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)

In order to study the influence of erbB-2 protein overexpression on outcome of patients with gastric cancer after attempted curative resection with or without adjuvant chemotherapy, paraffin embedded sections from 109 cases of primary gastric cancer with defined treatments have been immunostained for erbB-2 protein in a retrospective study. Thirty four cases (31%) showed strong membrane staining of tumor cells. erbB-2 overexpression did not show significant effect on outcome when all patients were considered. However, erbB-2 overexpression was an indicator for poor disease free survival (p = 0.0474), local relapse free survival (p = 0.0293), and overall survival (p = 0.0310) of the patients treated with surgery only (N = 51), while it did not show any effect on outcome of patients treated with 5-FU plus Doxorubicin (FA) as adjuvant chemotherapy (N = 58). Furthermore, the apparent therapeutic benefit from FA regimen was restricted to patients with erbB-2 positive tumors. Combined predictive value of erbB-2 and FA regimen was found to be significant in predicting local relapse in multivariate analysis (p = 0.0439). The data suggests that erbB-2 may be associated with an improved response to FA regimen and that erbB-2 should be included as a potential confounding variable in the analysis of the data from the clinical trials for gastric cancer.
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PMID:Overexpression of erbB-2 protein in gastric adenocarcinoma--a potential role in therapeutic response to adjuvant 5-FU-doxorubicin regimen. 135 36

For the prediction of nodal status of early gastric cancer, sections of formalin-fixed, paraffin-embedded tissue from 220 early gastric cancers were analyzed immunohistochemically, using a polyclonal antibody against erbB-2 protein. The data of erbB-2 protein expression have been correlated with pathologic data, and a logistic regression analysis was made for the estimation of the significant factors responsible for lymph node metastasis. A pattern consistent with cell membrane staining was regarded as most specific for the erbB-2 expression. There were 22 (10%) cancers with evidence of erbB-2 protein expression. Positive staining was associated with only lymph node metastasis. The risk of lymph node metastasis was 3-fold greater in tumors having erbB-2 protein expression than in tumors without the expression. When the erbB-2 tissue status and clinicopathological parameters were entered into the logistic regression analysis, erbB-2 protein expression emerged as one of the independent significant factors for lymph node metastasis. These results indicate that early gastric cancer with erbB-2 protein expression may represent a potential risk of lymph node metastasis.
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PMID:Correlation of c-erbB-2 protein expression and lymph node status in early gastric cancer. 135 59

erbB-2 protein is believed to be a cell membrane receptor for the recently identified ligand gp30. When overexpressed, erbB-2 is an indicator of poor prognosis in adenocarcinomas of breast, stomach, lung, and endometrium. Even more important, clinical data suggest that erbB-2 overexpression may be an indicator of poor response to at least some commonly used adjuvant regimens. However, there is preliminary evidence that these tumors might respond as well to doxorubicin regimen as do erbB-2 negative tumors, at least in gastric cancer. The efficacy of doxorubicin-containing regimen in the treatment of tumors with erbB-2 overexpression needs to be explored further by retrospective analysis of finished clinical trials. Combination of chemotherapeutics with reagents that block erbB-2 signal transduction pathway may be another effective approach.
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PMID:Clinical significance of erbB-2 (HER-2/neu) protein. 135 10

The expression of the c-erbB-2 mRNA in human embryonic lung fibroblasts, a gastric cancer cell line, mature placenta, and 25 gastric cancer tissues was examined by using the polymerase chain reaction following reverse transcription. This technique can be used to examine c-erbB-2 mRNA expression in a small endoscopic biopsy specimen before surgery.
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PMID:Specific detection of c-erbB-2 mRNA expression in gastric cancers by the polymerase chain reaction following reverse transcription. 137 62

The pathogenesis of cutaneous paraneoplastic syndromes is still under discussion. Since many of these syndromes, including acanthosis nigricans, are proliferative skin disorders it is believed that products secreted by the tumour stimulate the keratinocytes to proliferate. Growth factors like transforming growth factor alpha (TGF-alpha) are known to be highly mitogenic for keratinocytes in vitro. Here we report on a patient with a poorly differentiated gastric cancer and a full clinical picture of acanthosis nigricans characterized by diffuse hyperkeratosis and multiple papillomatous lesions of the skin with involvement of the conjunctivae. In Southern blot analysis of the tumour tissue from this patient amplification of the epidermal growth factor (EGF) receptor, the common ligand for TGF-alpha and EGF, was shown. Immunohistochemically, prominent staining was found throughout the tumour using anti-TGF-alpha antibodies. In a series of 25 investigated gastric tumour biopsies, four tumours showed amplification of the EGF receptor and one additional biopsy was positive for TGF-alpha. Since there is no other report describing the link between TGF-alpha and acanthosis nigricans, except that of Ellis et al. 1987, we present a new case suggesting a possible link between growth factors and acanthosis nigricans maligna.
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PMID:Further evidence that acanthosis nigricans maligna is linked to enhanced secretion by the tumour of transforming growth factor alpha. 144 75

