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[A case of advanced gastric cancer (type 3) with pyloric stenosis, multiple liver and lymph node metastases responding to UFT-E granules and lentinan].

The patient was a 80-year-old male with advanced gastric cancer (Type 3) accompanied by multiple liver and lymph node metastases. Histological findings in the stomach showed poorly differentiated adenocarcinoma. He had nausea, vomiting and anorexia due to pyloric stenosis, and was treated with 600 mg of UFT E granules/day orally for 5 consecutive days followed by 2 drug-free days (weekly-5 method), and 2 mg of lentinan intravenously twice a week. After 4 weeks of treatment, the primary tumor and metastatic lesions of the liver and lymph nodes were markedly reduced. His symptoms had completely disappeared along with lessening of the pyloric stenosis after 6 weeks of treatment. The patient survived for 7 months in a state of CR and PR. The adverse effects were very mild and negligible. A weekly-5 method of UFT, in comparison with conventional daily administration, may induce maximal antitumor effects with minimal adverse effects.

Adenocarcinoma↗

Immunoregulatory effects of the antitumor polysaccharide lentinan on Th1/Th2 balance in patients with digestive cancers.

BACKGROUND: Recent studies demonstrated that patients with advanced cancer may have impaired cell-mediated immunity caused by an imbalance between Th1 and Th2 responses. We evaluated the ability of lentinan (LNT) to modulate Th1 and Th2 responses in patients with digestive cancers. METHODS: Peripheral blood samples were collected preoperatively from 28 patients with digestive cancers before and after intravenous administration of LNT (2 mg x 3 times/week). The proportions of CD4+ T-cells producing intracellular cytokines were determined with flow cytometry. RESULTS: After LNT treatment, CD4+ IFN-gamma+ T-cell percentages increased significantly (p < 0.05), whereas CD4+ IL-4+ T-cell and CD4+ IL-6+ T-cell percentages decreased significantly (p < 0.02). No significant change occurred in proportions of CD4+ IL-10+ T-cells. The after/before LNT treatment percentages ratio of CD4+ IFN-gamma+ T-cells correlated negatively with that of CD4+ IL-4+ T-cells (p < 0.01). The after/before treatment percentage ratio of CD4+ IL-4+ T-cells correlated positively with that of CD4+ IL-6+ T-cells (p < 0.05). CONCLUSION: LNT apparently can cancel Th2-dominant condition in patients with digestive cancers and may improve the balance between Th1 and Th2.

Adjuvants, Immunologic↗

[Relationship between prolonged life span and changes of serum IAP and albumin induced by the therapy of lentinan plus tegafur in inoperable and recurrent gastric cancer].

Relationship between prolonged life span and changes of serum IAP and albumin induced by the therapy of lentinan plus tegafur were analysed on 43 cases with inoperable and recurrent gastric cancer. Antitumor effect was observed only in one case (2%). Other clinical effects such as improvement of performance status (PS), appetite or pain were observed in 18 cases (42%). Decrease of serum IAP was observed in 25 cases (58%) and increase of albumin was observed in 20 cases (47%). The changes of these two factors seemed to be reversely correlated. Among 30 cases which didn't show decrease of albumin, we found no increase of serum-IAP in 22 cases (72%). In the cases which showed decrease of serum IAP from abnormally high level (more than 500 mu/ml) and increase of albumin from abnormally low level (less than 3.5g/dl), prolonged life span was observed by comparison with the other cases. The cases with any clinical effect contained 78% of the cases without increase of serum IAP, and 72% of the cases without decrease of albumin. These results suggested that life prolongation effect or improvement of clinical symptoms by our therapy was closely related to the change of these serum factors.

Antineoplastic Combined Chemotherapy Protocols↗

[Pilot study of TS-1 combined with lentinan in patients with unresectable or recurrent advanced gastric cancer].

