Investigation on the efficiency of lentinan for injection combining cisplatin on treating malignant pleural effusion based on systematic review and meta-analysis.

BACKGROUND: Malignant pleural effusion (MPE) is a frequently observed complication in advanced malignant tumors. Clinical studies have shown that lentinan for injection (LNT) is beneficial for improving patients' quality of life and prolonging their survival. The purpose of this meta-analysis is to evaluate the efficacy and safety of LNT combining cisplatin in the treatment of MPE. METHODS: Randomized controlled trials (RCTs) of LNT combining cisplatin in the treatment of MPE were searched in 6 literature databases from the establishment time of each database by 2 researchers. According to the inclusion criteria, 2 researchers independently screened studies, assessed the risk of bias and conducted subgroup analyses for different outcome indicators according to the specific characteristics of the included literature. Analyzing the data by Revman software, and evaluating the stability of the results by Stata software. RESULTS: A total of 52 RCTs were included. The results showed that combined use of LNT and cisplatin could improve the treatment effect, and the difference between groups was statistically significant (RR = 1.40, 95%CI: 1.33 ~ 1.46, P < .001). And the combined use of LNT could increase the quality of life (RR = 1.45, 95%CI: 1.35 ~ 1.56, P < .001). The using of LNT could significantly decrease the incidence of gastrointestinal reactions (RR = 0.86, 95%CI: 0.78 ~ 0.94, P < .001). Sensitivity analysis results showed that there were no qualitative changes in the indicator, and suggested the possibility of publication bias. CONCLUSIONS: Available evidence suggested the combined use of LNT and cisplatin showed better efficacy in treating MPE without increasing ADR incidence than using cisplatin alone. LNT is an ideal treatment for MPE, which has high clinical application value.

Lentinan progress in inflammatory diseases and tumor diseases.

Shiitake mushrooms are a fungal food that has been recorded in Chinese medicine to nourish the blood and qi. Lentinan (lLNT) is an active substance extracted from shiitake mushrooms with powerful antioxidant, anti-inflammatory, anti-tumor functions. Inflammatory diseases and cancers are the leading causes of death worldwide, posing a serious threat to human life and health and posing enormous challenges to global health systems. There is still a lack of effective treatments for inflammatory diseases and cancer. LNT has been approved as an adjunct to chemotherapy in China and Japan. Studies have shown that LNT plays an important role in the treatment of inflammatory diseases as well as oncological diseases. Moreover, clinical experiments have confirmed that LNT combined with chemotherapy drugs has a significant effect in improving the prognosis of patients, enhancing their immune function and reducing the side effects of chemotherapy in lung cancer, colorectal cancer and gastric cancer. However, the relevant mechanism of action of the LNT signaling pathway in inflammatory diseases and cancer. Therefore, this article reviews the mechanism and clinical research of LNT in inflammatory diseases and tumor diseases in recent years.

Lentinan alleviates diabetic cardiomyopathy by suppressing CAV1/SDHA-regulated mitochondrial dysfunction.

Diabetic cardiomyopathy (DCM), characterized by mitochondrial dysfunction and impaired energetics as contributing factors, significantly contributes to high mortality in patients with diabetes. Targeting key proteins involved in mitochondrial dysfunction might offer new therapeutic possibilities for DCM. Lentinan (LNT), a ß-(1,3)-glucan polysaccharide obtained from lentinus edodes, has demonstrated biological activity in modulating metabolic syndrome. In this study, the authors investigate LNT's pharmacological effects on and mechanisms against DCM. The results demonstrate that administering LNT to db/db mice reduces cardiomyocyte apoptosis and mitochondrial dysfunction, thereby preventing DCM. Notably, these effects are fully negated by Caveolin-1 (CAV1) overexpression both in vivo and in vitro. Further studies and bioinformatics analysis uncovered that CAV1 bound with Succinate dehydrogenase subunit A (SDHA), triggering the following ubiquitination and degradation of SDHA, which leads to mitochondrial dysfunction and mitochondria-derived apoptosis under PA condition. Silencing CAV1 leads to reduced apoptosis and improved mitochondrial function, which is blocked by SDHA knockdown. In conclusion, CAV1 directly interacts with SDHA to promote ubiquitination and proteasomal degradation, resulting in mitochondrial dysfunction and mitochondria-derived apoptosis, which was depressed by LNT administration. Therefore, LNT may be a potential pharmacological agent in preventing DCM, and targeting the CAV1/SDHA pathway may be a promising therapeutic approach for DCM.

