進階搜尋


下載電子全文  
系統識別號 U0026-3012201508335600
論文名稱(中文) 功能性食物芝麻成分對健康之影響:發炎與癌症
論文名稱(英文) Effects of functional food sesame seed ingredients on health: inflammation and cancer
校院名稱 成功大學
系所名稱(中) 環境醫學研究所
系所名稱(英) Institute of Environmental and Occupational Health
學年度 104
學期 1
出版年 104
研究生(中文) 朱珮儀
研究生(英文) Pei-Yi Chu
學號 S78961056
學位類別 博士
語文別 英文
論文頁數 133頁
口試委員 指導教授-劉明毅
口試委員-許德榮
口試委員-吳明娟
口試委員-王應然
口試委員-鄭宏祺
召集委員-許漢銘
中文關鍵字 芝麻子  芝麻酚  發炎  前發炎物質  巨噬細胞  核因子-kB  半胱氨酸  黑色素細胞瘤  細胞增生  老化  活化小眼症相關轉錄因子  硫化氫   
英文關鍵字 sesame seeds  sesamol  inflammation  pro-inflammatory mediator  macrophage  nuclear factor-kB  cysteine  melanoma  proliferation  senescence  microphthalmia-associated transcription factor  hydrogen sulfide  rodent 
學科別分類
中文摘要 芝麻,是人類長久以來食用的植物種子,富含油、木酯素與蛋白質氨基酸。其具有抗氧化、抗發炎的能力,也有助於癌症病人康復的潛能,被認為是重要的功能性食物,因此芝麻的功能性成分,可能有保護發炎引起的傷害及影響癌症發展的潛力。本研究目的(一)探討芝麻酚對發炎引起的傷害之影響;(二)探討半胱氨酸對黑色素細胞瘤的影響。第一部份:在以細菌酯多醣體誘導肺部發炎之傷害中,芝麻酚抑制其肺部傷害,降低發炎細胞浸潤、蛋白質、前發炎物質細胞壞死因子及一氧化氮之產生;芝麻酚對胰臟炎也透過降低胰臟傷害與發炎細胞浸潤有保護作用。芝麻酚對活化的巨噬細胞,具有抑制其前發炎物質細胞壞死因子、介白質、一氧化氮與誘導型一氧化氮合成酶之產生,並且明顯抑制轉錄因子核因子KB的活化。由此推測芝麻酚可透過抑制巨噬細胞轉錄因子核因子KB的活化,降低前發炎物質的產生,保護發炎引起的相關傷害。第二部分:半胱氨酸在不影響正常細胞的存活率的情況下,明顯抑制黑色素細胞瘤的生存;並會降低細胞增生、延遲細胞週期進行、增加細胞老化與老化相關蛋白p21與p53活化表現,抑制小眼症相關轉錄因子之活化;同時半胱氨酸之處理會造成細胞明顯縮小並聚集、維管聚解、細胞內鈣離子降低之現象,並顯著增加具有鈣離子通道抑制作用的半胱氨酸代謝物硫化氫表現;皮下注射半胱氨酸會明顯抑制小鼠黑色素細胞瘤的生長速度。因此,半胱氨酸可能透過小眼症相關轉錄因子之抑制與增加硫化氫的表現,抑制細胞增生、促進維管聚解、誘導細胞老化,而降低了老鼠黑色素細胞瘤之生長速度。總之,功能性食物芝麻所富含的芝麻酚與半胱氨酸,具有抗發炎與對抗癌症的作用,可能對發炎與癌症病人有益處,然而未來在臨床上的應用,仍需有更多相關的研究。
英文摘要 Sesame seed is an important crop used as food from ancient times. Sesame seeds are rich in oil, lignan, and protein/amino acid. It is reported that sesame seeds possess anti-oxidative and anti-inflammatory properties and are beneficial to recovery for cancer patients. The functional ingredients may protect against inflammation-induced organ injury and affect cancer development. Therefore, the aims of the study are to investigate the effects of sesamol on (1) lipopolysaccharide (LPS)-induced inflammatory lung injury and cerulein-induced acute pancreatitis in rats and (2) the effects of cysteine on melanoma growth. In the first part of the study, sesamol inhibited pulmonary inflammatory injury, reduced cell infiltration and protein leakage in bronchoalveolar lavage fluid (BALF), and decreased tumor necrosis factor (TNF)-a and nitric oxide production in both BALF and lung tissue in LPS-treated rats. Sesamol also reduced inflammation in pancreatitis rats. Furthermore, sesamol decreased pro-inflammatory mediators TNF-a, interleukin-1b, nitric oxide, and iNOS protein expressions and inhibited the nuclear factor (NF)-kB activation in LPS-activated macrophages. It is suggested that sesamol protects inflammatory injury by inhibiting macrophage pro-inflammatory mediator productions through blocking the NF-kB pathway, at least partially. In the second part of the present study, cysteine inhibited melanoma proliferation, delayed cell cycle progression, and induced melanoma senescence. Cysteine activated the p21–p53 pathway and inhibited microphthalmia-associated transcription factor (MiTF) activation. Cysteine changed the morphology and cytoskeleton structure, significantly decreased intracellular calcium levels, and increased hydrogen sulfide levels in melanoma. In addition, cysteine significantly decelerated the growing speed of melanoma tumor in mice. It is suggested that cysteine decelerates melanoma growth by regulating proliferation through inducing MiTF-p21-p53 pathway-related senescence and hydrogen sulfide-associated microtubule destabilization, at least partially. In summary, functional food sesame seeds-related ingredients sesamol and cysteine possess anti-inflammatory and anti-cancer properties which may be beneficial to inflammatory disease and cancer patients. However, more investigations will be needed.
