跳到主要內容

臺灣博碩士論文加值系統

(216.73.217.127) 您好!臺灣時間:2026/07/30 10:25
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:羅美婷
研究生(外文):Lo, mei ting
論文名稱:1-苄基咔唑-4-醛類緣化合物誘導人類血癌細胞株凋亡之探討
論文名稱(外文):Apoptosis induced by 1-benzyl carbazole-4-carboxaldehyde derivatives in human leukemia cell lines
指導教授:李妙蓉
學位類別:碩士
校院名稱:中國醫藥學院
系所名稱:藥物化學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
中文關鍵詞:細胞凋亡細胞週期人類血癌細胞株
外文關鍵詞:apoptosiscell cyclehuman leukemia cell lines
相關次數:
  • 被引用被引用:0
  • 點閱點閱:495
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
摘要
藉由細胞週期停滯、誘導細胞凋亡與細胞分化以達到抑制癌細胞的增殖,是目前用來篩選有效抗癌藥的重要指標。 我們探討一系列合成之1-■基■■-4-醛類緣化合物對人類血癌細胞株生長增殖之作用。 以PI螢光染色法偵測經此系列化合物處理24小時後HL60、U937及K562之細胞增殖率,結果發現此系列所有的化合物皆有抑制細胞增殖率的作用,且成劑量依存性。 但其中以LCY-12有最強的細胞生長抑制作用,其對HL60、U937及K562細胞之IC50 分別為2.58、0.77、19.49 μM。 觀察以LCY處理之細胞形態及DAPI染色之細胞核,發現這些細胞呈現凋亡的形態特徵,細胞形狀有皺縮的現象,核內染色質凝聚,核呈斷裂的情形,同時伴隨有凋亡小體的產生。 利用DNA電泳檢測分析LCY-11、12、15、16及LCY-12、14、16、42經IC50 濃度處理後HL60及U937細胞之DNA,發現細胞DNA斷裂成小片段。 除此之外,利用西方墨點法觀察以LCY-12處理之HL60細胞,其蛋白質表現量的變化,發現Bcl-2表現量增加,Bax表現量減少,caspase 3、8、9被活化,且PARP被分解。  Caspase專一性抑制劑明顯地減少了LCY-12或LCY-16處理的細胞內caspase的活性,並且提昇了細胞增殖率。  LCY-12、LCY-16會使HL60細胞週期抑制在G2/M期,而使U937細胞週期抑制在S期,細胞週期抑制發生的時間是在明顯細胞凋亡之前。  為了探討細胞週期抑制可能的機制,我們以西方墨點法分析cyclin、CKI蛋白質表現的變化,發現LCY-12處理之HL60細胞,其cyclin B、cdc25c、p21表現量增加,而cyclin A表現量不變。 以上結果顯示,LCY-12抑制癌細胞增殖的作用,可能與誘導細胞凋亡及抑制細胞週期進行有關。
Abstract
Synthesized 1-benzyl carbazole-4-carboxaldehyde derivatives ( LCY ) examined for their growth inhibition effects in human leukemia cell lines. HL60, U937, and K562 cells were treated with these compounds for 24 hours and their proliferation was determined by the propidium iodide DNA staining method. A dose-dependent decrease in the cell proliferation rate was observed for all compounds. LCY-12 had the highest growth inhibitory, and its IC50 were 2.58, 0.77, and 19.49 μM for HL60, U937, and K562 cells, respectively. DAPI-stained cells revealed evident characteristics of apoptosis, which include cell shrinking, chromatin condensation, fragmentation of nuclei, and formation of apoptotic bodies. DNA from treated HL60 and U937 cells displayed a characteristic inter-nucleosomal ladder of DNA fragments. Furthermore, down-regulation of Bcl-2, up-regulation of Bax, activation of caspase 3, 8, and 9, and cleavage of PARP were detected by Western blotting method in LCY-12-treated HL60 cells. Caspase inhibitors significantly reduced LCY-12-induced caspase activity and cell death. In addition, LCY-12 and LCY-16 induced G2/M arrest in HL60 cells, and S arrest in U937 cells. The induction of cell cycle arrest occurred before the onset of apoptosis. Western blotting analysis of cyclins and CKIs revealed that LCY-12 induced the expression of cyclin B, cdc25c and p21 proteins. These results indicated that the ability of LCY-12 to inhibit cell proliferation may be mediated by the induction of apoptosis and cell cycle arrest.
