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PubMed1982

[Preoperative immunochemotherapy for gastric cancer patients--immunomodulating effect of levamisole and lentinan on cell-mediated immunity and regional lymph node].

The effects of two immunomodulators, levamisole and lentinan, on cell-mediated immunity and regional lymph nodes of patients with gastric cancer were studied, including reference to some literature. 1) The counts of active T-cells and total T-cells in the peripheral blood showed a tendency of increase after administration of levamisole. 2) PHA lymphocyte blastoformation in the peripheral blood with and without autoserum was enhanced by the administration of levamisole and lentinan. 3) The percentage of active T-cells and PHA lymphocyte blastoformation in the peripheral blood with and without autoserum in proximal regional lymph nodes were increased by the administration of levamisole and lentinan. 4) The percentage of active T-cells and PHA lymphocyte blastoformation in the peripheral blood with and without autoserum in distal regional lymph nodes were increased by the administration of levamisole. 5) Postoperative depression of PHA and PPD skin tests was enhanced by preoperative administration of levamisole, and that of PHA skin test was enhanced by the administration of lentinan.

Adjuvants, Immunologic↗
PubMed1994

[Effect of lentinan for advanced prostate carcinoma].

A prospective, randomized multi-center study was conducted to assess the clinical effectiveness of Lentinan, an immunomodulatory agent, in the metastatic prostate cancer. Of seventy-five patients enrolled from July 1987 to June 1992, 69 were eligible. All patients received hormonal therapy and chemotherapy using Tegafur p.o. at a dose of 400-800 mg/day. While 33 patients received Lentinan i.m. for at least three months, the other 36 did not. The dose of Lentinan was 2 mg weekly for inpatients and 4 mg every other week for outpatients. The mean age of treated and control patients was 70 (range; 53-83) and 71 (range; 50-86), respectively. The 50% survival length of treated and control patients was 48 and 35 months, respectively. The five-year survival rate of treated patients was 43% according to the Kaplan-Meier method, while that of control patients was 29% (p < 0.05). We conclude that Lentinan is effective in metastatic prostate cancer when incorporated into hormonochemotherapy.

Aged↗
PubMed1988

[Combined use of lentinan with X-ray therapy in an experimental mouse tumor system (Part 3). Combined effect on metastatic tumors].

Combination effect of lentinan with X-ray irradiation on the metastatic mouse tumors, L1210, KLN205 and Lewis lung carcinoma were studied. Combination use of lentinan with X-ray therapy prolonged the life of BDF1 mice bearing L1210 leukemia in the suitable combination conditions. Combination effects of lentinan with X-ray therapy were also observed on the suppression of the growth of KLN205 squamous cell carcinoma and on the suppression of the metastasis of Lewis lung carcinoma. Especially, in the case that lentinan was administered before or after X-ray local irradiation in the pulmonary metastasis system of Lewis lung carcinoma, a marked suppression of pulmonary metastasis was observed and 2 to 4 mice among 8 tested mice were tumor free.

Animals↗
PubMed2004

Lentinan from shiitake mushroom (Lentinus edodes) suppresses expression of cytochrome P450 1A subfamily in the mouse liver.

Induction of xenobiotics metabolizing enzymes is related to the formation and chemoprevention of cancer. Since cytochrome P450s (CYPs) including CYP1A subfamily metabolize certain pro-carcinogens to their ultimate forms, down-regulation of CYP1As by food factors leads to the prevention of cancer. Mushroom polysaccharides, especially beta-glucans such as lentinan from Lentinus edodes, possess the anti-tumor and immunomodulating activities through the cytokine production from immunocytes. Recent our studies have demonstrated that lentinan suppresses hepatic CYP1As expression in the both constitutive and inducible levels through the production of tumor necrosis factor-alpha and an increase in the DNA-binding activity of nuclear factor-kappaB. This paper discusses on the effective lentinan dosage and route of administration for suppression of CYP1As.

Animals↗
PubMed1996

Two genes controlling acute phase responses by the antitumor polysacch aride, lentinan.

Lentinan, a beta-1,6;1,3-glucan, is tumor-specific for transplantable mouse solid-type tumors and it also stimulates the production of acute phase proteins (APPs). The APP response to lentinan is of the delayed type (DT-APR) and differs from that to lipopolysaccharide, which is acute. We found that the responses were genetically controlled in mice and that low responsiveness is dominant (Maeda et al. 1991). Using 123 segregants of crosses between SWR/J (a high responder) and Mus spretus (a low responder), we analyzed the linkage between DT-APR responsiveness and the DNA polymerase chain reaction-simple sequence length polymorphism (PCR-SSLP) phenotype using 80 chromosome-specific microsatellite markers. We identified two loci (ltn1.1 and ltn1.2) responsible for DT-APR. ltn1.1 is closely linked to D3Mit11 on chromosome 3 and ltn1.2 to D11Nds9 on chromosome 11 (P <0.001). The linkage analysis also suggested that ltn1.2 is the major determinant for DT-APR. Correlation between lentinan-specific IL-6 mRNA expression (the late expression) controlled recessively and DT-APR induction suggests that the ltn1 loci control some process(es) of IL-6 expression in the regulation step before NF-IL6.

