簡易檢索 / 詳目顯示

回結果列表
研究生： 朱敬儀
Ching-yi Chu
論文名稱： P388D1老鼠巨噬細胞分泌胞殺素誘導漿細胞瘤自戕現象之研究
Induction of apoptosis in plasmacytoma cells by a cytotoxic factor secreted by P388D1 mouse macrophage-like cell line
指導教授： 曾哲明
Tseng, Jer-Ming
學位類別： 博士
Doctor
系所名稱： 生命科學系
Department of Life Science
畢業學年度： 87
語文別： 中文
中文關鍵詞： 巨噬細胞 、漿細胞瘤胞殺素 、自戕
英文關鍵詞： Macrophage, PCF(plasmacytoma cytotoxic factor), Apoptosis, Fas, FasL, bCL-2, Caspase 3, PARP
論文種類： 學術論文
相關次數： 點閱：372  下載：7 
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報

    • 巨噬細胞的重要功能之一為對腫瘤細胞的胞殺作用。本研究發現老鼠巨噬細胞P388D1細胞株培養基上清液對MOPC-315漿細胞瘤細胞株具有胞殺作用， 對MPC-11也有胞殺作用， 但對J558細胞株卻完全沒有胞殺作用。本實驗先以40~60%飽和度之硫酸銨沉澱胞殺活性物質，再利用抗漿細胞瘤胞殺素之單株抗體CB7.C2製備之親和性色層分析管柱，純化漿細胞瘤胞殺素(Plasmacytoma Cytotoxic Factor ; 簡稱PCF)。純化之PCF經SDS-PAGE、Native Gel電泳分析及西方吸漬法鑑定，得知PCF為一由分子量62及103 kDa次單位所組成之蛋白質。其對1x104個MOPC-315細胞的50%胞殺作用為3.11μg/ml 。以TUNEL(Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)分析經PCF處理之MOPC-315細胞，發現細胞有明顯之DNA斷裂現象，為細胞自戕的典型徵兆。由Annexin V-FITC 法測試得知，PCF處理之MOPC-315細胞瘤細胞膜上，磷酯酉先絲氨酸(phosphatidylserine)由內膜移位至外膜，進一步證明其細胞自戕現象。以PI(Propidium iodide)染色，也發現PCF處理之MOPC -315細胞，DNA顯著流失。此細胞自戕現象能被單株抗體CB7.C2所中和，更進一步證實PCF為誘導MOPC-315細胞自戕作用的主要因子。由RT-PCR方法證實 , PCF處理24小時之MOPC-315細胞的Fas mRNA表現量增加10倍, FasL mRNA則呈暫時性增加3.7倍 ; 而與抑制細胞自戕有關的胞內因子Bcl-2 mRNA及蛋白表現量減低 。 由Fas誘導的細胞內傳遞因子CPP32/Caspase 3活性增強 , CPP32的受質PARP﹝poly(ADP-ribose)polymerase﹞斷裂現象增加。顯示PCF誘導細胞自戕的胞內途徑可能與Fas-FasL 自戕路線相似 , 並受到抗自戕基因Bcl-2 的調控。

    Tumoricidal activity is one of the major effector functions of activated macrophages. In this study, the culture supernatant of P388D1 murine macrophage-like cells was found having a cytotoxic effect on Plasmacytoma MOPC-315 and MPC-11, but not on J558 myeloma cells. Large-scaled purification of the plasmacytoma cytotoxic factor （PCF）in the culture supernatant of P388D1 macrophage-like cells was done by ammonium sulfate fractionation（40~60% saturation）, followed by immunoaffinity chromatography using anti-PCF monoclonal antibody, CB7.C2. The affinity-purified PCF had 50% cytotoxicity of 3.11 mg/ml for 15104 MOPC-315 cells and composed of two major bands of the estimated molecular weights of 62 & 103KDa on SDS-PAGE gel and a single band on native gel. However , CB7.C2 recognized the single band of 62KDa in Western blotting of the SDS-PAGE gel and a single band in Western blotting of native gel, suggesting that the native form of PCF could be composed of 62 & 103 kDa subunits. Data from TUNEL〔terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphasphate（dUTP）nick-end-labeling〕indicated that a significant amount of DNA fragmentation was induced in PCF-treated MOPC-315 cells. Using Annexin V staining technique, the PCF-induced apoptosis can be confirmed by phosphatidylserine redistribution on the plasma membrane of PCF-treated cells. Furthermore, the result of PI permeability assay suggested that PCF-mediated apoptosis involved DNA loss in apoptotic cells and was shown dose-dependent, time-dependent ,which can be neutralized by CB7-C2 monoclonal antibody. Measuring the expression of Fas , FasL and Bcl-2 mRNA level by RT-PCR showed that the expression of Fas and FasL mRNA were increased, but the expression of Bcl-2 mRNA was suppressed in PCF-treated MOPC-315 cells. Analyzing by immunoblotting, the expression of Bcl-2 protein was also reduced. CPP32/caspase 3 activity increased in the early stage and PARP[poly（ADP-ribose） polymerase ] was cleavaged in 36 hour after the PCF-treatment. Taken together, these observations indicated that a new protein which composed of 62 & 103 kDa subunits was secreted by P388D1 macrophage-like cells. This protein showed its apoptotic effect on MOPC-315 plasmacytoma cells via the signal pathway of Fas-FasL system that was regulated by Bcl-2.

