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J Burchell

Publications and source records attributed to J Burchell.

50 records · Page 3Linked to original sources
PubMed1986

Detection of the urinary 'PUM' polymorphism by the tumour-binding monoclonal antibodies Ca1, Ca2, Ca3, HMFG1, and HMFG2.

A series of human urinary mucin-like glycoproteins, previously detected using lectins to stain gels after electrophoresis, and showing genetic polymorphism (Karlsson et al., 1983) can also be detected using the tumour-binding monoclonal antibodies, Ca1, Ca2, Ca3, HMFG1, and HMFG2. The evidence from immunoprecipitation and immunoadsorbant chromatography experiments is that the epitopes recognized by these antibodies are carried on the same molecules as the lectin-binding determinants. The discovery that the antibodies bind specifically to a family of molecules which show genetic polymorphism provides a powerful new tool for the analysis of the material expressed aberrantly in cancer.

Antibodies, Monoclonal↗
PubMed1985

Production and characterization of monoclonal antibodies to human casein. A monoclonal antibody that cross-reacts with casein and alpha-lactalbumin.

Four hybridomas have been produced that secrete monoclonal antibodies to human beta-casein, a protein synthesized by fully differentiated breast epithelial cells. The antibodies have been characterized on immunoblots and have been shown to react with methanol: acetone-fixed sections of human lactating mammary gland. Immunoblots show that three of these antibodies react with casein whereas one, F20.10, also recognizes an epitope present on human alpha-lactalbumin. Computer analysis of the amino acid sequences of these two milk proteins reveals very little sequence homology, leading to the conclusion that the three-dimensional shape, rather than the primary sequence, is important in this cross-reactivity.

Amino Acid Sequence↗
PubMed1985

Radioimmunodetection in patients with suspected ovarian cancer.

Twenty-five patients, having either unilateral ovarian tumors of unknown etiology or suspected of having ovarian cancer recurrence were investigated by the method of immunoscintigraphy to rule out primary and/or metastatic tumor sites. Four-hundred micrograms of the tumor-associated monoclonal mouse antibody HMFG-2, raised against human milk fat globulin membranes and labeled with 123I, were used for each patient to display the tumor sites by external scintigraphy. The dose ranged between 0.5 and 2.2 mCi, the specific activity between 1.25 and 5.5 mCi per mg of antibody. Nineteen of the patients underwent operations a few days after immunoscintigraphy. The remaining six patients were investigated by transmission computed tomography (TCT) to establish the presence or absence of tumor of the imaging. In 22 of the 25 cases the scintigraphic results correlated with the situation found at the subsequent operation, or by TCT, respectively, as well as with the histological diagnosis of the tumor type. Overall, there were just two false-negative and one false-positive scan report, the latter due to faulty reading of the scintigrams. Sixteen out of 18 tumor sites in 25 patients could be revealed by immunoscintigraphy, the smallest one being 1.5 cm in diam. In four of the patients immunoscintigraphy was the only noninvasive investigation method that could reveal the malignant tumor sites prior to the operation.

Adult↗
PubMed1984

Detection of the tumour-associated antigens recognized by the monoclonal antibodies HMFG-1 and 2 in serum from patients with breast cancer.

The levels of the human milk fat globule 1 and 2 antigens have been measured in the sera of patients with advanced breast cancer, using a "sandwich" type radioimmune assay which exploits the carbohydrate nature of the antigenic determinants. In the series studied, 30% of sera from advanced breast cancer patients contained elevated levels of the HMFG-I antigen as compared with 6% of sera from healthy control women, whereas 53% of the advanced breast cancer patients showed elevated levels of HMFG-2 antigen compared with 16,6% of the controls. By means of the immune blotting technique, the components carrying the antigenic determinants in sera have been identified and compared for size with those molecules expressing the determinants in primary and secondary breast tumours. Both antibodies react with similar molecular weight components of 320kd and 280kd which are present in serum and tumour samples, although lower molecular weight bands of 230kd and 190kd can be seen in some tumours. These components are much smaller than the glycoprotein (greater than 400kd) present in the human milk fat globule, which carries the antigenic determinants recognized by HMFG-I and 2.

Antibodies, Monoclonal↗
PubMed1984

[Visualization of malignant tumors in the abdomen using radiolabelled monoclonal antibodies].

The production of monoclonal antibodies by the hybrid technique introduced by Köhler and Milstein in 1975, led to new dimensions in the diagnosis and therapy of malignant diseases. Labelling such monoclonal antibodies, directed against tumour cells, by a radioactive isotope, makes them usable for visualising malignant tumours and their metastases. Early detection of cancer may represent a major step forward in cases where early detection is not possible with common noninvasive methods, such as ovarian cancer in gynaecological oncology. Radioimmunoscintigrams (RIS) were performed in seven patients, all of whom were suspect of having ovarian cancer. The RIS-results showed very good correlations with the operation reports. According to these first results we assume that the RIS method using I123-labelled monoclonal antibodies directed against tumour cells may be successful in the early detection of ovarian cancer. Other important information supplied by radioimmunoscanning is determination of tumour status, localisation, extent or metastatic spread.

