臺灣博碩士論文加值系統

1. 慢性疾病自2005年後已逐漸成為世界人口死亡主因，其中癌症占13 %，而肝癌一直位於惡性腫瘤發生及致死率前五位。從流行病學的研究中，B型肝炎與C型肝炎病毒的感染為導致肝癌的重要危險因子，而亞洲地區為其高盛行率區域，故關於護肝的健康議題更加受到亞洲人的重視。本研究目的以四氯化碳誘導大鼠肝損傷模式，評估由順天生技所提供的中草藥複方(HC)是否具有保肝的功效；HC主要包含維他命C、薑黃及綠茶萃取物這三種已被證實具有抗氧化的功效。由實驗結果顯示，相較於CCl4負對照組，我們發現給予高劑量HC (375 mg/kg bw/day)後，可顯著降低血液中肝臟生化功能指標酵素ALT及AST指數，表示肝損傷獲得改善。而在抗氧化酵素活性測試中，亦可看出HC相較於CCl4負對照組，可提高GPx、GRd、CAT及SOD的活性與GSH含量，表示HC (375 mg/kg bw/day)具有恢復抗氧化系統功能的效果。另外HC亦能顯著降低肝臟中TBARS及TG的含量，顯示HC可以改善脂肪過氧化的現象；組織切片的部分，HC對肝臟空泡化有降低的趨勢，顯示其對肝臟之脂肪變性具有抑制的效果，而高劑量樣品具有降低肝纖維化之潛力。從以上結果顯示中草藥複方HC應對護肝有正面的助益。
2. 肝癌與肝相關疾病為台灣死亡人口中的主要死因，且亞洲人罹患肝炎的比例是世界為最，慢性的B、C型肝炎患者為演變成肝癌的高危險群，此外，在臨床上，治療肝癌的藥物往往具有副作用，目前傳統的癌症治療方法，常引起嚴重的副作用(side effects)，導致病人無法負荷甚至威脅到性命，而依賴醫療方式，癒後病患之五年存活率平均約40%。近年來科學家致力研究癌症的分子及基因調控機制，並積極找尋可減輕癌症症狀或是延緩腫瘤生長速度的療法，現今著重於利用天然物質(natural products)達到癌症預防及促進健康的效果且無副作用之影響，而食用天然食品已為現代人生活保健的趨勢。此外，西方國家亦漸漸對於亞洲傳統中草藥(traditional Chinese medicine)賦予肯定，認為某些癌症發生率較低可能基於亞洲人的飲食因素，故揭開complementary and alternative medicine (CAM)治療功能的潛力。
巴西洋菇發酵產物之乙醇萃出物(ABE)，在體外MTT實驗中，對人類肝癌細胞Hep 3B cells具有毒殺作用，IC50為138 μg/ml。利用MTT實驗推估裸鼠之動物實驗所需劑量分別為60, 120, 600 mg/kg/day，在接種腫瘤前，先給於ABE兩週，觀察ABE是否具有預防肝癌效果。實驗發現ABE對腫瘤的抑制率為42%，對罹患肝癌裸鼠的生存率可提高56%，此外，相對於正對照組，ABE對於裸鼠的的身體負荷較小，體重較正對照組為重且飲食狀況較佳。因此根據活體實驗，ABE似乎具有抗肝癌的潛力。

1. Herbal complex (HC) was offered by Sun-Ten Phytotech. Company. It consists of Vitamin C, green tea, and turmeric which were reported previously with the antioxidant capability. The aim of this study was to evaluate the protective effect of HC against carbon tetrachloride (CCl4)-induced chronic liver damage in rats. Experimental groups were: (1) normal control, (2) Silymarin-positive control, (3) CCl4 -treated group, and (4) HC (4.2-375 mg/kg bw/day) + CCl4 treated groups. After administrated with CCl4 alone on rats for 8 weeks, marked rises of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride, cholesterol, and lipid peroxidation were noted; while the activities of antioxidant enzymes such as glutathione peroxidase (GPx), GRd (glutathione rductase), superoxide dismutase (SOD), and catalase (CAT) were decreased. HC (375 mg/kg bw/day) attenuated successfully all of the negative effects stated above of CCl4 in rats and also elevated the glutathione (GSH) content and inhibited the formation of steatosis as well as fibrosis in the liver as compared with the CCl4 group (p<0.05). These results suggest HC may usefully protect the liver against the oxidative stress induced by CCl4.
2. Over the last decade, the basidiomycete fungus Agaricus blazei Murill has been studied and developed as a novel functional food in some Asian countries after it was reported to be a source of anti-tumor and immuno-active compounds. According to tradition, it also helps against a variety of diseases, including diabetes, hyperlipidemia, atherosclerosis and chronic hepatitis. However, the fruiting body of A. blazei is relative expensive, due to its low yield, and a cheap and stable source of A. blazei fermentation products is desirable to promote in commercial products. In Taiwan, the incidence of liver diseases is high, such as chronic hepatitis, liver cirrhosis and hepatoma which are the leading causes of death in 2006. Furthermore, the effect of the fermentation product of A. blazei cultured in the medium containing soybean and black soybean on liver tumor, we use nude mice with immunodeficiency as a hepatocellular carcinoma (HCC)-induced model. In vitro assay, we found that the ethanolic extract of the fermentation product of A. blazei (ABE) can inhibit Hep 3B cells with IC50, 138 μg/ml. Prior to tumor-inducing, the nude mice received oral administration of ABE in two weeks with preventive goal of food. In vivo model, oral administration of ABE has potential to reduce the tumor volume as compared with negative control and the inhibition rate is 42% on day 51 after tumor-inducing. Moreover, ABE also prolongs the survival time of tumor-bearing mice and the survival rate is 56%. In conclusion, ABE may show the potency to prevent from HCC and is possible to be a candidate for increasing the life span of patients who suffer liver cancer.

