Induction of apoptosis by Acanthopanax senticosus HARMS and its component, sesamin in human stomach cancer KATO III cells.

Antitumor effect of the stem bark of Acanthopanax senticosus HARMS (ASH) from Hokkaido (Japanese name: Ezoukogi) on human stomach cancer KATO III cells was investigated. The extract of the stem bark of ASH prepared with hot water was dissolved in distilled water and used for the assay of antitumor effect on the KATO III cells. The exposure of KATO III cells to ASH led to both growth inhibition and induction of apoptosis. Morphological change showing apoptotic bodies was observed in the cells treated with ASH. The fragmentation by ASH of DNA to oligonucleosomal-sized fragments that are characteristics of apoptosis was observed to be concentration- and time-dependent. We have investigated which component in ASH is effective on the induction of apoptosis. Among chlorogenic acid, syringaresinol di-o-beta-D glucoside, syringin, and sesamin, components of the n-butanol extract prepared from ASH, sesamin suppressed the growth and induced apoptosis in the cells. These findings suggest that growth inhibition by ASH results from the apoptosis induced by sesamin, a component of ASH.

[Japanese cedar pollinosis in infants in the allergy clinic].

Recently, the number of patients with Japanese cedar (Cryptomeria japonica) pollinosis has increased, especially in children. However, little is known about the incidence in infants. We studied on the rate of sensitization and the onset of pollinosis in children under 6 years old. The percentage of positive CAP-RAST to Japanese cedar pollen was 27.6%, in 76 infants (51 male and 25 female, 2 months-5 years old) who visited National Mie Hospital pediatric allergy clinic due to bronchial asthma and/or atopic dermatitis. The youngest child who has been sensitized to pollen was 1 year 8 month old boy. The percentage of positive rate of CAP-RAST to house dust mite was 61.8%. Twenty-seven infants (20 male and 7 female, 2-5 years of age) were diagnosed as Japanese cedar pollinosis in National Mie Hospital Otorhinolaryngology clinic in 1999 and 2000. The youngest child with pollinosis was 2 year 5 month old boy. Most of the 27 infants complained of rhinorrhea and/or eye symptoms and some of them complained cough, snoring, or epistaxis. About 40% were sensitized to Japanese cedar and/or cupressaceae pollen alone, 60% were also sensitized to house dust mite. In conclusion, it is possible that the sensitization to Japanese cedar pollen occurs after 2 season of pollen exposure and pollinosis occurs in 2 years old. Japanese cedar pollen has been an important allergen not only in school children, but also in infants.

Surgical resection combined with intrathoracic hyperthermic perfusion for thymic carcinoma with an intrathoracic disseminated lesion: a case report.

Thymic undifferentiated carcinoma has a poor prognosis. We encountered a patient with thymic carcinoma associated with an intrathoracic disseminated lesion, who underwent surgery combined with intrathoracic hyperthermic perfusion after systemic chemotherapy and showed good results. The 45-year-old man was diagnosed as having a thymoma with an intrathoracic disseminated lesion. After he underwent three courses of systemic chemotherapy, he was admitted to our hospital. An anterior mediastinal tumor and an intrathoracic disseminated lesion remained, and were treated by surgical resection combined with intrathoracic hyperthermic perfusion. The tumors were histopathologically diagnosed as thymic undifferentiated carcinomas with pleural dissemination. At present, approximately 16 months after surgery, the patient is alive without recurrence.

Comprehensive treatment of advanced neuroblastoma involving autologous bone marrow transplant.

Encouraging results are reported with high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation in the treatment of advanced neuroblastoma. However, relapse remains a significant problem. We used high-dose chemotherapy, surgery, intraoperative radiation and an autologous bone marrow transplant treated in vitro to remove tumor cells followed by 13-cis-retinoic acid to treat 36 children with advanced neuroblastoma. This comprehensive treatment appears to improve the survival rate of patients with advanced neuroblastoma, including those with N-myc amplification and bony involvement. The disease-free survival rate was 66% (95% confidence interval, 49-84%) at 3 years. All patients who received 13-cis-retinoic acid developed cheilitis, but no bone marrow depression occurred in these patients. Five patients developed hemolytic uremic syndrome (HUS) post-transplant. This may have been related to the procedure used for total body irradiation. Patients who had their kidneys shielded during this procedure did not develop this syndrome. Patients who received local irradiation at the primary site showed no evidence of relapse in this region, indicating that such therapy may help to prevent a relapse. These data suggest a high rate of 3 year disease-free survival with this treatment strategy. The nonrandomized nature of the study and use of multiple modalities precludes analysis of the specific contribution of each.

Effect of dietary fat and fiber on fecal flora, bacterial metabolites, and fecal properties in Japanese volunteers.