TS-1, an anticancer, antimetabolis agent, has shown clinically superior antitumor activity against unresectable advanced or recurrent gastric cancer (UARG). A biological response modifier, lentinan (LNT) prolonged the survival period of patients with UARG when combined with tegafur (FT). To assess the efficacy, the safety and prognostic factors of chemo-immunotherapy using TS-1, a FT derivative, and LNT, we conducted a multi-institutional pilot study in patients with UARG. Patients were treated with TS-1 at 80 mg/m2/day (bid) for 4-weeks, and LNT was given at 2 mg/body (i.v.) in a week, followed by a 2-week rest for 4 cycles. Twenty-two patients were entered from 4 institutes and 19 patients were eligible. The median survival time in eligible patients was 400 days. The incidence of hematological toxicity (grade 2 leukopenia), and non-hematological toxicity (grade 3 nausea or fatigue) was 5.3% (1/19) and no grade 4 toxicity was observed. The response ratio was 37.5% in 8 patients who had been administered the planned dose of TS-1. In subset analyses, the survival period of the patients with normal (< 500 micrograms/ml) serum immunosuppressive acidic protein level was significantly (p < 0.0001) better than that of the higher one. The survival period for those patients whose granulocytes/lymphocytes ratio was not more than 2 tended to be better. From the prolonged survival periods, chemo-immunotherapy using TS-1 combined with LNT would seem to have a benefit against UARG, and reduced toxicity. Future clinical trials are warranted to confirm its potency.

Aged↗

[A case of long survival with UFT and lentinan treatment in a patient with peritoneal metastasis of gastric carcinoma].

The patient was a 50-year-old female with peritoneal metastasis of Type 4 gastric cancer. She underwent a relative curative resection with total gastrectomy and peritonectomy. Postoperative chemotherapy with 5'-DFUR following 5-FU and CDDP was performed. Thirteen months after surgery, cancer recurrence was suspected due to elevated levels of the serum tumor markers carcinoembryonic antigen (8.9 ng/ml) and alpha fetoprotein (85.8 ng/ml). She was additionally treated with UFT 300 mg/day and Lentinan 2 mg/week. The serum tumor markers decreased gradually returned to normal levels. At 5 years and 8 months after surgery, she is alive without any sign of recurrence.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of advanced gastric cancer with liver metastasis completely responding to a combined immunochemotherapy with UFT, mitomycin C and lentinan].

A 74-year-old man with advanced gastric cancer of Borrmann type III and liver metastasis was treated by combined administration of UFT (400 mg/day, p. o.), Mitomycin C (14 mg/body/4w., i.v.) and Lentinan (2 mg/w., i.v.). Five and half months after the therapy, endoscopic examination and ultrasonography showed the primary and liver-metastatic lesions had completely disappeared. Ten months after the therapy, total gastrectomy and intraoperative liver wedge biopsy were performed and complete disappearance of cancer cells was histologically confirmed. The total dose of UFT, MMC and LNT administered until the operation was 76.4 g, 42 mg and 74 mg, respectively. However, the patient eventually died of the recurrence of liver metastases three years after the initial immunochemotherapy.

Adenocarcinoma↗

[S-1 combined with lentinan in patients with unresectable or recurrent gastric cancer].

Lentinan (LNT) is a beta-glucan known to have a life-prolonging effect in combination with chemotherapy for patients with unresectable or recurrent gastric cancer. Thus, a multi-center trial of chemo-immunotherapy using S-1 combined with LNT may benefit patients with unresectable or recurrent gastric cancer with acceptable toxicity. With such a regimen, the median survival time in 32 patients was 559 days. Regardless of change to second-line chemotherapy, the mean period of using S-1+LNT for patients with long NC above 400 days was 725 days. In subset analyses, the survival period of the patients with G/L ratio of equal to or less than 2 was significantly better than that of the higher one (p<0.0001). The incidence of hematological toxicity (grade 3 leukopenia and thrombocytopenia) was 6.3% (2/32), and non-hematological toxicity (grade 2 dysgeusia) was 6.3% (2/32), while no grade 4 toxicity was observed. S-1 and LNT combination immunotherapy was carried out safely with high QOL and allowed a prolonged administration. S-1+LNT regimen may prolong NC periods in patients with unresectable or recurrent gastric cancer.

