• BMB Reports
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• v.35 no.6
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• pp.615-622
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• 2002

The purpose of this study was to determine the effects of dietary garlic powder on diethylnitrosamine (DEN)-induced hepatocarcinogenesis and cytochrome P450 (CYP) enzymes in weaning male Sprague-Dawley rats by using the medium-term bioassay system of Ito et al. The rats were fed diets that contained 0, 0.5, 2.0 or 5.0% garlic powder for 8 weeks, beginning the diets with the intraperitoneal (i.p.) injection of DEN. The areas of placental glutathione S-transferase (GST-P) positive foci, an effective marker for DEN-initiated lesions, were significantly decreased in the rats that were fed garlic-powder diets; the numbers were significantly decreased only in the 2.0 and 5.0% garlic-powder diets. The p-nitrophenol hydroxylase (PNPH) activities and protein levels of CYP 2E1 in the hepatic microsomes of the rats that were fed the 2.0 and 5.0% garlic powder diet were much lower than those of the basal-diet groups. Pentoxyresorufin O-dealkylase (PROD) activity and CYP 2B1 protein level were not influenced by the garlic-powder diets and carcinogen treatment. Therefore, the suppression of CYP 2E1 by garlic in the diet might influence the formation of preneoplastic foci during hepatocarcinogenesis in rats that are initiated with DEN.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3931-3936
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• 2013

Background: Iran is a country with very high incidences of stomach cancer, especially in Northern parts. Here we assessed prognostic value of serum screening biomarkers among people >50 years old for early detection of precancerous lesions in a hot spot for gastric carcinoma in Guilan Province, North Iran. Methods: A cross-sectional population-based survey was conducted on 1,390 residents of Lashtenasha city with the mean age (SD) of 61.8 (9.02) years old (50.8% females) to assess the association of gastrin and the pepsinogen (PG) I/II ratio with premalignant gastric lesions. Blood samples were taken for CBC, blood group, and serologic exams (PGI, PGII, and gastrin 17) from each subject. Expert gastroenterologists performed upper GI endoscopy and ROC curves were generated to determine appropriate cutoff points. Results: Mean values of PGI, PGII, PGI/PGII and gastrin were significantly different between patients with and without atrophy or metaplasia (P<0.05). To diagnose atrophy and intestinal metaplasia, a significantly higher AUC was observed for the PGI/PGII ratio (70 and 72%, respectively) compared to the PGI (56, 55%), PGII (63, 64%) and gastrin (59, 61%) (all p<0.001). Conclusions: Biomarker tests such as the PGI/II ratio can be used in the screening and diagnosis of subjects at high gastric cancer risk in our region.

• Food Science and Biotechnology
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• v.15 no.6
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• pp.980-985
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• 2006

The goal of this study was to investigate the effects of a newly developed functional food containing Bacillus polyfermenticus (BP) and other physiologically active materials on the antioxidant system and the process of colon carcinogenesis in male F344 rats. Following a one-week adaptation period, the rats were divided into 3 groups and fed either a high-fat, low-fiber diet (control and DMH groups), or a high-fat, low-fiber diet supplemented with B. polyfermenticus ($3.1{\times}10^8\;CFU/day$) and other physiologically active materials (chitosan, chicory, ${\alpha}$-tocopherol, and flavonoids) (DMH+BP group). One week after the initiation of the diets, 2 groups of rats were subjected to six weeks of treatment with 1,2-dimethylhydrazine (DMH, 180 mg/kg BW, s.c.). The dietary treatments remained consistent throughout the entire experimental period. Nine weeks after the initial DMH injection, the rats supplemented with B. polyfermenticus had significantly lower numbers of aberrant crypt foci than those in the DMH group. Injections with DMH resulted in significantly higher leukocytic DNA damage and plasma lipid peroxidation levels, as well as in a lower plasma total antioxidant potential. These effects were reversed following supplementation with B. polyfermenticus and other physiological materials. Our results indicate that a functional food containing B. polyfermenticus exerts a protective effect on the antioxidant system and on the process of colon carcinogenesis, thereby suppressing the development of preneoplastic lesions.