Lentinan-laden microspheres reprogram the tumor microenvironment and improve anti-PD-L1 efficacy.

Immunotherapies are a promising new class of anticancer treatments, but the immunosuppressive tumor microenvironment (TME) hinders their broader implementation. Here, we designed a '3C' strategy based on the conventional drug lentinan (LNT), applying the convertible material polylactic acid with controlled release of LNT (LNT@Mic). Our findings revealed that LNT@Mic exhibited effective biocompatibility coupled with controlled long-term release of LNT. Due to these characteristics, LNT@Mic reprogramed the immunosuppressive TME and demonstrated substantial antitumor activity in the MC38 tumor model. Furthermore, it served as a facile and generalizable cancer immunotherapy strategy for augmenting LNT bioavailability while enhancing the efficacy of anti-programmed death-ligand 1 therapy against the 'cold' 4T1 tumor model. These findings provide a reference for tumor immunotherapy strategies for the further study and application of LNT.

Lentinan confers protection against type 1 diabetes by inducing regulatory T cell in spontaneous non-obese diabetic mice.

BACKGROUND: Lentinan (LNT) is a complex fungal component that possesses effective antitumor and immunostimulating properties. However, there is a paucity of studies regarding the effects and mechanisms of LNT on type 1 diabetes. OBJECTIVE: In the current study, we investigated whether an intraperitoneal injection of LNT can diminish the risk of developing type 1 diabetes (T1D) in non-obese diabetic (NOD) mice and further examined possible mechanisms of LNT's effects. METHODS: Pre-diabetic female NOD mice 8 weeks of age, NOD mice with 140-160 mg/dL, 200-230 mg/dL or 350-450 mg/dL blood glucose levels were randomly divided into two groups and intraperitoneally injected with 5 mg/kg LNT or PBS every other day. Then, blood sugar levels, pancreas slices, spleen, PnLN and pancreas cells from treatment mice were examined. RESULTS: Our results demonstrated that low-dosage injections (5 mg/kg) of LNT significantly suppressed immunopathology in mice with autoimmune diabetes but increased the Foxp3+ regulatory T cells (Treg cells) proportion in mice. LNT treatment induced the production of Tregs in the spleen and PnLN cells of NOD mice in vitro. Furthermore, the adoptive transfer of Treg cells extracted from LNT-treated NOD mice confirmed that LNT induced Treg function in vivo and revealed an enhanced suppressive capacity as compared to the Tregs isolated from the control group. CONCLUSION: LNT was capable of stimulating the production of Treg cells from naive CD4 + T cells, which implies that LNT exhibits therapeutic values as a tolerogenic adjuvant and may be used to reverse hyperglycaemia in the early and late stages of T1D.

Lentinan enhances the antitumor effects of Delta-like 1 via neutrophils.

BACKGROUND: Selective activation of Delta-like 1 (DLL1)-Notch signaling is a new approach to activate CD8+ T cell and suppress tumor growth, while the efficacy remains modest. Lentinan (LNT) is a clinically used immunomodulation agent. Thus, we hypothesized that LNT could improve the efficacy of DLL1. METHODS: The effects of LNT combined with DLL1 on tumor growth were evaluated by growth curve and tumor weight in EO771 breast and LAP0297 lung tumor models. The impacts on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR. Neutrophil depletion was used to investigate the mechanism of the combination therapy on tumor growth. The data sets were compared using unpaired student's t-test or ordinary one-way ANOVA. RESULTS:  LNT treatments additively improved the antitumor effects of DLL1 in EO771 breast tumor growth. Remarkably, LNT treatments synergistically enhanced the suppression of DLL1 on LAP0297 lung tumor growth, resulting in tumor regression. Mechanically, the combination of LNT and DLL1 interventions not only promoted the accumulation and activation of CD8+ T cells, but also increased intratumoral CD45+CD11b+Ly6G+ neutrophils. Reduced neutrophils by anti-Gr1 antibody administrations reversed the improved antitumor effects by LNT treatments in LAP0297 lung tumor. These results suggest that LNT treatments improve the inhibition of DLL1 on tumor growth via neutrophils. CONCLUSIONS: Our findings indicates that LNT and DLL1 may induce synergistical antitumor immunity via simultaneous modulating lymphoid and myeloid cell populations regardless of the type of tumor, providing a potential new strategy to potentiate cancer immunotherapy.