目 錄
目 錄I
表 目 錄II
圖 目 錄III
中 文 摘 要1
英 文 摘 要2
第一章 緒論
第一節 白血病3
第二節 白血病的治療8
第三節 細胞凋亡11
第四節 細胞週期16
第二章 研究動機20
第三章 實驗材料與方法
第一節 實驗材料與儀器21
第二節 實驗方法24
第四章 實驗結果31
第五章 討論37
參考文獻73
表 目 錄
表一. Bcl-2 family15
表二. 一系列不同濃度LCY化合物對於HL60、U937、K562
血癌細胞株增殖率的影響43
表三. 各LCY化合物對HL60、U937、K562血癌細胞株增殖率之IC5047
表四. HL60血癌細胞株經化合物處理,觀察細胞週期的改變
49
表五. U937血癌細胞株經化合物處理,觀察細胞週期的改變
50
表六. HL60、U937、K562血癌細胞株之比較51
圖 目 錄
圖一. 造血幹細胞之分化4
圖二. Receper-mediated caspase cascades12
圖三. Stress-induced caspase cascades13
圖四. Expression of cyclins during the mammalian cell cycle
17
圖五. CDK的活化18
圖六. CDK 與CDKI19
圖七. 一系列不同濃度化合物對於血癌細胞株增殖率的影響52
圖八. HL60血癌細胞株經化合物處理,利用位向差倒立顯微鏡觀察
細胞型態的改變53
圖九. U937血癌細胞株經化合物處理,利用位向差倒立顯微鏡觀察
細胞型態的改變54
圖十. HL60血癌細胞株經化合物處理,利用DAPI螢光染色,在倒立
螢光顯微鏡下觀察細胞型態的改變55
圖十一. U937血癌細胞株經化合物處理,利用DAPI螢光染色,在倒
立螢光顯微鏡下觀察細胞型態的改變56
圖十二. HL60血癌細胞株經化合物處理,利用DNA電泳分析法觀察
DNA斷裂的情形57
圖十三. U937血癌細胞株經化合物處理,利用DNA電泳分析法觀察
DNA斷裂的情形58
圖十四. HL60血癌細胞株經藥物處理,以流式細胞儀分析Sub-G1細
胞核族群的改變59
圖十五. U937血癌細胞株經藥物處理,以流式細胞儀分析Sub-G1細
胞核族群的改變60
圖十六. HL60血癌細胞株經LCY-12處理,觀察細胞週期的改變…61
圖十七. HL60血癌細胞株經LCY-16處理,觀察細胞週期的改變…62
圖十八. U937血癌細胞株經藥物處理,觀察細胞週期的改變……63
圖十九. U937血癌細胞株經藥物處理,利用DiOC6螢光染色觀察粒線
體膜電位的改變64
圖二十. HL60血癌細胞給予LCY-12及不同濃度之caspase專一性抑
制劑培養細胞增殖率的改變65
圖二十一. U937血癌細胞給予LCY-12及不同濃度之caspase專一性
抑制劑培養,觀察細胞增殖率的改變66
圖二十二. HL60、U937血癌細胞株給予LCY-12培養,觀察caspase 3、
8、9活性的改變67
圖二十三. 不同濃度化合物對於正常人類白血球細胞增殖率的影響
68
圖二十四. Western blot分析LCY-12處理之HL60細胞內cyclin A、cyclin B、cdc25、p21的表現69
圖二十五. Western blot分析LCY-12處理之HL60細胞內Bax、Bcl-2的表現70
圖二十六. Western blot分析LCY-12處理之HL60細胞內cytochrome c的表現71
圖二十七. Western blot分析LCY-12處理之HL60細胞內caspase 8、
caspase 9、caspase 3、PARP的表現72
參考文獻
1.Mark Bamford, Gail Walkinshaw, Robin Brown (2000) Therapeutic applications of apoptosis research. Experimental Cell Research 256; 1-11
2.H. N. Crans, K. M. Sakamoto (2001) Transcription factors and translocations in lymphoid and myeloid leukemia. Leukemia 15; 313-331
3.血液學 ( TEXTBOOK OF HEMATOLOGY ) 第二版 何敏夫 編著
4.Bayard L. Powell (2001) Acute progranulocytic leukemia. Current Opinion in Oncology 13; 8-13
5.Amit Verma, Wendy Stock (2001) Management of acute lymphoblastic leukemia: moving toward a risk-adapted approach. Current Opinion in Oncology 13; 14-20
6.Michael J. Mauro, Brian J. Druker (2001) Chronic myelogenous leukemia. Current Opinion in Oncology 13; 3-7
7.T. A. McDonald, N.T. Holland, C. Skibola, P. Duramad, M. T. Smith (2001) Hypothesis: phenol and hydroquinone derived mainly from diet and gastrointestinal flora activity are causal factors in leukemia. Leukemia 15; 10-20
8.X. Cai, Y. L. Shen, Q Zhu, P. M. Jia, Y. Yu, L. Zhou, Y. Huang, J. W. Zhang, S. M. Xiong, S. J. Chen, Z. Y. Wang, Z. Chen, G. Q. Chen (2000) Arsenic trioxide-induced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia. Leukemia 14; 262-270
9.G. Q. Chen, J. Zhu, X. G. Shi, J. H. Ni, H. J. Zhong, G. Y. Si, X. L. Jin, W. Tang, X. S. Li, S. M. Xong, Z. X. Shen, G. L. Sun, J. Ma, P. Zhang, T. D. Zhang, C. Gazin, T. Naoe, S. J. Chen, Z. Y. Wang, Z. Chen (1996) In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RARα/PML proteins. Blood 88; 1052-1061
