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PubMed1989

[Change of blood lentinan level in patients with advanced cancers].

A conventional limulus test can detect not only endotoxin but also beta(1----3) glucan. Therefore, with a quantitative limulus test, the limulus colorimetric test, we studied the pharmacokinetics of lentinan, an antitumor beta(1----3) glucan preparation, in the blood of 10 healthy volunteers and 20 patients with advanced cancers. The calibration curve of lentinan in the human plasma was linear in the range of 0 to 100 ng/ml. Two mg of lentinan was administered once a week and blood samplings for the measurement were done immediately before the next lentinan administration to document trough-levels serially at a week interval. Trough-levels tended to rise gradually and showed a rapid elevation between 4 and 8 weeks after beginning of administration. This phenomenon may correlate closely with the antitumor effect of lentinan and, therefore, deserves further investigations.

Antineoplastic Agents↗
PubMed1987

[A comparative clinical trial with tegafur plus lentinan treatment at two different doses in advanced cancer].

In order to evaluate the clinical efficacy of combined tegafur plus lentinan treatment, a comparative trial was performed on patients with advanced cancer using two different doses, a conventional-dose group and a high-dose group. Thirty-four patients were evaluable in this trial. The doses of medication were 600 mg of tegafur p.o. daily and 1-2 mg of lentinan i.v. weekly in the conventional-dose group, and 1,200-800 mg of tegafur p.o. daily and 4 mg of lentinan i.v. weekly in the high-dose group. The response was evaluated using the criteria of Koyama. The response rates were 14.3% for the conventional-dose group and 25.0% for the high-dose group, although no statistical difference was observed. Acute toxicities such as oppression in the anterior chest and dryness of the throat, which were considered to be probably due to lentinan, were noted in patients given rapid administration with 20 ml of solution. However, these effects disappeared with slow-drip infusion using 100-200 ml of solution. These results suggest that the combined tegafur plus lentinan treatment would be better administered at a dose higher than the conventional one for the treatment for advanced cancers.

Adult↗
PubMed1987

[Granulopoietic effects of lentinan, an antitumor polysaccharide in BALB/c nude mice].

The effect of lentinan on granulopoiesis in BALB/c nude mice (Nu/Nu) was compared with that in their heterozygotes (Nu/+). Lentinan-injected Nu/+ showed enhanced serum colony-stimulating activity (CSA), and increased diphasically granulocyte-macrophage colony forming cells (GM-CFC) in bone marrow and spleen (i.e., first peak on day 1-2 and second peak on day 6). On the other hand, in Nu/Nu, lentinan did not enhance serum CSA, although the control level was higher than the enhanced level in Nu/+. Monophasic increase in GM-CFC was observed in Nu/Nu, but the second peak seen in Nu/+ was not observed. Reconstitution of Nu/+ splenocytes to Nu/Nu increased GM-CFC on day 6, and the increase was augmented by lentinan administration. These results suggest that mature T-cells participate in regulation of granulopoiesis in vivo and that lentinan augments granulopoiesis at least in part via mature T-cell populations.

Animals↗
PubMed1987

[Age-dependent anti-tumor activity of lentinan in mice].

During the course of aging, the weight percentage of organs such as kidney to body weight remain almost unchanged, whereas the weight of the thymus decreases significantly. The antitumor activity of Lentinan is constant in mice younger than 1 year (52 weeks). From 52 weeks, aging has a suppressive effect on antitumor activity. Even in aged mice, administration of Lentinan was shown to be effective, and better results were obtained through chronic administration, even with a smaller dose. Lentinan enhanced delayed cutaneous hypersensitivity in aged mice similarly to that in young mice. Thymus homogenate showed synergism with Lentinan in 2-year-old mice for suppression of tumor growth, although thymus homogenate alone showed no effect. These results show that Lentinan is effective as an anticancer immunopotentiator in aged animals in a similar way to young animals.

Adjuvants, Immunologic↗
PubMed1987

[Suppressive effect of lentinan on pulmonary metastases in murine tumors].

