A Quality-of-Life Study in Healthy Adults Supplemented with Lentinex® Beta-Glucan of Shiitake Culinary-Medicinal Mushroom, Lentinus edodes (Agaricomycetes).

Lentinus edodes (=Lentinula edodes) is a culinary-medicinal mushroom with a long tradition of use in Asia. The major active substance in L. edodes is a beta-(1-3,1-6)-glucan (lentinan). GlycaNova produces Lentinex®, which contains this beta-glucan from L. edodes mycelia, in a proprietary process that maintains the triple helix molecular structure and high molecular weights. This study was carried out to investigate the effect of Lentinex supplementation on the well-being of adults. We evaluated the effect of Lentinex in healthy adult subjects in a randomized, placebo-controlled, double-blind trial. Sixty-three subjects, randomly allocated to two groups, took orally either 1-2 mL/day Lentinex (1-2 mg beta-glucan) or placebo for four weeks. The participants completed a well-being questionnaire prior to commencing supplementation and again at the end of the in-home study. The results showed an important and statistically significant improvement in well-being over the period in the treated group compared with the placebo group. The degree of improvement in the treated group, including relative to placebo, was higher for subjects who had lower initial well-being than for subjects with higher initial well-being. In conclusion, the lower an individual's initial well-being, the more Lentinex helped.

Lentinan in-situ coated tungsten oxide nanorods as a nanotherapeutic agent for low power density photothermal cancer therapy.

Development of high photothermal performance and biocompatible nanotherapeutic agents is of great importance for photothermal cancer treatment. In this paper, we have developed lentinan decorated tungsten oxide nanorods (W18O49@LTN NRs) via a mild one-step solvothermal route. Owing to the numerous surface hydroxyl groups of polymer chains, the presence of lentinan layer in the surface of W18O49 NRs lead to good biocompatibility. The lentinan layer also affects the crystal structure of W18O49 and improves near-infrared absorption (~1.7 × 109 M-1 cm-1 at 980 nm), which is two orders of higher than previously reported PEGylated W18O49 nanowires. Even under near-infrared (NIR) laser irradiation at a very low power density of 0.4 W/cm2, the temperature of W18O49@LTN NRs aqueous dispersion (125 µg/mL) could increase by 15.1 °C. The photothermal conversion efficiency of W18O49@LTN NRs reaches 33.86%, which is higher than previously reported WO3-x hierarchical nanostructures (28.1%). Importantly, when cancer cells were treated with W18O49@LTN NRs (200 µg/mL) and 980 nm laser (0.4 W/cm2), a significant photo-induced cell killing behavior was observed. This work demonstrates that W18O49@LTN NRs have the potential for precise cancer treatment.

Mushroom polysaccharide lentinan for treating different types of cancers: A review of 12 years clinical studies in China.

Lentinula edodes has been used to improve general health for thousands of years in Asia. It is the second largest cultivated and the most popular edible mushroom in the world known as "Xianggu" in China and "Shiitake" in Japan. Lentinan is a polysaccharide extracted from Lentinula edodes. ß-Glucan is the major bioactive component in lentinan with immunostimulatory effect. The antitumor property of lentinan was reported in 1960s. Biochemical studies indicate that immunocytes can be activated by lentinan through multiple signaling pathways, such as TLR4/Dectin1-MAPK and Syk-PKC-NFκB pathways. Though it has been approved as an adjuvant therapeutic drug both in China and Japan for treating cancers since 1980s, a systematic review of clinical studies of lentinan has not been conducted elaborately. In this review, over 9474 reported lentinan-associated cancer treatment cases are evaluated and summarized from 135 independent studies in China during the past 12 years (2004-2016) based on CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP Chinese Scientific Journals Database) and Wanfang database. The 9474 reported lentinan-associated cancer treatment cases include lung cancer (3469 cases), gastric cancer (3039 cases), colorectal cancer (1646 cases), ovarian cancer (183 cases), cervical cancer (130 cases), Non-Hodgkin lymphoma (70 cases), pancreatic cancer (15 cases), cardiac cancer (15 cases), nasopharyngeal cancer (14 cases), duodenal cancer (1 case) and 110 cancer cases with no classifying patient information. Overall clinical data show solid effect of lentinan on improving the quality of life and on promoting the efficacy of chemotherapy and radiation therapy during cancer treatment.

