[A case of probable autoimmune hepatitis from which the persistence of hepatitis A IgM antibody, and the improvement was pathologically obtained by ursodeoxycholic acid medication].

We present a 68 years old woman who was referred to our department due to impaired liver function. Hepatitis A IgM antibody and anti-nuclear antibody were positive, IgG, and gamma-globulin were elevated. Percutaneous liver biopsy was performed and autoimmune hepatitis was suspected pathologically. Oral administration of ursodeoxycholic acid was started and liver function was normalized three months later. The improvement of a hepatitis image was examined by percutaneous liver biopsy one year later. Although hepatitis A IgM antibody was positive throughout the course, hepatitis A virusemia was not considered the cause of persistent positive hepatitis A. IgM antibody could not be clarified. There was a possibility of a non-specific reaction and abnormalities in antibody production control were considered possible. We present this case and discuss the previous literature.

[Case of primary malignant fibrous histiocytoma of the diaphragm discovered by liver function disorder].

We present the case of a 67-year-old man with primary malignant fibrous histiocytoma (MFH) of the diaphragm. He was admitted to our hospital with anorexia and loss of body weight. High serum levels of AST, ALT, ALP and gamma-GTP were observed. Several imaging studies disclosed a large tumor on the right side of the diaphragm to the right lobe of the liver. The entire tumor was resected, and histopathological examination of the specimen revealed the characteristics of MFH. MFH originating from the diaphragm is very rare, and we present the case of this patient in addition to a discussion of previous literature.

Role of oxygen-derived free radicals in Helicobacter pylori water extract-induced mouse skin carcinogenesis.

Helicobacter pylori (H. pylori) infection, the main cause of chronic gastritis, increases gastric cancer risk. The infection causes inflammatory cells to produce reactive oxygen metabolites that may damage DNA and promote carcinogenesis. However, its precise role in gastric carcinogenesis is as yet unknown. Recently we reported that H. pylori water extract (HPE) has an initiating activity on two-stage mouse skin carcinogenesis. In this study, we investigated the effects of anti-oxidants, ascorbic acid and a combination of superoxide dismutase (CuZnSOD)and catalase, on two-stage mouse skin carcinogenesis. Ascorbic acid and CuZnSOD/catalase were given to mice during the period of HPE-initiation. Both the ascorbic acid and CuZnSOD/catalase treatment attenuated the incidence of tumor formation. The present results suggest that HPE induces tumor formation via reactive oxygen species (ROS) production.

Astaxanthin limits exercise-induced skeletal and cardiac muscle damage in mice.

Dietary antioxidants may attenuate oxidative damage from strenuous exercise in various tissues. Beneficial effects of the antioxidant astaxanthin have been demonstrated in vitro, but not yet in vivo. We investigated the effect of dietary supplementation with astaxanthin on oxidative damage induced by strenuous exercise in mouse gastrocnemius and heart. C57BL/6 mice (7 weeks old) were divided into groups: rested control, intense exercise, and exercise with astaxanthin supplementation. After 3 weeks of exercise acclimation, both exercise groups ran on a treadmill at 28 m/min until exhaustion. Exercise-increased 4-hydroxy-2-nonenal-modified protein and 8-hydroxy-2'-deoxyguanosine in gastrocnemius and heart were blunted in the astaxanthin group. Increases in plasma creatine kinase activity, and in myeloperoxidase activity in gastrocnemius and heart, also were lessened by astaxanthin. Astaxanthin showed accumulation in gastrocnemius and heart from the 3 week supplementation. Astaxanthin can attenuate exercise-induced damage in mouse skeletal muscle and heart, including an associated neutrophil infiltration that induces further damage.

Chemopreventive effects of emodin and cassiamin B in mouse skin carcinogenesis.

In continuation of our works of natural and synthetic products as cancer chemopreventive agents, we have examined emodin and cassiamin B, which were isolated from Cassia siamea. These compounds exhibited the remarkable anti-tumor promoting effect on two-stage carcinogenesis test of mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter by both topical application. Furthermore, emodin exhibited potent inhibitory activity on two-stage carcinogenesis test of mouse skin tumors induced by nitric oxide donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamide as an initiator and TPA as a promoter.

Cancer chemopreventive activity of Achyranthes aspera leaves on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.

Achyranthes aspera leaves have been assessed for chemopreventive activity. The MeOH extract, alkaloid, non-alkaloid and saponin fractions exhibited significant inhibitory effects (concentration 100 microg) on the Epstein-Barr virus early antigen activation induced by the tumor promotor 12-O-tetradecanoylphorbol-13-acetate in Raji cells. In this in vitro assay the non-alkaloid fraction containing mainly non-polar compounds showed the most significant inhibitory activity (96.9%; 60% viability). In the in vivo two-stage mouse skin carcinogenesis test the total methanolic extract possessed a pronounced anticarcinogenic effect (76%). The present study suggests that A. aspera leaf extract and the non-alkaloid fraction are valuable antitumor promotors in carcinogenesis.

Tumor initiating activity of Helicobacter pylori water extract on mouse skin carcinogenesis.

