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研究生:花士哲
研究生(外文):Shih-Che Hua
論文名稱:評估reversine對甲狀腺癌細胞株的抑癌效果及其機制之探討
論文名稱(外文):The anti-tumor effect evaluation and mechanistic investigation of reversine on thyroid cancer cell lines
指導教授:張天鈞張天鈞引用關係
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:臨床醫學研究所
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:2010
畢業學年度:98
語文別:中文
論文頁數:77
中文關鍵詞:reversine甲狀腺癌aurora kinase細胞週期凋亡腫瘤異種移植裸鼠
外文關鍵詞:reversinethyroid canceraurora kinasecycle cycleapoptosisxenograft nude mice
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研究背景:
在內分泌腫瘤中,甲狀腺癌是最常見的癌症,雖然以手術或合併原子碘治療甲狀腺分化癌預後非常好,但對於已轉移且對原子碘治療無效的分化癌或是甲狀腺未分化癌,目前臨床治療效果非常不理想,急待新藥物之開發。染色體非整倍體變異,為腫瘤細胞的重要特徵,包括甲狀腺癌在內,與惡性度高和預後差有關。Aurora kinase (Aur)為調控細胞週期正常進行的重要激酶之ㄧ。癌細胞會表現過量的Aur,反之抑制Aur則會抑癌生長,Aur抑制劑會導致細胞週期阻滯和染色體多套體化及癌細胞凋亡,目前已有數個Aur抑制劑在進行臨床試驗中。甲狀腺癌也會表現過量的Aur,並會隨著未分化程度增加而表現增加。近來發現reversine為purine類似物的合成小分子,也能有效抑制與腫瘤生長有關的激酶,包括Aur,而去抑制急性骨髓癌和多發性骨髓瘤,但尚未有應用在甲狀腺癌的研究。
研究目的與假說:
針對目前臨床上對於甲狀腺癌的治療困境,研究新的有效治療藥物有其重要性和急迫性。本研究假說是reversine能抑制甲狀腺癌細胞株的腫瘤生長,並干擾細胞分裂週期之進行,和誘發細胞凋亡。
研究方法:
先利用活體外實驗,以MTT分析法檢驗reversine對於人類甲狀腺未分化癌細胞株(ARO)、人類濾泡癌細胞株 (WRO) 及人類分化不良甲狀腺癌細胞株 (SW579),是否能抑制腫瘤細胞之生長;同時進行動物實驗,利用腫瘤異種移植的裸鼠去探討reversine抑制甲狀腺癌的活體效果;若發現有抑癌效果,則進一步利用流式細胞儀探討reversine導致細胞週期之變化和細胞死亡的抑癌機轉。若發現有細胞凋亡之現象,則利用西方墨點法去偵測是否有caspase 3、caspase 8、或caspase 9的活化,而加入泛caspase抑制劑是否能阻斷reversine所造成的細胞死亡,進一步探討凋亡訊息傳遞是屬粒腺體依賴型或非依賴型路徑。
研究結果:
活體外 reversine能有效抑制甲狀腺癌細胞株生長,但此三細胞株的易感性不同,分化良好的WRO細胞較有抗性;動物實驗研究,只能成功建立ARO腫瘤異種移殖的裸鼠,reversine能有效抑制ARO腫瘤生長,然而reversine的劑量增加並不能增強抑癌效果;細胞週期分析方面,reversine處理後會導致ARO、WRO、SW579等三甲狀腺癌細胞株的G2/M期阻滯;在細胞死亡分析方面,三細胞株死於凋亡比率會隨暴露於reversine的時間和濃度之增加而增加,但三細胞株的易感性亦不同,SW579細胞最為顯著,ARO和WRO細胞則不顯著。進一步探討reversine所造成SW579細胞的凋亡,發現caspase 8和caspase 3會被活化,而caspase 9不會被活化,顯示屬非粒腺體依賴型路徑,而反之泛caspase抑制劑能阻斷reversine的細胞死亡效果。
研究結論:
本研究首次證實reversine對甲狀腺癌細胞株腫瘤有抑癌效果並探討其抑癌機轉,reversine抑制ARO和WRO細胞主要是造成細胞週期進行阻滯,而抑制SW579細胞主要是造成細胞週期進行阻滯和細胞凋亡。Reversine所導致的凋亡訊息傳遞機轉是屬粒腺體非依賴型路徑,而泛caspase抑制劑能抑制凋亡。Reversine為日後進入甲狀腺抗癌藥物臨床試驗的新潛力用藥。

Background:
Thyroid cancer is the most common cancer among endocrine malignancies. Although current management with surgical resection followed by radioactive iodine therapy has been proved effective in treating differentiated thyroid cancer, but there have been no available effective treatment modalities for metastatic radio-resistant differentiated thyroid cancer and anaplastic thyroid cancer. Aneupolidy represents a hallmark of solid cancers including thyroid cancer and is associated with poor prognosis. Aurora kinases (Aur) are important kinases in the regulation of normal cell cycle, which are overexpressed in various type of cancer cells and aurora kinases inhibition will suppress tumor growth. Currently, several Aur inhibitors are undergoing clinical trials. Thyroid cancer has also been proved to have Aur overexpression which is related to undifferentiated phenotypes. Recently, a small synthetic molecule named reversine, a purine analogue, has proved anti-tumor effective in acute myeloid leukemia cells and multiple myeloma cells. However, up to date, there has been no study aimed at thyroid cancer treatment by reversine.