Lentinan Enhances the Function of Oxaliplatin on the Esophageal Tumors by Persuading Immunogenic Cell Death.

Objective: The focus of this research was to look at the effects of the combination of the lentinan (LNT) and oxaliplatin (Oxa) on the apoptosis of human esophageal cancer cells, as well as the underlying mechanism. Methods: LNT and Oxa were used to treat EC-109 human esophageal cancerous cells at various doses, and the cell survival rate was measured using the Cell Counting Kit-8 (CCK-8) assay. In addition, 24 h after treatment of EC-109 cells with a combination of LNT and Oxa, flow cytometry was used to analyze their apoptotic effect on these cells. Additionally, LNT on EC-109 cell apoptotic upshot was assessed via measuring the consequence of LNT on the mRNA and protein expression levels pertaining to immunogenic cell death factors CALR, HSP90, and HSP70 by qPCR (quantitative real-time polymerase chain reaction) and western blot analysis, correspondingly. Results: Cell proliferation was inhibited only when EC-109 cells were added with LNT at 1,200 µg/mL to the maximum concentrations, but the combination of LNT and Oxa at a low dose (800 µg/mL and 20 µM, respectively) significantly increased their sensitivity to Oxa and reduced their proliferation (P < 0.05), and their apoptosis was significantly increased by LNT (P < 0.05). The immunogenic cell death-related genes CALR, HSP90, and HSP70 had dramatically enhanced mRNA and protein expression levels after therapy with a combination of LNT and Oxa (P < 0.05). Conclusion: These data imply that LNT increases the susceptibility of esophageal cancerous cells to Oxa by driving EC-109 cells to display immunogenic death. Therefore, LNT combined with Oxa may be an effective method in esophageal cancer management.

Anti-Influenza Effect and Mechanisms of Lentinan in an ICR Mouse Model.

Influenza virus is a serious threat to global human health and public health security. There is an urgent need to develop new anti-influenza drugs. Lentinan (LNT) has attracted increasing attention in recent years. As potential protective agent, LNT has been shown to have anti-tumor, anti-inflammatory, and antiviral properties. However, there has been no further research into the anti-influenza action of lentinan in vivo, and the mechanism is still not fully understood. In this study, the anti-influenza effect and mechanism of Lentinan were studied in the Institute of Cancer Research (ICR) mouse model. The results showed that Lentinan had a high degree of protection in mice against infection with influenza A virus, delayed the emergence of clinical manifestations, improved the survival rate of mice, significantly prolonged the middle survival days, attenuated the weight loss, and reduced the lung coefficient of mice. It alleviated the pathological damage of mice infected with the influenza virus and improved blood indices. Lentinan treatment considerably inhibited inflammatory cytokine (TNF-α, IL-1ß, IL-4, IL-5, IL-6) levels in the serum and lung and improved IFN-γ cytokine levels, which reduced cytokine storms caused by influenza virus infection. The underlying mechanisms of action involved Lentinan inhibiting the inflammatory response by regulating the TLR4/MyD88 signaling pathway. This study provides a foundation for the clinical application of Lentinan, and provides new insight into the development of novel immunomodulators.

The esterified lentinan bilayer nanofibrous membrane for promoting wound healing.

Host reactions following implantation of biomaterials, especially the macrophages' responses could significantly affect the wound healing process. Therefore, it is meaningful to develop immunostimulatory active wound dressing to accelerate wound healing. In this study, lentinan (LNT) was esterified with different carboxylic acids, and the bilayer nanofibrous membrane (BilayerM) based on the esterified LNT was designed. BilayerM exhibited good water absorption, red blood cells (RBC), platelets, and fibronectin adhesion abilities. The ELISA results indicated that BilayerM stimulated macrophages to secrete pro-inflammatory and pro-regenerative cytokines. Moreover, cell migration results showed that BilayerM promoted the migration and proliferation of NIH3T3 and HUVECs. The wound healing efficacy studies demonstrated that BilayerM significantly accelerated the wound healing rate in a full-thickness skin defect model. Therefore, these results indicate that this bioactive dressing is a hopeful candidate for clinical treatment of cutaneous wounds.

