Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amplification or overexpression of the human neu oncogene has been shown to correlate with the number of lymph node metastases in breast cancer patients, suggesting that expression of the neu oncogene may be associated with increased metastatic potential. However, there has been no systematic study on the role of the neu oncogene in metastasis to support this correlation. In our study, mouse embryo fibroblast 3T3 cells transformed by the mutation-activated rat neu oncogene exhibited metastatic properties both in vitro and in vivo, while parental 3T3 cells did not. Monoclonal antibodies capable of inducing down-regulation of the neu-encoded p185 protein reduced the metastatic potential induced by neu. These data provide strong experimental evidence that neu oncogene expression is sufficient for the induction of metastasis in the 3T3 cell system and supply a molecular basis supporting the correlations found in clinical observation. The results also suggest that neu-specific monoclonal antibodies may have preventative or therapeutic potential for neu-induced metastasis.
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PMID:Expression of activated rat neu oncogene is sufficient to induce experimental metastasis in 3T3 cells. 168 65

The human homolog of the rat neu oncogene, HER2 (also termed c-erbB2) has been demonstrated in amplified form in human breast tumors with poor prognosis. Although amplification of the gene correlates with expression of a 185-kDa transmembrane glycoprotein, no extensive information is available regarding the extent of tissue and tumor specificity of this gene product. We have addressed this issue by immunohistochemically evaluating the expression of p185 HER2 in normal tissue and various tumors using monoclonal antibodies (MAbs) to distinct epitopes of its extracellular domain. No detectable levels of p185 HER2 were found in fetal tissues analyzed, with the exception of renal tubules in 2 out of 3 specimens tested and in intestinal epithelium. In adult tissues, detectable levels of this glycoprotein were found in a restricted number of cell types, the expression being heterogeneous among individuals and cell histotypes. Among the neoplasms assayed p185 HER2 was expressed in 46% of primary breast cancers, in 28% of ovarian tumors and in 30% of colon rectum malignancies. No male breast adenocarcinomas were p185-positive. A large number of other tumors tested revealed only a low incidence of expression of the p185. In metastatic breast tumors p185 HER2 was demonstrated homogeneously among multiple autologous lesions and almost invariably (80%) the expression of p185 in the primary lesion correlated with that of the deriving metastases. Our findings indicate that the expression of the p185 HER2 represents a tumor marker of clinical relevance in breast cancer. Whether this holds true for other malignancies remains to be explored.
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PMID:Expression of the p185 encoded by HER2 oncogene in normal and transformed human tissues. 196 37

On the prognostic value of c-erbB2-encoded protein p185 in breast cancer there are controversal opinions. With the outlook of an evaluation of the prognostic value of p185 expression in breast cancer the relationships between p185 expression and known prognosis factors were investigated. Using polyclonal antibody against p185 33% out of 163 primary breast carcinomas are p185-positive. Within the various histological types of tumors the percentage of p185 expression differs. It is suggested that p185 indicates a certain type of biological behavior and plays a role in the pathogenesis of breast cancer. Thus the determination of p185 could allow definition of biological subclasses. A statistically significant correlation between expression of p185 and the presence of lymph node metastases or tumor size can not be proved. Nevertheless p185 expression is increased in cases with more than three positive lymph nodes. Expression of p185 correlates statistically significantly positively with histological grade and epidermal growth factor receptor, and negatively with steroid receptor status. Furthermore, high-proliferating tumors are more common in p185-positive cases than in p185-negative cases. It is concluded that p185 may be associated with an increased malignancy and proliferation activity of tumors.
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PMID:c-erbB2 expression in correlation to other biological parameters of breast cancer. 196 2