Adenocarcinoma↗

[Anti tumor activities of lentinan and micellapist in tumor-bearing mice].

Although Lentinan (LNT) is sold as a medicine, and Micellapist (MME) sold as a food supplement, both LNT and MME are beta-glucans isolated from the Shiitake mushroom (Lentinula edodes). These two substances have been thought to be the same component of Shiitake. In the present study, we evaluated anti tumor activities of LNT and MME in tumor-bearing mice (B10.D2 mice implanted with S908D2 tumor cells) and examined the mechanism of immunopotentiation of these substances. The tumor growth was significantly suppressed in the LNT-treated group. In ex vivo evaluation, the tumor cytotoxicity was significantly reduced by a treatment of splenocytes with anti-CD8 antibody in the LNT-treated group. Furthermore, the tumor cytotoxicity of the LNT-treated group was also significantly reduced by a treatment of splenocytes with anti-CD8 antibody and its complement and with an anti-CD4 and its complement in the effector phase and the induction phase, respectively. A significant prolongation of the survival of tumor-bearing mice as compared to the untreated control group was noted in the LNT-treated group. In the mice treated intraperitoneally with LNT, CD8-positive cells appeared to have suppressed tumor cell proliferation. CD4-positive cells appeared to be involved in this activity of CD8-positive cells. On the other hand, orally administered MME has exerted no clear cytotoxic effects.

Adjuvants, Immunologic↗

[Scanning electron microscopic observation of mouse ascitic carcinoma cells after intraperitoneal administration of lentinan].

Direct action of lentinan (LNT) on tumor cells in an in vivo system was observed by scanning electron microscopy. LNT was injected intraperitoneally 7 consecutive days (0.1 mg/mouse/day) in to C3H/He mice along with MM2 ascitic carcinoma cells. MM2 tumor cells adhering to the peritoneal wall were examined every day until the day after the last LNT injection, and compared with cells of non-treated tumor bearing mice. On the day after the first LNT injection, LNT was observed as granulated material both on the tumor cells, which were degenerated and on the mesothelial cells, which were not changed. On the 7th day, almost all tumor cells were seen to be surrounded by many lymphocytes in the LNT-treated mice. Retention of ascitic fluid and fibrin deposition were almost the same as or less than in non-treated mice. From these results, it is suggested that direct action of LNT on tumor cells contributed to enhancement of antitumor immunity, although LNT did not have direct killing activity against tumor cells.

Animals↗

[A case report of advanced gastric cancer remarkably responding to mitomycin C, aclacinomycin A, SF-SP and lentinan combination therapy].

A 63-year-old female diagnosed as inoperable gastric cancer was treated with combination immunochemotherapy of Mitomycin C, Aclacinomycin A, SF-SP and Lentinan. In this case, the tumor directly invaded the pancreas and the peritoneal dissemination, metastasis to the para-aortic lymph nodes and Virchow's metastasis were identified. As the result of this therapy, the primary tumor was remarkably reduced in size. The subjective symptoms and the metastasis of the para-aortic lymph nodes and Virchow's metastasis disappeared. The side effect was only mild thrombocytopenia.

Aclarubicin↗

[An advanced gastric carcinoma which responded to combined administration of mitomycin C, FT-207, and lentinan immunochemotherapy].

A 59-year-old man with a gastric cancer underwent a laparotomy and was found to have an unresectable tumor that formed a large mass with metastatic lymph nodes around the aorta. He therefore was treated by a combined administration of Mitomycin C, FT-207, and Lentinan for 3 months. Remarkable tumor reduction was observed endoscopically, and a subtotal gastrectomy was performed. The immunochemotherapy then was resumed, and the patient has survived for 16 months despite the remnant lymph node metastases. A histological examination of the resected stomach revealed a marked degeneration of the tumor.

Adenocarcinoma↗

[Successful therapy with tegafur and lentinan after TAE for hepatocellular carcinoma--a case report].

