
PMID:Resistance of human cervical carcinoma cells to tumor necrosis factor correlates with their increased sensitivity to cisplatin: evidence of a role for DNA repair and epidermal growth factor receptor. 138 Aug 90

We are evaluating strategies for the inhibition of growth or the selective killing of tumor cells. Cell surface antigens which are exclusively expressed or which are enhanced in their expression in tumor cells might provide the means to target cytotoxic or cytostatic agents to these cells. Few tumor specific cell surface antigens have been found, but the enhanced expression of growth factor receptors has been described for several types of tumors. A prominent example is the overexpression of the c-erbB-2 receptor in a high percentage of primary breast and ovarian carcinomas. We have derived monoclonal antibodies against the extracellular domain of the c-erbB-2 receptor. The antibody molecules were genetically engineered to minimize their size and to allow for their functional modification. For this purpose the cDNA sequences corresponding to the variable domains of one monoclonal antibody (FRP5) were molecularly cloned and joined by a short linker. The resulting single chain antibody molecule (scFv) was expressed in bacteria and purified. We show in an immunoprecipitation experiment that this molecule retains its ability to recognize the c-erbB-2 extracellular domain. This molecule could become a valuable vehicle to specifically transport anti-tumor agents to breast cancer cells.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Diminution of antibodies directed against tumor cell surface epitopes: a single chain Fv fusion molecule specifically recognizes the extracellular domain of the c-erbB-2 receptor. 138 44

This study investigated the effect of two major ingredients in cigarette smoke, benzo[a]pyrene (BP) and nicotine, on epidermal growth factor (EGF) receptor binding and EGF-mediated cellular functions in rat buccal mucosa. Rat buccal tissue was incubated in DMEM in the absence (control) and presence of 10 microM BP or nicotine for 2.5 h at 25 degrees C. There were no significant differences in [125I]EGF binding to the buccal mucosal membranes between the control and treatment groups. Protein tyrosine kinase assay showed that EGF stimulated phosphorylation of a 170-kDa protein band in the controls, but not in the BP- and nicotine-treated samples. The basal [3H]thymidine incorporations were not significantly different between the groups. Nevertheless, addition of 5 nM EGF increased [3H]thymidine incorporation by 22% in the control, but not in the BP- or nicotine-treated group. The results demonstrate that BP and nicotine change the buccal mucosal functions associated with alteration of EGF receptor.
Toxicol Lett 1992 Sep
PMID:Benzo[a]pyrene and nicotine impair epidermal growth factor mediated cellular functions of buccal mucosa. 141 11

A 94 year old man with an invasive ductal carcinoma of the breast (T4N2M1, stage IV), underwent a modified radical mastectomy to improve his quality of life. The estrogen receptor status of both the breast tumor and the metastatic axillar lymph nodes was high. Immunohistochemical staining for epidermal growth factor, epidermal growth factor receptor, or c-erbB-2 protein was negative. The patient received only tamoxifen continuously for 3 months, and later apparently showed a complete remission. Therefore, in advanced male breast cancer with a high estrogen receptor status, operation in conjunction with hormone therapy may lead to a favorable result in some cases.
J Surg Oncol 1992 Sep
PMID:A 94 year old male stage IV breast cancer patient showing complete remission under tamoxifen treatment after operation. 151 97

A monoclonal antibody (TAb 250) specific to an extracellular epitope of the c-erbB-2 protein (gp185) inhibited the in vitro proliferation of human breast tumor cell lines that overexpress c-erbB-2 in a dose-dependent manner. Treatment of cells with combinations of cis-diammedichloroplatinum (CDDP) and TAb 250 resulted in a significantly enhanced cytotoxic effect. This synergistic cytotoxicity was apparent over a wide range of antibody concentrations (200 pg/ml-100 micrograms/ml) including concentrations that showed no inhibitory effect alone. TAb 250 did not increase the cytotoxic effect of CDDP in a cell line exhibiting no detectable level of gp185. Athymic mice bearing s.c. xenografts of human tumor cells expressing high levels of gp185 showed a greatly enhanced inhibition of tumor growth when treated with TAb 250 and CDDP compared to treatment with the antibody or CDDP alone. This effect was specific inasmuch as TAb 250 did not enhance the growth-inhibitory effect of CDDP on tumor xenografts which were not expressing gp185.
Cancer Res 1991 Sep 01
PMID:A monoclonal antibody against the c-erbB-2 protein enhances the cytotoxicity of cis-diamminedichloroplatinum against human breast and ovarian tumor cell lines. 167 83

