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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A murine monoclonal antibody, TA1, is directed against an epitope on the extracellular domain of the HER-2/neu (c-erbB-2) gene product. Requirements for TA1-induced internalization of c-erbB-2 have been studied using the SKBr3 human breast cancer cell line and several rat fibroblast cell lines that express either wild-type or mutant human c-erbB-2. Internalization of TA1 was monitored by assaying protease-resistant uptake of 125I-labeled TA1, by electron microscopy of gold-labeled TA1, and by inhibition of clonogenic growth of cells incubated with TA1 that had been conjugated with blocked ricin. Similar rates of internalization of TA1 were observed in SKBr3 and in rat fibroblasts that expressed human c-erbB-2. The route of endocytosis was the same as that observed with antibodies against other membrane receptors. Anti-c-erbB-2 and anti-transferrin receptor cointernalized through clathrin-coated pits, coated vesicles, endosomes, and multivesicular bodies. Products of mutant c-erbB-2 that lacked a portion of the tyrosine kinase domain or that lacked most of the cytoplasmic domain were endocytosed in the presence of TA1 as promptly as the wild-type c-erbB-2 product. Slightly more rapid internalization of TA1 was observed in rat cells that expressed c-erbB-2 with a single point mutation in the transmembrane domain. Taken together, our data suggest that neither the intracytoplasmic domain nor receptor phosphorylation is required for antibody-mediated endocytosis of c-erbB-2.
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PMID:Requirements for the internalization of a murine monoclonal antibody directed against the HER-2/neu gene product c-erbB-2. 168 May 47

This study reports the characterization of a breast cancer-associated antigen identified by murine monoclonal antibody (MoAb) RCC-1 (formerly called 24-17.1). Immunoperoxidase staining indicated that RCC-1 recognized an antigen highly expressed in malignant tumours of breast origin, and no reactivity was noted with connective tissue, muscle or lymph nodes, which is an important consideration in its successful use in immunolymphoscintigraphy. The RCC-1 was shown to consist of 94,000 dalton disulfide-bonded dimers which were shown to be different from the transferrin receptor. In addition, the antibody RCC-1 did not react with components of human milk or with an antigenic peptide derived from the core protein of a mammary mucin. Chemical treatment and enzymatic digestion suggested that the epitope recognized by antibody RCC-1 was protein as it was resistant to neuraminidase and periodate treatment but was sensitive to trypsin. The RCC-1-defined antigen detects a novel breast cancer associated antigen.
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PMID:Characteristics of a breast cancer-associated antigen defined by RCC-1 antibody. 169 83

The primary tumour cells and tumour infiltrating lymphocytes (TILs) of 31 breast cancer patients have been analysed by dual colour flow cytometry to determine whether the phenotype and/or activation status of the TILs bears any relationship to the expression of MHC antigens on the tumour cells. The phenotype and activation status of 5000 TILs were studied using Mabs to CD4, CD8, HLA DR, CD25 (the low affinity inducible IL-2 receptor) and the transferrin receptor and related to Class I and Class II MHC expression on 5000 primary tumour cells. On the tumour cells, Class I MHC expression ranged from 1-74%, averaging 12.9%. HLA DR expression ranged from 1-69% averaging 14.3%. When the phenotypic proportions of the lymphocytic infiltrate were analysed there was found to be a correlation between tumour expression of Class I MHC and the proportion of both CD4+ (P less than 0.05) and CD8+ (P less than 0.02) T cells within the tumour. No such relationship was found with the MHC Class II antigen. When TIL activation markers were analysed, the percentage of CD8+ TILs positive for HLA DR expression correlated strongly with the expression of Class I (P less than 0.001) and Class II (P less than 0.001) antigens on the tumour cells. The percentage of CD4+ TILs positive for HLA DR expression also correlated significantly, but less strongly with the expression of Class I (P less than 0.01) and Class II (P less than 0.02) antigen expression on the tumour cells. The percentage of CD4+ TILs positive for CD25 expression correlated with both Class I (P less than 0.05) and Class II (P less than 0.03) expression on the tumour cells while the percentage of CD8+ TILs positive for CD25 did not. The percentage of TILs bearing the transferrin receptor showed no measurable correlation with the expression of either class of MHC antigen on the tumour. The data suggest that MHC expression on the tumour cells has a selective effect on the response capacity of different parts of the immune system.
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PMID:Flow cytometric analysis of tumour infiltrating lymphocyte activation and tumour cell MHC class I and II expression in breast cancer patients. 173 Jan 39