第一部分 中文摘要 I
第一部分 英文摘要 II
第二部分 中文摘要 III
第二部分 英文摘要 IV
目錄 V
圖次 IX
表次 X
第一部分 1
在四氯化碳誘導大鼠肝損傷模式下中草藥複方對於護肝的效果之探討 1
Hepatoprotective Effect of Herbal Complex on Liver Damage Induced by Carbon Tetrachloride in Rats 1
第一章、 前言 2
第二章、 文獻回顧 3
第一節、 肝臟生理功能與組織結構 3
第二節、 肝相關疾病簡介 5
第三節、 Reactive oxygen species (ROS)簡介 6
一、 ROS種類及生成途徑 7
二、 ROS與肝疾病相關性 8
第四節、 細胞抗氧化防禦系統 9
一、 酵素性抗氧化系統 9
二、 非酵素性抗氧化系統 11
第五節、 四氯化碳誘導肝損傷模式 11
一、 四氯化碳之毒性 11
二、 四氯化碳誘發肝損傷之機制 11
第六節、 本實驗之中草藥複方簡介 12
一、 薑黃(Curcuma longa L.) 12
二、 綠茶(Camellia sinensis) 15
三、 維他命C (L-ascorbic acid) 17
第三章、 實驗架構 24
第一節、 急性實驗架構 24
第二節、 慢性實驗架構 25
第四章、 實驗材料與方法 26
第一節、 實驗材料 26
第二節、 實驗方法 26
一、 實驗動物飼養 26
二、 四氯化碳誘導大鼠肝損傷的方法 26
(一) 短期實驗方法 26
(二) 四氯化碳誘導大鼠短期肝損傷實驗模式 27
(三) 慢性實驗方法 27
(四) 四氯化碳誘導大鼠慢性肝損傷實驗模式 27
三、肝功能生化指數的檢測 28
(一) 脂質過氧化（lipid peroxidation, LPO）之分析 28
(二) 還原態麩胱甘肽（reduced-form glutathione, GSH）濃度之分析 29
(三) 麩胱甘肽過氧化酶（glutathione peroxidase, GPx）活性之分析 30
(四) 麩胱甘肽還原酶（glutathione reductase, GRd）活性之分析 30
(五) 麩胱甘肽硫轉移酶（glutathione S-transferase, GST）活性之分析 31
(六) 超氧化物歧化酶（Superoxide dismutase, SOD）之活性分析 31
(七) 過氧化氫酶（Catalase, CAT）之活性分析 31
(八) 蛋白質濃度之測定 32
(九) 肝臟三酸甘油酯(triglyceride, TG)及總膽固醇(cholesterol, Chol)的定量分析 32
四、 組織病理學的觀察 32
五、 統計方法 33
第五章、 實驗結果 35
第一節、 短期實驗結果 35
第二節、 慢性實驗結果 37
第六章、 實驗結果與討論 41
第七章、 結論 46
第二部分 69
探討巴西洋菇發酵產物之乙醇萃取物對接種肝癌細胞株Hep3B之裸鼠的影響 69
Effects of the Ethanolic Extract of the Fermentation Product of Agaricus blazei on Hepatocellular Carcinoma (Hep 3B Cells)- implanted in Nude Mice 69
第一章、 前言 70
第二章、 文獻回顧 71
第一節、 癌症的形成 71
第二節、 癌症的特徵 71
第三節、 肝癌 74
第四節、 人類肝癌細胞株(Hep3B) 77
第五節、 巴西洋菇(Agaricus blazei)生物學特性 77
第六節、 巴西洋菇及其生物活性與藥理功效 78
一、 巴西洋菇的基本成分與活性成分 78
二、 巴西洋菇的生理活性 79
三、 巴西洋菇的安全性 80
第七節、 裸鼠腫瘤引導模式 81
一、 裸鼠生物學特徵 81
二、 裸鼠模式之人類腫瘤研究 81
第三章、研究目的與實驗架構 86
第四章、 實驗材料與方法 87
第一節、 實驗材料 87
一、 巴西洋菇發酵產物 87
二、 人類肝癌細胞株 87
三、 動物來源與管理 87
四、 儀器設備 88
五、 耗材 89
六、 化學試劑與溶劑 89
七、 細胞實驗用之溶液配置 90
第二節、 實驗方法 91
一、 巴西洋菇乙醇萃取物製備 91
二、 以體外試驗測試巴西洋菇乙醇萃取物活性表現 91
三、 巴西洋菇乙醇萃取物抗癌功效之動物試驗 92
四、 統計方法 94
第五章、 實驗結果 96
第一節、 巴西洋菇發酵物之乙醇萃取物(ABE)的活性分析 96
in vitro 96
一、 ABE對Hep 3B細胞生存率的影響 96
第二節、 巴西洋菇發酵物之乙醇萃取物(ABE)的活性分析 96
in vivo 96
一、 裸鼠體重變化 96
二、 ABE對腫瘤大小的影響 96
三、 ABE對裸鼠生存率的影響 97
第六章、 實驗結果與討論 98
第一節、 裸鼠腫瘤動物模式之合理性 98
第二節、 裸鼠腫瘤動物模式之規劃 99
第三節、 ABE抗肝癌之功效 100
第七章、 結論 103
第八章、 參考文獻 111
附錄…………………128

1.WHO Hepatitis B; World Health Organization: 2002; p 76.
2.WHO Hepatitis C; World Health Organization: 2000; p 4.
3.WHO World health statistics 2006; World health organization: 2006; p 14.
4.行政院衛生署。死因統計。行政院衛生署Ed。行政院衛生署。2007。Vol. 1： pp 6-16
5.Gunawan, B.; Kaplowitz, N., Textbook of hepatology: from basic science to clinical practice. Blackwell: 2003; Vol. 2, p 1270-1271.
6.Padayatty, S. J.; Katz, A.; Wang, Y.; Eck, P.; Kwon, O.; Lee, J.-H.; Chen, S.; Corpe, C.; Dutta, A.; Dutta, S. K.; Levine, M., Vitamin C as an Antioxidant: Evaluation of Its Role in Disease Prevention. J Am Coll Nutr 2003, 22, (1), 18-35.
7.Frei, B.; Higdon, J. V., Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. J Nutr 2003, 133, (10), 3275S-84S.
8.Pozharitskaya, O. N.; Ivanova, S. A.; Shikov, A. N.; Makarov, V. G., Separation and free radical-scavenging activity of major curcuminoids of Curcuma longa using HPTLC-DPPH method. Phytochem Analysis 2007.
9.Rhodin; Johannes, A. G., 組織學. 環球書社: 1985; Vol. 30, p 580-594.
10.Dahle, M. K.; Myhre, A. E.; Aasen, A. O.; Wang, J. E., Effects of Forskolin on Kupffer Cell Production of Interleukin-10 and Tumor Necrosis Factor Alpha Differ from Those of Endogenous Adenylyl Cyclase Activators: Possible Role for Adenylyl Cyclase 9 American Society for Microbiology 2005, 73, (11), 7290-7296.
11.Reuben, A., Ito becomes a star. Hepatology 2002, 35, (2), 503-4.
12.廖雯慧。南方靈芝三萜類抗腫瘤生物活性與藥理功效之研究。台灣師範大學, 台北。2004
13.Stevens, A.; Lowe, J., Hepatobiliary system. In Histology, Gower Medical: 1992; Vol. 11, pp 176-183.
14.宋瑞樓。陳定信。廖運範。肝炎，肝硬化與肝癌。橘井文化事業股份有限公司。 2006。p 396
15.陳秀雯。酒精性肝損傷。食品工業。2002。pp.3-5
16.Wan, L.; Tsai, C. H.; Tsai, Y.; Hsu, C. M.; Lee, C. C.; Tsai, F. J., Mutation analysis of Taiwanese Wilson disease patients. Biochem Biophys Res Commun 2006, 345, (2), 734-8.
17.賴鴻緒。陳慧君。肝臟疾病。臨床營養學 靜脈暨腸道營養。楊榮森Ed。時新出版有限公司。2005。Vol. 25：pp 404-434.
18.陳秀雯。肝功能及肝損傷。食品工業。 2002。pp.1-2
19.Valko, M.; Izakovic, M.; Mazur, M.; Rhodes, C. J.; Telser, J., Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem 2004, 266, (1-2), 37-56.
20.Kruidenier, L.; Verspaget, H. W., Review article: oxidative stress as a pathogenic factor in inflammatory bowel disease--radicals or ridiculous? Aliment Pharmacol Ther 2002, 16, (12), 1997-2015.
21.Wiseman, H.; Halliwell, B., Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J 1996, 313 ( Pt 1), 17-29.
22.Valko, M.; Rhodes, C. J.; Moncol, J.; Izakovic, M.; Mazur, M., Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 2006, 160, (1), 1-40.
23.Inoue, M.; Sato, E. F.; Nishikawa, M.; Park, A. M.; Kira, Y.; Imada, I.; Utsumi, K., Mitochondrial generation of reactive oxygen species and its role in aerobic life. Curr Med Chem 2003, 10, (23), 2495-505.
