(18.204.227.34) 您好!臺灣時間:2021/05/14 08:38
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:林安安
研究生(外文):An-An Lin
論文名稱:柚皮素增敏人類口腔癌SAS細胞促進TRAIL引起的細胞凋亡機轉之研究
論文名稱(外文):The Study of Naringenin Sensitizes Human Oral Cancer SAS Cells to TRAIL-induced Apoptosis
指導教授:陳信銘陳信銘引用關係
指導教授(外文):Hsin-Ming Chen
口試委員:郭彥彬江俊斌
口試委員(外文):Yen-Ping KuoChun-Pin Chiang
口試日期:2013-07-18
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:口腔生物科學研究所
學門:醫藥衛生學門
學類:牙醫學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:56
中文關鍵詞:口腔癌柚皮素TRAILDR5XIAP細胞凋亡
外文關鍵詞:Oral cancernaringeninTRAILDR5XIAPapoptosis
相關次數:
  • 被引用被引用:0
  • 點閱點閱:359
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
口腔癌發生率與死亡率的排名居高不下,且口腔癌為癌症個案數增加之前5名。目前口腔癌的治療仍以手術為第一線,放射線治療、化學治療和免疫療法佐以輔助手術治療。在化學治療方面,其使用藥物經常會影響生長快速的細胞,因此,患者可能會產生抵抗力降低、失去食慾、噁心、嘔吐或口腔潰瘍等副作用出現。
如何找到毒性低的化學治療藥物,具有良好的抗癌效用並不會對正常細胞造成影響,以改善目前的癌症治療方法,成為目前癌症研究的主要趨勢之一。
柚皮素(Naringenin)屬於黃烷酮類,是類黃酮的一種。已有不少研究指出,柚皮素具有降血脂、抗發炎、抗氧化、抗腫瘤增生及轉移等作用。而TRAIL[Tumor necrosis factor (TNF) related apoptosis-inducing ligand]在近年來被視為良好的抗癌藥劑,可以有效地在癌症細胞而不在正常細胞引發細胞凋亡,但許多種人類的癌症細胞對於TRAIL有阻抗性的現象產生,導致不少病患對TRAIL的治療沒有反應。因此本實驗來探討柚皮素與TRAIL合併使用後,其對於人類口腔癌細胞株SAS的影響,並了解其可能的作用機制。
結果顯示,不論以柚皮素或TRAIL處理細胞,皆不會造成顯著細胞存活率變化,但以柚皮素與TRAIL合併使用後,可以顯著地降低細胞存活率。以各種螢光染色分析及流式細胞儀分析發現柚皮素與TRAIL兩者合併使用後,皆比個別分別使用時,可以顯著地增加細胞凋亡的比例。
之後以西方墨點法分析顯示柚皮素與TRAIL協同造成的細胞凋亡主要是經由外生性細胞凋亡路徑的活化。進一步研究發現,隨著柚皮素濃度與時間的增加,不論是在蛋白質或mRNA方面,會使DR5表現上升及XIAP表現量下降,也因此造成外生性細胞凋亡路徑的活化,進而誘發細胞凋亡。
總結來說,柚皮素可以藉由增加DR5的表現及降低XIAP、cIAP-1的表現,促進外生性細胞凋亡路徑,因此加上低濃度TRAIL時,便會加乘性地造成細胞凋亡。