論文目次 Abstract in Chinese………………………………..…………………………….…2
Abstract………………………………………………..……………………………3
Acknowledgement………………………………………………………………….5
Contents…………………………………………………………………………….6
Figure contents………………………………………………..……………………11
Abbreviation……………………………………………………..………………...13
Introduction……………….………………………………………..……………...15
Functional foods…………………………………………………………...…15
Ingredients in functional foods………………………………………………15
Sesame…………………………………………………………………...........16
Sesame seeds………………………………………………………………….16
Cultivation and usage of sesame seeds……………………………………...17
Function of sesame seeds on inflammation…………………………………17
Inflammation…………………………………………………………………18
Inflammatory mediators………………………………………………….…19
Regulation of inflammation…………………………………………………21
Animal model of inflammation………………………………………...……22
Role of sesame seeds on cancer…………………………………………...…22
Melanoma………………………………………………………………..…...23
Managing cancer: cell death and apoptosis ………………………………..23
Managing cancer: proliferation control and cell cycle………………….…24
Proliferation control: senescence……………………………………………25
MITF in melanoma…………………………………………………………..25
Cytoskeleton regulation in cancer ………………………………………….26
The aim of this study………………………………………………………...27
Material and methods……………………………………………………………..28
Materials……………………………………………………………………...28
Animals…………………………………………………………………….....28
RAW 264.7 cell line…………………………………………………………..29
B16F10 cell line…………………………………………………………….…29
Preparing peritoneal macrophages……………………………………….…29
Isolating monocytes……………………………………………………..……30
Experimental design………………………………………………………….30
Experiment 1. Effects of sesamol on acute lung inlfammation in LPS-treated rats…………………………………………………………….....30
Experiment 2. Effects of sesamol on acute pancreatitis in cerulein-treated rats ………………………………………………………………………….....31
Experiment 3. Effects of sesamol on pro-inflammatory mediator production in macrophages…………………………………………………...31
Experiment 4. Time-course of cysteine on melanoma viability ……..…31
Experiment 5. Dose response of cysteine on non-cancer cell viability... 32
Experiment 6. Combination effect of cisplatin or dacarbazine puls cysteine on melanoma viability……………………………………………….32
Experiment 7. Effect of cysteine on melanoma death…………………..32
Experiment 8. Effect of cysteine on regulation of proliferation on melanoma ………………………………………………………………….….32
Experiment 9. Effect of cysteine on cytoskeleton on melanoma……….32
Experiment 10. Role of cysteine-incorporated proteins in cysteine-exerted anti-melanoma effect………………………………………………………….33
Experiment 11. Effect of cysteine on melanoma tumor growth in vivo...33
Assessing pulmonary edema……………………………………………….....33
Histological examination……………………………………………………...33
Collecting BALF……………………………………………………………..34
Determining TNF- and IL-1 levels…………………………………...….34
Measuring nitrite concentrations…………………………………………...35
Blood biochemistry analysis………………………………………………....35
Assessing pancreatic edema……………………………………………........35
Assaying cell viability…………………………………………......................35
Cytotoxicity and apoptosis assay…………………………………................36
Cell count……………………………………………………………………...36
Proliferation assay………………………………………...............................36
Cell cycle analysis………………………………………................................36
Senescence-associated SA-β-galactosidase (β-Gal) staining……………….37
Detecting IB, NF-B, p21Cip1, p53, and MiTF expression ……………….37
Morphology…………………………………………………………………...38
Immunohistochemistry……………………………………………...............38
Calcium assay………………………………………………………………...38
Hydrogen sulfide assay………………………………………………............38
Statistical analysis…………………………………………………................39
Results………………………………………………………………….................40
Study I: The effects of sesamol on LPS-induced inflammatory lung injury……..40
Effects of sesamol on pulmonary injury in LPS-treated rats………………40
Effects of sesamol on the inflammatory indicators in BALF in LPS-treated rats……………………………………………………………………………..…...40
Effects of sesamol on lung inflammation in LPS-treated rats…………….40
Effects of sesamol on pancrease injury in cerulein-induced acute pancreatitis in rats………………………………………………………………...41
Effects of sesamol on histological changes in the rat pancreas in cerulein-induced acute pancreatitis…………………………………………........41
Effects of sesamol on regulation of pro-inflammatory mediators produce in activated macrophages……………………………………………………..……...41
Effects of sesamol on macrophage viability………………………………...42
Effect of sesamol on NF-B pathway in activated macrophages…….……42
Study II: The effects of amino acids on melanoma growth…………………….....42
Effects of amino acids on melanoma viability………………………………42
Time course study of the effect of cysteine on melanoma cell number……43
Effects of cysteine on non-cancer cells cytotoxicity………………………...43
Combination effects of cisplatin or dacarbazine puls cysteine on melanoma viability………………………………………………………………….................43
Effects of cysteine on melanoma cytotoxicity ……………………………...44
Effects of cysteine on cell proliferation and cell cycle progression in melanoma…………………………………………………………………............44
Effect of cysteine on melanoma senescence and p21-p53 pathway activation…………………………………………………………………......44
Effects of cysteine on MITF activation in melanoma……………………...45
Effects of cysteine on melanoma cytoskeleton……………………………...45
Effects of cysteine on intracellular calcium levels in melanoma…………..45
Role of cysteine-incorporated protein production on cysteine-exerted anti-melanoma effects……………………………………….................................46
Effects of cysteine on hydrogen sulphide levels in melanoma……………..46
Effects of cysteine on melanoma tumor growth in vivo…………………...46
Discussion………………………………………………………………….............47
Conclusions………………………………………………………………………...54
References………………………………………………………………….............55
Tables & Figures…………………………………………………………………..67
Publication list………………………………………………………………….....103
參考文獻 Abraham E. NF-kappaB activation. Crit Care Med 28:N100-N104, 2000.