Objective and hypothesis:
Because of the current clinical treatment dilemma in incurable differentiated thyroid cancer, poorly differentiated thyroid cancer or anaplastic thyroid cancer, a novel and effective treatment modality is urgently needed. We propose reversine could suppress thyroid cancer tumor growth by inducing cell cycle arrest and cell apoptosis.
Methods:
First, we in vitro examined the anti-tumor effects of reversine on human anaplastic thyroid cancer cell line (ARO), human follicular thyroid cancer cell line (WRO), and human poorly-differentiated thyroid cancer cell line (SW579) by MTT assay; simultaneously, we in vivo examined the anti-tumor effects of reversine on ARO by xenograft nude mice model; if anti-tumor effects proved, we further investigated reversine’s effects on cell cycle and cell death by flow cytometry analysis. If apoptosis is proved by flow cytometry, to clarify the apoptotic signal transduction pathway, further activated caspase 3, caspase 8, and caspase 9 would be detected by western blot. Pan-caspase inhibitor would be tested its ability to reverse cell death caused by reversine.
Results:
Reversine suppressed these 3 thyroid cancer lines (ARO, WRO, SW579) growth in vitro, although with different susceptibility, e.g. well-differentiated WRO cells more resistant to reversine. Only ARO xenograft nude mice model was successfully established. Reversine was also validated to suppress ARO tumor growth in vivo, but the anti-tumor was not in a dose-dependent manner. In the aspect of cell cycle analysis, these 3 thyroid cancer cells treated by reversine were shown G2/M phase arrest. In the aspect of cell death analysis, apoptotic ratio increased in a time and dose-dependent manner in these 3 thyroid cancer cell lines, but also with different susceptibility. SW579 cells treated by reversine were susceptible to apoptosis, but neither ARO nor WRO cells. SW579 cells treated by reversine activated caspase 8 and capase 3, not caspase 9. And cell death after treatment of reversine was attenuated by pan-caspase inhibitor.
Conclusion:
This study is the first to prove anti-tumor effects of reversine on thyroid cancer cell lines in vitro and in vivo. Besides, we investigated reversine’s anti-tumor mechanisms. Reversine inhibits ARO and WRO cells mainly by cell cycle progression arrest. However, reversine inhibits SW579 cells mainly by cell cycle arrest and inducing cell apoptosis. The apoptotic mechanisms were via mitochondria-independent extrinsic pathway. Reversine is a novel potential anti-thyroid cancer drug and may enter clinical trials in the future.

口試委員會審定書 ii
誌謝 iii
中文摘要 iv
Abstract vi
第一章 緒論 1
第二章 研究方法與材料 8
第三章 結果 14
第四章 討論 19
第五章 展望 23
English summary 24
參考文獻 44
圖目錄 60
附錄 76


Amabile G, D''Alise AM, Iovino M, Jones P, Santaguida S, Musacchio A, Taylor S, Cortese R. The Aurora B kinase activity is required for the maintenance of the differentiated state of murine myoblasts. Cell Death Differ. 2009 Feb;16(2):321-30.