To investigate critical factors influencing the localization and antitumor effects of monoclonal antibodies (MAb) or toxic conjugates, we have adapted a single rat sarcoma, HSN, for preferential growth in the lungs, liver, and lymph nodes (the major sites of metastasis in humans) and have raised a panel of syngeneic rat MAbs to a stably-expressed cell surface antigen. Using this model we have shown that localization in tumors is significantly influenced by their anatomical location and vascularization, and the degree of MAb interaction with host cells. Uptake in small hepatic tumors was excellent, but access to lung tumors was limited by the poor permeability of pulmonary vessels. HSN cells transfected with th human IL-2 gene and coinjected in low numbers with parental tumors secreted sufficient cytokine to enhance the local permeability of vessels and doubled MAb localization in tumors without any systemic toxicity, suggesting that regional delivery of IL-2 may be used to enhance MAb localization in this situation. In order to extent the applicability of the model to studies of MAbs raised against human tumor targets, we have transfected the human c-erb B-2 gene (homolog of the rat neu) into the highly metastatic HSN.LV subline. MAbs raised against the external domain of the p185 product can now be screened for their ability to localize in metastases, and for various conjugates to inhibit tumor growth either independently of, or in association with, a fully functional immune system.
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PMID:Monoclonal antibodies for the treatment of metastases. Evaluation of strategies using a syngeneic rat model. 788 38

Concentrations of a fragment of the c-erbB-2 translational product (p185 fragment) were measured in serum of 70 breast cancer patients, 19 healthy blood donors, and 18 pregnant women using a heterogenic enzyme immunoassay. The serum concentrations of blood donors and pregnant women were below 30 kU/l. Breast cancer patients showed serum concentrations up to 578 kU/l. All 9/70 patients with serum concentrations higher than 30 kU/l had clinical evidence of metastatic disease and the serum levels of all 35/70 patients without metastasis lay within the normal range. From 9/37 patients with p185 overexpression of the primary tumor in immunohistochemical analysis 3/9 patients with metastatic disease had elevated serum levels higher than 30 kU/l. In all, 6/9 patients without metastasis serum levels were below 30 kU/l. The data of the present study suggest that determination of serum p185 fragment concentrations may be useful as a diagnostic tool in postoperative follow-up of breast cancer patients with c-erbB-2 overexpression of the primary tumor.
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PMID:Determination of a fragment of the c-erbB-2 translational product p185 in serum of breast cancer patients. 809 50

The total cellular p185(HER-2/neu) protein (p185) content was measured by ELISA in 346 invasive primary breast cancers, and the results were compared with those of estrogen (ER) and progesterone (PR) receptors, pS2 and Cathepsin D (Cat D) content. At a cut-off level of 260 fmol/mg protein, 53 of the 346 tumors (15%) were p185-positive. A significant positive correlation was observed between p185 levels and those of Cat D, and a weaker, though significant, positive correlation with ER, and pS2 levels, but not with those of PR. However, when only the 293 p185-negative tumors were considered, the correlation between p185 and ER improved substantially, and statistical significance was reached for PR. p185-positive tumors exhibited lower ER and PR content and higher Cat D content than p185-negative tumors. The pS2 content, in contrast, did not undergo significant variation. Tumors considered to be p185-positive were significantly more frequently positive for Cat D at the cut-off of 45 pmol/mg protein, and were more frequently negative for ER and/or PR, but only significant at the cut-off of 15 fmol/mg or higher for both steroid receptors. Finally, p185 status was not associated with menopausal status, tumor size, axillary-lymph-node invasiveness or distant metastases. These results suggest that 260 fmol/mg protein as the cut-off for p185 allows the identification of a tumoral sub-population with a more aggresive phenotype.
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PMID:Quantitative analysis of p185(HER-2/neu) protein in breast cancer and its association with other prognostic factors. 913 51

Our aim was to compare the prognostic value of c-erbB-2 gene amplification analyzed by Southern blot with that of protein (p185) over-expression measured by immunohistochemistry in 172 patients with operable breast cancer (BC). Amplification and p185 over-expression were found in 31 (18%) and 51 (30%) BCs, respectively. All but 1 of the tumors showed both amplification and over-expression, while 21 (12%) tumors displayed over-expression without amplification. The risk of death associated with c-erbB-2 gene amplification and p185 over-expression was evaluated by multivariate analysis, taking into account tumor size, histoprognostic grade, hormone receptors and axillary node status. During a mean follow-up of 9.5 (+/-2) years, node involvement (p < 0.001), c-erbB-2 gene amplification (p = 0.02) and negative hormone receptors (p = 0.02) were found to be independent prognostic indicators of the risk of death. Over-expression of p185 with no amplification was not correlated with this risk. When the risk of death associated with c-erbB-2 amplification was studied according to chemo- and hormone therapy, no significant difference was observed between subgroups of subjects. Amplification was also associated (p = 0.02) with the risk of multifocal distant metastases (i.e., metastases detected concomitantly in at least 2 sites) and, thus, with BC aggressiveness. These data show the importance of c-erbB-2 gene amplification in predicting the long-term outcome of patients and in selecting eligible patients for c-erbB-2-targeted therapies.
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PMID:c-erbB-2 (HER-2/neu) gene amplification is a better indicator of poor prognosis than protein over-expression in operable breast-cancer patients. 1140 Jan 21

