A polysaccharide extracted from rice bran fermented with Lentinus edodes enhances natural killer cell activity and exhibits anticancer effects.

The objective of this study was to investigate the activation of natural killer (NK) cells and anticancer effects of exo-biopolymer from rice bran cultured with Lentinus edodes [rice bran exo-biopolymer (RBEP)]. Oral administration of RBEP induced the activation of NK cells in a dose-dependent manner. RBEP also prolonged the life spans of mice transplanted with Sarcoma-180 cells and inhibited growing Sarcoma-180 cells in intraperitoneum. Solid tumor growth was also suppressed by oral administration of RBEP in C57/Bl6 mice transplanted with B16/Bl6 melanoma. Intraperitoneal injection of RBEP was more effective than oral administration at the same dosage in mice with transplanted tumor cells. According to this result, when RBEP directly contacts immune cells, the anticancer activity is higher than by indirectly inducing an immune response through oral administration. Therefore, we suggest that the administration of RBEP may be effective for preventing and/or treating cancer through NK cell activation. However, further studies are needed to elucidate the possible mechanisms of the anticancer activity and to investigate the other beneficial effects of RBEP for the development of a new biological response modifier.

[Effect of reducing caloric intake on mice transplanted with S180 ascitic cancer].

OBJECTIVE: To examine the effect of different reduced caloric intake on mice transplanted with S180 ascitic tumor. METHODS: The institute for cancer research (ICR) mice were randomly divided into control group, 3.0 standard feed (SF) group, 2.0 SF group and 1.3 SF group. The mice in control group were fed enough (about 5 g/d) dietary intake, while the amounts of dietary intake in the latter three groups were scaled down in the proportion of 65%, which were 3.0 g, 2.0 g and 1.3 g standard feed respectively. Meanwhile the essential vitamins were added to the latter three groups to keep the amount of intake the same as that of the control's. RESULTS: For most of the mice, the caloric intake obviously prolonged the mean survival days and improved the life quality was 7.14 kcal/d, and the fasting blood glucose level was 2-3 mmol/L. CONCLUSION: Properly reduced caloric intake and keeping lower blood glucose level is beneficial to prolonging the survival time of mice transplanted with S180 ascitic cancer.

Evaluation of naphthal-NU, a 2-chloroethylnitrosourea derivative of naphthalimide, as a mixed-function anticancer agent.

Naphthal-NU, 2-[2-[3-(2-chloroethyl)-3-nitrosoureido]ethyl]-1H-benz[de]isoquinoline-1,3-dione (Compound 1) has been synthesized as a rationally designed new mixed-function anticancer agent from 1,8-naphthalic anhydride. Its chemical alkylating activity compared with CCNU as standard compound indicated that it possesses greater alkylating activity than the latter. Its antitumour efficacy was assessed in vivo in two murine ascites tumours namely Sarcoma-180 (S-180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median survival times (MST) of drug treated (T) over untreated control (C) mice. Three clinical drugs namely CCNU (lomustine), endoxan (cyclophosphamide) and 5-fluorouracil (5-FU) were used as positive controls for comparison. Compound 1 has displayed excellent and reproducible antitumoural activity having curative effects in these tumours comparable with CCNU and 5-FU. It has also significantly increased the life span of mice bearing highly advanced tumour for 10 days before the drug challenge. Its toxicity was also assessed in vivo in normal and in S-180 bearing mice by measuring drug-induced changes in hematological parameters, femoral bone marrow and splenic cellularity sequentially on days 9, 15 and 21 following drug treatment at the optimum dose of 50 mg/kg from day 1 to 7. The results indicated that the compound did not adversely affect hematopoiesis. Drug-induced hepatotoxicity and nephrotoxicity were also evaluated at its optimum dose on those days but no such toxicities were detected. It was further screened in vitro in 6 different human tumour cell lines but no significant activity was observed in those lines.

Effects of hyperbaric oxygen on S-180 sarcoma in mice.

The contents of oxygen free radicals (OFRs) and malondialdehyde (MDA) in S-180 sarcoma tissues were measured in four groups of mice: an untreated normoxic group, a normoxic hyperbaric group, a hyperbaric oxygen group, and an HBO group treated with superoxide dismutase (SOD). Measurements were done by electron resonance and spectrophotometry, and observations were made on the volume, weight, necrosis incidence rate of sarcoma tissues, and mortality in all groups. The OFR and MDA content in sarcoma tissues in the HBO group was significantly higher than those of the control groups (P < 0.001); necrosis incidence of sarcoma tissues and the survival rate of mice were higher; the time required for necrosis was shorter, and the volume and weight of sarcoma tissues were smaller and lighter than those of the control groups (P < 0.01). The results suggest that SOD cannot completely eliminate OFRs produced by hyperbaric exposure, although the role of HBO in producing more OFRs can be counterbalanced by SOD to a certain degree. Apparently HBO can check the growth rate of sarcoma and accelerate the necrosis of S-180 sarcoma cells.

