• Journal of Nutrition and Health
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• v.27 no.4
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• pp.347-355
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• 1994

Indolo[3,2-b]carbazole(ICZ) is a potent Ah receptor agonist with biological activities similar in several respects to those of the potent environmental toxin, TCDD. ICZ is produced during the oilgomerization of indole-3-carbinol(I3C), a breakdown product of the glucobrassicin present in food plants of the Brassica genus. In the present study we examined ICZ levels in tissues and excreta of rats treated with I3C or dietary cabbage of established glucobrasicin content, and in feces of conventional and germfree rats fed on a basal diet, and of humans. We also examined the levels of cytochrome P4501A1 induction, as determined by the ethoxyresorufin ο-deethylase assay, in tissues of animals that received cabbage-supplemented diets, or which were treated with purified I3C or ICZ. Our findings indicated that incorporation of either homogenized or whole freeze-dried cabbage in the feed led to large increases(16-60 fold) in the levels of ICZ in the feces and lower gastrointestinal tract of rats. We observed that whereas ICZ is readily detectable at about the same levels(2.00$\pm$0.50 ppb) in the feces of conventional rats fed on a purified diet and in human feces, levels of ICZ in the feces of germfree animals fed on the basal diet were at the limits of detection(0.40$\pm$0.20 ppb), indication that gut bacteria are important for the production of ICZ from essential dietary constituents in the basal diet. We showed that in contrast to the near 7000-fold difference in CYP1A1 inducing potencies of ICZ and TCDD in cells in culture, their inducing potencies differ by only about an order of magnitude in rats. Nonetheless, the levels of ICZ remaining in livers twenty hours after I3C treatment appear too low to account for the induced activity. This result indicates that ICZ may be rapidly cleared from the liver or that substances other than, or in addition to, ICZ be responsible for the enzyme-inducing activity of orally administered I3C or its precursors.

• Natural Product Sciences
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• v.3 no.2
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• pp.81-88
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• 1997

NAD(P)H:quinone reductase (QR) is one of the protective phase II enzymes against toxicity that accomplishes the capacity of detoxification by modulating the effects of mutagens and carcinogens. The detoxification mechanism is that quinone reductase promotes the 2-electron reduction of quinones to hydroquinones which are less reactive. This study is to search new inducers of quinone reductase from natural products, which can be used as cancer chemopreventive agents. Plant extracts were evaluated by using quinone reductase generating system With Hepa 1c1c7 murine hepatoma cell lines for enzyme inducing properties and crystal violet staining method for the measurement of cytotoxicity provoked. We have tested approximately 106 kinds of natural products after partition into n-hexane, ethyl acetate and aqueous layers from 100% methanol extracts of natural products. The ethyl acetate fractions of Vitex rotundifolia $(fruits,\;2FC:\;12.7\;{\mu}g/ml)$, Cnidium officinale $(aerial\;parts,\;2FC:\;10.5\;{\mu}g/ml)$, Chrysanthemum sinese $(flowers,\;2FC:\;17.4{\mu}g/ml)$ and the hexane fractions of Angelica gigas $(roots,\;2FC:\;13.2\;{\mu}g/ml)$, Smilax china $(roots,\;2FC:\;l1.9\;{\mu}g/ml)$, Sophora flavescens $(roots,\;2FC:\;16.3\;{\mu}g/ml)$ revealed the significant induction of quinone reductase in a murine hepatic Hepa 1c1c7 cell culture system.

• Toxicological Research
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• v.17
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• pp.139-144
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• 2001

Chewing betel quid is associated with an increased risk of oral cancer. The betel quid chewed in Taiwan includes the inflorescence of Piper betle, which contains high concentrations of safrole (15 mg/fresh weight). Piper betle leaf is also used in betel quid; however, the concentration of safrole in betel leaf has not been documented. Chewing betel quid may contribute to safrole exposure in man (420 mm in saliva). Using $a^{32}$P-postlabeling method, we have recently demonstrated the presence of stable safrole-like DNA adducts in human oral tissues following betel quid chewing. Safrole is a rodent hepatocar-cinogen, and the real nature of safrole-DNA adducts in human tissues beside oral has not been elucidated. In this paper, we tested the safrole DNA adducts forming potential in human hepatic and oral derived cells by the ${32}^P$-postlabeling technique. The results suggest that oral cancer derived cell OC-2 alone is not able to form safrole-DNA adduct. However, safrole DNA adducts can be detected following I'-hydroxysafrole, a proximate safrole metabolite, treatment. In addition, pretreament of cytochrome P450 inducers also enhanced the formation of previously undetectable safrole DNA adducts. This finding couples with our previous results suggest that oral may serve as a target tissue for safrole, and safrole may be involved in oral carcinogenesis.