Acute-Phase Reaction↗
PubMed1998

Four dominant loci for the vascular responses by the antitumor polysaccharide, lentinan.

Lentinan, beta-1,6;1,3-glucan, showing an antitumor effect against mouse solid type tumors, can induce marked vascular dilation and hemorrhage (VDH) in very localized areas such as the ears, feet, and tails of mice in the early stages after its administration (Maeda et al. 1984). VDH has been found to be one of the T-cell-mediated responses triggered by lentinan. We reported previously that the responsiveness of mice to lentinan with respect to VDH induction is controlled by a dominant gene(s), Ltn2 (formerly), and that no sex difference was observed (Maeda et al. 1991). To determine the chromosomal location of the Ltn2 gene(s), we typed genomic DNAs of 193 N2 segregants of crosses between a high responder MA/MyJ and a low responder AKR/J by the polymerase chain reaction-simple sequence length polymorphism technique using 83 chromosome-specific microsatellite markers. We identified one major gene (Ltnr3) and three minor genes (Ltnr4, Ltnr5, and Ltnr6) responsible for the VDH induction. Ltnr3 was closely linked to D6Mit135 on chromosome 6 (P <0.00000) and Ltnr4, Ltnr5, and Ltnr6 to D9Mit161 on chromosome 9 (P <0.00032), D15Mit147 on chromosome 15 (P <0.00014) and D16Mit4 on chromosome 16 (P <0.00014), respectively.

Alleles↗
PubMed2005

Characterization of the Lentinula edodes exg2 gene encoding a lentinan-degrading exo-beta-1,3-glucanase.

Lentinan, an antitumor substance purified from Lentinula edodes, is degraded during post-harvest preservation as a result of increased glucanase activity. We isolated an exo-beta-1,3-glucanase encoding gene, exg2, from L. edodes which is a homologue of an exo-glucanase-encoding gene conserved in ascomycetous fungi. The exg2 gene was cloned as an approximately 2.4-kbp cDNA, and as a genomic sequence of 3.9-kbp. The product of the exg2 gene is predicted to contain 759 amino acids with a molecular weight of 79 kDa and a pI value of 4.6. The putative N-terminus of EXG2 is identical to the N-terminal sequences of lentinan-degrading enzymes, GNase I and II, and a custom-made anti-EXG2 peptide anti-serum cross-reacted with purified GNase I and II. Transcription and translation of exg2 was low in the gills of mature fruiting bodies, but increased after harvesting. We conclude that the exg2 gene is a lentinan-degrading enzyme-encoding-gene in L. edodes.

Amino Acid Sequence↗
PubMed1991

Genetic control of the expression of two biological activities of an antitumor polysaccharide, lentinan.

In order to make clear whether the expression of biological activities and antitumor polysaccharides are under genetic control, the responses of mice to lentinan, a beta-1,6;1,3-glucan, in the induction of several acute phase proteins (APPs) and T-cell-mediated vascular dilation and hemorrhage (VDH) were investigated. Twenty inbred strains of mice were divided into two groups according to their phenotypes in the induction of APPs when they were administered lentinan i.p. at a dose of 10 mg/kg; sensitive strains showed a marked increase in levels of APPs and resistant strains showed as low a level of APPs as non-treated control mice. No sex-related differences and no relation with H-2 halotypes were found in the responses. Only low-level responses were observed in F1 hybrid mice obtained by crosses between a sensitive and a resistant strain, indicating that the low APP response to lentinan is dominant. The N2 progeny between the F1 and a high responder segregated into high and low responders at a ratio of almost 1:1. These results suggest that a single major gene on an autosome is responsible for the induction of APPs. The induction of VDH also depended on the strains of mice. However, the strain distribution pattern of the VDH phenotype was distinct from that of the APP phenotype, indicating that the VDH-controlling gene was different from the APP-controlling gene. Further analyses with F1 hybrid and backcross progeny mice suggested that the high VDH response was dominant, and that the phenotype was determined by a single major gene.

Acute-Phase Proteins↗
PubMedDate not supplied

Down-regulation of tumor necrosis factor-alpha, moderate reduction of interleukin-1beta, but not interleukin-6 or interleukin-10, by glucan immunomodulators curdlan sulfate and lentinan.

