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Quercetin, a flavonoid, widely distributed in many fruits and vegetables, is well known to have an antitumor effect despite its mutagenicity. In this study, we examined the effect of dietary quercetin on duodenum-tumorigenicity of mice induced by a chemical carcinogen, N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG). Eight-week-old male C57BL/6 mice were divided into 4 groups; ENNG without quercetin (group A), ENNG with 0.2% quercetin (group B), ENNG with 2% quercetin (group C), and 2% quercetin without ENNG (group D). ENNG was given in drinking water for the first 4 weeks, and thereafter quercetin was given in a mixed diet. At week 20, the average number of duodenal tumors per mouse was significantly higher in group C (mean±SE, 7.26±1.75, p<0.05) than in group A (2.32±0.31). The size of the duodenal tumors increased significantly in group B (1.79±0.09 mm, p<0.001) compared with group A (1.43±0.09 mm). In contrast, no duodenal tumor was induced in group D. The present findings suggest that excessive intake of quercetin occasionally is a risk factor for carcinogenesis of some specific organs such as the upper intestine.

Squalene inhibited the effect of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), such as increased 32Pi incorporation into phospholipids of HeLa cell membrane, induction of Epstein-Barr-virus early antigen in Raji cell and induction of ornithine decarboxylase in mouse skin. Squalene also markedly suppressed the promoting activity of TPA on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice.

Although beta-carotene has been considered to be a key cancer preventive agent in green and yellow vegetables, other types of carotenoids, such as alpha-carotene, may also contribute to anticarcinogenic action, since these carotenoids usually coexist with beta-carotene and are detectable in human blood and tissues. In this study, we compared the inhibitory effect of natural alpha-carotene, obtained from palm oil, with that of beta-carotene on spontaneous liver carcinogenesis in C3H/He male mice. The mean number of hepatomas per mouse was significantly decreased by alpha-carotene supplementation (per os administration in drinking water at a concentration of 0.05%, ad libitum) as compared with that in the control group (P < 0.001, Student's t test). On the other hand, beta-carotene, at the same dose as alpha-carotene, did not show any such significant difference from the control group. Furthermore, we also compared the antitumor-promoting activity of alpha-carotene with that of beta-carotene against two-stage mouse lung carcinogenesis (initiator, 4-nitroquinoline 1-oxide; promoter, glycerol). alpha-Carotene, but not beta-carotene, reduced the number of lung tumors per mouse to about 30% of that in the control group (P < 0.001, Student's t test). The higher potency of the antitumor-promoting action of alpha-carotene compared to beta-carotene was confirmed in other experimental systems; e.g., alpha-carotene was also found to have a stronger effect than beta-carotene in suppressing the promoting activity of 12-O-tetradecanoylphorbol-13-acetate on skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated mice. These results suggest that not only beta-carotene, but also other types of carotenoids, such as alpha-carotene, may play an important role in cancer prevention.

We have reported that fucoxanthin, a natural carotenoid, inhibited the growth of human neuroblastoma GOTO cells. In the present study, we show that a metabolite of fucoxanthin, halocynthiaxanthin, which is isolated from sea squirt Halocynthia roretzi, has a more potent inhibitory effect. Halocynthiaxanthin (5 micrograms/ml) caused complete suppression of GOTO cell proliferation, whereas fucoxanthin reduced the growth rate by only 88.8% compared with the control, at day 2 after the drug treatment. Furthermore, halocynthiaxanthin also inhibited the growth of other human malignant tumor cells. Thus halocynthiaxanthin seems to be a promising anti-neoplastic agent.

