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Biomedical subjects

P Stelos

Publications and source records attributed to P Stelos.

9 recordsLinked to original sources

Circulating immune complexes in patients following clinically curative resection of colorectal cancer.

Sixty-nine patients have been followed prospectively after curative resection of Dukes-Kirklin B-2 or C colorectal cancer. Serial plasma samples were studied in selected patients to determine changes in circulating immune complex concentrations (CIC) following primary tumor resection, and to compare serial plasma CIC and carcinoembryonic antigen (CEA) levels. CIC was determined in an average of seven serial samples per patient by inhibition of antibody-dependent cell-mediated cytotoxicity (ADCC). CEA assays were performed by the Hanson Z-gel method. Two distinct patterns of serial CIC have emerged. In seven patients with no known tumor recurrences, serial CEA levels and CIC oscillated regularly and were inversely related. In seven of eight patients whose tumors recurred, both CEA and CIC rose together. In three patients with elevated plasma CEA levels due to inflammatory bowel disease, serial Ag-Ab complex concentrations did not vary, nor did separated Ag or Ab fractions inhibit ADCC. These data suggest that, in patients following curative resection of colorectal cancer, serial changes in circulating immune complexes may discriminate between transient CEA elevations which occur despite no known tumor recurrence and tumor recurrence which is beyond the capacity of adequate host antitumor defense.

Adenocarcinoma

Inhibition of lymphoma cell proliferation by supernatant from fibrosarcoma cultures: preliminary evidence that the inhibitory material is prostaglandin E.

Supernatants obtained from mouse fibrosarcoma cultures 48 hr after the addition of fresh medium contained dialyzable material which inhibited the proliferation of syngeneic lymphoma cells in vitro, as measured by 3H-thymidine incorporation. Three lines of evidence indicate that the supernatant inhibitory material is probably prostaglandin (PG) E. First, the supernatant and dialysis of the supernatant contained a substance with the same characteristics as PGE1 or PGE2 as detected by thin layer chromatography. Second, PGE2-treatment of lymphoma cells mimicked the inhibition of proliferation observed with supernatant inhibitory substance. Third, indomethacin, treatment of fibrosarcoma cultures reduced the amount of supernatant inhibitory substance present.

Animals

The role of effector cells and antiserum in the inhibition of cell-mediated cytotoxicity of allogeneic tumor cells.

Previous experiments in this laboratory demonstrated a progressive decrease in cell-mediated cytotoxicity (CMC) against allogeneic tumor cells by immune spleen cells from mice repeatedly immunized with those tumor cells. In the present study, immune spleen cells, obtained at specified intervals during the course of multiple immunizations of BALB/c mice with EL-4 lymphoma cells, were tested for CMC against EL-4 target cells pretreated with anti-EL-4 serum which had been obtained from singly or repeatedly immunized animals. Cytolysis of EL-4 cells was measured by a 51Cr-release assay. The results indicate that blocking of CMC in an allogeneic tumor model may occur by two pathways. First, antigen or antigen-antibody complexes present in the immunized animal may bind in vivo to the antigen receptor sites of of sensitized effector cells that are used in the in vitro CMC assay, thereby blocking their interaction with tumor cells. Second, immune serum that is added to the in vitro CMC assay may contain highly avid antibodies, as well as antigen-antibody complexes, that bind to tumor cells and thereby block interaction with sensitized effector cells. The identification of these elements may be of prognostic significance in certain clinical situations.

Animals

The immune response of mice repeatedly injected with allogeneic tumor cells.

The development and kinetics of cell-mediated cytotoxicity (CMC), antibody-mediated complement-dependent cytotoxicity (C'DC), and antibody-dependent cellular cytotoxicity (ADCC) were studied in an allogeneic model. Using microcytotoxic assays of 51Cr release from labeled EL-4 tumor cells, C'DC, ADCC, and CMC were measured at 14 intervals during the 77-day course of the experiment. The results obtained demonstrate the oscillating nature of the immune response. The rise and fall of activity was almost synchronous for the three functions studied. A generalized trend of increasing antibody-dependent functions and a simultaneous dampening of CMC was noted.

Animals