The effects of glucan-based immunomodulators curdlan sulfate (CRDS) and lentinan on cytokine production stimulated by lipopolysaccharide (LPS) in bacillus Calmette-Guerin (BCG)-primed mice were investigated. Pretreatment with CRDS or lentinan before LPS administration induced a striking inhibition of up to 89% of circulating tumor necrosis factor-alpha (TNF), a moderate reduction of 25% of interleukin (IL)-1beta, no significant differences in IL-6 or IL-10 levels, and a marked depression of chemiluminescence activity. Animals receiving CRDS prior to infection with alpha-hemolysin positive Escherichia coli inhibited measurable TNF production by 63%. The ability of CRDS and lentinan to significantly reduce the TNF production in vivo indicates the potential of glucans in possible therapeutic strategies that are based on down-regulation of TNF.

Adjuvants, Immunologic↗
PubMed1996

Monocyte function associated with intermittent lentinan therapy after resection of gastric cancer.

The effect of lentinan administration on monocyte function in the peripheral blood were examined in 33 patients who underwent resection of gastric cancer. As parameters of monocyte function, IL-1 production, C3b receptor, Fc gamma receptor and monocyte ratio were determined every 4 weeks for a maximum of 24 weeks. Among patients who were taking combined therapy with lentinan, an increase in IL-1 beta production of more than 50% was found 8 weeks (2 months) after the initiation of therapy in 8 of 12 patients given 2 mg at 2-week intervals, and in 11 of 16 patients given the same dose at 4-week intervals. This increase was particularly clear in stage II or more advanced cases. There were no significant changes in the other parameters studied. It has been considered that lentinen is effective when administered once a week. The results of the present study, however, suggest that lentinan given every 4 weeks also stimulates monocyte function enough to maintain immunological activity.

Adjuvants, Immunologic↗
PubMed2006

Lentinula edodes tlg1 encodes a thaumatin-like protein that is involved in lentinan degradation and fruiting body senescence.

Lentinan is an antitumor product that is purified from fresh Lentinula edodes fruiting bodies. It is a cell wall component, comprising beta-1,3-glucan with beta-1,6-linked branches, which becomes degraded during postharvest preservation as a result of increased glucanase activity. In this study, we used N-terminal amino acid sequence to isolate tlg1, a gene encoding a thaumatin-like (TL) protein in L. edodes. The cDNA clone was approximately 1.0 kb whereas the genomic sequence was 2.1 kb, and comparison of the two indicated that tlg1 contains 12 introns. The tlg1 gene product (TLG1) was predicted to comprise 240 amino acids, with a molecular mass of 25 kD and isoelectric point value of 3.5. The putative amino acid sequence exhibits approximately 40% identity with plant TL proteins, and a fungal genome database search revealed that these TL proteins are conserved in many fungi including the basidiomycota and ascomycota. Transcription of tlg1 was not detected in vegetative mycelium or young and fresh mushrooms. However, transcription increased following harvest. Western-blot analysis demonstrated a rise in TLG1 levels following harvest and spore diffusion. TLG1 expressed in Escherichia coli and Aspergillus oryzae exhibited beta-1,3-glucanase activity and, when purified from the L. edodes fruiting body, demonstrated lentinan degrading activity. Thus, we suggest that TLG1 is involved in lentinan and cell wall degradation during senescence following harvest and spore diffusion.

Amino Acid Sequence↗
PubMed1984

Antitumor effect of bacterial lipopolysaccharide (LPS) alone and in combination with lentinan on MH-134 tumors in C3H/He mice.

Using C3H/He mice, the antitumor effect of lipopolysaccharide (LPS) alone and in combination with Lentinan extracted from Lentinus edodes was studied. The influence of LPS on cellular immunity and the antitumor effect of the tumor necrosis factor (TNF) were also examined. LPS, which was administered into mice with tumor, induced hemorrhagic necrosis of the tumor within 48 h, demonstrating a high antitumor effect. When LPS was used in combination with Lentinan, the tumor growth was significantly inhibited as compared to that in the control mice. The combination of LPS and Lentinan prevented a decrease in the delayed type hypersensitivity in tumor bearing mice. Application of rabbit serum containing TNF resulted in hemorrhagic necrosis of the tumor within 48 h, as with LPS.

Animals↗
PubMed1988

Effects of lentinan on cytotoxic functions of human lymphocytes.

The in vitro effects of lentinan on natural killer (NK), antibody-dependent cell-mediated cytotoxicity (ADCC), lectin-dependent cell-mediated cytotoxicity (LDCC) and mitogen-induced blast transformation were studied in patients with solid tumors and chronic lymphocytic leukemia (CLL). NK activity was measured against 51Cr-labelled K-562 targets, ADCC against antibody-coated chicken red cells. LDCC and natural cell-mediated cytotoxicity (NCMC) was assessed using 3H-thymidine prelabelled HEp-2 targets. Mitogen (PHA- and Con A-) induced blast transformation was measured by thymidine incorporation. Blastogenesis and LDCC was not influenced by lentinan. 1 microgram/ml lentinan increased NCMC of tumor-bearing subjects. The most prominent enhancement of NK and ADCC activity was seen in CLL patients, where a dose-related increase was seen (from 0.01 to 1 microgram/ml).