24.Gutierrez, J.; Ballinger, S. W.; Darley-Usmar, V. M.; Landar, A., Free radicals, mitochondria, and oxidized lipids: the emerging role in signal transduction in vascular cells. Circ Res 2006, 99, (9), 924-32.
25.Sturgill, M. G.; Lambert, G. H., Xenobiotic-induced hepatotoxicity: mechanisms of liver injury and methods of monitoring hepatic function. Clin Chem 1997, 43, (8 Pt 2), 1512-26.
26.Jaeschke, H.; Gores, G. J.; Cederbaum, A. I.; Hinson, J. A.; Pessayre, D.; Lemasters, J. J., Mechanisms of hepatotoxicity. Toxicol Sci 2002, 65, (2), 166-76.
27.Medina, J.; Moreno-Otero, R., Pathophysiological basis for antioxidant therapy in chronic liver disease. Drugs 2005, 65, (17), 2445-61.
28.McClain, C. J.; Mokshagundam, S. P.; Barve, S. S.; Song, Z.; Hill, D. B.; Chen, T.; Deaciuc, I., Mechanisms of non-alcoholic steatohepatitis. Alcohol 2004, 34, (1), 67-79.
29.Benzie, I. F., Evolution of antioxidant defence mechanisms. Eur J Nutr 2000, 39, (2), 53-61.
30.Blankensteijn, J. D.; Terpstra, O. T., Liver preservation: the past and the future. Hepatology 1991, 13, (6), 1235-50.
31.Deshpande, U. S.; Deshpande, S. S.; Salunkhe, D. K., Nutritional and health aspects of food antioxidants. In Food antioxidants: Technological, toxicological, and health perspectives, Madhavi, D. L.; Deshpande, S. S.; Salunkhe, D. K., Eds. Marcel Dekker, Inc: 1995; Vol. 6, pp 361-461.
32.Howie, A. F.; Forrester, L. M.; Glancey, M. J.; Schlager, J. J.; Powis, G.; Beckett, G. J.; Hayes, J. D.; Wolf, C. R., Glutathione S-transferase and glutathione peroxidase expression in normal and tumour human tissues. Carcinogenesis 1990, 11, (3), 451-8.
33.Rahman, Q.; Abidi, P.; Afaq, F.; Schiffmann, D.; Mossman, B. T.; Kamp, D. W.; Athar, M., Glutathione redox system in oxidative lung injury. Crit Rev Toxicol 1999, 29, (6), 543-68.
34.Bozdech, Z.; Ginsburg, H., Antioxidant defense in Plasmodium falciparum--data mining of the transcriptome. Malar J 2004, 3, 23.
35.Fouw, J. d., Carbon Tetrachloride. In world health organization: 1999; Vol. 1,2,6,7,8,10, p 176.
36.Dhawan, D.; Goel, A., Further evidence for Zinc as a hepatoprotective agent in rat liver toxicity. Exp Mol Pathol 1995, 63, 110-117.
37.Sheweita, S. A.; El-Gabar, M. A.; Bastawy, M., Carbon tetrachloride changes the activity of cytochrome P450 system in the liver of male rats: role of antioxidants. Toxicology 2001, 169, (2), 83-92.
38.McGregor, D.; Lang, M., Carbon tetrachloride: genetic effects and other modes of action. Mutat Res 1996, 366, (3), 181-95.
39.Plant, N., Molecular Toxicology. BIOS Scientific: 2003; Vol. 2, 3, 5, p 145.
40.Weber, L. W.; Boll, M.; Stampfl, A., Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol 2003, 33, (2), 105-36.
41.Janakat, S.; Al-Merie, H., Optimization of the dose and route of injection, and characterisation of the time course of carbon tetrachloride-induced hepatotoxicity in the rat. J Pharmacol Toxicol Methods 2002, 48, (1), 41-44.
42.Wu, Y.; Li, L.; Wen, T.; Li, Y.-Q., Protective effects of echinacoside on carbon tetrachloride-induced hepatotoxicity in rats. Toxicology 2007, 232, (1-2), 50-56.
43.Raja, S.; Ahamed, K. F.; Kumar, V.; Mukherjee, K.; Bandyopadhyay, A.; Mukherjee, P. K., Antioxidant effect of Cytisus scoparius against carbon tetrachloride treated liver injury in rats. J Ethnopharmacol 2007, 109, (1), 41-7.
44.張賢哲。道地藥材圖鑑。中國醫藥大學。2007。Vol. 3：p 917，942
45.Araujo, C. C.; Leon, L. L., Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz 2001, 96, (5), 723-8.
46.Luper, S., A review of plants used in the treatment of liver disease: part two. Altern Med Rev 1999, 4, (3), 178-88.
47.Miyakoshi, M.; Yamaguchi, Y.; Takagaki, R.; Mizutani, K.; Kambara, T.; Ikeda, T.; Zaman, M. S.; Kakihara, H.; Takenaka, A.; Igarashi, K., Hepatoprotective effect of sesquiterpenes in turmeric. Biofactors 2004, 21, (1-4), 167-70.
48.Adhvaryu, M. R.; Reddy, N.; Parabia, M. H., Effects of four Indian medicinal herbs on Isoniazid-, Rifampicin- and Pyrazinamide-induced hepatic injury and immunosuppression in guinea pigs. World J Gastroenterol 2007, 13, (23), 3199-205.
49.Wei, Q.-Y.; Chen, W.-F.; Zhou, B.; Yang, L.; Liu, Z.-L., Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues. Biochimica et Biophysica Acta (BBA) - General Subjects 2006, 1760, (1), 70-77.
50.Sugiyama, T.; Nagata, J.-i.; Yamagishi, A.; Endoh, K.; Saito, M.; Yamada, K.; Yamada, S.; Umegaki, K., Selective protection of curcumin against carbon tetrachloride-induced inactivation of hepatic cytochrome P450 isozymes in rats. Life Sciences 2006, 78, (19), 2188-2193.
51.Nonn, L.; Duong, D.; Peehl, D. M., Chemopreventive anti-inflammatory activities of curcumin and other phytochemicals mediated by MAP kinase phosphatase-5 in prostate cells. Carcinogenesis 2007, 28, (6), 1188-96.
52.Maheshwari, R. K.; Singh, A. K.; Gaddipati, J.; Srimal, R. C., Multiple biological activities of curcumin: A short review. Life Sciences 2006, 78, (18), 2081-2087.
53.Aggarwal, S.; Ichikawa, H.; Takada, Y.; Sandur, S. K.; Shishodia, S.; Aggarwal, B. B., Curcumin (Diferuloylmethane) Down-Regulates Expression of Cell Proliferation and Antiapoptotic and Metastatic Gene Products through Suppression of I{kappa}B{alpha} Kinase and Akt Activation. Mol Pharmacol 2006, 69, (1), 195-206.
54.Mazumder, A.; Raghavan, K.; Weinstein, J.; Kohn, K. W.; Pommier, Y., Inhibition of human immunodeficiency virus type-1 integrase by curcumin. Biochem Pharmacol 1995, 49, (8), 1165-70.
55.Erik De, C., Current lead natural products for the chemotherapy of human immunodeficiency virus (HIV) infection. Med Res Rev 2000, 20, (5), 323-349.
56.Kim, K. J.; Yu, H. H.; Cha, J. D.; Seo, S. J.; Choi, N. Y.; You, Y. O., Antibacterial activity of Curcuma longa L. against methicillin-resistant Staphylococcus aureus. Phytother Res 2005, 19, (7), 599-604.
