博碩士論文 102323051 詳細資訊




以作者查詢圖書館館藏 以作者查詢臺灣博碩士 以作者查詢全國書目 勘誤回報 、線上人數:7 、訪客IP:3.237.66.86
姓名 游天賜(Tein-Ssu Yu)  查詢紙本館藏   畢業系所 機械工程學系
論文名稱 流體剪應力對膀胱癌細胞週期的影響
(The effects of fluid shear stress on the cell cycle of urothelial carcinoma)
相關論文
★ 溫度調變對二元合金固液介面形態穩定的影響★ 濃度調變對二元合金固液介面形態穩定的影響
★ 圓錐平板型生物反應器週期性流場研究★ 圓錐平板型生物反應器二次週期流場研究
★ 圓錐平板型生物反應器脈動式流場研究★ 濃度調變對單向固化形態穩定的影響
★ 圓錐平板型生物反應器脈動式二次流場研究★ 模擬注流式生物反應器之流場及細胞生長
★ 週期式圓錐平板裝置之設計與量測★ 模擬注流式生物反應器之細胞培養研究
★ 軟骨細胞在組織工程支架之培養研究★ 細胞在組織工程支架之生長與遷移
★ 冷電漿沉積類鑽碳膜之製程模擬分析★ 格狀自動機探討組織工程細胞體外培養研究
★ 細胞在注流式生物反應器之生長研究★ 週期式圓錐平板裝置之流場分析
檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   [檢視]  [下載]
  1. 本電子論文使用權限為同意立即開放。
  2. 已達開放權限電子全文僅授權使用者為學術研究之目的,進行個人非營利性質之檢索、閱讀、列印。
  3. 請遵守中華民國著作權法之相關規定,切勿任意重製、散佈、改作、轉貼、播送,以免觸法。

摘要(中) 細胞不受控制的持續分裂是發展成腫瘤的原因,已經有許多研究指出此不受控制的癌細胞中細胞週期素(cyclins)與細胞週期蛋白依賴性激酶(Cyclin-dependent kinases, CDKs)過度表現、細胞週期蛋白依賴性激酶抑制物(cyclin-dependent kinase inhibitors, CKIs)以及腫瘤抑制因子(tumor suppressor)突變或是缺失,導致細胞週期內檢查點機制受到破壞或干擾,使癌細胞無法做出適當回應,獲得抗凋亡的能力,最終發展成腫瘤。治療膀胱癌方法中,最常見就是在手術切除後,在膀胱灌入化學藥物,使藥物在膀胱內停留一段時間,徹底殺死殘留之癌細胞,減少疾病復發機率,藥物停留時間便會增加膀胱內壓力,有研究發現此壓力能抑制癌細胞生長,且與化學藥物配合更能提高細胞凋亡效果,體內有許多機械力存在,流體剪應力也是常見的一種,許多研究發現流體剪應力能使加速細胞生長、走向分化甚至能使細胞凋亡,那流體剪應力對於膀胱癌細胞是否也與壓力有類似效果呢?如果有那又是扮演什麼樣的角色又是透過什麼樣的機制來調控。因此本研究希望透過符合生理條件之流體剪應力刺激膀胱癌細胞,觀察膀胱癌細胞週期的變化。
本研究以剪應力生物反應器刺激膀胱癌細胞BFTC905細胞株,透過流式細胞儀、MTT細胞活性分析以及西方墨點法證實,以流體剪應力12 刺激24小時後,雖然無法誘導細胞週期蛋白依賴性激酶抑制物p18和腫瘤抑制因子p53的表現,但在G1期細胞比例卻增加,此可得知流體剪應力會誘導G1期停滯。再利用MTT分析,也發現在受流體剪應力刺激後,生長被抑制了,最後根據西方墨點法觀察,細胞週期素cyclin D1及細胞週期蛋白依賴性激酶CDK4/6表現量均下降,細胞週期素cyclin E(E1、E2)、cyclin A2和cyclin B1也都下降,但細胞週期蛋白依賴性激酶CDK2與CDC2不受流體剪應力影響,故可知細胞週期停滯在G1前期。然後發現在流體剪應力刺激後,細胞週期蛋白依賴性激酶抑制物p21和p27表現量均上升,p27上升更是明顯,所以cyclin D1-CDK4/6活性下降是透過p21和p27來抑制,並不是透過p18來調控。接著發現在受流體剪應力刺激後,視網膜母細胞瘤蛋白Rb總量下降的非常明顯,可能是細胞慢慢走向凋亡退出細胞週期,因此觀察細胞凋亡與自噬相關蛋白,發現輕鏈3蛋白LC3B與Beclin表現上升,細胞走向自噬(autophagy),而原態caspase 3(native caspase) 3和原態 caspase 8(native caspase 8)表現量也有上升趨勢,但是截切 caspase 8(cleaved caspase 8)表現量卻沒上升,細胞處於預凋亡(proapoptosis)。故受流體剪應力刺激後透過p53非依賴性路徑調控p21和p27,來抑制cyclin D1-CDK4/6之活性,造成G1期停滯,間接使細胞慢慢退出細胞週期造成細胞自噬與預凋亡。
摘要(英) Uncontrolled cells continuously grow that is the cause of tumor developments. Substantial researches have pointed that overexpression cyclins and CDKs, mutation or deletion of CKIs and tumors suppressors are common in uncontrolled cells. These situations will destroy or interfere with the checkpoint mechanism of cell cycle. As a result, the cells obtain anti-apoptosis ability and divide inappropriately. Finally it leads to tumorigenesis.
