• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4689-4695
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• 2014

Background: A great number of studies have shown that cytochrome P450 1A1 (CYP1A1) genetic polymorphisms, CYP1A1 Msp I and CYP1A1 Ile/Val, might be risk factors for digestive tract cancers, including esophageal cancer (EC), gastric cancer (GC), hepatic carcinoma (HC), as well as colorectal cancer (CC), but the results are controversial. In this study, a meta-analysis of this literature aimed to clarify associations of CYP1A1 genetic polymorphisms with digestive tract cancers susceptibility in Chinese populations. Materials and Methods: Eligible case-control studies published until December 2013 were retrieved by systematic literature searches from PubMed, Embase, CBM, CNKI and other Chinese databases by two investigators independently. The associated literature was acquired through deliberate search and selection based on established inclusion criteria. Fixed-effects or random-effects models were used to estimate odds ratios (ORs and 95%CIs). The meta-analysis was conducted using Review Manager 5.2 and Stata 12.0 softwares with stability evaluated by both stratified and sensitivity analyses. Moreover, sensitivity analysis and publication bias diagnostics confirmed the reliability and stability. Results: Eighteen case-control studies with 1,747 cases and 2,923 controls were selected for CYP1A1 MspI polymorphisms, and twenty case-control studies with 3, 790 cases and 4, 907 controls for the CYP1A1 Ile/Val polymorphisms. Correlation associations between CYP1A1 Ile/Val polymorphisms and digestive tract cancers susceptibility were observed in four genetic models in the meta-analysis (GG vs AA:OR= 2.03, 95%CI =1.52- 2.72; AG vs AA: OR=1.26, 95%CI =1.07-1.48; [GG+AG vs AA] :OR =1.42, 95%CI=1.20-1.68, [GG vs AA+AG]:OR=1.80, 95%CI =1.40-2.31). There was no association between CYP1A1 Msp I polymorphisms and digestive tract cancers risk. Subgroup analysis for tumor type showed a significant association of CYP1A1 Ile/Val genetic polymorphisms with EC in China. However, available data collected by the study failed to reveal remarkable associations of GC or HC with CYP1A1 Ile/Val genetic polymorphisms and EC, GC or CC with CYP1A1 MspI genetic polymorphisms. Conclusions: Our results indicated that CYP1A1 Ile/Val genetic polymorphisms, but not CYP1A1 Msp I polymorphisms, are associated with an increased digestive tract cancers risk in Chinese populations. Additional well-designed studies, with larger sample size, focusing on different ethnicities and cancer types are now warranted to validate this finding.

• The Korea Journal of Herbology
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• v.25 no.3
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• pp.1-9
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• 2010

Objectives : This study was undertaken to verify the effects of Gyeongshingangjeehwan18 (GGEx18) on obesity using ob/ob male mice. Methods : Eight-week old mice (wild-type C57BL/6J and ob/ob) were used for all experiments. Wild-type C57BL/6J mice were used as lean control and obese ob/ob mice were randomly divided into 5 groups: obese control, GGEx15, GGEx16, GGEx17, and GGEx18. After mice were treated with several kinds of GGEx for 11 weeks, body weight gain, feeding efficiency ratio, plasma lipid and glucose metabolism. Results : 1. Compared with obese controls, GGEx-treated mice had lower body weight gain and feeding efficiency ratio, the magnitudes of which were prominent in GGEx16 and GGEx18. 2. Consistent with their effects on body weight gain, GGEx16 and GGEx18 not only decreased plasma triglycerides levels, but also increased HDL-cholesterol concentration. 3. CT analysis revealed that visceral fat areas were decreased in all treatment groups compared with obese control mice. The decrease in visceral fat area was prominent in GGEx16 and GGEx18, although they were not statistically significant. 4. The size of adipocytes were significantly decreased by GGEx18, whereas the adipocyte number per unit area was significantly increased, suggesting that GGEx18 decreased the number of large adipocytes. Hepatic lipid accumulation was decreased by GGEx16 and GGEx18, and the inhibitory effect was most effective in GGEx18. 5. Plasma GOT and GPT concentrations were significantly lower following GGEx16 and GGEx18 treatment compared with obese controls. Organ weights were not changed by GGEx treatment, indicating GGEx do not show any toxic effects. Conclusions : These results suggest that GGEx may regulate obesity. Of the 4 compositions, GGEx18 seems to be most effective in improving obesity and lipid disorders.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4969-4976
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• 2014

