Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Computer-assisted image analysis was used to demonstrate in exponentially proliferating human tumor cells the uneven postmitotic apportionment of several oncogene-encoded proteins (ras p21; erbB-2 p185; fos p55; myc p62). This observation may provide the explanation for the high degree of heterogeneity of postmitotic cells and the asynchrony in cell cycle traverse of cultured cells.
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PMID:Asymmetric distribution of oncogene products at mitosis. 135 Jun 77

K1 is a murine monoclonal antibody (MAb) derived from a hybridoma generated by the fusion of splenocytes of BALB/c mice immunized with a human ovarian tumor cell line, OVCAR-3. This antibody reacts strongly with epithelial ovarian tumors and mesotheliomas. The antigen recognized by MAb K1, designated CAK1, has recently been characterized as a 40-kDa protein probably anchored to the cell surface by glycosyl-phosphatidylinositol. Using immunoperoxidase histochemical methods, we examined 37 squamous-cell carcinoma (SqCC) samples from cervix, lung, esophagus and other origins, and 12 normal squamous epithelia of the cervix and esophagus for their reactivity with MAb K1. Of the SqCC specimens, 81% showed K1 reactivity with variable intensity, but none of 12 normal tissue samples of squamous epithelia did so. Two patterns of CAK1 expression in tumor samples were found, i.e., a heterogeneous pattern with strong intensity, and a homogeneous pattern with weak intensity. Three carcinomas in situ of the larynx, vulva and esophagus were moderately positive with K1, suggesting that CAK1 antigen may occur in the early stage of carcinogenesis of SqCC. The expression of CAK1 was also compared with expression of CA125, HER-2/neu, p53 and P-glycoprotein, and MAb K1 was found to react most consistently with SqCC. Since K1 reacts with a majority of cervical and esophageal carcinomas but has no detectable reactivity in normal epithelia of the cervix uteri and esophagus, MAb K1 could be of value as a reagent to help distinguish between normal and neoplastic cells on sections as well as in cytological samples.
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PMID:Frequent expression of the tumor antigen CAK1 in squamous-cell carcinomas. 135 Oct 45

The hormonally induced changes in the breast during pregnancy make the diagnosis of breast cancer difficult. Furthermore, examinations during pregnancy tend to concentrate only on the pregnancy itself. In this report the clinical, pathological and immunohistochemical results from 7 patients with breast cancer during pregnancy are presented. All women first noticed the tumor by self-examination. The time periods between discovery of the tumor and medical treatment were between 4 and 22 weeks. An overexpression of c-erbB-2-oncogene coded transmembrane protein p185 could be demonstrated in 4 cases. Of the seven patients, 5 have already passed away. Three of the deceased had p185-positive tumors, and died 4, 8 and 21 months after diagnosis. The two p185-negative patients lived 34 and 65 months post diagnosis. Despite the small amount of cases presented, a trend can be seen that p185 may be an additional prognostic factor for breast cancer in pregnancy.
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PMID:[Breast carcinoma in pregnancy. Clinical, histological and immunohistochemical findings]. 135 30

In previous studies, combinations of immunotoxins reactive with different cell-surface antigens have exerted additive cytotoxicity against tumor cells in culture. In this report we describe a combination of 2 immunotoxins that produce synergistic cytotoxic activity. Recombinantly derived ricin A chain (RTA) was conjugated with murine monoclonal antibodies (MAbs) 317G5, 260F9, 454A12 and 741F8 that bound to cell-surface determinants of 42, 55, 180 (transferrin receptor) and 185 kDa (HER-2/neu) expressed by the SKBr3 human breast-cancer cell line. When inhibition of clonogenic growth was measured in a limiting dilution assay, the combination of 260F9-RTA and 454A12-RTA produced synergistic cytotoxic activity against SKBr3 and 2 other breast-cancer cell lines. All other combinations produced only additive inhibition of clonogenic growth. Simultaneous binding of 260F9 and 454A12 was not supra-additive, but sub-populations of cells which lacked one or the other antigen could be detected. Kinetic studies of internalization, using antibodies conjugated with gold particles, indicated that 454A12 remained within peripheral endosomes for a longer interval in the presence of 260F9. This change in the traffic of the transferrin receptor may contribute to synergy between 260F9-RTA and 454A12-RTA.
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PMID:A combination of two immunotoxins exerts synergistic cytotoxic activity against human breast-cancer cell lines. 135 85