Oral cancer incidence and mortality rank high, and the increased number of oral cancer cases are within the top 5 in Taiwan. Currently the frontline therapy of oral cancer is still surgery. Radiation therapy, chemotherapy and immunotherapy are combined as an adjunctive therapy. The drugs used in chemotherapy often affect the fast-growing cells, so patients may cause low immunity, loss of appetite, nausea, vomiting, mouth ulcers and other side effects. How to find chemotherapeutic agents with low toxicity that does not affect normal cells is one of the main trends in cancer research.
Naringenin is a flavonoid that is believed to have a bioactive effect on human health. Several previous studies had demonstrated that naringenin exhibits aorta dilatory, antioxidant, antiestrogenic, anti-proliferative and antimetastatic effects.
TRAIL[Tumor necrosis factor (TNF) related apoptosis-inducing ligand] has attracted even more attention because TRAIL can induce apoptosis in most cancer cells and not affect normal cells. The emergence of resistance to TRAIL is a major problem that limits its utility as a therapeutic. In this study, we investigated the effect and the possible mechanism of naringenin plus TRAIL in human oral cancer SAS cells.
Our results revealed that naringenin and TRAIL could not change cell viability individually. When naringenin combined with TRAIL, cellular activity was significantly decreased and the proportion of apoptosis was increased by a variety of fluorescent staining and flow cytometry.
Then we found out that the apoptosis caused by naringenin plus TRAIL is mainly through the activation of extrinsic pathway. Further studies showed that naringenin dose -and time-dependently up-regulates DR5 expression and down-regulates XIAP expression in protein and mRNA level. Thus, the activated extrinsic pathway caused apoptosis.
Summary, our results showed that naringenin may enhance the apoptotic extrinsic pathway by up-regulating DR5 expression and down-regulating XIAP、cIAP-1 expression. Furthermore, co-treatment with naringenin and TRAIL resulted in apoptosis synergistically.


目錄
口試委員會審定書 Ⅰ
致謝 Ⅱ
中文摘要 Ⅲ
英文摘要 Ⅳ
目錄 1
第一章 導論
第一節 口腔癌 3
1. 口腔癌簡介 3
2. 口腔癌診斷與分期 3
3. 口腔癌治療 4
第二節 柚皮素(Narigenin) 5
第三節 細胞凋亡(Apoptosis) 6
1. 外生性細胞凋亡路徑(Extrinsic pathway) 6
2. 內生性細胞凋亡路徑(Intrinsic pathway) 7
第四節 細胞凋亡抑制蛋白質The inhibitors of apoptosis (IAP) proteins…………..9
第五節 細胞自噬(Autophagy) 10
第二章 實驗材料與方法 11
第一節 細胞株培養 11
1. 細胞培養條件 11
2. 繼代培養 11
第二節 細胞存活率試驗 (MTT assay) 11
1. 原理 11
2. 實驗步驟 12
第三節 細胞螢光染色法 12
1. Hoechst stain 12
2. PI stain 13
3. Live/dead Assay 13
第四節 流式細胞儀 (Flow cytometry) 14
1. Tunel assay 14
第五節 西方墨點法 (Western blot) 15
1. 收集細胞 15
2. 蛋白質萃取 15
3. 蛋白質濃度測定(Bicinchoninic acid protein assay)………………………………15
4. 膠體配置 16
5. 膠體電泳 16
6. 轉漬 16
7. 抗體結合 16
8. 顯影呈色 17
第六節 抑制劑使用 17
第七節 細胞RNA萃取 17
第八節 反轉錄即時定量聚合酶連鎖反應 (qRT-PCR) 17
1. 原理 17
2. 實驗步驟 18
第三章 實驗結果 19
第一節 Naringenin及TRAIL不會影響口腔癌細胞株之細胞存活率 19
1. Naringenin細胞存活率試驗 19
2. TRAIL細胞存活率試驗 19
第二節 Naringenin與TRAIL合併作用後,會顯著地增加口腔癌細胞株之細胞凋亡比例 19
1. 細胞存活率試驗 19
2. 細胞螢光染色分析 20
3. 細胞凋亡比例變化 20
第三節 Naringenin與TRAIL合併作用後,不會影響口腔黏膜纖維母細胞株OMF之細胞存活率 21
第四節 Naringenin與TRAIL合併作用後,會明顯增加外生性細胞凋亡路徑之表現 21
1. 內生性與外生性路徑比較 21
2. 細胞DR5蛋白質及mRNA表現 22
第五節 Naringenin作用後,會顯著地降低細胞抗凋亡蛋白質XIAP之表現.22
1 細胞抗凋亡蛋白質與促凋亡蛋白質表現 22
2. 細胞XIAP蛋白質表現 23
第六節 處理ROS抑制劑後,會降低Naringenin誘導之細胞DR5蛋白質表現 23
第七節 高濃度Naringenin使用,會增加細胞自噬路徑之LC3蛋白質表現 24
第四章 討論 25
圖與表 29
附圖 45
第五章 參考文獻 49



Abou El Naga, R. N., S. S. Azab, E. El-Demerdash, S. Shaarawy, M. El-Merzabani and S. M. Ammar el (2013). "Sensitization of TRAIL-induced apoptosis in human hepatocellular carcinoma HepG2 cells by phytochemicals." Life Sci 92(10): 555-561.