When estradiol stimulation was performed on hormone-responsive MCF-7 human breast cancer cells maintained in phenol red-containing medium until 24h before experiments, the cell number and the cell surface transferrin receptor level, an early marker of estradiol stimulation, were strongly increased. In contrast, similar treatment performed on MCF-7 cells grown in phenol red-free medium up to 12 months before experiments induced no stimulating effect on the cell number, although transferrin receptors were still enhanced. Since the appearance of transferrin receptors occurs before the cells begin DNA synthesis in late G1 phase, we assumed that the discrepancy between cell counts and cell surface transferrin receptors might involve cell kinetic perturbations. The proportion of cells in the (S + G2) phases and the duration of the cell cycle phases were analysed using the SAMBA 200 cell image processor. The data presented in this study failed to indicate any block in the cell cycle and the duration of the S and G2 phases were found to be unchanged. The lack of effect of estradiol stimulation on the growth of MCF-7 cells maintained several months without phenol red is not thus a consequence of cell cycle perturbations.
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PMID:Cell kinetics (SAMBA 200) of estradiol stimulated long-term phenol red withdrawn cultured breast cancer cells. 238 77

Catecholestrogens and especially 2-hydroxyestrone (2OH-E1) are estradiol metabolites locally formed in breast cancer cells. The present study demonstrates that the two parent compounds, estradiol (E2) and its metabolite 2OH-E1, exert opposite effects on hormone-sensitive breast cancer cell growth assessed by cell counts and transferrin receptor levels, and also on cell differentiation assessed by secreted proteins such as alpha-lactalbumin and gross cystic disease fluid protein (GCDFP-15). The present findings may highlight estradiol regulation in hormone-sensitive breast cancer cells.
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PMID:Opposite effects of estrogen and catecholestrogen on hormone-sensitive breast cancer cell growth and differentiation. 253 43

A presently undefined nuclear antigen recognized by the monoclonal antibody Ki-67, and the transferrin receptor (TR), both expressed by proliferating cells, were visualized in cryostat sections of 40 consecutive cases of primary breast cancer using a three-step immunoperoxidase technique. The percentages of Ki-67 and TR positive cells were determined. A strong positive correlation was observed between these two indices of proliferation (p less than 0.01). Moreover, each of them was positively related to the histological tumour grade (p less than 0.01), although the scatter in the number of proliferating cells within each grade was large. No significant relation (p greater than 0.05) was found between the percentages of Ki-67 and TR positive cells and tumor size and between these values and axillary node status. These correlations are similar to those recently reported in the relevant literature and suggest that immunohistochemical assessment of proliferative activity may prove to be an objective indicator of biological behaviour and therefore be of clinical and therapeutical importance.
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PMID:Correlation of proliferative activity with pathological features in breast carcinoma. 262 76

