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P Alexander

Publications and source records attributed to P Alexander.

At least 181 records · Page 10Linked to original sources
PubMed1973

Radioimmunoassay of tumour specific transplantation antigen of a chemically induced rat sarcoma: circulating soluble tumour antigen in tumour bearers.

The tumour specific transplantation antigen (TSTA) from a chemically induced rat sarcoma has been isolated as an electrophoretically homogeneous soluble material by affinity chromatography using a Sepharose bound antibody raised to the tumour in syngeneic rats. The TSTA is specific for the particular tumour used (the MC-1 sarcoma) and does not cross-react with material extracted from other rat sarcomata. In addition, a material with different physicochemical properties which cross-reacted with different sarcomata was also eluted from the antibody column and this may be the previously identified onco-embryonic antigen (OEA1) which is immunogenic in the syngeneic host.The purified TSTA labelled with (125)I was used in a radioimmunoassay which detected soluble TSTA in rats bearing a MC-1 sarcoma. The assay shows that tumour transplantation is associated with a persisting release of soluble antigen into the circulation. This antigenic burden is present continuously and renewed as long as the tumour mass exists.

Animals↗
PubMed1973

The presence of tumour-specific membrane antigen in the serum of rats with chemically induced sarcomata.

Antibodies to the tumour-specific transplantation type antigen (TSTA) of a transplanted methylcholanthrene-induced sarcoma (MC-1) in syngeneic rats were studied using the techniques of indirect membrane immunofluorescence and mixed haemadsorption with a (51)Cr-labelled indicator cell. After tumour excision, anti-TSTA antibody was readily measurable in both serum and lymph. In contrast, the tumour-bearing animal had no measurable anti-TSTA antibody in the serum but low titres in the lymph. Consequently, we formed the hypothesis that in the presence of a growing tumour the serum contained antigen-antibody complexes with antigen in excess.To test this hypothesis, tumour-bearing serum was examined for the presence of free antigen and antigen-antibody complexes by 2 different methods. In the first method, tumour-bearing serum was cross-linked with glutaraldehyde and was found to absorb specifically the anti-TSTA antibody, indicating free circulating TSTA. Next, antigen-antibody complexes were split with salt or acid and separated into a low molecular weight (or "antigen") fraction (<100,000) and a high molecular weight (or "antibody") fraction (>100,000). The low M.W. fraction specifically inhibited the anti-TSTA antibody when tested by either membrane immunofluorescence or mixed haemadsorption, indicating the presence of antigen from antigen-antibody complexes in the tumour-bearing circulation. The possible effect on the host's immune response of circulating free tumour antigen and antigen-antibody complexes are discussed.

Animals↗
PubMed1973

Similarities of the anti-tumour actions of endotoxin, lipid A and double-stranded RNA.

Double stranded RNA (dsRNA) whether isolated from a fungal virus or prepared synthetically (i.e., Poly I Poly C) and endotoxin were found to exert very similar effects on syngeneic murine lymphomata and fibrosarcomata. They cause complete regressions of some established subcutaneous (s.c.) or intradermal (i.d.) tumours but not of intraperitoneal (i.p.) tumours when administered either systemically or directly into the tumour. To achieve this effect the tumours must be fully established and the best results were obtained when treatment was started 7 days after transplant. If treatment is started within the first 3 days following the transplantation of the tumour then only a slight inhibition of growth rate was observed. These agents can also act prophylactically and protect mice against a subsequent challenge but only if this is given i.p. and not if given s.c. or i.d. The prophylactic action is explained by the action of dsRNA and endotoxin on peritoneal macrophages which cause them to become cytotoxic to tumour cells (i.e., to become activated).The therapeutic effect of systemically administered endotoxin and dsRNA on established tumours is not the result of a direct action on the tumour cells themselves but is a complex process requiring the co-operation of several host factors. Haemorrhagic necrosis involving coagulation is essential (i.e., heparinization reduces the regression of tumours) but is not itself sufficient. Immunosuppression by whole body irradiation or by antilymphocyte serum also interferes with the antitumour action of dsRNA and endotoxin in spite of the fact that haemorrhagic necrosis still occurs. Also, the magnitude of the antitumour action correlated in a series of different tumours with their antigenicity. The observed tumour regressions are probably brought about by (1) vascular damage in the tumour which permits immune defence mechanisms of the host to gain access to the tumour and (2) activation of macrophages present within the tumour. The relative contribution of these two mechanisms may depend on the nature of the tumour and the route of administration of the active agents.Dibenyline, which protects against the lethal action of endotoxin by preventing the action of the catecholamines on the α-adrenergic receptors, makes it possible to increase the effectiveness of endotoxin in tumours by allowing a large dose to be given. Lipid A, a derivative of endotoxin which does not contain polysaccharide, has similar antitumour action to dsRNA and endotoxin. Some common features of the chemical structure of lipid A and dsRNA are discussed.

