• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5331-5339
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• 2013

Colorectal cancer is one of the leading causes of cancer death, both in men and women. This study investigated the effects of Amorphophallus campanulatus tuber methanolic extract (ACME) on aberrant crypt foci (ACF) formation, colonic cell proliferation, lipid peroxidative damage and the antioxidant status in a long term preclinical model of 1, 2-dimethylhydrazine (DMH) induced colon carcinogenesis in rats. Male Wistar rats were divided into six groups, viz., group I rats served as controls; group II rats treated as drug controls receiving 250 mg/kg body weight of ACME orally; group III rats received DMH (20 mg/kg body weight) subcutaneously once a week for the first 15 weeks; groups IV, V and VI rats received ACME along with DMH during the initiation, post-initiation stages and the entire period of the study, respectively. All the rats were sacrificed at the end of 30 weeks and the intestinal and colonic tissues from different groups were subjected to biochemical and histological studies. Administration of DMH resulted in significant ($p{\leq}0.05$) intestinal and colonic lipid peroxidation (MDA) and reduction of antioxidants such as catalase, glutathione peroxidase, glutathione reductase, glutathione-Stransferase and reduced glutathione. Whereas the supplementation of ACME significantly ($p{\leq}0.05$) improved the intestinal and colonic MDA and reduced glutathione levels and the activities of antioxidant enzymes in DMH intoxicated rats. ACME administration also significantly suppressed the formation and multiplicity of ACF. In addition, the DMH administered rats showed amplified expression of PCNA in the colon and decreased expression of this proliferative marker was clearly noted with initiation, post-initiation and entire period of ACME treatment regimens. These results indicate that ACME could exert a significant chemopreventive effect on colon carcinogenesis induced by DMH.

• Archives of Plastic Surgery
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• 제34권1호
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• pp.8-12
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• 2007

Purpose: Protein tyrosine kinase(PTK), protein kinase C(PKC), oxidase, as a mediator, have been known to take a role in signal transduction pathway of angiogenesis. The authors confirmed that PKC is the most noticeable mediator for abnormal proliferation of vascular endothelial cells through in vitro study model using the inhibitors, targeting the formation of three co-enzymes. In this study, we would investigate which isoform of PKC play an important role in abnormal angiogenesis of vascular endothelial cell. Methods: In 96 well plates, $10^4$ HUVECs(human umbilical vein endothelial cells) were evenly distributed. Two groups were established; the control group without administration of DMH(1,2-dimethylhydrazine) and the DMH group with administration of $7.5{\times}10^{-9}M$ DMH. RNA was extracted from vascular endothelial cell of each group and expression of the PKC isoform was analyzed by RT-PCR(reverse transcriptase-polymerase chain reaction) method. Results: RT-PCR analysis showed that $PKC{\alpha}$, $-{\beta}I$, $-{\beta}II$, $-{\eta}$, $-{\mu}$ and $-{\iota}$ were expressed in vascular endothelial cells of each group. DMH incresed the expression of $PKC{\alpha}$ and $PKC{\mu}$, and decreased $PKC{\beta}I$, $PKC{\beta}II$ expression dominantly. Conclusion: Based on the result of this study, it was suggested that $PKC{\alpha}$ and $PKC{\mu}$ may have significant role in abnormal proliferation of vascular endothelial cell.

• Toxicological Research
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• 제23권4호
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• pp.321-330
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• 2007

Garlic (Allium sativum L.) with the food supplement material and medicine was used traditionally in Asia and Europe. Epidemiological studies revealed that the intake of garlic reduced incidences of various cancer including digestive system. The present study was designed to investigate the effect of garlic ethanol extract on the development of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH) in male F344 rats. Five-week-old rats were given four times for two weeks to subcutaneous injections by DMH (30 mg/kg body weight) to induce ACF. The animals were divided into groups that fed diet containing garlic ethanol extract at five different doses (0.1, 0.2, 0.5, 2, 5%), respectively, animals were evaluated for the total number of ACF and total aberrant crypts (AC) per colon detected from methylene blue-stained rat colon. ACF were formed in animals in DMH-treated group. The feeding suppressed potently the appearance ACF in the colon of rats. Especially, fed diet containing garlic ethanol extract at intermediate dose (0.5%) significantly reduced the number of ACF and AC per colon (p < 0.05). Garlic ethanol extract inhibited DMH-induced overexpression of Activator Protein-1 (AP-1) and ${\beta}-catenin$ genes related to cell proliferation that also upregulated the expression of p21Waf1/Cip1 mRNA, a cell cycle-regulating gene. These results suggested that garlic ethanol extract may inhibit ACF formation, ${\beta}-catenin$ gene as the early preneoplastic marker of malignant potential in the process of colon carcinogenesis.

• 한국양식학회:학술대회논문집
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• 한국양식학회 2004년도 수산관련학회 공동학술대회 발표요지집
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• pp.146-147
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• 2004

• 한국영양학회:학술대회논문집
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• 한국영양학회 2003년도 연합학술대회
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• pp.134-134
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• 2003

• 대한화학회지
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• 제23권5호
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• pp.307-313
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• 1979

N-Aryllsufonylbenzimidoyl chloride를 출발물질로 사용하여 다음과 같은 7가지 새로운 히드라진 유도체들을 합성하였다. ${\beta}-({\alpha}-Benzenesulfonamidobenzal)hydrazine\;(II),\;{\beta}-({\alpha}-Benzenesulfonamidobenzal)dimethylmethylenehydrazine\;(III),\;{\beta}-({\alpha}-Benzenesulfonamidobenzal)phenylhydrazine\;(VII),\;{\beta}-({\alpha}-Benzenesulfonamidobenzal)-4-nitrophenylhydrazine\;(VIII),\;{\beta}-({\alpha}-Benzenesulfonamidobenzal)-2,4-dinitrophenylhydrazine\;(IX),\;{\beta}-({\alpha}-Benzenesulfonamidobenzal)dimethylhydrazine\;(X),\;{\beta}-({\alpha}-Benzenesulfonamidobenzal)-p-methylphenylhydrazine\;(XI)$ 이 유도체들의 구조를 원소분석, ir, nmr, mass 스펙트럼 및 기타 화학적인 방법을 통해서 확인하였다. 일반적으로 이 치환반응은 극성인 용매에서, 그리고 친핵체인 페닐히드라진 유도체에 전자를 끄는기가 있을 때 수득율이 높았다.