Anastasia L, Sampaolesi M, Papini N, Oleari D, Lamorte G, Tringali C, Monti E, Galli D, Tettamanti G, Cossu G, Venerando B. Reversine-treated fibroblasts acquire myogenic competence in vitro and in regenerating skeletal muscles. Cell Death Differ. 2006 Dec;13(12):2042-51.
Are C, Shaha AR. Anaplastic thyroid carcinoma: biology, pathogenesis, prognostic factors, and treatment approaches. Ann Surg Oncol. 2006 Apr;13(4):453-64.
Arlot-Bonnemains Y, Baldini E, Martin B, Delcros JG, Toller M, Curcio F, Ambesi-Impiombato FS, D''Armiento M, Ulisse S. Effects of the aurora kinase inhibitor VX-680 on anaplastic thyroid cancer-derived cell lines. Endocr Relat Cancer. 2008 Jun;15(2):559-68.
Arlot-Bonnemains Y, Klotzbucher A, Giet R, Uzbekov R, Bihan R, Prigent C. Identification of a functional destruction box in the Xenopus laevis aurora-A kinase pEg2. FEBS Letters. 2001 Nov;508(1):149-52.
Bischoff JR, Anderson L, Zhu Y, Mossie K, Ng L, Souza B, Schryver B, Flanagan P, Clairvoyant F, Ginther C, Chan CS, Novotny M, Slamon DJ, Plowman GD. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J. 1998 Jun;17(11):3052-65.
Carmena M, Earnshaw WC. The cellular geography of aurora kinases. Nat Rev Mol Cell Biol. 2003 Nov;4(11):842-54.
Casara D, Rubello D, Saladini G, Masarotto G, Favero A, Girelli ME, Busnardo B. Different features of pulmonary metastases in differentiated thyroid cancer: natural history and multivariate statistical analysis of prognostic variables. J Nucl Med. 1993 Oct;34(10):1626-31.
Chan F, Sun C, Perumal M, Nguyen QD, Bavetsias V, McDonald E. Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity. Mol Cancer Ther. 2007;6:3147–57.
Chen S, Zhang Q, Wu X, Schultz PG, Ding S. Dedifferentiation of lineage-committed cells by a small molecule. J Am Chem Soc. 2004 Jan;126(2):410-1.
Chen ST, Shieh HY, Lin JD, Chang KSS, Lin KH. Overexpression of thyroid hormone receptor β1 is associated with thyroid receptor gene expression and proliferation in a human thyroid carcinoma cell line. J Endocrinol. 2000 May;165(2):379-89.
Chieffi P, Cozzolino L, Kisslinger A, Libertini S, Staibano S, Mansueto G, De Rosa G, Villacci A, Vitale M, Linardopoulos S, Portella G, Tramontano D. Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation. Prostate. 2006 Feb;66(3):326-33.
Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Sherman SI, Tuttle RM; American Thyroid Association Guidelines Taskforce. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2006 Feb;16(2):109-42.
D''Alise AM, Amabile G, Iovino M, Di Giorgio FP, Bartiromo M, Sessa F, Villa F, Musacchio A, Cortese R. Reversine, a novel Aurora kinases inhibitor, inhibits colony formation of human acute myeloid leukemia cells. Mol Cancer Ther. 2008 May;7(5):1140-9.
Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 2006 May;295(18):2164-7.
Dar AA, Belkhiri A, Ecsedy J, Zaika A, El-Rifai W. Aurora kinase A inhibition leads to p73-dependent apoptosis in p53-deficient cancer cells. Cancer Res. 2008 Nov;68(21):8998-9004.
Dinneen SF, Valimaki MJ, Bergstralh EJ, Goellner JR, Gorman CA, Hay ID. Distant metastases in papillary thyroid carcinoma: 100 cases observed at one institution during 5 decades. J Clin Endocrinol Metab. 1995 Jul;80(7):2041-5.
Ditchfield C, Johnson VL, Tighe A, Ellston R, Haworth C, Johnson T. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol. 2003;161:267–80.