    中文摘要 ..................................................................................................................................................................... Ⅰ 英文摘要 ..................................................................................................................................................................... Ⅱ 圖 次 ............................................................................................................................................................................ Ⅳ 表 次 ............................................................................................................................................................................. Ⅶ 縮寫字對照表 ............................................................................................................................................................... Ⅷ 第壹章 導論 ..................................................................................................................................................................... 1 一、文獻探討 ........................................................................................................................................................... 2 二、研究動機與目的 ................................................................................................................................................6 三、實驗流程圖 ..................................................................................................................................................... 8 第貳章 P388D1老鼠巨噬細胞分泌胞殺素 誘導MOPC-315漿細胞瘤自戕 .......................................................... 9 中文摘要 ............................................................................................................................................................... 10 壹、緒論 ............................................................................................................................................................... 11 貳、實驗材料 ....................................................................................................................................................... . 13 一、細胞株(cell lines)及融合瘤 (hybridoma) ...................................................................................................... 13 二、實驗動物 ........................................................................................................................................................ 13 三、細胞培養液及其配方 .................................................................................................................................. 14 1.Dulbecco's Modified Eagle Medium (DMEM) 培養液 .............................................................................. . 14 2.無血清DMEM培養液 .................................................................................................................................. 14 3.RPMI-1640培養液 ........................................................................................................................................ 14 4.無血清RPMI-1640培養液 ............................................................................................................................ 14 四、試劑及其配方 ................................................................................................................................................ 14 1.Phosphate Buffered Saline(PBS) ....................................................................................................................... 15 2.純化IgG單株抗體試劑 ................................................................................................................................. 15 3.製備免疫親和性色層分析 管柱試劑 ........................................................................................................ 15 4.免疫親和性色層分析管柱純化漿細胞瘤胞殺素(PCF)試劑 ................................................................. 15 5.蛋白質微量定量分析試劑 ........................................................................................................................... 16 6.SDS PAGE試劑 ................................................................................................................................................ 16 7.自然膠體電泳 .................................................................................................................................................. 16 8.銀染法試劑 ....................................................................................................................................................... 17 9.西方吸漬法試劑 .............................................................................................................................................. 17 10.MTT assay試劑 .................................................................................................................................................. 18 11.TNF-α定量測定試劑 ..................................................................................................................................... 18 12.蛋白質微定序樣品製備試劑 ........................................................................................................................ 19 五、一般化學藥品 .................................................................................................................................................... 20 六、儀器設備 ..............................................................................................................................................................20 參、實驗方法 ................................................................................................................................................................22 第一部分: 漿細胞瘤胞殺素(Plasmacytoma Cytotoxic Factor) 的純化與鑑別 ......................................................22 一、CB7.C2單株抗體親和性 管柱的備製 ....................................................................................................... 22 1.CB7.C2單株抗體之備製 ............................................................................................................................. 22 2.CB7.C2單株抗體之純化 ............................................................................................................................ 22 3.CB7.C2單株抗體親和性膠柱之備製 ....................................................................................................... 23 二、PCF之純化 ................................................................................................................................................ ....23 1.P388D1巨噬細胞株培養液之收集 ....................................................................................................... .. 23 2.硫酸銨鹽析 ................................................................................................................................................. 24 3.CB7.C2單株抗體親和性膠柱純化漿細胞瘤胞殺素 ............................................................................ 24 4.PCF的濃縮 ................................................................................................................................................... 24 三、PCF之定量及鑑別 ........................................................................................................................................ 24 1.BIO-RAD微量蛋白質定量法......................................................................................................................24 2.蛋白質SDS-PAGE電泳分析 ...................................................................................................................... 24 A.備製10%聚丙醯電泳膠(Separating gel)及4%stacking 膠體 ................................................................. 25 B.電泳 .............................................................................................................................................................25 3.自然膠片(Native gel)電泳分析 .................................................................................................................. .25 A. 備製7.5%聚丙醯電泳膠(Separating gel)及4%Stacking 膠體 ........................................................... . 25 B.電泳 .......................................................................................................................................................... 25 4.銀染法(Silver Stain) ...................................................................................................................................... 25 5.西方吸漬法(Western Blotting) ..................................................................................................................... 26 6.蛋白質微定序(Micro-Sequencing) ............................................................................................................... 26 四、PCF對MOPC-315，J558，MPC-11等腫瘤細胞株胞殺作用的影響: MTT試驗 ........................................................................................................................................................... 27 五、TNF-α對MOPC-315及L929細胞株胞殺作用之比較: MTT試驗 ........................................................................................................................................................... 27 六、40~60%飽和硫酸銨鹽析的P388D1細胞株培養液中TNF-α含量之測定: 酵素免疫分析法(Enzyme-linked Immunoassay ;ELISA) .............................................................................. 28 第二部分 PCF誘導MOPC-315漿細胞瘤 細胞自戕 .................................................................................................29 一、TUNEL試驗 ...................................................................................................................................................... 29 二、Annexin V-FITC試驗 ...................................................................................................................................... 30 肆、結果 ......................................................................................................................................................................... 31 第一部份 PCF的純化、鑑別及其胞殺作用........................................................................................................... 31 1.P388D1培養液以硫酸銨鹽鹽析處理 ........................................................................................................ 31 2.部份純化之PCF對MOPC-315，MPC-11，J558等漿細胞瘤細胞株胞殺作用的影響........................31 3.不同濃度硫酸銨鹽析之P388D1培養液對MOPC-315漿細胞瘤細胞株胞殺作用之影響 ................ 31 4.純化PCF對MOPC-315漿細胞瘤細胞株胞殺作用及CB7.C2單株抗體中和試驗之影響................... 32 5.TNF-α對MOPC-315及L929細胞株胞殺作用之比較...............................................................................32 6.CB7.C2單株抗體親和性色層分析法純化PCF.......................................................................................... 33 7.PCF之N-端氨基酸微定序 ............................................................................................................................33 第二部份 PCF誘發MOPC-315 漿細胞瘤細胞株自戕........................................................................................... 34 Ⅰ. TUNEL試驗................................................................................................................................................... 34 Ⅱ. Annexin V-FITC試驗..................................................................................................................................... 35 Ⅲ. PCF誘發MOPC-315漿細胞瘤細胞株自戕，胞內DNA含量之變化................................................... 