Aigner T, Soeder S, Haag J. IL-1beta and BMPs-interactive players of cartilage matrix degradation and regeneration. Eur Cell Mater 12:49-56, 2006.
Astiz ME, Rackow EC. Septic shock. Lancet 351:1501-1505, 1998.
Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A Jr, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF. Final version of the American joint committee on cancer stage system for cutaneous melanoma. J Clin Oncol 19:3635- 4648, 2001.
Baldwin AS. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14: 649-683, 1996.
Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 357:539–545, 2001.
Balkwill F. Tumor necrosis factor or tumor promoting factor? Cytokine Growth Factor Rev 13:135–141, 2002.
Banerjee A, Kaul A, Bache E, Parberry A, Doran J, and Nicholson M. An audit of fatal acute pancreatitis. Postgrad Med J 71:472-475, 1995.
Barnard ND, Reilly JK. The Cancer Survivor's Guide. Book Publishing Company, 2010.
Bech-Larsen T, Grunert KG, Poulsen JB. The acceptance of functional foods in Denmark, Finland and the United States. A study of consumers’ conjoint evaluations of the qualities of functional food and perceptions of general health factors and cultural values. Working Paper No. 73. Aarhus, Denmark: MAPP. 2001.
Bedigian D. History and lore of sesame in Southwest Asia. Econ Bot 58:329-353, 2004.
Bellingan G. Inflammatory cell activation in sepsis. Br Med Bull 55:12-29, 1999.
Ben-Porath I, Weinberg RA. The signals and pathways activating cellular senescence. Int J Biochem Cell Biol 37:961-976,2005.
Bernardes de Jesus B, Blasco MA. Assessing cell and organ senescence biomarkers. Circ Res 111:97-109, 2012.
Bhakdi S, Walev I, Jonas D, Plamr M, Weller U, Suttorp N, Grimminger F, Seeger W. Pathogenesis of sepsis syndrome: possible relevance of pore-forming bacterial toxins. Curr Top Microbiol Immunol 216:101-118, 1996.
Blajeski AL, Phan VA, Kottke TJ, Kaufmann SH. G(1) and G(2) cell-cycle arrest following microtubule depolymerization in human breast cancer cells. J Clin Invest 110:91-99, 2002.
Bone RC. The pathogenesis of sepsis. Ann Intern Med 115:457-469, 1991.
Bone RC. Toward a theory regarding the pathogenesis of systemic inflammatory response syndrome: what we do and do not know about cytokine regulation. Crit Care Med 24:163-172, 1996.
Boone Lauri. Powerful Plant-Based Superfoods: The Best Way to Eat for Maximum Health, Energy, and Weight Loss. Fair Winds Press, 2013.
Bradley JR. TNF-mediated inflammatory disease. J Pathol 214:149-160, 2008.
Braude S, Nolop KB, Hughes JMB, Barnes PJ, Royston D. Comparison of lung vascular and epithelial permeability indices in the adult respiratory distress syndrome. Am Rev Respir Dis 133:1002-1005, 1986.
Brewster DH, Horner MJ, Rowan S, Jelfs P, de Vries E, Pukkala E. Left-sided excess of invasive cutaneous melanoma in six countries. Eur J Cancer 43:2634-2637, 2007.
Brouckaert P, Fiers W. Tumor necrosis factor and the systemic inflammatory response syndrome. Curr Top Microbiol Immunol 216:167-182, 1996.
Capiod T. Cell proliferation, calcium influx and calcium channels. Biochimie 93:2075-2079, 2011.
Carreira S, Goodall J, Denat L, Rodriguez M, Nuciforo P, Hoek KS, Testori A, Larue L, Goding CR. Mitf regulation of Dia1 controlsmelanoma proliferation and invasiveness. Genes Dev 20:3426-3439, 2006.
Cayabyab RG, Kwong K, Jones C, Minoo P, Durand M. Lung inflammation and pulmonary function in infants with meconium aspiration syndrome. Pediatr Pulmonol 42:898-905, 2007.
Chandra A, Enkhbaatar P, Nakano Y, Traber LD, Traber DL. Sepsis: emerging role of nitric oxide and selectins. Clinics (Sao Paulo) 61:71-76, 2006.
Charles AD. Blocking IL-1 in systemic inflammation. J Emerg Med 201:1355-1359, 2005.
Chen H, Cowan MJ, Hasday JD, Vogel SN, Medvedev AE. Tobacco smoking inhibits expression of proinflammatory cytokines and activation of IL-1R-associated kinase, p38, and NF-kappa B in alveolar macrophages stimulated with TLR2 and TLR4 agonists. J Immunol 179:6097-6106, 2007.
Chen PR, Chien KL, Su TC, Chang CJ, Liu TL, Cheng H, Tsai C. Dietary sesame reduces serum cholesterol and enhances antioxidant capacity in hypercholesterolemia. Nutr Res 25:559-567, 2005.
Chen YH, Leu SF, Jen CY, Huang BM. Effects of sesamol on apoptosis and steroidogenesis in MA-10 mouse Leydig tumor cells. J Agric Food Chem 59:9885-9891, 2011.
Chen YJ, Huang YC, Tsai TH, Liao HF. Effect of wasabi component 6-(methylsulfinyl)hexyl isothiocyanate and derivatives on human pancreatic cancer cells. Evid Based Complement Alternat Med 2014:494739, 2014.
Clark MA, Plank LD, Connolly AB, Streat SJ, Hill AA, Gupta R, Monk DN, Shenkin A, Hill GL. Effect of a chimeric antibody to tumor necrosis factor-a on cytokine and physiologic responses in patients with severe sepsis – a randomized, clinical trial. Crit Care Med 26:1650-1659, 1998.
Coussens LM, Werb Z. Inflammation and cancer. Nature 420:860-867, 2002.