Lentinan has been shown to have a suppressive effect on the natural pulmonary metastasis of Lewis lung carcinoma, though its effect seems to depend on the timing of the administration. Administration of lentinan after the amputation of tumor was found to be more effective than before administration. Additionally, lentinan also has shown a marked suppressive effect on the pulmonary metastasis of MC-CS-1 fibrosarcoma, a high sensitive tumor for lentinan in any administration examined. These date suggest the usefulness of lentinan in suppressing tumor metastasis.

Animals↗
PubMed1979

Potentiation of schistosome granuloma formation. By lentinan--a T-cell adjuvant.

Lentinan is a fungal polysaccharide which acts as a T-cell adjuvant. When this glucan was administered to thymus-intact mice by intraperitoneal injection, conspicuously enlarged lung granulomas formed in response to either Schistosoma mansoni or S japonicum eggs or to antigen-coated polyacrylamide beads. Liver granulomas in cercaria-induced S mansoni infection were augmented up to eight-fold in volume. By contrast, nude mice showed a complete absence of hypersensitivity granulomas, regardless of whether they received lentinan. Lentinan-potentiated granulomas show a distinctive histopathologic picture characterized by abundant, large, pale-staining macrophages; reduced and redistributed eosinophil populations; and frequent, extensive central necrosis, uncommon in unpotentiated schistosome foci. They also differ in their distributions of egg antigen and of host immunoglobulins. Optimal lentinan effects followed a single 1-mg dose when given to sensitized mice on the day of intravenous challenge with S mansoni eggs rather than at the time of intraperitoneal sensitization or following challenge. This adjuvant appears to act on effector T cells or on macrophages interacting with T cells; its effect on macrophages in a latex bead foreign body granuloma was minimal. A number of other lentinan-associated systemic effects on parasite and host were noted and described, including reduced female schistosome egg output.

Adjuvants, Immunologic↗
PubMed1994

[Study on intratumor administration of lentinan--primary changes in cancerous tissues].

Lentinan was administered for gastric cancer in order to determine what type of changes would occur as a consequence. In an experimental study, the intraperitoneal administration of lentinan on cancerous tissues caused a marked development of reticular fibers, along with an enhanced interstitial response. Findings which support the relationship between a marked development of reticular fibers and an anti-tumor effect, were also obtained. Furthermore, lentinan was administered for human gastric cancer to evaluate whether or not an increase in interstitial response would be observed. As a result, reticular fibers developed in tumor sites with a resultant fragmentation of cancer cell nests. Many T lymphocytes infiltrated cancer sites where the lentinan was administered. These findings suggest that the intratumor administration of lentinan enhanced an interstitial response and also activated an anti-tumor immune response in the human gastric cancer tissues.

Animals↗
PubMedDate not supplied

Augmentation of lymphokine-activated killer cell activity by lentinan.

Lymphokine-activated killer (LAK) activity stimulated by interleukin 2 (IL-2) and/or lentinan was examined in the peripheral blood of 9 healthy subjects and 7 cancer patients. After 4 and 8 days culture, LAK killer activity stimulated by IL-2 and lentinan against autologous tumor and K562 cells was greater than that stimulated by IL-2 alone. The optimal concentration of lentinan for the generation of killer cells ranged from 25-500 ng/ml, a level which can be achieved in vivo by the administration of clinical doses of this agent. The expression of CD25 antigen, the alpha chain of the IL-2 receptor on the activated killer cells was increased by lentinan. Thus it was shown that LAK cells stimulated with IL-2 plus lentinan had strong cytotoxicity and might be useful as effector cells for adoptive immunotherapy.

Cytotoxicity, Immunologic↗
PubMed2005

Effects of excluded volume and polydispersity on solution properties of lentinan in 0.1 M NaOH solution.