Human epidermal growth factor receptor 2 (p185 HER2) oncoprotein immunohistochemical expression and DF3 antigen distribution were evaluated in 129 patients with primary breast cancer. p185 HER2 overexpession was positively correlated with the degree of differentiation, metastatic disease, progesterone receptors, and cytoplasmic distribution of DF3 antigen. p185 HER2 overexpression had prognostic significance for the disease-free interval.
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PMID:Immunohistochemical study of p185 HER2 and DF3 in primary breast cancer and correlation with CA-15-3 serum tumor marker. 1186 May 39

p185(HER-2/neu), a tyrosine kinase receptor, is one of the target molecules for cancer therapy, and its expression may reduce the sensitivity of tumor cells to anti-cancer drugs. p21(CIP1/WAF1) is a cyclin-dependent kinase inhibitor, and its expression may also be involved in chemoresistance. Non-small cell lung cancer (NSCLC) is a potentially systemic disease, and systemic therapies play an important role in its treatment. However, there have been no studies comparing the expression of these molecules between primary and metastatic tumors. We investigated the expression of p185(HER-2/neu) and p21(CIP1/WAF1) in 57 paired samples of primary NSCLC tumors and corresponding lymph node metastases by immunohistochemistry. Expression of each of p185(HER-2/neu) and p21(CIP1/WAF1) was highly correlated between primary tumors and lymph node metastases, and similar correlations were also obtained when adenocarcinoma and squamous cell carcinoma cases were analyzed individually. However we failed to detect any correlation between p185(HER-2/neu) and p21(CIP1/WAF1) expression. Our results suggested that expression of both p185(HER-2/neu) and p21(CIP1/WAF1) is concordant between primary and metastatic tumors.
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PMID:p185(HER-2/neu) and p21(CIP1/WAF1) expression in primary tumors and lymph node metastases in non-small cell lung cancer. 1235 54

Much debate exists on factors predicting the development of persistent gestational trophoblastic disease (pGTD). Diagnosis is still limited by following persistently elevated or rising postevacutation beta-human chorionic gonadotropin (beta-hCG) titers. The aim of the present work was to evaluate the hypothesis that the presence of c-erbB-2 oncogene amplification and expression, in combination with parameters such as DNA-content and karyotype of the sex chromosomes, confer an increased risk of developing pGTD. Clinicopathological characteristics were evaluated in 36 cases of gestational trophoblastic diseases (GTD) and analyzed for c-erbB-2 amplification and protein p185 expression using differential polymerase chain reaction (DPCR) and immunohistochemical (IHC) techniques. The DNA-content was determined by image analysis on Feulgen stained nuclear cell preparations and karyotyping for XY chromosomes was performed by fluorescence in situ hybridization (FISH). The data was correlated with histopathological characteristics of GTD. Seventy-five percent (n = 27) of the examined cases showed spontaneous regression after evacuation, including 2 patients who received additional chemotherapy. Twenty-five percent (n = 9) resulted in a persistent or metastatic disease. The median time between antecedent pregnancy and GTD was 45.4 months. Complete remission was achieved in all patients with pGTD after administration of chemotherapeutic agents or adjuvant surgical procedures. Cases with cerbB-2 amplification and expression in combination with DNA hyperploidy showed higher proliferation and more aggressive behavior (2 complete hydatidiform moles with lung and liver metastases, 2 invasive moles and 1 choriocarcinoma). XY karyotype was evident in the choriocarcinoma and in 2 complete hydatidiform moles with advanced stage and DNA hyperploidy. From these results we conclude that c-erbB-2 amplification and/or protein expression in combination with DNA-content show a significant correlation with the proliferative and aggressive potential of GTD, suggesting their combined use as a possible marker for pGTD.
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PMID:Clinicopathologic profile of gestational trophoblastic disease. 1265 8


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