• Journal of Food Hygiene and Safety
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• v.13 no.1
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• pp.29-33
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• 1998

The effect of ellagic acid (EA) on hepatocarcinogenesis induced by diethylnitrosamine (DEN), and promoted by phenobarbital (PB), and hepatectomized partially was investigated in male Wi star rats. All rats were injected 200 mg of DEN intraperitoneally, received 0.05 % of PB in drinking water at week 2, and hepatectomized 2/3 of liver at week 3. Rats of group 2, 3 and 4 were fed diet containing 400ppm EA for 1 week before DEN administration, for 9 weeks from beginning of experiment to sacrifice and for 6 weeks from PB treatment to sacrifice respectively. Rats of group 5, 6 and 7 were fed 800 ppm EA in the same manner as group 2, 3 and 4. Animals were killed at 8 weeks after DEN administration. The number and area of preneoplastic lesions were quantified the glutathione-S-transferase placental-form (GST-P) positive foci using immunohistochemical method. Decrease of number and area of the positive foci was observed in the rats fed 400 ppm EA for 9 weeks. In addition, the reduction of the foci can examine in all group fed 800 ppm EA. In conclusion, EA inhibited the hepatocarcinogenesis induced by DEN when it was administrated 800 ppm.

• Preventive Nutrition and Food Science
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• v.2 no.1
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• pp.49-54
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• 1997

The modifying effects of Chelidonium majus L/(Papaeracea)herb extract(CH) ,and analgesic traditionally prescribed for gastric and duodenal ulcer patients, on gastric tumor development given Ν-methyl-Ν'-nitro-Ν-nitrosogyanidine(MNNG) were studied in sixty-four 6 week-old male Wistar rats. Group 1 rats were ini-tially given MNNG(200mg/kg b/w.) by gavage ar days 0 and 14 as well as saturated sodium chloride solution(S-NaCI, 1ml per rat) every 3 days during weeks 0 to 3(6 times) and then placed on basal diet containing 0.1 or 0.2% CH ofr 16 weeks from week 4. Rats of Groups 2 and 3 were treated with MNNG together with S-NaCI or saline(0.9% NaCI, 21ml per rat) respectively, timed as in Group 1 but without further treatment. All survival animals were killed at week 20 and histopathologically investigate. in the glandular stomach, the number of preneoplastic pepsinogen 1 altered pyloric glands(PAPGs) in the MNNG+S-NaCI→CH(0.1%) group(Group 1) was significantly smaller than in the MNNG+S-NaCI group(Group 2)(p<0.02). The inci-dences of forestomach neoplastic lesions (Papillomas and squamous cell carcinomas)also showed a tendency for decrease with the CH treatment. The results thus indicate that C"H exerts inhibitory effects on glandular for decrease with the CH treatment. The results thus indicate that CH exerts inhibitory effects on glandular stomach carcinogenesis in the rat, so that it may have potential as a chemopreventive agent for stomach cancer in man.

• Korean Journal of Bronchoesophagology
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• v.3 no.1
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• pp.70-78
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• 1997