Lentinan as an immunotherapeutic for treating lung cancer: a review of 12 years clinical studies in China.

PURPOSE: Lentinan is a polysaccharide extracted from Shiitake mushrooms that have been used to improve general health for thousands of years in Asia. Lentinan injection is a clinically approved drug in several countries in Asia. The purpose of this study is to review the structure, preclinical and clinical studies, and molecular mechanisms of lentinan. Most importantly, the clinical effectiveness of lentinan as an adjuvant therapeutic drug in treating patients with lung cancer in China during the past 12 years is analyzed statistically. METHODS: We carried out literature search of randomized controlled trials (RCTs) published from 2004 to 2016 based on CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP Chinese Scientific Journals Database) and Wanfang database, and 38 eligible RCTs of lentinan-associated lung cancer treatment were identified, containing 3,117 patients. RESULTS: The structure and function relationship and underlying molecular mechanism of lentinan as an immunostimulant has been summarized. The mean value of overall response rate in treating lung cancer was increased from 43.3% of chemotherapy alone to 56.9% of lentinan plus chemotherapy [p < 0.001, 95% confidence interval (CI) 0.102-0.170]. Compared with chemotherapy alone, lentinan plus chemotherapy showed more efficacy in treating lung cancer (pooled RR 0.79, 95% CI 0.74-0.85) and no statistical heterogeneity was found among studies (I2 = 11%). CONCLUSION: Clinical data presented in the past 12 years shows that lentinan is effective not only in improving quality of life, but also in promoting the efficacy of chemotherapy during lung cancer treatment.

Activation of the NRF2-ARE signalling pathway by the Lentinula edodes polysaccharose LNT alleviates ROS-mediated cisplatin nephrotoxicity.

The nephrotoxicity of cisplatin (cis-DDP) limits its general clinical applications. Lentinan (LNT), a dextran extracted from the mushroom Lentinula edodes, has been shown to have multiple pharmacological activities. The primary objective of the current study was to determine whether and how LNT alleviates cis-DDP- induced cytotoxicity in HK-2 cells and nephrotoxicity in mice. LNT did not interfere with cisplatin's anti-tumour efficacy in vitro and functioned cooperatively with cis-DDP to inhibit activity in HeLa and A549 tumour cells. LNT alleviated the cis-DDP-induced decrease in HK-2 cell viability, caspase-3 activation and cleavage of the DNA repair enzyme PARP, decreased HK-2 cell apoptosis and inhibited reactive oxygen species (ROS) accumulation in HK-2 cells. The inhibitor of ROS (N-acetyl-L-cysteine, NAC) could decreased the apoptosis of HK-2 cell. In addition, LNT significantly prevented cis-DDP-induced kidney injury in vivo. LNT itself could not eliminate ROS levels in vitro. Further studies demonstrated that LNT induced NF-E2 p45-related factor 2 (Nrf2) protein and mRNA expression in a time- and dose-dependent manner. LNT promoted Nrf2 translocation to the nucleus and binding to the antioxidant-response element (ARE) sequence and induced the transcription and translation of heme oxygenase 1 (HO-1), aldo-keto reductases 1C1 and 1C2 (AKR1C), and NADP(H):quinone oxidoreductase 1 (NQO1). Finally, we used hNrf2 siRNA and an Nrf2 agonist (tBHQ) to inhibit or enhance Nrf2 expression. The results demonstrated that the LNT-mediated alleviation of cis-DDP-induced nephrotoxicity was achieved by preventing the accumulation of ROS in a manner that depended on the activation of the Nrf2-ARE signalling pathway.