The effects of dietary fat and dietary fiber (DF) levels in diet on fecal flora, activities of three fecal enzymes, putrefactive metabolites, fecal mutagenicity and fecal properties were studied in eight healthy volunteers. They were given low fat and low DF diet (LF: fat energy ratio was 13.9%, and DF intake was 9.0 g/day) for 10 days, high fat and low DF diet (HF: fat energy ratio was 52.7%, and DF intake was 7.1 g/day) for 10 days, and high fat and high DF diet (HFF: fat energy ratio was 52.0%, and DF intake was 24.8 g/day) for 10 days. No change of fecal flora at the bacterial group level was observed throughout the experimental period, except that the population of lactobacilli showed a tendency to increase in HF period. Fecal activities of beta-glucuronidase, beta-glucosidase and nitroreductase and some putrefactive products were unchanged between LF and HF, while these values decreased in HFF period. No significant change of fecal properties was observed between LF and HF, while by HFF supplementation fecal weight increased and fecal pH value was lower than that in LF and HF. Excretions of iron, zinc and calcium in feces did not increase by high DF supplementation.

Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats.

Effect of Gymnema sylvestre, R.Br. (G. sylvestre; GS4) on glucose homeostasis was studied in rats. In the first set of experiments, the acute effect of GS4 was examined in both non-diabetic and streptozocin (30 mg/kg)-induced mildly diabetic rats. Administration of 1 g/kg body weight of GS4 to 18-h fasted non-diabetic rats significantly attenuated the serum glucose response to oral administration of 1 g/kg glucose. The immunoreactive insulin (IRI) response in GS4-administered rats was lower, but not significantly, than that in control rats. In mildly diabetic rats, a 60 min increment in serum glucose concentrations was significantly reduced by GS4 administration. No IRI response was observed in these diabetic rats irrespective of GS4 administration. In the second set of experiments, the chronic effect of GS4 was examined in mildly diabetic rats. Two weeks after the induction of diabetes, the rats were divided into two groups that had similar impairment of glucose tolerance assessed by an oral glucose loading test. The rats were fed for 32-35 days with either a control diet or a diet supplemented with GS4. After 4 weeks, GS4 showed a tendency to reduce the serum glucose concentrations in the fed state and to improve the glucose tolerance. Gain in body weight, food intake, pancreas weight and the pancreatic contents of IRI, protein, amylase and trypsinogen were unaltered in the GS4-treated group compared with the control. These results suggest the usefulness of G. sylvestre in the treatment of certain classes of non-insulin-dependent diabetes mellitus.

Therapeutic in vivo and in vitro effects of argon dye laser and hematoporphyrin derivative in lung cancer.

In clinical and experimental study the therapeutic efficacy of argon dye laser irradiation with hematoporphyrin derivative (HpD) was evaluated in lung cancer. A total of 14 lung cancer cases including 12 squamous cell, 1 adeno- and 1 small cell carcinomas were irradiated superficially 48 hours or more after i.v. injection of 3 mg/kg of HpD (100-300 mW, 20-30 min.). Human adenocarcinoma cells implanted subcutaneously into nude mice were photoirradiated (200 mW, 20 min.) 48 h after i.p. injection of HpD. The in vitro effect of phototherapy was studied in the same cell line after incubation in medium containing HpD compared to untreated, only irradiated or only in HpD incubated cells. Among 3 early stage squamous cell carcinoma cases 2 complete and 1 partial remissions were obtained. Among 11 cases including 10 with advanced and 1 with recurrent disease 7 demonstrated partial remission. In vivo, two of 9 mice had a complete tumor remission. In the in vitro study, tumor cells incubated in 30 micrograms HpD/ml showed severe cytotoxic effects resulting in cell death 12 hours after photo irradiation, whereas cells incubated in 30 micrograms HpD/ml only regenerated after initial cytotoxic reaction. Laser irradiation only had no effects. HpD phototherapy demonstrated a considerable antitumor efficacy and must be considered as one of the promising endoscopic treatments in cases with early stage primary lung cancer.

[Transfer factor immunochemotherapy for primary lung cancer--evaluation of histologic types].

The clinical effect of leucocyte dialysate, including Transfer Factor (TF), on different histologic types of primary resected lung cancer was studied. This TF immunotherapy protocol included 171 patients. Eligible cases for evaluation were randomly chosen; the TF group and control group consisted of 75 and 74 patients, respectively. The TF group included 40 adenocarcinomas, 29 epidermoid carcinomas and 6 other histologic types of carcinoma. The control group included 42 adenocarcinomas, 25 epidermoid carcinomas and 7 other histologic types of carcinoma. The distribution of clinical features in the TF and control group was very similar, not only in adenocarcinoma but also in epidermoid carcinoma. The postoperative follow-up term was 2 to 55 months in both groups. Survival in the TF group of patients with adenocarcinoma of stages I + II or curative resection was significantly better than in the control group (p less than 0.005, Cox-Mantel test). There was no significant intergroup difference in patients with stages III + IV, relative curative or noncurative resection. Survival in the TF group of patients with epidermoid carcinoma of stages I + II or III + IV was about 20% better than in the control, however, there was no significant difference between the 2 groups. On the other hand, survival in the TF group of patients undergoing relative curative resection was significantly better than in the control (p less than 0.005, Cox-Mantel test). There was no significant difference among patients who underwent curative or noncurative resection. Time-versus-recurrence curves were evaluated by the Kaplan-Meier method; there was a significant difference between patients with stages I + II, but not between patients with stages III + IV. The frequency of recurrence of regional or intrapulmonary distant metastasis was lower in the TF group. It is suggested that TF suppresses postoperative recurrence and that it may be beneficial as postoperative adjuvant immunochemotherapy in primary resected lung cancer patients, especially those with relatively early stage cancer.