Antibody-Dependent Cell Cytotoxicity↗
PubMed1989

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. No significant antioxidant (free radical scavenger) effect has been observed in NADPH-induced and Fe3+-stimulated lipid peroxidation and in xanthine-xanthine oxidase system.

Animals↗
PubMed1998

[Immune modulatory and therapeutic effect of lentinan on condyloma acuminatum].

OBJECTIVE: To observe the immune modulatory and therapeutic effect of lentinan on condyloma acuminatum (CA). METHODS: Thirty-six CA patients were randomly divided into two groups, 19 in the test group treated with lentinan plus CO2 laser irradiation and 17 in the control group treated with laser irradiation alone. Their T-lymphocyte subsets of peripheral blood and level of serum interleukin-2 (IL-2) and soluable interleukin-2 receptor (SIL-2R) were determined before and after treatment, and the recurrence rates of the two groups were compared. RESULTS: After treatment, in the test group, the CD4/CD8 ratio, serum IL-2 raised and serum SIL-2R lowered significantly (P < 0.05, 0.05, 0.05 respectively) as compared with before treatment, while those parameters were not changed significantly in the control group. The recurrence rate of the test group was lower than that of the control group, P < 0.05. CONCLUSION: Lentinan could modulate the cellular immunofunction of CA patients and reduce the recurrence rate of CA.

Adjuvants, Immunologic↗
PubMed2003

[Usefulness of TS-1 and lentinan combination immunochemotherapy in advanced or recurrent gastric cancer--pilot study aiming at a randomized trial].

The quality of life (QOL) of patients with advanced or recurrent gastric cancer is poor and their immunocompetence is low, making it important to conduct chemotherapy while at the same time improving their QOL and maintaining their immunocompetence. To improve QOL and increase compliance by reducing the side effects but not the antitumor effect of TS-1, a 2-week regime with 2-week administration of TS-1, and a 1-week drug-free interval in combination with the immunotherapeutic agent lentinan (LNT) was started in 5 patients with advanced or recurrent gastric cancer. Toxicity, efficacy, QOL, and immunological parameters were investigated preliminarily to examine whether or not usefulness of lentinan could be evaluated. QOL scores for appetite, nausea/vomiting, and abdominal pain/diarrhea showed improvement, although not in statistically significant values. The Th2 (CD4-positive, IL4-positive T cells) response in peripheral blood decreased significantly. TS-1 and lentinan combination immunotherapy was carried out safely with advanced recurrent gastric cancer. In order to examine the usefulness of LNT combined use, it was thought that a randomised trial using toxicity with not only efficacy but QOL and immunological parameters as indicators would be beneficial.

Adult↗
PubMed2003

[TS-1 and lentinan combination immunochemotherapy for advanced or recurrent gastric cancer: a preliminary report].

The immunocompetence and nutritional state of patients with advanced or recurrent gastric cancer is low, making it important to conduct chemotherapy while at the same time improving or maintaining their immunocompetence and nutritional state. To reduce the side effects but not the antitumor effect of TS-1, a 2-week regime of TS-1, and 1-week drug-free interval, in combination with the immunotherapeutic agent lentinan (LNT) was started in 5 patients with advanced or recurrent gastric cancer. Toxicity, efficacy, immunocompetence and nutritional state were investigated preliminarily to examine whether or not usefulness of lentinan could be evaluated. The IAP tended to decrease. TS-1 and lentinan combination immunochemotherapy was able to be carried out safely in patients with advanced recurrent gastric cancer. In order to examine the usefulness of combined LNT, it is thought to be necessary to perform a randomized trial using toxicity and not only efficacy but QOL and immunological and nutritional parameters as indicators.

Adjuvants, Immunologic↗
PubMed1979

Depressed prostaglandin release from peritoneal cells induced by a T cell adjuvant, lentinan.

PGE and PGF release from peritoneal exudate cells was studied in mice after injection with two beta (1-3) glucans, the antitumor active lentinan and the inactive pachyman, 4 days after injection of both polysaccharides, the spontaneous and phagocytosis-induced PGE and PGF release was markedly suppressed. However, only the immunopotentiator lentinan induced peritoneal exudate cells which exhibited a longer lasting diminished PG release. The data suggest that the T cell adjuvant lentinan may potentiate cellular immune responses by reducing synthesis of immune suppressive prostaglandins from peritoneal exudate cells.

Adjuvants, Immunologic↗