Almasan, A. and A. Ashkenazi (2003). "Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy." Cytokine Growth Factor Rev 14(3-4): 337-348.

Anand, K., A. Sarkar, A. Kumar, R. K. Ambasta and P. Kumar (2012). "Combinatorial antitumor effect of naringenin and curcumin elicit angioinhibitory activities in vivo." Nutr Cancer 64(5): 714-724.

Arul, D. and P. Subramanian (2013). "Naringenin (Citrus Flavonone) Induces Growth Inhibition, Cell Cycle Arrest and Apoptosis in Human Hepatocellular Carcinoma Cells." Pathol Oncol Res.

Ashkenazi, A., P. Holland and S. G. Eckhardt (2008). "Ligand-based targeting of apoptosis in cancer: the potential of recombinant human apoptosis ligand 2/Tumor necrosis factor-related apoptosis-inducing ligand (rhApo2L/TRAIL)." J Clin Oncol 26(21): 3621-3630.

Bertrand, M. J., S. Milutinovic, K. M. Dickson, W. C. Ho, A. Boudreault, J. Durkin, J. W. Gillard, J. B. Jaquith, S. J. Morris and P. A. Barker (2008). "cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination." Mol Cell 30(6): 689-700.
Chen, D., M. S. Chen, Q. C. Cui, H. Yang and Q. P. Dou (2007). "Structure-proteasome-inhibitory activity relationships of dietary flavonoids in human cancer cells." Front Biosci 12: 1935-1945.

Chen, Y. C., S. C. Shen and H. Y. Lin (2003). "Rutinoside at C7 attenuates the apoptosis-inducing activity of flavonoids." Biochem Pharmacol 66(7): 1139-1150.
Cory, S. and J. M. Adams (2002). "The Bcl2 family: regulators of the cellular life-or-death switch." Nat Rev Cancer 2(9): 647-656.

Deeb, D., Y. X. Xu, H. Jiang, X. Gao, N. Janakiraman, R. A. Chapman and S. C. Gautam (2003). "Curcumin (diferuloyl-methane) enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in LNCaP prostate cancer cells." Mol Cancer Ther 2(1): 95-103.

Deveraux, Q. L., R. Takahashi, G. S. Salvesen and J. C. Reed (1997). "X-linked IAP is a direct inhibitor of cell-death proteases." Nature 388(6639): 300-304.

Eskelinen, E. L. and P. Saftig (2009). "Autophagy: a lysosomal degradation pathway with a central role in health and disease." Biochim Biophys Acta 1793(4): 664-673.

Feldstein, A. E. and G. J. Gores (2005). "Apoptosis in alcoholic and nonalcoholic steatohepatitis." Front Biosci 10: 3093-3099.

Galati, G., M. Y. Moridani, T. S. Chan and P. J. O''Brien (2001). "Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation." Free Radic Biol Med 30(4): 370-382.

Galluzzo, P., P. Ascenzi, P. Bulzomi and M. Marino (2008). "The nutritional flavanone naringenin triggers antiestrogenic effects by regulating estrogen receptor alpha-palmitoylation." Endocrinology 149(5): 2567-2575.

Glick, D., S. Barth and K. F. Macleod (2010). "Autophagy: cellular and molecular mechanisms." J Pathol 221(1): 3-12.

Grotzer, M. A., A. Eggert, T. J. Zuzak, A. J. Janss, S. Marwaha, B. R. Wiewrodt, N. Ikegaki, G. M. Brodeur and P. C. Phillips (2000). "Resistance to TRAIL-induced apoptosis in primitive neuroectodermal brain tumor cells correlates with a loss of caspase-8 expression." Oncogene 19(40): 4604-4610.

Harmon, A. W. and Y. M. Patel (2004). "Naringenin inhibits glucose uptake in MCF-7 breast cancer cells: a mechanism for impaired cellular proliferation." Breast Cancer Res Treat 85(2): 103-110.

