跳到主要內容

臺灣博碩士論文加值系統

(216.73.216.73) 您好!臺灣時間:2026/06/14 12:39
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:李怡琛
研究生(外文):Yi-Chen Lee
論文名稱:脂肪細胞激素在乳癌中之角色
論文名稱(外文):The role of adipocytokines in breast cancer
指導教授:侯明鋒侯明鋒引用關係
指導教授(外文):Ming-Feng Hou
學位類別:博士
校院名稱:高雄醫學大學
系所名稱:醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:英文
論文頁數:92
中文關鍵詞:乳癌脂肪細胞激素
外文關鍵詞:Breast cancerAdipocytokines
相關次數:
  • 被引用被引用:0
  • 點閱點閱:149
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
乳癌是全世界婦女最常見的惡性腫瘤,其患病率正以一個令人驚訝的速度快速地增加,從以往的研究清楚地發現,肥胖與乳癌發生的風險和預後有關。脂肪細胞激素是一群由脂肪細胞所分泌的賀爾蒙且已被證實與許多的腫瘤發生有關。本實驗即在探討visfatin和resistin這兩種新發現的脂肪細胞激素在乳癌病患當中的表現情形並研究其與病人的臨床病理病徵之相關性。
從實驗結果發現,visfatin和resistin的表現主要是在乳癌組織中,與其相鄰的正常乳腺組織則無明顯地觀察到visfatin和resistin的表現。另外在乳癌患者其血清中之visfatin和resistin偵測值亦較正常女性血清內之visfatin和resistin偵測值有顯著增加。Visfatin在乳癌病患中與腫瘤大小、陰性雌激素受體和陰性助孕激素受體有著顯著相關性。Resistin在乳癌病患中則與腫瘤分期、腫瘤大小、淋巴結轉移及陽性雌激素受體有著顯著相關性。在乳癌病患表現高visfatin和resistin的群體中,假如其有接受賀爾蒙的治療則會減少其復發的機會,但在乳癌病患接受放射治療或化學藥物治療者則無此情況發生。另外乳癌病患表現較高之visfatin和resistin則會造成病人較差的存活率,Cox回歸分析還顯示,visfatin和resistin的表現可當作一個預測乳癌發生風險的獨立因子。當MCF-7細胞給予visfatin和resistin時,其會增加MCF-7細胞的增殖速率和刺激細胞進入G1-S細胞週期的進程。
高表現之visfatin和resistin在乳癌病患中與惡性的臨床病理病徵以及較差的病人存活率相關。因此visfatin和resistin可能作為乳癌病患於診斷上一個獨立的預後預測因子,及在配合賀爾蒙治療上作為一個有潛力的標靶治療目標。


Breast cancer is the most common malignancy in women worldwide, and its prevalence is increasing at a surprisingly rapid rate and previous studies clearly showed that obesity is correlated with the risk and prognosis of breast cancer. Adipocytokines are adipocyte-derived hormones and well documented to be involved in carcinogenesis. The expression of visfatin and resistin, the newly discovered adipocytokines, in breast cancer patients was determined and correlated with patient clinicopathological variables in this study.
High visfatin and resistin expression was predominantly observed in breast cancer tissues but not the adjacent normal breast tissues. Serum levels were increased significantly for visfatin and resistin in the breast cancer patients, in comparison to controls. High visfatin expression in breast cancer patients was significantly correlated with tumor size, estrogen receptor negativity, and progesterone receptor status negativity. High resistin expression in breast cancer patients was correlated significantly with tumor stage, tumor size, lymph node metastasis and estrogen receptor status. Hormone therapy, but not radiotherapy or chemotherapy, decreased the recurrence rate in patients with high visfatin and resistin expression. While high visfatin and resistin expression was associated with poor patient survival, Cox regression analysis also revealed that visfatin and resistin was an independent predictor of patient survival. Administration of visfatin and resistin increased cell proliferation and activated G1-S phase cell cycle progression in MCF-7 cells.
High visfatin and resistin expression in breast cancer patient is associated with a more malignant clinicopathological status as well as poor patient survival. Visfatin and resistin may therefore hold promise as an independent prognosis predictor for breast cancer, as a marker for hormone therapy stratification and as a potential therapeutic target.

