Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0278488 (metastatic breast cancer)
7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epithelial mucins have obtained increasing clinical relevance since they were found in the serum of cancer patients and were shown to be elevated in metastatic disease. We report here the characterization of the monoclonal antibody (MAb) 436 which recognises the protein core of the polymorphic epithelial mucin (PEM) of the human breast. MAb 436 was generated by immunizing Balb/c mice with membrane-enriched fractions prepared from metastatic lesions in the axillary lymph nodes. The antigenic determinant recognized by the MAb 436 is expressed on the surface of breast cancer cells and was measured by ELISA on all of 50 cytosol preparations of primary breast tumors. Immunohistochemistry showed 98% of primary and 100% of metastatic breast cancer lesions to be positive with the 436 antigenic determinant expressed both in the cytoplasm and at the plasma membrane level of the tumor cells. Moreover, the antigen was expressed in a homogeneous fashion (80-100% of the total number of tumor cells) in more than 60% of the tumors. Reactivity with normal tissues was rare and scattered and restricted to glandular structures particularly at the luminal border level except for the distal and collecting tubules of adult and fetal kidney, where a cytoplasmic 436 antigen distribution was observed. Other cancers proved positive but the reactivity was always variable and heterogeneous. The antigen recognized by MAb 436 appears in Western Blotting as a M(r) of more than 200,000 daltons protein resolved in two bands. Epitope mapping experiments using overlapping octapeptides in the repeat unit of the PEM identified in the RPAP (Arg-Pro-Ala-Pro) sequence the binding site of the 436 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of monoclonal antibody 436 recognizing the Arg-Pro-Ala-Pro sequence of the polymorphic epithelial mucin (PEM) protein core in breast carcinoma cells. 137 74

The immunohistochemical expression of DF3 antigen and serum concentrations of CA15-3, a breast carcinoma-associated antigen recognized by the monoclonal antibodies (MAbs) 115D8 and DF3, was investigated in breast cancer patients. The levels of serum CA15-3 in 23 primary breast cancer patients did not correlate to the percentage cytoplasmic reactivity of MAb DF3 with the carcinoma cells in tissue specimens from each respective patient. In 17 patients who subsequently developed metastatic breast cancer, however, the serum CA15-3 concentrations generally correlated well to the cytoplasmic reactivity of MAb DF3 with the carcinoma cells in specimens obtained at initial biopsy or mastectomy. Elevated levels of serum CA15-3 were seen in metastatic breast cancer patients when the carcinoma cells in their primary specimens expressed enhanced levels of cytoplasmic DF3 antigen. The results of this study suggest that the immunohistochemical demonstration of DF3 antigen in tissue specimens, together with the periodical measurement of circulating CA15-3 antigen, may be important for monitoring the clinical course of breast cancer patients.
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PMID:The correlation between the immunohistochemical expression of DF3 antigen and serum CA15-3 in breast cancer patients. 164 3

Monoclonal antibody (mAb) 83D4 was generated using formol-fixed paraffin-embedded human breast carcinoma tissue as the immunogen. Previous studies demonstrated that it was reactive with breast carcinoma tissues, but not with normal breast. The antigen identified by mAb 83D4 was detected, using ELISA, in MCF7 breast carcinoma cell line membrane extracts, in primary breast and colon carcinoma tissue extracts and in pleural effusion fluid from patients with metastatic breast cancer. No reactivity with 83D4 was found in either human milk fat globule membranes or skimmed milk. 83D4 reactive antigen was found to be a heterogeneous high molecular weight (MW) protein (apparent Mr:300-400 to over 1000 kDa) by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. The antigen was purified from MCF7 cells, breast and colon carcinomas and effusion fluid, by perchloric acid solubilisation followed by immunoaffinity chromatography with 83D4. The immunopurified antigen from MCF7 cells and pleural effusion fluid was further analysed by gel filtration and ion-exchange chromatography, which confirmed the high MW and indicated the charge heterogeneity of the reactive molecules. The 83D4 reactive antigen strongly bound to wheat-germ agglutinin and weakly to peanut lectin. No binding was found with lentil lectin or concanavalin A. Antigenic activity was strongly reduced by trypsin and subtilysin digestion and by treatment with sodium periodate, but it was not affected by neuraminidase. These results imply the glycoprotein nature of the 83D4-defined antigen and the involvement of carbohydrate, but probably not sialic acid, in the epitope. Purified 83D4 antigen did not display reactivity for mAb HMFG-1, directed against a polymorphic epithelial mucin, PEM, using ELISA, but bound mAb CC49 and weakly mAb B72.3, antibodies which define a tumour associated glycoprotein, TAG-72. Moreover CC49 and 83D4 showed similar reactivity pattern in immunoblotting assays. A double determinant radioimmunoassay confirmed that 83D4 antigen carries epitopes for mAb B72.3 and CC49. Competition radioimmunoassays clearly distinguished the 83D4 defined epitope from those recognised by B72.3 and CC49, demonstrating that antibody 83D4 identifies a unique epitope. It is suggested that the antigens identified by mAb 83D4 and by mAb B72.3 and CC49 may form part of the same family of carcinoma associated glycoproteins.
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PMID:Purification and characterisation of a breast-cancer-associated glycoprotein not expressed in normal breast and identified by monoclonal antibody 83D4. 170 94

