Purification, characterization and anti-tumor activity of a new cytokine, histiocyte-secreted-factor (HSF).

Purification of cytokines was carried out while monitoring their in vivo anti-tumor activity and in vitro cytotoxic activities. As a result, purified new cytokines were obtained from culture supernatant of a histiocytic cell line from rabbit serum. Briefly, a new cytokine (HSF, histiocyte-secreted-factor) was purified from the culture of supernatant of the histiocytic cell line (TYH) which we established from the peripheral blood of a malignant-lymphoma patient.

Combination therapy with traditional Chinese medicines and Streptococcus pyogenes products (OK 432) for endogenous tumor necrosis factor therapy. A preliminary report.

The antitumor activity of combination therapy with traditional Chinese medicines and OK432 (Streptococcus pyogenes) for cancer patients was investigated. Excellent antitumor activity of this treatment was achieved in one patient with hepatocellular carcinoma. The present report describes the clinical course of this patient and examines the contribution of production of tumor necrosis factor (TNF) and interferon-gamma (IFN).

Antitumor activity of recombinant human tumor necrosis factor in combination with hyperthermia against heterotransplanted human prostatic carcinoma and its lymph node metastasis in nude mice.

The antitumor activity of recombinant human tumor necrosis factor (rhTNF) against heterotransplanted human prostatic carcinoma (PC-3) and spontaneous lymphatic tumor metastasis was studied in vivo. The spontaneous lymphatic metastasis of PC-3 tumor was found in approximately 50% of cases. Significant antitumor activity was observed with repeated intratumoral administration of a large dose of rhTNF, not only on the subcutaneous tumor xenografts but also on the lymph node metastases.

Preventive effect of several drugs against Pseudomonas aeruginosa infection and the toxicity of combined tumor necrosis factor with lipopolysaccharide: relationship between lethality and the arachidonic cascade.

The participation of tumor necrosis factor (TNF) and lipopolysaccharide (LPS) in Pseudomonas aeruginosa (Pa) infection was examined. The lethal challenge of Pa or TNF and LPS injection could be prevented by pretreatment with anti-TNF antibody, polymyxin B, ONO 1078, or Shosaiko-to. The combined effects of TNF and LPS may be deeply related to the lethality of Pa infection.

Therapy combining tumor necrosis factor with tumor-specific antibody against Meth A sarcoma.

We have investigated the antitumor activity of tumor necrosis factor (TNF) against numerous. It appears that the efficacy of TNF against highly immunogenic tumor cell lines is greater than that against low immunogenic cell lines. Tumor cells express immunogenic tumor-associated antigen and sometimes shed antigens.

Japanese modified traditional Chinese medicines as preventive drugs of the side effects induced by tumor necrosis factor and lipopolysaccharide.

It was found that the capacity for tumor necrosis factor (TNF) production by Japanese modified traditional Chinese medicines and crude drugs broadly paralleled their antitumor activity. Pretreatment with these drugs prevented the lethal and marked side effects of recombinant human TNF (rhTNF) and lipopolysaccharide (LPS) without impairing their antitumor activity. These drugs are thought to decrease the oxygen radicals and stabilize the cell membranes, with a deep relation to the arachidonic cascade.

Preventive effects of several chemicals against lethality of recombinant human tumor necrosis factor.

Toxicity has been observed in mice receiving recombinant human tumor necrosis factor (rhTNF). In the present experiments, several chemicals were used to determine whether they could prevent the lethality of rhTNF without impairing its antitumor activity. Injection of phospholipase A2, cyclooxygenase, and lipoxygenase inhibitors at the same time as rhTNF administration could prevent the lethality of rhTNF, but the antitumor activity was also reduced.

Antitumor activity of combination therapy with traditional Chinese medicine and OK432 or MMC.

To examine the effects of combination therapy with traditional Chinese preparations (Syô-saiko-tô, Zyûzen-taiho-tô or Cinnamomum cortex) and OK432 or mitomycin C on the antitumor activities and TNF producibility, an investigation was carried out using mice transplanted with Ehrlich or Meth A tumor cells. Development of the transplanted tumors was strongly inhibited by the combination therapy, and the tumor necrosis factor (TNF) producibility was increased with the combination of a traditional Chinese preparation and OK432. A significant negative correlation was observed between the TNF activities and tumor weight, and there was a positive correlation between the TNF activities and spleen weight in the Ehrlich-bearing DDY mice receiving traditional Chinese preparations or OK432.

Antitumor activity of recombinant human tumor necrosis factor in combination with hyperthermia, chemotherapy, or immunotherapy.