Dabrowski A, Konturek SJ, Konturek JW, Gabryelewicz AG. Role of oxidative stress in the pathogenesis of caerulein-induced acute pancreatitis. Euro J Pharmacol 377:1-11, 1999.
Damas P, Reuter A, Gysen P, Demonty J, Lamy M, Franchimont P. Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans. Crit Care Med 17:975-978, 1989.
Danik M. Martirosyan (Ed): Functional Foods and Chronic Diseases: Science and Practice. Food Science Publisher; 2011.
de Cárcer G, Pérez de Castro I, Malumbres M. Targeting cell cycle kinases for cancer therapy. Curr Med Chem 14:969-985, 2007.
Deng P, Wang C, Chen L, Wang C, Du Y, Yan X, Chen M, Yang G, He G. Sesamin induces cell cycle arrest and apoptosis through the inhibition of signal transducer and activator of transcription 3 signalling in human hepatocellular carcinoma cell line HepG2. Biol Pharm Bull 36:1540-1548, 2013.
Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92:9363-9367, 1995.
Dinarello CA. Biological basis for interleukin-1 in disease. Blood 87:2095-2147, 1996.
Dinarello CA. Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed. J Endotoxin Res 10:201-222, 2004.
Dinarello CA. Why not treat human cancer with interleukin-1 blockade? Cancer Metastasis Rev 29:317-329, 2010.
Enomoto S, Glowczewski L, Berman J. MEC3, MEC1, and DDC2 are essential components of a telomere checkpoint pathway required for cell cycle arrest during senescence in Saccharomyces cerevisiae. Mol Biol Cell 13:2626-2638, 2002.
Enomoto S, Glowczewski L, Lew-Smith J, Berman JG. Telomere cap components influence the rate of senescence in telomerase-deficient yeast cells. Mol Cell Biol 24:837-845, 2004.
Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature 411:342-348, 2001.
Evans SK, Lundblad V. Est1 and Cdc13 as comediators of telomerase access. Science 286:117-120, 1999.
Ewald JA, Desotelle JA, Wilding G, Jarrard DF. Therapy-induced senescence in cancer. J Natl Cancer Inst 102:1536-1546, 2010.
Ewald JA, Desotelle JA, Wilding G, Jarrard DF. Therapy-induced senescence in cancer. J Natl Cancer Inst 102:1536-1546, 2010.
Farley KS, Wang LF, Razavi HM, Law C, Rohan M, McCormack DG, Mehta S. Effects of macrophage inducible nitric oxide synthase in murine septic lung injury. Am J Physiol Lung Cell Mol Physiol 290:L1164-L1172, 2006.
Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 14:397-440, 1996.
Fibbe WE, van Damme J, Billiau A, Voogt PJ, Duinkerken N, Kluck PM, Falkenburg JH. Interleukin-1 (22-K factor) induces release of granulocyte-macrophage colony-stimulating activity from human mononuclear phagocytes. Blood 68:1316-1321, 1986.
Fife CM, McCarroll JA, Kavallaris M. Movers and shakers: cell cytoskeleton in cancer metastasis. Br J Pharmacol 171:5507-5523, 2014.
Fisher CJ Jr, Agosti JM, Opal SM, Lowry SF, Balk RA, Sadoff JC, Abraham E, Schein RM, Benjamin E. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. N Engl J Med 334:1697-1702, 1996.
Förstermann U, Closs EI, Pollock JS, Nakane M, Schwarz P, Gath I, Kleinert H. Nitric oxide synthase isozymes: characterization, purification, molecular cloning, and functions. Hypertension 23:1121–1131, 1994.
Fuentes L, Roszer T, Ricote M. Inflammatory mediators and insulin resistance in obesity: role of nuclear receptor signaling in macrophages. Mediators Inflamm 2010:219583, 2010.
Fujii Y, Goldberg P, Hussain SN. Contribution of macrophages to pulmonary nitric oxide production in septic shock. Am J Respir Crit Care Med 157:1645-1651, 1998.
Fukuda Y, Osawa T, Namiki M, and Ozaki T. Studies on antioxidative substances in sesame seed. Agric Biol Chem 49:301-306, 1985.
Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, Beroukhim R, Milner DA, Granter SR, Du J, Lee C, Wagner SN, Li C, Golub TR, Rimm DL, Meyerson ML, Fisher DE, Sellers WR. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436:117-122, 2005.
Gaskin F, Cantor CR, Shelanski ML. Biochemical studies on the in vitro assembly and disassembly of microtubules. Ann N Y Acad Sci 253:133-146, 1975.
Giuliano S, Cheli Y, Ohanna M, Bonet C, Beuret L, Bille K, Loubat A, Hofman V, Hofman P, Ponzio G, Bahadoran P, Ballotti R, Bertolotto C. Microphthalmia-associated transcription factor controls the DNA damage response and a lineage-specific senescence program in melanomas. Cancer Res 70:3813-3822.
Gorelick F, Pandol S, Thrower E. Protein kinase C in the pancreatic acinar cell. J Gastroenterol Hepatol 3:S37-S41, 2008.
Ha L, Ichikawa T, Anver M, Dickins R, Lowe S, Sharpless NE, Krimpenfort P, Depinho RA, Bennett DC, Sviderskaya EV, Merlino G. ARF functions as a melanoma tumor suppressor by inducing p53-independent senescence. Proc Natl Acad Sci U S A 104:10968-10973, 2007.
Håkansson HF, Smailagic A, Brunmark C, Miller-Larsson A, Lal H. Altered lung function relates to inflammation in an acute LPS mouse model. Pulm Pharmacol Ther 25:399-406, 2012.