A 46-year-old male (performance status 1) with hepatocellular carcinoma (HCC), which diffusely involved the anterior segment of the right lobe, occluded the second portal branch and metastased to the left lobe (stage IV-A), was on combined therapy with TAE of lipiodol (LPD), mitomycin C (MMC) 10 mg and gelatin sponge at the time of angiography on March 16, 1987. Immunochemotherapy with tegafur suppository (Teg sp) 1,000 mg/day and OK432 i.m. was performed for one month after TAE. Instead of OK432, lentinan (LNT) 2 mg in 20% glucose sol. 20 ml i.v./wk was combined with Teg sp 1,000 mg/day from May 13, 1987. Teg sp was reduced to 1,000 mg/2 days from June of the same year, and since then the same therapy of Teg + LNT has been continuing even now. Serum AFP values showing 150 X 10(4) ng/ml at maximum were decreased down to less than 20 ng/ml 13 months after this therapy (total doses: Teg ca. 250 g, LNT 108 mg), remaining still normal. Marked reduction in the size of the lesion (PR) by the therapy has also been proved by the body CT. His PS is now in grade 0. Although in this case the initial steep decline in AFP values was possibly brought about by TAE, the successive antitumor effect indicated by persistent low AFP values may have been mainly due to Teg + LNT. Collection of data on the therapy is needed to clarify this point.

Antineoplastic Combined Chemotherapy Protocols↗

[Basic studies on oral administration of lentinan (I)--influence on lymphocyte subsets in peripheral venous blood].

The effect of oral administration of lentinan (LTN), a biological response modifier, in the control of systemic immune function was studied in 6-week old male Wistar-Imamichi SPF rats. In the LTN group, 1 mg LTN dissolved in 1 ml physiological saline was administration forcibly into the stomach twice weekly. Physiological saline alone was administered in a similar fashion to the control group. Blood samples were obtained prior to and after four and eight weeks of administration. White blood cells and lymphocyte counts were obtained and lymphocyte subsets were measured using monoclonal antibodies W3/13, W3/25 and 0 X 8 (Sera-Lab), and a laser flow cytometry system (Orthospectrum III, Orthodiagnostic System). The T cell ratio, helper/inducer T (Th) cell ratio, and suppressor/cytotoxic T (Ts) cell ratio were measured. The peripheral white blood cell count and lymphocyte count were not significantly different between the control and LTN groups. After four weeks of LTN administration, however, the LTN group showed a significantly higher T cell ratio, Th cell ratio and Th/Ts cell ratio than did the control group, and the Ts cell ratio was significantly lower. In the groups undergoing administration for eight weeks, no difference was noted in the lymphocyte subsets between the two groups. Oral administration of LTN apparently modulates the systemic immune function through T cell stimulation, especially Th cells, but continued administration may induce a tolerance to the effect of LTN.

Administration, Oral↗

[A gastric cancer showing marked improvement (stage IV) with lentinan immunotherapy and 5-FU, MMC-chemotherapy].

A 59-year-old male undergoing an exploratory laparotomy for stage IV gastric cancer (H0P1N4S3) was treated concomitantly with Lentinan, 5-FU and MMC. The CEA values, fluoroscopic and endoscopic findings and histology by biopsy were investigated sequentially. Three months after the beginning of treatment, clinical symptoms had nearly disappeared. Body weight increase and recovery from anemia were observed. The CEA value which had shown a high preoperative level of 114.2 ng/ml decreased to 4.0 ng/ml. The marked improvement of endoscopic findings and no cancer cells were seen in several biopsy specimens. However, the condition of the patient deteriorated six months later. This patient showed clear improvement, although temporary, with immunochemotherapy.

Adenocarcinoma, Mucinous↗

Clinical efficacy of lentinan on patients with stomach cancer: end point results of a four-year follow-up survey.