Abdominal Neoplasms↗
PubMed1984

Monoclonal antibodies for successful tumour imaging.

The monoclonal antibody HMFG-2 which is directed to an oligosaccharide determinant on a large molecular weight mucin-like molecule found in the human milk fat globule reacts positively with breast and ovarian carcinomas. The purified antibody, labelled with 123I has been used successfully to locate ovarian tumours and their metastases in 20 out of 22 patients tested. Here we discuss those features of a) the antibody, b) the antigenic site it reacts with, c) the radioactive label and d) the scanning technique, which have contributed to the successful application of HMFG-2 to the effective imaging of ovarian tumours.

Antibodies, Monoclonal↗
PubMed1981

Monoclonal antibodies to epithelium-specific components of the human milk fat globule membrane: production and reaction with cells in culture.

Three hybridomas producing monoclonal antibodies (IgG), reacting with components of the human mammary milk fat globule have been isolated. When tested for binding to a wide range of human cell lines and strains, all three antibodies show negative reactions with fibroblasts, lymphoblastoid cells, and a large number of epithelial cell lines of non-breast origin. Two of the antibodies (1.10.F3 and 3.14.A3) reacted with seven out of eight breast cancer lines tested, and with epithelial cells cultured from human milk. The other antibody (3.15.C3) reacted with only two of the breast cancer cell lines.

Animals↗
PubMed1981

Production of fibronectin by normal and malignant human mammary epithelial cells.

The production and retention of fibronectin by primary cultures of cells derived from the human breast has been analyzed. Two examples of each of the following cell types were examined: (a) normal epithelium from milk; (b) metastatic breast cancer cells in pleural effusions; (c) fibroblasts; (d) tissue macrophages of milk. Cell-associated fibronectin could be detected by indirect immunofluorescent staining on normal and malignant mammary epithelium and on mammary fibroblasts, but not on milk macrophages. Immune precipitation followed by gel electrophoresis of 35S-labeled cell lysates and conditioned medium confirmed that fibronectin was indeed synthesized by both types of epithelial cells and by fibroblasts, but not by macrophages, and that much of the protein was released into the medium. Quantitative analysis with radioimmune assay of the fibronectin on cells and in media showed that both normal and malignant epithelial cells synthesized levels of protein comparable to that produced by fibroblasts, but only a small fraction (less than 10%) of the material synthesized was retained by the cells. Growth on collagen-coated plastic increased the percentage of fibronectin retained by normal and malignant epithelium but did not affect retention by fibroblasts.

Breast Neoplasms↗
PubMed1980

Differential effect of interferon on DNA synthesis, 2-deoxyglucose uptake and ornithine decarboxylase activity in 3T3 cells stimulated by polypeptide growth factors and tumor promotors.

Quiescent 3T3 cells can be stimulated to enter S by defined factors. When used in combination, three polypeptide hormones (EGF, vasopressin, and insulin), or a tumor promotor and insulin, are very effective in stimulating DNA synthesis. Like serum, the defined factors also stimulate deoxyglucose uptake and induce the synthesis of ornithine decarboxylase during G1. The second stage of deoxyglucose uptake and the induction of ornithine decarboxylase are protein synthesis-dependent events. When added with the growth factors, mouse interferon inhibits the synthesis of DNA and the induction of ornithine decarboxylase but has no effect on the uptake of deoxyglucose. Kinetic experiments comparing the effect of inhibitors of translation or transcription on induction of ornithine decarboxylase with the effect of interferon suggest that interferon may affect the synthesis of enzyme by inhibiting both transcription and translation of message. The findings provide further support for the proposition that interferon exerts a differential effect on mitogen-stimulated events events which are dependent on continuous protein synthesis.

Animals↗
PubMedDate not supplied

The breast tumour-associated epithelial mucins and the peanut lectin binding urinary mucins are coded by a single highly polymorphic gene locus 'PUM'.

A family of mucin-type glycoproteins, present in human urine, is coded by a single highly polymorphic gene locus PUM. We have previously shown that these glycoproteins carry epitopes recognized by a series of monoclonal antibodies, many of which were raised to the human milk-fat globule membrane, and which bind to a wide variety of carcinomas and certain normal epithelia. Here we show that in the normal human mammary gland, and in breast cancers the epitopes are present on the same family of molecules as that found in urine. Thus the genetically determined variation at the PUM locus accounts for much of the electrophoretic heterogeneity of the mucin-type glycoproteins present in breast cancer and serum from breast cancer patients that has been reported previously. Knowledge of this normal inherited polymorphism is essential to the interpretation of possible changes to these molecules in malignancy.

Antigens, Neoplasm↗