Strain differences in the cytotoxic activity and TNF production of murine macrophages stimulated by lentinan.

The effect of lentinan, a glucan type immunomodulatory polysaccharide was studied on the antitumor cytotoxicity and on the TNF secretion of peritoneal macrophages in inbred H-2 congeneic mouse strains under in vivo and in vitro conditions. The cytotoxic activity and TNF secretion of murine macrophages was found to be elevated by lentinan in vitro and in vivo conditions. The effectiveness of lentinan to induce cytotoxicity and TNF secretion was highly influenced by the genotype of the host.

Antitumor and immunological activity of lentinan in comparison with LPS.

Lentinan manifests marked antitumor and antimetastatic activity in numerous tumor/host systems, and prevents chemical and viral carcinogenesis. Modulation of immune or vascular functions by lentinan is involved in its antitumor effects. The impact of lentinan on the functions of macrophages is distinct from that of LPS.

Stimulation of microbicidal host defence mechanisms against aerosol influenza virus infection by lentinan.

The ability of polysaccharide immunomodulator lentinan to stimulate non-specific resistance against respiratory viral infections was investigated. Significant protection was conferred by lentinan administered intranasally before lethal influenza virus infection and could be corroborated by a reduction of the lung virus titres. Since the lung is the target organ of influenza virus infection, lentinan was also administered by the intravenous route.

Recent progress in immunopharmacology and therapeutic effects of polysaccharides.

Lentinan, a (1----3)-beta-D-glucan with (1----6)-beta-D-glucopyranoside branches and its related polysaccharides have marked antitumour activity in allogeneic, syngeneic and autochthonous primary hosts, suppress chemical and viral oncogenesis, and prevent cancer recurrence or metastasis after surgery. Results of the clinical application of lentinan have proven prolongation of life-span of the patients with advanced and recurrent stomach, colorectal and breast cancer with only little toxic side effect. These polysaccharides also increase host resistance to various kinds of bacterial, viral and parasitic infections including AIDS.

The effect of lentinan on proliferative processes in parenchymal organs of rats--I. The effect on pyrimidine and nucleic acid syntheses.

The present study investigated the effect of Lentinan on the biochemical events associated with the pyrimidine and nucleic acid syntheses in the liver, kidney, thymus and spleen of rats. Lentinan was used at a dose of 4 mg/kg/day (twice) and in a single dose of 20 mg/kg. The following changes were observed.

Effect of lentinan and mannan on phagocytosis of fluorescent latex microbeads by mouse peritoneal macrophages: a flow cytometric study.

Lentinan, an immunopotentiating beta-1,3-glucan polysaccharide stimulated the in vitro phagocytosis of BSA-coated, C3b- or monoclonal immunoglobulin (IgG2b)-coated fluorescent microspheres by resident or thioglycollate-elicited mouse macrophages in a dose-dependent manner. Analysis of flow cytometric data has shown that microbead phagocytosis of resident macrophages, which exhibit a lower basic phagocytic activity than the thioglycollate elicited ones, has been augmented by up to 900% due to lentinan. The percent ratio of phagocytes among peritoneal exudate cells, however, remained unchanged after short-term lentinan stimulation.

Effect of lentinan on superoxide dismutase enzyme activity in vitro.

The effects of lentinan on enzyme induced lipid peroxidation, xanthine-xanthine oxidase-induced cytochrome c reduction, and on the superoxide-dismutase (SOD) enzyme activity and expression of human lymphocytes and erythrtocytes were studied. Lentinan in low concentration decreased SOD activity of lymphocytes and erythrocytes from healthy subjects. In higher concentration (10 micrograms/ml) lentinan increased the pathologically low SOD activity of erythrocytes and lymphocytes of patients with cirrhosis of the liver.

[Evaluation and consideration of BRM-BRM and HDP (host defense potentiators)].

It should first be stressed that the term BRM is wrong and unscientific, since this would include potassium cyanide or cancer chemotherapeutics in the strict sense of the term. Therefore, in this article we discuss the evaluation of Host Defence Potentiators (HDP). IL-2 or TNF should not be included as HDP because their action is local and not selective to cancer cells, similar to the case of cancer chemotherapeutics.

Regression induced by lentinan, of peritoneal carcinomatoses in a model of colon cancer in rat.

Lentinan has been tested in a model of colon cancer in rats. Peritoneal carcinomatoses were induced in BDIX rats by i.p.

The effect of lentinan on the resistance of mice to Mesocestoides corti.

CBA/H mice were given the immunomodulator lentinan in multiple, ascending doses before (prophylactic) or after (therapeutic) inoculation with tetrathyridia of Mesocestoides corti or as a single prophylactic dose. The latter was without effect, but increasing multiple prophylactic and therapeutic doses of lentinan resulted in a marked reduction in the numbers of parasites in the peritoneal cavity, particularly in those mice that received lentinan therapeutically. In mice that received multiple doses of lentinan, liver granulomas were larger than in controls and there was more collagen deposition and fibrosis.

Antitumor and metastasis-inhibitory activities of lentinan as an immunomodulator: an overview.

The antitumor and metastasis-inhibitory activities, mode of action, and clinical application of lentinan, a strictly purified beta-1,6:beta-1,3-glucan, are reviewed. Lentinan exerts a prominent antitumor effect and prevents chemical and viral oncogenesis. The antitumor action of lentinan is host-mediated.

Effect of lentinan on pinocytosis in mouse peritoneal macrophages and the murine macrophage cell line C4M phi in vitro.