Hakkak R, Korourian S, Shelnutt SR, Lensing S, Ronis MJ, Badger TM. Diets containing whey proteins or soy protein isolate protect against 7,12-dimethylbenz(a)anthracene-induced mammary tumors in female rats. Cancer Epidemiol Biomarkers Prev 9:113-117, 2000.
Hawkes WC, Alkan Z. Regulation of redox signaling by selenoproteins. Biological Trace Element Research 134:235-251, 2010.
Hayden MS and Ghosh S. Signaling to NF-kappa B. Gene Dev 18: 2195-2224, 2004.
Hirata F, Fujita K, Ishikura Y, Hosoda K, Ishikawa T, Nakamura H. Hypocholesterolemic effect of sesame lignan in humans. Atherosclerosis 122:135-136, 1996.
Hoac T, Lundh T, Purup S, Onning G, Sejrsen K, Akesson B. Separation of selenium, zinc, and copper compounds in bovine whey using size exclusion chromatography linked to inductively coupled plasma mass spectrometry. Journal of Agricultural and Food Chemistry 55:4237-4243, 2007.
Hori T, Nakashima T, Take S, Kaizuka Y, Mori T, Katafuchi T. Immune cytokines and regulation of body temperature, food intake and cellular immunity. Brain Res Bull 27:309-313, 1991.
Hornef MW, Wick MJ, Rhen M, Normark S. Bacterial strategies for overcoming host innate and adaptive immune responses. Nat Immunol 3:1033-1040, 2002.
Hsu DZ, Chen KT, Chu PY, Li YH, Liu MY. Sesame oil protects against lead-plus-lipopolysaccharide-induced acute hepatic injury. Shock 27:334-337, 2007.
Hsu DZ, Chen KT, Li YH, Chuang YC, Liu MY. Sesamol delays mortality and attenuates hepatic injury after cecal ligation and puncture in rats: role of oxidative stress. Shock 25:528-532, 2006.
Hsu DZ, Chu PY, Liu MY. Effect of sesame oil on acidified ethanol-induced gastric mucosal injury in rats. JPEN J Parenter Enteral Nutr 33:423-427, 2009a.
Hsu DZ, Chu PY, Liu MY. Sesame seed (Sesamum indicum L.) extracts and their anti-Inflammatory effect. Emerging Trends in Dietary Components for Preventing and Combating Disease. Chapter 19, pp 335–341. American Chemical Society, 2012.
Hsu DZ, Chu PY, Liu MY. The non-peptide chemical 3,4-methylenedioxyphenol blocked lipopolysaccharide (LPS) from binding to LPS-binding protein and inhibited pro-inflammatory cytokines. Innate Immun 15:380-385, 2009b.
Hsu DZ, Su SB, Chien SP, Chiang PJ, Li YH, Lo YJ, Liu MY. Effect of sesame oil on oxidative-stress-associated renal injury in endotoxemic rats: involvement of nitric oxide and proinflammatory cytokines. Shock 24:276-280, 2005.
Ihling C, Menzel G, Wellens E, Mönting JS, Schaefer HE, Zeiher AM. Topographical association between the cyclin-dependent kinases inhibitor P21, p53 accumulation, and cellular proliferation in human atherosclerotic tissue. Arterioscler Thromb Vasc Biol 17:2218-2224, 1997.
Ikeda S, Tohyama T, Yamashita K. Dietary sesame seed and its lignans inhibit 2,7,8-trimethyl-2(2′-carboxyethyl)-6-hydroxychroman excretion into urine of rats fed gamma-tocopherol. J Nutr 132: 961-966, 2002.
Itahana K, Itahana Y, Dimri GP. Colorimetric detection of senescence-associated β galactosidase. Methods Mol Biol 965:143-156, 2013.
Janeway C, Travers P, Walport M, Shlomchik M. Immunobiology, pp. 41-43. Garland Science., New York, 2001.
Jinbo T, Sakamoto T, Yamamoto S. Serum alpha2-macroglobin and cytokine measurements in an acute inflammation model in rats. Lab Anim 36:153-157, 2002.
Jung YJ, Isaacs JS, Lee S, Trepel J, Neckers L. IL-1beta –mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway indentifies HIF-1as a critical link between inflammation and oncogenesis. FASEB J 17:2115-2117, 2003.
Jurkowska H, Uchacz T, Roberts J, Wróbel M. Potential therapeutic advantage of ribose-cysteine in the inhibition of astrocytoma cell proliferation. Amino Acids 41:131-139, 2011.
Karin M and Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-kappa B activity. Annu Rev Immunol 18: 621-663, 2000.
Karin M, Cao Y, Greten FR, Li ZW. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2:301-310, 2002.
Karne S, Gorelick F. Etiopathogenesis of acute pancreatitis. Surg Clin North Am 79:699-710, 1999.
Kasibhatla S, Tseng B. Why target apoptosis in cancer treatment? Mol Cancer Ther 2:573-580, 2003.
Kido K, Sumimoto H, Asada S, Okada SM, Yaguchi T, Kawamura N, Miyagishi M, Saida T, Kawakami Y. Simultaneous suppression of MITF and BRAF V600E enhanced inhibition of melanoma cell proliferation. Cancer Sci 100:1863-1869, 2009.
Kim JH, Lee JK. Sesamolin enhances NK cell lysis activity by increasing the expression of NKG2D ligands on Burkitt's lymphoma cells. Int Immunopharmacol 28:977-984, 2015.
Kohlmeier M. Nutrient metabolism. London: Academic Press. Chapter 8, 2003.
Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev 24:2463-2479, 2010.
Kullowatz A, Rosenfield D, Dahme B, Magnussen H, Kanniess F, Ritz T. Stress effects on lung function in asthma are mediated by changes in airway inflammation. Psychosom Med 70:468-475, 2008.