For treatments of bladder cancer, the most common method is the administration of chemicals such as mytomicin C after surgery. The administered chemicals kill the residual cancer cells, reducing the chance of disease recurrence. Increasing the residence time of chemical will increase the pressure within the bladder. Researches in cell biology suggest that pressure can inhibit the growth of cancer cells, and enhance cooperation with chemicals to cell death. There are other mechanical forces in vivo, such as fluid shear stress. Many literatures suggest that fluid shear stress can accelerate cell growth, differentiation or induce apoptosis. Whether fluid shear stress and pressure have a similar effect on bladder cancer cells? If it is true, what kinds of mechanisms regulate the cell cycle? This study aims to simulate bladder cancer cells by fluid shear stress, and investigates its effect on the cell cycle.
This study adopted the shear force bioreactor system to apply the fluid shear stress on BFTC905, a cell line of bladder cancer. The assessments of flow cytometry, MTT assay and Western blot were used to test the cells. For BFTC905 subjected to the fluid shear stress of 12 for 24 hrs, flow cytometry showed that most of the cells stayed in G1 phase, and the cell growth was also inhibited. Tumor suppressor p18 and p53 were not expressed for the cells in Western blot. Our Western blot data showed cyclin D1 and CDK4/6 were down-regulated. Cyclin E (E1, E2), cyclin A2 and cyclin B1 also were down-regulated. But CDK2 and CDC2 were not affected. These results concluded that fluid shear stress induced cell cycle arrest in G1 phase. In addition, p21 and p27 both were up-regulated. Especially p27 was much higher than control. This evidenced that cyclin D-CDK4/6 were regulated by p21 and p27 rather than p18. Moreover it was found that total Rb expression was down-regulated. This suggested that the cancer cells might undergo autophagy and apoptosis. To confirm this, we performed tests on LC3B and Beclin, the autophagy markers, which were shown to be up-regulated. We also found that native caspase 3/8, the apoptosis markers, were up-regulated, but nonetheless cleaved caspase 8 did not show apparent change. This suggested that the cells were not right in apoptosis, but might be in proapoptosis. To conclude our study, fluid shear stress induced G1 arrest by up-regulating p21 and p27 in a p53-independent pathway, which resulted in cyclin D1-CDK4/6 being down-regulated. The bladder cancer cells were then on the way toward autophagy and proapoptosis.