End-point results of a 4-yr followup survey and a randomized control trial of lentinan (LNT) on patients with advanced or recurrent stomach cancer have been investigated in order to evaluate the clinical efficacy of LNT in combination with chemotherapeutic agent tegafur (FT). Eligible (68) patients in control groups were administered with FT consecutively at doses of 600 mg/day, and eligible (96) patients in the treated group were administered LNT in combination with FT. LNT was injected intravenously 2 mg weekly. Remarkable lifespan prolongation effects of LNT have been observed both at the end of the control trial and at the end of the followup survey (p less than 0.01) using Kaplan-Meier's method and the generalized Wilcoxian test. Remarkable survival at 1, 2 and 3 years has been observed in the treated group using lifetable analysis. Side effects of LNT have been transitional and not serious. Thus, LNT should be effective in combination with FT for patients with stomach cancer.

Adult↗

[Effects of lentinan in advanced or recurrent cases of gastric, colorectal, and breast cancer].

In order to evaluate clinical efficacy of Lentinan (LNT), a purified polysaccharide extracted from Lentinus edodes, randomized controlled studies with envelope method have been conducted on the patients with advanced or recurrent, stomach, colo-rectal and breast cancer. Administration condition of LNT for gastrointestinal cancer was designed as the following: LNT was administered intravenously at doses of 1 mg/person/day twice a week or 2 mg/person/day once a week in combination with mitomycine C + 5-FU (MF) or tegafur (FT). Control therapy was the administration of MF or FT alone. Survival curve drawn by Kaplan-Meier's method showed that life span prolongation effect of LNT was observed with statistical significance (P less than 0.05 or P less than 0.01) by use of generalized Wilcoxon's test. Moreover, improvement of host immune responses was observed in LNT treated group, and hematological survey showed that incidence rate of abnormal value was significantly low in LNT treated group. Thus, LNT should be effective for the patients with advanced or recurrent stomach or colo-rectal cancer in combination with chemotherapeutic agents such as MF or FT. Regarding advanced or recurrent breast cancer, study is underway. LNT has been administered as an agent for supportive therapy to the patients with complete response, partial response or stable diseases which were induced by prior surgery of oophorectomy. Again, life span prolongation effect of LNT has been observed with statistical significance (P less than 0.05). This result suggests that LNT would also be effective for the patients with advanced or recurrent breast cancer as an agent for supportive therapy.

Adjuvants, Immunologic↗

Combination therapy of murine tumors with lentinan, bacterial lipopolysaccharide and a Streptococcus preparation, OK432.

Combination therapy by intralesional injection of OK432 followed by intraperitoneal administration of lentinan and bacterial lipopolysaccharide caused almost complete regression of solid-type tumor MH134. All three components were needed for maximal antitumor activity. Mice in which MH134-tumor had regressed due to this combination therapy showed an augmented antitumor delayed hypersensitivity reaction (measured by the footpad test) and resistance to rechallenge with MH134, but they had no cytolytic antibodies in their serum detectable by the complement cytotoxicity test. The possible importance of local inflammation induced by OK432 in this combination therapy is discussed.

Animals↗

Induction of cytotoxic peritoneal exudate cells by T-cell immune adjuvants of the beta(1 leads to 3) glucan-type lentinan and its analogues.

Eight distinct polysaccharides (PS) of beta(1 leads to 3) glucan type were tested for their capacity to render murine peritoneal exudate cells (PEC) cytotoxic. After intraperitoneal injection of lentinan, pachymaran and HE-pachyman 3 and 4 highly cytotoxic PEC were induced. Pachyman and HE-pachyman 1 and 2 were of moderate effect, whereas CM-pachymaran and HE-pachyman 3 and 4, highly cytotoxic PEC were induced. Pachyman and HE-pachymacrophages. The induction of PEC-dependent cytotoxicity exhibited a strict dose relationship. Optimal administration of PS resulted in the induction of cytotoxicity, which persisted for more than 25 days. Surprisingly, none of the PS tested was capable of rendering normal or thioglycollate-induced PEC cytoxic under in vitro conditions. It is suggested that the capacity of PS to render in vivo macrophages cytotoxic is related to the potency of these PS to activate the alternative pathway of complement system (APC) in so far as C3b may be the essential component required to render macrophages cytotoxic.

Adjuvants, Immunologic↗