Several lines of evidence have demonstrated that expression of the c-erbB-2 gene product contributes to the malignant phenotype. We and others have determined that c-erbB-2 is substantially expressed in most ductal in situ carcinomas of the comedo type, but not in other patterns of ductal carcinoma in situ or in atypical ductal hyperplasia of the breast. In the present investigation, by immunohistochemistry we inquired whether invasive ductal adenocarcinomas retained the c-erbB-2 expression status of the in situ carcinomas from which they derived. Of twelve specimens containing both cribriform/micropapillary in situ and derivative invasive adenocarcinomas in the same section, all tumor cells were negative for c-erbB-2 expression. In thirteen in situ carcinomas of the comedo type, with identifiable invasive components, ten had definite c-erbB-2 expression, and in every case there was comparable c-erbB-2 protein staining of in situ and invasive components; in three of these ten cases the staining in the in situ component tended to be more intense. These findings imply that a significant proportion of invasive mammary adenocarcinomas expressing c-erbB-2 protein is derived from ductal in situ carcinomas of the comedo type.
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PMID:Expression of c-erbB-2 in in situ and in adjacent invasive ductal adenocarcinomas of the female breast. 135 87

In this paper we describe the isolation and characterization of four monoclonal antibodies (FRP5, FSP16, FWP51, and FSP77) which specifically recognize the human erbB-2 protein. All of the antibodies recognize epitopes on the extracellular domain of the receptor protein. FRP5 and FSP16 compete with one another for binding while FWP51 and FSP77 each recognize a different epitope. The effects of the antibodies on the erbB-2 receptor protein have been analyzed. Two different erbB-2-expressing cell lines, SKBR3 breast tumor cells and HC11 R111 cells, were examined. The SKBR3 cells express approximately 1 x 10(6) molecules of the erbB-2 protein/cell; HC11 R111 cells, a clone of mouse mammary epithelial cells derived by transfection of a human erbB-2 expression plasmid, contain 10-fold less erbB-2 protein than the SKBR3 cells. Treatment of the two cell lines with FRP5, FSP16, and FWP51 led to a rapid increase in the phosphotyrosine content of the erbB-2 protein. Three of the antibodies, FRP5, FSP16, and FSP77, stimulated the turnover of the erbB-2 protein. Binding of the antibodies did not stimulate DNA synthesis in HC11 R111 cells. Thus, the erbB-2-specific monoclonal antibodies behave as partial ligand agonists. The antibodies were examined for their effects upon the growth of SKBR3 and HC11 R111 cells. The growth of SKBR3 cells was inhibited by 90% following long term treatment of the cells with FSP77.
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PMID:Monoclonal antibodies against the extracellular domain of the erbB-2 receptor function as partial ligand agonists. 135 79

With the aim of developing an effective cancer immunotherapy for common epithelial cancer, a new class of bifunctional antibody (BFA) was developed; one arm of this BFA recognized c-erbB-2 gene product, and the other arm recognized CD3 epsilon, a T-cell specific surface antigen. Application of this BFA with human peripheral blood lymphocytes exhibited specific anti-tumor activity in vitro on a breast tumor cell line, ZR-75-1, which expressed abundant c-erbB-2 gene product on its cell surface. These results indicate that BFA recognizing an oncogene product on cell surface is a potential new agent for cancer immunotherapy.
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PMID:In vitro anti-tumor activity of anti-c-erbB-2 x anti-CD3 epsilon bifunctional monoclonal antibody. 135 52