57.Srivivasan, A.; Menon, V. P.; Periaswamy, V.; Rajasekaran, K. N., Protection of pancreatic beta-cell by the potential antioxidant bis-o-hydroxycinnamoyl methane, analogue of natural curcuminoid in experimental diabetes. J Pharm Pharm Sci 2003, 6, (3), 327-33.
58.Ganiger, S.; Malleshappa, H. N.; Krishnappa, H.; Rajashekhar, G.; Ramakrishna Rao, V.; Sullivan, F., A two generation reproductive toxicity study with curcumin, turmeric yellow, in Wistar rats. Food Chem Toxicol 2007, 45, (1), 64-69.
59.Babich, H.; Zuckerbraun, H. L.; Weinerman, S. M., In vitro cytotoxicity of (-)-catechin gallate, a minor polyphenol in green tea. Toxicol Lett 2007, 171, (3), 171-80.
60.Beltz, L. A.; Bayer, D. K.; Moss, A. L.; Simet, I. M., Mechanisms of Cancer Prevention by Green and Black Tea Polyphenols. Anti-Cancer Agents in Med Chem 2006, 6, (5), 389-406.
61.Hengartner, M. O., The biochemistry of apoptosis. Nature 2000, 407, (6805), 770-776.
62.Shammas, M. A.; Neri, P.; Koley, H.; Batchu, R. B.; Bertheau, R. C.; Munshi, V.; Prabhala, R.; Fulciniti, M.; Tai, Y. t.; Treon, S. P.; Goyal, R. K.; Anderson, K. C.; Munshi, N. C., Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications. Blood 2006, 108, (8), 2804-2810.
63.Foda, H. D.; Zucker, S., Matrix metalloproteinases in cancer invasion, metastasis and angiogenesis. Drug Discovery Today 2001, 6, (9), 478-482.
64.Oku, N.; Matsukawa, M.; Yamakawa, S.; Asai, T.; Yahara, S.; Hashimoto, F.; Akizawa, T., Inhibitory effect of green tea polyphenols on membrane-type 1 matrix metalloproteinase, MT1-MMP. Biol Pharm Bull 2003, 26, (9), 1235-8.
65.Lee S. R.; Im K.J.; Suh S.; Jung J. G., Protective effect of green tea polyphenol (-)-epigallocatechin gallate and other antioxidants on lipid peroxidation in gerbil brain homogenates. Phytother Res 2003, 17, (3), 206-209.
66.Erba, D.; Riso, P.; Bordoni, A.; Foti, P.; Biagi, P. L.; Testolin, G., Effectiveness of moderate green tea consumption on antioxidative status and plasma lipid profile in humans. J Nutr Biochem 2005, 16, (3), 144-149.
67.Helieh S. Oz, C. J. M. H. T. N. M. B. R. W. J. S. d. V. T. S. C., Diverse antioxidants protect against acetaminophen hepatotoxicity. J Biochem Mol Toxic 2005, 18, (6), 361-368.
68.Zhang, X. G.; Xu, P.; Liu, Q.; Yu, C. H.; Zhang, Y.; Chen, S. H.; Li, Y. M., Effect of tea polyphenol on cytokine gene expression in rats with alcoholic liver disease. Hepatobiliary Pancreat Dis Int 2006, 5, (2), 268-72.
69.Iso, H.; Date, C.; Wakai, K.; Fukui, M.; Tamakoshi, A., The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults. Ann Intern Med 2006, 144, (8), 554-62.
70.Wu, L. Y.; Juan, C. C.; Ho, L. T.; Hsu, Y. P.; Hwang, L. S., Effect of green tea supplementation on insulin sensitivity in Sprague-Dawley rats. J Agric Food Chem 2004, 52, (3), 643-8.
71.Chantre, P.; Lairon, D., Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. Phytomedicine 2002, 9, (1), 3-8.
72.Lin, J.; Della-Fera, M. A.; Baile, C. A., Green Tea Polyphenol Epigallocatechin Gallate Inhibits Adipogenesis and Induces Apoptosis in 3T3-L1 Adipocytes. Obesity Res 2005, 13, (6), 982-990.
73.Hung, P.-F.; Wu, B.-T.; Chen, H.-C.; Chen, Y.-H.; Chen, C.-L.; Wu, M.-H.; Liu, H.-C.; Lee, M.-J.; Kao, Y.-H., Antimitogenic effect of green tea (-)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the ERK and Cdk2 pathways. Am J Physiol Cell Physiol 2005, 288, (5), C1094-1108.
74.Watson, J. L.; Vicario, M.; Wang, A.; Moreto, M.; McKay, D. M., Immune cell activation and subsequent epithelial dysfunction by Staphylococcus enterotoxin B is attenuated by the green tea polyphenol (-)-epigallocatechin gallate. Cellular Immunology 2005, 237, (1), 7-16.
75.Hisano, M.; Yamaguchi, K.; Inoue, Y.; Ikeda, Y.; Iijima, M.; Adachi, M.; Shimamura, T., Inhibitory effect of catechin against the superantigen staphylococcal enterotoxin B (SEB). Arch Dermatol Res 2003, 295, (5), 183-9.
76.Friedman, M., Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas. Mol Nutr Food Res 2007, 51, (1), 116-34.
77.Galati, G.; Lin, A.; Sultan, A. M.; O''Brien, P. J., Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins. Free Radic Biol Med 2006, 40, (4), 570-80.
78.呂鋒洲。天然類胡蘿蔔素的保健功能。立德文化有限公司。2006。p 32
79.Linster, C. L.; Van Schaftingen, E., Vitamin C. Biosynthesis, recycling and degradation in mammals. Febs J 2007, 274, (1), 1-22.
80.Zaidi, S. M.; Al-Qirim, T. M.; Hoda, N.; Banu, N., Modulation of restraint stress induced oxidative changes in rats by antioxidant vitamins. J Nutr Biochem 2003, 14, (11), 633-6.
81.El-Demerdash, F. M.; Yousef, M. I.; Zoheir, M. A., Stannous chloride induces alterations in enzyme activities, lipid peroxidation and histopathology in male rabbit: Antioxidant role of vitamin C. Food Chem Toxicol 2005, 43, (12), 1743-1752.
82.Carcamo, J. M.; Pedraza, A.; Borquez-Ojeda, O.; Golde, D. W., Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation. Biochemistry 2002, 41, (43), 12995-3002.
83.Farris, P. K., Topical Vitamin C: A Useful Agent for Treating Photoaging and Other Dermatologic Conditions. Dermatol Surg 2005, 31, (7p2), 814-818.
84.Oplander, C.; Cortese, M. M.; Korth, H.-G.; Kirsch, M.; Mahotka, C.; Wetzel, W.; Pallua, N.; Suschek, C. V., The impact of nitrite and antioxidants on ultraviolet-A-induced cell death of human skin fibroblasts. Free Radical Bio Med 2007, 43, (5), 818-829.
85.Riordan, N. H.; Riordan, H. D.; Meng, X.; Li, Y.; Jackson, J. A., Intravenous ascorbate as a tumor cytotoxic chemotherapeutic agent. Med Hypotheses 1995, 44, (3), 207-213.
86.Yang, Y.-S.; Ahn, T.-H.; Lee, J.-C.; Moon, C.-J.; Kim, S.-H.; Jun, W.; Park, S.-C.; Kim, H.-C.; Kim, J.-C., Protective effects of Pycnogenol(R) on carbon tetrachloride-induced hepatotoxicity in Sprague-Dawley rats. Food Chem Toxicol 2007, In Press, Corrected Proof.