The development of preneoplastic and neoplastic squamous cell proliferations of body sites such as the skin, female lower genital tract, and larynx is strongly associated with specific types of human papillomaviruses (HPV). Antitumor $CD^{8+}$ cells recognize peptide antigens presented on the surface of tumor cells by major histocompatibility complex (MHC) class I molecules. The MHC class I molecule is a heterodimer composed of an integral membrane glycoprotein designated the alpha chain and a noncovalently associated, soluble protein called beta-2-microglobulin( $\beta$ -2-m). Loss of $\beta$-2-m generally eliminates antigen recognition by antitumor $CD^{8+}$ T cells. We evaluated the expression of $\beta$-2-m as a potential means of tumor escape from immune recognition and the presence of HPV DNA as a cause of laryngeal squamous cell carcinomas (SCCs). Laryngeal SCCs (n=39) were analyzed for MHC class I expression by immunohistochemistry and for presence of HPV by in situ hybridization technique. The results were as follows : 1) HPV DNA was detected in 10 (25.64%) out of 39 cases in laryngeal squamous cell carcinomas. 2) MHC class I down-regulation (heterogenous and negative expression) in HPV positive lesions was higher than HPV negative lesions. 3) The expression of MHC class I was related to cellular differentiation regardless of T-stage and nodal involvement. In conclusion, HPV was thought to be the etiological factor of SCC of larynx, and we found that the down-regulation of MHC class I was a common phenomenon In laryngeal SCC and may provide a way for tumor cells to escape from immune surveillance.

• Korean Journal of Veterinary Research
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• v.35 no.4
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• pp.793-807
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• 1995

This study was carried out to investigate the effects of diethyl maleate(DEM) on the carcinogenesis of forestomach and pyloric glandular stomach in rats caused by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG). A total of 60 male 6-week-old Wistar rats were given twice intragastric injection of MMNG(200mg/kg BW), then were given diets containing 5% NaCl for 3 weeks until 4th week of the experiment. And then the animals of groups of 1 and 2 were placed on diets containing 0.2% DEM for 16 weeks until the end of 20 weeks of the experiment. On the other hand, the animals of groups of 3 and 4 were placed on basal diets for the same periods. The tissues of forestomach and liver of each group were frozen in liquid nitrogen and the activities of quinone reductase(QR) were determined by measurement of the dicoumarol-sensitive reduction of dichloro-indophenol by NADPH at 600nm. All rats were sacrificed at the end of 20 weeks of the experiment. Every animal was fasted for 24 hrs prior to sacrifice. The forestomach was fixed in 10% neutral phosphate buffered formalin for histology and the pyloric gland was fixed in sublimated formalin for immunohistochemistry of pepsinogen 1 altered pyloric gland(PAPG). The final body weight of the group given MNNG and treated with 5% NaCI and DEM was significantly decreased compared with that of the group 4(p<0.05). Food and water consumption rates were not significantly changed. The preneoplastic and neoplastic lesions of the forestomach given MNNG and treated with 5% NaCI and DEM were significantly increased compared to those of the group 4(p<0.0l). The incidence of PAPG in the groups treated with 0.2% DEM was significantly increased compared with that of the group 4(group 1:p<0.01, group 2:p<0.05). The activities of QR of forestomach in the groups treated with 0.2% DEM were significanitly increased compared with those of the group 4(p<0.001), but those of liver were not significant. These results indicate that DEM exert the enhancing effect of forestomach and glandular stomach carcinogenesis in rats pretreated with MNNG and NaCl.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6447-6453
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• 2012

Background: The mucin components of the gastric gel layer function as a protective and lubricating factor against luminal acid and proteolytic enzymes. Alteration of mucin expression in gastric preneoplastic and neoplastic lesions has suggested potential roles in neoplastic processes. This study aimed to assess the clinicopathological and prognostic significance of MUC-2, MUC-4 and MUC-5AC in Japanese gastric cancer. Methods: Expression of MUC-2, -4 and -5AC was evaluated on tissue microarrays of gastric carcinomas and adjacent non-cancerous mucosa specimens by immunohistochemistry and compared with clinicopathological parameters and survival time of the patients. Results: The three mucins were found to be expressed to a lesser extent in gastric carcinomas in comparison with non-cancerous mucosa (p<0.05). MUC-2 expression was negatively correlated with tumor size, depth of invasion, and TNM staging of gastric cancer (p<0.05), while that of MUC-5AC was negatively associated with the depth of invasion, venous invasion, lymph node metastasis and TNM staging (p<0.05), but positively with MUC-4 and MUC-2 expression (p<0.05). There was higher MUC-2 expression in intestinal- than diffuse-type carcinomas (p<0.05). Kaplan-Meier analysis indicated no relationship between expression of the three mucins and the cumulative survival rate of patients, even stratified according to the depth of invasion (p>0.05). Conclusion: Down-regulated expression of MUC-2, -4 and -5AC may be involved in pathogenesis, invasion, metastasis or differentiation of gastric carcinoma. Their altered expression might therefore be employed as an indicator of pathobiological behavior.

