Role of cytokines in GVL (ESb lymphoma) and GVHD after adoptive transfer of allogeneic T lymphocytes in mice.

ESb lymphoma cells injected i.v. into DBA/2 (H-2d) mice multiply rapidly in the liver and kill all mice in a few days.

The essential role of endogenous IFN alpha/beta in the anti-metastatic action of sensitized T lymphocytes in mice injected with Friend erythroleukemia cells.

Adoptive transfer of splenic T lymphocytes from DBA/2 mice immunized against Friend erythroleukemia cells (FLC) inhibited the development of visceral metastases and increased the survival time of DBA/2 mice challenged i.v. with parental FLC 24 hr to 2 months later.

Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice.

Transgenic mice have been used to address the issue of the oncogenic potential of mutant guanine nucleotide stimulatory factor (Gs) alpha subunit in the thyroid gland. The expression of the mutant Arg-201-->His Gs alpha subunit transgene has been directed to murine thyroid epithelial cells by bovine thyroglobulin promoter. The transgenic animals develop hyperfunctioning thyroid adenomas with increased intracellular cAMP levels and high uptake of [125I]iodine and produced elevated levels of circulating triiodothyronine and thyroxine.

Sensitized T lymphocytes render DBA/2 beige mice responsive to IFN alpha/beta therapy of Friend erythroleukemia visceral metastases.

Interferon alpha/beta (IFN alpha/beta) is highly effective in inhibiting the development of Friend erythroleukemia cell (FLC) visceral metastases in DBA/2 mice injected intravenously (i.v.) with FLC, but does not protect FLC-injected DBA/2 beige (bg/bg) mice.

Inhibition of Friend leukemia cell visceral metastases by a new monoclonal antibody and role of the immune system of the host in its action.

We developed a syngeneic mouse IgG2a monoclonal antibody (MAb) A9D41 directed against the Friend leukemia virus envelope gp70 antigen present on the cell surface membranes of virus producer 3C18 Friend leukemia cells (FLC). A9D41 showed a marked antitumor activity in DBA/2 mice given injections of gp70 positive 3C18 FLC, but it was ineffective in mice given injections of gp70 negative 745 FLC or unrelated tumor cells. A9D41 was particularly effective in inhibiting the development of 3C18 FLC liver and spleen metastases.

Host humoral and cellular immune mechanisms in the continued suppression of Friend erythroleukemia metastases after interferon alpha/beta treatment in mice.

DBA/2 mice were injected intravenously with 2 x 10(6) 3C18 Friend erythroleukemia cells (FLC), a cell line resistant to interferon alpha/beta (IFN-alpha/beta). Although daily administration of mouse IFN-alpha/beta markedly increased the mean survival time, most IFN-treated mice continued to harbor FLC in different organs. To investigate the mechanisms responsible for this persistent suppression of FLC growth in IFN-treated mice, we undertook a series of adoptive transfer experiments with sera and spleen cells.

Anti-tumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend erythroleukemia cells. VIII. Role of the immune system in the inhibition of visceral metastases.

DBA/2 mice were injected i.v. with IFN alpha/beta-resistant 3CI8 Friend erythroleukemia cells (FLC) which metastasize to the liver and spleen.

Effectiveness of mouse interferon alpha/beta compared to single-agent chemotherapy in increasing survival time of mice after intravenous inoculation of Friend erythroleukemia cells.

DBA/2 mice received an iv injection of 2 X 10(6) Friend erythroleukemia cells (FLCs; approximately equal to 4 X 10(5) lethal dose50), which multiplied rapidly in the liver and spleen and killed all untreated or control treated mice between 7 and 12 days. Daily interferon (IFN) treatment resulted in a very marked increase in survival time and apparent cure of 4 of 22 tumor-inoculated mice. In contrast, treatment of tumor-injected (iv) mice with cyclophosphamide, 5-fluorouracil, and methotrexate increased survival time by only a few days; and treatment of mice with cisplatin, vincristine, doxorubicin, bleomycin, or etoposide was ineffective.

Interferon treatment markedly inhibits the development of tumor metastases in the liver and spleen and increases survival time of mice after intravenous inoculation of Friend erythroleukemia cells.

To investigate the effect of interferon treatment on the development of tumor metastases, DBA/2 mice were injected i.v. with 2 X 10(6) Friend erythroleukemia cells (FLC) (equivalent to about 5 X 10(5) LD50).

Effects of interferons alpha,beta,gamma alone or in combination on the phenotype of human colon carcinoma cells.

The ability of interferons (IFNs) alpha,beta,gamma, alone or in combination, to induce reversion of the phenotype of cloned human colon carcinoma cells during long-term treatment was studied. The phenotypic characteristics examined were proliferation, cellular aggregation and tumorigenicity. The combination of IFN-beta and IFN-gamma showed more antiproliferative activity than that of IFN-delta and IFN-gamma or of either IFN alone.

Anti-tumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant friend leukemia cells. IV. Definition of optimal treatment regimens.