• Journal of Applied Biological Chemistry
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• v.50 no.2
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• pp.78-84
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• 2007

The anti-fibrotic effects of hot water extract of adventitious root culture of Panax ginseng (ARCP) and the possible mechanisms were investigated on $CCl_4-induced$ hepatotoxicity model mice. Fibrosis was induced by a mild treatment of $CCl_4$. Then silymarin as a positive control drug and ARCP or carrier alone as a negative control were treated. Serum GPT, GOT and ALP activity levels were lowered by 25, 21 and 11% for silymarin treated group and by 48, 39 and 14% for ARCP treated group compared to carrier treated alone. Hepatic collagen for ARCP treatment group was reduced by 18% and MDA contents decreased a little more. Pro-fibrotic gene ($TGF-{\beta}1$, TIMP-1 and ${\alpha}-SMA$) expression increased following the $CCl_4$ treatment, but both the silymarin and the ARCP treatments decreased the expressions of these genes by 20% to 50%. The antioxidant effect of ARCP was studied by DPPH free radical scavenging activity. In addition, a generation of reactive oxygen species (ROS) was also reduced in $H_2O_2-treated$ HepG2 cells upon the ARCP treatment. In summary, ARCP has antioxidant property, and can have some protection against oxidative stress; more importantly, ARCP can efficiently protect mice against $CCl_4-induced$ fibrosis.

• Korean Journal of Veterinary Research
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• v.51 no.1
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• pp.63-67
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• 2011

Supernumerary ectopic limb(s) (SEL) is a congenital anomaly defined as the presence of accessory limb(s) attached to various body regions. This paper describes a case of SEL with ectopic lung and ectopia cordis in a newborn calf, based on macroscopic, microscopic and radiographic findings. External features of multiple congenital anomalies included an ectopic lung growing over the middle of the backbone and covered with normal haired skin. Ectopia cordis was found in the abdominal cavity and attached to the liver. Two extra abnormal limbs originated separately from within the ectopic lung. Most of the abdominal organs were exposed to the outside through the opened abdominal cavity. Microscopically the ectopic lung tissue had edema in the connective tissue around the bronchus and artery. Changes in other organs included congestion of the renal medulla, infiltration of inflammatory cells (lymphocytes and eosinophils) around the hepatic portal tract, and edema surrounding blood vessels and neurons in the brain. The rudimentary humerus of the forelimb was attached to the thoracic spine, as viewed radiographically. The hindlimb was consisted of an irregularly shaped femur, short tibia and fibula, two tarsal bones, one metatarsal bone, and three phalanges. This is the first description of congenital anomalies involving the SEL, ectopic lung and ectopia cordis in a calf.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8079-8083
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• 2016

Metformin is an oral anti-hyperglycemic agent, which is the most commonly prescribed medication in the treatment of type-2 diabetes mellitus. It is purportedly associated with a reduced risk for various cancers, mainly exerting anti-proliferation effects on various human cancer cell types, such as pancreas, prostate, breast, stomach and liver. This mini-review highlights the risk and benefit of metformin used for cholangiocarcinoma (CCA) prevention and therapy. The results indicated metformin might be a quite promising strategy CCA prevention and treatment, one mechanism being inhibition of CCA tumor growth by cell cycle arrest in both in vitro and in vivo. The AMPK/mTORC1 pathway in intrahepatic CCA cells is targeted by metformin. Furthermore, metformin inhibited CCA tumor growth via the regulation of Drosha-mediated expression of multiple carcinogenic miRNAs. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. Clinical trials and epidemiological studies of the benefit of metformin use for CCA should be conducted. To date, whether metformin as a prospective chemotherapeutic for CCA is still questionable and waits further atttention.