Lentinan alleviates arsenic-induced hepatotoxicity in mice via downregulation of OX40/IL-17A and activation of Nrf2 signaling.

BACKGROUND: Arsenic, existing ubiquitously in soil, drinking water, or food, is well known to be an environmental pollutants concerned by European Food Safety Authority. Lentinan, a beta-1,6;1,3-glucan extracts from Lentinus edodes, which has the properties of antioxidant and immunomodulation, present study explored the pharmacological effects of Lentinan on arsenic induced hepatotoxicity in mice. METHODS: Mice experiments were performed by sodium arsenite (SA) treatment or Lentinan intervention, then histopathology, ELISA, Flow Cytometry, or Western-Blotting were applied to evaluate hepatic injury, oxidative stress, CD4+ type 17 helper T (Th17) cells, CD4+CD25+Foxp3+ regulatory T cells (Tregs), T cells receptor OX40/CD134, IL-17A, NLRP3, Nrf2, and NQO1. RESULTS: SA treatment showed hepatic pathological injury and the elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in serum, and induced the increases of malondialdehyde (MDA), Th17 cells, OX40 or IL-17A in liver tissues, which were consistently ameliorated by Lentinan intervention. Further, immunoblotting experiments showed that Lentinan intervention downregulated the levels of OX40, IL-17A, and NLRP3 signals, while elevated the levels of anti-oxidative Nrf2, NQO1 signals compared to arsenic treatment group. For Tregs, Lentinan intervention showed no significant difference from SA treatment group. CONCLUSION: Lentinan antagonizes SA-induced hepatotoxicity in mice, may be involved in the downregulations of pro-inflammatory OX40 or IL-17A and the activation of anti-oxidative Nrf2, NQO1 signals.

The Dectin-1 Receptor Signaling Pathway Mediates the Remyelination Effect of Lentinan through Suppression of Neuroinflammation and Conversion of Microglia.

Demyelinating diseases such as multiple sclerosis (MS) are chronic inflammatory autoimmune diseases and involve demyelination and axonal degeneration. Microglia rapidly respond to changes in the environment by altering morphotype and function during the progressive disease stage. Although substantial progress has been made in the drug development for MS, treatment of the progressive forms of the disease remains unsatisfactory. There is great interest in identifying novel agents for treating MS. Lentinus edodes is a traditional food, which can improve physiological function. Lentinan (LNT), a type of polysaccharide extracted from mushroom Lentinus edodes, is an anti-inflammatory and immunomodulatory agent. Here, we studied the remyelination effects of LNT and its therapeutic target in regulating the functions of neuroinflammation. We found that LNT enhanced remyelination and rescued motor deficiency by regulating dectin-1 receptor to inhibit neuroinflammation and microglial cell transformation. LNT promoted the conversion of microglial cells from the M1 status induced by LPS to the M2 status, enhanced the anti-inflammatory markers IL-10 and BDNF, inhibited inflammatory markers TNF-α and IL-1ß, and downregulated the microglia activation and oligodendrocyte and astrocyte proliferation by modulating dectin-1. If we injected the dectin-1-specific inhibitor laminarin (Lam), the remyelination effects induced by LNT were completely abolished. Thus, these results suggest that LNT is a novel and potential therapeutic agent that can rescue MS neuroimmune imbalance and remyelination through a dectin-1 receptor-dependent mechanism.

Lentinan inhibited colon cancer growth by inducing endoplasmic reticulum stress-mediated autophagic cell death and apoptosis.

Lentinan (SLNT) has been shown to be directly cytotoxic to cancer cells. However, this direct antitumour effect has not been thoroughly investigated in vivo, and the mechanism remains unclear. We aimed to examine the direct antitumour effect of SLNT on human colon cancer and the mechanism in vivo and in vitro. SLNT significantly inhibited tumour growth and induced autophagy and endoplasmic reticulum stress (ERS) in HT-29 cells and tumour-bearing nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Experiments with the autophagy inhibitors chloroquine (CQ) and 3-methyladenine (3-MA) showed that autophagy facilitated the antitumour effect of SLNT. Moreover, ERS was identified as the common upstream regulator of SLNT-induced increases in Ca2+concentrations, autophagy and apoptosis by using ERS inhibitors. In summary, our study demonstrated that SLNT exerted direct antitumour effects on human colon cancer via ERS-mediated autophagy and apoptosis, providing a novel understanding of SLNT as an anti-colon cancer therapy.