87.Sun, Y. X.; Zheng, Q. S.; Li, G.; Guo, D. A.; Wang, Z. R., Mechanism of ascorbic acid-induced reversion against malignant phenotype in human gastric cancer cells. Biomed Environ Sci 2006, 19, (5), 385-91.
88.Hamilton, K. L., Antioxidants and cardioprotection. Med Sci Sports Exerc 2007, 39, (9), 1544-53.
89.Bejjani, S.; Pullakhandam, R.; Punjal, R.; Nair, K. M., Gastric digestion of pea ferritin and modulation of its iron bioavailability by ascorbic and phytic acids in caco-2 cells. World J Gastroenterol 2007, 13, (14), 2083-8.
90.Kelly, K. A.; Havrilla, C. M.; Brady, T. C.; Abramo, K. H.; Levin, E. D., Oxidative stress in toxicology: established mammalian and emerging piscine model systems. Environ Health Perspect 1998, 106, (7), 375-84.
91.Spolarics, Z., Endotoxemia, pentose cycle, and the oxidant/antioxidant balance in the hepatic sinusoid. J Leukoc Biol 1998, 63, (5), 534-541.
92.Weber, L. W. D.; Boll, M.; Stampfl, A., Hepatotoxicity and Mechanism of Action of Haloalkanes: Carbon Tetrachloride as a Toxicological Model. Crit Rev Toxicol 2003, 33, (2), 105 - 136.
93.Cooper, R.; Morré, D. J.; Morré, D. M., Medicinal Benefits of Green Tea: Part I. Review of Noncancer Health Benefits. J Altern Complem Med 2005, 11, (3), 521-528.
94.Saller, R.; Meier, R.; Brignoli, R., The use of silymarin in the treatment of liver diseases. Drugs 2001, 61, (14), 2035-63.
95.Kuntz, E.; Kuntz, H. D., Alcohol-induced liver damage. In Hepatology: Principles and practice Springer: 2003.
96.Lin, J. M.; Lin, C. C.; Chiu, H. F.; Yang, J. J.; Lee, S. G., Evaluation of the anti-inflammatory and liver-protective effects of anoectochilus formosanus, ganoderma lucidum and gynostemma pentaphyllum in rats. Am J Chin Med 1993, 21, (1), 59-69.
97.張冠群。李伯鵬。劉付傳雄。朱莉芬。李美珠。鐘傳新。肝炎1號對大白鼠慢性肝損傷的作用。中草藥。 1996。27 (9)：549-551
98.Lin, S. C.; Lin, Y. H.; Chen, C. F.; Chung, C. Y.; Hsu, S. H., The hepatoprotective and therapeutic effects of propolis ethanol extract on chronic alcohol-induced liver injuries. Am J Chin Med 1997, 25, (3-4), 325-32.
99.Reitman, S.; Frankel, S., A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957, 28, (1), 56-63.
100.Ohkawa, H.; Ohishi, N.; Yagi, K., Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979, 95, (2), 351-8.
101.Lowry, O. H.; Rosebrough, N. J.; Farr, A. L.; Randall, R. J., Protein measurement with the Folin phenol reagent. J Biol Chem 1951, 193, (1), 265-75.
102.Reed, D. J.; Babson, J. R.; Beatty, P. W.; Brodie, A. E.; Ellis, W. W.; Potter, D. W., High-performance liquid chromatography analysis of nanomole levels of glutathione, glutathione disulfide, and related thiols and disulfides. Anal Biochem 1980, 106, (1), 55-62.
103.Lawrence, R. A.; Burk, R. F., Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 1976, 71, (4), 952-8.
104.Bellomo, G.; Mirabelli, F.; DiMonte, D.; Richelmi, P.; Thor, H.; Orrenius, C.; Orrenius, S., Formation and reduction of glutathione-protein mixed disulfides during oxidative stress. A study with isolated hepatocytes and menadione (2-methyl-1,4-naphthoquinone). Biochem Pharmacol 1987, 36, (8), 1313-20.
105.Habig, W. H.; Pabst, M. J.; Jakoby, W. B., Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974, 249, (22), 7130-9.
106.Aebi, H., Catalase in vitro. Methods Enzymol 1984, 105, 121-6.
107.Mazur, A.; Nassir, F.; Gueux, E.; Cardot, P.; Bellanger, J.; Lamand, M.; Rayssiguier, Y., The effect of dietary copper on rat plasma apolipoprotein B, E plasma levels, and apolipoprotein gene expression in liver and intestine. Biol Trace Elem Res 1992, 34, (2), 107-13.
108.Jonker, A. M.; Dijkhuis, F. W.; Boes, A.; Hardonk, M. J.; Grond, J., Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats. Hepatology 1992, 15, (3), 423-31.
109.Batts, K. P.; Ludwig, J., Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol 1995, 19, (12), 1409-17.
110.Burt, A. D.; Portmann, B. C.; Ferrell, L. D., Acute and chronic viral hepatitis. In MacSween''s Pathology of The Liver, 5th edition ed.; Churchill Livingstone: 2007; Vol. 8, pp 418-420.
111.Kus, I.; Ogeturk, M.; Oner, H.; Sahin, S.; Yekeler, H.; Sarsilmaz, M., Protective effects of melatonin against carbon tetrachloride-induced hepatotoxicity in rats: a light microscopic and biochemical study. Cell Biochem Funct 2005, 23, (3), 169-74.
112.Okumura, H.; Katoh, M.; Minami, K.; Nakajima, M.; Yokoi, T., Change of drug excretory pathway by CCl4-induced liver dysfunction in rat. Biochem Pharmacol 2007, 74, (3), 488-495.
113.Jeong, H. G., Inhibition of cytochrome P450 2E1 expression by oleanolic acid: hepatoprotective effects against carbon tetrachloride-induced hepatic injury. Toxicol Lett 1999, 105, (3), 215-22.
114.Rochling, F. A., Evaluation of abnormal liver tests. Clinical Cornerstone 2001, 3, (6), 1-12.
115.Baydas, G.; Yilmaz, O.; Celik, S.; Yasar, A.; Gursu, M. F., Effects of Certain Micronutrients and Melatonin on Plasma Lipid, Lipid Peroxidation, and Homocysteine Levels in Rats. Archives of Medical Research 2002, 33, (6), 515-519.
116.Ishii K.; Wang D.H.; Zhen L.X.; Satho M.; Taketa K., An Enhanced Liver Injury Induced by Carbon Tetrachloride in Acatalasemic Mice. In Liver and Environmental Xenobiotics, Rana S.V.S.; K., T., Eds. Narosa Publishing House: 1997; Vol. 4, pp 40-52.
117.Nishimura T.; Yoshida Y.; Watanabe F.; Koseki M.; Nishida T.; Tagawa K.; Kawashima Y., Blood level of mitochondrial aspartate aminotransferase as an indicator of the extent of ischemic necrosis of the rat liver. Hepatology 1986, 6, (4), 701-707.
118.Sugiyama, K.; He, P.; Wada, S.; Saeki, S., Teas and Other Beverages Suppress D-Galactosamine-Induced Liver Injury in Rats. J. Nutr. 1999, 129, (7), 1361-1367.
119.Deshpande U.R.; Gadre S.G.; Raste A.S.; Pillai D.; Bhide S.V.; A.M., S., Protective effect of turmeric (Curcuma longa L.) extract on carbon tetrachloride-induced liver damage in rats. Indian J Exp Bio 1998, 36, (6), 573-577.