中文摘要…………………………………………………………………01
Abstract..………………………………………………………………02
Introduction……………………………………………………………03
Overview of breast cancer…………………………………………03
Overview of adipocytokines…………………………………………04
Sex hormones and breast cancer……………………………………07
Interplay of adipocytokines and sex hormones…………………10
Materials and methods…………………………………………………12
Tissue sample collection……………………………………………12
Tissue microarray………………………………………………………13
Immunohistochemistry…………………………………………………13
Evaluation of immunohistochemical staining……………………14
Radioimmunoassay………………………………………………………15
Cell culture……………………………………………………………15
XTT cell proliferation assay………………………………………15
Flow cytometry analysis of cell cycle distribution…………16
Statistical Analysis…………………………………………………16
Results…………………………………………………………………18
Visfatin expression in breast cancer tissues…………………18
Visfatin expression in sera of breast cancer patients………21
Resistin expression in breast cancer tissues…………………25
Resistin expression in sera of breast cancer patients………28
Discussion………………………………………………………………32
References………………………………………………………………38
Appendix…………………………………………………………………50
Table1. Clinicopathological characteristics of breast cancer patients (visfatin) …………………………………………………50
Table2. Immunohistochemistry for visfatin expression in breast cancer and adjacent normal breast tissues ……………51
Table3. Correlation of visfatin expression with clinicopathological characteristics of breast cancer patients…………………………………………………………………52
Table4. Correlation of visfatin expression with disease recurrence with/without radiotherapy, chemotherapy or hormone therapy…………………………………………………………53
Table5. Univariate and multivariable analysis of disease free survival for breast cancer……………………………………54
Table6. Univariate and multivariable analysis of overall survival for breast cancer…………………………………………55
Table7. Clinical characteristics of breast cancer patients and normal controls (serum visfatin)……………………………56
Table8. Clinicopathological characteristics in breast cancer patients…………………………………………………………………57
Table9. Correlation of serum visfatin levels with clinicopathological characteristics of breast cancer patients…………………………………………………………………58
Table10. Correlation of serum visfatin levels with disease recurrence with/without radiotherapy, chemotherapy or hormone therapy…………………………………………………………59
Table11. Univariate and multivariable analysis of disease free survival for breast cancer……………………………………60
Table12. Univariate and multivariable analysis of overall survival for breast cancer…………………………………………61
Table13. Clinicopathological characteristics of breast cancer patients (resistin)…………………………………………62
Table14. Immunohistochemistry of resistin expressions in breast cancer and adjacent normal breast tissues ……………63
Table15. Correlation of resistin expression with clinicopathological characteristics in breast cancer patients…………………………………………………………………64
Table16. Correlation of resistin expression with disease recurrence with/without radiotherapy, chemotherapy or hormone therapy…………………………………………………………65
Table17. Univariate and multivariable analysis of disease free survival for breast cancer……………………………………66
Table18. Univariate and multivariable analysis of overall survival for breast cancer…………………………………………67
Table19. Clinical characteristics of breast cancer patients and normal controls (serum resistin)……………………………68
Table20. Clinicopathological characteristics of breast cancer patients…………………………………………………………69
Table21. Correlation of resistin expression with clinicopathological characteristics of breast cancer patients…………………………………………………………………70
Table22. Correlation of resistin expression with disease recurrence with/without radiotherapy, chemotherapy or hormone therapy…………………………………………………………71
Table23. Univariate and multivariable analysis of disease free survival for breast cancer……………………………………72
Table24. Univariate and multivariable analysis of overall survival for breast cancer…………………………………………73
Figure1. The immunohistochemistry results for visfatin expression in breast cancer tissues………………………………74
Figure2. Kaplan-Meier survival curves generated for disease-free and overall survival…………………………………75
Figure3. Kaplan–Meier survival curves for survival of the low and high visfatin expression groups receiving or not adjuvant radiotherapy, chemotherapy and hormone therapy……77
Figure4. Kaplan-Meier survival curves generated for disease-free and overall survival (serum visfatin) …………79
Figure5. Kaplan–Meier survival curves for survival of the low and high visfatin expression groups receiving or not adjuvant radiotherapy, chemotherapy and hormone therapy …80
Figure6. The effect of visfatin on proliferation of human breast cancer cells………………82