10.G. Q. Chen, X. G. Shi, W. Tang, S. M. Xiong, J. Zhu, X. Cai, Z. G. Han, J. H. Ni, G. Y. Shi, P. M. Jia, M. M. Liu, K. L. He, C. Niu, J. Ma, P. Zhang, T. D. Zhang, P. Paul, T. Naoe, K. Kitamura, W. Miller, S. Waxman, Z. Y. Wang, Hugues de The, S. J. Chen, Z. Chen (1997) Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): I. As2O3 exerts dose-dependent dual effects on APL cells. Blood 89; 3345-3353
11.Marcia I. Dawson, Elena Elstner, Masahiro Kizaki, Dan-Lin Chen, Seppo Pakkala, Berit Kerner, H. Phillip Koeffler (1994) Myeloid differentiation mediated through retinoic acid receptor/ retinoic X recepter (RXR) not RXR/RXR pathway. Blood 84; 446-452
12.Anna Dipietrantonio, Tze-chen Hsieh, Joseph M. Wu (1996) Differential effects of retinoic acid (RA) and N-(4- Hydroxyphenyl) retinamide (4-HPR) on cell growth, induction of differentiation, and changes in p34cdc2, Bcl-2, and actin expression in human promyelocytic HL-60 leukemia cells. Biochemical and Biophysical Research Communications 224; 837-842
13.Yves Carpentier, Philippe Mayer, Helene Bobichon, Bernard Desoize (1998) Cofactors in vitro induction of apoptosis in HL60 cells by all-trans retinoic acid (ATRA). Biochemical Pharmacology 55; 177-184
14.Z. X. Shen, G. Q. Chen, J. H. Ni, X. S. Li, S. M. Xiong, Q. Y. Qiu, J. Zhu, W. Tang, G. L. Sun, K. Q. Yang, Y. Chen, L. Zhou, Z. W. Fang, Y. T. Wang, J. Ma, P. Zhang, T. D. Zhang, S. J. Chen, Z. Chen, Z. Y. Wang (1997) Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. clinical efficacy and pharmacokinetics in relapsed patients. Blood 89; 3354-3360
15.M. E. Huang, Y. C. Ye, S. R. Chen, J. R. Chai, J. X. Lu, L. Zhoa, L. J. Gu, Z. Y. Wang (1988) Use of all-trans retinoic acid in treatment of acute promyelocytic leukemia. Blood 72; 567-572
16.Stanley R. Frankel, Anna Eardley, Gregory Lauwers, Mark Weiss, Raymond P. Warrell (1992) The “retinoic acid syndrome” in acute promyelocytic leukemia. Annals of Internal Medicine 117; 292-296
17.J. F. Kerr, A. H. Willie, A. R. Currie (1972) Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer 26; 239-257
18.A. H. Willie, J. F. Kerr, A. R. Currie (1980) Cell death: the significance of apoptosis. Int. Rev. Cytol. 68; 251-306
19.J. F. Kerr, C. M. Winterford, B.V. Harmon (1994) Apoptosis-its significance in cancer and cancer therapy. Cancer 73; 2013-2026
20.Alan G. Porter, Reiner U. Janicke (1999) Emerging roles of caspase-3 in apoptosis. Cell death and differentiation 6; 99-104
21.Clemens A. Schmitt, Scott W. Lowe (1999) Apoptosis and therapy. Journal of pathology 187; 127-137
22.Paul A. Colussi, Sharad Kumar (1999) Targeted disruption of caspase genes in mice: What they tell us about the functions of individual caspases in apoptosis. Immunology and Biology 77; 58-63
23.Kay-Oliver Kliche, Klaus Hoffken (1999) The role of apoptosis in hematologic malignancies and modulation of apoptosis as a new therapeutic approach. J. Cancer Res. Clin. Oncol. 125; 226-231
24.Scott W. Lowe, Athena W. Lin (2000) Apoptosis in cancer. Carcinogenesis 21; 485-495
25.S. Bialik, T. Gottlieb (2000) Death at the dead sea. Cell Death and Differeatiation 7; 851-859