Seven lentinan fractions of various weight-average molecular weights (M(w)), ranging from 1.45 x 10(5) to 1.13 x 10(6) g mol(-1) were investigated by static light scattering and viscometry in 0.1M NaOH solution at 25 degrees C. The intrinsic viscosity [eta] - M(w) and radius of gyration s(2)(z) (1/2) - M(w) relationships for lentinan in 0.1M NaOH solution were found to be represented by [eta] = 5.1 x 10(-3)M(w) (0.81) cm(3) g(-1) and s(2)(z) (1/2) = 2.3 x 10(-1)M(w) (0.58) nm, respectively. Focusing on the effects of the M(w) polydispersity with the Schulz-Zimm distribution function, the data of M(w), s(2)(z) (1/2), and [eta] was analyzed on the basis of the Yoshizaki-Nitta-Yamakawa theory for the unperturbed helical wormlike chain combined with the quasi-two-parameter (QTP) theory for excluded-volume effects. The persistence length, molecular weight per unit contour length, and the excluded-volume strength were determined roughly to be 6.2 nm, 980 nm(-1), and 0.1, respectively. Compared with the theoretical value calculated by the Monte Carlo model, the persistence length is longer than that of the single (1 --> 3)-beta-(D)-glucan chain. The results revealed that lentinan exists as single-stranded flexible chains in 0.1M NaOH solution with a certain degree of expansion due to the electrostatic repulsion from the interaction between the OH(-) anions and lentinan molecules.

Carbohydrate Conformation↗
PubMed1980

Effect of lentinan on the production of migration inhibitory factor induced by syngeneic tumor in mice.

Attempts were made to reveal the mechanism of the inhibitory effect of lentinan on methylcholanthrene-induced transplantable fibrosarcoma (A/Ph.MC.SI) isografts. Since the involvement of a delayed-type hypersensitivity response can be supposed to operate against this syngeneic tumor, the enlargement of regional lymph nodes, the DNA synthesis activity and the migration inhibitory factor producing capacity of the regional lymph-node cells were studied in the control and lentinan-treated, tumor-bearing mice at different times after tumor implantation. The only parameter affected until the first sign of tumor inhibition on the 8th day was the MIF-producing capacity. Regional lymph-node cells in the lentinan-treated mice showed a peak response at this time while practically no MIF was produced by cells of non-treated mice. The early phase of the developing anti-tumor reaction (enlargement of and proliferation in the lymph nodes) was initiated in all recipients but only some of them could reject the tumor in the non-treated animals that rejected the tumors in all cases. It can be supposed that a tumor-induced immunosuppression emerges in the tumor-bearers and can be overcome by lentinan treatment, most likely through enhancement of the MIF production. For measurement of MIF activity a continuously dividing in vitro macrophage-like cell line was established and employed in the micro-wound migration assay.

Animals↗
PubMed1983

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. Therefore, lentinan is suitable for clinical application for cancer patients from the results in its preclinical animal model experiments.

Adjuvants, Immunologic↗
PubMed1993

Effect of lentinan on lymphocyte subsets of peripheral blood, lymph nodes, and tumor tissues in patients with gastric cancer.

The effect of lentinan on lymphocyte subsets of peripheral blood, lymph nodes, and tumor tissues in gastric cancer patients was investigated. A 2-mg dose of lentinan was administered to 12 patients intravenously twice, the first at 3-9 days before and the second the day before surgery. The results were then compared with a control group without lentinan administration comprising 12 patients. Regarding peripheral blood and lymph nodes without metastasis, lymphocyte subsets defined with anti-CD3, anti-CD4, anti-CD8, anti-Leu7, and anti-Leu11 were analyzed by flow-cytometry. As for tumor tissues, lymphocyte subsets defined with anti-CD3, anti-CD4, anti-CD8, anti-Leu11, and anti-M3 were analyzed after immunohistochemical staining. There were no significant changes in the lymphocyte subsets of peripheral blood between the two groups. In the lymph nodes, the CD4 cell ratios increased; otherwise in regard to tumor-infiltrating lymphocytes (TILs), the number of CD4, Leu11 and LeuM3 cells showed a prominent increase. Therefore, lentinan was observed to produce different effects in accordance with the subjective organs.

Aged↗
PubMed1988

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. Encapsulated parasites were dead or dying, and such damage appeared to be mediated by increased numbers of macrophages and giant cells.