Figure7. The effect of visfatin on cell cycle distribution of human breast cancer cells………………………………………83
Figure8. The immunohistochemistry results for resistin expression in breast cancer…………………………………………84
Figure9. Kaplan-Meier survival curves generated for disease-free and overall survival…………………………………85
Figure10. Kaplan–Meier survival curves for survival of the low and high visfatin expression groups receiving or not adjuvant radiotherapy, chemotherapy and hormone therapy …86
Figure11. Kaplan-Meier survival curves generated for disease-free and overall survival (serum resistin) …………88
Figure12. Kaplan–Meier survival curves for survival of the low and high resistin expression groups receiving or not adjuvant radiotherapy, chemotherapy and hormone therapy …89
Figure13. The effect of visfatin on proliferation of human breast cancer cells……………………………………………………91
Figure14. The effect of visfatin on cell cycle distribution of human breast cancer cells………………………………………92


1. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55 (2):74-108. doi:55/2/74 [pii]
2. Willett LL, Albright ES (2004) Achieving glycemic control in type 2 diabetes: a practical guide for clinicians on oral hypoglycemics. South Med J 97 (11):1088-1092
3. Viswanathan AN, Schernhammer ES (2009) Circulating melatonin and the risk of breast and endometrial cancer in women. Cancer Lett 281 (1):1-7. doi:S0304-3835(08)00875-6 [pii]
10.1016/j.canlet.2008.11.002
4. Hamajima N, Hirose K, Tajima K, Rohan T, Calle EE, Heath CW, Jr., Coates RJ, Liff JM, Talamini R, Chantarakul N, Koetsawang S, Rachawat D, Morabia A, Schuman L, Stewart W, Szklo M, Bain C, Schofield F, Siskind V, Band P, Coldman AJ, Gallagher RP, Hislop TG, Yang P, Kolonel LM, Nomura AM, Hu J, Johnson KC, Mao Y, De Sanjose S, Lee N, Marchbanks P, Ory HW, Peterson HB, Wilson HG, Wingo PA, Ebeling K, Kunde D, Nishan P, Hopper JL, Colditz G, Gajalanski V, Martin N, Pardthaisong T, Silpisornkosol S, Theetranont C, Boosiri B, Chutivongse S, Jimakorn P, Virutamasen P, Wongsrichanalai C, Ewertz M, Adami HO, Bergkvist L, Magnusson C, Persson I, Chang-Claude J, Paul C, Skegg DC, Spears GF, Boyle P, Evstifeeva T, Daling JR, Hutchinson WB, Malone K, Noonan EA, Stanford JL, Thomas DB, Weiss NS, White E, Andrieu N, Bremond A, Clavel F, Gairard B, Lansac J, Piana L, Renaud R, Izquierdo A, Viladiu P, Cuevas HR, Ontiveros P, Palet A, Salazar SB, Aristizabel N, Cuadros A, Tryggvadottir L, Tulinius H, Bachelot A, Le MG, Peto J, Franceschi S, Lubin F, Modan B, Ron E, Wax Y, Friedman GD, Hiatt RA, Levi F, Bishop T, Kosmelj K, Primic-Zakelj M, Ravnihar B, Stare J, Beeson WL, Fraser G, Bullbrook RD, Cuzick J, Duffy SW, Fentiman IS, Hayward JL, Wang DY, McMichael AJ, McPherson K, Hanson RL, Leske MC, Mahoney MC, Nasca PC, Varma AO, Weinstein AL, Moller TR, Olsson H, Ranstam J, Goldbohm RA, van den Brandt PA, Apelo RA, Baens J, de la Cruz JR, Javier B, Lacaya LB, Ngelangel CA, La Vecchia C, Negri E, Marubini E, Ferraroni M, Gerber M, Richardson S, Segala C, Gatei D, Kenya P, Kungu A, Mati JG, Brinton LA, Hoover R, Schairer C, Spirtas R, Lee HP, Rookus MA, van Leeuwen FE, Schoenberg JA, McCredie M, Gammon MD, Clarke EA, Jones L, Neil A, Vessey M, Yeates D, Appleby P, Banks E, Beral V, Bull D, Crossley B, Goodill A, Green J, Hermon C, Key T, Langston N, Lewis C, Reeves G, Collins R, Doll R, Peto R, Mabuchi K, Preston D, Hannaford P, Kay C, Rosero-Bixby L, Gao YT, Jin F, Yuan JM, Wei HY, Yun T, Zhiheng C, Berry G, Cooper Booth J, Jelihovsky T, MacLennan R, Shearman R, Wang QS, Baines CJ, Miller AB, Wall C, Lund E, Stalsberg H, Shu XO, Zheng W, Katsouyanni K, Trichopoulou A, Trichopoulos D, Dabancens A, Martinez L, Molina R, Salas O, Alexander FE, Anderson K, Folsom AR, Hulka BS, Bernstein L, Enger S, Haile RW, Paganini-Hill A, Pike MC, Ross RK, Ursin G, Yu MC, Longnecker MP, Newcomb P, Kalache A, Farley TM, Holck S, Meirik O (2002) Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 87 (11):1234-1245. doi:10.1038/sj.bjc.6600596
5. Bertelsen L, Bernstein L, Olsen JH, Mellemkjaer L, Haile RW, Lynch CF, Malone KE, Anton-Culver H, Christensen J, Langholz B, Thomas DC, Begg CB, Capanu M, Ejlertsen B, Stovall M, Boice JD, Jr., Shore RE, Bernstein JL (2008) Effect of systemic adjuvant treatment on risk for contralateral breast cancer in the Women''s Environment, Cancer and Radiation Epidemiology Study. J Natl Cancer Inst 100 (1):32-40. doi:djm267 [pii]
10.1093/jnci/djm267
6. Dumitrescu RG, Cotarla I (2005) Understanding breast cancer risk -- where do we stand in 2005? J Cell Mol Med 9 (1):208-221. doi:009.001.20 [pii]
7. Dent R, Warner E (2007) Screening for hereditary breast cancer. Semin Oncol 34 (5):392-400. doi:S0093-7754(07)00139-X [pii]
