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At least 145 records · Page 8Linked to original sources
PubMed1994

[Postoperative immunochemotherapy for gastric carcinoma with peritoneal dissemination--the effects with the combination of CDDP, 5-FU and lentinan].

Three cases of postoperative gastric cancer with peritoneal dissemination were treated by combined administration of CDDP, 5-FU and Lentinan. CDDP was given intravenously at 20 mg/body on days one to five. At the same time, 5-FU was infused continuously 250-500 mg/body per day for more than two weeks, and Lentinan was given at a dose of 2 mg per week. Two courses were repeated every 3 weeks. This combination treatment was very effective because the median survival rate for the three patients was 13 months with no sign of recurrence, and the quality of life has been good.

Adenocarcinoma, Mucinous↗
PubMed1997

[Clinical effects of postoperative immunochemotherapy with a combination of 5-FU, CDDP and lentinan for stage IVb gastric carcinoma and long-term pharmacokinetic studies on CDDP and 5-FU].

Eleven patients with postoperative-stage IVb gastric cancer were treated by combined administration of CDDP, 5-FU and Lentinan. CDDP was given intravenously at 20 mg/body on days one to five. At the same time, 5-FU was continuously administered 250 or 500 mg/body/day via the central venous catheter for more than two weeks, while Lentinan was given at the dose of 2 mg per week. Two courses were repeated every 3 weeks. The mean response duration and survival period for the eleven patients were 13 and 21 months, respectively, and one- and two year survival rates were 82% and 27%. This combination therapy was thus considered to be very effective. Next, the pharmacokinetics of long-term CDDP and 5-FU was studied. Our method could maintain the optimum serum concentration of total CDDP. Furthermore, the continuous infusion of 5-FU at a daily dose of 250 mg/day could sufficiently maintain the effective plasma concentration, although its peak fluctuated over time. Thus, in the plasma level of 5-FU in patients in poor condition requires periodic measurement.

Aged↗
PubMed1976

Combined effect of cyclocytidine and lentinan of spontaneous mammary tumors in mice.

Cytotoxic cytidine analog, cyclocytidine, and antitumor immunopotentiator, lentinan, offered an opportunity of testing the effect of combined modality of cytocidal agent and immunopotentiator on spontaneous mammary tumors of mice. Lentinan did not improve the therapeutic effect of cyclocytidine; it only prevented the early toxic death of mice due to cyclocytidine in one strain of mice but not in the other strain.

Animals↗
PubMed2002

Antitumor effects induced by the combination of TNP-470 as an angiogenesis inhibitor and lentinan as a biological response modifier in a rabbit spontaneous liver metastasis model.

PURPOSE: An angiogenesis inhibitor, TNP-470 (TNP), has shown promising results in tumor dormancy therapy, and we have been studying its antitumor effects using a rabbit spontaneous liver metastasis model. However, because inhibition was observed only at the step of micrometastasis, we examined the effects of combining TNP in the same model with a nonspecific immunopotentiator, lentinan (LNT), as a biological response modifier. METHODS: The model was established by the inoculation of VX-2 tumors into the colon, and colectomy was subsequently performed, including the primary tumor. Combination (TNP + LNT) effects were evaluated in terms of the number and volume of metastatic nodules, microvessel density (MVD), expression of proliferating cell nuclear antigen (PCNA), and apoptosis, using immunohistochemical staining with anti-CD31, anti-PCNA monoclonal antibody, and the TUNEL (in situ nick end-labeling) method, respectively. RESULTS: Angiogenesis was significantly inhibited in the TNP + LNT group, and the apoptotic index was also significantly higher than in the TNP or LNT groups. The positive expression of PCNA in the VX2 cells was reduced in the LNT alone and TNP + LNT groups, but not in the TNP alone group. CONCLUSION: These findings indicate that TNP-470 and lentinan could prove useful for preventing the development of metachronous liver metastases from colorectal cancers after curative resection.

Angiogenesis Inhibitors↗
PubMed1979

Reduction of serum X-prolyl dipeptidyl-aminopeptidase activity in tumour-bearing mice and reversal of reduced enzyme activity by lentinan, an anti-tumour polysaccharide.