關鍵字(中) ★ 流體剪應力
★ 膀胱癌細胞
★ 細胞週期
★ G1期停滯
★ 自噬
★ 預凋亡
關鍵字(英) ★ fluid shear stress
★ bladder cancer
★ cell cycle
★ G1 arrest
★ autophagy
★ proapoptosis
論文目次 摘要 i
Abstract iii
誌謝 v
目錄 vi
圖目錄 ix
第一章 緒論 1
1.1研究動機 1
1.2文獻回顧 6
1.2.1物理刺激對細胞影響 6
1.2.2剪應力生物應器 9
1.2.3細胞週期 11
1.3研究目的 18
第二章 實驗方法 25
2.1 細胞來源 26
2.2 細胞培養 26
2.3實驗前置準備 28
2.4剪應力刺激實驗 31
2.5流體剪應力 33
2.5.1馬達轉速設定 33
2.5.2 定常轉速剪應力之計算 35
2.6實驗條件 37
2.7流式細胞儀分析 (Flow cytometric analysis) 37
2.8 細胞活性分析 (MTT assay) 39
2.9蛋白質定量分析 39
2.10蛋白質體電泳 (SDS-PAGE) 41
2.11西方墨點分析法(western blot analysis) 44
第三章 結果與討論 48
3.1 實驗前言 48
3.2 細胞週期各階段之分布率 49
3.3生長曲線分析 52
3.4西方墨點分析法之結果與討論 54
3.4.1 流體剪應力對cyclins與CDKs之影響 55
3.4.2 流體剪應力刺激對於CKIs之影響 60
3.4.3 流體剪應力刺激對Rb之影響 63
3.4.4 流體剪應力刺激對凋亡和自噬相關蛋白之影響 65
3.4.5 流體剪應力刺激誘導p53-非依賴性之G1停滯進而造成自噬與預凋亡 69
第四章 結論與未來展望 71
參考文獻 73
附錄-實驗耗材、藥品與儀器 86
參考文獻 Alberts B., Alexander J ., Julian L., Martin R., Keith R. and Peter W., 2002. Molecular biology of the cell. Garland Science.
Akimoto, S., M. Mitsumata, T. Sasaguri and Y. Yoshida (2000). "Laminar shear stress inhibits vascular endothelial cell proliferation by inducing cyclin-dependent kinase inhibitor p21(Sdi1/Cip1/Waf1)." Circ Res 86(2): 185-190.
Andres, V. (2004). "Control of vascular cell proliferation and migration by cyclin-dependent kinase signalling: new perspectives and therapeutic potential." Cardiovasc Res 63(1): 11-21.
Antonucci, L. A., J. V. Egger and N. A. Krucher (2014). "Phosphorylation of the Retinoblastoma protein (Rb) on serine-807 is required for association with Bax." Cell Cycle 13(22): 3611-3617.
Bai, K., Y. Huang, X. Jia, Y. Fan and W. Wang (2010). "Endothelium oriented differentiation of bone marrow mesenchymal stem cells under chemical and mechanical stimulations." J Biomech 43(6): 1176-1181.
Bincoletto, C., A. Bechara, G. J. Pereira, C. P. Santos, F. Antunes, J. Peixoto da-Silva, M. Muler, R. D. Gigli, P. T. Monteforte, H. Hirata, A. Jurkiewicz and S. S. Smaili (2013). "Interplay between apoptosis and autophagy, a challenging puzzle: new perspectives on antitumor chemotherapies." Chem Biol Interact 206(2): 279-288.
Blackman, B.R., Barbee, K.A., a nd Thibault, L.E., 2000. In vitro cell shearing device to investigate the dynamic response of cells in a controlled hydrodynamic environment. Biomedical Engineering Society 28, p.363-372
Blackman, B.R, García Cardeña, G., and Gimbrone, M.A., 2002. A new in vitro model to evaluate differential responses of endothelial cells to simulated arterial shear stress waveforms. Journal of Biomechanical Engineering 124, p.397-407
Blomen, V. A. and J. Boonstra (2007). "Cell fate determination during G1 phase progression." Cell Mol Life Sci 64(23): 3084-3104.