120.Faroon, O.; Taylor, J.; Roney, N.; Fransen, M. E.; Bogaczyk, S.; Diamond, G., Toxilogical profile for carbon tetrachloride. In U.S. department of health and human services, Ed. Agency for Toxic Substances and Disease Registry: 2005; Vol. 10, p 361.
121.Baydas, G.; Yilmaz, O.; Celik, S.; Yasar, A.; Gursu, M. F., Effects of Certain Micronutrients and Melatonin on Plasma Lipid, Lipid Peroxidation, and Homocysteine Levels in Rats. Arch Med Res 2002, 33, (6), 515-519.
122.Kuo, K. L.; Weng, M. S.; Chiang, C. T.; Tsai, Y. J.; Lin-Shiau, S. Y.; Lin, J. K., Comparative studies on the hypolipidemic and growth suppressive effects of oolong, black, pu-erh, and green tea leaves in rats. J Agric Food Chem 2005, 53, (2), 480-9.
123.Rukkumani, R.; Aruna, K.; Varma, P. S.; Rajasekaran, K. N.; Menon, V. P., Comparative effects of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative stress. J Pharm Pharm Sci 2004, 7, (2), 274-83.
124.Szymonik-Lesiuk, S.; Czechowska, G.; Stryjecka-Zimmer, M.; Slomka, M.; Madro, A.; Celinski, K.; Wielosz, M., Catalase, superoxide dismutase, and glutathione peroxidase activities in various rat tissues after carbon tetrachloride intoxication. J Hepatobiliary Pancreat Surg 2003, 10, (4), 309-15.
125.Rana, S. V. S., Oxidative stress and liver injury by environmental xenobiotics. In Liver and Environmental Xenobiotics, Rana S.V.S.; K., T., Eds. Narosa Publishing House: 1997; Vol. 10, pp 114-134.
126.Crespy, V.; Williamson, G., A review of the health effects of green tea catechins in in vivo animal models. J Nutr 2004, 134, (12 Suppl), 3431S-3440S.
127.Natarajan, S. K.; Thomas, S.; Ramamoorthy, P.; Basivireddy, J.; Pulimood, A. B.; Ramachandran, A.; Balasubramanian, K. A., Oxidative stress in the development of liver cirrhosis: A comparison of two different experimental models. J Gastroen Hepatol 2006, 21, (6), 947-957.
128.Tilg, H.; Kaser, A.; Moschen, A. R., How to modulate inflammatory cytokines in liver diseases. Liver Inter 2006, 26, (9), 1029-1039.
129.Zhen, M.-c.; Wang, Q.; Huang, X.-h.; Cao, L.-q.; Chen, X.-l.; Sun, K.; Liu, Y.-j.; Li, W.; Zhang, L.-j., Green tea polyphenol epigallocatechin-3-gallate inhibits oxidative damage and preventive effects on carbon tetrachloride-induced hepatic fibrosis. J Nutr Biochem 2006, In Press, Corrected Proof.
130.Bruck, R.; Ashkenazi, M.; Weiss, S.; Goldiner, I.; Shapiro, H.; Aeed, H.; Genina, O.; Helpern, Z.; Pines, M., Prevention of liver cirrhosis in rats by curcumin. Liver Inter2007, 27, (3), 373-383.
131.Feng, Q.; Torii, Y.; Uchida, K.; Nakamura, Y.; Hara, Y.; Osawa, T., Black tea polyphenols, theaflavins, prevent cellular DNA damage by inhibiting oxidative stress and suppressing cytochrome P450 1A1 in cell cultures. J Agric Food Chem 2002, 50, (1), 213-20.
132.Yu, R.; Jiao, J. J.; Duh, J. L.; Gudehithlu, K.; Tan, T. H.; Kong, A. N., Activation of mitogen-activated protein kinases by green tea polyphenols: potential signaling pathways in the regulation of antioxidant-responsive element-mediated phase II enzyme gene expression. Carcinogenesis 1997, 18, (2), 451-456.
133.Feng, W. Y., Metabolism of green tea catechins: an overview. Curr Drug Metab 2006, 7, (7), 755-809.
134.Kojo, S., Vitamin C: basic metabolism and its function as an index of oxidative stress. Curr Med Chem 2004, 11, (8), 1041-64.
135.Wei, D. Z.; Yang, J. Y.; Liu, J. W.; Tong, W. Y., Inhibition of liver cancer cell proliferation and migration by a combination of (-)-epigallocatechin-3-gallate and ascorbic acid. J Chemother 2003, 15, (6), 591-5.
136.Intra, J.; Kuo, S.-M., Physiological levels of tea catechins increase cellular lipid antioxidant activity of vitamin C and vitamin E in human intestinal Caco-2 cells. Chemico-Biological Interactions 2007, 169, (2), 91-99.
137.Chang, R.; White, J. D., Asian therapies for cancer--coming of age. J Altern Complement Med 2002, 8, (5), 541-3.
138.Reddy, L.; Odhav, B.; Bhoola, K. D., Natural products for cancer prevention: a global perspective. Pharmacol Ther 2003, 99, (1), 1-13.
139.Yao, X.; Hu, J. F.; Daniels, M.; Yien, H.; Lu, H.; Sharan, H.; Zhou, X.; Zeng, Z.; Li, T.; Yang, Y.; Hoffman, A. R., A novel orthotopic tumor model to study growth factors and oncogenes in hepatocarcinogenesis. Clin Cancer Res 2003, 9, (7), 2719-26.
140.Ohno, N.; Furukawa, M.; Miura, N. N.; Adachi, Y.; Motoi, M.; Yadomae, T., Antitumor beta glucan from the cultured fruit body of Agaricus blazei. Biol Pharm Bull 2001, 24, (7), 820-8.
141.Mizuno, M.; Minato, K.; Ito, H.; Kawade, M.; Terai, H.; Tsuchida, H., Anti-tumor polysaccharide from the mycelium of liquid-cultured Agaricus blazei mill. Biochem Mol Biol Int 1999, 47, (4), 707-14.
142.Kawagishi, H.; Inagaki, R.; Kanao, T.; Mizuno, T.; Shimura, K.; Ito, H.; Hagiwara, T.; Nakamura, T., Fractionation and antitumor activity of the water-insoluble residue of Agaricus blazei fruiting bodies. Carbohydr Res 1989, 186, (2), 267-73.
143.Ker, Y. B.; Chen, K. C.; Chyau, C. C.; Chen, C. C.; Guo, J. H.; Hsieh, C. L.; Wang, H. E.; Peng, C. C.; Chang, C. H.; Peng, R. Y., Antioxidant capability of polysaccharides fractionated from submerge-cultured Agaricus blazei mycelia. J Agric Food Chem 2005, 53, (18), 7052-8.
144.Izawa, S.; Inoue, Y., A screening system for antioxidants using thioredoxin-deficient yeast: discovery of thermostable antioxidant activity from Agaricus blazei Murill. Appl Microbiol Biotechnol 2004, 64, (4), 537-42.
145.Mizuno, M.; Morimoto, M.; Minato, K.; Tsuchida, H., Polysaccharides from Agaricus blazei stimulate lymphocyte T-cell subsets in mice. Biosci Biotechnol Biochem 1998, 62, (3), 434-7.