Lentinan, an immunopotentiating polysaccharide, stimulated the pinocytosis of horseradish peroxidase (HRP) or FITC-dextran by resident or thioglycollate-elicited mouse macrophages from 10 to 50% in a dose dependent manner. Pinocytosis of HRP and FITC-dextran by C4M phi cells, a murine macrophage cell line, exhibiting a lower basic pinocytic activity than peritoneal cells, was augmented up to 310 and 120%, respectively, by lentinan. Mannan inhibited the HRP uptake by peritoneal macrophages via specific mannose receptors.

Macrophage-mediated acute-phase transport protein production induced by lentinan.

A new bioactive factor capable of stimulating the production of acute-phase transport proteins, haptoglobin, hemopexin and ceruloplasmin, was found in mouse serum soon after the administration of lentinan, an immunomodulatory polysaccharide. This factor (APPIF) was produced by macrophages, and may regulate the production of acute-phase transport proteins in hepatocytes. The mice given the serum obtained from donor mice 2-6 h after an injection of 10 mg/kg of lentinan showed a marked increase of the acute-phase transport proteins in their serum 4 days after the serum injection.

[Experimental studies on growth inhibition and regression of cancer metastases].

The most important target in pharmaceutical therapy against cancer is complete suppression of metastases and recurrence after curative surgical operation. It is fundamentally, a growth inhibition and regression of small number of autochthonous tumors scattering in the host, and coexistence between tumor and host is also important. As immunosuppressive anticancer drugs have detrimental effects for patients in such cases, application of strong immunopotentiators such as lentinan should be expected.

Effect of lentinan on the chemiluminescence produced by human neutrophils and the murine macrophage cell line C4M phi.

Lentinan, an immunopotentiating polysaccharide, stimulates the production of chemiluminescence (CL) by human neutrophils and the murine macrophage cell line C4M phi. The CL enhancing effect of lentinan opsonized in human serum is greater than that of lentinan itself. Lentinan's stimulation of neutrophil CL was increased by 1/2 when opsonized in human serum inactivated at 56 degrees C to remove complement, while the CL was increased two fold by lentinan opsonized in whole serum.

Superoxide anion, superoxide dismutase and lipid peroxidation in the murine macrophage cell line C4M phi.

A remarkable increase in the production of superoxide radicals and SOD activity was measured in suspension of the murine macrophage cell line C4M phi treated with Lentinan (4-10 X 10(3) micrograms/5 X 10(6) cells). In activated macrophages the decrease of lipid peroxidation could be interpreted as a consequence of enhanced SOD activity.

Antitumor activity of lentinan in murine syngeneic and autochthonous hosts and its suppressive effect on 3-methylcholanthrene-induced carcinogenesis.

The antitumor effect of lentinan in syngeneic and autochthonous tumor-host systems and its suppressive effect on 3-methylcholanthrene (MC)-induced carcinogenesis were confirmed using DBA/2 and SWM/Ms hosts. The regressive activity of lentinan against the solid form of Sarcoma 180 was the most effective in DBA/2, SWM/Ms, or A/J mice and less effective in C3H/He or C57BL/6 mice. The growth of a syngeneic MC-induced DBA/2.

T-cell mediated vascular dilatation and hemorrhage induced by antitumour polysaccharides.

Antitumour polysaccharide lentinan, capable of potentiating T-cell dependent reactions and some other antitumour polysaccharides such as pachymaran, carboxymethyl-pachymaran and zymosan were found to induce vascular dilatation and hemorrhage(VDH) in CD-1 normal mice starting the following day after a single injection. Polysaccharides which do not have the tumour-regressing activity, several immunopotentiators such as BCG, lipopolysaccharide, dextran sulfate and concanavalin A, and chemical mediators of inflammation such as histamine, serotonin and prostaglandin E1 did not induce VDH in mice. This response seems to be mediated by T-cells and macrophages, because VDH was not observed in CD-1 nu/nu mice treated with lentinan, and carrageenan, an antimacrophage drug, inhibited the appearance of VDH by lentinan.

Mechanism of the A/Ph.MC.S1 tumor graft rejection in syngeneic mice.

A considerable number of normal mice injected with a low dose of A/Ph.MC.S1 syngeneic methylcholanthrene-induced tumor cells showed regression of the tumor after a transient period of growth.

Preclinical evaluation of lentinan in animal models.

Lentinan exerts prominent antitumor effects in allogeneic, syngeneic and autochthonous hosts and prevents chemical and viral carcinogenesis, and increases host-resistance to bacterial, viral and parasitic infections. Lentinan augments helper T cell mediated cytotoxic T cell activity, NK cell activity and humoral immune responses, and activates nonspecific cytotoxicity of macrophages in vivo. Lentinan is a representative of a unique class of T cell adjuvants, and has no toxicity.

Current status and perspectives of immunomodulators of microbial origin.

The chemical structure and characteristics, the antitumour activity, the antibacterial, antiviral, antifungal, antiparasitic activities, immunological properties and mode of action of immunomodulators of microbial origin, especially antitumour polysaccharide lentinan, have been discussed immunopharmacologically in comparison with pachymaran, schizophyllan, DiLuzio's yeast glucan, Coriolus preparation PS-K, Streptococcal preparation OK-432, Nocardia rubra cell wall skeleton N-CWS together with BCG and Corynebacterium parvum. Lentinan exerts its inhibitory action not only on allogeneic tumours but also on syngeneic and autologous tumours, and prevents chemical and viral carcinogenesis. The phase III randomized control study of lentinan in cancer patients with gastric and colo-rectal cancer showed the clinical efficacy of lentinan in prolonging the life span and improving host immune responses.