Animals↗
PubMed1973

A cross-reacting embryonic antigen in the membrane of rat sarcoma cells which is immunogenic in the syngeneic host.

An analysis of the constituents of the plasma membrane of a methylcholanthrene-induced sarcoma (the MC1 tumour) in a hooded rat revealed four tumour-associated macromolecules. Two of these were antigenic in the syngeneic host, one was unique to the MC1 tumour and could not be detected in embryo tissue and has the properties to be expected from the well established tumour-specific transplantation-type antigen while the other, referred to as OEA I, was present in all rat sarcomata tested as well as in early embryos. Two other embryonic components were detected in the sarcoma but these were not immunogenic in the rat. The properties of these tumour-associated "antigens" in the membrane of rat sarcomata are summarized below: [Table: see text]

Animals↗
PubMed1973

Antibodies and soluble tumour-specific antigens in blood and lymph of rats with chemically induced sarcomata.

In confirmation of other studies it has been shown that antibody directed against the tumour specific transplantation-type antigens (TSTAs) cannot be detected in rats with a tumour growing intramuscularly but appears within a few days after excision of the tumour. Circulating antibody is found in the serum of rats with lymph node metastasis following excision of the primary. Absorption by the intramuscular tumour of circulating antibody does not account for the absence of antibody since the antibody levels in thoracic duct lymph in rats with tumours in the leg are also very low and rise rapidly after tumour excision. Antibody is released by the draining nodes directly into the lymph and must pass through the thoracic duct before entering the blood. Under these conditions low levels of antibody activity in lymph cannot be ascribed to absorption by the tumour.It is postulated that TSTA is released from the tumour into the lymph. Following injection of tumour cells into immunized rats the level of antibody falls and this is attributed to release of TSTA from the injected cells. The possible role of antigen release from tumours in determining the host reaction to the tumour is discussed.

Absorption↗
PubMed1972

Thymus-derived lymphocytes produce an immunologically specific macrophage-arming factor.

Spleen cells from mice immunized with an allogeneic tumor when cultured with the specific tumor cells release into the supernatant a specific macrophage-arming factor(s) (SMAF) which binds nonspecifically to macrophages from both mice and rats and renders these cytotoxic to the specific tumor cells. SMAF also binds in an immunologically specific way to the target cells. SMAF-treated target cells grow normally in the absence of macrophages but are killed in the presence of normal macrophages. Thymus-derived cells are necessary for the production of SMAF since (a) after treatment with anti-theta serum immune spleen cells fail to release SMAF; (b) spleen cells from immunized T cell-deprived mice (thymectomized as adults followed by whole body irradiation and restored with bone marrow) fail to produce SMAF on stimulation with the specific target cells. While SMAF has the properties of a cytophilic antibody, it does not belong to one of the established classes of immunoglobulin since high activity is found after column separation in a fraction having a molecular weight between 50,000-60,000 daltons.

Animals↗
PubMed1972

Role of plasma carcinoembryonic antigen in diagnosis of gastrointestinal, mammary, and bronchial carcinoma.

Our studies have confirmed that raised plasma levels of carcinoembryonic antigen (C.E.A.) occur with many but not all malignant tumours, particularly those of the gastrointestinal tract, breast, and bronchus. However, the incidence of raised values may reach 30% in diseases associated with inflammation or regeneration or both. Consequently, it cannot serve yet as a routine screening test for cancer. Effective surgical therapy results in high plasma C.E.A. levels returning to normal. Subsequent rises appear to develop with tumour recurrence or spread. At present the most useful role for C.E.A. seems to be in monitoring patients during the post-therapeutic followup period. Further basic work is required before C.E.A. can become of routine medical value.

Adult↗
PubMed1972

Thymocytes from mice immunized against an allograft render bone-marrow cells specifically cytotoxic.

Thymocytes from C57BL mice immunized with the DBA/2 lymphoma L5178Y exert in vitro an immunologically specific cytotoxic action against the target cells in the presence of bone-marrow cells. Neither the nonimmune bone marrow nor the immune thymocytes are by themselves cytotoxic. The cells in the bone marrow which take part in the cytotoxic action adhere to glass and are sensitive to anti-macrophage serum. These bone-marrow cells can also be rendered specifically cytotoxic by exposure to the supernatant obtained from a culture of immune thymocytes with the specific target cells. The thymocytes before they are confronted with the specific target cells are very radiosensitive; however, on coming into contact with the target cells, an immunologically specific increase in RNA synthesis occurs and thereafter the thymocytes' capacity to render bone-marrow cells cytotoxic is relatively radioresistant. Two classes of immune lymphocytes occur in mice immunized with allogeneic cells, those that are capable of killing target cells directly and those that produce a factor capable of rendering macrophages (or monocytes) specifically cytotoxic. In the thymus of immune animals only the latter are found while both categories are present in the spleen and lymph nodes of immune animals.

Animals↗