The antitumor activity of recombinant human tumor necrosis factor (rhTNF) against methylcholanthrene A-induced sarcoma (Meth A sarcoma) and human tumors in vivo was studied. On systemic administration of rhTNF to Meth A sarcoma-bearing mice, tumor regression was achieved with a large dose or with repeated administration of a small dose. Strong antitumor activity could be achieved in the Meth A sarcoma model by administration of a small dose of rhTNF in combination with moderate temperature hyperthermia (p less than 0.

Antitumour effects of tumour necrosis factor: cytotoxic or necrotizing activity and its mechanism.

The antitumor activity of murine, rabbit and recombinant human tumour necrosis factor (TNF) was examined in an experimental animal model. TNF showed an excellent curative effect against the murine and human tumours tested. Strong antitumour activity was obtained by combining a small dose of TNF with moderate hyperthermia (40 degrees C for 40 min).

Necrotizing activity of tumor necrosis factor: histopathological investigation using Meth A sarcoma and granulation tissue.

The action of tumor necrosis factor (TNF) was investigated histopathologically in mice using methylcholanthrene A (Meth A)-induced sarcomas and granulation tissue induced by autotransplantation of fragments of liver and spleen. Highly purified murine TNF caused hemorrhagic necrosis of both the tumors and the granulation tissue. Proliferation of tumor capillaries, demonstrated microangiographically, occurred 2 h after TNF administration and hyperemia of tumor vessels was obvious after 3-6 h.

Effects of tumor necrosis factor (TNF) on transplanted tumors induced by methylcholanthrene in mice. A histopathologic study.

The effects of a highly purified tumor necrosis factor (TNF) on transplanted methylcholanthrene (Meth A)-induced murine tumors were compared with those of lipopolysaccharide (LPS). TNF caused immediate subepidermal edema and hyperemia followed 2 h later by fibrin thrombi in tumor blood vessels. Finally hemorrhagic necrosis with dispersal of tumor cells occurred.

Inhibition of tumor-induced migration of bovine capillary endothelial cells by mouse and rabbit tumor necrosis factor.

The effect of tumor necrosis factor (TNF) on the tumor-induced endothelial migration was evaluated with the use of a phagokinetic track assay. TNF from both ddy mice and Japanese albino rabbits (sp act, 3-5 X 10(5) U/mg, respectively) was found to inhibit the migration of bovine capillary endothelial (BCE) cells stimulated by factors from tumor cells, such as the medium conditioned with mouse sarcoma 180 cells or human meningioma extract. These TNF preparations, however, did not affect the spontaneous migration of the BCE cells.

Macrophage cell line, J774, producing a tumor necrosis factor.

Cytotoxic factor was produced from murine macrophage-like cell line, J774, after stimulation with 12-o-tetradecanoyl phorbol-13-acetate (TPA) and lipopolysaccharide (LPS). J774-derived cytotoxic factor is a glycoprotein with a molecular weight of 39,000 by gel filtration and 18,000 by SDS-PAGE, and with an isoelectric point of below 4.3.

Purification, characterization, and antitumor activity of nonrecombinant mouse tumor necrosis factor.

Mouse tumor necrosis factor (TNF) was purified from serum through a series of steps, and each step was monitored for L-cell cytotoxicity in vitro and tumor-necrotizing activity in vivo. The two activities copurified and could not be dissociated. Purified mouse TNF has a specific activity of 2.

Actions of tumor necrosis factor on cultured vascular endothelial cells: morphologic modulation, growth inhibition, and cytotoxicity.

Exposure to highly purified preparations of murine tumor necrosis factor (TNF) resulted in distinct morphologic changes and proliferation inhibition of cultured endothelial cells from the bovine aorta and capillary and of those from the human umbilical vein. The TNF preparation also inhibited the proliferation of bovine aortic smooth muscle cells but failed to inhibit the proliferation of bovine and human fibroblasts. The cytotoxic activity of the TNF preparation was prominent only in bovine capillary endothelial cells.

Purification and partial amino acid sequence of rabbit tumor necrosis factor.

Good production of tumor necrosis factor (TNF) in the rabbit was obtained using Propionibacterium acnes IID 912 as a priming agent and subsequent administration of lipopolysaccharide. The physicochemical characteristics of rabbit TNF were very similar to those of murine TNF. The molecular weight of rabbit TNF was 39,000 as estimated by gel filtration, and 18,000 by SDS-PAGE.

Establishment and characterization of human myelomonocytic (TYS) and histiocytic (TYH) cell lines.

Two human hematopoietic cell lines (TYS and TYH) with monocytic characteristics were derived from the peripheral blood of a patient with acute myelomonocytic leukemia and of another with a follicular large-cell type of malignant lymphoma. The TYS cells, derived from the leukemia patient, revealed a monocytic appearance with microvilli at one side and had many granules and vacuoles. They showed strongly positive reactions with alpha-NBE, NASDAE, and AcP, and were reactive with monoclonal antibodies such as OKlal, 12 and Bl.