• Journal of Food Hygiene and Safety
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• v.6 no.1
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• pp.13-26
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• 1991

This study was performed for searching for non-hepatectomy medium-term bioassay model by using newborn female rats. Newborn female Sprague-Dawley rats (1 day old) were given an intraperitoneal injection of 150 mg/kg of diethylnitrosamine (DENA). After three weeks, all rats were weaned and divided into three groups. Group 1 were fed on diets containing 0.01% 2-acetylaminofluorene (2-AAF) as a promoter for three weeks. Group 2 were given 0.05% phenobarbital (PB) in drinking water as a promoter for 8 weeks. Group 3 was control group. The autopsy was carried out at 4 weeks and 8 weeks after weaning. Preneoplastic lesions were indentified with immunohistochemical staining for glutathione S-transferase placental form (GST-P). In liver weight to body weight ratios, group 2 showed significant difference from group 1 (p<0.001) at 4 weeks after weaning. Group 1 and group 2 showed significant difference from group 3 at 8 weeks after weaning (p<0.0I, p<0.001), respectively. In quantitative analysis for GST-P positive lesion area by using Image Analyzer, group 1 and group 2 represented significant difference in comparison with group 3 at early 4 weeks after weaning (p

• Korean Journal of Community Nutrition
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• v.2 no.5
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• pp.735-744
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• 1997

The effect of green tea drinking on the hepatocellular chemical cacinogenesis have been studied. Placental glutathione S-transferase(GST-P) positive foci area in a liver tissue, contents of thiobarbituric acid reactive substances(TBARS), total cytochrome P450 and glucose 6-phospphatase(G6P) activity in hepatic microsomes were investigated. Weaning Sprague-Dawley male rats were fed AIN-76A diet with deionized water or green tea infusion, Rats of CTR and CTR+ groups were provided deionized water while GTI and GTI+ groups were provided green tea instead of deionized water for the entire experimental period of 13weeks. Rats of GTP and GTP + groups had deionized water for the first 6 weeks and switched to green tea for the last 7weeks of the experimental period. CTR+, GTI +, and GTP + groups were carcinogen treated groups, Diethylnitrosamine(DEN) was injected as a single dose of 200mg/kg body weight intraperitoneally after 4 weeks of feeding. 2-Acetyla-minofluorene(AAF) was used as a carcinogen proliferater and suppled in the diets of carcinogen treated rats as 0.02% content for the last 6weeks starting from 2weeks after DEN injection. Rats were sacrificed after 13week weeks of feeding. The area and number of GST-P positive foci detected in carcinogen treated rats were decreased by green tea ingestion but when timing and duration of green tea ingestion was delayed after promotion period as in GTP + group, GST-P positive foci were not decreased as much as in GTI+ group. TBARS contents of carcinogen treated rats decreased by 13weeks of green tea ingestion but GTP groups did not show statiscally significant differences. G6P activities tended to decrease by carcinogen treatment but changes were not statiscally significant by green tea ingestion. Total cytochrome P450 contents were increased by carcinogen treatment. Thirteen weeks of green tea ingestion (GTI) also increased to total cytochrome P450 contents while 7weeks of green tea ingestion(GTP) did show any effects. These results suggest that green tea has suppressive effects on hepatocellular chemical carcinogenesis probably through the activities of antioxidant compounds. (Korean J Community utrition 2(5) : 735∼744, 1997)