Background: miR-152 is involved in the genesis and development of several malignancies. However, its role in HCC has not been fully clarified. The aim of this study was to investigate the clinicopathological significance of miR-152 and its effect on the malignant phenotype of HCC cells. Methods: miR-152 expression was detected using real-time quantitative RT-PCR in 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissues. Functionally, in vitro effects and mechanisms of action of miR-152 on proliferation, viability, caspase activity, apoptosis and motility were explored in HepG2, HepB3 and SNU449 cells, as assessed by spectrophotometry, fluorimetry, fluorescence microscopy, wound-healing and Western blotting, respectively. Results: miR-152 expression in HCC was downregulated remarkably compared to that in adjacent hepatic tissues. miR-152 levels in groups of advanced clinical stage, larger tumor size and positive HBV infection, were significantly lower than in other groups. A miR-152 mimic could suppress cell growth, inhibit cell motility and increase caspase activity and apoptosis in HCC cell lines. Furthermore, Western blotting showed that the miR-152 mimic downregulated Wnt-1, DNMT1, ERK1/2, AKT and TNFRS6B signaling. Intriguingly, inverse correlation of TNFRF6B and miR-152 expression was found in HCC and bioinformatics confirmed that TNFRF6B might be a target of miR-152. Conclusions: Underexpression of miR-152 plays a vital role in hepatocarcinogenesis and lack of miR-152 is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis. miR-152 may act as a tumor suppressor miRNA by also targeting TNFRSF6B and is therefore a potential candidate biomarker for HCC diagnosis, prognosis and molecular therapy.

• Journal of Acupuncture Research
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• v.28 no.5
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• pp.39-55
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• 2011

Objectives : Inchinohryungsan has been used for treatment of hepatobiliary diseases. This study was designed to investigate the effect of Inchinohryungsan pharmacopuncture on hepatocellular carcinoma in rats. Sprague Dawley(SD) rats of the control and experimental groups received intraperitoneal injection of 50 mg/kg DEN, weekly for 12 weeks. Methods : Rats were divided into 5 groups. Normal group was not induced hepatocellular carcinoma and not treated. Control group was induced hepatocellular carcinoma and injected with Inchinohryungsan pharmacopuncture into the root of tail. Experimental groups were induced hepatocellular carcinoma. BL group was injected with Inchinohryungsan pharmacopuncture into the $BL_{18}$ and $LR_{14}$, BG group was injected into the $BL_{19}$ and $GB_{24}$ and CSC group was injected into the $CV_{12}$, $ST_{25}$ and $CV_4$. Thereafter, the changes of the body weight, the liver weight and the weight of liver/100g body weight, WBC, neutrophil, lymphocyte and the activities of AST, ALT, ALP, LDH, AFP and SOD were measured. And gross anatomy, light and electron microscopy were performed. Results : The significant results were as follows, 1. The activities of LDH were significantly decreased in CSC group compared with control group. 2. The activities of AFP were significantly decreased in the BL, BG, CSC groups compared with control group. 3. The activities of SOD were increased in the BL, BG, CSC groups compared with control group and CSC group was significantly increased than normal group. 4. According to the gross anatomical observation, the control and BL, BG, CSC groups showed multi-nodular hepatocellular carcinoma. But the size and numbers of the hepatocellular carcinoma in experimental groups were smaller than control group. 5. The numbers of hepatic p53 positive cells were decreased in the BL, BG groups compared with control group. 6. According to the light and electron microscopical observation, the BL, BG and CSC groups were mildly improved than control group in morphological and histopathological changes. Conclusions : These results suggested that Inchinohryungsan pharmacopuncture may have some effects on hepatocellular carcinoma induced by DEN in rats.

• YAKHAK HOEJI
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• v.34 no.4
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• pp.238-243
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• 1990

Pharmacokinetic characteristics of recombinant human interleukin-2 (rH IL-2) wre studied in the rat. First, different doses of rH IL-2 ranging from 6,400 to 1,600,000 U/kg were injected intravenously and the effect of dose size on the pharmacokinetics was examined. There was no dose dependency in the pharmacokinetics of rHIL-2 in the dose range of 6,400-40,000 U/kg. But at the dose of 1,600,000 U/kg, there was a severe hemolysis throughout the experiment and the pharmacokinetic parameters such as Vdss and CLt were significantly increased compared to those obtained from lower doses. It also showed that this drug is hardly distributed to the peripheral tissues and hardly eliminated from the body, since the valume of distribution (Vdss) and total body clearance (CLt) were 45-75 ml/kg and 1-2 ml/min/kg, respectively. The Vdss is close to the actual plasma volume and the CLt is less than glomerular filtration rate (GFR). Therefore it seemed that rH IL-2 is distributed only in the plasma pool and hardly filtered in the kidney due to its very large molecular weight. Second, rH IL-2 was administered to the rat via several routes such as hepatic portal vein (PV), intraperitoneal (IP), peroral (PO) and intranasal (IN) routes. The bioavailabilities (BA) of PV, IP, PO and IN routes were 96.8, 4.9, 0 and 0.1%, respectively. The addition of some nasal absorption enhancers such as taurocholate, taurodeoxycholate, glycocholate and glycodeoxycholate did not increase the BA of intranasaly administered rH IL-2. The result is contrast to the effect of these bile salts on the nasal absorption of ${\alpha}-inteferon$. Considering it together with the pharmacokinetic parameters, very large molecular weight of rH IL-2 seemed again to be the cause to very poor membrane permeability.