Dobashi Y, Sakamoto A, Sugimura H, Mernyei M, Mori M, Oyama T, Machinami R. Overexpression of p53 as a possible prognostic factor in human thyroid carcinoma. Am J Surg Pathol. 1993 Apr;17(4):375-81.
Dreier MR, Grabovich AZ, Katusin JD, Taylor WR. Short and long-term tumor cell responses to Aurora kinase inhibitors. Exp Cell Res. 2009;315:1085–99.
Du J, Hannon GJ. Suppression of p160ROCK bypasses cell cycle arrest after aurora-A/STK15 depletion. Proc Natl Acad Sci USA. 2004;101:8975-80.
Durante C, Haddy N, Baudin E, Leboulleux S, Hartl D, Travagli JP, Caillou B, Ricard M, Lumbroso JD, De Vathaire F, Schlumberger M. Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. Clin Endocrinol Metab. 2006 Aug;91(8):2892-9.
Fagin JA. Minireview: branded from the start-distinct oncogenic initiating events may determine tumor fate in the thyroid. Mol Endocrinol. 2002 May;16(5): 903–11.
Fagin JA, Matsuo K, Karmakar A, Chen DL, Tang SH, Koeffler HP. High prevalence of mutations of p53 gene in poorly differentiated human thyroid carcinomas. J Clin Invest. 1993 Jan;91(1):179-84.
Fu J, Bian M, Jiang Q, Zhang C. Roles of aurora kinases in mitosis and tumorigenesis. Mol Cancer Res. 2007 Jan;5(1):1-10.
Gautschi O, Heighway J, Mack PC, Purnell PR, Lara PN Jr, Gandara DR. Aurora kinases as anticancer drug targets. Clin Cancer Res. 2008 Mar 15;14(6):1639-48.
Gilliland FD, Hunt WC, Morris DM, Key CR. Prognostic factors for thyroid carcinoma. A population-based study of 15,698 cases from the Surveillance, Epidemiology and End Results (SEER) program 1973-1991. Cancer. 1997 Feb;79(3):564-73.
Gizatullin F, Yao Y, Kung V, Harding MW, Loda M, Shapiro GI. The Aurora kinase inhibitor VX-680 induces endoreduplication and apoptosis preferentially in cells with compromised p53-dependent postmitotic checkpoint function, Cancer Res. 2006;66:7668–77.
Grieco M, Santoro M, Berlingieri MT, Melillo RM, Donghi R, Bongarzone I, Pierotti MA, Della Porta G, Fusco A, Vecchio G. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell.1990 Feb;60(4):557–63.
Harrington EA, Bebbington D, Moore J, Rasmussen RK, Ajose-Adeogun AO, Nakayama T, Graham JA, Demur C, Hercend T, Diu-Hercend A, Su M, Golec JM, Miller KM. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med. 2004 Mar;10(3):262-7.
Hata T, Furukawa T, Sunamura M, Egawa S, Motoi F, Ohmura N, Marumoto T, Saya H, Horii A. RNA interference targeting aurora kinase a suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells. Cancer Res. 2005 Apr;65(7):2899-905.
Hsieh TC, Traganos F, Darzynkiewicz Z, Wu JM. The 2,6-disubstituted purine reversine induces growth arrest and polyploidy in human cancer cells. Int J Oncol. 2007 Dec;31(6):1293-300.
Ito T, Seyama T, Mizuno T, Tsuyama N, Hayashi Y, Dohi K, Nakamura N, Akiyama M. Unique association of p53 mutations with undifferentiated but not differentiated carcinomas of the thyroid gland. Cancer Res. 1992 Mar;52(5):1369-71.
Katayama H, Ota T, Jisaki F, Ueda Y, Tanaka T, Odashima S, Suzuki F, Terada Y, Tatsuka M. Mitotic kinase expression and colorectal cancer progression. J Natl Cancer Inst. 1999 Jul;91(13):1160-2.
Katayama H, Sasai K, Kawai H, Yuan ZM, Bondaruk J, Suzuki F, Fujii S, Arlinghaus RB, Czerniak BA, Sen S. Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet. 2004 Jan;36(1):55-62.