Borghese, L., D. Dolezalova, T. Opitz, S. Haupt, A. Leinhaas, B. Steinfarz, P. Koch, F. Edenhofer, A. Hampl and O. Brustle (2010). "Inhibition of notch signaling in human embryonic stem cell-derived neural stem cells delays G1/S phase transition and accelerates neuronal differentiation in vitro and in vivo." Stem Cells 28(5): 955-964.
Burdette, J. E., J. S. Jeruss, S. J. Kurley, E. J. Lee and T. K. Woodruff (2005). "Activin A mediates growth inhibition and cell cycle arrest through Smads in human breast cancer cells." Cancer Res 65(17): 7968-7975.
Burke, J. R., G. L. Hura and S. M. Rubin (2012). "Structures of inactive retinoblastoma protein reveal multiple mechanisms for cell cycle control." Genes Dev 26(11): 1156-1166.
Caldon, C. E. and E. A. Musgrove (2010). "Distinct and redundant functions of cyclin E1 and cyclin E2 in development and cancer." Cell Div 5: 2.
Chang, S. F., C. A. Chang, D. Y. Lee, P. L. Lee, Y. M. Yeh, C. R. Yeh, C. K. Cheng, S. Chien and J. J. Chiu (2008). "Tumor cell cycle arrest induced by shear stress: Roles of integrins and Smad." Proc Natl Acad Sci U S A 105(10): 3927-3932.
Chen, K., W. Fan, X. Wang, X. Ke, G. Wu and C. Hu (2012). "MicroRNA-101 mediates the suppressive effect of laminar shear stress on mTOR expression in vascular endothelial cells." Biochem Biophys Res Commun 427(1): 138-142.
Chiu, J. J., L. J. Chen, P. L. Lee, C. I. Lee, L. W. Lo, S. Usami and S. Chien (2003). "Shear stress inhibits adhesion molecule expression in vascular endothelial cells induced by coculture with smooth muscle cells." Blood 101(7): 2667-2674.
Cinatl, J., Jr., J. U. Vogel, R. Kotchetkov and H. Wilhelm Doerr (2004). "Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: a novel role for viral infection in tumor progression." FEMS Microbiol Rev 28(1): 59-77.
Gandhi, A. K., J. Kang, L. Capone, A. Parton, L. Wu, L. H. Zhang, D. Mendy, A. Lopez-Girona, T. Tran, L. Sapinoso, W. Fang, S. Xu, G. Hampton, J. B. Bartlett and P. Schafer (2010). "Dexamethasone synergizes with lenalidomide to inhibit multiple myeloma tumor growth, but reduces lenalidomide-induced immunomodulation of T and NK cell function." Curr Cancer Drug Targets 10(2): 155-167.
Garcia-Garcia, A., H. Rodriguez-Rocha, M. T. Tseng, R. Montes de Oca-Luna, H. S. Zhou, K. M. McMasters and J. G. Gomez-Gutierrez (2012). "E2F-1 lacking the transcriptional activity domain induces autophagy." Cancer Biol Ther 13(11): 1091-1101.
Gudas, J. M., M. Payton, S. Thukral, E. Chen, M. Bass, M. O. Robinson and S. Coats (1999). "Cyclin E2, a novel G1 cyclin that binds Cdk2 and is aberrantly expressed in human cancers." Mol Cell Biol 19(1): 612-622.
Hale, A. N., D. J. Ledbetter, T. R. Gawriluk and E. B. Rucker, 3rd (2013). "Autophagy: regulation and role in development." Autophagy 9(7): 951-972.
Han, Z., Y. Miwa, H. Obikane, M. Mitsumata, F. Takahashi-Yanaga, S. Morimoto and T. Sasaguri (2008). "Aryl hydrocarbon receptor mediates laminar fluid shear stress-induced CYP1A1 activation and cell cycle arrest in vascular endothelial cells." Cardiovasc Res 77(4): 809-818.