Serum from patients with systemic breast cancer was found to contain elevated levels of polymorphic epithelial mucin (PEM) as detected using an immunoradiometric assay employing the monoclonal antibody NCRC-11. PEM was partially purified from pooled sera from these patients and the complex, polymorphic, high-molecular-mass (greater than 400 kDa) mucin was identified by sodium dodecylsulphate/polyacrylamide gel electrophoresis, Western blotting and immunostaining with the NCRC-11 antibody. Serial serum samples from 16 patients with metastatic breast cancer were assayed for circulating PEM defined by the monoclonal antibody NCRC-11. The clinical course of disease in these patients was assessed independently as progressive, static or responsive. Increasing NCRC-11 antigen levels correlated with disease progression in 6/7 patients, and decreasing antigen levels correlated with an objective response to treatment in 5/6 patients. Measurement of NCRC-11-defined PEM antigen in patients undergoing therapy for metastatic breast cancer showed an overall accuracy of 75%.
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PMID:Detection of polymorphic epithelial mucins in the serum of systemic breast cancer patients using the monoclonal antibody, NCRC-11. 237 45

The murine monoclonal antibody (MAb), designated DF3, reacts with a 300-kilodalton (kd) mammary epithelial antigen. A sequential double-determinant enzyme-linked immunoassay (EIA) has been developed to monitor circulating DF3 antigen. Previous studies have demonstrated that the use of the DF3 EIA provides a new and potentially useful marker to follow the clinical course of patients with metastatic breast cancer. In the present study, we have monitored circulating DF3 antigen in the serum of patients with epithelial ovarian carcinomas and non-ovarian gynecologic malignancies. Twenty-one of 45 patients (47%) with ovarian carcinoma had elevated DF3 antigen levels (greater than or equal to 30 U/mL). In contrast, three of 20 patients (15%) with non-ovarian gynecologic malignancies, and only four of 59 control women (7%) had elevation of circulating DF3 antigen. The difference between DF3 antigen values from patients with ovarian cancer and from controls was significant (P less than .001). The elevation of circulating DF3 antigen in ovarian cancer patients has also been confirmed by transblot assays. MAb DF3 reactivity occurred predominately with circulating antigens of molecular weights (mol wt) ranging from 300 to 450 kd. Furthermore, DF3 antigen levels have been shown to correlate with progression of disease in six patients with ovarian cancer and after resection of disease in two others. The half-life of circulating DF3 antigen was approximately 45 to 60 days. The results also demonstrate that DF3 antigen is distinct from CA125, a glycoprotein associated with coelomic epithelium and developmental amnion. The use of both the DF3 EIA and the immunoradiometric assay previously described to detect circulating CA125 suggests that determining levels of both markers may enhance the sensitivity of monitoring the course of ovarian cancer. Furthermore, the use of both assays may be useful in distinguishing ovarian cancer from other malignancies.
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PMID:Circulating DF3 and CA125 antigen levels in serum from patients with epithelial ovarian carcinoma. 241 81