• Journal of Gastric Cancer
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• v.3 no.4
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• pp.191-194
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• 2003

Purpose: Neuroendocrine carcinomas of the stomach account for only about $0.3\%$ of all gastric tumors. The prognosis of this disease is very poor compared with the common type of gastric adenocarcinoma. The purpose of this retrospective study was to review the clinicopathologic features of 18 cases of this unusual gastric tumor and to establish a treatment strategy for this tumor. Materials and Methods: Excluding 2 cases of non-curative resection and 1 case of operative mortality, 18 cases of typical neuroendocrine carcinoma who had curative resection from January 1991 to December 2000 at Asan Medical Center were analyzed; 6841 gastric cancer patient were treated surgically during the same period. Results: The mean age at the time of diagnosis was 58.6 years (range: $35\∼75$ yr). Sixteen patients were male, and two were female. Eleven tumors ($61.1\%$) developed in the lower part of the stomach, three ($16.7\%$) in the middle part, and three ($16.7\%$) in the upper part. One tumor involved the entire stomach. Eight cases ($44.4\%$) were Borrmann type 2, and six case ($33.3\%$) were Borrmann type 3. The mean tumor size was 6.94 cm (range: $0.6\∼15$ cm). Nine cases ($50\%$) showed recurrence of the disease, and eight of them died within 20 months. Of the nine recurred cases, 7 cases ($77.8\%$) showed liver metastasis. The mean disease-free interval was 6.8 months (range: $2.5\∼11$ months) after surgical resection, and the mean survival was 17.9 months (range: $8\∼40$ months) for recurrence cases. One patient with liver metastasis was treated with a liver-wedge resection just after diagnosis and was still alive for 37.5 months postoperatively. There were 9 deaths after the median follow- up period of 40 months (range: $8\∼72$ months). Conclusion: Gastric neuroendocrine carcinomas frequently recur at the liver, even in early stage cancer, and have a poor prognosis. We experienced a case of successful control of hepatic metastasis by surgical resection and a case of a small cell carcinoma which was successfully controlled with systemic chemotherapy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.12
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• pp.1771-1778
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• 2015

The study aimed to investigate the anti-obesity effects of 1% Rhus verniciflua vinegar (RV) supplementation in high-fat-diet (60% fat)-induced obese rats. A total of 50 4-wk-old male Sprague-Dawley rats were fed normal chow diet or maintained on high-fat diet (HFD) for 12 weeks to induce obesity and were then randomized into five groups as follows: normal diet+ultra-pure water (CON), HFD+ultra-pure water (OB-DW), HFD+1% acetic acid (OBAA), HFD+1% RV (OB-RV), and HFD+0.1% caffeine (OB-CF). AA was used as a control for RV, and caffeine was used as a positive control due to its weight reducing effect. After 2 months, body weight, organ and adipose tissue weights, serum lipids, hepatic lipids, adipocyte size, and cell number per spot level were analyzed. As a result, food efficiency ratio, abdominal adipose tissue weight, serum levels of total cholesterol, triacylglycerol, free fatty acids, coronary artery index, and fecal lipid were significantly reduced in the RV treatment group. In this study, we found that dietary RV improved obesity by increasing lipid excretion and reducing lipogenesis. These results suggest that RV has potential as a functional anti-obesity food.

• Herbal Formula Science
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• v.19 no.2
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• pp.47-59
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• 2011