We report our study on the correlation between the types of anastomosis and the incidence of anastomotic stricture formation in the upper gastro-intestinal tract. Our experience with balloon dilatation is also reported. We examined the incidence of stricture formation among patients who had an anastomosis between the esophagus and stomach following subtotal esophagectomy for esophageal cancer, and esophagojejunostomy following proximal or total gastrectomy for gastric cancer in the past 17 years. Among 283 patients undergoing esophagojejunostomy, 7 cases of stricture (excluding 3 cases of cancer recurrence) were observed (conventional anastomosis 1.8%; stapling anastomosis 4.6%). There were 17 cases of stricture among 56 patients who had anastomosis between the esophagus and stomach following subtotal esophagectomy (conventional anastomosis 28.6%; stapling anastomosis 50.0%). One month or more after the operation, the diameter of the esophagojejunostomy was estimated using a barium study. The mean diameter of the anastomosis using the stapling method was 11.9 +/- 2.9 mm, whereas the mean diameter of serosubmucosal single layer hand-sewn anastomosis (Jourdan's) was 19.8 +/- 2.2 mm, and that of vertical mattress hand-sewn anastomosis was 19.0 +/- 2.0 mm. Balloon dilatation was used in 29 patients with anastomotic stricture of the upper gastro-intestinal tract (esophageal cancer, 19 patients, gastric cancer, 10 patients). With repeated dilatation, we were able to obtain satisfactory efficacy for benign strictures and there were no severe complications. We believe that balloon dilatation is an easy, safe and effective therapy for anastomotic stricture of the upper gastro-intestinal tract.

Anastomosis of the gastrointestinal tract has been made more secure by the use of the EEA (U. S. Surgical Corp.) stapler. The development of anastomotic strictures after stapling anastomosis is one of the major postoperative complications of this method. This study was done to compare the incidence of anastomotic stricture between stapling anastomosis and layer-to-layer handsewn anastomosis. Twelve dogs were divided into two groups. In each group, two colonic anastomoses were performed. Intestinal contents were not allowed to pass through one of the anastomotic sites created in an isolated segment of the colon, but were allowed to pass through the other site in the remaining colon. By the 28th postoperative day, anastomoses made with the EEA stapler, which had been excluded from contact with feces, had developed significantly more strictures when compared with the other anastomoses (p less than 0.05). The anastomotic strictures were membranous in nature when examined macroscopically and histologically.

The effects of palm carotene on chemical carcinogenesis was studied. Palm carotene suppressed mouse epidermal ornithine decarboxylase activity induced by glycocholic acid. In a two-stage mouse epidermal carcinogenesis experiment using 7,12-dimethylbenz(a)anthracene as the initiator, glycocholic acid as the 1st stage promoter, and mezerein as the 2nd stage promoter, palm carotene inhibited the promoting activity of glycocholic acid. Furthermore, in N-ethyl-N'-nitro-N-nitrosoguanidine-induced mouse duodenal carcinogenesis, 0.05% of palm carotene given in drinking water decreased the percentage of tumor-bearing mice significantly.

The effect of green tea polyphenol fraction (GTP) on azoxymethane(AOM)-induced colon carcinogenesis was investigated in male Fischer rats. The rats were given AOM (7.4 mg/kg body weight) s.c. once a week for 10 weeks. A week after the treatment, they were divided into three groups: AOM-control (26 rats), AOM-GTP1 (26 rats) and AOM-GTP2 (25 rats). AOM-GTP1 and AOM-GTP2 groups respectively received 0.01 and 0.1% GTP in drinking water from week 11 to 26. AOM-control group received tap water throughout this experiment. Autopsy on week 26 showed that tumor incidence and average numbers of tumors per rat in the AOM-GTP1 and AOM-GTP2 groups were significantly lower than those of the AOM-control group: 38.1% and 47.6% versus 77.3%; 0.6 and 0.7 versus 1.5. Thus, it was concluded that GTP inhibited the development of AOM-induced colon carcinogenesis. The inhibition by GTP did not show significant dose dependence.

The pharmacokinetics of a disulfide linked conjugate of a murine monoclonal antibody A7 with neocarzinostatin (A7-NCS) was studied following its intravenous administration to nude mice. Disappearance of the conjugate from the circulation was biphasic: an early rapid phase was followed by a much slower phase. The conjugate was removed from the blood circulation with a half-life of 12 hr, showing nearly the same kinetics as the free antibody. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that the disulfide linkage in A7-NCS was stable at least for 48 hr after administration of the conjugate to nude mice. The conjugate concentration in a human colon cancer SW1116 derived tumor reached maximum at 24 hr after injection and remained high for an additional 24 hr. The passive hemagglutination inhibition assay revealed that NCS in the conjugated form can be efficiently delivered to the target tissue. The present report indicates that A7-NCS was sufficiently stable in circulation to reach the target tumor without releasing NCS.