36 伍、討論.......................................................................................................................................................................... 37 第參章 PCF誘導MOPC-315漿細胞瘤細胞 自戕的細胞內傳訊機..............................................................................41 中文摘要......................................................................................................................................................................... 42 壹、緒論..........................................................................................................................................................................43 貳、實驗材料................................................................................................................................................................ 51 一、細胞株(cell lines)及融合瘤(hybridoma)........................................................................................................ 51 二、實驗動物......................................................................................................................................................... 51 　　　 三、細胞培養液及其配方...................................................................................................................................... 51 1.Dulbecco's Modified Eagle Medium （DMEM）培養液............................................................................. 51 2.無血清DMEM培養液................................................................................................................................... 51 3.RPMI-1640培養液..........................................................................................................................................51 4.無血清RPMI-1640培養液............................................................................................................................ 51 四、試劑及其配方..................................................................................................................................................51 1.Phosphate Buffered Saline (PBS）.................................................................................................................. 51 2.純化IgG單株抗體試劑................................................................................................................................. 51 3.RT-PCR試驗....................................................................................................................................................51 4.Bcl-2免疫吸漬法（Immunoblotting）試劑................................................................................................ 54 5.ApoAlertTM CPP32/Caspase-3 Assay Kit .................................................................................................... 55 6.PARP 免疫轉漬法（Immunoblotting）試劑............................................................................................. 56 五、儀器設備........................................................................................................................................................ 57 參、實驗方法................................................................................................................................................................ 59 一、抗漿細胞瘤胞殺素單株抗體CB7.C2的製備及純化.............................................................................. 59 1.抗漿細胞瘤胞殺素單株抗體CB7.C2之製備......................................................................................... 59 2.抗漿細胞瘤胞殺素單株抗體CB7.C2之純化..........................................................................................59 二、漿細胞瘤胞殺素（PCF）之收集及硫酸銨鹽析.................................................................................... 59 1.P388D1細胞株培養液之收集................................................................................................................... 59 2.硫酸銨鹽析 ................................................................................................................................................. 59 3. BIO-RAD微量蛋白質定量法................................................................................................................... 59 三、Fas、FasL、Bcl-2及β2m mRNA之RT-PCR分析 .................................................................................... 59 1.MOPC-315細胞株之處理........................................................................................................................... 59 A.Fas之分析................................................................................................................................................ 60 B.FasL之分析...............................................................................................................................................60 C.Bcl-2之分析 ............................................................................................................................................ 60　　　　 2.Total RNA的萃取........................................................................................................................................ 60 3.單股cDNA之合成 .......................................................................................................................................62 4.PCR分析....................................................................................................................................................... 62 A.Fas之PCR分析 ....................................................................................................................................... 62 B.FasL之PCR分析...................................................................................................................................... 62 C.Bcl-2之PCF分析 ......................................................................................................................................63 D.β2m之PCR 分析....................................................................................................................................63 5.電泳分析....................................................................................................................................................... 63 四、Bcl-2免疫吸漬法（Immunoblotting）分析................................................................................................ 64 1.PCF對MOPC-315細胞株Bcl-2表現之影響 ..............................................................................................64 2.中和試驗 ..................................................................................................................................................... .64 五、CPP32 /Caspase 3酵素活性分析................................................................................................................. .65 1.PCF對MOPC-315細胞株CPP32/Caspase 3酵素活性之影響 ..................................................................65 2.中和試驗....................................................................................................................................................... 65 3.抑制作用....................................................................................................................................................... 65 4.CPP32/Caspase 3酵素作用的 人工產物pNA定量分析.......................................................................... 66 六、PARP免疫吸漬法（Immunoblotting）........................................................................................................66 PCF對MOPC-315細胞株PARP裂解之影響..............................................................................................66 肆、結果 ....................................................................................................................................................................... 68 一、Fas mRNA 分析............................................................................................................................................. 68 二、FasL mRNA 分析........................................................................................................................................... 68 三、Bcl-2 mRNA 分析.......................................................................................................................................... 69 四、PCF對MOPC-315漿細胞瘤細胞Bcl-2蛋白表現的影響.......................................................................... 69 五、PCF對MOPC-315漿細胞瘤細胞CPP32/Caspase-3酵素活性的影響 ..................................................... 70 六、PCF對MOPC-315漿細胞瘤細胞PARP裂解的影響................................................................................. 70 伍、討論 ....................................................................................................................................................................... 72 總論......................................................................................................................................................................................78 參考資料............................................................................................................................................................................ 80 圖表說明 ...........................................................................................................................................................................111 附錄 .................................................................................................................................................................................. 139 附錄一　CPP32/Caspase 3酵素作用的人工產物 pNA定量分析標準曲線圖 ...................................................139

    劉翠華,曾哲明. 1995. 抗漿細胞瘤抑制素單株抗體的製備與分析. 國立台灣師範大學生物研究所碩士論文
    Adams, D. O. 1980. Effector mechanisms of cytolytically activated macrophages. I. Secretion of neutral proteases and effect of protease inhibitors. J. Immunol. 124：286-292.
    Alnemri, E. S., Fernandes-Alnemri, T., and Litwack, G. 1995. Cloning and expression of four novel isoforms of human interleukin-1 beta converting enzyme with different apoptotic activities. J. Biol. Chem. 270 : 4312-4317.
    Aono, K., Isobe, K., Nakashima, I., Kondo, S., Miyachi, M., and Nimura, Y. 1994. Kupffer cells cytotoxicity against hepatoma cells is related to nitric oxide. Biochem. Biophys. Res. Commun. 201: 1175-1181.
    Arends, M. J., and Wyllie, A. H. 1991. Apoptosis : Mechanisms and roles in pathology. Int. Rev. Exp. Pathol. 32：223-254.
    Armstrong, R. C., Aja, T., Xiang, J., Gaur, S., Krebs, J. F., Hoang, K., Bai, X., Koresmeyer, S. J., Karanewsky, D. S., Fritz, L. C. and Tomaselli, K. J. 1996. Fas-induced activation of the cell death-related protease CPP32 is inhibited by Bcl-2 and by ICE-family protease inhibitors. J. Biol. Chem. 271：16850-16855.
    Aussel, C., Pelassy, C., and Breittmayer, J. P. 1998. CD95(Fas/APO-1) induces an increased phophatidylserine synthesis that precedes its externalization during programmed cell death. FEBS Lett. 431 : 195-199.
    Barry, M. A., Behnke, C. A., and Eastman, A. 1990. Activation of programmed cell death(apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia. Biochem. Pharmacol. 40：2353 -2362.
    Beltinger, C., Bohler, T., Karawajew, L., Ludwig, W. D., Schrappe, M., and Debatin, K. M. 1998. Mutation analysis of CD95(APO-1/Fas) in childhood B-lineage acute lymphoblastic leukaemia. Br. J. Haematol. 102 : 722-728.
    Ben-Eferaim, S., and Bonta, I. L. 1994. Modulation of antitumour activity of Macrophages by regulation of eicosanoids and cytokine production. Int. J. Immunopharmac. 16：397-399.
    Bernasconi, S., Peri, G., Sironi, M., and Mantovani, A. 1991. Involement of leukocyte (β2) integrins (CD18/CD11) in human monocyte tumoricidal activity. Int. J. Cancer. 49：267-273.
    Bitzer, M., Prinz, F., Bauer, M., Spiegel, M., Neubert, W. J., Gregor, M., Schulze-Osthoff, K., and Lauer, U. 1999. Sendai virus infection induces apoptosis through activation of caspase-8(FLICE) and caspase-3 (CPP32). J. Virol. 73 : 702-708.
    Bortner, C. D., Oldenburg, N. B. E., and Cidlowski, J. A. 1995. The role of DNA fragmentation in apoptosis. Trends. Cell Biol. 5：21-26.