The use of lentinan for treating gastric cancer.

Natural compounds containing fungal ß-glucans have been used to improve general health for thousands of years in China and Japan. Lentinan, the backbone of ß-(1, 3)-glucan with ß-(1, 6) branches, is one of the active ingredients purified from Shiitake mushrooms and has been approved as a biological response modifier for the treatment of gastric cancer in Japan. Despite recent advances in chemotherapeutic agents, unresectable or recurrent gastric cancer remains an incurable disease, with survival rates being far from satisfactory. Recent clinical studies have shown that chemo-immunotherapy using lentinan prolongs the survival of patients with advanced gastric cancer, as compared to chemotherapy alone. In addition, trastuzumab, an antibody against HER2/neu growth factor receptor, has been used for the treatment of gastric cancer in combination with cytotoxic chemotherapeutic agents. Lentinan may exert a synergistic action with anti-cancer monoclonal antibodies to activate complement systems through the mechanism of antibody-dependent cellular cytotoxicity and complement dependent cytotoxicity. Because a better understanding of its biological activities should enable us to use lentinan more efficiently in the treatment of gastric cancer, immunological effects provided by ß-glucans, a possible mode of action of lentinan, and its clinical application including future potential uses are discussed in the present review.

[Clinical observation of thermotherapy combined with thoracic injection of lentinan in treatment of cancerous hydrothorax of patients with lung cancer].

OBJECTIVE: To study the therapeutic effect and mechanism of thermotherapy combined with thoracic injection of lentinan in treatment of cancerous hydrothorax (CH) in patients with lung cancer. METHODS: Sixty lung cancer patients complicated with CH were randomly assigned to the observation group and the control group, 30 in each. CH was released by closed drainage of the thoracic cavity in all patients. Thermotherapy was given to patients in the observation group after lentinan was thoracically injected, while lentinan was thoracically injected to patients in the control group. RESULTS: The total effective rate of CH improvement was 73.3% (22/30) in the control group and 83.3% (25/30) in the observation group, showing insignificant difference (P>0.05). The stability rate and the weight stability rate by Karnofsky's performance scoring in the observation group were superior to those of the control group, showing significant difference (P<0.05). No hematological reaction, hepatic or renal damage occurred before and after treatment in both groups. Fever, thoracalgia, dyspnea, rash, nausea and vomit appeared in few patients of the two groups, showing insignificant difference (P>0.05). CD3+, CD4+, CD4+/CD8+, and NK obviously increased and CD8+ decreased in the observation group after treatment, showing significant difference from those before treatment (P<0.05). Compared with the control group after treatment, CD3+, CD4+, CD4+/CD8+, and NK obviously increased, CD8+ increased in the observation group (P<0.05). CONCLUSION: Thermotherapy combined with thoracic injection of lentinan showed better effect in treatment of CH in patients with lung cancer. No obvious adverse reaction was seen.

Lentinan: hematopoietic, immunological, and efficacy studies in a syngeneic model of acute myeloid leukemia.

Lentinan, a beta-glucan nutritional supplement isolated from the shitake mushroom (Lentula edodes), is a biological response modifier with immunostimulatory properties. Concomitantly, the role of beta-glucans as chemoimmunotherapeutic in a number of solid cancers has been widely documented. We investigated the effects of nutritional grade lentinan upon BN rats and in a preclinical syngeneic model of acute myeloid leukemia. BN rats supplemented daily with lentinan exhibited weight gains, increased white blood cells, monocytes, and circulating cytotoxic T-cells; and had a reduction in anti-inflammatory cytokines IL-4, IL-10, and additionally IL-6. Lentinan treatment of BN rats with BNML leukemia resulted in improved cage-side health and reduced cachexia in the terminal stage of this aggressive disease. Combination of lentinan with standards of care in acute myeloid leukemia, idarubicin, and cytarabine increased average survival compared with monotherapy and reduced cachexia. These results indicate that nutritional supplementation of cancer patients with lentinan should be further investigated.

