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At least 19 recordsLinked to original sources

PubMed1986

[Randomized study of lentinan on patients with advanced gastric and colorectal cancer. Tohoku Lentinan Study Group].

A randomized study of mitomycin C (MMC)+5-FU [control group] vs MMC+5-FU+lentinan (LNT) [LNT group] was conducted in order to evaluate the effect of LNT against advanced gastric and colorectal cancers by the envelope method in 166 patients, comprising of 115 cases of gastric cancer and 51 cases of colorectal cancer. Significant increases were observed in the survival rates for the LNT group (p less than 0.05) for both patients with gastric and colorectal cancer. No significant difference was observed in response rates between the aforesaid two groups, though the response rate in the LNT group was slightly higher than the control group. These results suggest that LNT in combination with anticancer drugs prolong the survival time of patients with advanced gastric and colorectal cancer.

Adult↗

PubMed1985

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

Lentinan, an immunopotentiating polysaccharide, stimulates the production of chemiluminescence (CL) by human neutrophils and the murine macrophage cell line C4M phi. The CL enhancing effect of lentinan opsonized in human serum is greater than that of lentinan itself. Lentinan's stimulation of neutrophil CL was increased by 1/2 when opsonized in human serum inactivated at 56 degrees C to remove complement, while the CL was increased two fold by lentinan opsonized in whole serum. This indicates that C3b and immunoglobulin contribute separate signals in the activation process mediated by opsonized lentinan. The distinct roles of the C3b and Fc receptors was further illuminated by the finding that an Fc receptor-negative cell line was unresponsive to lentinan opsonized in heat inactivated serum (56 degrees C), whereas it exhibited a five fold increase in CL in response to lentinan opsonized in serum containing complement. Lentinan in an opsonized form can stimulate the production of CL via C3b and Fc receptors. This mechanism may be considered as one mode of action of lentinan and other similar immunopotentiating and antitumour glucan-type polysaccharides.

Animals↗

PubMed1992

In vitro generation of activated natural killer cells and cytotoxic macrophages with lentinan.

The in vitro effect of lentinan in inducing activation of killer cells and cytotoxic macrophages has been examined. Human peripheral blood mononuclear cells were cultured with lentinan for 2, 4 and 8 days. After 4 days cytotoxicity was increased 4% by lentinan less than 1,000 ng/ml. After 8 days, it was increased 12% by 25 and 1,000 ng/ml lentinan. The phenotype of the killer cells induced by lentinan was CD2+, CD16+ and CD56+, suggesting that they were natural killer cells. Macrophages separated from the spleens of 6 patients with gastric cancer were cultured with lentinan for 7 days, and their cytotoxicity increased 19%. The optimal concentration of lentinan was from 25 to 100 ng/ml. The findings suggest that the antitumour effect of lentinan is due to the activation of killer cells in vivo, because the optimal concentration of lentinan for the induction of killer cells in vitro was equivalent to the plasma concentration obtained after clinical doses of this agent.

Antigens, Surface↗

PubMed1989

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

Lentinan, an immunopotentiating beta-1,3-glucan polysaccharide stimulated the in vitro phagocytosis of BSA-coated, C3b- or monoclonal immunoglobulin (IgG2b)-coated fluorescent microspheres by resident or thioglycollate-elicited mouse macrophages in a dose-dependent manner. Analysis of flow cytometric data has shown that microbead phagocytosis of resident macrophages, which exhibit a lower basic phagocytic activity than the thioglycollate elicited ones, has been augmented by up to 900% due to lentinan. The percent ratio of phagocytes among peritoneal exudate cells, however, remained unchanged after short-term lentinan stimulation. Preincubation of the cells with lentinan resulted in increased ingestion of the microbeads. Activation of phagocytosis by lentinan is therefore due in part to the direct stimulation of the cells, however, lentinan also serves as supplementary opsonin for C3b-coated beads. Mannan inhibited the ingestion of C3b-coated microspheres by 75%, which was abolished in part when lentinan was also added to the cells. Mannan did not influence the phagocytosis of BSA-coated or IgG-coated beads. Our data, based solely on in vitro studies, suggest a beta-glucan receptor mediated activation of phagocytes by lentinan. These receptors are different from the C3b, Fc or mannose receptors. It is very likely that stimulation of phagocytic activity of macrophages by lentinan may contribute to the antitumor action of this immunopotentiating polysaccharide.