26.Ella Bossy-Wetzel, Douglas R. Green (1999) Apoptosis: checkpoint at the mitochondrial frontier. Mutation Research 434; 243-251
27.Shawn B. Bratton, Marion MacFarlane, Kelvin Cain, Gerald M. Cohen (2000) Protein complexes activate distinct caspase cascades in death receptor and stress-induced apoptosis. Experimental Cell Research 256, 27-33
28.Shigekazu Nagata (2000) Apoptosis DNA fragmentation. Experimental cell research 256; 12-18
29.Bruno Antonsson, Jean Claude Martinou (2000) The Bcl-2 protein family. Experimental Cell Research 256; 50-57
30.K. M. Murphy, V. Ranganathan, M.L. Farnsworth, M. Kavallaris, R. B. Lock (2000) Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death and Differentiation 7; 102-111
31.Liam O’Connor, David CS Huang, Lorraine A O’Reilly, Andreas Strasser (2000) Apoptosis and cell division. Current Opinion in Cell Biology 12; 257-263
32.Jing Yang, Sally Kornbiuthm (1999) All aboard the cyclin train: subcellular trafficking of cyclins and their CDK partners. Cell Biology 9; 207-210
33.E. Hulleman, J. Boonstra (2001) Regulation of G1 phase progression by growth factors and the extracellular matrix. Cell Mol. Life Sci. 58; 80-93
34.Robin Leake. The cell cycle and regulation of cancer cell growth. Annals New York Academy of Sciences; 252-262
35.Giulio Draetta, Jens Eckstein (1997) Cdc25 protein phosphatases in cell proliferation. Biochimica et Biophysica Acta 1332; 53-63
36.J. Slingerland, M. Pagano (2000) Regulation of the Cdk inhibitor p27 and its deregulation in cancer. Journal of Cellular Physiology 183; 10-17
37.G. Paolo Dotto (2000) p21WAF1/Cip1: more than a break to the cell cycle. Biochimica et Biophysica Acta 1471; 43-56
38.Masataka Itoigawa, Yoshiki Kashiwada, Chihiro Ito, Hiroshi Furukawa, Yoko Tachibana, Kenneth F. Bastow, Kuo-Hsiung Lee (2000) Anticancer agents. 203 carbazole alkaloid murrayaquinone A and related synthetic carbazolequinones as cytotoxic agents. Journal of Natural Products 63; 893-897
39.Lawrence S. Chin, Susan F. Murray, Patrick F. Doherty, Satyendra K.Singh. (1999) K252a induces cell cycle arrest and apoptosis by inhibiting cdc2 and cdc25c. Cancer Investigation 17; 391-395
40.Yoshinari Tomoki, Matsumoto Mami, Arakawa Hiroharu, Okada Hiromasa, Noguchi Kazuo, Suda Hiroyuki, Okura Akira, Nishimura Susumu. (1995) Novel anticancer indolocarbazole compound 6-N-formylamino-12,13-dihydro-1,11-dihydro-13-(β-D-glucopyranosyl)-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione(NB-506):Induction of topoisomerase I-mediated DNA cleavage and mechanisms of cell line-selective cytotoxicity. Cancer Reaearch 55; 1310-1315
41.H. P. Koeffler, D. W. Golde (1980) Human myeloid leukemia cell lines: A review. Blood 56; 344-350
42.Christer Sundstrom, Kenneth Nilsson (1976) Establishment and characterization of a human histiocytic lymphoma cell line (U937) Int. J. Cancer 17; 565-577
43.Richard M. Lewis, John C. Morrill, Peter B. Jahrling, Thomas M. Cosgriff. (1989) Replication of hemorrhage fever viruses in monocytic cells. Reviews of Infectious Diseases 11; S736-S742