    Bouaboula, M., Legoux, P., Pessegue, B., Delpech, B., Dumont, X., Piechaczyk, M., Casellas, P., and Shire, D. 1992. Standardization of mRNA titration using a polymerase chain reaction method involving co-amplification with a multispecific internal control. J. Biol. Chem. 267 : 21830-21838.
    Broome, H. E., Dargan, C. M., Krajewski, S., and Reed, J. C. 1995. Expression of Bcl-2, Bcl-x, and Bax after T cell activation and IL-2 withdrawal. J. Immunol. 155：2311-2317.
    Brunda, M. J., Luistro, L., Warriet, R. R., Wright, R. B., Hubbard, B. R., Murphy, M., Wolf, S. F., and Gately, M. K. 1993. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J. Exp. Med. 178：1223-1230
    Buechner, S. A., Wernli, M., Harr, T., Hahn, S., Itin, P., and Erb, P. 1997. Regression of basal cell carcinoma by intralesional interferon-alpha treatment is mediated by CD95(Apo-1/Fas)-CD95 ligand-induced suicide. J. Clin. Invest. 100 : 2691-2696.
    Buttyan, R., C. A. Olsson, J. Pintar, C. Chang, M. Bandyk, P-Y. Ng, and I. S. Sawczuk. 1989. Induction of the TRPM-2 gene in cells undergoing programmed death. Mol. Cell Biol. 99：3473-3481.
    Casciola-Rosen, L. A., Miller, D. K., Anhalt, G. J., and Rosen, A. 1994. Specific cleavage of the 70-KDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death. J.Biol. chem. 269：30757-30760.
    Caricchio, R., Reap, E. A., and Cohen, P. L. 1998. Fas/Fas ligand interaction are involved in ultraviolet-B-induced human lymphocyte apoptosis. J. Immunol. 161 : 241-251.
    Carson, D. A., Seto, S., Wasson, D. B., and Carrera, C. J. 1986. DNA strand breaks, NAD metabolism, and programmed cell death. Exp. Cell Res. 164：273-281.
    Cerretti, D. P., Kozlosky, C. J., Mosley, B., Nelson,N., Ness, N., Greenstreet, T. A., March, C. J., Kronheim, S. R., Druk, T., Cannizzaro, L. A., Huebner, K., and Black, R. A. 1992. Molecular cloning of the interleukin-1β-converting enzyme. Science. 256：97-100.
    Chen, L., Mory, Y., Zilberstein, A., and Revel, M. 1988. Growth inhibition of human breast carcinoma and leukemia/lymphoma cell lines by recombinant interferon-beta 2. Proc. Natl. Acad. Sci. USA. 85：8037-8041.
    Chinnaiyan, A. M., O' Rourke, K., Tewari, M., and Dixit, V. M. 1995. FADD, a novel death-domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell. 81：505-512.
    Chu, C. Y., Liu, T., and Tseng, H. J. 1998 . Induction of apoptosis in plasmacytoma cells by a cytotoxic factor secreted by P388D1 macrophage-like cell line. Inter. J. Immunotherapy. 14：69-81.
    Compton, M. M., and Cidlowski, J. A. 1992. Thymocyte apoptosis. A model of programmed cell death. Trend. Endocrinol Metab. 3：17-23.
    Cohen, J. J. 1991. Programmed cell death in immunity. Adv. Immunol. 50：55-85.
    Cuende, E., Ales-Martinez, J. E., Ding, L., Gonzalez-Garcia, M., Martinez, C., and Nunez, G. 1993. Programmed cell death by bcl-2-dependent and independent machanisms in B lymphoma cells. EMBO J. 12 : 1555-1560.
    Currie, G. A.. 1978. Activated macrophages kill tumor cells by releasing arginase. Nature. 273：758-759.
    Cuvillier, O., Rosenthal, D. S., Smulson, M. E., and Spiegel, S. 1998. Sphingosine 1-phosphate inhibits activation of caspases that cleave poly(ADP-ribose) polymerase and lamins during Fas- and ceramide- mediated apoptosis in Jurkat T lymphocytes. J. Biol. Chem. 273 : 2910-2916.
    Darmon, A. J., Nichoson, D. W., and Bleackley, R. C. 1995. Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B. Nature. 377：446-448.
    Daoust, P. Y., Wobeser, G., and Newstead, J. D. 1984. Acute Pathological effects of Inorganic mercury and copper in gills of rainbow trout. Vet. Pathol. 21：93-101.
    Debatin, K. M., and Krammer, P. H. 1995. Resistance to APO-1(CD95) induced apoptosis in T-ALL is determined by a BCL-2 independent anti-apoptotic program. Leukemia. 9 : 815-820.
    Dhein, J., Walczak, H., Baumler, C., Debatin, K. M., and Krammer, P. H. 1995. Autocrine-T-cell suicide mediated by Apo-1(Fas/CD95). Nature(Lond.). 373 ：438-441.
    Dingemans, K. P., Pels, E., and Den Otter, W. 1981. Destruction of murine lymphoma cells by allogeneic immune pweritoneal macrophages in vitro: an ultrastructure study. J. Nat. Cancer Inst. 66 : 67-79.
    Dirks, W., Schone, S., Uphoff, C., Quentmeier, H., Pradella, S., and Drexler, H. G. 1997. Expression and function of CD95(Fas/APO-1) in leukaemia- lymphoma tumour lines. Br. J. Haaematol. 96 : 584-593.
    Duke, R. C., Ojcius, D. M., and Young, J. D. 1996. Cell Suicide in health and disease. Sci.American. 275 : 80-87.
    Duvell, E., Wyllie, A. H., and Morris, R. G. 1985. Macrophage recognition of cells undergoing programmed cell death (apoptosis). Immunology. 56 ：351-358.
    Egle, A., Villunger, A., Marschitz, I., Kos, M., Hittmair, A., Lukas, P., Grunewald, K., and Greil, R. 1997. Expression of Apo-1/Fas(CD95), Bcl-2, Bax and Bcl-x in myeloma cell lines： relationship between responsiveness to anti-Fas mab and p53 functional status. British J. Haematology. 97：418-428.
    Ellis, H. M., and Horvitz, H. R. 1986. Genetic control of programmed cell death in the nematode C. elegans. Cell. 44：817-829.
    Ellis, R. E., Yuan, J., and Horvitz, H. R. 1991. Mechanisms and functions of cell death. Annu. Rev. Cell Biol. 7：663-698.
    Enari, M., Hase, A., and Nagata, S. 1995. Apoptosis by a cytosolic extract from Fas-activated cells. EMBO J. 14 : 5201-5208.
