A tumor growth inhibitory factor and a tumor growth promoting factor isolated from unfertilized ova of shad (Alosa sapidissima).

In the present study, a cytostatic tumor growth inhibitory peptide and a tumor growth promoting peptide with molecular weights of 20,000-30,000 Da have been identified in the supernatant fraction of unfertilized ova from Shad. The factors can be separated by gel chromatography, thus indicating that the factors are individual molecules. Both of the factors are nondialyzable, heat stable, and resistant to trypsin digestion and periodate oxidation.

A possible role of glucocorticoids: an intrinsic inhibitor of the cytotoxic activity of tumor necrosis factor.

The cytotoxic activity of tumor necrosis factor (TNF) against L929 fibroblasts in vivo was noncompetitively inhibited by physiological concentrations of glucocorticoids such as hydrocortisone (10(-7) M), corticosterone (5 X 10(-8) M) and dexamethasone (5 X 10(-9) M). The inhibition was abolished by the addition of actinomycin D (0.5 microgram/ml) or cycloheximide (4 microM). A phospholipase A2 inhibitor, quinacrine (2 X 10(-6) M), also inhibited the TNF cytotoxicity. These findings suggest that the antitumor cytotoxic reaction by TNF is regulated by glucocorticoid through some mechanism involving de novo transcription and translation and that this regulatory mechanism may involve inhibition of phospholipase A2 activity.

Antibody directed targeting of methotrexate-containing small unilamellar vesicles.

The potential of antibody-linked SUVs containing MTX in anticancer therapy was investigated. The SUVs, mean diameter 50 +/- 20 nm, were prepared by probe sonication of MTX-containing MLVs and were covalently linked either to a RAMG or NRG. After incubation with M21 melanoma cells for 2 h, RAMG-linked SUVs showed 2 and 4 times more binding than NRG-linked MTX-containing SUVs or MTX-containing SUVs unlinked to any Ig. Furthermore, on incubating M21 melanoma cells with RAMG-linked 3H MTX-containing SUVs for 2, 4, and 8 h at 4 degrees C or 37 degrees C, a higher radioactivity was associated with cells at 37 degrees C than at 4 degrees C. Membrane immunofluorescence revealed aggregation of and cap formation by RAMG-linked SUVs after 2 h (37 degrees C) and endocytosis at 4 and 8 h at 37 degrees C. Electron microscopic and autoradiographic studies confirmed aggregation of 3H MTX-containing SUVs around and on the surface of M21 cells. Electron microscopy also revealed these SUVs inside invaginations of and under the plasma membrane of melanoma cells. A colony inhibition assay showed that RAMG-linked, MTX-containing SUVs were 60 times, 8 times, and 4.5 times more growth inhibitory than free MTX, NRG-linked MTX-containing SUV, and MTX-containing SUVs unlinked to any Ig, but not toxic to a human kidney cancer line (that did not react with RAMG).

A monoclonal antibody to the carbohydrate chain on human hepatocellular carcinoma-associated antigen which suppressed tumor growth in nude mice.

There have been few reports stating that monoclonal antibody alone inhibits human solid tumor growth in vivo. The present study demonstrated that monoclonal antibody S1 (IgG2a), which recognized the antigenic determinant of the carbohydrate moiety, showed antibody-dependent cell (or macrophage)-mediated cytotoxicity (ADCC or ADMC) in conjunction with murine splenocytes of both BALB/c and athymic mice. In vivo experiments demonstrated that the antibody S1 clearly prolonged the survival of athymic mice which had been inoculated with a human liver carcinoma cell line. In addition, the antibody S1 significantly suppressed the human hepatoma line transplanted s.c. into nude mice. 125I-Labeled monoclonal antibody S1 revealed that the antibody accumulated significantly in the tumor mass. Many mononuclear cells were observed surrounding tumor cells when the antibody was given. This model system might be useful for analyzing the ADCC (or ADMC) mechanism in vivo.

The influence of thymus factor X (TFX) and of anti-TFX globulin on the growth of Lewis lung carcinoma in mice.

The influence of thymus factor X--TFX (Polfa) and an anti-TFX rabbit gammaglobulin (RATFX) on the growth of Lewis lung carcinoma in mice was studied. The preparations were administered subcutaneously into the peritumoral region. Tumor growth was significantly retarded in the RATFX-treated groups, while a low dose TFX therapy was ineffective. No significant differences in peritumoral inflammatory reaction in treated and untreated mice were found.

Natural and recombinant human interleukin 1-beta is cytotoxic for human melanoma cells.

Human peripheral blood monocytes stimulated with LPS were found to release an activity that was cytotoxic for the A375 melanoma. Biochemical and immunological characterization of the activity indicated that IL 1-beta was the cytotoxic agent. Human recombinant IL 1-beta, purified to homogeneity, was directly cytotoxic for A375. Tumor necrosis factor, also released by activated monocytes, was not cytotoxic for the A375 melanoma.

Human interleukin 1 is a cytocidal factor for several tumor cell lines.

Highly purified interleukin 1 (IL 1) obtained from stimulated human monocytes appeared to be growth inhibitory and cytocidal for a human melanoma cell line, A375. Although IL 1 did not have an immediate cytolytic effect, with time in culture the growth of the target cells was irreversibly inhibited. The cells eventually lysed and decreased markedly in number; the IL 1 effect can therefore be said to be cytocidal. IL 1 activity could not be separated from the cytocidal activity by a variety of chromatography procedures by using conventional and high-performance liquid chromatography (HPLC). The A375 melanoma cell line was also sensitive to another human cytokine alpha-lymphotoxin (alpha-LT) derived from a human B cell line. IL 1 also appeared to be partially growth inhibitory and cytocidal for a LT-sensitive mouse fibroblast cell line, L929; but not for LT-resistant cells, including a subline of L929; a human epithelial carcinoma cell line, HeLa; a human osteosarcoma cell line, HOS; and a mouse SV40-transformed kidney cell line, TU5. However, the LT-sensitive mouse fibroblast cell line, L-M, was resistant to IL 1. Therefore, the cytocidal activity of IL 1 only partially overlapped the target cell selectivity of alpha-LT. Although natural IFN-alpha and recombinant IFN-beta were appreciably growth inhibitory for the A375 cell line, natural and recombinant IFN-alpha and recombinant IFN-beta and IFN-gamma exhibited little cytocidal activity. Purified IL 1 did not have any antiviral activity, and conversely, IFN and alpha-LT were not co-mitogenic for thymocytes. Furthermore, by ELISA and radioimmunoassays, antibodies against human alpha-LT, tumor necrosis factor, and IFN-gamma did not react with IL 1, indicating that IL 1 is antigenically distinct from these other cytokines. These in vitro results suggest that IL 1 may play a role in host defense against some tumors as a cytocidal factor.

[Selenium compounds and carcinogenesis]. / Selenverbindungen und Kanzerogenese.

Starting with a brief outline of the general toxic effects of selenium compounds, their biological importance for the organism as a trace element and with an analysis of the different hypotheses on the action mechanism of selenium and selenium compounds, a survey is provided in which way selenium compounds may influence malignant transformation and related processes in vivo and in vitro. Furthermore, observations are viewed on the effects of selenium compounds on spontaneously developing, chemically or virally induced tumors. Based on the data available so far it cannot, at present, be assessed whether selenium and its compounds can be used in the future for chemoprevention of cancer.