Kim YK, Choi HY, Kim NH, Lee W, Seo DW, Kang DW, Lee HY, Han JW, Park SW, Kim SN. Reversine stimulates adipocyte differentiation and downregulates Akt and p70(s6k) signaling pathways in 3T3-1 cells. Biochem Biophys Res Commun. 2007 Jun;358(2):553–8.
Knauf JA, Ma X, Smith EP, Zhang L, Mitsutake N, Liao XH, Refetoff S, Nikiforov YE, Fagin JA.. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res. 2005 May;65(10):4238-45.
Kojima K, Konopleva M, Tsao T, Nakakuma H, Andreeff M. Concomitant inhibition of Mdm2-p53 interaction and Aurora kinases activates the p53-dependent postmitotic checkpoints and synergistically induces p53-mediated mitochondrial apoptosis along with reduced endoreduplication in acute myelogenous leukemia. Blood. 2008 Oct;112(7):2886–95.
Kroll TG, Sarraf P, Pecciarini L, Chen CJ, Mueller E, Spiegelman BM, Fletcher JA.. PAX8-PPAR-1 fusion in oncogene human thyroid carcinoma. Science. 2000 Aug;289(5483):1357-60.
Kurai M, Shiozawa T, Shih HC, Miyamoto T, Feng YZ, Kashima H, Suzuki A, Konishi I. Expression of Aurora kinases A and B in normal, hyperplastic, and malignant human endometrium: Aurora B as a predictor for poor prognosis in endometrial carcinoma. Hum Pathol. 2005 Dec;36(12):1281-8.
Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96.
Lapenna S, Giordano A. Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
Lee EK, Bae GU, You JS, Lee JC, Jeon YJ, Park JW, Park JH, Ahn SH, Kim YK, Choi WS, Kang JS, Han G, Han JW. Reversine increases the plasticity of lineage-committed cells toward neuroectodermal lineage. J Biol Chem. 2009 Jan;284(5):2891-901.
Li M, Jung A, Ganswindt U, Marini P, Friedl A, Daniel PT, Lauber K, Jendrossek V, Belka C. Aurora kinase inhibitor ZM447439 induces apoptosis via mitochondrial pathways. Biochem Pharmacol. 2010;79(2):122-9.
McMillin DW, Delmore J, Weisberg E, Negri JM, Geer DC, Klippel S, Mitsiades N, Schlossman RL, Munshi NC, Kung AL, Griffin JD, Richardson PG, Anderson KC, Mitsiades CS. Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity. Nat Med. 2010 Apr;16(4):483-9.
Manfredi MG, Ecsedy JA, Meetze KA, Balani SK, Burenkova O, Chen W, Galvin KM, Hoar KM, Huck JJ, LeRoy PJ, Ray ET, Sells TB, Stringer B, Stroud SG, Vos TJ, Weatherhead GS, Wysong DR, Zhang M, Bolen JB, Claiborne CF. Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. Proc Natl Acad Sci U S A. 2007 Mar;104(10):4106-11.
Mazzaferri, EL. Undifferentiated thyroid carcinoma and unusual thyroid malignancies. In: Endocrine Tumors, Mazzaferri, EL, Samaan, NA (Eds), Blackwell Scientific Publications, Boston 1993. p.378.
Miyoshi Y, Iwao K, Egawa C, Noguchi S. Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers. Int J Cancer. 2001 May 1;92(3):370-3.
Murray-Zmijewski F, Lane DP, Bourdon JC. p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress. Cell Death Differ. 2006 Jun;13(6):962-72.
Nikiforova MN, Kimura ET, Gandhi M, Biddinger PW, Knauf JA, Basolo F, Zhu Z, Giannini R, Salvatore G, Fusco A, Santoro M, Fagin JA, Nikiforov YE. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003; 88(11):5399-404.
Nigg EA. Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol 2001 Jan;2(1):21-32.
Neben K, Korshunov A, Benner A, Wrobel G, Hahn M, Kokocinski F, Golanov A, Joos S, Lichter P. Microarray-based screening for molecular markers in medulloblastoma revealed STK15 as independent predictor for survival. Cancer Res. 2004 May;64(9):3103-11.
Oke A, Pearce D, Wilkinson RW, Crafter C, Odedra R, Cavenagh J, Fitzgibbon J, Lister AT, Joel S, Bonnet D. AZD1152 rapidly and negatively affects the growth and survival of human acute myeloid leukemia cells in vitro and in vivo. Clin Cancer Res. 2009 May;69(10):4150-8.
