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)

The monoclonal antibodies that define the tumor markers CA15.3, MCA, CAM26 and CAM29 were found to react with coexisting epitopes present on mucin-like glycoproteins. Despite their immunologic relationship, the markers showed distinct concentration levels in various body fluids. Particularly, MCA and CAM26 were high in urine and amniotic fluid. Sera collected from pregnant or lactating women and especially human milk samples contained considerable amounts of CAM29 and MCA, but comparably small quantities of CAM26 and CA15.3. The concentrations of CA15.3, MCA, CAM26 and CAM29 were correlated in serum samples from patients with metastatic breast cancer. The discrepancy between immunologic relationship and dissimilar biologic behavior could be explained by a limited coexistence of epitopes on subsets of heterogeneous polymorphic mucins. All mucin markers which were investigated showed improved sensitivity for metastatic breast cancer compared with the established marker CEA.
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PMID:CA15.3, MCA, CAM26, CAM29 are members of a polymorphic family of mucin-like glycoproteins. 206 12

The Breast Cancer Mucin (BCM) enzyme immunoassay utilizes two monoclonal antibodies (Mab), M85/34 and F36/22, for the identification of a mucin-like glycoprotein in serum of breast cancer patients. We have compared BCM with CA 15-3, another member of the human mammary epithelial antigen family. Serum BCM was evaluated in 151 and CA 15-3 in 134 patients with breast cancer, in 30 normal controls, in 9 pregnant women, and in 13 cancer patients (non-breast). Neither the normal controls nor the pregnant women had BCM levels greater than 25 U/ml. In contrast, 87 of 115 patients (75%) with metastatic breast cancer had BCM levels greater than 25 U/ml. All control persons had CA 15-3 levels less than 25 U/ml, but 2 out of 9 pregnant women (22%) had levels greater than 25 U/ml. Seventy-four out of 97 patients (76%) with metastatic breast cancer had CA 15-3 levels greater than 25 U/ml. A statistically significant correlation was found between BCM and CA 15-3 in the breast cancer patient group (r = 0.883, p less than 0.001, n = 134) and in the normal control group (r = 0.743, p less than 0.001, n = 30). BCM and CA 15.3 both showed no correlation with CEA in breast cancer patients (r = 0.060, n = 81; and r = 0.146, n = 78, respectively). BCM had a range of sensitivity similar to that of the CA 15-3 RIA. Our results suggest that BCM may be a useful new marker for monitoring the clinical course of patients with breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of breast cancer mucin (BCM) and CA 15-3 in human breast cancer. 209 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

Serum levels of mucin-like carcinoma associated antigen (MCA) were measured in 80 healthy women, 109 patients with breast cancer at presentation and in samples taken from 45 patients with active metastatic breast cancer. The MCA levels in controls had an upper limit of normal of 19.6 U ml-1 in post-menopausal and 16.4 U ml-1 in premenopausal women. The levels at presentation in stages I and II and III were not significantly different from the post-menopausal controls. Longitudinal studies over 5-9 years in 20 patients with stage I and II disease who had remained tumour-free showed a narrow MCA range for each individual patient, but the mean and range of a single measurement in a further 63 of these patients were similar to those of the normal controls. Rising MCA levels occurred in 12/14 patients who developed metastases in 2-8 years after surgery, but local recurrence was not associated with a rise of MCA. Eighty per cent of patients with active metastatic disease had MCA levels greater than 15 U ml-1. MCA levels fell during clinical responses to therapy in metastatic cancer. In the context of follow-up serum MCA levels appear to be a sensitive indicator of metastatic disease; caution is required in the interpretation of isolated measurements.
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PMID:An evaluation of mucin-like carcinoma associated antigen (MCA) in breast cancer. 273 16

The diagnostic value of mucin-like carcinoma-associated antigen (MCA) was compared to that of carcinoembryonic antigen (CEA) and/or CA 15.3 in patients with breast cancer. A total of 368 patients with breast cancer were studied, of whom 253 were free of metastases, whereas 94 had either skeletal or visceral metastases or diffuse metastatic disease. The diagnostic sensitivity of MCA proved to be comparable to that of CA 15.3 and superior to that of CEA in patients with metastatic breast cancer. In contrast, the specificity of MCA was superior to that of CA 15.3. Finally, the diagnostic sensitivity of each of the tested tumour markers, i.e. MCA, CEA and CA 15.3, could be improved by their combined use. We conclude that MCA, either alone or in combination with CA 15.3 and CEA, can improve the monitoring of disease progression in patients with metastatic breast cancer.
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PMID:Diagnostic value of mucin-like carcinoma-associated antigen (MCA) in breast cancer. 275 62