146.Choi, Y. H.; Yan, G. H.; Chai, O. H.; Choi, Y. H.; Zhang, X.; Lim, J. M.; Kim, J. H.; Lee, M. S.; Han, E. H.; Kim, H. T.; Song, C. H., Inhibitory effects of Agaricus blazei on mast cell-mediated anaphylaxis-like reactions. Biol Pharm Bull 2006, 29, (7), 1366-71.
147.李門輝。癌的形成、生長、轉移及散播。癌的基礎科學。合記圖書出版社。1987。Vol. 8：pp 104-109
148.Surh, Y. J., Cancer Chemoprevention with Dietary Phytochemicals. Nat Rev Cancer 2003, 3, (10), 768-780.
149.童嬿臻。巴西洋菇(Agaricus blazei)發酵產物乙醇萃取物抑制人類肝癌細胞株生長與侵犯之研究。國立台灣大學。台北。2006
150.Weinberg, R. A., 細胞反叛. 天下文化: 2000; p 177.
151.Goyns, M. H., Cancer and you. Harwood academic publishers: 1999; p 159.
152.Murray, A.; Hunt, T., Basic Properties of the Cell Cycle. In the Cell Cycle: an introduction, Oxford University Press: 1993; Vol. 1, pp 3-12.
153.Malumbres, M.; Barbacid, M., Mammalian cyclin-dependent kinases. Trends Biochem Sci 2005, 30, (11), 630-41.
154.Heemels, M.-T., nature insight Apoptosis. Nature 2000, 407, (6805), 769.
155.Hengartner, M. O., The biochemistry of apoptosis. Nature 2000, 407, (6805), 770.
156.Oakes, S. A.; Lin, S. S.; Bassik, M. C., The control of endoplasmic reticulum-initiated apoptosis by the BCL-2 family of proteins. Curr Mol Med 2006, 6, (1), 99-109.
157.Hanahan, D.; Weinberg, R. A., The hallmarks of cancer. Cell 2000, 100, (1), 57-70.
158.Naik, T. U.; Naik, M. U.; Naik, U. P., Junctional adhesion molecules in angiogenesis. Front Biosci 2008, 13, 258-62.
159.Mj Duffy, P. M. M. W. M. G., Cancer invasion and metastasis: changing views. The Journal of Pathology 2007, 9999, (9999), n/a.
160.Farazi, P. A.; DePinho, R. A., Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006, 6, (9), 674-687.
161.Thorgeirsson, S. S.; Lee, J. S.; Grisham, J. W., Functional genomics of hepatocellular carcinoma. Hepatology 2006, 43, (2 Suppl 1), S145-50.
162.Lee, H. C.; Kim, M.; Wands, J. R., Wnt/Frizzled signaling in hepatocellular carcinoma. Front Biosci 2006, 11, 1901-15.
163.Lemmer, E. R.; Friedman, S. L.; Llovet, J. M., Molecular diagnosis of chronic liver disease and hepatocellular carcinoma: the potential of gene expression profiling. Semin Liver Dis 2006, 26, (4), 373-84.
164.Villanueva, A.; Newell, P.; Chiang, D. Y.; Friedman, S. L.; Llovet, J. M., Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis 2007, 27, (1), 55-76.
165.White, D. L.; Li, D.; Nurgalieva, Z.; El-Serag, H. B., Genetic Variants of Glutathione S-Transferase as Possible Risk Factors for Hepatocellular Carcinoma: A HuGE Systematic Review and Meta-Analysis. Am J Epidemiol 2007.
166.Cervello, M.; Montalto, G., Cyclooxygenases in hepatocellular carcinoma. World J Gastroenterol 2006, 12, (32), 5113-21.
167.Potočnik, U.; Glavač, M. R.; Golouh, R.; Glavač, D., The role of P-glycoprotein (MDRI) polymorphisms and mutations in colorectal cancer. Pflügers Archiv European Journal of Physiology 2001, 442, (7), 182-183.
168.Knowles, B. B.; Howe, C. C.; Aden, D. P., Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science 1980, 209, (4455), 497-9.
169.Bressac, B.; Galvin, K. M.; Liang, T. J.; Isselbacher, K. J.; Wands, J. R.; Ozturk, M., Abnormal structure and expression of p53 gene in human hepatocellular carcinoma. Proc Natl Acad Sci U S A 1990, 87, (5), 1973-7.
170.水野卓。川合正允。菇類的化學•生化學。國立編譯館。1997。Vol.V-48：p 248-255
171.Mizuno, T., Medicinal properties and clinical effects of culinary-medicinal mushroom Agaricus blazei murill (Agaricomycatideae) (Review). International Journal of Medicinal Mushroom 2002, 4, 299-312.
172.黃雅惠。巴西洋菇分子生物鑑定系統之研究。台灣大學。台北。1999
173.黃大斌。李開本。陳體強。姬松茸生物學特性研究初報。中國食用菌 1994。13：12
174.黃年來。巴西洋菇值得研究和推廣。中國食用菌 1994。13 (11)：3
175.Kimura, Y.; Kido, T.; Takaku, T.; Sumiyoshi, M.; Baba, K., Isolation of an anti-angiogenic substance from Agaricus blazei Murill: its antitumor and antimetastatic actions. Cancer Sci 2004, 95, (9), 758-64.
176.Kim, Y. W.; Kim, K. H.; Choi, H. J.; Lee, D. S., Anti-diabetic activity of beta-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei. Biotechnol Lett 2005, 27, (7), 483-7.
177.Mukai, H.; Watanabe, T.; Ando, M.; Katsumata, N., An Alternative Medicine, Agaricus blazei, May Have Induced Severe Hepatic Dysfunction in Cancer Patients. Jpn. J. Clin. Oncol. 2006, 36, (12), 808-810.
178.Barbisan, L. F.; Miyamoto, M.; Scolastici, C.; Salvadori, D. M.; Ribeiro, L. R.; Eira, A. F.; de Camargo, J. L., Influence of aqueous extract of Agaricus blazei on rat liver toxicity induced by different doses of diethylnitrosamine. J Ethnopharmacol 2002, 83, (1-2), 25-32.
179.Chen, L.; Shao, H. J.; Su, Y. B., Coimmunization of Agaricus blazei Murill extract with hepatitis B virus core protein through DNA vaccine enhances cellular and humoral immune responses. Int Immunopharmacol 2004, 4, (3), 403-9.
180.Hashimoto, T.; Nonaka, Y.; Minato, K.; Kawakami, S.; Mizuno, M.; Fukuda, I.; Kanazawa, K.; Ashida, H., Suppressive effect of polysaccharides from the edible and medicinal mushrooms, Lentinus edodes and Agaricus blazei, on the expression of cytochrome P450s in mice. Biosci Biotechnol Biochem 2002, 66, (7), 1610-4.
181.Jin, C. Y.; Choi, Y. H.; Moon, D. O.; Park, C.; Park, Y. M.; Jeong, S. C.; Heo, M. S.; Lee, T. H.; Lee, J. D.; Kim, G. Y., Induction of G2/M arrest and apoptosis in human gastric epithelial AGS cells by aqueous extract of Agaricus blazei. Oncol Rep 2006, 16, (6), 1349-55.
182.Jin, C. Y.; Moon, D. O.; Choi, Y. H.; Lee, J. D.; Kim, G. Y., Bcl-2 and caspase-3 are major regulators in Agaricus blazei-induced human leukemic U937 cell apoptosis through dephoshorylation of Akt. Biol Pharm Bull 2007, 30, (8), 1432-7.