Hunter, A. M., E. C. LaCasse and R. G. Korneluk (2007). "The inhibitors of apoptosis (IAPs) as cancer targets." Apoptosis 12(9): 1543-1568.

Imoto, I., H. Tsuda, A. Hirasawa, M. Miura, M. Sakamoto, S. Hirohashi and J. Inazawa (2002). "Expression of cIAP1, a target for 11q22 amplification, correlates with resistance of cervical cancers to radiotherapy." Cancer Res 62(17): 4860-4866.

Jin, C. Y., C. Park, J. H. Lee, K. T. Chung, T. K. Kwon, G. Y. Kim, B. T. Choi and Y. H. Choi (2009). "Naringenin-induced apoptosis is attenuated by Bcl-2 but restored by the small molecule Bcl-2 inhibitor, HA 14-1, in human leukemia U937 cells." Toxicol In Vitro 23(2): 259-265.

Jung, E. M., J. H. Lim, T. J. Lee, J. W. Park, K. S. Choi and T. K. Kwon (2005). "Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5)." Carcinogenesis 26(11): 1905-1913.

Kabeya, Y., N. Mizushima, T. Ueno, A. Yamamoto, T. Kirisako, T. Noda, E. Kominami, Y. Ohsumi and T. Yoshimori (2000). "LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing." EMBO J 19(21): 5720-5728.

Kanno, S., A. Shouji, K. Asou and M. Ishikawa (2003). "Effects of naringin on hydrogen peroxide-induced cytotoxicity and apoptosis in P388 cells." J Pharmacol Sci 92(2): 166-170.

Kanno, S., A. Shouji, R. Hirata, K. Asou and M. Ishikawa (2004). "Effects of naringin on cytosine arabinoside (Ara-C)-induced cytotoxicity and apoptosis in P388 cells." Life Sci 75(3): 353-365.

Kanno, S., A. Tomizawa, T. Hiura, Y. Osanai, A. Shouji, M. Ujibe, T. Ohtake, K. Kimura and M. Ishikawa (2005). "Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice." Biol Pharm Bull 28(3): 527-530.

Kanno, S., A. Tomizawa, T. Ohtake, K. Koiwai, M. Ujibe and M. Ishikawa (2006). "Naringenin-induced apoptosis via activation of NF-kappaB and necrosis involving the loss of ATP in human promyeloleukemia HL-60 cells." Toxicol Lett 166(2): 131-139.

Kelley, R. F., K. Totpal, S. H. Lindstrom, M. Mathieu, K. Billeci, L. Deforge, R. Pai, S. G. Hymowitz and A. Ashkenazi (2005). "Receptor-selective mutants of apoptosis-inducing ligand 2/tumor necrosis factor-related apoptosis-inducing ligand reveal a greater contribution of death receptor (DR) 5 than DR4 to apoptosis signaling." J Biol Chem 280(3): 2205-2212.

Kim, J. Y., E. H. Kim, S. S. Park, J. H. Lim, T. K. Kwon and K. S. Choi (2008). "Quercetin sensitizes human hepatoma cells to TRAIL-induced apoptosis via Sp1-mediated DR5 up-regulation and proteasome-mediated c-FLIPS down-regulation." J Cell Biochem 105(6): 1386-1398.

Kroemer, G. and J. C. Reed (2000). "Mitochondrial control of cell death." Nat Med 6(5): 513-519.

Le Marchand, L., S. P. Murphy, J. H. Hankin, L. R. Wilkens and L. N. Kolonel (2000). "Intake
of flavonoids and lung cancer." J Natl Cancer Inst 92(2): 154-160.

Lentini, A., C. Forni, B. Provenzano and S. Beninati (2007). "Enhancement of transglutaminase activity and polyamine depletion in B16-F10 melanoma cells by flavonoids naringenin and hesperitin correlate to reduction of the in vivo metastatic potential." Amino Acids 32(1): 95-100.

Li, H., H. Zhu, C. J. Xu and J. Yuan (1998). "Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis." Cell 94(4): 491-501.

Lopez, J. and P. Meier (2010). "To fight or die - inhibitor of apoptosis proteins at the crossroad of innate immunity and death." Curr Opin Cell Biol 22(6): 872-881.