• KSBB Journal
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• v.11 no.4
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• pp.453-461
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• 1996

We compared the effects of two different systems of collagen matrix protein application on the survival and the biological functions of cultured primary hepatocytes. The rat liver primary hepatocytes were grown for approximately 40 days in vitro either on single collagen gel or between collagen sandwich gels. The morphological changes were observed for this culture period. While the hepatocytes grown on single gel began to die around at 7 days of culture, the cells grown between collagen gels still maintained their viability and began to die after 15 days. As markers for liver hepatic functions, we determined the biochemical activities of hepatocytes such as the secretions of albumin, fibronectin, fibrinogen, urea, and the reduction of secreted ammonia. We found that the rat hepatocytes cultured between collagen gels maintained fairly good biochemical functions than the hepatocytes cultured on single gel did. Therefore, the application of an extracellular matrix protein, collagen, in sandwich form was confirmed as a better choice for maintaining the functional hepatocytes culture for long term in vitro.

• BMB Reports
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• v.48 no.9
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• pp.513-518
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• 2015

Factors that modulate cholesterol levels have major impacts on cardiovascular disease. Niemann-Pick C1-like 1 (NPC1L1) functions as a sterol transporter mediating intestinal cholesterol absorption and counter-balancing hepatobiliary cholesterol excretion. The liver receptor homolog 1 (LRH-1) had been shown to regulate genes involved in hepatic lipid metabolism and reverse cholesterol transport. To study whether human NPC1L1 gene is regulated transcriptionally by LRH-1, we have analyzed evolutionary conserved regions (ECRs) in HepG2 cells. One ECR was found to be responsive to the LRH-1. Through deletion studies, LRH-1 response element was identified and the binding of LRH-1 was demonstrated by EMSA and ChIP assays. When SREBP2, one of several transcription factors which had been shown to regulate NPC1L1 gene, was co-expressed with LRH-1, synergistic transcriptional activation resulted. In conclusion, we have identified LRH-1 response elements in NPC1L1 gene and propose that LRH-1 and SREBP may play important roles in regulating NPC1L1 gene. [BMB Reports 2015; 48(9): 513-518]

• Nuclear Medicine and Molecular Imaging
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• v.42 no.sup1
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• pp.66-70
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• 2008

Reports about FDG PET in biliary tumor are limited and there are almost no reports regarding its efficacy. Biliary tumor is divided to intrahepatic and extrahepatic bile duct cancer, and intrahepatic bile duct cancer can be further divided to peripheral type which occurs at lobular duct and hilar type which occurs at hepatic hilum. Surgical resection is the only curative method for bile duct tumor, and accurate staging plays an important role in deciding treatment modality. Among intrahepatic bile duct tumors, peripheral type and hilar type have the same histological characteristics, but different clinical manifestations and tumor growth pattern. On PET image, FDG uptake is also different between peripheral type and hilar type. Most of the former shows high FDG uptake at primary and metastasis site so it is very useful for determining stage and changing treatment plans. However, the later is diversified among low uptake and very high uptake. The FDG uptake pattern of hilar type is similar to that of extrahepatic bile duct cancer, and mucinous component is an important factor, which affects FOG uptake. When tumor cells are scattered in desmoplatsic stroma, then FDG uptake is low as well. In contrast, when FDG uptake is high, it is likely to be tubular type which has high tumor density. Tumor growth pattern also affects FDG uptake. Nodular type mostly takes higher FDG compared to infiltrative type. There are many cases where benign inflammatory diseases take high FDG that PET alone can not distinguish malignant lesion from benign lesion. In conclusion, studies about PET using FDG are still limited. Thus, it is hard to make accurate conclusion about the roles of PET or PET/CT in biliary cancers, but peripheral type intrahepatic bile duct cancers and mass forming hilar and extrahepatic bile duct cancers appear to be good indications performing FDG PET or PET/CT.

• Journal of Life Science
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• v.22 no.1
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• pp.1-6
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• 2012

The present study examined the effects of consumption of Jeju ground water containing vanadium components on oxidative stress in obese (ob/ob) mice. Intake of Jeju ground water decreased the generation of oxidative stress induced-lipid peroxidation in the liver of ob/ob mice It also enhanced the enzymatic antioxidant defense system by increasing the protein expression and activity of superoxide dismutase, catalase, and glutathione peroxidase in liver tissues. Jeju ground water intake also upregulated the intracellular content of reduced glutathione. The induction of antioxidant enzyme expression by consumption of Jeju ground water was mediated by the erythroid transcription factor NF-E2 (Nrf2). Increased nuclear expression of phospho Nrf2 was observed in ob/ob mouse liver cells following ntake of Jeju ground water. These results suggest that consumption of Jeju ground water stimulated the antioxidant defense system in the livers of ob/ob mice via induction of Nrf2.