The murine monoclonal antibody (MAb), designated DF3, reacts with a 300,000-mol wt mammary epithelial antigen. A sequential double-determinant radioimmunoassay (RIA) has been developed to monitor circulating DF3 antigen. Using this assay, we have demonstrated that 33 of 36 normal women had plasma RIA antigen levels less than 150 U/ml. In contrast, 33 of 43 patients (76%) with metastatic breast cancer had RIA DF3 antigen levels greater than or equal to 150 U/ml. The difference between these two groups was statistically significant (P less than 0.001). Similar results have been obtained with a double-determinant enzyme-linked immunoassay (EIA). Only 6 of 111 age-matched normal subjects had EIA DF3 antigens levels greater than or equal to 30 U/ml, while 42 of 58 patients (72%) with breast cancer had levels equal to or above this value. Thus, similar patterns of specificity are obtained with the EIA or RIA. The elevation of circulating DF3 antigen levels in breast cancer patients has been confirmed by transfer blot assays. MAb DF3 reactivity occurred predominantly with circulating antigens of three different molecular weights ranging from 300,000 to approximately 400,000 mol wt. We also demonstrate that patients with both primary and metastatic breast cancer who were free of detectable disease at the time of sampling have DF3 antigen levels that are similar to those obtained from normal subjects. While patients with hepatoma (27%) and ovarian carcinoma (47%) also had elevated circulating DF3 antigen levels, the results suggest that DF3 antigen levels may be useful in distinguishing breast cancer patients from those with esophageal, gastric, colorectal, pancreatic, and lung carcinomas. Furthermore, the results of the RIA, EIA, and transblot analyses demonstrate that the measurement of circulating DF3 antigen levels provides a new and potentially useful marker to follow the clinical course of patients with metastatic breast cancer.
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PMID:Use of a murine monoclonal antibody for detection of circulating plasma DF3 antigen levels in breast cancer patients. 388 57

Specific tumour imaging with radiolabelled monoclonal antibodies has been extensively investigated. Although some success has been reported, there are many limitations due to the slow kinetics, poor extravasation, catabolism by the reticuloendothelial system, and non-specific uptake of macromolecules such as antibodies. We have tried to overcome some of the problems associated with monoclonal antibodies while retaining their specificity by using an antibody-derived synthetic peptide. A synthetic pentadecapeptide (alpha M2) derived from the third heavy-chain complementarity-determining region (CDR-3H) of a tumour-associated monoclonal antibody was produced and shown to retain its specificity against the pan-carcinoma cell-surface antigen, polymorphic epithelial mucin, detected by the parent antibody. The peptide was radiolabelled with technetium-99m and injected intravenously to image malignant lesions in 26 women with primary, recurrent, or metastatic breast cancer. Visualisation of breast tumours and their metastases was obtained shortly after administration of alpha M2, and was optimum by 3 h. Overall, 57 (77%) of 74 sites were visualised. Successful imaging was achieved in 14 of 15 primary tumour sites and all of eight local recurrences. Five of six metastases in the opposite breast, eight of 15 metastatic axillary lymph nodes, and all of six metastatic supraclavicular lymph nodes were imaged. Metastatic sites in the lungs, mediastinum, chest wall, and liver were poorly visualised because of background cardiac blood pool. alpha M2 detected small lesions ( < 2 cm) as efficiently as larger ones. The peptide was rapidly (3 h) cleared from the circulation. No acute or chronic adverse reactions due to the alpha M2 were observed. Specific tumour targeting with the radiolabelled anticancer peptide alpha M2 offers new opportunities for breast cancer imaging and possibly therapy.
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PMID:Breast cancer imaging with radiolabelled peptide from complementarity-determining region of antitumour antibody. 855 23

IIB-BR-G is an undifferentiated, highly heterogeneous, hormone receptor negative human breast cancer cell line previously established in our laboratory from a patient's primary tumor. An in vitro growing cell line (IIB-BR-G) and a xenotransplanted tumor growing in nude mice (IIB-BR-G(NUDE)) were derived. To further characterize these systems, immunocytochemical analysis was performed for differentiation antigens (PEM 200 kDa, CEA, NCA 90 kDa), blood-group related antigens (Le(x), sTn), oncogenes and tumor suppressor gene products (Her-2/neu protein, p53), metastasis-related cathepsin D and CD63/5.01 Ag, and the chemokine monocyte chemotactic protein 1 (MCP-1). Expression of markers was heterogeneous in these different systems. Previously reported karyotypic analysis has shown extensive chromosomal alterations including double min. Searching for oncogene amplification, we detected augmented copy number of c-myc and c-fos, the last one with two rearranged fragments. No amplification was found for c-erbB-2 in the cell line or in IIB-BR-G(NUDE), although this oncogene was amplified in the patient's primary tumor DNA. The differences observed between the patient's tumor, the cell line and the IIB-BR-G(NUDE) tumors are probably due to clonal expansion of cell variants not present in the original tumor. Electron microscopy of IIB-BR-G growing cells revealed epithelial characteristics with abundant dense granules, presumably secretory, distributed all over the cytoplasm and great nuclear pleomorphism. In vitro, IIB-BR-G cells showed a significant number of invading cells by Matrigel assay. After nearly 40 sequential subcutaneous passages of the original xenograft through nude mice, 80% of recipients developed spontaneous metastases, primarily to the lung and lymph nodes. Since this experimental model allowed to analyze changes produced in cancer cells from the primary tumor during adaptation to in vitro and in vivo growth, our results provide novel insights on the behaviour of hormone independent metastatic breast cancer.
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PMID:The human breast cancer cell line IIB-BR-G has amplified c-myc and c-fos oncogenes in vitro and is spontaneously metastatic in vivo. 962 Apr 46