Animals↗

PubMed1988

Denaturation and renaturation of a beta-1,6;1,3-glucan, lentinan, associated with expression of T-cell-mediated responses.

Correlation between the higher structure and biological functions of lentinan, a beta-1,6;1,3-glucan capable of potentiating T- and non-T-cell-mediated responses, were investigated by measurements of optical rotation and some biological responses. The addition of urea or dimethyl sulfoxide decreased specific rotation at 589 nm, [alpha]D, of lentinan in a concentration-dependent manner and the removal of these denaturants resulted in the recovery of [alpha]D values. Measurements of optical rotatory dispersion in the spectral region between 600 and 200 nm showed the change in the higher structure of lentinan more clearly. Denaturation and renaturation of lentinan using urea and dimethyl sulfoxide were associated with the decrease and the recovery of antitumor activity against P-815 mastocytoma and vascular dilation and hemorrhage-inducing activity, found to be T-cell-mediated responses. Lentinan was also denatured by NaOH and the transition of [alpha]D values and optical rotatory dispersion curves were seen in the manner of two concentration-dependent phases. Removal of NaOH led to the recovery of optical rotation of lentinan and its antitumor and vascular dilation and hemorrhage-inducing activity. However, recovery of these bioactivities was more difficult in the case of the higher concentrations of NaOH above 2% than the lower ones. During the process of renaturation of lentinan, random aggregation may take place. An increase of serum acute phase proteins, a non-T-cell-mediated response caused by lentinan, was not affected by the change of the higher structure of lentinan.

Acute-Phase Proteins↗

PubMed1987

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

The antitumor and metastasis-inhibitory activities, mode of action, and clinical application of lentinan, a strictly purified beta-1,6:beta-1,3-glucan, are reviewed. Lentinan exerts a prominent antitumor effect and prevents chemical and viral oncogenesis. The antitumor action of lentinan is host-mediated. Compared to other well-known immunostimulants, such as bacille Calmette Guérin (BCG), Corynebacterium parvum, and lipopolysaccharide (LPS), lentinan appears to represent a unique class of immunopotentiator, a T cell-oriented adjuvant. Lentinan triggers the increased production of various kinds of bioactive serum factors associated with immunity and inflammation, such as IL-1, CSF, IL-3, vascular dilation inducer, and acute-phase protein inducer, by the direct impact of macrophages or indirectly via lentinan-stimulated T cells, which results in the induction of many immunobiological changes in the host. Augmented IL-1 production amplifies the maturation of immature effector cells to mature cells capable of responding to lymphokines such as IL-2 and T cell-replacing factors. Because of this mode of action, intact T cell compartments for antitumor activity of lentinan are required. Lentinan has little toxic side effects. Excellent results were obtained in a 4 year follow-up of the randomized control study of lentinan in phase III on patients with advanced and recurrent stomach and colorectal cancer.

Adjuvants, Immunologic↗

PubMed1989

Synergistic induction of lymphokine (IL-2)-activated killer activity by IL-2 and the polysaccharide lentinan, and therapy of spontaneous pulmonary metastases.

Spleen cells of C57BL/6N mice bearing lung metastases were induced to the cytotoxic state by subcutaneous injection of recombinant human interleukin-2 (IL-2) at a minimum dose of 5 x 10(4) U/mouse three times a day for 3 consecutive days. A single intraperitoneal injection of lentinan alone at concentrations of up to 10 mg/kg body weight did not render spleen cells cytotoxic to P-29 cells, but a combination of subthreshold doses of these agents (5 x 10(4) U/ml IL-2 and 5 mg/kg lentinan) induced significant in vivo lymphokine-activated killer activity in spleen cells of tumor-bearing mice. Similarly, spleen cells from mice treated i.p. with lentinan became cytotoxic on in vitro treatment with IL-2. The in vitro responsiveness of spleen cells to IL-2 was maximal 3 days after i.p. injection of lentinan. Synergism between IL-2 and lentinan was also observed in mice bearing spontaneous lung micrometastases: neither IL-2 (less than 5 x 10(4) U/mouse) nor lentinan (less than 2.5 mg/kg) alone had a therapeutic effect, but multiple injections of IL-2 with a single injection of lentinan resulted in significant inhibition of spontaneous pulmonary metastases. From these results we conclude that IL-2 and lentinan in combination are more effective than either one alone for inducing destruction of pulmonary metastases.