    Enari, M., Hug, H., and Nagata, S. 1995. Involvement of an ICE-like protease In Fas-mediated apoptosis. Nature. 375：78-81.
    Enari, M., Talanian, R. V., Wong, W. W., and Nagata, S. 1996. Sequential Activation of ICE-like and CPP32-like proteases during Fas-mediated Apoptosis. Nature. 380：723-726.
    Facchinetti, A., Tessarollo, M., Kingston, R., Collavo, D., and Biasi, G. 1991. An improved method for the detection of DNA fragmentation. J. Immunol. Methods. 136：125-131.
    Fadok, V. A., Voelker, D. R., Campbell, P. A., Cohen, J. J., Bratton, D. L., and Henson, P. M. 1992. Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages. J. Immunol. 148：2207-2216.
    Fernandes-AlnemFri, T., Litwack, G., and Alnemri, E. S. 1994. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta -converting enzyme. J. Biol. Chem. 269 : 30761-30764.
    Fernandes-AlnemFri, T., Takahashi, A., Armstrong, R., Salvesen, J. G., Earnshaw, W. C., Litwack, G., and Alnemri, E. S. 1995a. Mch3, a novel human apoptotic cysteine protease highly related to CPP32. Cancer Res. 55：6045-6052.
    Fernandes-AlnemFri, T., Litwack, G., and Alnemri, E. S. 1995b. Mch2, a new member of the apoptotic Ced-3/ICE protease gene family. Cancer Res. 55 : 2737-2742.
    Friesen, C., Herr, I., Krammer, P.H., and Debatin, K.M. 1996, Involvement of the CD95(APO-1/FAS) receptor/ ligand system in dug-induced apoptosis in leukemia cells. Nat Med , 2 : 574-577.
    Froelich, C. J., Dixit, V. M., and Yang, X. 1998. Lymphocyte granule-mediated apoptosis：matters of viral mimicry and deadly proteases. Immunol. Today. 19：30-36.
    Fulda, S., Los, M., Friesen, C., and Debatin, K. M. 1998. Chemosensitivity of solid tumor cells in vitro is related to activation of the CD95 system. Int. J. Cancer. 76 : 105-114.
    Fulda, S., Scaffidi, C., Pietsch, T., Krammer, P. H., Peter, M. E., and Debatin, K. M. 1998a. Activation of CD95(APO-1/Fas) pathway in drug- and gamma-irradiation-induced apoptosis of brain tumor cells. Cell Death Diff. 5 : 884-893.
    Fulda, S., Susin, S. A., Kroemer, G., and Debatin, K. M. 1998b. Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells. Cancer Res. 58 : 4453-4460.
    Galle, P. R., and Krammer, P. K. 1998. CD95-induced apoptosis in human liver disease. Semin. Liver Dis. 18 : 141-151.
    Gazitt, Y., and Hu, W. X. 1998. Fas(APO-1/CD95)-mediated apoptosis is independent of bcl-2: A study with cell lines overexpressing bcl-2 and with bcl-2 transfected cell lines. Int. J. Oncol. 12 : 211-220.
    Gotlieb, W. H., Watson, J. M., Rezai, A., Johnson, M., Maza, O. M., and Berek, J. S. 1994. Cytokine-induced modulation of tumor suppressor gene expression in ovarian cancer cells : up-regulation of p53 gene expression and induction of apoptosis by tumor necrosis factor-α. Am. J. Obstet. Gyneco. 170：1121-1128.
    Gratas, C., Tohma, Y., Barnas, C., Hainaut, P., and Ohgaki, H. 1998. Up-regulation of Fas(APO-1/CD95)ligand and down-regulation of Fas expression in human esophageal cancer. Cancer Res. 15 : 2057-2062.
    Greil, R., Egle, A., and Villunger, A. 1998. On the role and significance of Fas(Apo-1/CD95) ligand (FasL) expression in immune privileged tissues and cancer cells using multiple myeloma as a model. Leuk. Lymphoma. 31 : 477-490.
    Green, D. R. 1997. A myc-induced apoptosis pathway surfaces. Science. 278：1246-1247.
    Hakuno, N., Koji, T., Yano, T., Kobayashi, N., Tsutsumi, O., Taketani, Y., and Nakane, P. K. 1996. Fas/APO-1/CD95 system as a mediator of granulosa cell apoptosis in ovarian follicle atresia. Endocrinology 137 : 1938-1948.
    Hasegawa, J., Kamada, S., Kamiike, W., Shimizu, S., Imazu, T., Matsuda, H., and Tsujimoto, Y. 1996. Involvement of CPP32/Yama(-like) proteases in Fas-mediated apoptosis. Cancer Res. 15 : 1713-1718.
    Hata, H., Matsuzaki, H., Takeya, M., Yoshida, M., Sonoki, T., Nagasaki, A., Kuribayashi, N., Kawano, F., and Takatsuki, K. 1995. Expression of Fas/Apo-1(CD95) and apoptosis in tumor cells from patients with plasma cell disorders. Blood. 86 : 1939-1945.
    Henderson, S., Rowe, M., Gregory, C., Croom-Carter, D., Wang, F., Longnecker, R., Kieff, E., and Rickinson, A. 1991. Induction of bcl-2 expression by Epstein-Barr virus latent programmed membrane protein 1 protects infected B cells from cell death. Cell. 65：1107-1115.
    Higuchi, M., Higashi, N., Taki, H., and Osawa, T. 1990. Cytolytic mechanisms of activated macrophages: tumor necrosis factor and L-arginine-dependent mechanisms act synergistically as the major cytolytic mechanisms of activated macrophages. J. Immunol, 144：1425-1431.
    Hockenbery, D., Nunez, G., Milliman, C., Schreiber, R. D., and Korsmeyer, S. J. 1990. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature, 348：334-336.
    Hsu, H., Xiong, J., Hueber, D., A-O., Zornig, M., Lyon, D., Suda, T., Nagata, S., and Goeddel, V. 1995. The TNF receptor 1-associated protein TRADD Signals cell death and NF-κB activation. Cell. 81 : 495-504.
    Hueber, A. O., Zornig, M., Lyon, D., Suda, T., Nagata, S., and Evan, G. I. 1997. Requirement for the CD95 receptor-ligand pathway in c-myc-induced apoptosis. Science. 278 : 1305-1309.
    Hug, H. 1997. Fas-mediated apoptosis in tumor formation and defense. Biol. Chem. 378 : 1405-1412.