Mouse interferon alpha/beta exerted a similar anti-tumor effect in DBA/2 mice injected i.p. with Friend erythroleukemia cells (FLC) either sensitive or resistant to interferon as determined by both in vitro and in vivo assays.

Injection of mice with antibody to mouse interferon alpha/beta decreases the level of 2'-5' oligoadenylate synthetase in peritoneal macrophages.

Injection of conventional or axenic weanling mice with potent sheep or goat antibody to mouse interferon alpha/beta resulted in a decrease in the basal level of 2-5A synthetase in resting peritoneal macrophages and rendered these cells permissive for vesicular stomatitis virus. There was a good inverse correlation between the level of 2-5A synthetase in peritoneal macrophages and the permissivity of these cells for vesicular stomatitis virus. The peritoneal macrophages of 1- and 2-week-old mice had low levels of 2-5A synthetase and were permissive for vesicular stomatitis virus, whereas at 3 weeks (and after) there was a marked increase in the level of 2-5A synthetase in peritoneal macrophages, and these cells were no longer permissive for vesicular stomatitis virus.

Injection of mice with antibody to interferon enhances the growth of transplantable murine tumors.

Injection of DBA/2, C57Bl/6, or BALB/c mice with antibody to mouse interferon alpha/beta enhanced the i.p. transplantability of six different murine tumors, as manifested by an increase in the percentage of tumor-bearing mice and a decrease in survival time.

Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. III. Inhibition of growth and necrosis of tumors implanted subcutaneously.

Administration of highly purified interferon to DBA/2 mice inhibited the growth of interferon-sensitive or interferon-resistant Friend erythroleukemia cells implanted subcutaneously. Injection of interferon at the site of tumor inoculation was more effective than injection of interferon intraperitoneally. Histologic examination of tumors in interferon-treated mice showed extensive areas of tumor-cell necrosis in the absence of an obvious host-cell infiltrate.

Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. II. Role of host mechanisms.

We have attempted to determine what host mechanisms are responsible for inducing a rapid decrease in the number of Friend leukemia cells (FLC) in the peritoneal cavity of interferon-treated mice. By injecting radiolabelled FLC, we showed that there was a greater loss of radioactivity from individual interferon-treated mice than from control mice. Thus, it was likely that fewer cells were recovered from the peritoneal cavity of interferon-treated mice because of cell destruction.

Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. I.

Interferon-sensitive (745) and interferon-resistant (3C1-8) Friend leukemia cells (FLC) are highly tumorigenic for DBA/2 mice. The phenotype of interferon sensitivity or resistance does not change with in vivo passage. Daily administration of mouse interferon markedly enhanced the survival time of mice injected with either 745 or 3C1-8 cells.

Immunological comparison of ovarian and colonic CEA.

Ovarian and colonic CEA were compared immunologically by means of antisera prepared against each of them. CEAs of both origins were found identical by immunodiffusion methods. In radioimmunological experiments, slight differences were observed between some but not all ovarian CEAs and colonic CEAs and also between different preparations of colonic CEA: no organ specificity of ovarian CEA could be demonstrated.

Interferon induces peripheral lymphadenopathy in mice.

Inoculation (i.p. or i.

Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. VI. Polyoma virus infection.

We have determined the effect of a single injection of potent sheep anti-mouse interferon globulin on polyoma-virus-induced early runting disease and tumor formation in Swiss mice. When newborn mice were injected with greater than or equal to 9 X 10(6) PFU of polyoma virus, 16% (7/44) of mice runted and died in contrast to 96% (45/47) of mice injected with virus and anti-interferon globulin. Likewise, a greater percentage of mice injected with lower doses of virus and anti-interferon globulin developed tumors than did control virus-injected mice.

[Immunocytochemical location of the centrosphere of human cancer cells using natural rabbit antibodies].

Sera of 40 normal nonimmunized rabbits were eprouved by immunoperoxidase on cultural human cells. Four sera contain centrosphere-reactive antibodies and for the strongest serum the centrospheres were still stained with the 1/600 dilution. This last serum visualized the centrospheres within the height human cell lines eprouved, whatever the phase of the mitotic cycle.

Role of endogenous interferon in the anti-tumor effect of poly I-C and statolon as demonstrated by the use of anti-mouse interferon serum.

We have determined the effect of sheep anti-mouse interferon globulin on the anti-tumor effects of poly I-C, statolon, tilorone, pyran copolymer and BCG in mice inoculated with Ehrlich ascites or L 1210 lymphoma cells. Whereas the anti-tumor effects of poly I-C and statolon were nulified when mice were injected with immunoglobulins, the anti-tumor effects of pyran copolymer and BCG were not modified by this treatment. We conclude that interferon mediates the anti-tumor activity of poly I-C and statolon in these experimental systems.

Use of a permanent cell line extracts to study the tumor associated immune reactions in colorectal cancer patients by leucocyte migration inhibition test.

Crude extracts of colorectal surgical tumors, either individual or pooled, and HT29 line cells were compared in leucocyte migration inhibition test. HT29 cell extract gave more positive reactions with leucocytes of colorectal cancer patients than the other ones, and less with control leucocytes. It was thus used for all the subsequent experiments.