Amplification of the c-erbB-2 protooncogene has been associated with a poor prognosis in human breast and ovarian cancers. Our study was undertaken to examine whether amplification, rearrangement, or overexpression of c-erbB-2 and other protooncogenes was frequently observed in epithelial ovarian cancers. c-erbB-2 was expressed in 87% of 22 ovarian cancers analyzed, but expression was significantly increased in only one of the 22 tumor specimens. In this case elevated c-erbB-2 expression was associated with dramatic amplification of the gene. In another tumor a 3.8 kb EcoRI fragment was found, in addition to the usual 4.4 and 6.0 kb fragments; this is consistent with a possible gene rearrangement or a restriction fragment length polymorphism. To place these results in perspective, expression of several other protooncogenes has been examined in ovarian carcinomas. The c-fos, c-myc, n-myc, c-fms, and c-Ha-ras protooncogenes were expressed in different fractions of tumors, but expression of l-myc, c-erbB, c-myb, c-sis, and c-mos was not detectable. Aside from c-erbB-2, neither amplification nor rearrangement was observed among the other protooncogenes studied. Expression of c-erbB-2, c-fms, c-myc, n-myc, c-fos, and c-Ha-ras deserves further evaluation as a prognostic factor in ovarian cancer.
Am J Obstet Gynecol 1991 Sep
PMID:Expression and amplification of the HER-2/neu (c-erbB-2) protooncogene in epithelial ovarian tumors and cell lines. 167 63

We examined samples of tumors of human breast, ovary, and colon of various degrees of malignancy for the expression of p53 protein, using a panel of anti-p53 antibodies and peroxidase immunohistochemistry. Of 66 tumor cases (24 cases of ovarian carcinoma, 23 cases of colon adenocarcinoma, and 19 cases of breast carcinoma), 36 (53%) showed high levels of expression of p53 using a human-specific antibody, and 16 (24%) showed high expression of a mutant form of p53. In the mutant p53-positive breast tumor samples, six (86%) were positive for HER-2/neu reactivity, compared with colon (0/4) and ovarian tumors (1/5). The pattern of p53 intracellular localization and tissue distribution, and the relationship between the expression of mutant p53 and cell differentiation, were also examined; poorly differentiated cells showed either overexpression of p53 or higher levels of mutant p53 in comparison with more normal cells.
J Histochem Cytochem 1991 Sep
PMID:Immunohistochemical analysis of p53 and HER-2/neu proteins in human tumors. 168 Aug 97

A novel multiparameter flow-cytometric method was used to quantify the expression of epidermal growth factor receptor (EGFR) and c-erbB-2 oncoprotein on 85 cryopreserved normal tissues (30 ovary, 29 endometrium, 16 cervix) and 67 carcinomas (31 ovarian, 18 cervical, 15 endometrial, 3 vulvar). Overexpression of the EGFR and c-erbB-2 oncoproteins was found in respectively 3/31 (9%) and 10/31 (32%) ovarian carcinomas, 13/18 (72%) and 7/18 (38%) cervical carcinomas, and 2/15 (13%) and 2/15 (13%) endometrial carcinomas. Oncoprotein expression was significantly higher in the malignant tumors (for all tumor sites) than in the corresponding normal tissues (P less than 0.034 for all combinations). Aneuploid tumors expressed levels of EGFR and c-erbB-2 oncoprotein significantly higher than those of DNA diploid tumors (P = 0.042 and P = 0.048, respectively). Oncoprotein could be detected in nearly all normal tissues: expression was higher in premenopausal than in postmenopausal patients (EGFR, P = 0.07; c-erbB-2, P less than 0.001). The present study supports the idea that EGFR and c-erbB-2 may play an important role in the autocrine, paracrine, and/or endocrine growth control and differentiation of normal tissues. Alteration in the expression of these oncoproteins is probably involved in malignant transformation and tumorigenesis.
Gynecol Oncol 1991 Sep
PMID:Multiparameter flow-cytometric quantitation of epidermal growth factor receptor and c-erbB-2 oncoprotein in normal and neoplastic tissues of the female genital tract. 168 31


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