    Hunt, J. S., Vassmer, D., Ferguson, T. A., and Miller, L. 1997. Fasligand is positioned in mouse uterus and placenta to prevent trafficking of activated leckocytes between the mother and the conceptus. J. Immunol. 4122-4128.
    Ichinose, Y., Tsao, J. Y., and Fidler, I. J. 1988. Destruction of tumor cells by monokines released from activated human blood monocytes : evidence for parallel and additive effects of IL-1 and TNF. Cancer Immunol. Immunother. 27 : 7-12.
    Ito, M. R., Terasaki, S., Itoh, H., Yonehara, S., and Nose, M. 1997. Rheumatic diseases in an MRLstrain of mice with a deficit in the functional Fas ligand. Arthritis Rheum. 40 : 1054-1063.
    Itoh, N., Tsujimoto, Y., and Nagata, S. 1993. Effect of bcl-2 on Fas antigen-mediated cell death. J. Immunol. 151：621-627.
    Kaufmann, S. H. 1989. Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs：a cautionary note. Cancer Res. 49 : 5870-5878.
    Kaufmann, S. H., Desnoyers, S., Ottaviano, Y., Davidson, N. E., and Poirier, G. G. 1993. Specific proteolytic cleavage of poly(ADP)-ribose polymerase： an early marker of chemotherapy-induced apoptosis.. Cancer Res. 53 : 3976-3985.
    Kerr, J. F., Harmon, B., and Searle, J. 1974. An electron-microscope study of cell deletion in the anuran tadpole tail during spontane ous metamorphosis with special reference to apoptosis of striated muscle fibers. Cell Sci. 14 : 571-585.
    Kerr, J. F., Wyllie, A. H., and Currie, A. R. 1972. Apoptosis： a basic biological Phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer. 26 : 239-257.
    Komada, Y., and Sakurai, M. 1997. Fas receptor (CD95)-mediated apoptosis in leukemic cells. Leuk Lymphoma, 25 : 9-21.
    Kondo, S., Ishizaka, Y., Okada, T., Kondo, Y., Hitomi, M., Tanaka, Y., Haqqi, T., and Barnett, G. H. 1998. FADD gene therapy for malignant gliomas in vitro and in vivo. Hum. Gene Ther. 9 : 1599-1608.
    Kondo, Y., and Takano, F. 1994. Nitric oxide production in mouse peritoneal macrophages enhanced with glycyrrhizin. Biol. Pharm. Bull. 17 : 759-761.
    Koopman, G., Reutelinsperger, C. P. M., Kuijten, G. A. M., Keehnen, R. M. J., Pals, S. T. and van Oers, M. H. J. 1994. Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood.84 : 1415-1420.
    Koren, H. S., Handwerger, B. S., and Wunderlich, J. R. 1975. Identification of macrophage-like characteristics in a cultured murine tumor line. J. Immunol. 114 : 894-897.
    Kroemer, G., Petit,P., Gamjami, N., Vayssiere, J.L., and Mignote, B. 1995.The biochemistry of programmed cell death. FASEB. J. 9：1277-1287.
    Kroemer, G., Zamzami, N., and Susin, S. A. 1997. Mitochondrial control of apoptosis. Immunol. Today, 18：44-51
    Kuida, K., Lippke, J. A., Ku, G., Harding, M. W., Livingston, D. J., Su, M. S., and Flavell, R. A. 1995. Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme. Science. 267 : 2000-2003.
    Kurokawa, H., Nishio, K.,Fukumoto, H., Tomonari, A., Suzuki, T., and Saijo, N. 1999. Alteration of caspase-3(CPP32/Yama/apopain) in wild-type MCF-7, breast cancer cells. Oncol. Rep. 6 : 33-37.
    Lachman, L. B., Dinarello, C. A., Llansa, N. D., and Fidler, I. J. 1986. Natural and recombinant human interlerleukin-1β is cytotoxic for human melanoma cells. J. Immunol. 136 : 3098-3102.
    Lam, M., Dubyak, G., Chen, L., Nunez,G., Miesfeld, R. L., and Distelhorst, C. W. 1994. Evidence that Bcl-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca+2 fluxes. Proc. Natl. Acad. Sci. USA. 91 : 6569-6573.
    Lazebnik, Y. A., Kaufmann, S. H., Desnoyers, S. G., Poirier, G., and Earnshaw, W. C. 1994. Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature. 371 : 346-347.
    Lazebnik, Y. A., Takahashi, A., Moir, R. D., Golman, R. D., Poirier, G. G., Kaufmann, S. H., and Earnshaw, W. C. 1995. Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution. Proc. Natl. Acad. Sci. USA. 92 : 9042-9046.
    Lejeune, P., Reisser, D., Onier, N., Lagadec, P., and Jeannin, J-F. 1994. Interleukin-8 has antitumor effects in the rat which are not assciated with polymorphonuclear leukocyte cytotoxity. Cancer Immunol. Immunother. 38 : 167-170.
    Li, P., Allen, H., Banerjee, S., Franklin, S., Herzog, L., Johnston, C., McDowell, J., Paskind, M., Rodman, L., and Salfeld, J. 1995. Mice deficient in IL-1 beta-converting enzyme are defective in production of mature IL-1beta and resistant to endotoxic shock. Cell. 80 : 401-411.
    Liu, Y. J., Mason, D. Y., Johnson, G. D., Abbot, S., Gregory, C. D., Hardie, D. L., Gordon, J., and MacLennan, I. C. 1991. Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis. Eur. J. Immunol. 21 : 1905-1910.
    Lovett, D., Kozan, B., Hadam, M., Resch, K., and Gemsa, D. 1986. Macrophage cytotoxicity:Interleukin 1 as a mediator of tumor cytostasis. J. Immunol. 136 : 340-347.
    Lu, X., and Lane, D. P. 1993. Differential induction of transcriptionally active p53 following UV or ionizing radiation： defects in chromosome Instability syndromes ? Cell. 75 : 765-778.
    Mandal, M., Maggirwar, S. B., Sharma, N., Kaufmann, S. H., Sun, S. C., and Kumar, R. 1996. Bcl-2 prevents CD95(Fas/APO-1)-induced degradation of lamin B and poly(ADP-ribose) polymerase and restores the NF-kappaB signaling pathway. J. Biol. Chem. 29 : 30354-30359.
    Mannel, D. N., Moore, R. N., and Mergenhagen, S. E. 1980. Macrophages as a source of tumoricidal activity (tumor necrotizing factor). Infect. Immunol. 30 : 523-530.