Kwan ML, Weltzien E, Kushi LH, Castillo A, Slattery ML, Caan BJ. Dietary patterns and breast cancer recurrence and survival among women with early-stage breast cancer. J Clin Oncol 27:919-926, 2009.
Lander HM, Sehajpal P, Levine DM, Novogrodsky A. Activation of human peripheral blood mononuclear cells by nitric oxide-generating compounds. J Immunol 150:1509-1516, 1993.
Lasekan O. Exotic berries as a functional food. Curr Opin Clin Nutr Metab Care 17:589-595, 2014.
Lau Benjamin. Stop Cancer with Phytotherapy. WestBow Press, 2014.
Lawrence T. The Nuclear Factor NF-κB Pathway in Inflammation. Cold Spring Harb Perspect Biol 1:a001651, 2009.
Ledda A, Bottari A, Luzzi R, Belcaro G, Hu S, Dugall M, Hosoi M, Ippolito E, Corsi M, Gizzi G, Morazzoni P, Riva A, Giacomelli L, Togni S. Cranberry supplementation in the prevention of non-severe lower urinary tract infections: a pilot study. Eur Rev Med Pharmacol Sci 19:77-80, 2015.
Lerch MM, Saluja AK, Dawra R, Ramarao P, Saluja M, Steer ML. Acute necrotizing pancreatitis in the opossum: earliest morphological changes involve acinar cells. Gastroenterology 1:205-213, 1992.
Leung PS, Ip SP. Pancreatic acinar cell: its role in acute pancreatitis. Int J Biochem Cell Biol 38:1024-1030, 2006.
Levy C, Khaled M, Fisher DE. MITF: master regulator of melanocyte development and melanoma oncogene. Trends Mol Med 12:406-414, 2006.
Lin WJ, Yeh WC. Implication of toll-like receptor and tumor necrosis factor alpha signaling in septic shock. Shock 24:206-209, 2005.
Lin WJ, Yeh WC. Implication of toll-like receptor and tumor necrosis factor a signaling in septic shock. Shock 24:206-209, 2005.
Lirk P, Hoffmann G, Rieder J. Inducible nitric oxide synthase--time for reappraisal. Curr Drug Targets Inflamm Allergy. 1:89-108, 2002.
Liu SF, Malik AB. NF-kB activation as a pathological mechanism of septic shock and inflammation. Am J Physoiol Lung Cell Mol Physiol 290: 622-645, 2006.
Lopez-Bojorquez LN, Dehesa AZ, Reyes-Teran G. Molecular mechanisms involved in the pathogenesis of septic shock. Arch Med Res 35:465-479, 2004.
Luo C, Merz PR, Chen Y, Dickes E, Pscherer A, Schadendorf D, Eichmüller SB. MiR-101 inhibits melanoma cell invasion and proliferation by targeting MITF and EZH2. Cancer Lett 341:240-247, 2013.
Machado A, Herrera AJ, Venero JL, Santiago M, de Pablos RM, Villarán RF, Espinosa-Oliva AM, Argüelles S, Sarmiento M, Delgado-Cortés MJ, Mauriño R, Cano J. Inflammatory Animal Model for Parkinson's Disease: The Intranigral Injection of LPS Induced the Inflammatory Process along with the Selective Degeneration of Nigrostriatal Dopaminergic Neurons. ISRN Neurol 2011:476158, 2011.
MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Ann Rev Immunol 15:323-350, 1997.
Maitra SR, Wojnar MM, Lang CH. Alterations in tissue glucose uptake during the hyperglycemic and hypoglycemic phases of sepsis. Shock 13:379-385, 2000.
Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem Sci 30:630–641, 2005.
Mann D, Hershman M, Hittinger R, Glazer G. Multicentre audit of death from acute pancreatitis. Br J Surg 81:890-893, 1994.
Marcinkiewicz J, Grabowska A, Chain B. Nitric oxide up-regulates the release of inflammatory mediators by mouse macrophages. Eur J Immunol 25:947-951, 1995.
Marshall K. Therapeutic applications of whey. Altern Med Rev 9:136-156, 2004.
Martinez-Taboada VM, Alvarez L, RuizSoto M, Marin-Vidalled MJ, Lopez-Hoyos M. Giant cell arteritis and polymyalgia rheumatica: role of cytokines in the pathogenesis and implications for treatment. Cytokine 44:207-220, 2008.
Matthay MA, Zimmerman GA. Acute lung injury and the acute respiratory distress syndrome: four decades of inquiry into pathogenesis and rational management. Am J Respir Cell Mol Biol 33:319-327, 2005.
McPherson RA, Hardy G. Clinical and nutritional benefits of cysteine-enriched protein supplements. Curr Opin Clin Nutr Metab Care 14:562-568, 2011.
Michel T, Feron O. Nitric oxide synthases: which, where, how, and why? J Clin Invest. 100:2146-2152, 1997.
Moazzami AA, Haese SL, Kamal-Eldin A. Lignan contents in sesame seeds and products. Eur J Lipid Sci Technol 109:1022-1027, 2007.
Moncada S, Palmer RM, Higgs DA. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43:109-42, 1992.
Mukhopadhyay S, Hoidal JR, Mukherjee TK. Role of TNF alpha in pulmonary pathophysiology. Respir Res 7:125, 2006.
Munaron L, Avanzato D, Moccia F, Mancardi D. Hydrogen sulfide as a regulator of calcium channels. Cell Calcium 53:77-84, 2013.
Murphy G, Fan JH, Mark SD, Dawsey SM, Selhub J, Wang J, Taylor PR, Qiao YL, Abnet CC. Prospective study of serum cysteine levels and oesophageal and gastric cancers in China. Gut 60:618-623, 2011.
Murray MJ. Sepsis: clinical dilemmas. Yale J Bio Med 71:485-491, 1998.
Murray MJ. Sepsis: clinical dilemmas. Yale J Biol Med 71:485-491, 1998.