Ota T, Suto S, Katayama H, Han ZB, Suzuki F, Maeda M, Tanino M, Terada Y, Tatsuka M. Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability. Cancer Res. 2002 Sep;62(18):5168-77.
Pacini F, Schlumberger M, Dralle H, Elisei R, Smit JW, Wiersinga W; European Thyroid Cancer Taskforce. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium. Eur J Endocrinol. 2006 Jun;154(6):787-803.
Parry EM, Ulucan H, Wyllie FS, Wynford-Thomas D, Parry JM. Segregational fidelity of chromosomes in human thyroid tumour cells. Chromosoma. 1998 Dec;107(6-7):491-7.
Quiros RM, Ding HG, Gattuso P, Prinz RA, Xu X. Evidence that one subset of anaplastic thyroid carcinomas are derived from papillary carcinomas due to BRAF and p53 mutations. Cancer. 2005 Jun;103(11):2261-8.
Ries LAG, Eisner, MP, Kosary, CL, et al. SEER Cancer Statistics Review, 1975-2002. National Cancer Institute, Bethesda.
Sakakura C, Hagiwara A, Yasuoka R, Fujita Y, Nakanishi M, Masuda K, Shimomura K, Nakamura Y, Inazawa J, Abe T, Yamagishi H. Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation. Br J Cancer. 2001 Mar;84(6):824-31.
Sasai K, Katayama H, Stenoien DL, Fujii S, Honda R, Kimura M, Okano Y, Tatsuka M, Suzuki F, Nigg EA, Earnshaw WC, Brinkley WR, Sen S. Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells. Cell Motil Cytoskeleton. 2004 Dec;59(4):249-63.
Saraiya M, Nasser R, Zeng Y, Addya S, Ponnappan RK, Fortina P, Anderson DG, Albert TJ, Shapiro IM, Risbud MV. Reversine enhances generation of progenitor-like cells by dedifferentiation of annulus fibrosus cells. Tissue Eng Part A. 2010 Apr;16(4):1443-55.
Schellens JH, Boss D, Witteveen PO. Phase I and pharmacological study of the novel aurora kinase inhibitor AZD1152. J Clin Oncol. 2006;24:122s.
Sen S, Zhou H, Zhang RD, Yoon DS, Vakar-Lopez F, Ito S, Jiang F, Johnston D, Grossman HB, Ruifrok AC, Katz RL, Brinkley W, Czerniak B. Amplification/overexpression of a mitotic kinase gene in human bladder cancer. J Natl Cancer Inst. 2002 Sep;94(17):1320-9.
Sherman SI. Thyroid carcinoma. Lancet. 2003 Feb 8;361(9356):501–11.
Shahedian B, Shi Y, Zou M, Farid NR. Thyroid carcinoma is characterized by genomic instability: evidence from p53 mutations. Mol Genet Metab. 2001 Feb;72(2):155-63.
Soncini C, Carpinelli P, Gianellini L, Fancelli D, Vianello P, Rusconi L, Storici P, Zugnoni P, Pesenti E, Croci V, Ceruti R, Giorgini ML, Cappella P, Ballinari D, Sola F, Varasi M, Bravo R, Moll J. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res. 2006 Jul;12(13):4080-9.
Sorrentino R, Libertini S, Pallante PL, Troncone G, Palombini L, Bavetsias V, Spalletti-Cernia D, Laccetti P, Linardopoulos S, Chieffi P, Fusco A, Portella G. Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation. J Clin Endocrinol Metab. 2005 Feb;90(2):928-35.
Suarez HG, du Villard JA, Severino M, Caillou B, Schlumberger M, Tubiana M, Parmentier C, Monier R. Presence of mutations in all three ras genes in human thyroid tumors. Oncogene. 1990 Apr;5(4):565-70.
Tallini G, Asa SL. RET oncogene activation in papillary thyroid carcinoma. Adv Anat Pathol. 2001 Nov;8(6):345–54.