    Mariani, S. M., Matiba, B., Sparna, T., and Krammer, P. H. 1996. Expression of biologically active mouse and human CD95/APO-1/FAS ligand in the baculovirus system. J. Immunol. Methods. 14 : 63-70.
    Martin, J-H. J., and Edwards, S. W. 1993. Changes in mechanisms of monocyte/macrophage-mediated cytotoxicity during culture. J. Immunol. 150 : 3478-3486.
    Martin, S. J., Reutelingsperger, C. P., McGahon, A. J., Rader, J. A., van Schie, R. C., LaFace, D. M., and Green, D. R. 1995a. Early redistribution of plasma membrane phophatidylserine is a general feature of apoptosis regardless of the initiating stimulus: Inhibition by overexpression of Bcl-2 and Abl. J. Exp. Med. 182 : 1545-1556.
    Martin, S. T., Newmeyer, D. D., Mathias, S., Farschon, D. M., Wang,H. G., Reed, J. C., Kolesnick, R. N., and Green, D. R. 1995b. Cell-free reconstitution of Fas-, UV radiation- and ceramide-induced apoptosis. EMBO J. 14 : 5191-5200.
    Matiba, B., Mariani, S. M., and Krammer, P. H. 1997. The CD95 system and the death of a lymphocyte. Semin. Immunol. 9 : 59-68.
    McCall, C. A., and Cohen, J. J. 1991. Programmed cell death in terminally differentiating keratinocytes: role of endogenous endonuclease. J. Invest. Dermatol. 97 : 111-114.
    McDonnell, T. J., Deane, N., Platt, F. M., Nunez, G., Jaeger, U., Mckearn, J. P., and Koresmeyer, S. J. 1989. Bcl-2-immuno globulin transgenic mice demonstrate extended B Cell survival and follicular lymphoproliferation. Cell. 57 : 79-88.
    Mercer, M. E., Shields, M. T., Amin, M., Sauve, G. J., Appella, E., Romano, J. W., And Ullrich, S. J. 1990. Negative growth regulation in a glioblastoma tumor Cell line that conditionally expresses human wild type p53. Proc. Natl. Acad. Sci. USA. 87：6166-6170.
    Micheau, O., Solary, E., Hammann, A., Martin, F., and Dimanche-Boitrel, M. T. 1997. Sensitization of cancer cells treated with cytotoxic drugs to fas-mediated cytotoxicity. J. Natl. Cancer Inst. 89 : 783-789.
    Miller, D.K. 1997. The role of the caspase family of cysteine proteases in apoptosis. Immunology. 9 : 35-49.
    Miyashita, T., Krajewski, S., Krajewski, M., Wang, H. G., Lin, H. K., Liebermann, Dan A., Hoffman, B., and Reed, J. C. 1994. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 9 : 1799-1805.
    Moers, C., Warskulat,U., Muschen, M., Even, J., Niederacher, D., Josien, R., Koldovsky, U., Beckmann,M. W. and Haussinger D. 1999, Regulation of CD95(Apo-1/Fas) receptor expression in squamous-cell carcinoma by interferon and cisplatin. Int. J. Cancer, 9 : 564-572.
    Moller, P., von Reyher, U., Leithauser, F., and Strater, J. 1996. [CD95(APO-1/Fas) and CD95-ligand (CD95L). Implications of these apoptosis mediating receptor/ligand systems in the pathogenesis of autoimmune diseases]. Verh. Dtsch. Ges. Pathol. 80 : 12-20.
    Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival：application to proliferation and cytotoxicity assays. J. Immunol. Meth. 65 : 55-63.
    Muller, M., Srand, S., Hug, H., Heinemann, E. M., Walczak, H., Hofmann, W. J., Stremmel, W.,Krammer, P. H., and Galle, P. R. 1997. Drug-induced apoptosis in hepatoma cells is mediated by the CD95(APO-1/Fas) receptor/ligand system and involves activation of wild-type p53. J. Clin. Invest. 99 : 403-413.
    Munker, R., Midis, G., Owen-Schaub, L., and Andreff, M. 1996. Soluble FAS(CD95) is not elevated in the serum of patients with myeloid leukemias, myeloproliferative and myelodysplastic syndromes. Leukemia 10 : 1531-1533.
    Munn, D. H., Pressey, J., Beall, A. C., Hudes, R., and Alderson, M. R. 1996. Selective activation-induced apoptosis of peripheral T cells imposed by macrophages. A potential mechanism of antigen-specific peripheral lymphocyte deletion. J. Immunol. 156 : 523-532.
    Muschen, M., Warskulat, U., Peters-Regehr, T., Bode, JG., Kubitz, R.,and Haussinger, D. 1999. Involvement of CD95(Apo-1/Fas) ligand expressed by rat Kupffer cells in hepatic immunoregulation. Gastroenteroiogy , 116 : 666-677.
    Muschen, M., Warskulat, U., Douillard P., Gilbert E., and Haussinger, D. 1998a. Regulation of CD95(Apo-1/Fas) receptor and ligand expression by lipolysaccharide and dexamethasone in parenchymal and nonparenchymal rat liver cells. Hepatology, 27 : 200-208.
    Muschen, M., Warskulat, U., Schmidt, B., Schulz, W. A., and Haussinger, D. 1998b. Regulation of CD95(Apo-1/Fas) ligand and receptor expression in human embryonal carcinoma cells by interferon gamma and all-trans retinoic acid. J. Biol. Chem. 379 : 1083-1091.
    Muzio, M., Chinnaiyan, A. M., Kischkel, F. C., O'Rourke, K., Shevchenko, A., Scaffidi, C., Ni, J., Bretz, J. D., Zhang,M., Gentz, R., Mann, M., Krammer, P. H., Peter, M. E., and Dixit, V. M. 1996. FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95(Fas/Apo-1) death-inducing signaling complex. Cell. 85 : 817-827.
    Nakajima, T., Ichii, S., Furuyama, J., Tamaoki, T., and Hashimoto, T. 1996. A new alternative splice variant of the mouse Fas antigen with a deletion in the N-terminal portion of the extracellular domain. Life Sciences. 58 : 761-768.
    Nathan, C. F. 1987. Secretory products of macrophages. J. Clin. Invest. 79 : 319-326.
    Neamati, N., Fernandez, A., Wright, S., Kiefer, J., and McConkey, D. J. 1995. Degradation of lamin B1 precedes oligonucleosomal DNA fragmentation in apoptotic thymocytes and isolated thymocyte nuclei. J. Immunol. 154 : 3788-3795.