Serum X-prolyl dipeptidyl-aminopeptidase activity which had been shown to be depressed in cancer patients was clearly reduced in mice with Ehrlich carcinoma and Sarcoma 180, and slightly reduced in mice with methylcholanthrene-induced sarcomas. The reduced enzyme activity was completely reversed during tumour regression of sarcoma 180 by administration of lentinan, which causes regression of sarcoma 180.

Animals↗
PubMed1996

In vitro and in vivo analysis of human leukocyte binding by the antitumor polysaccharide, lentinan.

Lentinan (LNT), a (1-->3)-beta-D-glucan with (1--6)-beta-D-glucopyranoside branches, has marked antitumor effects in syngeneic and autochtonous hosts. Clinically, LNT has proved effective with chemotherapeutic agents in patients with recurrent gastric and colorectal cancer. However, the mechanism that triggers subsequent immunologic reactions remains obscure. We hypothesized that LNT must first bind to the host cells. Accordingly, we analyzed LNT binding to host cells in healthy volunteers after incubating their cells under a variety of conditions as well as intravenously injecting LNT then subjecting them to flow cytometry and immunofluorescent staining using monoclonal antibody (anti-LNT mAb). LNT bound to monocytes and neutrophils, but not to lymphocytes in vitro. The most avid LNT binding was to monocytes. The percentage of LNT-bound monocytes after 60 min incubation at 4 degrees C was greater than that at 37 degrees C. The binding of LNT to monocytes was inhibited slightly by anti-iC3b receptor (anti-CR3) mAb, strongly by anti-C3b receptor (anti-CR1) mAb, and completely by anti-CR1 and anti-CR3 mAb together. The percentages of LNT-binding monocytes in the peripheral blood increased significantly 3 and 4 after 2 mg LNT-injection and returned to low levels 5 h later. However, no increase in LNT-binding neutrophils and lymphocytes was observed. We concluded that binding of LNT to human monocytes may initiate the influence of this compound on the immune system and differ between individuals. Its binding site may be similar to the C3b receptor.

Adult↗
PubMed1981

The effect of lentinan on fertility and general reproductive performance of the rat.

Lentinan, a polysaccharide [(1 leads to 3)-beta-D-glucan], at 0.01, 0.10 or 1.0 mg/kg/day, was administered i.v. once daily to male rats for 9 weeks and to females for 2 weeks before mating. Some animals continued to be treated until they were killed during gestation: others were killed on day 21 post partum. Selected animals of the F1 generation were retained without further treatment, to provide F2 offspring. Reactions to treatment were generally dose-related and included bruising and cutaneous lesions of the tail and swelling and discolouration of the pinnae. In males given 1.0 mg/kg/day there was a clear evidence of gonadal damage and impairment of reproductive capacity; this effect was less marked at 0.1 mg/kg/day and much reduced at 0.01 mg/kg/day. However, the reproductive performance of the selected F1 pups did not appear to have been affected by the treatment of the F0 parents at any dosage. In animals of both sexes there was a dose-related enlargement of the spleen, with evidence of macrophage infiltration.

Abnormalities, Drug-Induced↗
PubMed1981

The effect of lentinan on pregnancy of the New Zealand white rabbit.

Lentinan at 0.1, 0.3 and 1.0 mg/kg/day was administered i.v. to the New Zealand White rabbit, once daily, on days 6--18 of gestation. There were no significant treatment-related effects of post implantation loss, mean litter size and weight, mean foetal weight or the incidence of minor skeletal or visceral anomalies.

Abnormalities, Drug-Induced↗
PubMed1981

The effect of lentinan on the in utero embryonic and foetal development of the rat and on postnatal development of the F1 offspring.

Lentinan, a polysaccharide [(1 leads to 3)-beta-D-glucan], at 0.10, 1.0 or 5.0 mg/kg/day was administered i.v. to rats once daily from day 6 until, and including, day 17 of pregnancy. Some animals were killed on day 20 of gestation, others were killed on day 21 post partum. Selected animals of the F1 offspring were retained without further treatment, to provide F2 offspring. Reactions to treatment were generally dose-related and included swelling and discolouration of the pinnae, with occasional cutaneous lesions of the tail and swelling of the hind feet. Spleen weight was increased at all dosages. Litter characteristics at day 20 of pregnancy, including the incidence of abnormality, were not affected by treatment. For dams allowed to litter, mean pup weights were slightly increased, with slight acceleration of some physiological markers before weaning. There was no evidence that treatment of the F0 parents affected the reproductive performance of the F1 offspring.