Harbour, J. W. and D. C. Dean (2000). "Rb function in cell-cycle regulation and apoptosis." Nat Cell Biol 2(4): E65-67.
Harbour, J. W. and D. C. Dean (2000). "The Rb/E2F pathway: expanding roles and emerging paradigms." Genes Dev 14(19): 2393-2409.
He, J., Y. Li, X. Yang, X. He, H. Zhang, J. He and L. Zhang (2012). "The feedback regulation of PI3K-miR-19a, and MAPK-miR-23b/27b in endothelial cells under shear stress." Molecules 18(1): 1-13.
Heilmann, A. M. and N. J. Dyson (2012). "Phosphorylation puts the pRb tumor suppressor into shape." Genes Dev 26(11): 1128-1130.
Herman, J. G., A. Merlo, L. Mao, R. G. Lapidus, J. P. Issa, N. E. Davidson, D. Sidransky and S. B. Baylin (1995). "Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers." Cancer Res 55(20): 4525-4530.
Horowitz, J. M., S. H. Park, E. Bogenmann, J. C. Cheng, D. W. Yandell, F. J. Kaye, J. D. Minna, T. P. Dryja and R. A. Weinberg (1990). "Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells." Proc Natl Acad Sci U S A 87(7): 2775-2779.
Huang, Y., X. Jia, K. Bai, X. Gong and Y. Fan (2010). "Effect of fluid shear stress on cardiomyogenic differentiation of rat bone marrow mesenchymal stem cells." Arch Med Res 41(7): 497-505.
Jain, A. K., K. Allton, M. Iacovino, E. Mahen, R. J. Milczarek, T. P. Zwaka, M. Kyba and M. C. Barton (2012). "p53 regulates cell cycle and microRNAs to promote differentiation of human embryonic stem cells." PLoS Biol 10(2): e1001268.
Jia, X., J. Yang, W. Song, P. Li, X. Wang, C. Guan, L. Yang, Y. Huang, X. Gong, M. Liu, L. Zheng and Y. Fan (2013). "Involvement of large conductance Ca(2+)-activated K (+) channel in laminar shear stress-induced inhibition of vascular smooth muscle cell proliferation." Pflugers Arch 465(2): 221-232.
Jiang, H., V. Martin, C. Gomez-Manzano, D. G. Johnson, M. Alonso, E. White, J. Xu, T. J. McDonnell, N. Shinojima and J. Fueyo (2010). "The RB-E2F1 pathway regulates autophagy." Cancer Res 70(20): 7882-7893.
Kang, R., H. J. Zeh, M. T. Lotze and D. Tang (2011). "The Beclin 1 network regulates autophagy and apoptosis." Cell Death Differ 18(4): 571-580.
Kang, Y. G., J. W. Shin, S. H. Park, M. J. Oh, H. S. Park, J. W. Shin and S. H. Kim (2014). "Effects of flow-induced shear stress on limbal epithelial stem cell growth and enrichment." PLoS One 9(3): e93023.
Kehn, K., L. Deng, C. de la Fuente, K. Strouss, K. Wu, A. Maddukuri, S. Baylor, R. Rufner, A. Pumfery, M. E. Bottazzi and F. Kashanchi (2004). "The role of cyclin D2 and p21/waf1 in human T-cell leukemia virus type 1 infected cells." Retrovirology 1: 6.
Kim, J. S., F. Pirnia, Y. H. Choi, P. M. Nguyen, B. Knepper, M. Tsokos, T. W. Schulte, M. J. Birrer, M. V. Blagosklonny, O. Schaefer, J. F. Mushinski and J. B. Trepel (2000). "Lovastatin induces apoptosis in a primitive neuroectodermal tumor cell line in association with RB down-regulation and loss of the G1 checkpoint." Oncogene 19(52): 6082-6090.
Kim, K. M., Y. J. Choi, J. H. Hwang, A. R. Kim, H. J. Cho, E. S. Hwang, J. Y. Park, S. H. Lee and J. H. Hong (2014). "Shear stress induced by an interstitial level of slow flow increases the osteogenic differentiation of mesenchymal stem cells through TAZ activation." PLoS One 9(3): e92427.