The Truquant BR radioimmunoassay (RIA) using monoclonal antibody BR 27.29 to recognize a peptide sequence on the MUC-1 gene product for quantification of the CA 27.29 antigen in serum was used in this report to evaluate in 145 patients with breast cancer and compared the other conventional serum markers such as CA15-3 and CEA. The upper limit of normal (25 u/ml) was determined from CA27.29 values 12.4 +/- 4.1 u/ml (mean +/- 3 S.D.) for 112 female subjects apparently free of disease. The CA15-3 levels above 25 u/ml and CEA levels above 5 ng/ml were considered positive values. Thirty-seven cases of 145 patients studied had elevated CA 27.29 levels (sensitivity: 25.5%), 35 of 145 had positive CA15-3 levels (sensitivity 24.1%) and 27 of 145 patients had positive CEA levels (sensitivity: 18.6%) (p < 0.05). One hundred and ten cases of the breast cancer patients (75.8%) did not have metastatic disease. In this group CA 27.29 sensitivity was 6.4%, while CA15-3 sensitivity was 5.5% and CEA sensitivity was 4.5% (p > 0.05). Mean values were 10.2 +/- 9.2 u/ml for CA 27.29, 14.1 +/- 5.6 u/ml for CA 15-3 and 1.7 +/- 1.5 ng/ml for CEA. Thirty-five patients (24.2%) had metastatic disease. In this group CA 27.29 sensitivity was 85.7%, CA15-3 sensitivity was 82.8% and CEA sensitivity was 62.8% (p < 0.05). Mean values for CA27.29 was 152.6 +/- 131.6 u/ml, CA15-3 was 123.1 +/- 107.6 u/ml and 21.8 +/- 36.9 ng/ml of CEA. With regard to the correlation of three tumor markers with clinical stages, patients had significantly higher levels of CA27.29 than CEA, but they were similar to CA 15-3 in metastatic breast cancer. These results suggest CA27.29 to be more sensitive and specific than CEA, but that it is similar to CA15-3 for metastatic breast cancer detection and monitoring.
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PMID:Evaluation of serum CA27.29, CA15-3 and CEA in patients with breast cancer. 1056 76

This study was designed to determine whether in vitro exposure of isolated short-term human primary and metastatic breast tumor cell cultures to interferon-gamma (IFN-gamma) could enhance expression of the breast tumor associated DF3 antigen in association with the intercellular adhesion molecule 1 (ICAM-1) and MHC class II molecules. Cell cultures were established from primary solid tumors and metastatic cells as previously described (Sgagias et al., 1995). Data show that recombinant human IFN-gamma treatment, in vitro, dramatically increased the breast tumor associated DF3 antigen, in association with ICAM-1, and MHC class II antigens in primary breast cancer cell cultures. All primary breast tumor cell cultures constitutively expressed high levels of HLA-class I antigen. Metastatic breast cancer cell cultures expressed high levels of DF3 and recombinant human IFN-gamma treatment, in vitro, upregulated ICAM-1 and MHC class II antigens before and after passage of the metastatic cells through the nude mouse. Metastatic breast cancer cells similar to primary breast cancer cells constitutively expressed high levels of MHC class I antigens. In addition, three LAK cell lines significantly lysed the primary and the metastatic breast tumor cell cultures to the same degree before and after passage of the metastatic cancer cells through the nude mouse. These data indicate the upregulation of the breast tumor associated DF3 antigen in vitro after IFN-gamma treatment and its persistence in vivo, after passage of the metastatic breast cancer cells through the nude mouse. The ability of IFN-gamma to upregulate the breast tumor associated DF3 antigen in association with the ICAM-1 and HLA class II antigens may play an important role in eliciting an immune response which may contribute to the immunodiagnosis, and immunotherapy of breast cancer.
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PMID:Upregulation of DF3, in association with ICAM-1 and MHC class II by IFN-gamma in short-term human mammary carcinoma cell cultures. 1085 35


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