44.C. D. Jun, H. O. Pae, J. C. Yoo, H. J. Kwak, R. K. Park, H. T. Chung (1998) Cyclin adenosine monophosphate inhibits nitric oxide-induced apoptosis in human leukemia HL-60 cells. Cellular Immunology 183; 13-21
45.Y. J. Surh, Y. J. Hurh, J. Y. Kang, E. Lee, G. Kong, S. J. Lee (1999) Resveratrol, an antioxidant present in red wine, induced apoptosis in human promyelocytic leukemia (HL60) cells. Cancer Letters 140; 1-10
46.Consuelo Gajate, Isabel Barasoain, Jose M. Andreu, Faustino Mollinedo (2000) Induction of apoptosis in leukemia cells by the reversible microtubule-disrupting agent 2-methoxy-5-(2’,3’,4’-tri methoxyphenyl)- 2,4,6-cycloheptatrien-1-one:protection by Bcl-2 and Bcl-XL and cell cycle arrest. Cancer Research 60; 2651-2659
47.F. Durrieu, F. Belloc, L. Lacoste, P. Dumain, J. Chabrol, J. Dachary-prigent, H. Morjani, M. R. Boisseau, J. Reiffers, Ph. Bernard, F. Lacombe (1998) Caspase activation is an early event in anthracyclin- induced apoptosis and allows detection of apoptosis cells before they are ingested by phagocytes. Experimental Cell Research 240; 165-175
48.Nariyoshi Shinomiya, Yukie Kuno, Fuyumi Yamamoto, Masashi Fukasawa, Atsushi Okumura, Megumi Uefuji, Makoto Rokutanda (2000) Different mechanisms between premitotic apoptosis and postmitotic apoptosis in X-irradiated U937 cells. Int. J. Radiation Oncology Biol. Phys. 47; 767-777
49.Catheryne Chen, Hong Lin, Chachata Karanes, Georeg R. Pettit, Ben D. Chen (2000) Human THP-1 monocytic leukemia cells induced to undergo monocytic differentiation by Bryostatin 1 are refractory to Proteasome inhibitor-induced apoptosis. Cancer Research 60; 4377-4385
50.Min Lu, Jack Levin, Eric Sulpice, Anabelle Sequeira-Le Grand, Monica Alemany, Jacques P. Caen, and Zhong Chao Han (1999) Effect of arsenic trioxide on viability, proliferation, and apoptosis in human megakaryocytic leukemia cell lines. Experimental Hematology 27; 845-852
51.Shougang Zhuang, Mary C. Lynch, Irene E. Kochevar (1999) Caspase-8 mediates caspase-3 activation and cytochrome c release during singlet oxygen-induced apoptosis of HL-60 cells. Experimental Cell Research 250; 203-212
52.A. Benito, A. Lerga, M. Silva, J. Leon, L.J.L. Fernandez (1997) Apoptosis of human myeloid leukemia cells induced by an inhibitor of protein phosphatases (okadaic acid) is prevented by Bcl-2 and bcl-x(L). Leukemia 11; 940-944
53.William R Taylor, George R Stark (2001) Regulation of the G2/M transition by p53. Oncogene 20; 1803-1815
54.Faina Vikhanskaya, Sara Vignati, Patrizia Beccaglia, Cristina Ottoboni, Patrizia Russo, Maurizio D’Incalci, Massimo Broggini (1998) Inactivation of p53 in human ovarian cancer cell line increases the sensitivity to paclitaxel by inducing G2/M arrest and apoptosis. Experimental Cell Research 241; 96-101
55.Masaaki Shiohara, Makoto Akashi, Adrian F. Gombart, Rong Yang, H. Phillip Koeffler (1996) Tumor necrosis factor α:posttranscriptional stabilization of WAF1 mRNA in p53-deficient human leukemic cells. Journal of Cellular Physiology 166; 568-576
