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)

There is increasing evidence that genes involved in normal cell growth and differentiation (oncogenes) or genes that encode for growth factors are important in determining the development and biologic aggressiveness of gastric carcinoma. This study was undertaken to define the prognostic value of the overexpression of p53 protein, c-erbB-2 protein, EGFr protein and PCNA in gastric carcinomas. Using monoclonal antibodies, immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections from 84 primary gastric carcinomas. Overall, 34% of gastric carcinomas had nuclear-staining for p53 protein, 34% of carcinomas membrane staining for the c-erbB-2 and 74% of carcinomas membrane and cytoplasmic staining for EGFr, showing distribution in a heterogeneous fashion. PCNA was expressed as Grade 2 and 3 in 75% of patients with gastric carcinomas. Both c-erbB-2 and p53 staining was significantly associated with high grade expression of PCNA. p53 staining tended to be associated with positive nodal status and metastasis, and c-erbB-2 staining with positive nodal status only. Multivariate analysis using the Cox model showed that overexpression of p53 protein, c-erbB-2 protein and PCNA was not an independent prognostic variable in gastric carcinoma. These results suggest that expressions of p53 and c-erbB-2 protein are heterogeneous and that p53 and c-erbB-2 overexpressions are significantly associated with high proliferative activity in gastric carcinoma.
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PMID:Immunohistochemical detection of p53 protein, c-erbB-2 protein, epidermal growth factor receptor protein and proliferating cell nuclear antigen in gastric carcinoma. 791 Oct 25

The HER-2/neu proto-oncogene (HER-2) encodes a transmembrane protein whose expression is enhanced in a number of breast and ovarian tumors and correlates with tumor aggressiveness. Because of its expression on normal epithelial cells, HER-2 can be defined as a tumor associated antigen and is of interest as a target of a therapeutic anti-tumor T cell response. To investigate whether oligopeptides analogs of HER-2 isolated from a likely target area of T cells can induce an anti-tumor CTL response, peripheral blood mononuclear cells were stimulated in vitro with HER-2 synthetic peptides. CTL cultures generated recognized peptides used as immunogen. A CD3+CD8+CD4- line isolated from these cultures lysed HLA-A2+, HER-2+ ovarian tumors but not natural killer target K562 cells, and showed significantly higher lysis of HER-2high than of HER-2low ovarian tumors. This lysis was inhibited by HER-2 peptide-pulsed HLA-A2+ targets, suggesting that similar epitopes are presented on tumor cells associated with HLA-A2. The observation that peptide analogs of a proto-oncogene can induce CTL in vitro which express tumor lysis dependent on the levels of expression of HER-2 is novel for human tumor systems. Targeting by T cells of HER-2 may prove useful for understanding the mechanisms of recognition, tolerance, and therapeutic use of human tumor reactive T cells.
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PMID:Oligopeptide induction of a cytotoxic T lymphocyte response to HER-2/neu proto-oncogene in vitro. 791 3

The human c-erbB-2 protooncogene product (erbB-2 protein) is a 185 kilodalton glycoprotein closely related to epidermal growth factor receptor protein. In this study, we measured the concentration of circulating erbB-2 protein in cancer patients by means of a new immunoradiometric assay (IRMA). Two monoclonal antibodies (MoAbs), SV2-61 gamma and 6G10, recognize erbB-2 protein but bind to separate epitopes. SV2-61 gamma was used as an immunoadsorbent and 6G10 as an 125I-labeled probe. A serum was considered positive for erbB-2 protein if the percent binding exceeded the mean of the normal group by more than 3 standard deviations. Eleven of 21 patients with advanced breast cancer and 1 of 15 with advanced gastric cancer were positive. Serum erbB-2 protein levels correlated well with the therapy and the status of the patients with breast cancer. On the contrary, all patients with advanced colon, ovarian, or pancreatic cancers, showed levels below the cut-off value. These results suggest that circulating erbB-2 protein can be measured using the newly constructed IRMA. Since c-erbB-2 protooncogene amplification and overexpression are accepted as a good marker of aggressiveness, relapsing potency, and poor prognosis, this IRMA should be a promising tool with which to help manage breast cancer patients.
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PMID:Construction of immunoradiometric assay for circulating c-erbB-2 protooncogene product in advanced breast cancer patients. 809 2