Luo, X., I. Budihardjo, H. Zou, C. Slaughter and X. Wang (1998). "Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors." Cell 94(4): 481-490.

Massey, A., R. Kiffin and A. M. Cuervo (2004). "Pathophysiology of chaperone-mediated autophagy." Int J Biochem Cell Biol 36(12): 2420-2434.

Micheau, O. and J. Tschopp (2003). "Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes." Cell 114(2): 181-190.

Mijaljica, D., M. Prescott and R. J. Devenish (2011). "Microautophagy in mammalian cells: revisiting a 40-year-old conundrum." Autophagy 7(7): 673-682.

Miller, E. G., J. J. Peacock, T. C. Bourland, S. E. Taylor, J. M. Wright, B. S. Patil and E. G. Miller (2008). "Inhibition of oral carcinogenesis by citrus flavonoids." Nutr Cancer 60(1): 69-74.

Miller, L. K. (1999). "An exegesis of IAPs: salvation and surprises from BIR motifs." Trends Cell Biol 9(8): 323-328.

Miura, K., W. Fujibuchi, K. Ishida, T. Naitoh, H. Ogawa, T. Ando, N. Yazaki, K. Watanabe, S. Haneda, C. Shibata and I. Sasaki (2011). "Inhibitor of apoptosis protein family as diagnostic markers and therapeutic targets of colorectal cancer." Surg Today 41(2): 175-182.

Nachmias, B., Y. Ashhab and D. Ben-Yehuda (2004). "The inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer." Semin Cancer Biol 14(4): 231-243.

Nahmias, Y., J. Goldwasser, M. Casali, D. van Poll, T. Wakita, R. T. Chung and M. L. Yarmush (2008). "Apolipoprotein B-dependent hepatitis C virus secretion is inhibited by the grapefruit flavonoid naringenin." Hepatology 47(5): 1437-1445.

Nakagawa, Y., S. Abe, M. Kurata, M. Hasegawa, K. Yamamoto, M. Inoue, T. Takemura, K. Suzuki and M. Kitagawa (2006). "IAP family protein expression correlates with poor outcome of multiple myeloma patients in association with chemotherapy-induced overexpression of multidrug resistance genes." Am J Hematol 81(11): 824-831.

Park, J. H., C. Y. Jin, B. K. Lee, G. Y. Kim, Y. H. Choi and Y. K. Jeong (2008). "Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells." Food Chem Toxicol 46(12): 3684-3690.

Plummer, R., G. Attard, S. Pacey, L. Li, A. Razak, R. Perrett, M. Barrett, I. Judson, S. Kaye, N. L. Fox, W. Halpern, A. Corey, H. Calvert and J. de Bono (2007). "Phase 1 and pharmacokinetic study of lexatumumab in patients with advanced cancers." Clin Cancer Res 13(20): 6187-6194.

Ruh, M. F., T. Zacharewski, K. Connor, J. Howell, I. Chen and S. Safe (1995). "Naringenin: a weakly estrogenic bioflavonoid that exhibits antiestrogenic activity." Biochem Pharmacol 50(9): 1485-1493.


Sensintaffar, J., F. L. Scott, R. Peach and J. H. Hager (2010). "XIAP is not required for human tumor cell survival in the absence of an exogenous death signal." BMC Cancer 10: 11.

Sheridan, J. P., S. A. Marsters, R. M. Pitti, A. Gurney, M. Skubatch, D. Baldwin, L. Ramakrishnan, C. L. Gray, K. Baker, W. I. Wood, A. D. Goddard, P. Godowski and A. Ashkenazi (1997). "Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors." Science 277(5327): 818-821.

Stennicke, H. R., C. A. Ryan and G. S. Salvesen (2002). "Reprieval from execution: the molecular basis of caspase inhibition." Trends Biochem Sci 27(2): 94-101.

Tamm, I., S. M. Kornblau, H. Segall, S. Krajewski, K. Welsh, S. Kitada, D. A. Scudiero, G. Tudor, Y. H. Qui, A. Monks, M. Andreeff and J. C. Reed (2000). "Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias." Clin Cancer Res 6(5): 1796-1803.

