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Biomedical subjects

M J Embleton

Publications and source records attributed to M J Embleton.

At least 73 records · Page 4Linked to original sources
PubMed1980

Multiple antigenic specificities within primary 3-methylcholanthrene-induced rat sarcomas and metastases.

Sarcomas were induced in WAB/Not rats by subcutaneous injection of 10, 5 or 1 mg 3-methylcholanthrene (MCA) but not by 0.1 mg. Although tumours appeared earlier in rats given 10 mg MCA, compared with 1 mg, the majority of transplant lines from primary tumours were immunogenic and there was no correlation between the inducing dose of carcinogen and the growth characteristics or immunogenicities of the transplant lines. Most importantly sublines established from opposite poles of primary sarcomas were antigenically distinct in a substantial portion of cases, indicating that the primary tumours consisted of antigenically heterogeneous populations of cells. Furthermore, with one rat, renal and pulmonary metastases were antigenically distinct from a peritoneal secondary and the primary growth. These findings indicate that primary carcinogen-induced tumours may be polyclonal in origin and this has implications for both the understanding of the carcinogenic process, and for the immunotherapy of malignant disease.

Animals↗
PubMed1979

Tumour-related antigen specificities associated with 3-methylcholanthrene-treated rat embryo cells.

Rat embryo cells were treated in vitro for 18 h with 10 micrograms/ml 3-methylcholanthrene (MCA). Syngenetic male rats were immunized with several inocula of treated cells to prepare antisera which were screened for membrane immunofluorescence reactivity against panels of established chemically-induced syngeneic rat tumours. Three separate antiserum pools raised against MCA-treated cells reacted with certain chemically-induced tumours, whereas antisera to control (DMSO-treated) cells were completely negative. The reactions observed were reproducible and highly specific for particular target tumours. Absorption studies indicated that each antiserum contained antibodies to several different antigens, present on different tumours. Antiserum prepared against extranuclear membrane from MCA-treated cells, rather than intact MCA-treated cells, was negative. This suggests that the antibody responses were directed against antigens arising subsequently to MCA treatment and injection into syngeneic hosts. It is postulated that carcinomgen treatment results in the acquisition of multiple neoantigens among a treated cell population, which represent an early change in a sequence of events leading to malignant transformation.

Animals↗
PubMed1978

Surface antigens of rat liver epithelial cells grown in medium containing foetal bovine serum.

Cultured rat liver cells induced a strong antibody response in syngeneic rats, directed against foetal calf serum components which were incorporated into the liver cell surface from the cell-culture medium. This antibody could be removed by absorption with liver cells or glutaraldehyde-fixed foetal calf serum. It is possible that the antigenic cross-reactivity observed in earlier studies with cultured cells treated with carcinogens could be due to this foetal calf serum component.

Animals↗
PubMed1978

Immunological monitoring in a controlled trial of immunotherapy in stage IIB malignant melanoma.

Fifteen patients undergoing surgery for Stage IIb malignant melanoma were randomly allocated either to a group who received a vaccine of BCG mixed with irradiated autologous melanoma cells, or a control group who received no further treatment. All patients were monitored sequentially for immunological competence and tumour-directed immunity, using a wide range of techniques, and the results were compared retrospectively with their clinical course. Three months after surgery, there was a trend towards inhibition of PHA-induced lymphocyte transformation by autologous serum in patients who developed recurrent tumour within 12 months after treatment. Serum from patients who remained tumour-free for 12 months did not inhibit stimulation of autologous lymphocytes by PHA. Apart from this test, no other immunological parameters correlated either with clinical course or with the type of treatment received.

Antibody Formation↗
PubMed1977

Controlled trial of active immunotherapy in management of stage IIB malignant melanoma.

The prognosis for patients who undergo surgery for stage IIB malignant melanoma is poor. Animal studies have suggested that BCG and tumour cell vaccines given together may provide effective immunotherapy. To assess the effectiveness of this treatment 15 patients with stage IIB malignant melanoma who had their tumour excised were studied. Seven were treated conservatively, and eight were vaccinated with BCG and autologous irradiated cells. Three vaccinated patients suffered widespread recurrence within three months. All four vaccinated patients who suffered a recurrence within the first year died, while none of the three controls with recurrent disease died. In view of this alarming trend the trial was stopped after a year. BCG and the tumour cells may have enhanced the tumour growth, although there was no apparent reason for this. The results of uncontrolled or unrandomised trials that have suggested that this treatment is beneficial should be treated with scepticism.

BCG Vaccine↗
PubMed1976

Influence of cell-free tumour-associated antigen preparations on the development of immunity to chemically induced rat tumours.