Knudsen E. S. and Knudsen K. E (2006). "Retinoblastoma tumor suppressor: Where cancer meets the cell cycle." Exp. Biol. Med. 231:1271-1281.
Korotayev, K. and D. Ginsberg (2008). "Many pathways to apoptosis: E2F1 regulates splicing of apoptotic genes." Cell Death Differ 15(12): 1813-1814.
Lange, C., W. B. Huttner and F. Calegari (2009). "Cdk4/cyclinD1 overexpression in neural stem cells shortens G1, delays neurogenesis, and promotes the generation and expansion of basal progenitors." Cell Stem Cell 5(3): 320-331.
Lasorella, A., G. Rothschild, Y. Yokota, R. G. Russell and A. Iavarone (2005). "Id2 mediates tumor initiation, proliferation, and angiogenesis in Rb mutant mice." Mol Cell Biol 25(9): 3563-3574.
Lee, W. S., R. J. Chen, Y. J. Wang, H. Tseng, J. H. Jeng, S. Y. Lin, Y. C. Liang, C. H. Chen, C. H. Lin, J. K. Lin, P. Y. Ho, J. S. Chu, W. L. Ho, L. C. Chen and Y. S. Ho (2003). "In vitro and in vivo studies of the anticancer action of terbinafine in human cancer cell lines: G0/G1 p53-associated cell cycle arrest." Int J Cancer 106(1): 125-137.
Leontieva, O. V. and M. V. Blagosklonny (2013). "CDK4/6-inhibiting drug substitutes for p21 and p16 in senescence: duration of cell cycle arrest and MTOR activity determine geroconversion." Cell Cycle 12(18): 3063-3069.
Lien, S. C., S. F. Chang, P. L. Lee, S. Y. Wei, M. D. Chang, J. Y. Chang and J. J. Chiu (2013). "Mechanical regulation of cancer cell apoptosis and autophagy: roles of bone morphogenetic protein receptor, Smad1/5, and p38 MAPK." Biochim Biophys Acta 1833(12): 3124-3133.
Liu, Y., Y. Cao, W. Zhang, S. Bergmeier, Y. Qian, H. Akbar, R. Colvin, J. Ding, L. Tong, S. Wu, J. Hines and X. Chen (2012). "A small-molecule inhibitor of glucose transporter 1 downregulates glycolysis, induces cell-cycle arrest, and inhibits cancer cell growth in vitro and in vivo." Mol Cancer Ther 11(8): 1672-1682.
Luo, W., W. Xiong, J. Zhou, Z. Fang, W. Chen, Y. Fan and F. Li (2011). "Laminar shear stress delivers cell cycle arrest and anti-apoptosis to mesenchymal stem cells." Acta Biochim Biophys Sin (Shanghai) 43(3): 210-216.
Malek, A. M., S. L. Alper and S. Izumo (1999). "Hemodynamic shear stress and its role in atherosclerosis." Jama 282(21): 2035-2042.
Masamha, C. P. and D. M. Benbrook (2009). "Cyclin D1 degradation is sufficient to induce G1 cell cycle arrest despite constitutive expression of cyclin E2 in ovarian cancer cells." Cancer Res 69(16): 6565-6572.
Narasimha, A. M., M. Kaulich, G. S. Shapiro, Y. J. Choi, P. Sicinski and S. F. Dowdy (2014). "Cyclin D activates the Rb tumor suppressor by mono-phosphorylation." Elife 3.
Nie, J., L. Liu, W. Zheng, L. Chen, X. Wu, Y. Xu, X. Du and W. Han (2012). "microRNA-365, down-regulated in colon cancer, inhibits cell cycle progression and promotes apoptosis of colon cancer cells by probably targeting Cyclin D1 and Bcl-2." Carcinogenesis 33(1): 220-225.