Response of mouse sarcoma-180 to bleomycin in combination with radiation and hyperthermia.

The response of a transplantable mouse tumor, S-180, grown intradermally in inbred Balb/c mice, to bleomycin (BLM), irradiation (RT) and hyperthermia (HT) was studied by observing tumor growth changes up to 120 days after treatment. BLM, at 20 mg/kg body weight, and 10 Gy gamma radiation individually produced identical tumor cure, while hyperthermia at 42 degrees C, 60' or 43 degrees C, 30' resulted in a higher tumor response. Treatment with 43 degrees C, 30' after BLM was more effective than hyperthermia after radiation in effecting tumor cure as well as in inducing regrowth delay. In the drug +HT combination the low drug dose was almost equal in effect as the higher drug dose when followed by 43 degrees C, 30'. Combining the three modalities resulted in 100% tumor cure without any local recurrence during the observation period. The micronucleus study 24 h after treatment indicated enhanced cytogenetic damage by the combination treatments.

Combined therapy of mitomycin C and Chinese medical herbs on experimental liver cancer.

In this research, ICR male mice were chosen for intrahepatic implantation of sarcoma 180 tumor cells (1 x 10(7)). The mice were randomly divided into various groups 24 hours after implantation. One of the groups was the tumor control, the others were singly or combinedly treated with mitomycin C (MMC) and Shih Chuan-Ta-Pu-Tang (SCTPT) or Shi-Hung-One (SHO). The results revealed that the mortality rate (MR60) in the tumor control was 100% and the mean survival time (MST60) was 21.11 +/- 10.69 days. The best therapeutic effect appeared in the group treated with the combination of MMC and SHO, its MR6o was 55.0% and MST 60 was 47.0 +/- 13.4 days.

[Controlled prospective trial to evaluate Syosakiko-to in preventing hepatocellular carcinoma in patients with cirrhosis of the liver].

A controlled prospective study was conducted to evaluate the potential of Syo-saiko-to (Xiao-Chai-Hu-Tang) for the prevention of hepatocellular carcinoma (HCC). Pairs of patients were matched for age, sex, presence of HBs antigen and the scores of the severity of liver dysfunction from 260 cirrhotic subjects. We randomly assigned each patient to receive either a conventional medicine (control group), or 7.5 g/day of Syo-saiko-to (trial group). The patients were monitored during 34 months of treatment, and the incidence of HCC in the two groups were compared. Seventeen patients were found to have HCC in the control group, and nine were found to have HCC in the trial group. The incidence of HCC was significantly lower in the trial group. The results of this study suggested that Syo-saiko-to may prevent or delay the emergence of latent HCC in patients with cirrhosis of the liver.

Optimization of high-dose methotrexate with leucovorin rescue therapy in the L1210 leukemia and sarcoma 180 murine tumor models.

An analysis of dose and schedule dependence of calcium leucovorin rescue during high-dose methotrexate therapy of ascitic forms of l1210 leukemia and Sarcoma 180 is reported. Schedules with very delayed "low-dose" leucovorin rescue following lethal doses of methotrexate were highly effective in preventing toxicity and achieved a pronounced antitumor effect in both ascites tumor models. Best results were obtained on a schedule of methotrexate (400 mg/kg s.c.) followed 16 to 20 hr later by calcium leucovorin (12 mg/kg s.c.) given once every 2 hr for a total of 5 doses. Progressive increases in the calcium leucovorin dosage on any schedule reduced both toxicity and the antitumor effect of methotrexate in each model. Following a single course of therapy, essentially no toxicity was observed, and the antitumor effects were 2-fold (L1210 leukemia) and 4-fold (Sarcoma 180) greater than a single, maximally tolerated dose (24/kg s.c.) methotrexate alone. An increase in the methotrexate dosage to 800 mg/kg s.c. with or without an increase in calcium leucovorin dosages on the same schedule did not appreciably increase the antitumor effect observed. Two courses of high-dose methotrexate (400 mg/kg s.c.) with leucovorin rescue (24 mg/kg s.c. 16, 20, and 24 hr after drug) given with an 8-day interval between courses doubled the total antitumor effect in each model with no substantial increase in toxicity and gave long-term survivors with Sarcoma 180. The results, overall, are in close agreement with prior prediction for schedule and dose dependence made on the basis of related pharmacokinetic and biochemical studies in murine tumor models reported from this laboratory.