A carboxymethyl lentinan layer by layer self-assembly system as a promising drug chemotherapeutic platform.

Surface functionalization of mesoporous silica nanoparticles (MSNs) has been proposed as an efficient strategy for enhancing the biocompatibility and efficiency of an MSN-based carrier platform. Herein, natural polyelectrolyte multilayers composed of poly-l-ornithine (PLO) and carboxymethyl lentinan (LC) were coated on the surface of MSNs through a layer-by-layer (LbL) self-assembly technique, and were characterized by ζ-potential, FTIR, 13C NMR, SEM, TEM, XRD, and TG. The prepared carrier presented alternating positive and negative potentials when coated with the polyelectrolytes, and the surface of MSN-PLO/LC was rougher compared to the naked MSNs. The biocompatibility tests, including cytocompatibility, hemocompatibility, and histocompatibility, showed that MSNs biocompatibility could be improved by modifying LC. A high loading and sustained release drug delivery system was constructed after loading doxorubicin (DOX) into the prepared MSN-PLO/LC, which exhibited significant anti-proliferative efficiency in human cervical cancer cell lines (Hela). Therefore, the PLO/LC LbL NPs (layer-by-layer self-assembled nanoparticles coated with PLO/LC layers) based on MSNs, which is easily prepared by electrostatic interactions, can be considered a promising drug chemotherapeutic platform and delivery technique for future human cervical cancer therapy.

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.

Evaluation of Efficacy and Safety for Lentinan in the Control of the Malignant Pleural Effusions via Intrapleural Injection.

BACKGROUND: Many studies have investigated the efficacy and safety of lentinan combined with cisplatin versus cisplatin alone for controlling malignant pleural effusion (MPE). This study is a meta-analysis of available evidence. MATERIALS AND METHODS: Seventeen studies reporting lentinan combined with cisplatin versus cisplatin alone for controlling MPE were reviewed. Pooled odds ratios and hazard ratio with 95% confidence intervals were calculated using the fixed effects model of meta-analysis. RESULTS: The overall response rate (ORR) of lentinan combined with cisplatin for controlling MPE was significantly higher than that of cisplatin alone (P < 0.001). In addition, lentinan combined with cisplatin showed a better benefit of quality of life (QOL) compared with cisplatin alone (P < 0.001). The main adverse effects (AEs) found in the control plan were hematological reactions, nausea/vomiting, chest pain and fever. However, the presence of lentinan did not have an extra influence on the incidence of AEs (P > 0.05). CONCLUSIONS: Intrapleural injection of lentinan combined with cisplatin had a better benefit of ORR and QOL for controlling MPE, compared with cisplatin alone. Moreover, lentinan combined with cisplatin had a similar incidence of AEs with cisplatin alone.

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.

Lentinan diminishes apoptotic bodies in the ileal crypts associated with S-1 administration.

S-1 is an oral agent containing tegafur (a prodrug of 5-fluorouracil) that is used to treat various cancers, but adverse effects are frequent. Two pilot clinical studies have suggested that lentinan (LNT; ß-1,3-glucan) may reduce the incidence of adverse effects caused by S-1 therapy. In this study, we established a murine model for assessment of gastrointestinal toxicity associated with S-1 and studied the effect of LNT. S-1 was administered orally to BALB/c mice at the effective dose (8.3mg/kg, as tegafur equivalent) once daily (5days per week) for 3weeks. Stool consistency and intestinal specimens were examined. We investigated the effect of combined intravenous administration of LNT at 0.1mg, which is an effective dose in murine tumor models. We also investigated the effect of a single administration of S-1. During long-term administration of S-1, some mice had loose stools and an increase in apoptotic bodies was observed in the ileal crypts. An increase in apoptotic bodies was also noted after a single administration of S-1 (15mg/kg). Prior or concomitant administration of LNT inhibited the increase in apoptotic bodies in both settings. Administration of LNT also increased the accumulation of CD11b+TIM-4+ cells in the ileum, while depletion of these cells by liposomal clodronate diminished the inhibitory effect of LNT on S-1 toxicity. Combined administration of LNT with S-1 led to a decrease in apoptotic bodies in the ileal crypts, possibly because LNT promoted phagocytosis of damaged cells by CD11b+TIM-4+ cells.