This study was aimed at comparing screen-detected and symptomatic breast carcinomas with regard to the prevalence of positive immunostaining for c-erb-B-2 oncoprotein. Paraffin sections of 81 breast carcinomas detected through the National Screening Programme were examined for the over-expression of c-erbB-2 oncoprotein using the avidin-biotin immunoperoxidase technique and 2 different specific antibodies: 21N and 4D5. Twenty-one other carcinomas detected in symptomatic patients were similarly examined for comparison. The screen-detected lesions were of 2 types: palpable and impalpable which required needle localization prior to surgical removal. Of the 81 screen-detected tumours, only 8 were c-erbB-2 positive, compared with 5 out of 21 non-screen-detected tumours. When only invasive carcinomas were considered, 5 out of 63 screen-detected cases were positive, compared with 5 out of 15 symptomatic cases. Four out of the 5 screen-detected positive invasive carcinomas were clinically palpable. Our results show an obvious trend towards a lower prevalence of c-erbB-2 oncoprotein over-expression in screen-detected carcinomas. As this over-expression is thought to be associated with increased tumour aggressiveness, the findings suggest a low prevalence of aggressive tumours in screen-detected lesions, particularly impalpable invasive carcinomas, identified so far.
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PMID:c-erbB-2 oncoprotein in screen-detected breast carcinoma: an immunohistological study. 810 30

A molecule that is immunologically related to the c-erbB-2 oncogene product (p185HER2/neu) was detected in the conditioned culture medium from neu-overexpressing tumor cell lines and in sera of advanced-stage breast carcinoma patients. Using a sensitive (in the range of 0.5 ng ml-1) double-determinant radioimmunoassay (DDIRMA) with two monoclonal antibodies (MAbs) directed against the neu extracellular domain (ECD), soluble oncoproteins were detected in supernatants from several neu-positive tumor cell lines, independent of the levels of membrane p185HER2 expression. The molecule detected did not react with a MAb directed against an intracytoplasmic epitope of the p185HER2. Western blot analysis of the concentrated supernatant revealed a protein of approximately 110 kDa molecular mass, which closely matches the predicted size of the glycosylated p185HER2 ECD. Immunoprecipitation of culture supernatant from cell surface-radioiodinated cells confirmed the 110 kDa molecular mass of the glycosylated shed protein, which migrated to 86 kDa after deglycosylation. Proteolytic cleavage of the p185HER2 molecule was demonstrated in release assays carried out with protease inhibitors. The combined use of leupeptin and EDTA completely inhibited release of the molecule. Analysis of sera from breast carcinoma patients and healthy donors by DDIRMA revealed the presence of soluble neu in 15% of pathologic sera but none of the normal sera. A good correlation was found between neu-overexpression in the primary tumor and the soluble marker in serum of patients with advanced disease; sera of early-stage patients were always negative, independent of neu-overexpression in the tumor. These results suggest the usefulness of soluble neu as an indicator of tumor aggressiveness but not as a diagnostic marker of breast cancer.
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PMID:The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage. 810 38

The interaction between laminin and the oncoprotein encoded by the c-erbB-2 oncogene was studied in vitro and in vivo in human breast carcinomas. In vitro analysis of breast carcinoma cell lines overexpressing p185HER2 revealed that laminin, but not fibronectin, induced tyrosine phosphorylation and down-modulation of oncoprotein membrane expression. Laminin also specifically inhibited growth of p185HER2-positive cell lines. No direct binding between the recombinant extracellular domain of p185HER2 and laminin was found. Induction of oncoprotein down-modulation by anti-integrin antibodies and coprecipitation of the oncoprotein with the beta 4 integrin subunit indicate that the interaction between p185HER2 and laminin occurs through integrin molecules. The relevance of this in vitro observation was verified in vivo by analysing the prognostic value of p185HER2 overexpression as a function of laminin production on archival paraffin-embedded sections of 887 primary breast tumours. The results revealed an association between p185HER2 overexpression and unfavourable prognosis in tumours negative for laminin production, whereas in laminin-producing tumours, the oncoprotein overexpression was not associated with tumour aggressiveness.
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PMID:Laminin activates the p185HER2 oncoprotein and mediates growth inhibition of breast carcinoma cells. 891 40

DNA amplification seems to be particularly frequent in human breast tumours and has been associated with cancer evolution and aggressiveness. Recent data indicate that new events should be added to the list, such as the amplifications at chromosome 20q13 or the MDM2 gene. The present work aimed at determining the incidence and clinicopathological signification of these amplifications in a large series of breast and ovarian tumours. We tested 1371 breast and 179 ovarian tumours by Southern blotting and observed amplification of 20q13 in 5.4% breast and 2.8% ovarian carcinomas, whereas MDM2 was found amplified in 5.3% and 3.8% of breast and ovarian tumours respectively. MDM2 RNA expression levels were analysed in a subset of 57 breast tumours and overexpression was observed in 4/57 (7%) of the tumours. Elevated expression levels coincided with amplification of the gene. In breast cancer, 20q13 and MDM2 amplifications seem to define subsets of aggressive tumours. Indeed, 20q13 was correlated to axillary nodal involvement and occurred preferentially in younger patients (< 50 years). Furthermore, 20q13 correlated, as did MDM2 amplification, to aneuploidy. In parallel, we had also tested our tumour DNAs for amplification of CCND1, ERBB-2 and MYC, which made it possible to test for correlations with 20q13 or MDM2 amplifications. Whereas 20q13 showed a very strong correlation to CCND1 amplification, that of MDM2 was prevalent in MYC-amplified tumours. Interestingly, 20q13 and MDM2 amplifications showed some degree of correlation to each other, which may possibly be owing to the fact that both events occurred preferentially in aneuploid tumours. In ovarian cancer, no statistically significant correlation was observed. However, 20q13 amplification occurred preferentially in stage 3 tumours and MDM2 was correlated to ERBB-2 amplification. This may suggest that in ovarian tumours also, 20q13 and MDM2 amplifications occur in late or aggressive cancers.
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PMID:DNA amplifications at 20q13 and MDM2 define distinct subsets of evolved breast and ovarian tumours. 898 Apr 1