Clinical efficacy of superfine dispersed lentinan (beta-1,3-glucan) in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Recently, complementary alternative medicine is actively performed for cancer therapy. We investigated the effectiveness of supplementary food containing superfine dispersed lentinan (beta-1,3-glucan) in patients with unresectable or recurrent hepatocellular carcinoma in a multi-center study. METHODOLOGY: Peripheral blood was collected prior to the test food ingestion and was incubated with fluorescein-labeled lentinan. The rates of lentinan-binding CD14+ monocytes were determined by flow cytometry. Patient survival times were followed up for 3 years. RESULTS: Thirty-six patients were eligible among 40 enrolled patients. Median survival time of eligible patients was 13.6 months (95% confidence interval, 8.7-18.9 months). Survival times of patients who ingested test food for a mean period of 47 weeks (range, 26 to 145 weeks) were significantly longer than that of patients who ingested for 7 to 12 weeks (p < 0.05). The rates of lentinan-binding cells in CD14+ monocytes showed individual variations (0.1-19.7%; Median, 1.6%). Survival times (median survival time, 16.3 months) of lentinan-high-binding group were significantly longer than those (median survival time, 12.5 months) of lentinan-low-binding group (p < 0.05). CONCLUSIONS: A superfine dispersed lentinan-containing supplementary food is effective for hepatocellular carcinoma patients' survival. Long-time ingestion is preferable. Assessment of lentinan-binding CD14+ monocytes is a promising prognostic predictor.

Efficacy of oral administered superfine dispersed lentinan for advanced pancreatic cancer.

BACKGROUND/AIMS: Recently, complementary alternative medicine is actively performed for cancer therapy. Superfine dispersed lentinan (beta-1,3-glucan)--an oral effective form--was recently developed and available. We investigated the effectiveness of superfine dispersed lentinan in advanced pancreatic cancer patients in a multi-center study. METHODOLOGY: Twenty-nine patients with unresectable and recurrent pancreatic cancer were enrolled, and adverse events and quality of life scores were assessed. Survival times were evaluated according to results of a 3-year follow-up survey. RESULTS: Although a diarrhea of grade-1 adverse event dependent on the test article (3.4%) was observed, the symptom was remitted without any treatment. This indicates that test article was free of anything harmful. Median survival time was 12.1 months (95% confidence interval: 7.3-25.7 months) in 25 eligible patients. Five (20%) out of 25 patients were alive for 3 years. There was a significant correlation between the quality of life scores after the superfine dispersed lentinan treatment and survival times. CONCLUSIONS: A superfine dispersed lentinan is deemed safe and effective for advanced pancreatic patients' survival and improvement of quality of life. And the assessment of quality of life status after the administration of superfine dispersed lentinan is a promising prognostic predictor.

The shiitake mushroom-derived immuno-stimulant lentinan protects against murine malaria blood-stage infection by evoking adaptive immune-responses.

Lentinan, a (1-3)-beta glucan from Lentinus edodes, is an effective immunostimulatory drug. We tested the effects of lentinan during blood-stage infection by Plasmodium yoelii 17XL (P.y17XL). Pre-treatment of mice with lentinan significantly decreased the parasitemia and increased their survival after infection. Enhanced IL-12, IFN-gamma and NO production induced by lentinan in spleen cells of infected mice revealed that the Th1 immune response was stimulated against malaria infection. In vitro and in vivo, lentinan can result in enhanced expression of MHC II, CD80/CD86, and Toll-like receptors (TLR2/TLR4), and increased production of IL-12 in spleen dendritic cells (DCs) co-cultured with parasitized red blood cells (pRBCs). Moreover, both the number of CD4(+)CD25(+) regulatory T cells (Tregs) and the levels of IL-10 secreted by Tregs were reduced by pre-treatment with lentinan in the spleen of malaria-infected mice. Meanwhile, apoptosis of CD4(+) T cell in spleens of mice pretreated with lentinan was significantly reduced. In summary, lentinan can induce protective Th1 immune responses to control the proliferation of malaria parasites during the blood-stage of P.y17XL infection by stimulating maturation of DCs to inhibit negative regulation of the Th1 immune response by Tregs. Taken together, our findings suggest that lentinan has prophylactic potential for the treatment of malaria.