183.Takimoto, H.; Wakita, D.; Kawaguchi, K.; Kumazawa, Y., Potentiation of cytotoxic activity in naive and tumor-bearing mice by oral administration of hot-water extracts from Agaricus brazei fruiting bodies. Biol Pharm Bull 2004, 27, (3), 404-6.
184.Ellertsen, L. K.; Hetland, G.; Johnson, E.; Grinde, B., Effect of a medicinal extract from Agaricus blazei Murill on gene expression in a human monocyte cell line as examined by microarrays and immuno assays. Int Immunopharmacol 2006, 6, (2), 133-43.
185.Bernardshaw, S.; Johnson, E.; Hetland, G., An extract of the mushroom Agaricus blazei Murill administered orally protects against systemic Streptococcus pneumoniae infection in mice. Scand J Immunol 2005, 62, (4), 393-8.
186.Kuroiwa, Y.; Nishikawa, A.; Imazawa, T.; Kanki, K.; Kitamura, Y.; Umemura, T.; Hirose, M., Lack of subchronic toxicity of an aqueous extract of Agaricus blazei Murrill in F344 rats. Food Chem Toxicol 2005, 43, (7), 1047-53.
187.Mecklenburg, L.; Nakamura, M.; Sundberg, J. P.; Paus, R., The nude mouse skin phenotype: the role of Foxn1 in hair follicle development and cycling. Exp Mol Pathol 2001, 71, (2), 171-8.
188.Kojima, A.; Matsuyama, M.; Shisa, H.; Zhang, M.; Hiai, H., Single dosage effects of the nude gene. In Immune-dificient animals in experimental medicine, Wu BQ, Z. J., Ed. Karger: 1989; pp 32-37.
189.Shultz, L. D., Single gene models of immunodeficiency diseases. In Immune-deficient animals in experimental medicine., Wu BQ, Z. J., Ed. Karger: 1989; pp 19-20.
190.Ye YL; Zhou XX; LG., W., Reproduction of nude mice and their application in experimental oncology. Laboratory animal science and management 2005, 22, (1), 6-8.
191.Fidler, I. J., Rationale and methods for the use of nude mice to study the biology and therapy of human cancer metastasis. Cancer Metastasis Rev 1986, 5, (1), 29-49.
192.Inoue, S.; Kubota, T.; Arisaya, Y.; Suto, A.; Kuzuoka, M.; Oka, S.; Ishibiki, K.; Abe, O., Comparative study of concentrations of antitumor agents in serum and tumor in nude mouse and human In Immune-deficient animals in experimental medicine., Wu BQ, Z. J., Ed. Karger: 1989; pp 323-325.
193.Kerrigan, R. W., Agaricus subrufescens, a cultivated edible and medicinal mushroom, and its synonyms. Mycologia 2005, 97, (1), 12-24.
194.Mosmann, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983, 65, (1-2), 55-63.
195.Longley, D. B.; Harkin, D. P.; Johnston, P. G., 5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 2003, 3, (5), 330-338.
196.Costi, M. P.; Ferrari, S.; Venturelli, A.; Calò, S.; Tondi, D.; Barlocco, D., Thymidylate Synthase Structure, Function and Implication in Drug Discovery. Current Medicinal Chemistry 2005, 12, (19), 2241-2258.
197.Wheatley, J. M.; Rosenfield, N. S.; Heller, G.; Feldstein, D.; LaQuaglia, M. P., Validation of a technique of computer-aided tumor volume determination. J Surg Res 1995, 59, (6), 621-6.
198.Tomayko, M. M.; Reynolds, C. P., Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol 1989, 24, (3), 148-54.
199.Mantel, N.; Haenszel, W., Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959, 22, (4), 719-48.
200.Friedman, S. L.; Shaulian, E.; Littlewood, T.; Resnitzky, D.; Oren, M., Resistance to p53-mediated growth arrest and apoptosis in Hep 3B hepatoma cells. Oncogene 1997, 15, (1), 63-70.
201.Mecklenburg, L.; Tychsen, B.; Paus, R., Learning from nudity: lessons from the nude phenotype. Exp Dermatol 2005, 14, (11), 797-810.
202.Balani, S. K.; Miwa, G. T.; Gan, L. S.; Wu, J. T.; Lee, F. W., Strategy of utilizing in vitro and in vivo ADME tools for lead optimization and drug candidate selection. Curr Top Med Chem 2005, 5, (11), 1033-8.
203.Xue, F.; Dong, C. Y.; Su, Y.; Zhu, H.; Ling, W.; Liu, Y.; Xu, H.; Xiao, W.; Zhou, S.; Qi, Y. P., Tumor-targeted therapy with a conditionally replicating mutant of HSV-1 induces regression of xenografted human hepatomas. Cancer Biol Ther 2005, 4, (11), 1234-9.
204.Park, R.; Chang, C. C.; Liang, Y. C.; Chung, Y.; Henry, R. A.; Lin, E.; Mold, D. E.; Huang, R. C., Systemic treatment with tetra-O-methyl nordihydroguaiaretic acid suppresses the growth of human xenograft tumors. Clin Cancer Res 2005, 11, (12), 4601-9.
205.Itoh, H.; Ito, H.; Amano, H.; Noda, H., Inhibitory action of a (1-->6)-beta-D-glucan-protein complex (F III-2-b) isolated from Agaricus blazei Murill ("himematsutake") on Meth A fibrosarcoma-bearing mice and its antitumor mechanism. Jpn J Pharmacol 1994, 66, (2), 265-71.
206.Barbisan, L. F.; Scolastici, C.; Miyamoto, M.; Salvadori, D. M.; Ribeiro, L. R.; da Eira, A. F.; de Camargo, J. L., Effects of crude extracts of Agaricus blazei on DNA damage and on rat liver carcinogenesis induced by diethylnitrosamine. Genet Mol Res 2003, 2, (3), 295-308.
207.陳宣瑜。巴西洋菇對人類白血病U937細胞生長抑制機制及對Balb/c鼠尾靜脈注射CT26細胞之腫瘤轉移抑制效果。台灣大學。台北。2004
208.Lee, Y. L.; Kim, H. J.; Lee, M. S.; Kim, J. M.; Han, J. S.; Hong, E. K.; Kwon, M. S.; Lee, M. J., Oral administration of Agaricus blazei (H1 strain) inhibited tumor growth in a sarcoma 180 inoculation model. Exp Anim 2003, 52, (5), 371-5.
209.Bernardshaw, S.; Hetland, G.; Grinde, B.; Johnson, E., An extract of the mushroom agaricus blazei Murill protects against lethal septicemia in a mouse model of fecal peritonitis. Shock 2006, 25, (4), 420-5.
210.楊俐穎。巴西楊菇水溶性多醣物之特徵。台灣大學。台北。2005
211.Lin, J. H.; Yang, S. S., Mycelium and polysaccharide production of Agaricus blazei Murrill by submerged fermentation. J Microbiol Immunol Infect 2006, 39, (2), 98-108.
212.Su, Z.; Hwang, L.; Kuo, Y.; Shu, C.; Sheen, L., Isolation and identification of active components with anti-hepatoma activity in the ethanolic extract of fermentation product of Agaricus blazei. In IUFOST 13th World Congress of Food Science and Technology, Nantes, France, 2006.
213.Hirotani, M.; Sai, K.; Hirotani, S.; Yoshikawa, T., Blazeispirols B, C, E and F, des-A-ergostane-type compounds, from the cultured mycelia of the fungus Agaricus blazei. Phytochemistry 2002, 59, (5), 571-7.