A mucin-like carcinoma-associated antigen (MCA) was recently identified on the surface of established breast cancer cell lines by several monoclonal antibodies. The antibody b-12 was used in a sandwich enzyme immunoassay to measure MCA concentrations in serum samples and other biological fluids. The upper limit for noncancerous women and men was 14 U/ml. MCA levels were independent of estrogen or prolaction secretion, 63% of patients with metastatic breast cancer had elevated serum concentrations of MCA. Elevated MCA levels were also associated with cervical, ovarian or endometrial cancer and carcinoma of the prostate. In metastatic breast cancer, MCA and CA 15.3 showed similar sensitivity. Carcinoembryonic antigen levels did not correlate with MCA. Serum concentrations of MCA increased during pregnancy and remained elevated in nursing mothers. Amniotic fluid was found to be rich in MCA. In contrast, CA 15.3 showed only small changes during pregnancy and was low in amniotic fluid. From binding tests with antibodies used in the MCA and CA 15.3 assays, we conclude that the monoclonal antibodies b-12 as well as 115-D8 and DF3 (CA 15.3 assay) recognize coexisting epitopes on mucin-like antigens, which belong to a polymorphic family of glycoproteins suitable for tumor monitoring. Differences in the behavior of MCA and CA 15.3 may emerge from the complexity and heterogeneity of these mucin-like antigens.
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PMID:MCA, a monoclonal-antibody-defined breast-tumor-associated antigen and its relation to CA 15.3. 281 32

Serum levels of carcinoembryonic antigen (CEA), mucin-like carcinoma-associated antigen (MCA), CA 15.3 and CA 549 were concurrently assayed in patients with metastatic breast cancer. Overall sensitivity in detecting metastatic breast cancer (201 pts) was CEA 45%, MCA 59%, CA 15.3 71% and CA 549 72% (P < 0.01). Sensitivity increased by only 6% to 8% when two or more antigens were simultaneously considered. An overall sensitivity of correlation with objective response (n = 71) was observed in the range of 53-67% (P = n.s.) in patients with abnormal baseline marker values, and in the range of 42-87% (P < 0.05) in patients with normal baseline values. The combination of two or more markers did not improve sensitivity, but decreased specificity of correlation with objective response. In conclusion, CA 15.3 and CA 549 have individually higher sensitivity in detecting metastatic breast cancer. No clinical advantage was observed for using two or more markers concurrently over CA 15.3 or CA 549 alone in the monitoring of metastatic breast cancer.
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PMID:CEA, MCA, CA 15.3 and CA 549 and their combinations in expressing and monitoring metastatic breast cancer: a prospective comparative study. 748 11

Several investigators have shown that the expression of the sialyl-Tn (STn) epitope on cancer associated mucins is associated with a poor prognosis in several human cancers suggesting that STn may have functional significance in metastasis. We postulate that antibodies against the STn-epitope can inhibit metastasis. We generated a synthetic "mimic", NANA alpha (2-->6)GalNAc alpha-O-Crotyl (STn-crotyl), of the natural O-linked epitope on mucins, NANA alpha (2-->6)GalNAc alpha-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier protein KLH through the crotyl linker arm and a "vaccine" containing STn-KLH plus Detox adjuvant was formulated. The immunogenicity of the vaccine was evaluated in BALB/c mice and in metastatic breast cancer patients. The specificity and titres of IgG antibodies were evaluated by ELISA on ovine submaxillary mucin (OSM) solid phases. OSM is a convenient source of repeating, natural O-linked STn-serine structures. Mice immunized three times with as little as 0.25 microgram of STn-KLH produced a median IgG titre of over 1:5000 on solid phase OSM. Anti-OSM IgG monoclonal antibodies generated from these mice were completely inhibited in their binding to solid phase OSM equally well by STn-serine and STn-crotyl synthetic haptens but not by several other closely related synthetic haptens. Breast cancer patients immunized 2-8 times with 25 or 100 micrograms of the same vaccine produced median peak IgG titres 1:1280 measured on STn-HSA and 1:80 on OSM. Once again, hapten inhibition experiments with the human sera demonstrated the specificities of the IgG antibodies for STn-crotyl and STn-serine, but not against several other related synthetic haptens. We found little or no evidence that the artificial linker arm (crotyl linker) contributed significantly to either the titre or affinity of the antibodies generated in either mice or human breast cancer patients. This suggests that the antibodies recognized the cancer-associated disaccharide NANA alpha (2-->6)GalNAc. Evidence of a clinical response was noted in several of the immunized breast cancer patients with other patients showing prolonged disease stability.
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PMID:Specificity of the IgG response in mice and human breast cancer patients following immunization against synthetic sialyl-Tn, an epitope with possible functional significance in metastasis. 752 78