    Nicholson, D. W., Ali,A., Thomberry, N. A., Vaillancourt, J. P., Ding, C. K.,Gallant, M., Gareau, Y., Griffin, P. R., Labelle, M., and Lazebnik, Y. A. 1995. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. 376 : 37-43.
    Nishioka, A., Ogawa, Y., Kubonishi, I., Kataoka, S., Hamada, N., Tershima, M., Inomata, T., and Yoshida, S. 1999. An augmentation of Fas(CD95/APO-1) antigen induced by radiation: Flow cytometry analysis of lymphoma and leukemia cell lines. Int. J. Mol. Med. 3 : 275-278.
    Odaka, C., Kizaki,H., and Tadakuma, T. 1990. T cell receptor-mediated DNA fragmentation and cell death in T cell hybridomas. J. Immunol. 144 : 2096-2101.
    Ohtsuki, T., Micallef, M. J., Kohno, K., Tanimoto, T.,Ikeda, M., and Kurimoto, M. 1997. Interleukin 18 enhances Fas ligand expression and induces apoptosis in Fas-expressing human myelomonocytic KG-1 cells. Anticancer Res. 17 : 3253-3258.
    Oppenheim, R.W. 1985. Naturally occurring cell death during neural development. Trends. Neurosci. 8 : 487-493.
    Orth, K., Chinnaiyan, A. M., Garg, M., Froelich, C. J.,and Dixit, V. M. 1996. The CED3/ICE-like protease Mch2 is activated during apoptosis and cleaves the death substrate lamin A. J. Biol. Chem. 271 : 16443-16446.
    Osborne, B. A., and Schwartz, L. M. 1994. Essential genes that regulate apoptosis. Trends Cell Biol. 4 : 394-397.
    Owen-Schaub, L. B., Angelo, L. S. , Radinsky, R., Ware, C. F., Gesner, T. G., and Bartos, D. P. 1995a. Soluble Fas/APO-1 in tumor cells : a potential regulator of apoptosis ? Cancer Lett. 94 : 1-8.
    Owen-Schaub, L. B., Zhang, W., Cusack, J. C., Angelo, L. S., Santee, S. M., Fujiwara, T., Roth, J. A., Deisseroth, A. B., Zhang, W. W., and Kruzel, E. 1995b. Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol. Cell. Biol. 15 : 3032-3040.
    Perandones, C. E., Illera, V. A., Peckham, D., Stunz, L. L., and Ashman, R. F. 1993. Regulation of apoptosis in vitro in mature murine spleen T cells. J. Immunol. 151 : 3521-3529.
    Rehemtulla, A., Hamilton, C.A., Chinnaiyan A.M., and Dixit, V. M. 1997. Ultraviolet radition-induced apoptosis is mediated by action of CD-95 (Fas/APO-1). J. Biol. Chem. 10 : 25783-25786.
    Reisser, D., Lejeune, P., Lagadec, P., Onier, N., Dasilva, C., Lindley, I., and Jeannin, J-F. 1994. Interleukin-8 antitumour effect is associated with a local infiltration but not with a systemic activation of T lymphocyte. Anticancer Res. 14 : 977-979.
    Roitt, I. M. 1988. Essential Immunology. (6th ed.) Blackwell Scientific Publication, Oxford. pp4.
    Roth, M., Fontana, A., Trepel, M., Reed, J. C., Dichgans, J., and Weller, M. 1997. Immunochemotherapy of malignant glioma: synergistic activity of CD95 ligand and chemotherapeutics. Cancer Immunol. Immunother. 44 : 55-63.
    Rubbo, H., Denciola, A., and Radi, R. 1994. Peroxynitrite inactivates thiol-containing enzymes of Trypanosoma cruzi energetic metabolism and inhibits cell respiration. Arch. Biochem. Biophys. 308 : 96-102.
    Santoro, M. G., Philpott, G. W., and Jaffe, B. M. 1976. Inhibition of tumour growth in vivo and in vitro by prostaglandin E. Nature. 263 : 777-779.
    Savill, J., Dransfield, I., Hogg, N., and Haslett, C. 1990. Vitronectin receptor-mediated phagocytosis of cells undergoing apoptosis. Nature. 343 : 170-173.
    Savill, J., Fadok, V., Henson, P., and Haslett, C. 1993. Phagocyte recognition of cells undergoing apoptosis. Immunol. Today. 14 : 131-136.
    Schwartz, L. M., Myer , A., Kosz , L., Engelstein, M., and Maier, C. 1990. Gene expression Activation is required for developmentally programmed cell death. Proc. Natl. Acad. Sci. USA. 87 : 6594-6598.
    Schwartzman, R. A., and Cidlowski, J. A. 1993. Apoptosis: the biochemistry and molecular biology of programmed cell death. Endo. Reviews. 14：133-151.
    Shima, Y., Nishimoto, N., Yoshizaki, K., and Kishimoto, T. 1996. Fas antigen/APO-1(CD95) expression on myeloma cells. Leuk. Lymphoma 23 : 521-531.
    Shinagawa, T., Yoshioka, K., Kakumu, S., Wakita, T., Ishikawa, T., Itoh, Y., and Takayanagi, M. 1991. Apoptsis in cultured rat hepatocytes： the effects of tumour necrosis factorαand interferonγ. J. Pathol. 165 : 247-253.
    Srinivasula, S. M., Ahmad, M., Fernandes-Alnemri, T., Litwack, G., and Alnemri, E. S. 1996. Molecular ordering of the Fas-apoptotic pathway： the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases. Proc. Natl. Acad. Sci. USA. 93 : 14486-14491.
    Steller, H. 1995. Mechanisms and genes of cellular suicide. Science. 267 : 1445-1449.
    Strasser, A., Whittingham, S., Vaux, D. L., Bath, M. L., Adams, J. M., Cory, S., and Harris, A. W. 1990. Enforced bcl-2 expression in B-lymphoid cells prolongs antibody responses and elicits antoimmune disease. Proc. Natl. Acad. Sci. USA. 88 : 8661-8665.
    Strater, J., and Moller, P. 1998. Pathogenesis of primary biliary cirrhosis: CD95-induced apoptosis at last? Eur. J. Gastroenterol. Hepatol. 10 : 539-541.
    Stuehr, D. J., and Nathan, C. F. 1989. Nitric oxide: a macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J. Exp. Med. 169 : 1543-1555.
    Suda, T., Takahashi, T., Golstein, P., and Naga

    下載圖示
    QR CODE