Ngkelo A, Meja K, Yeadon M, Adcock I, Kirkham PA. LPS induced inflammatory responses in human peripheral blood mononuclear cells is mediated through NOX4 and Giα dependent PI-3kinase signalling. J Inflamm (Lond) 9:1, 2012.
Niculescu AB 3rd, Chen X, Smeets M, Hengst L, Prives C, Reed SI. Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication. Mol Cell Biol 18:629-643, 1998.
Ninomiya Y, Cui X, Yasuda T, Wang B, Yu D, Sekine-Suzuki E, Nenoi M. Arsenite induces premature senescence via p53/p21 pathway as a result of DNA damage in human malignant glioblastoma cells. BMB Rep 47:575-580, 2014.
Nishida E, Sakai H. Calcium-sensitivity of the microtubule reassembly system. J Biochem (Tokyo) 82:303-306, 1977.
Old JL. Tumor necrosis factor (TNF). Science 230: 630-632, 1985.
Olmsted JB, Borisy GG. Ionic and nucleotide requirements for microtubule polymerization in vitro. Biochemistry 14:2996- 3005, 1975.
Onsaard E. Sesame Proteins. Int Food Res J 19:1287-1295, 2012.
Opal SM, Fisher CJ Jr, Dhainaut JF, Vincent JL, Brase R, Lowry SF, Sadoff JC, Slotman GJ, Levy H, Balk RA, Shelly MP, Pribble JP, LaBrecque JF, Lookabaugh J, Donovan H, Dubin H, Baughman R, Norman J, DeMaria E, Matzel K, Abraham E, Seneff M. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Crit Care Med 25:1115-1124, 1997.
Orth JD, Loewer A, Lahav G, Mitchison TJ. Prolonged mitotic arrest triggers partial activation of apoptosis, resulting in DNA damage and p53 induction. Mol Biol Cell 23:567-576, 2012.
Oz HS, Chen TS, Neuman M. Nutrition intervention: A strategy against systemic inflammatory syndrome. JPEN J Parenter Enteral Nutr 33:380-389, 2009.
Parihar VK, Prabhakar KR, Veerapur VP, Kumar MS, Reddy YR, Joshi R, Unnikrishnan MK, Rao CM. Effect of sesamol on radiation-induced cytotoxicity in Swiss albino mice. Mutat Res 611:9-16, 2006.
Pierrat MJ, Marsaud V, Mauviel A, Javelaud D. Expression of microphthalmia-associated transcription factor (MITF), which is critical for melanoma progression, is inhibited by both transcription factor GLI2 and transforming growth factor-β. J Biol Chem 287:17996-8004, 2012.
Prasad NR, Menon VP, Vasudev V, Pugalendi KV. Radioprotective effect of sesamol on gamma-radiation induced DNA damage, lipid peroxidation and antioxidants levels in cultured human lymphocytes. Toxicology 209:225-235, 2005.
Qian Y, Chen X. Tumor suppression by p53: making cells senescent. Histol Histopathol 25:515-526, 2010.
Rayburn ER, Ezell SJ, Zhang R. Anti-Inflammatory agents for cancer therapy. Mol Cell Pharmacol 1:29–43, 2009.
Rodier F, Campisi J. Four faces of cellular senescence. J Cell Biol 192:547-556, 2011.
Ryu K, Park C, Lee Y. Hypoxia-inducible factor 1 alpha represses the transcription of the estrogen receptor alpha gene in human breast cancer cells. Biochem Biophys Res Commun 407:831-836, 2011.
Sabroe I, Jones EC, Usher LR, Whyte MK, Dower SK. Toll-like receptor (TLR)2 and TLR4 in human peripheral blood granulocytes: a critical role for monocytes in leukocyte lipopolysaccharide responses. J Immunol 168:4701-4710, 2002.
Samarakoon KW, Ko J, Lee J, Kwon O, Kim S, Jeon Y. Apoptotic anticancer activity of a novel fatty alcohol ester isolated from cultured marine diatom, Phaeodactylum tricornutum. J Funct Foods 6:231-240, 2014.
Schulz HU, Niederau C, Klonowski-Stumpe H, Halangk W, Luthen R, and Lippert H. Oxidative stress in acute pancreatitis. Hepatogastroenterology 46:2736-2750, 1999.
Schwartz MA, McRoberts K, Coyner M, Andarawewa KL, Frierson HF Jr, Sanders JM, Swenson S, Markland F, Conaway MR, Theodorescu D. Integrin agonists as adjuvants in chemotherapy for melanoma. Clin Cancer Res 14:6193-6197, 2008.
Schwartzentruber DJ. Guidelines for the safe administration of high-dose interleukin-2. J Immunother 24:287-293, 2001.
Seo JY, Masamune A, Shimosegawa T, Kim H. Protective effect of lycopene on oxidative stressinduced cell death of pancreatic acinar cells. Ann N Y Acad Sci 1171:570-575, 2009.
Sewerynek E, Melchiorri D, Reiter RJ, Ortiz GG, Lewinski A. Lipopolysaccharide-induced hepatotoxicity is inhibited by the antioxidant melatonin. Eur J Pharmacol 293:327-334, 1995.
Shembade N, Harhaj NS, Liebl DJ, Harhaj EW. Essential role for TAX1BP1 in the termination of TNF-alpha-, IL-1- and LPSmediated NF-kappaB and JNK signaling. EMBO J 26:3910-3922, 2007.
Shen HN, Lu CL. Incidence, resource use, and outcome of acute pancreatitis with/without intensive care. A nationwide population-based study in Taiwan. Pancreas 40:10-15, 2011.
Shen XH, Xu SJ, Jin CY, Ding F, Zhou YC, Fu GS. Interleukin-8 prevents oxidative stress-induced human endothelial cell senescence via telomerase activation. Int Immunopharmacol 16:261-267, 2013.