• Nutrition Research and Practice
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• 제2권2호
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• pp.55-61
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• 2008

We investigated the combinatorial effects of different doses of dietary soy isoflavones (SI) and fructooligosaccharide (FOS) in a rat model of colon cancer. We hypothesized that increased bioavailability of SI metabolites due to dietary FOS may increase production of bioactive equol and affect colon carcinogenesis in a dose-dependent manner. Sprague-Dawley male rats were injected with 12-dimethylhydrazine (DMH) and were providec experimental diets that contained 0, 10, 50, 150, or 500 mg SI per kg of diet and 6% FOS for 12 weeks. The number of aberrant crypt foci (ACF) and the expression of cyclooxygenase-2 (COX-2) in colonic tissues were significantly decreased in the 6% FOS-fed groups compared to the control group. Gut transit time and fecal pH were significantly lower, and fecal concentrations of bifidobacteria were increased with 6% FOS. However, dietary SI supplementation in combination with 6% dietary FOS did not affect ACF formation or COX-2 expression. Plasma equol concentrations were dose-dependently increased by supplementation of SI up to 500 mg/kg of diet. In conclusion, SI supplementation up to 500 mg/kg of diet appeared to have no additive beneficial effects in rats with chemically-induced colon cancer that were fed 6% FOS, although plasma equol was dose-dependently increased.

• Archives of Pharmacal Research
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• 제24권6호
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• pp.564-567
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• 2001

The fecal ${\beta}-glucuronidase$ activity of patients with colon cancer and healthy controls were measured to determine the relationship between the fluctuation of intestinal bacterial ${\beta}-glucuronidase$ and colon cancer. The fecal ${\beta}-glucuronidase$ activity of patients with colon cancer was 1.7 times higher than that of the healthy controls. However, when these fecal specimens were sonicated, the enzyme activity of patients with colon cancer was 12.1 times higher than that of the healthy controls. The fecal ${\beta}-glucuronidase$ activity of human Intestinal bacteria was drastically induced by its substrate or the bile secreted after a subcutaneous injection of 1,2-dimethylhydrazine (DMH) and benzo[a]pyrene into rats. DMH-and benzo[a]pyrene-treated biles induced ${\beta}-glucuronidase$ activity in the human intestinal microflora by approximately 1.5- and 2.3-fold, respectively. They also induced ${\beta}-glucuronidase$ in E. coli HGU-3, which is a ${\beta}-glucuronidase$-producing bacterium from the human intestine. D-saccharic acid 1,4-lactone similarly inhibited fecal ${\beta}-glucuronidase$ in several patients with colon cancer in addition to the healthy controls. This suggests that potent ${\beta}-glucuronidase$ activity is a prime factor in the etiology of colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4393-4402
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• 2012

Colon cancer is the third most common malignant neoplasm in the world and it remains an important cause of death, especially in western countries. The toxic environmental pollutant, 1, 2-dimethylhydrazine (DMH), is also a colon-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemically induced toxicity and also carcinogenesis. In the present study, we evaluated the chemopreventive efficacy of TA against DMH induced colon toxicity in a rat model. Efficacy of TA against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, histopathological changes and expression of early molecular markers of inflammation and tumor promotion. DMH treatment induced oxidative stress enzymes (p<0.001) and an early inflammatory and tumor promotion response in the colons of Wistar rats. TA treatment prevented deteriorative effects induced by DMH through a protective mechanism that involved reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression levels and TNF-${\alpha}$ (p<0.001) release. It could be concluded from our results that TA markedly protects against chemically induced colon toxicity and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.

• Food Science and Biotechnology
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• 제15권6호
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• pp.942-947
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• 2006

The effect of oat bran extracts on the formation of aberrant crypt foci (ACF) in the colon induced by 1,2-dimethylhydrazine (DMH) was studied in F344 male rats. Extracts were prepared using various combinations of temperature (40, 45, 50, 55, or 60$^{\circ}C:\;X_1$), ethanol concentration (0,5, 10, 15, or 20%: $X_2$), and pH (5, 6, 7, 8, or 9: $X_3$). Among the various extracts tested, one ethanol extract (EE; $45^{\circ}C$, 15% ethanol at pH 6) and one water extract (WE; $50^{\circ}C$ at pH 5) were selected based on their in vitro antitumor activity. The animals were fed with basal diet alone or basal diet supplemented with 0.25 or 0.5% of EE or WE for 6 weeks. During the initial 2 weeks of the 6-week test period, the rats were subcutaneously injected with DMH (30 mg/kg) 4 times for the induction of ACF. DMH induced an average of 322.7 and 142.9 aberrant crypts (AC) and ACF, respectively. A low dose (0.25%) of EE (containing 38.3% ${\beta}$-glucan) and WE (containing 22.8% ${\beta}$-glucan) greatly reduced the numbers of DMH-induced AC and ACF. Significantly, ACF consisting of more than 3 AC were reduced by half in which the effect of EE, containing a higher concentration of ${\beta}$-glucan, was superior to that of WE. These results demonstrate that oat bran extracts may confer protection against colon carcinogenesis.