[Study on effect of lentinan in enhancing anti-tumor action of dendritic cytoma vaccine and its mechanism].

OBJECTIVE: To improve the anti-tumor effect of dendritic cytoma vaccine (DCV) for finding an effective anti-tumor biotherapy. METHODS: DC vaccine prepared by transfection of adenovirus mediated melanoma-associated antigen gene (gp100) into bone marrow-derived dendritic cell (DC) was used to study the immuno-therapeutic effect and the mechanism of lentinan (LNT) in different dosages, used alone or combined with gp100-DC for treatment of B16 melanoma bearing mice. RESULTS: After being treated with LNT combining gp100-DC, the growth of malignant melanoma was inhibited with the tumor-free survival in the experimental animals being 66.7%. The treatment could also significantly enhance the activity of cytotoxicity T lymphocyte (CTL) and natural killer (NK) cells, elevate the levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) in splenocytes, and histological examination showed that a large amount of inflammatory cells infiltrated inside and around the tumor, and obvious necrosis of tumor cells was found. CONCLUSION: By combined use with LNT the anti-tumor immuno-reaction of DCV vaccine could be enhanced effectively.

Medicinal mushrooms and cancer therapy: translating a traditional practice into Western medicine.

Modern medical practice relies heavily on the use of highly purified pharmaceutical compounds whose purity can be easily assessed and whose pharmaceutical activity and toxicity show clear structure-function relationships. In contrast, many herbal medicines contain mixtures of natural compounds that have not undergone detailed chemical analyses and whose mechanism of action is not known. Traditional folk medicine and ethno-pharmacology coupled to bioprospecting have been an important source of many anticancer agents as well as other medicines. With the current decline in the number of new molecular entities from the pharmaceutical industry, novel anticancer agents are being sought from traditional medicine. As the example of medicinal mushrooms demonstrates, however, translating traditional Eastern practices into acceptable evidence-based Western therapies is difficult. Different manufacturing standards, criteria of purity, and under-powered clinical trials make assessment of efficacy and toxicity by Western standards of clinical evidence difficult. Purified bioactive compounds derived from medicinal mushrooms are a potentially important new source of anticancer agents; their assimilation into Western drug discovery programs and clinical trials also provides a framework for the study and use of other traditional medicines.

Mushrooms, tumors, and immunity.

Medicinal properties have been attributed to mushrooms for thousands of years. Mushroom extracts are widely sold as nutritional supplements and touted as beneficial for health. Yet, there has not been a critical review attempting to integrate their nutraceutical potential with basic science. Relatively few studies are available on the biologic effects of mushroom consumption, and those have been performed exclusively in murine models. In this paper, we review existing data on the mechanism of whole mushrooms and isolated mushroom compounds, in particular (1-->3)-beta-D-glucans, and the means by which they modulate the immune system and potentially exert tumor-inhibitory effects. We believe that the antitumor mechanisms of several species of whole mushrooms as well as of polysaccharides isolated from Lentinus edodes, Schizophyllum commune, Grifola frondosa, and Sclerotinia sclerotiorum are mediated largely by T cells and macrophages. Despite the structural and functional similarities of these glucans, they differ in their effectiveness against specific tumors and in their ability to elicit various cellular responses, particularly cytokine expression and production. Unfortunately, our data base on the involvement of these important mediators is still rather limited, as are studies concerning the molecular mechanisms of the interactions of glucans with their target cells. As long as it remains unclear what receptors are involved in, and what downstream events are triggered by, the binding of these glucans to their target cells, it will be difficult to make further progress in understanding not only their antitumor mechanisms but also their other biological activities.

[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.

A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial.