Ohno, M., G. H. Gibbons, V. J. Dzau and J. P. Cooke (1993). "Shear stress elevates endothelial cGMP. Role of a potassium channel and G protein coupling." Circulation 88(1): 193-197.
Ott, O. J., C. Rodel, C. Weiss, M. Wittlinger, F. St Krause, J. Dunst, R. Fietkau and R. Sauer (2009). "Radiochemotherapy for bladder cancer." Clin Oncol (R Coll Radiol) 21(7): 557-565.
Petrocca, F., R. Visone, M. R. Onelli, M. H. Shah, M. S. Nicoloso, I. de Martino, D. Iliopoulos, E. Pilozzi, C. G. Liu, M. Negrini, L. Cavazzini, S. Volinia, H. Alder, L. P. Ruco, G. Baldassarre, C. M. Croce and A. Vecchione (2008). "E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer." Cancer Cell 13(3): 272-286.
Polager, S. and D. Ginsberg (2009). "p53 and E2f: partners in life and death." Nat Rev Cancer 9(10): 738-748.
Qin, X., X. Wang, Y. Wang, Z. Tang, Q. Cui, J. Xi, Y. S. Li, S. Chien and N. Wang (2010). "MicroRNA-19a mediates the suppressive effect of laminar flow on cyclin D1 expression in human umbilical vein endothelial cells." Proc Natl Acad Sci U S A 107(7): 3240-3244.
Quelle, D. E., F. Zindy, R. A. Ashmun and C. J. Sherr (1995). "Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest." Cell 83(6): 993-1000.
Reininger, A. J., H. F. Heijnen, H. Schumann, H. M. Specht, W. Schramm and Z. M. Ruggeri (2006). "Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress." Blood 107(9): 3537-3545.
Rizzolio, F., C. Lucchetti, I. Caligiuri, I. Marchesi, M. Caputo, A. J. Klein-Szanto, L. Bagella, M. Castronovo and A. Giordano (2012). "Retinoblastoma tumor-suppressor protein phosphorylation and inactivation depend on direct interaction with Pin1." Cell Death Differ 19(7): 1152-1161.
Robert W., 2007. The biology of cancer. Garland Science.
Sa, G. and T. Das (2008). "Anti cancer effects of curcumin: cycle of life and death." Cell Div 3: 14.
Sai, K., S. Wang, V. Balasubramaniyan, C. Conrad, F. F. Lang, K. Aldape, S. Szymanski, I. Fokt, A. Dasgupta, T. Madden, S. Guan, Z. Chen, W. K. Alfred Yung, W. Priebe and H. Colman (2012). "Induction of cell-cycle arrest and apoptosis in glioblastoma stem-like cells by WP1193, a novel small molecule inhibitor of the JAK2/STAT3 pathway." J Neurooncol 107(3): 487-501.
Salomoni, P. and F. Calegari (2010). "Cell cycle control of mammalian neural stem cells: putting a speed limit on G1." Trends Cell Biol 20(5): 233-243.
Stoeckius, M., A. Erat, T. Fujikawa, M. Hiromura, A. Koulova, L. Otterbein, C. Bianchi, E. Tobiasch, Y. Dagon, F. W. Sellke and A. Usheva (2012). "Essential roles of Raf/extracellular signal-regulated kinase/mitogen-activated protein kinase pathway, YY1, and Ca2+ influx in growth arrest of human vascular smooth muscle cells by bilirubin." J Biol Chem 287(19): 15418-15426.
Strauss, R., P. Hamerlik, A. Lieber and J. Bartek (2012). "Regulation of stem cell plasticity: mechanisms and relevance to tissue biology and cancer." Mol Ther 20(5): 887-897.
Sucosky, P., K. Balachandran, A. Elhammali, H. Jo and A. P. Yoganathan (2009). "Altered shear stress stimulates upregulation of endothelial VCAM-1 and ICAM-1 in a BMP-4- and TGF-beta1-dependent pathway." Arterioscler Thromb Vasc Biol 29(2): 254-260.