Torricelli, P., P. Ricci, B. Provenzano, A. Lentini and C. Tabolacci (2011). "Synergic effect of alpha-tocopherol and naringenin in transglutaminase-induced differentiation of human prostate cancer cells." Amino Acids 41(5): 1207-1214.

Totta, P., F. Acconcia, S. Leone, I. Cardillo and M. Marino (2004). "Mechanisms of naringenin-induced apoptotic cascade in cancer cells: involvement of estrogen receptor alpha and beta signalling." IUBMB Life 56(8): 491-499.

Truneh, A., S. Sharma, C. Silverman, S. Khandekar, M. P. Reddy, K. C. Deen, M. M.
McLaughlin, S. M. Srinivasula, G. P. Livi, L. A. Marshall, E. S. Alnemri, W. V. Williams and M. L. Doyle (2000). "Temperature-sensitive differential affinity of TRAIL for its receptors. DR5 is the highest affinity receptor." J Biol Chem 275(30): 23319-23325.

van Meeuwen, J. A., N. Korthagen, P. C. de Jong, A. H. Piersma and M. van den Berg (2007). "(Anti)estrogenic effects of phytochemicals on human primary mammary fibroblasts, MCF-7 cells and their co-culture." Toxicol Appl Pharmacol 221(3): 372-383.

Vaux, D. L. and J. Silke (2003). "Mammalian mitochondrial IAP binding proteins." Biochem Biophys Res Commun 304(3): 499-504.
Vucic, D., V. M. Dixit and I. E. Wertz (2011). "Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death." Nat Rev Mol Cell Biol 12(7): 439-452.

Wang, B. D., Z. Y. Yang, Q. Wang, T. K. Cai and P. Crewdson (2006). "Synthesis, characterization, cytotoxic activities, and DNA-binding properties of the La(III) complex with Naringenin Schiff-base." Bioorg Med Chem 14(6): 1880-1888.

Wang, X., W. Chen, W. Zeng, L. Bai, Y. Tesfaigzi, S. A. Belinsky and Y. Lin (2008). "Akt-mediated eminent expression of c-FLIP and Mcl-1 confers acquired resistance to TRAIL-induced cytotoxicity to lung cancer cells." Mol Cancer Ther 7(5): 1156-1163.

Wu, G. S., T. F. Burns, E. R. McDonald, 3rd, W. Jiang, R. Meng, I. D. Krantz, G. Kao, D. D. Gan, J. Y. Zhou, R. Muschel, S. R. Hamilton, N. B. Spinner, S. Markowitz, G. Wu and W. S. el-Deiry (1997). "KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene." Nat Genet 17(2): 141-143.

Yodkeeree, S., B. Sung, P. Limtrakul and B. B. Aggarwal (2009). "Zerumbone enhances TRAIL-induced apoptosis through the induction of death receptors in human colon cancer cells: Evidence for an essential role of reactive oxygen species." Cancer Res 69(16): 6581-6589.

Yorimitsu, T. and D. J. Klionsky (2005). "Autophagy: molecular machinery for self-eating." Cell Death Differ 12 Suppl 2: 1542-1552.

Youle, R. J. and A. Strasser (2008). "The BCL-2 protein family: opposing activities that mediate cell death." Nat Rev Mol Cell Biol 9(1): 47-59.

Younes, A., J. M. Vose, A. D. Zelenetz, M. R. Smith, H. A. Burris, S. M. Ansell, J. Klein, W. Halpern, R. Miceli, E. Kumm, N. L. Fox and M. S. Czuczman (2010). "A Phase 1b/2 trial of mapatumumab in patients with relapsed/refractory non-Hodgkin''s lymphoma." Br J Cancer 103(12): 1783-1787.

Zhang, L. and B. Fang (2005). "Mechanisms of resistance to TRAIL-induced apoptosis in cancer." Cancer Gene Ther 12(3): 228-237.



Zhou, H. Z., R. A. Swanson, U. Simonis, X. Ma, G. Cecchini and M. O. Gray (2006). "Poly(ADP-ribose) polymerase-1 hyperactivation and impairment of mitochondrial respiratory chain complex I function in reperfused mouse hearts." Am J Physiol Heart Circ Physiol 291(2): H714-723.


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