Adjuvants, Immunologic↗

PubMed1992

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

The ability of polysaccharide immunomodulator lentinan to stimulate non-specific resistance against respiratory viral infections was investigated. Significant protection was conferred by lentinan administered intranasally before lethal influenza virus infection and could be corroborated by a reduction of the lung virus titres. Since the lung is the target organ of influenza virus infection, lentinan was also administered by the intravenous route. Lentinan conferred complete protection against a LD75 challenge dose of virulent influenza virus and significantly prolonged the survival time after a LD100 challenge. The effect on respiratory burst of broncho-alveolar macrophages was investigated by luminol-dependent chemiluminescence (CL) in response to stimulation by zymosan. Enhanced CL activity was present at an early stage in groups receiving lentinan. Significant nitric oxide activity could also be stimulated by culturing broncho-alveolar macrophages in the presence of lentinan. TNF activity could not be detected in lung lavage but measurable IL-6 was produced already after 6 h in animals administered lentinan alone and in lentinan-pretreated influenza virus-infected mice. Influenza virus alone did not induce measurable IL-6 at 6 h but high activity was present at later time periods.

Aerosols↗

PubMed1985

Depression of hepatic microsomal enzyme systems by lentinan in mice.

Studies were performed to determine the effects of an immunopotentiating agent, lentinan, on the hepatic drug-metabolizing enzymes in mice. Lentinan was injected twice a day for two days, and the enzyme activities were determined 12 hr after the last injection of lentinan. A lentinan dose of over 0.25 mg/kg was required to cause a significant decrease (20-40%) in the hepatic microsomal aminopyrine N-demethylase and aniline hydroxylase activities. The loss of drug-metabolizing activity by the treatment with lentinan agreed with the loss of cytochrome P-450 content in many cases. Strain and substrate differences concerning the effect of lentinan on the metabolism of drug were also observed. That is to say, the loss of cytochrome P-450 content by the treatment with lentinan was observed in the ddY, C57BL/6 and BDF1 strain mice, but was not observed in the DBA/2, C3H/He and C57BL/10 strain mice. The decrease in the activities of 7-ethoxycoumarin O-deethylase and biphenyl 2-hydroxylase by the treatment with lentinan was considerably less than that of aminopyrine N-demethylase and aniline hydroxylase in ddY mice.

Aminopyrine N-Demethylase↗

PubMed1986

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

Lentinan, an immunopotentiating polysaccharide, stimulated the pinocytosis of horseradish peroxidase (HRP) or FITC-dextran by resident or thioglycollate-elicited mouse macrophages from 10 to 50% in a dose dependent manner. Pinocytosis of HRP and FITC-dextran by C4M phi cells, a murine macrophage cell line, exhibiting a lower basic pinocytic activity than peritoneal cells, was augmented up to 310 and 120%, respectively, by lentinan. Mannan inhibited the HRP uptake by peritoneal macrophages via specific mannose receptors. This inhibitory effect was partly abolished, when lentinan was also added to the cells. Mannan was not able to inhibit pinocytosis of HRP by C4M phi macrophages, indicating little or no mannose receptor activity on these cells. Pinocytosis of FITC-dextran was not affected by mannan. Lentinan, opsonized in mouse sera inhibited the uptake of HRP by peritoneal macrophages by 30-35%. Opsonized lentinan and mannan added together caused 60% inhibition of HRP uptake in peritoneal macrophages indicating a possible functional relationship between the mannose and C3b receptors. The results demonstrate that lentinan activates the pinocytic function of macrophages predominantly via specific beta-glucan receptors. These mechanisms may contribute to the antitumor and immunopotentiating action of lentinan and other glucan-type polysaccharides.

Adjuvants, Immunologic↗

PubMed1989

Quantitative assay of lentinan in human blood with the limulus colorimetric test.

A conventional limulus test detects not only endotoxin but also beta (1----3) glucan. Therefore, using a quantitative limulus test (the limulus colorimetric test) we studied the pharmacokinetics of lentinan, an antitumor beta (1----3) glucan, in the blood of 10 health volunteers and three patients with advanced gastric cancer. The calibration curve of lentinan in the human plasma was linear in the range of 0 to 100 ng/ml. When incubated with human plasma at 37 degrees C in vitro, lentinan had the recovery of almost 100% as compared to the initial concentration even after 60-min incubation, indicating the stability of lentinan in human plasma. When 1 mg of lentinan was intravenously administered over a 2 hr period, lentinan concentration reached the maximum levels (50-80 ng/ml) at the end of the drip infusion and decreased gradually thereafter. In the near future, the more appropriate modes of lentinan administration will be determined by further investigation of its kinetics in the human body.