Objectives : We investigated the effects of gambigyeongsinhwan2(GGH(2)) on body weight and examined whether blood triglyceride levels and visceral fat are inhibited by it in high fat diet-fed obese male mice. Methods : 8 weeks old, high fat diet-fed obese male mice were divided into 5 groups: C57BL/6N normal, control, GGH(2)-1, GGH(2)-2 and GGH(2)-3. After mice were treated with GGH(2) for 8 weeks, we measured body weight gain, food intake, feeding efficiency ratio, fat weight, plasma leptin and lipid levels. We also did histological analysis for liver and fat on the mice. Results : 1. Compared with controls, GGH(2)-treated mice had lower body weight gain and adipose tissue weight, the magnitudes of which were prominent in GGH(2)-3. 2. Compared with controls, GGH(2)-treated mice had lower feeding efficiency ratio, the magnitude of which was prominent in GGH(2)-3. 3. Compared with controls, GGH(2)-treated mice had lower blood plasma triglyceride level. 4. Blood plasma AST and ALT concentrations were not changed by GGH(2), indicating GGH(2) do not show any toxic effects. 5. Consistent with their effects on body weight gain, the size of adipocytes were significantly decreased by GGH(2), whereas the adipocyte number per unit area was significantly increased, suggesting that GGH(2) decreased the number of large adipocytes. Hepatic lipid accumulation was decreased by GGH(2). Conclusions : These results demonstrate that GGH(2) effectively reduces body weight gain, feeding efficiency ratio, blood plasma triglyceride level and improves abdominal fat.

• Journal of Oriental Neuropsychiatry
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• v.21 no.4
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• pp.53-68
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• 2010

Objectives : We investigated the effects of Sopungsungj-won(Shufengshunqjvuan) (SSEx1, SSEx2) on the metabolic syndrome in high-fat diet induced obese mice. Methods: 8 weeks old, high fat diet induced obese male mice were divided into 4 groups: C57BL/6 lean control, obese vehicle control, SSEx1, SSEx2. After mice were treated with SSExl, SSEx2 for 12 weeks, we measured body weight gain, food intake, feeding efficiency ratio, fat weight, plasma leptin, insulin, glucose and lipid levels. We also observe the morphology and count for the numbers of Adipocyte and evaluate the weight of organs and it's function. Results: 1. Compared to Obese Control Group, SSEx1 gained significantly lower body weight and showed lower Feeding Efficiency Ratio. 2. Compared to Obese Control Group, SSEx1 showed lower weights of epididymal adipose tissue, troperitoneal adipose tissue, inguinal adipose tissue, brown adipose tissue. SSEx2 showed higher weights of epididymal adipose tissue, troperitoneal adipose tissue, inguinal adipose tissue, brown adipose tissue. 3. Compared to Obese Control Group, the size of adipocytes was significantly decreased by SSEx1, whereas the number of adipocites per unit was significantly increased. Hepatic lipid accumulation was decreased significantly by SSEx1. 4. Concerning the weights of Liver, Heart, Spleen, Kidney and Pancreas, SSEx1, SSEx2 showed little differences with those of Lean Control, Obese Control. 5. Compared to Obese Control Group, SSEX1, SSEx2 showed lower level of plasma triglyceride, but SSEx1 had significance only. SSEx1, SSEx2 showed little lower level of plasma HDL-cholesterol. LDL-cholesterol, total cholesterol, but had no significances. 6. Concerning the levels of plasma glucose, insulin and leptin, SSEx1 and SSEx2 showed littele changes with those of Lean Control, Obese Control. 7. The leves of Plasma AST, AST, ALT, free fatty acid, BUN, creatinine were in the physiological range at 4 groups all: Lean Control, Obese Control, SSEx1, SSEx2. Conclusions : These results showed SSEx1 can be used as therapeutic agent for Obesity and metabolic syndrome caused by long-period high fat diet.

• Applied Microscopy
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• v.31 no.1
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• pp.9-18
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• 2001

This study was designed to determine the effects of Protaetia Orientalis larva (Gory et Perchlon) on the in vivo lipid metabolism in Sprague Dawley rats with the administration of carbon tetrachloride to induce damage in the liver. At the end of 8th week, serum levels of GOP and GPT, hepatic cholesterol levels, HDL-cholesterol, triglycerides and phospholipids were determined. In addition, activities of antioxidative enzymes were also determined. The administration of carbon tetrachloride resulted in increase of serum GOT and GPT, liver triglyceride and total cholesterol. On the other hand, those fed in combination with carbon tetrachloride and Protaetia Orientalis larva decreased those lipid parameters . Carbon tetrachloride feeding resulted in decrease of liver phospholipid, whereas that of the rat fed in combination with carbon tetrachloride and Protaetia Orientalis larva was increased. In antioxidative defense system, carbon tetrachloride led to a significant decrease in activities of catalase, total SOD, Cu, Zn-SOD and glutathione-S-transferase. However, those activities of the rat fed in combination with carbon tetrachloride and Protaetia Orientalis larva was significantly increased. Hepatocytes of carbon tetrachloride administered rats showed increased lipid droplets and micro-filaments. However, those of the rat fed in combination with carbon tetrachloride and Protaetia Orientalis larva were reduced in the number and the size.