56.K. Saeki, A.You, E. Okuma, Y. Yazaki, S. A. susin, G. Kroemer, F. Takaku (2000) Bcl-2 down-regulation causes autophagy in a caspase-independent manner in human leukemic HL60 cells. Cell Death and Differentiation 7; 1263-1269
57.Marc-Antoine Belaud-Rotureau, Francis Lacombe, Francoise Durrieu, Jean-Philippe Vial, Laurent Lacoste, Philippe Brernard, Francis Belloc (1999) Ceramide-induced apoptosis occurs independently of caspases and is decreased by leupeptin. Death and Differentiation 6; 788-795
58.Oliver Micheau, Eric Solary, Arlette Hammann, Marie-Therese, Dimanche-Boitrel (1999) Fas ligand-independent, FADD-mediated activation of the Fas death pathway by anticancer drugs. The Journal of Biological Chemistry 274; 7987-7992
59.A. M. Ibrado, C. N. Kim, K. Bhalla (1998) Temporal relationship of CDK1 activation and mitotic arrest to cytosolic accumulation of cytochrome c and caspase 3 activity during Taxol-induced apoptosis of human AML HL-60 cells. Leukemia 12; 1930-1936
60.Yi-He Ling, Carmen Tornos, Roman Perez-Soler (1998) Phophorylation of Bcl-2 is a marker of M phase events and not a determinant of apoptosis. The Journol of Biological Chemistry 273; 18984-18991
61.Diane E. McCloskey, Scott H. Kaufmann, Laura J. Prestigiacomo, Nancy E. Davidson (1996) Paclitaxol induces programmed cell death in MDA-MB-468 human breast cancer cells. Clinical Cancer Research 847; 847-854
62.Dan L. Wod, Dulal Panda, Todd R. Wiernicki, Leslie Wilson, Mary Ann Jordan, Jai Pal Singh (1997) Inhibition of mitosis and microtubule function through direct tubulin binding by a novel antiproliferation naphthopyran LY290181. Molecular Pharmacology 52; 437-444
63.Susan L. Mooberry, Lizette Busquets, Georgia Tien (1997) Induction of apoptosis by cryptophycin 1, a new antimicrotubule agent. Int. J. Cancer 73; 440-448
64.Susan L. Mooberry, Georgia Tien, Anne H. Heranadez, Anuchit Plubrukarn, Bradley S. Davidson (1999) Laulimalide and isolaulimalide, new paclitaxel-like microtubule-stabilizing agents. Cancer Research 59; 653-660
65.Jian-Dong Jiang, Ashley S. Davis, Kim Middleton, Yi-He Ling, Roman Perez-Soler, James F. Holland, J. George Bekesi (1998) 3-(Indoacetamido)-benzoylurea:a novel cancericidal tubulin ligand that inhibits microtubule polymerization, phosphrylates bcl-2, and induces apoptosis in tumor cells. Cancer Research 58, 5389-5395
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
1. 劉弘煌,〈如何將社會治安工作落實於社區之中〉,《社區發展季刊》,1997,第77期。
2. 陳建志,〈守望相助工作現存問是題之探討與研究〉,《研考報導》,1993第23卷。
3. 陳祖輝,〈建構社區二元防禦體系:論「社區警政」與「環境預防」觀點〉,《社區發展季刊》,1998,第82期。
4. 劉弘煌,〈居民參與社區「守望相助」運動績效及滿意度的研究─以大直社區為例〉,《實踐學報》,1997,第28期。
5. 陳明傳,〈社區警政之意義與發展─未來派出所經營方向之芻議〉,《警學叢刊》,1997,第28卷第2期。
6. 劉淑娟、蘇秀娟、謝美娥:北市失能老人其主要照護者資源需求之初探。長期照護雜誌,1998;2(2):31-47。
7. 周麗芳:德國長期照護保險制度及財務規劃。保險專刊,1999;12;58:53-67。
8. 周麗芳:台灣地區長期照護財務抉擇。理論與政策,2000.03;14(1):103-114。
9. 林振賢:日本「介護保險法」之介述(上)(中)(下)。中國勞工,1999;11(998):10-14。
10. 林芸芸:新店民眾健康保險需求研究。公共衛生,1992;18(4):297-309。
11. 林芸芸:德國的長期照護保險-醫療、照護、保險的結合。醫院, 2000;33(3):14-25。
12. 林麗嬋、歐美、吳肖琪:長期照護中主要照顧者之家庭功能、社會支持與情緒,護理研究,1997;5(1):77-87。
13. 廖福村,〈社會控制概論〉,《警專學報》,1994,第7期。
14. 詹純鑑,〈社區發展的意義與推行途徑〉,《東方雜誌》,1982,第2卷第10期。
15. 葉毓蘭,〈警政新取向:談社區警政的理論與實際〉,《警學叢刊》,1996,第27卷第3期。