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)

The pathogenesis of polycystic liver disease is not well understood. The putative function of the associated proteins, hepatocystin and Sec63p, do not give insight in their role in cystogenesis and their tissue-wide expression does not fit with the liver-specific phenotype of the disease. We designed this study with the specific aim to dissect whether pathways involved in polycystic kidney diseases are also implicated in polycystic liver disease. Therefore, we immunohistochemically stained cyst tissue specimen with antibodies directed against markers for apoptosis, proliferation, growth receptors, signaling and adhesion. We analyzed genotyped polycystic liver disease cyst tissue (n=21) compared with normal liver tissue (n=13). None of the cysts showed proliferation of epithelial cells. In addition, anti-apoptosis marker Bcl-2 revealed slight increase in expression, with variable increase of apoptosis marker active caspase 3. Growth factor receptors, EGFR and c-erbB-2, were overexpressed and mislocalized. We found EGFR staining in the nuclei of cyst epithelial cells regardless of mutational state of the patient. Further, in hepatocystin-mutant polycystic liver disease patients, apical membranous staining of c-erbB-2 and adhesion markers, MUC1 and CEA, was lost and the proteins appeared to be retained in cytoplasm of cyst epithelia. Finally, we found loss of adhesion molecules E-cadherin and Ep-CAM in cyst epithelium of all patients. Nevertheless, we observed normal beta-catenin expression. Our results show that polycystic liver disease cystogenesis is different from renal cystogenesis. Polycystic liver disease involves overexpression of growth factor receptors and loss of adhesion. In contrast, proliferation or deregulated apoptosis do not seem to be implicated. Moreover differential findings for PRKCSH- and SEC63-associated polycystic liver disease suggest a divergent mechanism for cystogenesis in these two groups.
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PMID:Disrupted cell adhesion but not proliferation mediates cyst formation in polycystic liver disease. 1858 25

Employing CLIA and EIA methods simultaneously, we determined serum HER-2/neu levels a total of 92 times in 51 patients with metastatic breast cancer(MBC)and 3 patients with non-recurrent breast cancer, and compared the levels measured by both methods with the level of IHC-staining for HER-2 and the clinical course. Among 20 patients with IHC HER-2/3+ MBC (including FISH+MBC), 14(70%)showed high levels by the CLIA method (>cut-off value of 15.2 ng/mL), whereas only 4(20%)revealed high levels by the EIA method(>cut-off value of 6.5 ng/mL). None of the patients with CR or non-recurrent breast cancer exhibited high levels by either method. Some IHC HER-2(-) patients also frequently showed high levels by the CLIA method. The EIA method not only revealed low-level sensitivity, but also was subject to interference(abnormally low levels)due to trastuzumab administration. The results obtained by the CLIA method were in agreement with the clinical course. In 93 MBC patients(except CR patients)whose serum HER-2 levels were determined by the CLIA method, the initial HER-2 levels were compared with the CEA and CA15-3 levels. Of the 32 IHC HER-2/3+ patients, 25, 13, and 12 were noted to have high serum levels of HER-2, CEA, and CA15-3, respectively. These results indicate that the serum HER-2 level as assessed by the CLIA method is the most sensitive marker of HER-2-positive MBC.
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PMID:[Serum HER-2 determination using a centauer HER-2/neu kit (CLIA method) in metastatic breast cancer]. 1946 Nov 77

The prognosis of non small cell lung cancer (NSCLC) has remained disappointing over the last decades even in localized stages. Numerous prognostic factors have been investigated which might select patients for additional treatment. The objective of the current study was to assess the prognostic significance of telomerase activity, serum anti-p53 antibodies (anti-p53a), c-erbB-2 and CEA in patients with NSCLC. The study included 60 patients with histological proven NSCLC besides 60 controls (30 smokers and 30 nonsmokers). Patients were divided into four stages according to their histopathology. All patients were subjected to; determination of telomerase activity by telomeric repeat amplification protocol (TRAP) assay in tumor tissue specimens and adjacent normal lung tissues, also, determination of preoperative serum anti-p53a, c-erbB-2 and CEA. Telomerase activity was detected in 40 of 60 (66.6%) of NSCLC tissue specimens using the TRAP assay. As regard the stages, telomerase activity was positive in 5 of 15 patients (33.3%) with stage I NSCLC, in 11 of 20 patients (55%) with stage II NSCLC, in 9 of 10 patients (90%) with stage III NSCLC and in all patients (100%) with stage IV NSCLC. More cases of positive telomerase activity were observed in the group with advanced disease and in the group with poorly differentiated tumors. Telomerase activity was not detected in any normal lung tissue. The concentrations of serum anti-p53a, c-erbB-2, CEA were significantly higher in patients with NSCLC in comparison to the smoker and nonsmoker controls and their levels increased according to the stage of disease. Logistic regression test showed a relation between telomerase positivity and anti- p53a but no relation with c-erbB2, CEA. Telomerase activity was detected in most of NSCLC tissues; it was detected more frequently in advanced disease than early-stage disease. Anti-p53, c-erbB-2 and CEA were significantly higher in patients with NSCLC than controls and this increment was more evident in late stages of the disease. So, these biological markers might be useful predictors of prognosis. They may be helpful in defining groups of patients with NSCLC who could benefit from adjuvant treatments, also these markers can be used as therapeutic targets.
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PMID:Prognostic significance of telomerase activity and some tumor markers in non-small cell lung cancer. 2014 5

Tumor cells expressing HER-2/neu and CEA antigens are potentially ideal targets for antibody-targeted therapy. In this study, two large human combinatorial libraries have been generated from the lymph nodes of breast cancer patients that express HER2 and CEA antigens in their tumors. These 'immune' libraries have been constructed in two different formats of scFv, differing in the length of the peptide linker connecting the two variable VH and VL domains. Libraries derived from these patients may contain a larger pool of anti-tumor antigen antibodies and are useful repertoire for isolating scFvs against any tumor markers. The results of this study showed that we were successful in obtaining human scFvs against HER-2/neu and CEA. For HER-2, cell-panning strategy was performed and resulted in two scFv binders that detected the complete HER-2 receptor on the cell membrane and internalized to the cells. Also, preliminary ELISA data showed that several anti-CEA scFv binders were isolated by panning.
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PMID:Isolation of scFv antibody fragments against HER2 and CEA tumor antigens from combinatorial antibody libraries derived from cancer patients. 2384 93


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