Stomach cancer is one of the major cancers in Asia. Recent advances in diagnosis and surgical techniques have improved the survival of patients with gastric cancer. But radiation and chemotherapy had limited value in promoting the outcome of patients with gastric cancer. Hormonal therapy with tamoxifen had been tried with conflicting results. Previously, we have found that estrogen receptors (ER) were present in 50% cases of Chinese patients with gastric cancers. Recently, the amplification of c-erbB-2 oncogene and its overexpression have been found to correlate with the advancement of lung, ovarian, breast and gastric cancers. In addition, estrogen has been found to inhibit the expression of c-erbB-2 through ER in breast cancer cell lines. A hypothesis is that the same event may occur in ER-positive gastric cancer cell. Thus patients with gastric cancers whose tumors were positive for both ER and c-erbB-2 gene expression, may benefit from estrogen therapy rather than tamoxifen therapy.
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PMID:Hormonal therapy for stomach cancer. 146 Nov 75

Using a polyclonal antibody that is monospecific for the erbB-2 oncogene product, an immunohistochemical study of the expression of erbB-2 protein was performed in formalin-fixed paraffin-embedded tissue sections from 260 primary gastric cancers. erbB-2 protein expression in which the reaction was localized to the cell membranes was observed in 31 (11.9%) cancers. All nontumor cells and normal gastric epithelium were negative for membrane staining. There was not a significant association between erbB-2 staining and histological type or venous invasion. erbB-2 protein expression was associated with serosal invasion, lymph node metastasis, and lymphatic invasion. In addition, erbB-2 protein expression correlated with a high number of lymph node metastases. Furthermore, the risk of recurrence in lymph node was over 3 times higher in patients with erbB-2 protein-positive tumors than in those with erbB-2 protein-negative ones. When erbB-2 protein expression and the clinical parameters were entered simultaneously into the Cox regression model, erbB-2 protein expression emerged as an independent prognostic indicator. Patients with erbB-2 protein-positive tumors had 5-fold greater relative risk of death, as compared with those with erbB-2 protein-negative tumors. These results indicate that erbB-2 protein expression is an important independent prognostic indicator in gastric cancer. The high malignant potential of erbB-2 protein-positive tumors may be associated with the very high potential for lymph node metastasis.
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PMID:Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. 167 Sep 98

Esophageal and gastric cancers are highly virulent tumors with an especially poor prognosis. They are rather common tumors in the United States with an anticipated annual incidence of approximately 32,000 new patients in 1991. Adenocarcinomas of the proximal stomach and lower esophagus are rapidly increasing in incidence; the reasons for this remain unclear. Endoscopic ultrasonography has offered a new dimension to staging especially of the primary tumor but also shows promise for more accurate identification of nodal metastasis. While stage remains the single most important prognostic variable, biological studies investigating tumor markers are a high priority; aneuploidy and HER-2/neu amplification or overexpression may predict poor outcome in gastric cancer. Esophageal and gastric cancers have a high local and distant failure rate when treated with conventional therapy. New developments in chemotherapy in the neoadjuvant and postoperative setting are under intense investigation in an attempt to improve prognosis for these diseases.
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PMID:Therapy of upper gastrointestinal tract cancers. 174 44

K-SAM gene was originally isolated as an amplified gene in a stomach cancer cell line by in-gel DNA renaturation method. K-SAM encodes a membrane receptor with tyrosine kinase and is often amplified in poorly differentiated type of stomach cancer, while c-ERBB-2 is often amplified in well differentiated type of stomach cancer. There are several forms of K-SAM mRNAs which are generated by alternative splicing, and two types of K-SAM protein without transmembrane region. The ligand of K-SAM is considered to be growth factor(s) belonging to fibroblast growth factor (FGF) or heparin binding growth factor (HBFG) family. We have also frequently found amplification of HST-1 or HSTF1 gene in esophageal cancer. HST-1 gene, originally found as a transforming gene, is located on human chromosome 11q13, and it locates 35 kbp apart from its related gene, INT-2. Neither of the genes was expressed even in cancer cells with the co-amplification. By cosmid walking, we have identified at least two genes, designated tentatively as EXP1 and EXP2, on the same amplicon as HST-1 and INT-2, and the mRNAs for EXP1 and EXP2 genes were increased in amounts proportional to the degree of amplification.
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PMID:Biological significance of gene amplification in carcinogenesis. 184 51

We investigated the amplification and expression of oncogenes in human malignant tumors. The survival rates of patients with c-erbB, c-erbB-2, and int-2 oncogene amplification/expression were significantly lower than those of the patients without gene amplification/expression. Many distant organ metastases were observed in esophageal cancer patients with int-2 amplification, in gastric cancer patients with c-erbB-2 over-expression, and in breast cancer patients with int-2 and c-erbB-2 amplification. These results suggest that the amplification/expression of these oncogenes may serve as good markers for determining the biological malignancy of cancers.
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PMID:[Cancer metastasis and recurrence from the standpoint of amplification and expression of oncogenes in human malignant tumors]. 194 61


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