Inbred rats were treated with extranuclear tumour membrane fractions or 3 M KCl-solubilized extracts of two antigenically distinct 3-methylcholanthrene-induced sarcomas, Mc7 and Mc57. The rats developed tumour-specific humoral antibody responses, but were not immune to tumour challenge. Moreover, they were unresponsive to subsequent immunization with irradiated tumour grafts, this effect being immunologically specific for the tumour from which the cell-free extracts was derived. In vitro studies revealed a depressed state of cell-mediated tumour immunity in animals inoculated with cell-free tumour extracts, and this was associated with the presence of serum inhibitory factors and suppressor lymphoid cells which abrogated the cytotoxic effect of sensitized lymphoid cells in vitro. It is postulated that the development of an inappropriate immune response due to the effect of tumour antigen during the induction phase of tumour immunity may be relevant to the immunobiology of tumour-bearing hosts.

Animals↗
PubMed1976

Assessment of cell-mediated immunity to malignant mesothelioma by microcytotoxicity tests.

Cell cultures were established from pleural effusions of patients with pleural mesothelioma, and peripheral mononuclear effector cells were tested for cytotoxicity against these cells by means of microcytotoxicity assay. Effector cells were obtained from normal healthy donors and from persons exposed occupationally to asbestos, including apparently healthy persons, patients with benign pleural conditions and patients with malignant mesothelioma. The overall incidence of cytotoxicity was low, and there was no evidence of increased cytotoxicity in mesothelioma patients or other asbestos-exposed donors. It is concluded that little or no tumour-directed cell-mediated immunity is detectable against malignant mesothelioma by microcytotoxicity methods.

Asbestos↗
PubMed1976

Treatment of transplanted rat tumours with double-stranded RNA (BRL 5907). I. Influenced of systemic and local administration.

Growth of transplanted rat tumours was retarded and in some cases completely suppressed when cells were injected subcutaneously in admixture with double stranded RNA (ds-RNA). This response required intimate contact between ds-RNA and tumour cells and systemic treatment with the agent failed to prevent progressive growth of a range of rat tumours. Direct cytotoxic effects of ds-RNA may contribute to tumour suppression since the compound was cytotoxic in vitro for cultured tumour cells. The involvement of host factors is suggested, however, by the in vivo tests showing variations in susceptibility to ds-RNA mediated tumour suppression similar to that previously observed with bacterial adjuvants.

Animals↗
PubMed1976

Effect of BCG on cell-mediated cytotoxicity and serum blocking factor during growth of rat hepatoma.

Inbred rats were injected s.c. with cells of syngeneic hepatoma D23, D23 cells + BCG as a mixed inoculum, mixed inoculum one side and D23 alone contralaterally, or BCG alone. Their blood mononuclear cells were tested weekly for cytotoxicity against D23 target cells using a microcytotoxicity method and their serum was tested for blocking activity against cytotoxicity by lymph node cells from immunized rats. Tumour growth was suppressed when BCG was in contact with tumour cells but tumours grew unhindered if the BCG was given contralaterally. All rats receiving tumour cells, either alone or mixed with BCG, developed cell-mediated cytotoxicity which remained until termination at 35 days. Rats receiving BCG alone showed slight initial cytotoxicity which disappeared after 7 days. Blocking factors appeared in the serum of rats which developed growing tumours but not in rats whose tumours were suppressed by contact with BCG. Splenectomized rats did not differ markedly from intact rats in the in vitro studies or in vivo. It is concluded that development of cell-mediated immunity and blocking factors depends more upon treatment with tumour cells and the subsequent behaviour of the tumour than upon treatment with BCG per se.

Animals↗
PubMed1975

Neoantigens on chemically transformed cloned C3H mouse embryo cells.

Using an in vitro cytotoxicity test for cell-mediated immunity and a membrane immunofluorescence test, the appearance of new antigens was detected on cloned C3H mouse embryo cells undergoing malignant transformation in vitro following treatment with 3-methylcholanthrene or 7,12-dimethylbenz[a]anthracene. These antigens were recognized by specifically immunized syngeneic mice and were individually unique for each of eight chemically transformed cell lines tested, all of which were derived from the same control parent clone. Very few cross-reactions were seen between lymphoid cells or antibody from mice immunized against a given cell line and target cells of other cell lines. New antigens could not be detected on two spontaneously transformed lines. Lymphoid cells from multiparous pregnant or embryo-immunized cmice were used to search for fetal antigens on control and transformed cells. Fetal antigens were detected on seven of the chemically transformed cell lines and one spontaneous transformant, but not on nontransformed control cells. It is concluded that individually specific new antigens are characteristic of chemically transformed cells, but the expression of fetal antigens may be a more common feature of transformed cells in general.

9,10-Dimethyl-1,2-benzanthracene↗