Animals↗
PubMed1993

Effect of lentinan on macrophage cytotoxicity against metastatic tumor cells.

We studied the effect of lentinan, a fungal polysaccharide immunomodulator, on mouse peritoneal macrophages. The i.p. treatment of mice with 10 mg/kg lentinan affected the number, plastic-adherence, and endogen peroxidase activity of peritoneal cells. The cytotoxicity of lentinan-stimulated peritoneal macrophages was determined against several murine and human metastatic tumor targets: Lewis lung carcinoma (LLT) and two human melanomas, and was found to be significantly higher than that of the macrophages from control animals. However, the highly metastatic variant of LLT (LLT-HH) was resistant to the cytolytic effect of resident and lentinan-activated macrophages as well, indicating that the stimulation for cytotoxicity depends not only on the functional activity of the effector but also on the sensitivity of the target.

Animals↗
PubMed1992

Immunological analysis and clinical effects of intraabdominal and intrapleural injection of lentinan for malignant ascites and pleural effusion.

Twenty effusions in sixteen patients with malignant peritoneal and/or pleural effusions were treated with intracavitary injection of lentinan. Lentinan was injected at a dosage of 4 mg/week for 4 weeks. In total, sixteen (80%) of twenty lesions demonstrated clinical responses. Performance status was improved in seven patients. The average survival time in responders was 129 days, while, in non-responders, it was 49 days. Serious toxicities were not observed. NK activity of PBMC significantly decreased after lentinan injection. NK activity of PEC in responders was augmented significantly. Anti-Daudi and lymphokine activated killer activity were also augmented or maintained after lentinan injection.

Adult↗
PubMed1982

The effect of lentinan on production of interleukin-1 by human monocytes.

Activated human monocytes produce a monokine, interleukin-1 (IL-1) which can amplify the immune response by inducing antigen specific T cells to elaborate T cell growth factor, or interleukin-2, which in turn causes T cells to proliferate. The immune adjuvant lentinan has been shown in this study to augment IL-1 production by human monocytes. Stimulation of IL-1 by lentinan was seen as early as 5 hr, with some effect as late as 60 hr. Optimal effects were seen with very low concentrations, around 0.1 micrograms/ml. Lentinan was also able to stimulate IL-1 production by the leukemic cell line, K-562. The data reported here suggest that the previously reported adjuvant effects of lentinan may in part be mediated via its ability to stimulate IL-1 production.

Adjuvants, Immunologic↗
PubMed1989

Inhibition of mitomycin C-induced sister-chromatid exchanges in mouse bone marrow cells by the immunopotentiators Krestin and Lentinan.

We have carried out an investigation to determine whether or not the sister-chromatid exchange frequencies (SCEs) observed in bone marrow cells in mice treated with mitomycin C (MMC) are inhibited by the immunopotentiators Krestin and Lentinan. We found that mitomycin C (2 mg/kg, i.v.)-induced SCEs were inhibited in 27% of the mice treated with Krestin (300 mg/kg, i.p.) and in 23% of the mice treated with Lentinan (1 mg/kg, i.p.). The effects of Krestin were found to be dose-dependent in inhibition of MMC-induced SCEs while those of Lentinan were not. Our findings therefore suggest that Krestin and Lentinan are not only useful for cancer treatment as immunopotentiators in combination with anticancer drugs but may also prevent the increase of chromosomal damage induced by anticancer drugs.

Adjuvants, Immunologic↗
PubMed1984

Acting mechanisms of Lentinan in human--II. Enhancement of non-specific cell-mediated cytotoxicity as an interferon inducer.

The immunopotentiator "Lentinan" augmented the cell-mediated cytotoxicity in humans. (a) The activation of killer T cells by the mixed lymphocyte culture was accelerated only when responder cells were mixed with both a suboptimum number of stimulator cells and Lentinan. (b) The interferon level in the peripheral blood circulation of cancer patients was elevated in 12 h following Lentinan administration, and natural killer activity of peripheral mononuclear cells was enhanced in 48 h. These data indicate that Lentinan favorably affects the host mechanisms of man.

Adenoma, Bile Duct↗