Colorimetry↗

PubMed1991

[Diversity of complement activation by lentinan, an antitumor polysaccharide, in gastric cancer patients].

Lentinan, a pure polysaccharide, augments many immune responses in vivo but not in vitro. Therefore reaction with any factor is thought to be required for triggering of immunopotentiation by lentinan. To clarify the role of complement in this effect, we investigated whether lentinan could activate alternative pathway of complement or not and the relation with the immunopotentiation in 13 gastric cancer patients. C3, C3a, C5 and C5a levels as parameters of complement activation and interleukin-2 producing activity as parameter of immunopotentiation were assayed before and immediately after intravenous injection of lentinan. Among these complement components, remarkable change was observed only in C3a level. C3a level elevated to more than 1000ng/ml from less than 300ng/ml. And according to the degree and continuation of the elevation, these patients were classified into 3 types-(1) every time little elevation, (2) first remarkable and thereafter little elevation and (3) continuous remarkable elevation. Such an elevated C3a level returned to the level before lentinan injection within one day. When C3a level elevated to more than 1000ng/ml, leukocyte counts of peripheral blood decreased significantly and interleukin-2 producing activity increased concomitantly. Thus, there was diversity in response to lentinan and complement activation was suggested to have contribution in immunopotentiation by lentinan.

Adjuvants, Immunologic↗

PubMed1988

[Effects of endoscopic intratumoral injection of lentinan in patients with gastric cancer].

We studied the effects of endoscopic intratumoral injection of Lentinan in 7 patients with advanced gastric cancer. Ten to 14 days before surgery, Lentinan at a dose of 3 mg was endoscopically injected into the cancer tissues. The effects of Lentinan injection were evaluated by immunohistochemical staining for lymphocyte subsets in the resected specimens and by the natural killer (NK) activity of peripheral blood lymphocytes before and after injection. The distribution of lymphocyte subsets in cancer tissues was compared with those of 7 patients with advanced gastric cancer without Lentinan injection (control group). The ratios of CD 8+ cells and CD 25+ cells to CD 3+ cells in cancer tissues were statistically higher in the group given Lentinan injection than in the control group. The NK activity of peripheral blood lymphocytes significantly increased from 16.0 +/- 4.6% before injection to 21.1 +/- 5.1% after injection. However, there were no changes in lymphocyte subsets during this period. There were no side effects caused by the Lentinan injection. We conclude that endoscopic intratumoral injection of Lentinan may enhance local and systemic immunity in patients with gastric cancer.

Adult↗

PubMed1988

[Combined use of lentinan with X-ray therapy in an experimental mouse tumor system (Part 2). Combined effect on the MM102 syngeneic tumor].

C3H/He mice transplanted syngeneic MM102 tumor subcutaneously in the footpad were used to study the timing of administration of lentinan when combined with local irradiation of X-ray. In combination with 1,000 rads irradiation, the administration of lentinan after X-ray was not effective. When lentinan was administered in combination with 2,000 to 3,000 rads irradiation, the growth of tumor was decreased significantly in comparison with the groups which received radiotherapy alone and those that received lentinan alone. The administration of lentinan before irradiation was effective at the same degree in the group that received lentinan after irradiation. Life prolongation effect was also observed in the group that received lentinan before and after irradiation, and 4 mice among 8 tested mice were survived at 70th day after tumor transplantation.

Animals↗

PubMedDate not supplied

Effects of oral lentinan on T-cell subsets in peripheral venous blood.

The effect of oral lentinan, a biological response modifier, on the control of systemic immune function was studied in six-week-old male Wistar-Imamichi specific-pathogen free rats. In the lentinan-treated group, 1 mg of lentinan dissolved in 1 ml of physiological saline was administered forcibly into the stomach twice weekly for four or eight weeks. Physiological saline alone was administered in a similar fashion to the control group. Leukocyte and lymphocyte counts were made and lymphocyte subsets measured using monoclonal antibodies W3/13, W3/25, and OX8, and a laser flow cytometry system. The T-cell level, the helper/inducer T-cell level, and the suppressor/cytotoxic T-cell level were measured. The peripheral leukocyte and lymphocyte counts did not change significantly in either group during treatment. After four weeks of treatment, however, the lentinan group had a significantly higher T-cell level, helper-cell level, and helper-suppressor ratio, and a significantly lower suppressor-cell level than did the control group. No significant between-group differences in the lymphocyte subsets or the helper-suppressor ratio were noted after eight weeks of treatment. Oral administration of lentinan appears to modulate the systemic immune function through stimulation of T cells, especially helper cells. Continued administration produced less effect, possibly due to a tolerance to the effect of lentinan.