Recombinant ricin A chain was chemically linked to monoclonal antibodies directed toward human breast cancer cells, a human T-cell differentiation antigen, and mouse transferrin receptor. Three types of immunotoxins were prepared; in two of them the antibody was linked to recombinant ricin A chain by a disulfide bond and in the third, a nonreducible thioether bond was used. Immunotoxins containing a nonreducible linkage may have some advantage over conjugates containing a reducible linkage because of improved stability in vivo. Conjugation of recombinant ricin A chain through either the endogenous thiol group or through a derivatized amino group produced immunotoxins with comparable cytotoxicity. The thioether conjugate was 1000-fold less cytotoxic to target tumor cells than the respective disulfide-linked immunotoxin. However, addition of monensin, a monocarboxylic ionophore, greatly enhanced the cytotoxicity of the thioether-linked immunotoxin. Monensin increased the immunotoxin activity better than other lysosomotropic reagents that were tested. The increase in activity of recombinant ricin A chain-containing immunotoxins mediated by monensin argues against a role for contaminating ricin B chain in potentiation.
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PMID:Recombinant ricin A chain conjugated to monoclonal antibodies: improved tumor cell inhibition in the presence of lysosomotropic compounds. 278 83

Transferrin receptors were demonstrated on the cell membrane of breast cancer epithelial cells in primary or long-term culture. Diferric transferrin binding was saturable, specific and was not related to DNA content or clinical and histological features of the tumour. However a good correlation (p less than 0.01) was found between transferrin binding and thymidine incorporation. These results suggest the possibility of transferrin receptor measurement as a reflection of the proliferative activity of cultured breast tumour cells.
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PMID:Transferrin receptors in cultured breast cancer cells. 299 Dec 95

The transferrin receptor (TfR) has been identified as a marker for proliferation in cells in culture and can be accurately quantitated by specific radioimmunoassay. This study directly quantifies levels of TfR and compares them to levels of estrogen receptor (ER) and progesterone receptor (PgR) in biopsy material obtained from patients with infiltrating ductal carcinoma of the breast. A comparison of ER and TfR levels displayed an exponential distribution which was log-normalized to yield a linear inverse relationship (r = -.44). Although ER was strongly correlated with PgR, there was no correlation pattern between TfR and PgR. Multiple regression analysis indicated that 73% of ER levels could be predicted by a combination of the other two markers, PgR (representing degree of differentiation) and TfR (representing growth rate). Transferrin receptor levels were also found to be correlated (p less than .05) with menopausal status, with tumors from premenopausal patients exhibiting higher levels, whereas the opposite pattern was shown for estrogen receptor levels (p less than .02). Neither steroid receptor nor transferrin receptor levels were correlated to stage of disease or presence of nodal involvement. Addition of TfR level as an independent marker for proliferation may facilitate the decision-making process in the treatment of individual cases of carcinoma of the breast.
Breast Cancer Res Treat 1986
PMID:Transferrin receptor is inversely correlated with estrogen receptor in breast cancer. 301 49

The present study evaluates whether the in vitro activity of immunotoxins can be enhanced by verapamil or by various antagonists of calmodulin (dansylcadaverine, trifluoperazine, chlorpromazine). The following immunotoxins made with either Pseudomonas exotoxin (PE), recombinant ricin A chain (rRTA), or ricin A chain (RTA) were used: HB21-PE and 454A12-rRTA that both recognize the human transferrin receptor; and 260F9-rRTA and 454C11-RTA that both react with human ovarian and breast cancer cells. The cytotoxicity of these immunotoxins was determined in human ovarian carcinoma cell lines and KB cells. Verapamil, that was demonstrated previously to enhance the cell-killing activity of PE immunotoxins, enhanced the activity of several ricin A chain immunotoxins, including 454A12-rRTA, 260F9-rRTA, and 454C11-RTA. Comparing 50% inhibitory dose values for inhibition of protein synthesis by 454A12-rRTA, enhancement ranged from 2- to greater than 25-fold, was dependent on the concentration of verapamil, and was greatest at short incubation times. In addition, the cytotoxicity of HB21-PE and of selected RTA immunotoxins was increased up to 30-fold by the addition of various calmodulin antagonists. The enhancing drugs did not decrease the specificity of the immunotoxins.
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PMID:Enhancement of the activity of immunotoxins made with either ricin A chain or Pseudomonas exotoxin in human ovarian and epidermoid carcinoma cell lines. 326 Jan 28


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