In order to analyze the correlation between immunohistochemical positivity for c-erbB-2 oncoprotein and prognosis in patients with malignant salivary gland tumors, 59 cases of malignant tumors of the major salivary glands, including 35 parotid gland, 20 submaxillary gland and 4 sublingual gland tumors, were studied immunohistochemically using a polyclonal antibody against c-erbB-2 oncoprotein. Positive staining was observed in 13 (22%) of the 59 cases. Interestingly, positive results were obtained only in adenocarcinoma (6/20) and carcinoma in pleomorphic adenoma (7/15), and not in any other histological types such as adenoid cystic carcinoma, mucoepidermoid tumor, and squamous cell carcinoma. There was no correlation between the degree of differentiation of adenocarcinoma and c-erbB-2 positivity. Since the carcinoma in pleomorphic adenoma positive for c-erbB-2 oncoprotein was adenocarcinoma, adenocarcinoma and adenocarcinoma in pleomorphic adenoma were placed together (n = 33), and the presence or absence of c-erbB-2 oncoprotein in this group was examined for correlation with patients' survival and other clinicopathological features, including clinical stage, tumor size, surgical margins, and lymph node status. The c-erbB-2-positive tumors tended to be more advanced and larger than negative tumors. Similarly, c-erbB-2-positive tumors were difficult to resect completely, were associated with lymph node metastasis more frequently, and showed lower disease-free survival than negative cases (P less than .05). We conclude that immunohistochemical positivity for c-erbB-2 is an indicator of aggressiveness in both adenocarcinoma and adenocarcinoma in pleomorphic adenoma of the major salivary glands.
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PMID:Immunohistochemical study of c-erbB-2 oncoprotein overexpression in human major salivary gland carcinoma: an indicator of aggressiveness. 135 53

MCF-10A cells are a spontaneously immortalized untransformed human mammary epithelial cell line. We have previously shown that overexpression of a human point-mutated c-Ha-ras proto-oncogene, the rat c-neu (c-erbB-2) proto-oncogene, or the human transforming growth factor-alpha (TGF-alpha) gene in MCF-10A cells leads to in vitro transformation of such cells. To ascertain whether the introduction of two of these genes into MCF-10A human mammary epithelial cells induces a completely tumorigenic phenotype, we infected MCF-10A Ha-ras and MCF-10A TGF-alpha cells with a recombinant retroviral vector containing the human c-erbB-2 proto-oncogene and the hygromycin-resistance gene. Ten MCF-10A TGF-alpha/c-erbB-2 (MCF-10A TE) and 10 MCF-10A Ha-ras/c-erbB-2 (MCF-10A HE) hygromycin-resistant clones were randomly selected and expanded into cell lines. MCF-10A TE and MCF-10A HE clones expressed a 10-fold to 40-fold increase in p185 erbB-2 protein levels compared with parental uninfected cells. These cells exhibited a fourfold increase in their growth rate in serum-free medium and showed a strongly reduced mitogenic response to exogenous epidermal growth factor or TGF-alpha compared with MCF-10A cells. Moreover, both MCF-10A TE and MCF-10A HE clones exhibited a fivefold to 20-fold higher cloning efficiency in soft agar than MCF-10A Ha-ras, MCF-10A c-erbB-2, or MCF-10A TGF-alpha clones. However, neither MCF-10A TE nor MCF-10A HE cells were able to grow as tumors in vivo when they were injected into nude mice. These results suggest that c-Ha-ras, c-erbB-2, and TGF-alpha genes have an additive effect on the in vitro transformation of an immortalized human mammary epithelial cell line, but that additional genetic changes such as activation of other proto-oncogenes or inactivation of a tumor suppressor gene may be necessary to elicit a fully tumorigenic phenotype.
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PMID:Additive effects of c-erbB-2, c-Ha-ras, and transforming growth factor-alpha genes on in vitro transformation of human mammary epithelial cells. 135 42

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


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