Levels of mucin-like carcinoma-associated antigen (MCA), CA15.3 and carcinoembryonic antigen (CEA) were measured in consecutive serum samples of 40 women with metastatic breast cancer. A change in antigen level of more than 25%, either an increase or a decrease, was considered to predict progressive or responsive disease respectively. A change of less than 25% was considered to predict stable disease. MCA, CA15.3 and CEA were elevated in the serum of 68%, 76% and 48% of the patients respectively (P < 0.05). The overall prediction of clinical course was similar for all three markers. A more than 25% increase of MCA, CA15.3, and CEA was observed in 61%, 54% and 36% respectively. The predictive value of a more than 25% increase was high for all three markers: 94%, 94%, 83%. Changes in marker levels were correlated with each other. Logistic regression analysis showed that combining MCA and CA15.3 did not improve the prediction further. In conclusion, these tumour markers may help in evaluating the disease course and there is no advantage in combining MCA and CA15.3.
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PMID:The usefulness of CA15.3, mucin-like carcinoma-associated antigen and carcinoembryonic antigen in determining the clinical course in patients with metastatic breast cancer. 763 72

We generated a synthetic epitope, NANA alpha(2-6) GalNAc alpha-O-Crotyl (STn-crotyl), designed to "mimic" the natural O-linked epitope expressed on human carcinoma cells, NANA alpha(2-6)GalNAc alpha-O-Serine (STn-serine). STn-crotyl was conjugated to the carrier protein KLH through the crotyl linker arm, and a "vaccine" containing STn-KLH plus DETOX adjuvant was formulated. The immunogenicity of the vaccine was evaluated preclinically in CAF1 mice and subsequently in patients with metastatic breast cancer. The specificity and titers of IgG antibodies were evaluated by kinetic ELISA on synthetic STn-HSA and on ovine submaxillary mucin (OSM) solid phases. Ovine submaxillary mucin is a convenient source of repeating, natural O-linked STn-serine structures. Mice immunized three times with as little as 0.25 micrograms of STn-KLH produced IgG titers ranging from 1:10(4) to 1:10(5) when tested on solid phase OSM. Anti-OSM IgG, both polyclonal and monoclonal antibodies, generated from these mice were completely inhibited in their binding to solid phase OSM equally well by STn-serine and STn-crotyl synthetic haptens but not by several other closely related synthetic haptens. These monoclonal antibodies also bound to STn determinants on human tumor cell surfaces. Breast cancer patients immunized with 100 micrograms of the same vaccine produced median peak IgG titers 1:1280 measured on STn-HSA and 1:160 on OSM. Hapten inhibition experiments with the human sera demonstrated the specificities of the IgG antibodies for STn-crotyl and STn-serine, but not against several other related synthetic haptens. We found little evidence that the artificial linker arm (crotyl linker) contributed substantially to either the titer or affinity of the antibodies generated in either mice or human breast cancer patients. This suggests that the antibodies recognized the cancer-associated disaccharide NANA alpha(2-->6)-GalNAc. Small but not large doses of STn-KLH immunogen induced anti-STn DTH responses in mice that were inversely proportional to the antibody responses. Evidence of a clinical response was noted in some of the immunized breast cancer patients, with other patients showing prolonged disease stability.
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PMID:Immune responses of mice and human breast cancer patients following immunization with synthetic sialyl-Tn conjugated to KLH plus detox adjuvant. 769 Feb 15


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