The induction of ornithine decarboxylase (ODC), a key enzyme of polyamine biosynthesis, is an early and obligatory event in the tumor-promoting step in animal models. The enzyme activity is also elevated in some human premalignant lesions. We determined the ODC activity in human gastric cancer tissue and in the mucosa of cancer-bearing stomach. We concluded that gastric cancer tissue had significantly elevated ODC levels over those of mucosa (157.8 versus 45.7, respectively; P less than 0.05). Among mucosa of the stomach, that of the pyloric gland had higher ODC activity than that of the fundic gland (42.8 versus 21.6, respectively; P less than 0.05). Moreover, mucosa from the cancer-bearing stomach had high ODC activity compared with gastric mucosa without cancer. ODC activity in cancer tissue and mucosa from cancer-bearing stomach was activated by GTP. In rat experiments, the properties of ODC induced by gastric carcinogen were analyzed. Transiently induced ODC by a single gastric intubation of N-methyl-N'-nitro-N-nitrosoguanidine was not activated by GTP whereas constitutively expressed ODC of N-methyl-N'-nitro-N-nitrosoguanidine-induced cancer-bearing stomach was activated by GTP. These results suggest that some tumor-promoting stimuli may be concerned in human gastric carcinogenesis and that mucosal ODC activity may be a useful marker for assessing the risk of gastric malignancy.

A case of five-year survival of jejunal leiomyosarcoma with metastases to the liver and mesentery treated with four times surgery was reported here. Four metastatic lesions were detected in the sigmoid mesocolon once and in the liver three times and resected with hope of cure. The patient, a 37 years old male, tolerated surgical procedures including an extended right hepatic lobectomy and recovered each time. He is leading a satisfactory daily life 5 years and 3 months after the initial operation although multiple liver metastases were detected 10 months after the fourth operation. A positive surgical therapy is advocated in selected patients who have spreading leiomyosarcoma of the bowel.

Surgical specimens from 2 patients with chronic ulcerative colitis accompanied with colon cancer were evaluated by immunoperoxidative staining using monoclonal antibodies A7 (against human colon cancer), S202 (against human gastric cancer), and anti-carcinoembryonic antigen (CEA). The three monoclonal antibodies were reactive with cancerous tissue, anti-CEA antibody and monoclonal antibody S202 reacted with dysplasia tissues, whereas monoclonal antibody A7 did not. Using high-iron diamine technique for mucosubstances (sialomucin and sulfomucin), cancer and dysplasia showed no secretory elements. Surrounding mucosa showed both sialomucin and sulfomucin secretion.

(-)-Epigallocatechin gallate (EGCG) is the main polyphenolic constituent of green tea infusion and inhibits tumor promotion by teleocidin in two-stage carcinogenesis on mouse skin. In this work, EGCG was found to inhibit tumor promotion in the gastrointestinal tract in a model system of mouse duodenal carcinogenesis with N-ethyl-N'-nitro-N-nitrosoguanidine. The duodenal tumors that developed were studied stereomicroscopically and histologically.

alpha-Carotene inhibited the proliferation of the human neuroblastoma cell line GOTO in a dose- and time-dependent manner. In addition, it was about 10 times more inhibitory than beta-carotene. Northern blot analysis indicated that alpha-carotene caused maximum suppression of the level of the N-myc messenger RNA of GOTO cells. This suppression occurred within 18 hours of alpha-carotene treatment, after which the level of the N-myc messenger RNA gradually recovered to the basal level. Analysis by flow cytometry indicated that when GOTO cells were exposed to alpha-carotene, they were arrested in the G0-G1 phase of their cell cycle. However, as the level of the N-myc messenger RNA was recovering, these cells resumed normal cycling. These results indicate that the reduction in the level of the N-myc messenger RNA caused by alpha-carotene is closely linked with G0-G1 arrest.

Staurosporine, an antitumor-promoting agent, suppressed phorbol ester-enhanced phospholipid synthesis. The inhibitory effect of staurosporine was found to be dominant in the synthesis of phosphatidylcholine and phosphatidylethanolamine. The manner of this inhibitory action by staurosporine was similar to that of various kinds of antitumor-promoting agents, which have the ability to interact with Ca2(+)-calmodulin complex, although the effective dose of staurosporine was 1,000 times lower than these calmodulin-interacting agents. Furthermore, staurosporine was proved to interact directly with Ca2(+)-calmodulin complex. Thus, it is possible that staurosporine showed inhibitory effect on phospholipid metabolism via the modulation of Ca2(+)-calmodulin system.