10.1053/j.seminoncol.2007.07.002
8. Hou WK, Xu YX, Yu T, Zhang L, Zhang WW, Fu CL, Sun Y, Wu Q, Chen L (2007) Adipocytokines and breast cancer risk. Chin Med J (Engl) 120 (18):1592-1596
9. Brown A, Raynor P, Lee M (2011) Young mothers who choose to breast feed: the importance of being part of a supportive breast-feeding community. Midwifery 27 (1):53-59. doi:S0266-6138(09)00121-1 [pii]
10.1016/j.midw.2009.09.004
10. Begum P, Richardson CE, Carmichael AR (2009) Obesity in post menopausal women with a family history of breast cancer: prevalence and risk awareness. Int Semin Surg Oncol 6:1. doi:1477-7800-6-1 [pii]
10.1186/1477-7800-6-1
11. Wozniak SE, Gee LL, Wachtel MS, Frezza EE (2009) Adipose tissue: the new endocrine organ? A review article. Dig Dis Sci 54 (9):1847-1856. doi:10.1007/s10620-008-0585-3
12. Garg A (2006) Adipose tissue dysfunction in obesity and lipodystrophy. Clin Cornerstone 8 Suppl 4:S7-S13. doi:S1098-3597(06)80039-6 [pii]
13. Kang JH, Yu BY, Youn DS (2007) Relationship of serum adiponectin and resistin levels with breast cancer risk. J Korean Med Sci 22 (1):117-121. doi:200702117 [pii]
14. Tan BK, Adya R, Farhatullah S, Lewandowski KC, O''Hare P, Lehnert H, Randeva HS (2008) Omentin-1, a novel adipokine, is decreased in overweight insulin-resistant women with polycystic ovary syndrome: ex vivo and in vivo regulation of omentin-1 by insulin and glucose. Diabetes 57 (4):801-808. doi:db07-0990 [pii]
10.2337/db07-0990
15. Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115 (5):1111-1119. doi:10.1172/JCI25102
16. Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K, Charo I, Leibel RL, Ferrante AW, Jr. (2006) CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 116 (1):115-124. doi:10.1172/JCI24335
17. Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6 (10):772-783. doi:nri1937 [pii]
10.1038/nri1937
18. Dieudonne MN, Machinal-Quelin F, Serazin-Leroy V, Leneveu MC, Pecquery R, Giudicelli Y (2002) Leptin mediates a proliferative response in human MCF7 breast cancer cells. Biochem Biophys Res Commun 293 (1):622-628. doi:10.1016/S0006-291X(02)00205-X
S0006-291X(02)00205-X [pii]
19. Laud K, Gourdou I, Pessemesse L, Peyrat JP, Djiane J (2002) Identification of leptin receptors in human breast cancer: functional activity in the T47-D breast cancer cell line. Mol Cell Endocrinol 188 (1-2):219-226. doi:S0303720701006785 [pii]
20. Garofalo C, Sisci D, Surmacz E (2004) Leptin interferes with the effects of the antiestrogen ICI 182,780 in MCF-7 breast cancer cells. Clin Cancer Res 10 (19):6466-6475. doi:10/19/6466 [pii]
10.1158/1078-0432.CCR-04-0203
21. Dieudonne MN, Bussiere M, Dos Santos E, Leneveu MC, Giudicelli Y, Pecquery R (2006) Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun 345 (1):271-279. doi:S0006-291X(06)00919-3 [pii]
10.1016/j.bbrc.2006.04.076
22. Grossmann ME, Nkhata KJ, Mizuno NK, Ray A, Cleary MP (2008) Effects of adiponectin on breast cancer cell growth and signaling. Br J Cancer 98 (2):370-379. doi:6604166 [pii]
10.1038/sj.bjc.6604166
23. Chen DC, Chung YF, Yeh YT, Chaung HC, Kuo FC, Fu OY, Chen HY, Hou MF, Yuan SS (2006) Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett 237 (1):109-114. doi:S0304-3835(05)00544-6 [pii]
10.1016/j.canlet.2005.05.047
24. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I (2005) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307 (5708):426-430. doi:1097243 [pii]
10.1126/science.1097243
25. Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I (1994) Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol 14 (2):1431-1437
26. Revollo JR, Korner A, Mills KF, Satoh A, Wang T, Garten A, Dasgupta B, Sasaki Y, Wolberger C, Townsend RR, Milbrandt J, Kiess W, Imai S (2007) Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab 6 (5):363-375. doi:S1550-4131(07)00263-X [pii]
10.1016/j.cmet.2007.09.003
27. Kitani T, Okuno S, Fujisawa H (2003) Growth phase-dependent changes in the subcellular localization of pre-B-cell colony-enhancing factor. FEBS Lett 544 (1-3):74-78. doi:S0014579303004769 [pii]
28. Haider DG, Schindler K, Schaller G, Prager G, Wolzt M, Ludvik B (2006) Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding. J Clin Endocrinol Metab 91 (4):1578-1581. doi:jc.2005-2248 [pii]
10.1210/jc.2005-2248
29. Varma V, Yao-Borengasser A, Rasouli N, Bodles AM, Phanavanh B, Lee MJ, Starks T, Kern LM, Spencer HJ, 3rd, McGehee RE, Jr., Fried SK, Kern PA (2007) Human visfatin expression: relationship to insulin sensitivity, intramyocellular lipids, and inflammation. J Clin Endocrinol Metab 92 (2):666-672. doi:jc.2006-1303 [pii]
10.1210/jc.2006-1303
30. Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ, Lee YJ (2006) Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 91 (1):295-299. doi:jc.2005-1475 [pii]
10.1210/jc.2005-1475
31. Brentano F, Schorr O, Ospelt C, Stanczyk J, Gay RE, Gay S, Kyburz D (2007) Pre-B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix-degrading activities. Arthritis Rheum 56 (9):2829-2839. doi:10.1002/art.22833
32. Berndt J, Kloting N, Kralisch S, Kovacs P, Fasshauer M, Schon MR, Stumvoll M, Bluher M (2005) Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes 54 (10):2911-2916. doi:54/10/2911 [pii]
33. Hammarstedt A, Pihlajamaki J, Rotter Sopasakis V, Gogg S, Jansson PA, Laakso M, Smith U (2006) Visfatin is an adipokine, but it is not regulated by thiazolidinediones. J Clin Endocrinol Metab 91 (3):1181-1184. doi:jc.2005-1395 [pii]
10.1210/jc.2005-1395
34. Rasouli N, Kern PA (2008) Adipocytokines and the metabolic complications of obesity. J Clin Endocrinol Metab 93 (11 Suppl 1):S64-73. doi:93/11_Supplement_1/s64 [pii]
10.1210/jc.2008-1613
35. Folgueira MA, Carraro DM, Brentani H, Patrao DF, Barbosa EM, Netto MM, Caldeira JR, Katayama ML, Soares FA, Oliveira CT, Reis LF, Kaiano JH, Camargo LP, Vencio RZ, Snitcovsky IM, Makdissi FB, e Silva PJ, Goes JC, Brentani MM (2005) Gene expression profile associated with response to doxorubicin-based therapy in breast cancer. Clin Cancer Res 11 (20):7434-7443. doi:11/20/7434 [pii]
10.1158/1078-0432.CCR-04-0548
36. Bae SK, Kim SR, Kim JG, Kim JY, Koo TH, Jang HO, Yun I, Yoo MA, Bae MK (2006) Hypoxic induction of human visfatin gene is directly mediated by hypoxia-inducible factor-1. FEBS Lett 580 (17):4105-4113. doi:S0014-5793(06)00769-1 [pii]
10.1016/j.febslet.2006.06.052
37. Yonezawa T, Haga S, Kobayashi Y, Takahashi T, Obara Y (2006) Visfatin is present in bovine mammary epithelial cells, lactating mammary gland and milk, and its expression is regulated by cAMP pathway. FEBS Lett 580 (28-29):6635-6643. doi:S0014-5793(06)01330-5 [pii]
10.1016/j.febslet.2006.11.014
38. Kusminski CM, McTernan PG, Kumar S (2005) Role of resistin in obesity, insulin resistance and Type II diabetes. Clin Sci (Lond) 109 (3):243-256. doi:CS20050078 [pii]
10.1042/CS20050078
39. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA (2001) The hormone resistin links obesity to diabetes. Nature 409 (6818):307-312. doi:10.1038/35053000
40. de Luis DA, Sagrado MG, Aller R, Izaola O, Conde R, Romero E (2009) Ala54Thr polymorphism of fatty acid binding protein 2, role on insulin resistance and cardiovascular risk factors in presurgical morbid obesity patients. Obes Surg 19 (12):1691-1696. doi:10.1007/s11695-009-9859-x
41. Guzik TJ, Mangalat D, Korbut R (2006) Adipocytokines - novel link between inflammation and vascular function? J Physiol Pharmacol 57 (4):505-528
42. Graham JD, Yager ML, Hill HD, Byth K, O''Neill GM, Clarke CL (2005) Altered progesterone receptor isoform expression remodels progestin responsiveness of breast cancer cells. Mol Endocrinol 19 (11):2713-2735. doi:me.2005-0126 [pii]
10.1210/me.2005-0126
43. Metivier R, Penot G, Hubner MR, Reid G, Brand H, Kos M, Gannon F (2003) Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell 115 (6):751-763. doi:S0092867403009346 [pii]
44. Clemons M, Goss P (2001) Estrogen and the risk of breast cancer. N Engl J Med 344 (4):276-285. doi:10.1056/NEJM200101253440407
45. Thom MH, White PJ, Williams RM, Sturdee DW, Paterson ME, Wade-Evans T, Studd JW (1979) Prevention and treatment of endometrial disease in climacteric women receiving oestrogen therapy. Lancet 2 (8140):455-457
46. Chlebowski RT, Hendrix SL, Langer RD, Stefanick ML, Gass M, Lane D, Rodabough RJ, Gilligan MA, Cyr MG, Thomson CA, Khandekar J, Petrovitch H, McTiernan A (2003) Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women''s Health Initiative Randomized Trial. JAMA 289 (24):3243-3253. doi:10.1001/jama.289.24.3243
289/24/3243 [pii]
47. McTiernan A, Martin CF, Peck JD, Aragaki AK, Chlebowski RT, Pisano ED, Wang CY, Brunner RL, Johnson KC, Manson JE, Lewis CE, Kotchen JM, Hulka BS (2005) Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women''s Health Initiative randomized trial. J Natl Cancer Inst 97 (18):1366-1376. doi:97/18/1366 [pii]
10.1093/jnci/dji279
48. Eigeliene N, Harkonen P, Erkkola R (2006) Effects of estradiol and medroxyprogesterone acetate on morphology, proliferation and apoptosis of human breast tissue in organ cultures. BMC Cancer 6:246. doi:1471-2407-6-246 [pii]
10.1186/1471-2407-6-246
49. Hayashi S, Yamaguchi Y (2006) Basic research for hormone-sensitivity of breast cancer. Breast Cancer 13 (2):123-128. doi:JST.JSTAGE/jbcs/13.123 [pii]
50. Couse JF, Curtis Hewitt S, Korach KS (2000) Receptor null mice reveal contrasting roles for estrogen receptor alpha and beta in reproductive tissues. J Steroid Biochem Mol Biol 74 (5):287-296. doi:S0960-0760(00)00105-9 [pii]
51. Gustafsson JA (1999) Estrogen receptor beta--a new dimension in estrogen mechanism of action. J Endocrinol 163 (3):379-383. doi:JOE03353 [pii]
52. Krzysik-Walker SM, Ocon-Grove OM, Maddineni SR, Hendricks GL, 3rd, Ramachandran R (2008) Is visfatin an adipokine or myokine? Evidence for greater visfatin expression in skeletal muscle than visceral fat in chickens. Endocrinology 149 (4):1543-1550. doi:en.2007-1301 [pii]
10.1210/en.2007-1301
53. Pedersen SB, Bruun JM, Hube F, Kristensen K, Hauner H, Richelsen B (2001) Demonstration of estrogen receptor subtypes alpha and beta in human adipose tissue: influences of adipose cell differentiation and fat depot localization. Mol Cell Endocrinol 182 (1):27-37. doi:S0303720701005573 [pii]
54. Yi KW, Shin JH, Seo HS, Lee JK, Oh MJ, Kim T, Saw HS, Kim SH, Hur JY (2008) Role of estrogen receptor-alpha and -beta in regulating leptin expression in 3T3-L1 adipocytes. Obesity (Silver Spring) 16 (11):2393-2399. doi:oby2008389 [pii]
10.1038/oby.2008.389
55. Shang Y, Brown M (2002) Molecular determinants for the tissue specificity of SERMs. Science 295 (5564):2465-2468. doi:10.1126/science.1068537
295/5564/2465 [pii]
56. Wang B, Guan ZZ, Liu DG, Lin TY, Zhang L, Xia ZJ, Teng XY (2004) [Discordance of estrogen receptor (ER), progestin receptor (PR), and HER-2 receptor statuses between primary and metastatic focuses of breast cancer]. Ai Zheng 23 (12):1710-1713. doi:1000467X2004121710 [pii]
57. Cheung E, Acevedo ML, Cole PA, Kraus WL (2005) Altered pharmacology and distinct coactivator usage for estrogen receptor-dependent transcription through activating protein-1. Proc Natl Acad Sci U S A 102 (3):559-564. doi:0407113102 [pii]
10.1073/pnas.0407113102
58. Pietras RJ (2006) Biologic basis of sequential and combination therapies for hormone-responsive breast cancer. Oncologist 11 (7):704-717. doi:11/7/704 [pii]
10.1634/theoncologist.11-7-704
59. Kastner P, Bocquel MT, Turcotte B, Garnier JM, Horwitz KB, Chambon P, Gronemeyer H (1990) Transient expression of human and chicken progesterone receptors does not support alternative translational initiation from a single mRNA as the mechanism generating two receptor isoforms. J Biol Chem 265 (21):12163-12167
60. Condon JC, Hardy DB, Kovaric K, Mendelson CR (2006) Up-regulation of the progesterone receptor (PR)-C isoform in laboring myometrium by activation of nuclear factor-kappaB may contribute to the onset of labor through inhibition of PR function. Mol Endocrinol 20 (4):764-775. doi:me.2005-0242 [pii]
10.1210/me.2005-0242
61. Dressing GE, Hagan CR, Knutson TP, Daniel AR, Lange CA (2009) Progesterone receptors act as sensors for mitogenic protein kinases in breast cancer models. Endocr Relat Cancer 16 (2):351-361. doi:ERC-08-0281 [pii]
10.1677/ERC-08-0281
62. Boonyaratanakornkit V, Scott MP, Ribon V, Sherman L, Anderson SM, Maller JL, Miller WT, Edwards DP (2001) Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases. Mol Cell 8 (2):269-280. doi:S1097-2765(01)00304-5 [pii]
63. Boonyaratanakornkit V, McGowan E, Sherman L, Mancini MA, Cheskis BJ, Edwards DP (2007) The role of extranuclear signaling actions of progesterone receptor in mediating progesterone regulation of gene expression and the cell cycle. Mol Endocrinol 21 (2):359-375. doi:me.2006-0337 [pii]
10.1210/me.2006-0337
64. Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB (2003) The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Intern Med 163 (4):427-436. doi:ioi20116 [pii]
65. Tchernof A, Desmeules A, Richard C, Laberge P, Daris M, Mailloux J, Rheaume C, Dupont P (2004) Ovarian hormone status and abdominal visceral adipose tissue metabolism. J Clin Endocrinol Metab 89 (7):3425-3430. doi:10.1210/jc.2003-031561
89/7/3425 [pii]
66. Shojima N, Sakoda H, Ogihara T, Fujishiro M, Katagiri H, Anai M, Onishi Y, Ono H, Inukai K, Abe M, Fukushima Y, Kikuchi M, Oka Y, Asano T (2002) Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells. Diabetes 51 (6):1737-1744
67. Banerjee RR, Lazar MA (2003) Resistin: molecular history and prognosis. J Mol Med (Berl) 81 (4):218-226. doi:10.1007/s00109-003-0428-9
68. Chen YH, Lee MJ, Chang HH, Hung PF, Kao YH (2006) 17 beta-estradiol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor, extracellularly regulated kinase, and CCAAT/enhancer binding protein-alpha pathways. Endocrinology 147 (9):4496-4504. doi:en.2005-1655 [pii]
10.1210/en.2005-1655
69. MacLaren R, Cui W, Cianflone K (2007) Visfatin expression is hormonally regulated by metabolic and sex hormones in 3T3-L1 pre-adipocytes and adipocytes. Diabetes Obes Metab 9 (4):490-497. doi:DOM625 [pii]
10.1111/j.1463-1326.2006.00625.x
70. Wolk A, Gridley G, Svensson M, Nyren O, McLaughlin JK, Fraumeni JF, Adam HO (2001) A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control 12 (1):13-21
71. Calle EE, Thun MJ (2004) Obesity and cancer. Oncogene 23 (38):6365-6378. doi:10.1038/sj.onc.1207751
1207751 [pii]
72. Medina D (2005) Mammary developmental fate and breast cancer risk. Endocr Relat Cancer 12 (3):483-495. doi:12/3/483 [pii]
10.1677/erc.1.00804
73. Newman SC, Lees AW, Jenkins HJ (1997) The effect of body mass index and oestrogen receptor level on survival of breast cancer patients. Int J Epidemiol 26 (3):484-490
74. Harvie M, Hooper L, Howell AH (2003) Central obesity and breast cancer risk: a systematic review. Obes Rev 4 (3):157-173
75. Ermilova VD (1980) [International histological classification of breast cancer by the WHO (1968) and its prognostic value]. Arkh Patol 42 (4):13-19
76. Benson JR, Weaver DL, Mittra I, Hayashi M (2003) The TNM staging system and breast cancer. Lancet Oncol 4 (1):56-60. doi:S1470204503009616 [pii]
77. Frierson HF, Jr., Wolber RA, Berean KW, Franquemont DW, Gaffey MJ, Boyd JC, Wilbur DC (1995) Interobserver reproducibility of the Nottingham modification of the Bloom and Richardson histologic grading scheme for infiltrating ductal carcinoma. Am J Clin Pathol 103 (2):195-198
78. Yeh YT, Ou-Yang F, Chen IF, Yang SF, Wang YY, Chuang HY, Su JH, Hou MF, Yuan SS (2006) STAT3 ser727 phosphorylation and its association with negative estrogen receptor status in breast infiltrating ductal carcinoma. Int J Cancer 118 (12):2943-2947. doi:10.1002/ijc.21771
79. Housa D, Housova J, Vernerova Z, Haluzik M (2006) Adipocytokines and cancer. Physiol Res 55 (3):233-244. doi:848 [pii]
80. Hufton SE, Moerkerk PT, Brandwijk R, de Bruine AP, Arends JW, Hoogenboom HR (1999) A profile of differentially expressed genes in primary colorectal cancer using suppression subtractive hybridization. FEBS Lett 463 (1-2):77-82. doi:S0014-5793(99)01578-1 [pii]
81. Nakajima TE, Yamada Y, Hamano T, Furuta K, Gotoda T, Katai H, Kato K, Hamaguchi T, Shimada Y (2009) Adipocytokine levels in gastric cancer patients: resistin and visfatin as biomarkers of gastric cancer. J Gastroenterol 44 (7):685-690. doi:10.1007/s00535-009-0063-5
82. Adya R, Tan BK, Punn A, Chen J, Randeva HS (2008) Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis. Cardiovasc Res 78 (2):356-365. doi:cvm111 [pii]
10.1093/cvr/cvm111
83. Patel ST, Mistry T, Brown JE, Digby JE, Adya R, Desai KM, Randeva HS (2010) A novel role for the adipokine visfatin/pre-B cell colony-enhancing factor 1 in prostate carcinogenesis. Peptides 31 (1):51-57. doi:S0196-9781(09)00452-5 [pii]
10.1016/j.peptides.2009.10.001
84. Li Y, Zhang Y, Dorweiler B, Cui D, Wang T, Woo CW, Brunkan CS, Wolberger C, Imai S, Tabas I (2008) Extracellular Nampt promotes macrophage survival via a nonenzymatic interleukin-6/STAT3 signaling mechanism. J Biol Chem 283 (50):34833-34843. doi:M805866200 [pii]
10.1074/jbc.M805866200
85. Nowell MA, Richards PJ, Fielding CA, Ognjanovic S, Topley N, Williams AS, Bryant-Greenwood G, Jones SA (2006) Regulation of pre-B cell colony-enhancing factor by STAT-3-dependent interleukin-6 trans-signaling: implications in the pathogenesis of rheumatoid arthritis. Arthritis Rheum 54 (7):2084-2095. doi:10.1002/art.21942
86. Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, Tilg H (2007) Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 178 (3):1748-1758. doi:178/3/1748 [pii]
87. Yang HJ, Yen MC, Lin CC, Lin CM, Chen YL, Weng TY, Huang TT, Wu CL, Lai MD (2010) A combination of the metabolic enzyme inhibitor APO866 and the immune adjuvant L-1-methyl tryptophan induces additive antitumor activity. Exp Biol Med (Maywood) 235 (7):869-876. doi:235/7/869 [pii]
10.1258/ebm.2010.010001
88. Nahimana A, Attinger A, Aubry D, Greaney P, Ireson C, Thougaard AV, Tjornelund J, Dawson KM, Dupuis M, Duchosal MA (2009) The NAD biosynthesis inhibitor APO866 has potent antitumor activity against hematologic malignancies. Blood 113 (14):3276-3286. doi:blood-2008-08-173369 [pii]
10.1182/blood-2008-08-173369
89. Cea M, Zoppoli G, Bruzzone S, Fruscione F, Moran E, Garuti A, Rocco I, Cirmena G, Casciaro S, Olcese F, Pierri I, Cagnetta A, Ferrando F, Ghio R, Gobbi M, Ballestrero A, Patrone F, Nencioni A (2009) APO866 activity in hematologic malignancies: a preclinical in vitro study. Blood 113 (23):6035-6037; author reply 6037-6038. doi:113/23/6035 [pii]
10.1182/blood-2009-03-209213
90. Zoppoli G, Cea M, Soncini D, Fruscione F, Rudner J, Moran E, Caffa I, Bedognetti D, Motta G, Ghio R, Ferrando F, Ballestrero A, Parodi S, Belka C, Patrone F, Bruzzone S, Nencioni A (2010) Potent synergistic interaction between the Nampt inhibitor APO866 and the apoptosis activator TRAIL in human leukemia cells. Exp Hematol 38 (11):979-988. doi:S0301-472X(10)00356-5 [pii]
10.1016/j.exphem.2010.07.013
91. van der Veer E, Nong Z, O''Neil C, Urquhart B, Freeman D, Pickering JG (2005) Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase activity and promotes vascular smooth muscle cell maturation. Circ Res 97 (1):25-34. doi:01.RES.0000173298.38808.27 [pii]
10.1161/01.RES.0000173298.38808.27
92. Borradaile NM, Pickering JG (2009) Nicotinamide phosphoribosyltransferase imparts human endothelial cells with extended replicative lifespan and enhanced angiogenic capacity in a high glucose environment. Aging Cell 8 (2):100-112. doi:ACE453 [pii]
10.1111/j.1474-9726.2009.00453.x
93. Yang H, Lavu S, Sinclair DA (2006) Nampt/PBEF/Visfatin: a regulator of mammalian health and longevity? Exp Gerontol 41 (8):718-726. doi:S0531-5565(06)00179-3 [pii]
10.1016/j.exger.2006.06.003
94. Song H, Shojima N, Sakoda H, Ogihara T, Fujishiro M, Katagiri H, Anai M, Onishi Y, Ono H, Inukai K, Fukushima Y, Kikuchi M, Shimano H, Yamada N, Oka Y, Asano T (2002) Resistin is regulated by C/EBPs, PPARs, and signal-transducing molecules. Biochem Biophys Res Commun 299 (2):291-298. doi:S0006291X02025512 [pii]
95. Seo JB, Noh MJ, Yoo EJ, Park SY, Park J, Lee IK, Park SD, Kim JB (2003) Functional characterization of the human resistin promoter with adipocyte determination- and differentiation-dependent factor 1/sterol regulatory element binding protein 1c and CCAAT enhancer binding protein-alpha. Mol Endocrinol 17 (8):1522-1533. doi:10.1210/me.2003-0028
me.2003-0028 [pii]
96. Wakeling AE, Bowler J (1992) ICI 182,780, a new antioestrogen with clinical potential. J Steroid Biochem Mol Biol 43 (1-3):173-177. doi:0960-0760(92)90204-V [pii]
97. White R, Jobling S, Hoare SA, Sumpter JP, Parker MG (1994) Environmentally persistent alkylphenolic compounds are estrogenic. Endocrinology 135 (1):175-182
98. Lee MJ, Lin H, Liu CW, Wu MH, Liao WJ, Chang HH, Ku HC, Chien YS, Ding WH, Kao YH (2008) Octylphenol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor and extracellular signal-regulated kinase pathways. Am J Physiol Cell Physiol 294 (6):C1542-1551. doi:00403.2007 [pii]
10.1152/ajpcell.00403.2007
99. Li X, Zhang S, Safe S (2006) Activation of kinase pathways in MCF-7 cells by 17beta-estradiol and structurally diverse estrogenic compounds. J Steroid Biochem Mol Biol 98 (2-3):122-132. doi:S0960-0760(05)00456-5 [pii]
10.1016/j.jsbmb.2005.08.018
100. Harris RE, Chlebowski RT, Jackson RD, Frid DJ, Ascenseo JL, Anderson G, Loar A, Rodabough RJ, White E, McTiernan A (2003) Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women''s Health Initiative. Cancer Res 63 (18):6096-6101
101. Hefler LA, Grimm C, Lantzsch T, Lampe D, Leodolter S, Koelbl H, Heinze G, Reinthaller A, Tong-Cacsire D, Tempfer C, Zeillinger R (2005) Interleukin-1 and interleukin-6 gene polymorphisms and the risk of breast cancer in caucasian women. Clin Cancer Res 11 (16):5718-5721. doi:11/16/5718 [pii]
10.1158/1078-0432.CCR-05-0001
102. Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A (2005) Resistin, an adipokine with potent proinflammatory properties. J Immunol 174 (9):5789-5795. doi:174/9/5789 [pii]
103. Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O''Rahilly S (2001) Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 50 (10):2199-2202
104. Patel L, Buckels AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA (2003) Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 300 (2):472-476. doi:S0006291X02028413 [pii]
105. Filkova M, Haluzik M, Gay S, Senolt L (2009) The role of resistin as a regulator of inflammation: Implications for various human pathologies. Clin Immunol 133 (2):157-170. doi:S1521-6616(09)00758-X [pii]
10.1016/j.clim.2009.07.013
106. Sun CA, Wu MH, Chu CH, Chou YC, Hsu GC, Yang T, Chou WY, Yu CP, Yu JC (2010) Adipocytokine resistin and breast cancer risk. Breast Cancer Res Treat 123 (3):869-876. doi:10.1007/s10549-010-0792-4
107. Bertolani C, Sancho-Bru P, Failli P, Bataller R, Aleffi S, DeFranco R, Mazzinghi B, Romagnani P, Milani S, Gines P, Colmenero J, Parola M, Gelmini S, Tarquini R, Laffi G, Pinzani M, Marra F (2006) Resistin as an intrahepatic cytokine: overexpression during chronic injury and induction of proinflammatory actions in hepatic stellate cells. Am J Pathol 169 (6):2042-2053. doi:S0002-9440(10)62664-8 [pii]
10.2353/ajpath.2006.060081
108. Calabro P, Samudio I, Willerson JT, Yeh ET (2004) Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways. Circulation 110 (21):3335-3340. doi:01.CIR.0000147825.97879.E7 [pii]
10.1161/01.CIR.0000147825.97879.E7

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top