Animals↗

PubMed1988

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

Lentinan has been tested in a model of colon cancer in rats. Peritoneal carcinomatoses were induced in BDIX rats by i.p. injections of syngeneic cells isolated from a colon carcinoma, and established in a permanent cell line. The treatment consisted of five i.p. injections, 2 days apart, of 2 mg lentinan/kg at a concentration of 200 micrograms/ml. This was started on day 14 after tumor cell injection, when the rats bore numerous nodules of 1-5 mm. Lentinan significantly inhibited the growth of carcinomatoses. Eleven out of the 20 rats treated with the best lentinan therapy were tumor free at autopsy on day 42. Lentinan significantly increased the life span of carcinomatous rats. The half life following tumor cell injection was 42 days in the control and 70 days in the treated group. Four out of 10 treated rats were still alive on day 210. They were tumor free at autopsy, whereas all the controls died between the 40th and the 70th day. The effectiveness of lentinan was dependent on the number and frequency of the injections. A dose effect was obtained and a strong influence of the concentration was shown.

Animals↗

PubMed1990

Induction of endogenous lymphokine-activated killer activity by combined administration of lentinan and interleukin 2.

Lymphokine-activated killer activity in vivo (endogenous LAK activity) was found to be augmented by combined administration of lentinan, a beta (1-3) glucan with beta-1,6 branches, and interleukin 2 (IL-2). In contrast, addition of lentinan during culture in vitro did not augment LAK activity induced by IL-2. Surface marker analysis of endogenous LAK cells revealed that endogenous LAK cells induced by a combined administration of lentinan and IL-2 were all NK-type LAK cells, which express asialo-GM1 and lack T3, Thy-1 and Lyt2, whereas LAK cells generated in vitro were composed of both NK-type LAK and T-type LAK cells, which express T3 and Thy-1, and lack asialo-GM1. Furthermore, combined administration of lentinan and IL-2 was found to augment the endogenous LAK activity even in the tumor bearer, and show a substantial inhibition of tumor growth and a significant increase in survival rate in the C3H/HeN/MM46 system. Results of the present investigation offer a possible clinical application of a combination of lentinan and IL-2 for immunotherapy against cancer without detrimental side effects.

Animals↗

PubMed1990

[Antigenic phenotype of the lymphocytic component of regional lymph nodes in patients with cervical cancer and its modulation by lentinan].

Immunohistochemical study with various monoclonal antibodies to the mononuclear cell surface antigens was carried out on the regional lymph nodes in patients with cervical cancer to assess the augmentative effect of lentinan. Zero, 2, 4, or 6 mg of lentinan was administered i.v. one day prior to surgery to patients with cervical cancer (14 cases with FIGO stage 0 and 19 with FIGO stage Ib) and those with benign gynecologic tumors (8 cases with myoma uteri and 6 with ovarian tumor). Frozen sections of fresh pelvic lymph nodes obtained from these patients during surgery were stained by the ABC (avidin-biotin-peroxidase complex) method using several monoclonal antibodies to define the surface phenotype of mononuclear cells. The results were as follows: 1. Pelvic lymph nodes in patients with benign disease: In the absence of lentinan, lymphocytes stained with Leu 3a antibody were more numerous than those stained with Leu 2a, and both were observed mainly in the paracortical area (PC). The number of lymphocytes stained with Leu 4 antibody was practically equal to the sum of those stained with Leu 3a and Leu 2a. HLA-Dr positive lymphocytes were present in moderate numbers in PC and sinus. The above findings were not changed by the administration of lentinan. Cells stained with monoclonal antibodies including Leu 7, 11, M3, and IL-2 receptor (IL-2R) were very few or absent. 2. Pelvic lymph nodes in patients with cervical cancer receiving no lentinan: The findings obtained in these cases were much the same as those in patients with benign tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation↗