Helicobacter pylori (H. pylori) infection has been associated with gastric carcinogenesis, but responsible and detail mechanisms are insufficient by the absence of adequate data. To obtain direct evidence regarding the carcinogenicity of H. pylori, we investigated the initiating and promoting activity of H. pylori water extract (HPE) in two-stage mouse skin carcinogenesis model. HPE treatment, as an initiation, significantly enhanced tumor formation compared with control group. Moreover, HPE treatment increased production of 8-hydroxydeoxyguanosine in epidermal cells and HPE-initiated/TPA-promoted papillomas demonstrated a point mutation of the Ha-ras gene. These results suggest an initiating activity of HPE on two-stage mouse skin carcinogenesis.

Anoxia/reoxygenation down-regulates the expression of E-cadherin in human colon cancer cell lines.

The E-cadherin-mediated cell-cell adhesiveness is a critical factor for carcinoma cell invasion and metastasis. Anoxia/reoxygenation is known to occur in cancer tissues. In this study, we investigated whether anoxia/reoxygenation induces the down-regulation of E-cadherin expression in the human colon cancer cell lines HT-29, and SW1116. Colon cancer cells were exposed to anoxia (2 h) followed by reoxygenation (4-46 h). The subsequent expression of E-cadherin on the cell surface was examined by immunocytochemistry and enzyme-linked immunosorbent assays, the total amount of E-cadherin protein was examined by Western blotting, and the E-cadherin mRNA level was examined by a real-time polymerase chain reaction assay. The expression of E-cadherin on the cell surface and the total amount of E-cadherin protein were transiently reduced after anoxia/reoxygenation. On the other hand, the E-cadherin mRNA level was not decreased during reoxygenation. Pretreatment with actinomycin D or reagents that interfere with the activation of NF-kappaB significantly attenuated the down-regulation of E-cadherin, which implicated a role for the de novo protein synthesis. These results indicate that anoxia/reoxygenation induces a transient reduction of E-cadherin expression in human colon cancer cells through NF-kappaB dependent transcriptional pathway.

Cancer chemopreventive effects of oral feeding alpha-tocopherol on ultraviolet light B induced photocarcinogenesis of hairless mouse.

Ultraviolet light is the most common cause of skin cancers in humans and several effects of ultraviolet light B (UVB: 290-320 nm) are thought to contribute to skin photocarcinogenesis. The generation of free radicals and related oxidants produced by UVB exposure, result in photocarcinogenesis by directly damaging DNA. On the other side, activating of transcription factor, activator protein 1 (AP-1) induced by UVB exposure causes tumor promotion. alpha-tocopherol has two principal physiological activities and one is an antioxidant activity through which alpha-tocopherol protects unsaturated fatty acids, protein and DNA from oxidation. The other activity is to stabilize the structure of the biomembrane. In addition to these two activities, it has been recently established that alpha-tocopherol plays important roles in cell signal transduction. In course of these studies, we examined such effects of alpha-tocopherol on UVB induced skin photocarcinogenesis in hairless mice. These results indicate that oral feeding of alpha-tocopherol including diet exhibited a marked inhibitory effects on both tumor incidence and multiplicity in UVB induced mouse skin photocarcinogenesis.

Inhibitory effect of stabilized analogues of glycoglycerolipids on Epstein-Barr virus activation and mouse skin tumor promotion.

Nine new synthetic compounds, structurally related to the most active glycoglycerolipid analogues carrying a hexanoyl chain, were tested for their anti-tumor-promoting activity using a short-term in vitro assay for Epstein-Barr virus (EBV) activation. All these compounds, in which the ester function is replaced by different metabolically more stable groups, were almost as active as their ester reference compounds in inhibiting the EBV activation promoted by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Two of these, devoid of any functionality on the lipophilic chain, when tested in an in vivo two-stage carcinogenesis test, exhibited marked inhibitory effects on mouse skin tumor promotion.

Three new quassinoids, ailantinol E, F, and G, from Ailanthus altissima.

Three new quassinoids, ailantinol E (1), ailantinol F (2), and ailantinol G (3), and related compounds were isolated from Ailanthus altissima grown in Taiwan. Their structures were elucidated from spectral evidence. Each new quassinoid was evaluated for its antitumor promoting effects against Epstein-Barr virus early antigen activation introduced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. The new quassinoids were found to show potent activity without showing any cytotoxicity. The screening for inhibitors against nitric oxide donor action was also conducted using the new quassinoids and some standard samples.

Carotenoids in cancer chemoprevention.

Various natural carotenoids, besides beta-carotene, were proven to have anticarcinogenic activity, and some of them showed more potent activity than beta-carotene. Thus, these carotenoids (alpha-carotene, lutein, zeaxanthin, lycopene, beta-cryptoxanthin, fucoxanthin, astaxanthin, capsanthin, crocetin and phytoene), as well as beta-carotene, may be useful for cancer prevention. In the case of phytoene, the concept of 'bio-chemoprevention', which means biotechnology-assisted method for cancerchemoprevention, may be applicable. In fact, establishment of mammalian cells producing phytoene was succeeded by the introduction of crtB gene, which encodes phytoene synthase, and these cells were proven to acquire the resistance against carcinogenesis. Antioxidative phytoene-containing animal foods may be classified as a novel type of functional food, which has the preventive activity against carcinogenesis, as well as the ability to reduce the accumulation of oxidative damages, which are hazardous for human health.