Takahashi T, Futamura M, Yoshimi N, Sano J, Katada M, Takagi Y, Kimura M, Yoshioka T, Okano Y, Saji S. Centrosomal kinases, HsAIRK1 and HsAIRK3, are overexpressed in primary colorectal cancers. Jpn J Cancer Res. 2000 Oct;91(10):1007-14.
Tanaka E, Hashimoto Y, Ito T, Okumura T, Kan T, Watanabe G, Imamura M, Inazawa J, Shimada Y. The clinical significance of Aurora-A/STK15/BTAK expression in human esophageal squamous cell carcinoma. Clin Cancer Res. 2005 Mar;11(5):1827-34.
Tanaka T, Kimura M, Matsunaga K, Fukada D, Mori H, Okano Y. Centrosomal kinase AIK1 is overexpressed in invasive ductal carcinoma of the breast. Cancer Res. 1999 May;59(9):2041-4.
Tanner MM, Grenman S, Koul A, Johannsson O, Meltzer P, Pejovic T, Borg A, Isola JJ. Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. Clin Cancer Res. 2000 May;6(5):1833-9.
Tatsuka M, Sato S, Kitajima S, Suto S, Kawai H, Miyauchi M, Ogawa I, Maeda M, Ota T, Takata T. Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is impicated in oral carcinogenesis. Oncogene. 2005 Feb;24(6):1122-7.
Terada Y, Tatsuka M, Suzuki F, Yasuda Y, Fujita S, Otsu M. AIM-1: a mammalian midbody-associated protein required for cytokinesis. EMBO J. 1998 Feb;17(3):667-76.
Tsuno T, Natsume A, Katsumata S, Mizuno M, Fujita M, Osawa H. Inhibition of Aurora-B function increases formation of multinucleated cells in p53 gene deficient cells and enhances anti-tumor effect of temozolomide in human glioma cells. J Neurooncol. 2007;83:249–58.
Ulisse S, Delcros JG, Baldini E, Toller M, Curcio F, Giacomelli L, Prigent C, Ambesi-Impiombato FS, D''Armiento M, Arlot-Bonnemains Y. Expression of Aurora kinases in human thyroid carcinoma cell lines and tissues. Int J Cancer. 2006 Jul;119(2):275-82.
Vagnarelli P, Earnshaw WC. Chromosomal passengers: the four-dimensional regulation of mitotic events. Chromosoma. 2004 Nov;113(5):211-22.
Veness MJ, Porter GS, Morgan GJ. Anaplastic thyroid carcinoma: dismal outcome despite current treatment approach. ANZ J Surg. 2004 Jul;74(7):559-62.
Wang HM, Huang YW, Huang JS, Wang CH, Kok VC, Hung CM, Chen HM, Tzen CY. Anaplastic carcinoma of the thyroid arising more often from follicular carcinoma than papillary carcinoma. Ann Surg Oncol. 2007 Oct;14(10):3011-8.
Wang XX, Liu R, Jin SQ, Fan FY, Zhan QM. Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line, Cell Res. 2006 Apr;16:356–66.
Wilkinson RW, Odedra R, Heaton SP, Wedge SR, Keen NJ, Crafter C, Foster JR, Brady MC, Bigley A, Brown E, Byth KF, Barrass NC, Mundt KE, Foote KM, Heron NM, Jung FH, Mortlock AA, Boyle FT, Green S. AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin Cancer Res. 2007 Jun;13(12):3682-8.
Wreesmann VB, Ghossein RA, Patel SG, Harris CP, Schnaser EA, Shaha AR, Tuttle RM, Shah JP, Rao PH, Singh B. Genome-wide appraisal of thyroid cancer progression. Am J Pathol. 2002 Nov;161(5):1549-56.
Xu X, Quiros RM, Gattuso P, Ain KB, Prinz RA.. High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Cancer Res. 2003 Sep;63(18):5685-90.
Zhong WB, Liang YC, Wang CY, Chang TC, Lee WS. Lovastatin suppresses invasiveness of anaplastic thyroid cancer cells by inhibiting Rho geranylgeranylation and RhoA/ROCK signaling. Endocr Relat Cancer. 2005 Sep;12(3):615-29.
Zhou H, Kuang J, Zhong L, Kuo WL, Gray JW, Sahin A, Brinkley BR, Sen S. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet. 1998 Oct;20(2):189-93.

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