Wang, B., S. Ling and W. C. Lin (2010). "14-3-3Tau regulates Beclin 1 and is required for autophagy." PLoS One 5(4): e10409.
Wang, K. C., L. X. Garmire, A. Young, P. Nguyen, A. Trinh, S. Subramaniam, N. Wang, J. Y. Shyy, Y. S. Li and S. Chien (2010). "Role of microRNA-23b in flow-regulation of Rb phosphorylation and endothelial cell growth." Proc Natl Acad Sci U S A 107(7): 3234-3239.
Weinberg, R. A. (1995). "The retinoblastoma protein and cell cycle control." Cell 81(3): 323-330.
Willoughby, J. A., Sr., S. N. Sundar, M. Cheung, A. S. Tin, J. Modiano and G. L. Firestone (2009). "Artemisinin blocks prostate cancer growth and cell cycle progression by disrupting Sp1 interactions with the cyclin-dependent kinase-4 (CDK4) promoter and inhibiting CDK4 gene expression." J Biol Chem 284(4): 2203-2213.
Wilson, W. H., J. Teruya-Feldstein, T. Fest, C. Harris, S. M. Steinberg, E. S. Jaffe and M. Raffeld (1997). "Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance in non-Hodgkin′s lymphomas." Blood 89(2): 601-609.
Wirawan, E., L. Vande Walle, K. Kersse, S. Cornelis, S. Claerhout, I. Vanoverberghe, R. Roelandt, R. De Rycke, J. Verspurten, W. Declercq, P. Agostinis, T. Vanden Berghe, S. Lippens and P. Vandenabeele (2010). "Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria." Cell Death Dis 1: e18.
Wolter, F., B. Akoglu, A. Clausnitzer and J. Stein (2001). "Downregulation of the cyclin D1/Cdk4 complex occurs during resveratrol-induced cell cycle arrest in colon cancer cell lines." J Nutr 131(8): 2197-2203.
Wu, C. C., Y. C. Chao, C. N. Chen, S. Chien, Y. C. Chen, C. C. Chien, J. J. Chiu and B. Linju Yen (2008). "Synergism of biochemical and mechanical stimuli in the differentiation of human placenta-derived multipotent cells into endothelial cells." J Biomech 41(4): 813-821.
Zafonte, B. T., J. Hulit, D. F. Amanatullah, C. Albanese, C. Wang, E. Rosen, A. Reutens, J. A. Sparano, M. P. Lisanti and R. G. Pestell (2000). "Cell-cycle dysregulation in breast cancer: breast cancer therapies targeting the cell cycle." Front Biosci 5: D938-961.
Zhou, J., Y. S. Li, P. Nguyen, K. C. Wang, A. Weiss, Y. C. Kuo, J. J. Chiu, J. Y. Shyy and S. Chien (2013). "Regulation of vascular smooth muscle cell turnover by endothelial cell-secreted microRNA-126: role of shear stress." Circ Res 113(1): 40-51.
Zhu, R., S. T. Zou, J. M. Wan, W. Li, X. L. Li and W. Zhu (2013). "BTG1 inhibits breast cancer cell growth through induction of cell cycle arrest and apoptosis." Oncol Rep 30(5): 2137-2144.
劉威宏,2012,流體剪應力結合1-甲基-3-異丁基黃嘌呤對於人類胎盤幹細胞分化之影響
施秉玠,2013,靜水壓影響膀胱癌細胞之分子機制探討
陳紹寬,2014,靜水壓力增強絲裂霉素C對泌尿上皮癌感受性的基因途徑
指導教授 鍾志昂(Chih-Ang Chung) 審核日期 2016-8-25
推文 facebook   plurk   twitter   funp   google   live   udn   HD   myshare   reddit   netvibes   friend   youpush   delicious   baidu   
網路書籤 Google bookmarks   del.icio.us   hemidemi   myshare   

若有論文相關問題,請聯絡國立中央大學圖書館推廣服務組 TEL:(03)422-7151轉57407,或E-mail聯絡  - 隱私權政策聲明