Abnormalities, Drug-Induced↗
PubMed1981

The effect of lentinan on the in utero foetal development of the rat and on postnatal development of the F1 offspring.

Lentinan, a polysaccharide [(1 leads to 3)-beta-D-glucan], at 0.1, 1.0 and 5.0 mg/kg/day was administered i.v. to rats once daily from day 15 of pregnancy to day 21 post partum. All animals were allowed to deliver their young and selected animals of the F1 generation were retained without further treatment, to provide F2 offspring. Reactions to treatment were generally dose-related and included bruising of the tail and swelling and discolouration of the pinnae. Animals at 5.0 mg/kg/day sometimes showed swollen hind limbs and cutaneous lesions of the tail. Mean spleen weight in females was increased at all dosages, more so at 1.0 and 5.0 mg/kg/day. There was no evidence of an adverse effect on litter characteristics, including the pre-weaning development of the F1 offspring, or that treatment of the F0 parents adversely affected post-weaning development and reproductive performance of the F1 offspring.

Abnormalities, Drug-Induced↗
PubMed1981

Chronic intravenous administration of lentinan to the rhesus monkey.

The prolonged effects of overdosage with lentinan in the rhesus monkey are associated with foam cell reactions in lung, liver, kidney, spleen, lymph nodes and bone marrow and with varying degrees of vasculitis and associated reactions. A dose level of 0.5 mg/kg/day was without adverse effect.

Animals↗
PubMed1981

The intravenous toxicity of lentinan to the beagle dog.

The i.v administration of lentinan to the Beagle dog induced changes in the cytoplasm of macrophagic cells in the liver, spleen, kidney, lungs, lymph nodes, small intestine. Electron-lucent or filamentous inclusions were demonstrated in the liver, kidney and spleen. A dose level of 0.5 mg/kg/day was without adverse effect.

Animals↗
PubMed2003

Synthesis of two heptasaccharide analogues of the lentinan repeating unit.

beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->6)]-beta-D-Glcp (18) and the allyl glycoside of beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)[-beta-D-Glcp-(1-->6)]-alpha-D-Glcp (29) were synthesized as the analogues of the lentinan repeating heptaose by building the pentasaccharide backbones first, followed by attaching the side chains. 4,6-O-benzylidenated mono-13 or disaccharide 8 were used as the acceptor to ensure the beta linkage in the synthesis of 18, while 4,6-O-benzylidenated disaccharides 21 and 23 were used as the donor and acceptor, respectively, to ensure the beta linkage in the synthesis of 29.

Adjuvants, Immunologic↗
PubMed2005

Synthesis of heptasaccharide and nonasaccharide analogues of the lentinan repeating unit.

The allyl glycoside beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-alpha-D-Glcp (18) and the acetonyl glycoside of beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-alpha-D-Glcp (28) were synthesized as analogues of the lentinan heptaose repeating unit. 4,6-O-Benzylidenated monosaccharide donor 3 and 4,6-O-benzylidenated tetrasaccharide acceptor 14 were used to ensure the beta-linkage in the synthesis of 18, while 4,6-O-benzylidenated disaccharide acceptor 20, and 4,6-O-benzylidenated disaccharide donors 21 and 24 were used to ensure the beta-linkage in the synthesis of 28.

Carbohydrate Sequence↗
PubMed1997

Effects of lentinan on abnormal ingestive behaviors induced by tumor necrosis factor.

Lentinan (LNT), a beta-glucan derived from Lentinus edodes (Berk.) Sign., is known to work positively against cachexia in patients with malignant tumors. Because the cachectin/tumor necrosis factor (TNF) is supposed to be one of the factors that mediate cancer cachexia, we tested the effects of LNT on TNF-induced cachexia in rats. First, we analyzed in detail the cachectic actions of TNF (0.2 mg/kg/day, 5 days, IV) on food and water intake, body weight, and locomotor activity. The day after the first administration of TNF (acute phase), food and water intake, as well as body weight, of all rats decreased. However, over the next few days of treatment (chronic phase), the rats gradually developed a tolerance to the cachectic actions of TNF. Specifically, after the third administration, the rats treated with TNF had a higher amount of water intake than the control rats. This was mainly due to an increase in daytime water intake. We also analyzed the effects of LNT (0.1 or 1.0 mg/kg, twice/wk. IV) on TNF-induced cachexia, and compared the data with those from the rats treated with TNF alone. The higher dosage of LNT significantly suppressed TNF-induced daytime polydipsia and increased the amount of nighttime water intake, as well as the meal size of nighttime food intake. These results suggest that LNT partially normalizes TNF-induced cachexia in rats.