The number of primary breast cancers occurring in elderly women is increasing in Japan. Optimization of treatment regimens in this age group requires precise evaluation of the biological aggressiveness of these tumors as well as the performance status and extent of tumor spread. In 39 breast cancer patients who were at least 80 years old, we examined several parameters; the form of surgical therapy, the lymph node status, presence or absence of distant metastases, the histological type and grade of atypia, and overexpression of the c-erbB-2 oncoprotein in the cancer cells. They were correlated with the clinical outcome of the patient. Of the 33 patients who underwent a mastectomy and axillary lymph node dissection, five died from cancer recurrence. Only one out of 22 patients without lymph node metastases died from cancer, while four out of the eight patients with metastases to three or more lymph nodes died from cancer recurrence within 2.7 years of surgery. The overall survival curves also differed between patients with low-risk histological tumors or grade 1 or 2 invasive ductal carcinoma and those with grade 3 invasive ductal/lobular carcinoma. Overexpression of c-erbB-2 also affected survival. Regional recurrence occurred in three out of the six patients for whom only lumpectomy or simple mastectomy was performed. These results indicate that, although primary breast cancer occurring in patients over 80 years old was largely of low-grade malignancy, patients with three or more lymph node metastases, invasive ductal/lobular carcinomas of grade 3, or c-erbB-2 overexpression frequently exhibited an aggressive clinical course.
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PMID:Clinicopathological characteristics of primary breast cancer in older geriatric women: a study of 39 Japanese patients over 80 years old. 931 Jan 43

Pleomorphic adenoma of the lung is a rare neoplasm. Here we describe the first report on oncogenes and tumor suppressor genes in metastasizing pleomorphic adenoma of the lung. A 48-year-old Japanese woman presented with metastasizing pleomorphic adenoma in which both the primary lung tumor and metastatic lesions were composed of benign pleomorphic structures. The mechanism of the metastatic potential was examined by analyzing known oncogenes and tumor suppressor genes by DNA blot analysis and immunohistochemistry. No rearrangements amplifications or overexpressions of oncogenes, bcl-2, c-erbB-2, c-myc, L-myc, N-myc, Ha-ras and Ki-ras were found. In addition, immunohistochemical studies showed no aberrance in expressions of the tumor suppressor gene products, RB, p16 and p53 in the tumor. Some unknown mechanism(s) seems to be responsible for the aggressiveness of this metastasizing pleomorphic adenoma. This mechanism must be elucidated by studies on further case of this rare tumor.
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PMID:A case of pleomorphic adenoma of the lung with multiple distant metastases--observations on its oncogene and tumor suppressor gene expression. 967 59

Although natural killer (NK) cells have been described as non-MHC-restricted, new evidence suggests that NK activity can be either up- or down-regulated after interaction with the peptide-MHC-class-I complex expressed on target cells. However, the epitope(s) recognized by NK cells have remained ill-defined. We investigated NK cell recognition of synthetic peptides representing a portion of a self-protein encoded by the HER-2/neu (HER-2) proto-oncogene and presented by HLA-A2. HER-2 nonapeptides C85, E89, and E75 were found partially to protect T2 targets from lysis by freshly isolated and interleukin-2(IL-2)-activated NK cells (either HLA-A2(+) or A2(-)). This inhibition was not solely due to changes in the level of HLA-A2 expression or conformation of serological HLA-A2 epitopes. Using single-amino-acid variants at position 1 (P1) of two HER-2 peptides, we observed that protection of targets was dependent on the sequence and the side-chain. These results suggest similarities in the mechanism of target recognition by NK and T cells. This information may be important for understanding the mechanisms of tumor escape from immunosurveillance and could help explain the aggressiveness of HER-2-overexpressing tumor cells.
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PMID:HER-2/neu peptide specificity in the recognition of HLA-A2 by natural killer cells. 1050 54


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