Lentinan is a beta 1-->3 glucan isolated from Lentinus edodes (Shiitake mushroom) which has immune modulating properties. We have conducted two phase I/II placebo-controlled trials on a total of 98 patients. In one study at the San Francisco General Hospital (SFGH), ten patients each were administered 2, 5, or 10 mg of lentinan or placebo i.v. once a week for eight weeks. In the second study at the Community Research Initiative in New York (CRI), two groups of 20 patients each were administered 1 or 5 mg of lentinan i.v. twice a week for 12 weeks, and ten patients were administered placebo (vehicle containing mannitol plus dextran 40) i.v. twice a week. Entry criteria were an HIV positive test, CD4 levels of 200-500 cells, age 18-60 years, and without current opportunistic infections. This study confirms, in Caucasian subjects also, the good tolerability of lentinan observed in Japanese cancer patients. Side effects were mainly mild, especially when infusion was carried out over a 30-minute period. In the SFGH study, where administration was over a ten minute period, there were nine side effects severe enough to be reported to the FDA (one case each of anaphylactoid reaction, back pain, leg pain, depression, rigor, fever, chills, granulocytopenia and elevated liver enzymes) and there were four patients who discontinued therapy because of side effects. In the CRI study, where infusion was over a 30-minute period, there were no side effects reportable to the FDA and there were four dropouts due to side effects or personal preference. Most side effects resolved promptly after the discontinuation of medication, and all of them were relieved within 24 hours. Patients in the study have shown a trend toward increases in CD4 cells and in some patients neutrophil activity. Because of the small numbers, these values do not have statistical significance. Inasmuch as no side effects such as anemia, leukopenia, pancreatitis or neuropathy were seen, and in view of the positive effects of lentinan on certain surrogate markers (recognizing that these were small studies), we recommended a long-term clinical trial of lentinan in combination with didanosine (ddI) or zidovudine in HIV positive patients. Most patients in these trials did not have measurable p24 levels. In the CRI trials of ten patients with elevated p24 levels, eight on lentinan and two on placebo had decreased p24 levels. Of these decreases, those with lentinan and one with placebo were marked. These results were provocative and needed confirmation. Subsequent to this study, a trial of lentinan in combination with didanosine (ddI) showed a mean increase of 142 CD4 cells/mm3 over a twelve month period, in contrast to a decrease in CD4 cells in patients on ddI alone (Gordon et al. 1995).

Effects of Lentinus edodes, Grifola frondosa and Pleurotus ostreatus administration on cancer outbreak, and activities of macrophages and lymphocytes in mice treated with a carcinogen, N-butyl-N-butanolnitrosoamine.

ICR mice were treated with a carcinogen, N-butyl-N'-butanolnitrosoamine BBN), every day for 8 consecutive weeks and the effects of oral administration of edible mushrooms on the induction of urinary bladder carcinoma and on the activities of macrophages and lymphocytes were studied. Bladder carcinoma were found in all 10 mice (100%) treated with BBN alone, while we observed carcinoma only in 9 of 17 mice (52.9%), in 7 of 15 mice (46.7%) and 13 of 20 mice (65.0%) treated with Lentinus edodes, Grifola frondosa and Pleurotus ostreatus, respectively. Chemotactic activity of macrophages was suppressed in mice treated with BBN alone but maintained almost the normal level in mice treated with BBN plus Lentinus, Grifola or Pleurotus. Lymphocytes collected from mice treated with BBN plus each mushroom showed almost normal blastogenic response against concanavalin A, although those from mice treated with BBN alone completely retarded their response. Cytotoxic activity of lymphocytes against Yac-1 cells was also maintained at a normal level in mice treated with BBN plus each mushroom. Whereas in mice treated with BBN alone significant depression of NK cell activity occurred. Significantly higher cytotoxic activity against P-815 cells was observed in lymphocytes from mice treated with BBN plus each mushroom than that in lymphocytes from normal mice or mice treated with BBN alone.

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.