Animals↗
PubMedDate not supplied

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

Genetic studies were carried out on two in vivo responses of lentinan, delayed type-acute phase responses (DT-APR) and vascular dilation and hemorrhage (VDH). Linkage analyses showed that DT-APR was controlled by two recessive genes, ltnr1 and ltnr2, which were mapped on chromosome 3 and 11, respectively. VDH was also found to be controlled by polygenes. One dominant major gene, Ltnr3, and three dominant minor genes, Ltnr4, Ltnr5, and Ltnr6, were mapped on chromosomes 6, 9, 15 and 16, respectively.

Acute-Phase Reaction↗
PubMed2002

The skewing to Th1 induced by lentinan is directed through the distinctive cytokine production by macrophages with elevated intracellular glutathione content.

In vivo lentinan (LNT)-elicited peritoneal macrophages (Mps) showed the reduced release of prostaglandins (PGs), IL-10 and IL-6, while it endowed Mps with the elevated capability to produce IL-12 and nitric oxide (NO) upon in vitro triggering, due to the elevated intracellular glutathione (GSH) content in Mps. Deprivation of intracellular GSH completely ablated the production of IL-12. Conversely, lipopolysaccharide (LPS) induced peritoneal Mps with the reduced intracellular GSH content and the reciprocal profile of mediator production. Mps with the elevated intracelluar GSH is arbitrarily termed as reductive Mp (RMp) and that with reduced amount as oxidative Mp (OMp). OMp was converted to RMp when GSH was replenished with glutathione monoethylester (GSH-OEt). The IL-2 administration in combination with LNT exerted the synergistic induction of RMp, resulting in synergistic augmentation of IL-12, NO and reduction of IL-6 production. It was also confirmed that CD4+T cells derived of LNT-administered mice showed augmented IFN-gamma and reduced IL-4 production upon in vitro anti-CD3 stimulation. Taken together it is concluded that skewing of Th1/Th2 balance to Th1 by a beta-(1-3)-glucan, LNT, is directed through the distinctive production of IL-12 versus IL-6, IL-10 and prostaglandin E2 (PGE2) by Mps, depending on intracellular GSH redox status. To the efficient tumor immunotherapy, it may be one of the critical elements to induce a reductive form of Mps in tumor stromal tissues to maintain Th1 response.

Animals↗
PubMed1980

[Subacute toxicity study of lentinan in rats. 5-week intravenous treatment (author's transl)].

Male and female JCL : SD rats were treated intravenously with lentinan in 5% mannitol solution at dose levels of 0, 0.03, 3.0 and 30.0 mg/kg/day for 5 weeks. Rats receiving 0.3, 3.0 and 30.0 mg/kg/day showed reddening in ear, tail and scrotum and edema in legs and scrotum after day 3 of treatment. Males receiving 30.0 mg/kg/day gained less body weight than control. Occult blood was found in the urine of rats receiving 30.0 mg/kg/day. With regard to haematology, rats from the treatment groups had low mean values relating to red blood cell count, packed cell volume and haemoglobin, while high white blood cell count were recorded for these rats. Biochemical examinations revealed decreases in albumin level and A/G ratio and increases in beta-globulin and gamma-globulin levels for rats from the treatment groups. Slightly high values of BUN were showed for rats receiving 30.0 mg/kg/day. Organ weight analysis showed dose-dependent increase in the spleen, liver and adrenal. Histopathological changes attributable to treatment included (1) changes in reticuloendothelial system such as proliferation of reticular cells and micronodule of epithelioid cells in the spleen, liver and lymph nodes; (2) arteritis in many organs especially notable in epididymis, intestines and mesentery; (3) haemorrhagic changes in lung, intestines and urinary bladder and secondary changes such as increased chronic nephropathy, hypospermatogenesis, spermatic granuloma in epididymis and granulomatous inflammation in ear, tail and scrotum. The maxim safe dose was estimated to be smaller than 0.03 mg/kg/day for males and 0.03 mg/kg/day for females in the present study.

Animals↗