Shibuya N, Koike S, Tanaka M, Ishigami-Yuasa M, Kimura Y, Ogasawara Y, Fukui K, Nagahara N, Kimura H. A novel pathway for the production of hydrogen sulfide from D-cysteine in mammalian cells. Nat Commun 4:1366, 2013.
Siao AC, Hou CW, Kao YH, Jeng KC. Effect of sesamin on apoptosis and cell cycle arrest in human breast cancer mcf-7 cells. Asian Pac J Cancer Prev 16:3779-3783, 2015.
Sinclair DG, Braude S, Haslam PL, Evans TW. Pulmonary endothelial permeability in patients with severe lung injury. Clinical correlates and natural history. Chest 106:535-539, 1994.
Skrovankova S, Sumczynski D, Mlcek J, Jurikova T, Sochor J. Bioactive Compounds and Antioxidant Activity in Different Types of Berries. Int J Mol Sci 16:24673-24706, 2015.
Sriskandan S, Evans TJ, Cohen J. Bacterial superantigen-induced human lymphocyte responses are nitric oxide dependent and mediated by IL-12 and INF-g. J Immunol 156:2430-2435, 1996.
Strub T, Giuliano S, Ye T, Bonet C, Keime C, Kobi D, Le Gras S, Cormont M, Ballotti R, Bertolotto C, Davidson I. Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma. Oncogene 30:2319-2332, 2011.
Su CF, Yang FL, Chen HI. Inhibition of inducible nitric oxide synthase attenuates acute endotoxin-induced lung injury in rats. Clin Exp Pharmacol Physiol 34:339-346, 2007.
TakacsT, FarkasGJr,Czako L, Jarmay K,Mandi Y, and Lonovics J. Time-course changes in serum cytokine levels in two experimental acute pancreatitismodels in rats. Res Exp Med 196:153-161, 1996.
Takeuchi S, Takahashi A, Motoi N, Yoshimoto S, Tajima T, Yamakoshi K, Hirao A, Yanagi S, Fukami K, Ishikawa Y, Sone S, Hara E, Ohtani N. Intrinsic cooperation between p16INK4a and p21Waf1/Cip1 in the onset of cellular senescence and tumor suppression in vivo. Cancer Res 70:9381-9390, 2010.
Tavaf-Motamen H, Miner TJ, Starnes BW, Shea-Donohue T. Nitric oxide mediates acute lung injury by modulation of inflammation. J Surg Res 78:137-142, 1998.
Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 267:1456-1462, 1995.
Togbe D, Schnyder-Candrian S, Schnyder B, Doz E, Noulin N, Janot L, Secher T, Gasse P, Lima C, Coelho FR, Vasseur V, Erard F, Ryffel B, Couillin I, Moser R. Toll-like receptor and tumour necrosis factor dependent endotoxininduced acute lung injury. Int J Exp Pathol 88:387-391, 2007.
Tomashefski J. Pulmonary pathology of the adult respiratory distress syndrome. Clin Chest Med 11:593-619, 1990.
Tracey KJ, Cerami A. Metabolic responses to cachetin/TNF-a. Ann NY Acad Sci 587: 325-331, 1990.
Treon SP, Anand B, Ulevitch RJ, Broitman SA. CD14 mediated endogenous TNF-alpha release in HL60 AML cells: a potential model for CD14 mediated endogenous cytokine release in the treatment of AML. Leukoc Res 18:17-21, 1994.
Vergel M, Marin JJ, Estevez P, Carnero A. Cellular senescence as a target in cancer control. J Aging Res 2011:725365, 2010.
Vermeulen K, Van Bockstaele DR, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif 36:131-149, 2003.
Vonlaufen A, Apte MV, Imhof BA, Frossard JL. The role of inflammatory and parenchymal cells in acute pancreatitis. J Pathol 213:239-248, 2007.
Weisenberg RC. Microtubule formation in vitro in solutions containing low calcium concentrations. Science 177:1104-1105, 1972.
World Health Organization, Solar ultraviolet radiation: Global burden of disease from solar ultraviolet radiation. Environmental Burden of Disease Series, N.13. 2006.
World Health Organization. GLOBOCAN: Cancer Incidence, Mortality and Prevalence Worldwide, IARC Cancerbase No. 5, Version 1.0. Lyon: IARC. 2001.
Xu W, Liu LZ, Loizidou M, Ahmed M, Charles IG. The role of nitric oxide in cancer. Cell Res 12:311-320, 2002.
Yoshiura K, Nishishita T, Nakaoka T, Yamashita N, Yamashita N. Inhibition of B16 melanoma growth and metastasis in C57BL mice by vaccination with a syngeneic endothelial cell line. J Exp Clin Cancer Res 28:13, 2009.
Young D, Fan MZ, Mine Y. Egg yolk peptides up-regulate glutathione synthesis and antioxidant enzyme activities in a porcine model of intestinal oxidative stress. J Agric Food Chem 58:7624-7633, 2010.
Zalaudek I, Ferrara G, Argenziano G, Ruocco V, Soyer HP. Diagnosis and treatment of cutaneous melanoma: a practical guide. Skinmed 2:20-31, 2003.
Zhou L, Somasundaram R, Nederhof RF, Dijkstra G, Faber KN, Peppelenbosch MP, Fuhler GM. Impact of human granulocyte and monocyte isolation procedures on functional studies. Clin Vaccine Immunol 19:1065-1074, 2012.
Zimmermann KC, Bonzon C, Green DR. The machinery of programmed cell death. Pharmacol Ther 92:57-70, 2001.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2016-12-31起公開。
  • 同意授權校外瀏覽/列印電子全文服務,於2016-12-31起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw