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姓名	謝忻玲(Hsin-Ling Hsieh)  查詢紙本館藏	畢業系所	化學工程與材料工程學系
論文名稱	抗癌藥物的鑑定性用於分析大腸癌中癌幹細胞之研究 (Evaluation of Anti-cancer Drugs for Colon Cancers by Analyzing the Population of Cancer Stem Cells)
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摘要(中)	在西家裡，大腸癌是高居第二死亡率，且一半以上的病人在五年內死於其併發症。本研究利用人類大腸癌細胞株LoVo，培養在不同濃度之治癌藥物和含有血清之培養基裡。隨著治癌藥物濃度的提高，細胞裡的腫瘤胚胎抗原(CEA)濃度隨之增加；尤其，在高濃度之綜合抗癌藥物組合(FLOX)下，癌細胞密度隨之降低，但每一個癌細胞之腫瘤胚胎抗原釋放量是控制組的一百倍。顯示出大腸癌細胞，如 LoVo 和 CW2，利用抗癌藥物抑制(如阿斯匹靈)其生長過程，可有效提高癌細胞對腫瘤胚胎抗原的分泌量。 癌幹細胞是被定義為一群具有導致腫瘤性生長的少量癌細胞；因此，只有少數的大腸癌細胞(大腸癌幹細胞)能使腫瘤生長。在腦瘤和大腸癌中，藉由標記抗體CD133分辨並純化出癌幹細胞，其標記抗體也表現於原始細胞，如神經細胞、造血細胞、上皮和內皮細胞等細胞譜系。我們觀察大腸癌細胞LoVo在不同濃度的抗癌藥物裡癌幹細胞的表現(CD133low弱表現細胞和CD133high強表現細胞)，發現CD133llow弱表現細胞的比率會隨著抗癌藥物濃度的提高而降低；然而CD133high強表現細胞的比率會隨著抗癌藥物的提高而上升，此趨勢相反於回顧文獻中，肺癌細胞的生存率隨著抗癌藥物濃度增高而降低。因此，本研究提出此CD133high強表現性細胞為癌幹細胞或初始性癌細胞的假說。我們也將CD133high強表現細胞與CD133low弱表現細胞用於動物體內實驗來加以佐證上述的假說。 利用高濃度的抗癌藥物(5-FU)來針對大腸癌細胞LoVo，其癌幹細胞的存活率可達14.3%；相較於其他高濃度之抗癌藥物的結果，癌幹細胞的存活率少於或者甚至不到1%。而且複合性抗癌藥物(FLOX、Mayo Clinic、Roswell Park)的結果比起使用單一抗癌藥物還能更有效地降低大腸癌細胞中的癌幹細胞量。本研究提出一套具發展性的有效方法，是為利用抗癌藥物來分析CD133high強表現性的大腸癌幹細胞。
摘要(英)	Colorectal carcinoma is the second leading cause of cancer death in the Western countries with almost 50% of the patients dying for cancer related problems and with a dismal 5-year survival rate. In this study, human colorectal adenocarcinoma tumor (LoVo) cells are cultured in Ham’s media containing 20% fetal bovine serum (FBS) and the different concentrations of anti-cancer drugs. The production of carcinoembryonic antigen (CEA) per cell increased with increase of concentration of anti-cancer drugs in the culture media. Especially, the production of CEA per cell increased by up to one hundred fold compared to cultivation in normal media by adding combination of anti-cancer drugs of FLOX regime (5-FU:LV:OXA=6:6:1) in the culture media, while the cell density decreased by down to 1% of cell survival ratio. It is suggested that colorectal adenocarcinoma tumor such as LoVo cells as well as CW2 cells can produce CEA more effectively when the cell growth is suppressed by addition of toxic chemicals such as aspirin. It is generally recognized that only a few cancer cells are tumorigenic and that these tumorigenic cells could be considered as cancer stem cells (CSCs). Thus, only a small subset of colon cancer cells (i.e., cancer stem cells) is able to initiate tumor growth. Recently CSCs in brain tumor and colon carcinoma can be identified and isolated through the CD133 marker, which is expressed by normal primitive cells of the neural, hematopoietic, epithelial and endothelial lineages. We investigated the population of cancer stem cells (CD133low cells and CD133high cells) in LoVo cells, when the cells were treated with different combination and concentration of anti-cancer drugs. The ratio of CD133low cells (CD133 expressing cells) decreased with the increase of the concentration of anti-cancer drugs, while the ratio of CD133high cells (strong CD133 expressing cells) increased with the increase of the concentration of anti-cancer drugs of which tendency is the opposite to that found in lung cancer cells using cisplatin reported in the literature. We made a hypothesis that CD133high cells should be the cancer stem cells or cancer initiating cells in this study. The tumor generation on NOD mice by injection of CD133low cells and CD133high cells was investigated to verify this hypothesis. Cancer stem cells (CD133high cells) increased with the decrease of cell density by adding concentration of single anti-cancer drug of 5-FU into the culture medium of LoVo cells by up to 14.3% population, while the population of cancer stem cells was found to be less than 1% when combination of anti-cancer drugs was added into the culture medium of LoVo cells. The treatment of combination of anti-cancer drugs (Mayo clinic regime [5-FU:LV=25:1], Roswell Park regime [5-FU:LV=1:1], and FLOX regime [5-FU:LV:OXA=6:6:1]) to colon cancer cells (LoVo cells) was found to be extensively effective to suppress the cancer stem cell population compared to that of single anti-cancer drugs. The present study developed the evaluation method of anti-cancer drugs for cancer therapy by analyzing CD133high population in colon cancer cells.
關鍵字(中)	★ 癌幹細胞 ★ CD133表現 ★ 抗癌藥物	關鍵字(英)	★ Cancer stem cells ★ anti-cancer drugs ★ CD133 expression
論文目次	摘要 i Abstract ii 誌謝 iv Acknowledgement v Index of Contents vi Index of Figures viii Index of Tables xii Chapter 1 Introduction 1 1-1 Introduction 1 1-1-1 Definition of Cancer Stem Cells 1 1-2 Analysis of cancer stem cells 5 1-2-1 Flow cytometry analysis 8 1-2-1-1 Surface marker analysis of stem cells and cancer stem cells 10 1-2-1-2 Purification of CSCs by MACS 13 1-2-2 Anti-cancer therapy (Chemotherapy) 15 1-2-3 In vivo experiment 19 Chapter 2 Materials and Methods 21 2-1 Preparation of normal cell culture 21 2-2 Preparation of anti-cancer drugs culture media 23 2-3 Preparation of buffer solution 25 2-4 Treatment of cells with several anti-cancer drugs 25 2-5 CEA production analysis (contain cell morphology) 26 2-6 CD133 expression of cells measured by flow cytometry 28 2-7 MACS sorting of normal LoVo cell 28 2-8 Tumor generation in vivo 30 2-8-1 Transplantation of Colon Cancer Cells into NOD Mice 30 2-8-2 Immunohistochemistry 31 Chapter 3 Results and Discussion 33 3-1 Morphology of LoVo cells cultured with anti-cancer drugs (Chemotherapy) 33 3-2 CEA production of LoVo cells treated with chemotherapy 45 3-3 Surface marker analysis of cancer stem cell (CSC) 50 3-3-1 Definition of cancer stem cell (CSC) from size of LoVo cell 50 3-3-2 CD133 expression of cancer stem cells treated with anti-cancer drugs 54 3-3-3 Relationship between CEA production and CD133 expression 61 3-3-4 Cancer stem cell (CSC) purified by MACS method from LoVo cells 63 3-4 In Vivo Xenotransplantation Experiment 66 Chapter 4 Conclusion 70 Reference 71 Supplemental data 82
參考文獻	[1] Pardal R, Clarke MF and Morrison SJ. “Applying the principles of stem-cell biology to cancer”, Nat Rev Cancer, Vol. 3, pp. 895-902, December 2003. [2] Muhammad Al-Hajj and Michael F Clarke, “Self-renewal and solid tumor stem cells”, Oncogene, Vol. 23, pp. 7274–7282, 2004. [3] Vassilopoulos G, Wang PR and Russell DW. “Transplanted bone marrow regenerates liver by cell fusion”, Nature, Vol. 422, pp. 901-904, April 2003. [4] Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S and Grompe M. “Cell fusion is the principal source of bone-marrow-derived hepatocytes”, Nature, Vol. 422, pp. 897–901, April 2003. [5] Wagers AJ, Sherwood RI, Christensen JL and Weissman IL. “Little evidence for developmental plasticity of adult hematopoietic stem cells”, Science, Vol. 297, pp. 2256-2259, 2002. [6] Reya T., Morrison S.J., Clarke M.F. and Weissman I.L. “Stem Cells, Cancer and Cancer Stem Cells”, Nature, Vol. 414, pp. 105-111, November 2001. [7] Al-Hajj, M., Becker, M. W., Wicha, M., Weissman, I., and Clarke, M. F. “Therapeutic implications of cancer stem cells”, Curr Opin Genet Dev., Vol. 14, pp. 43-47, 2004. [8] Fialkow PJ, Gartler SM and Yoshida A. “Clonal origin of chronic myelocytic leukemia in man”, Proc Natl Acad Sci U S A., Vol. 58, pp. 1468–1471, 1967. [9] Hamburger AW and Salmon SE. “Primary bioassay of human tumor stem cells”, Science, Vol 197, pp. 461-463, July 1977. [10] Higuchi A., Uchiyama A., Demura M., Asakura T., Cho C.-S., Akaike T. et al. “Enhanced CEA production associated with aspirin in a culture of CW-2 cells on some polymeric films”, Cytotechnology, Vol. 31, pp. 233-242, January 1999. [11] Southam C, Brunschwig A, “Quantitative studies of autotransplantation of human cancer”, Cancer, Vol. 14, pp. 971–987, 1961. [12] Wodinsky, I., Swiniarski, J. and Kensler, C. J. “Spleen colony studies of leukemia L1210. I. Growth kinetics of lymphocytic L1210 cells in vivo as determined by spleen colony assay”, Cancer Chemother. Rep., Vol. 51, pp. 415–421, 1967. [13] Bergsagel D.E. and Valeriote F.A., “Growth characteristics of a mouse plasma cell tumor”, Cancer Res, Vol. 28, pp. 2187-2196, 1968. [14] Park IK, Qian D, Kiel M, BeckerMW, PihaljaM,Weissman IL, Morrison SJ and Clarke MF, “Bmi-1 is required for maintenance of adult self-renewing hematopoietic stem cells.”, Nature, Vol. 423, pp. 302-305, May 2003. [15] Salsbury, A. J., “The significance of the circulating cancer cell”, Cancer Treatment Rev., Vol. 2, pp. 55-72, 1975. [16] Heppner G.H., “Tumor heterogeneity”, Cancer Res., Vol. 44, pp. 2259-2265, 1984. [17] Henrique D, Hirsinger E, Adam J, Le Roux I, Pourquie O, Ish-Horowicz D and Lewis J., “Maintenance of neuroepithelial progenitor cells by Delta-Notch signalling in the embryonic chick retina”, Curr. Biol., Vol. 7, pp. 661-670, 1997. [18] Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri M and Dick J, “A cell initiating human acute myeloid leukaemia after transplantation into SCID mice”, Nature, Vol. 17, pp. 645-648, February 1994. [19] Bonnet D and Dick J., “Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell”, Nat Med., Vol. 3, pp. 730-737, July 1997. [20] Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF., “Prospective identification of tumorigenic breast cancer cells”, Proc Natl Acad Sci U S A., Vol. 100, pp. 3983-3988, 2003. [21] Ouhtit, A. et al., ”In vivo evidence for the role of CD44s in promoting breast cancer metastasis to the liver”, Am. J. Pathol., Vol. 171, pp. 2033–2039, 2007 [22] Shackleton, M. et al., ”Generation of a functional mammary gland from a single stem cell”, Nature, Vol. 439, pp. 84–88, 2006. [23] Patrawala, L. et al., “Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells”, Oncogene, Vol. 25, pp. 1696–1708, 2006. [24] Brown, M.D. et al., “Characterization of benign and malignant prostate epithelial Hoechst 33342 side populations”, Prostate, Vol. 67, pp. 1384–1396, 2007. [25] Burger, P.E. et al., ”Sca-1 expression identifies stem cells in the proximal region of prostatic ducts with high capacity to reconstitute prostatic tissue”, Proc. Natl. Acad. Sci. U. S. A., Vol. 102, pp. 7180–7185, 2005. [26] Goto, K. et al., “Proximal prostatic stem cells are programmed to regenerate a proximal–distal ductal axis”, Stem Cells, Vol. 24, pp. 1859–1868, 2006. [27] Wright, M.H. et al., “Brca1 breast tumors contain distinct CD44+/CD24_ and CD133+ cells with cancer stem cell characteristics”, Breast Cancer Res., Vol. 10, R10, 2008. [28] Richardson, G.D. et al., ”CD133, a novel marker for human prostatic epithelial stem cells”, J. Cell Sci., Vol. 117, pp. 3539–3545, 2004. [29] Collins, A.T. et al., “Prospective identification of tumorigenic prostate cancer stem cells”, Cancer Res., Vol. 65, pp. 10946–10951, 2005. [30] Signoretti, S. et al., “p63 is a prostate basal cell marker and is required for prostate development”, Am. J. Pathol., Vol. 157, pp. 1769–1775, 2000. [31] Wang, S. et al., “Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation”, Proc Natl Acad Sci U S A., Vol. 103, pp. 1480–1485, 2006. [32] Lawson, D.A. et al., ”Prostate stem cells and prostate cancer”, Cold Spring Harb. Symp. Quant. Biol., Vol. 70, pp. 187–196, 2005. [33] Roskams, T., ”Liver stem cells and their implication in hepatocellular and cholangiocarcinoma”, Oncogene, Vol. 25, pp. 3818–3822, 2006. [34] Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti M and Daidone MG, ”Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties”, Cancer Res., Vol. 65, pp. 5506–5511, 2005. [35] Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F and Vescovi A, “Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma”, Cancer Res., Vol. 64, pp 7011–7021, 2004. [36] Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C and De Maria R, “Identification and expansion of human colon-cancer-initiating cells”, Nature, Vol. 445, pp. 111–115, 2007. [37] Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C and Clarke MF, “Phenotypic characterization of human colorectal cancer stem cells”, Proc Natl Acad Sci U S A., Vol. 104, pp 10158–10163, 2007. [38] O’Brien CA, Pollett A, Gallinger S, Dick JE, “A human colon cancer cell capable of initiating tumour growth in immunodeficient mice”, Nature, Vol. 445, pp. 106–110, 2007. [39] Schatton T, Murphy GF, Frank NY, Yamaura K, Waaga- Gasser AM, Gasser M, Zhan Q, Jordan S, Duncan LM, Weishaupt C, Fuhlbrigge RC, Kupper TS, Sayegh MH, Frank MH, “Identification of cells initiating human melanomas”, Nature, Vol. 451, pp. 345–349, 2008. [40] Li C, Heidt DG, Dalerba P, Burant CF, Zhang L, Adsay V, Wicha M, Clarke MF and Simeone DM, “Identification of pancreatic cancer stem cells”, Cancer Res., Vol. 67, pp. 1030–1037, 2007. [41] Patrawala L, Calhoun-Davis T, Schneider-Broussard R and Tang DG, “Hierarchical organization of prostate cancer cells in xenograft tumors: the CD44+a2b1+ cell population is enriched in tumor-initiating cells”, Cancer Res., Vol. 67, pp. 6796–6805, 2007. [42] Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, Dombkowski D, Preffer F, Maclaughlin DT and Donahoe PK, ”Ovarian cancer side population defines cells with stem cell-like characteristics and mullerian inhibiting substance responsiveness”, Proc Natl Acad Sci U S A., Vol. 103, pp. 11154–11159, 2006. [43] Prince ME, “Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma”, Proc Natl Acad Sci U S A., Vol. 104, pp. 973–978, 2007. [44] Flow Cytometry: A Practical Approach, 3rd Edition. (Practical Approach Series). Edited by M.G. Ormerod. Oxford University Press, 2000. [45] Introduction to Flow Cytometry, First Paperback Editon. James V.Watson. Cambridge University Press, 2004. [46] Miraglia, S., et al. “A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning”. Blood, Vol. 90, pp. 5013–5021., 1997. [47] Yin, A.H., et al. “AC133, a novel marker for human hematopoietic stem and progenitor cells”, Blood, Vol. 90, pp. 5002–5012., 1997. [48] Weigmann, A., Corbeil, D., Hellwig, A., and Huttner, W.B., “Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells”, Proc Natl Acad Sci U S A., Vol. 94, pp. 12425–12430, 1997. [49] Peichev, M., et al. “Expression of VEGFR-2 and AC133 by circulating human CD34 (+) cells identifies a population of functional endothelial precursors”, Blood, Vol. 95, pp. 952–958, 2000. [50] Salven, P., Mustjoki, S., Alitalo, R., Alitalo, K., and Rafii, S.”VEGFR-3 and CD133 identify a population of CD34+ lymphatic/vascular endothelial precursor cells”, Blood, Vol. 101, pp. 168–172, 2003. [51] Shmelkov, S.V., et al. “Cytokine preconditioning promotes codifferentiation of human fetal liver CD133+ stem cells into angiomyogenic tissue”, Circulation, Vol. 111, pp. 1175–1183, 2005. [52] Uchida, N., et al. “Direct isolation of human central nervous system stem cells”, Proc. Natl. Acad. Sci. U. S. A., Vol. 97, pp. 14720–14725, 2000. [53] Lee, A., et al. “Isolation of neural stem cells from the postnatal cerebellum”, Nat. Neurosci., Vol. 8, pp. 723–729, 2005. [54] Sagrinati, C., et al. “Isolation and characterization of multipotent progenitor cells from the Bowman’s capsule of adult human kidneys”, J. Am. Soc. Nephrol., Vol. 17, pp. 2443–2456, 2006. [55] Kordes, C., et al. “CD133+ hepatic stellate cells are progenitor cells”, Biochem. Biophys. Res. Commun., Vol. 352, pp. 410–417, 2007. [56] Oshima, Y., et al. “Isolation of mouse pancreatic ductal progenitor cells expressing CD133 and c- Met by flow cytometric cell sorting”, Gastroenterology., Vol. 132, pp. 720–732, 2007. [57] Sugiyama, T., Rodriguez, R.T., McLean, G.W., and Kim, S.K. “Conserved markers of fetal pancreatic epithelium permit prospective isolation of islet progenitor cells by FACS”, Proc Natl Acad Sci U S A., Vol. 104, pp. 175–180, 2007. [58] Ito, Y., et al., “Isolation of murine hair-inducing cells using the cell surface marker prominin- 1/CD133”, J. Invest. Dermatol., Vol. 127, pp. 1052–1060, 2006. [59] Singh, S.K., et al., “Identification of a cancer stem cell in human brain tumors”, Cancer Res., Vol. 63, pp. 5821–5828, 2003. [60] Singh, S.K., et al., “Identification of human brain tumor initiating cells”, Nature, Vol. 432, pp. 396–401, 2004. [61] Suetsugu, A., et al.,”Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells”, Biochem. Biophys. Res. Commun., Vol. 351 , pp. 820–824, 2006. [62] Yin, S., et al., “CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity”, Int. J. Cancer., Vol. 120, pp. 1444–1450, 2007. [63] Hermann, P.C., et al., “Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer”, Cell Stem Cell, Vol. 1, pp. 313–323, 2007. [64] Olempska M, Eisenach PA, Ammerpohl O, Ungefroren H, Fandrich F, et al., “Detection of tumor stem cell markers in pancreatic carcinoma cell lines”, Hepatobiliary Pancreat Dis Int., Vol. 6, pp. 92–97, 2007. [65] Eramo, A., et al., “Identification and expansion of the tumorigenic lung cancer stem cell population”, Cell Death Differ., Vol. 15, pp. 504–514, 2008. [66] Bruno S, Bussolati B, Grange C, Collino F, Graziano ME, et al., “CD133+ renal progenitor cells contribute to tumor angiogenesis”, Am J Pathol., Vol. 169, pp. 2223–2235, 2006. [67] Todaro, M., et al., “Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4”, Cell Stem Cell, Vol. 1, pp. 389–402, 2007. [68] Maw MA, Corbeil D, Koch J, et al., “A frameshift mutation in prominin (mouse)-like 1 causes human retinal degeneration”, Hum Mol Genet., Vol. 9, pp. 27–34, 2000. [69] Miraglia S, Godfrey W, Yin AH, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning”, Blood, Vol. 90, pp. 5013–21, 1997. [70] Bhatia M., “AC133 expression in human stem cells”, Leukemia, Vol. 15, pp.1685–1688, 2001. [71] Ieta K, Tanaka F, Haraguchi N, et al., “Biological and genetic characteristics of tumor-initiating cells in colon cancer”, Ann Surg Oncol., Vol. 15, pp. 638–648, 2008. [72] Horst D, Kriegl L, Engel J, et al., “CD133 expression is an independent prognostic marker for low survival in colorectal cancer”, Br J Cancer., Vol. 99, pp.1285–1289, 2008. [73] Lin EH, Hassan M, Li Y, et al., “Elevated circulating endothelial progenitor marker CD133 messenger RNA levels predict colon cancer recurrence”, Cancer, Vol. 110, pp. 534–542, 2007. [74] Mehra N, Penning M, Maas J, et al., “Progenitor marker CD133 mRNA is elevated in peripheral blood of cancer patients with bone metastases”, Clin Cancer Res., Vol. 12, pp.4859–4866, 2006. [75] Florek, M., et al., “Prominin-1/CD133, a neural and hematopoietic stem cell marker, is expressed in adult human differentiated cells and certain types of kidney cancer”, Cell Tissue Res., Vol. 319, pp. 15–26, 2005. [76] Pfenninger, C.V., et al., “CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells”, Cancer Res., Vol. 67, pp. 5727–5736, 2007. [77] Corbeil, D., Roper, K., Fargeas, C.A., Joester, A., and Huttner, W.B., “Prominin: a story of cholesterol, plasma membrane protrusions and human pathology”, Traffic, Vol. 2, pp. 82–91, 2001. [78] Shmelkov, S.V., et al., “CD133 expression is not restricted to stem cells, and both CD133+ and CD133– metastatic colon cancer cells initiate tumors”, J. Clin. Invest., Vol. 118, pp. 2111–2120, 2008. [79] K. Kato, A. Radbruch, “Isolation and characterization of CD34+ hematopoietic stem cells from human peripheral blood by high-gradient magnetic cell sorting”, Cytometry, Vol. 14, pp. 384-392, 1993. [80] S. Miltenyi, W. Müller, W. Weichel, A. Radbruch, “High-gradient magnetic cell separation with MACS”, Cytometry, Vol. 11, pp. 231-238, 1990. [81] 81 Dingli, D. and Michor, F., “Successful therapy must eradicate cancer stem cells”, Stem Cells, Vol. 24, pp. 2603–2610, 2006. [82] Banerji, S. and Los, M., “Important differences between topoisomerase-I and -II targeting agents”, Cancer Biol. Ther., Vol. 5, pp. 965–966, 2006. [83] Ghavami, S. et al., “S100A8/9 induces cell death via a novel, RAGE-independent pathway that involves selective release of Smac/DIABLO and Omi/HtrA2”, Biochim. Biophys. Acta., Vol. 1783,pp. 297–311, 2008. [84] Rashedi, I. et al., “Autoimmunity and apoptosis – therapeutic implications”, Curr. Med. Chem., Vol. 14, pp. 3139–3159, 2007. [85] Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, et al.,”Cancer Stem Cells–Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem Cells”, Cancer Res., Vol. 66, pp. 9339–9344, 2006. [86] Elkind NB, Szentpe´tery Z, Apa´ti A ´ , Ozvegy-Laczka C, Va´rady G, et al., “Multidrug transporter ABCG2 prevents tumor cell death induced by the epidermal growth factor receptor inhibitor Iressa (ZD1839, Gefitinib)”, Cancer Res., Vol. 65, pp. 1770–1777, 2005. [87] Grem JL., “Fluoropyrimidines. In: Chabner BA, Longo DL, eds. Cancer Chemotherapy and Biotherapy: Principles and Practice”, 2nd ed. Philadelphia: Lippincot William and Wilkins, pp. 149-63, 1996. [88] Francini G, Petrioli R, Lorenzini L, Mancini S, Armenio S, Tanzini G, Marsili S, Aquino A, Marzocca G, Civitelli S, et al., “Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer”, Gastroenterology, Vol. 106, pp. 899-906, 1994. [89] O’Connell MJ, Laurie JA, Kahn M, Fitzgibbons Jr RJ, Erlichman C, Shepherd L, Moertel CG, Kocha WI, Pazdur R, Wieand HS, Rubin J, Vukov AM, Donohue JH, KrookJE, Figueredo A., “Prospectively randomized trial of postoperative adjuvant chemotherapy inpatients with high-risk colon cancer”, J Clin Oncol., Vol. 16, pp. 295-300, 1998. [90] Skibber JM, Minsky BD, Hoff PM. Cancer of the colon. In: De Vita V, Hellman S, Rosenberg SA, eds. “Cancer Principles and Practice of Oncology”, 6th ed. Philadelphia: Lippincott Williams and Wilkins, pp.1216-71, (USA CH 33.7), 2001. [91] Von Hoff DD., “Promising New agents for treatment of patients with colorectal cancer”, Semin Oncol. Vol. 5, pp. 47-52, 1998 [92] Goldenberg RM, Morton RF, Sargent DJ, Fuchs C, Ramanathan RK, Williamson S, Findlay B. NCCTG, CALGB, ECOG, SWOG, NCIC., “Oxaliplatin or CPT-11 + 5-fluorouracil /leucovorin or Oxa + CPT-11 in advanced colorectal cancer (ACRC), efficacy and safety results from a north americal gastrointestinal intergroup study (N9741). Perspectives In Colorectal Cancer”, A Consensus Meeting, 4th International Conference. Barcelona, (abs # 6), 2002. [93] van Rhenen A, Feller N, Kelder A, et al., “High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival”, Clin Cancer Res., Vol. 11, pp. 11:6520-6527, 2007. [94] Feller N, van der Pol MA, van Stijn A, et al., “MRD parameters using immunophenotypic detection methods are highly reliable in predicting survival in acute myeloid leukaemia”, Leukemia, Vol. 18, pp. 1380-1390, 2004. [95] Kelly PN, Dakic A, Adams JM, et al., “Tumor growth need not be driven by rare cancer stem cells”, Science, Vol. 317, pp. 337, 2007. [96] Vezzoni L, Parmiani G., “Limitations of the cancer stem cell theory”, Cytotechnology, Vol. 58, pp. 3-9, 2008. [97] Klonisch T, Wiechec E, Hombach-Klonisch S, Ande SR, Wesselborg S, Schulze-Osthoff K, Los M, “Cancer stem cell markers in common cancers - therapeutic implications”, Trends Mol Med., Vol. 14, pp.450-460, October 2008. [98] Chen YC, Hsu HS, Chen YW, Tsai TH, How CK, Wang CY, Hung SC, Chang YL, Tsai ML, Lee YY, Ku HH, Chiou SH., “Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells”, PLoS One., Vol. 3, pp. 2637, July 2008. [99] Mark A. LaBarge and Mina J. Bissell, “Is CD133 a marker of metastatic colon cancer stem cells?”, J Clin Invest., Vol. 118, pp. 2021–2024, 2008. [100] Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter, “Molecular Biology of the Cell”, published by Garland Science; 5 editions, ISBN-13: 978-0815341055.
指導教授	樋口亞绀(Akon Higuchi)	審核日期	2010-7-14
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