(35.175.212.130) 您好!臺灣時間:2021/05/18 03:23
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:吳渝樺
研究生(外文):Yu-Hauh Wu
論文名稱:箆蔴子毒蛋白質促使計劃性細胞凋亡的分子機制之研究―人類B型血球抗原係一與箆蔴子毒蛋白質-A鏈結合的細胞凋亡調控者
論文名稱(外文):Studies on the Molecular Mechanism of Ricin-triggered Programmed Cell Death—BAT3, a Ricin-A Chain Binding Apoptotic Regulator
指導教授:林榮耀林榮耀引用關係
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:生物化學暨分子生物學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:英文
論文頁數:102
中文關鍵詞:細胞凋亡子毒蛋白質-A鏈人類B型血球抗原
外文關鍵詞:Programmed Cell DeathBAT3apoptosisRicin-A Chain
相關次數:
  • 被引用被引用:0
  • 點閱點閱:152
  • 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
箆蔴子毒蛋白質屬於第二型核醣體去活性蛋白質家族的一員。箆蔴子毒蛋白質係由一具酵素活性的A-鏈 (RTA) 及一能與半乳醣結合的B-鏈 (RTB) 所組成。RTA與RTB之間以一對雙硫鍵互相連結。RTB與細胞表面含半乳糖單元的接受器結合後將導致整個箆蔴子毒蛋白質分子藉由內噬作用進入細胞。在細胞中,RTA被逆向轉運至內質網。之後,RTA利用其RNA N-醣苷水解酶活性專一性地將28S核醣體RNA上第4324號腺口票口 令 移除,並抑制蛋白質的生合成。
近年來釵h研究結果顯示箆蔴子毒蛋白質經由以下兩種途徑造成細胞死亡:抑制蛋白質轉譯反應及誘發計畫性細胞凋亡。為了要探索與箆蔴子毒蛋白質造成計畫性細胞死亡的相關分子,酵母菌雙雜合篩選系統在本研究中被用於找尋細胞內的RTA結合蛋白質。經過完整的篩選過程,我找到了三種RTA結合蛋白質。經由核苷酸序列分析及資料庫比對證實此三種純株分別可編譯出Nrf-3, hPLIC-2 及 BAT3 的一個片段 (BAT3614-1044)。有趣的是這三種RTA結合蛋白質皆屬於類ubiquitin 蛋白質家族的成員。因為由酵母菌雙雜合篩選系統中得到的RTA結合蛋白質中,以BAT3614-1044佔70 ﹪最多,所以本研究著重於探討BAT3在箆蔴子毒蛋白質造成計畫性細胞死亡中所扮演的關鍵角色。為了研究BAT3614-1044 在細胞中的位置及弁遄ABAT3614-1044 的cDNA被選殖入真核細胞表現載體中以利產生具有氮基端FLAG標籤的BAT3614-1044。經由免疫細胞染色及共軛焦顯微鏡觀察,發現BAT3614-1044均勻地分佈於細胞核及細胞質中。將細胞以處理箆蔴子毒蛋白質處理後,可造成BAT3614-1044被水解出一個片段。廣效型細胞凋亡酶(caspase)抑制劑及專一性第三型細胞凋亡致效器(caspase-3)抑制劑均可有效阻斷BAT3614-1044被水解,然而,依鈣蛋白質分解酵素或絲胺酸蛋白酶抑制劑無法阻斷BAT3614-1044被水解。 利用定位突變法成它a證實BAT3614-1044被切在符合第三型細胞凋亡酶的辨識序列(DEQD1001↓G)上。
為了進一步探討BAT3在箆蔴子毒蛋白質造成細胞死亡中所扮演的角色,全長的BAT3 cDNA經由EST mapping及直接以基因庫為模板的PCR反應所選殖。此外,一個BAG弁鈰炾麈吤◥慷AT3變異株也成它a被選殖。在箆蔴子毒蛋白質處理下,BAT3被第三型細胞凋亡酶所切割。以zDEVD-fmk前處理可抑制第三型細胞凋亡酶將BAT3水解的反應。
內生型的BAT3亦會被箆蔴子毒蛋白質所誘發的第三型細胞凋亡酶所切割,且產生一個羰基端131個胺基酸的片段(CTF-131)。在第三型細胞凋亡酶缺失的人類乳癌細胞株(MCF-7)中,BAT3在箆蔴子毒蛋白質處理下維持完整不被水解。完整的BAT3位於細胞核中;然而CTF-131則位於細胞質中。藉由胺基酸序列分析及定位突變法,一個新的核定位序列(Nuclear localization sequence)被鑑定出來。令人印象深刻的是,CTF-131表現後造成計畫性細胞凋亡的特徵包括細胞質皺縮圓起、染色質緊緻化及磷酯絲胺酸外露至細胞膜外。由CTF-�婿AG被轉運至細胞核中,且無法造成細胞型態變化的結果,顯示此BAG弁鈰牊鴭譗TF-131的弁鄐帣茩M內定位有重要貢獻。此外,CTF-131也造成肌纖蛋白質重組化,這可能是造成細胞型態變化的關鍵機制之一。大量表現BAT3可抑制箆蔴子毒蛋白質誘發的細胞色素c的釋出及計畫性細胞凋亡。這個反應可能透過誘發內生性Bcl-2過量表現來達成。利用反義寡核苷酸抑制內生性BAT3的表達,可降低箆蔴子毒蛋白質造成的細胞死亡。這些結果說明了BAT3在箆蔴子毒蛋白造成的細胞死亡過程中扮演了關鍵角色。在此研究中,由實驗證實了BAT3是一個箆蔴子毒蛋白質A-鏈的結合蛋白質及計畫性細胞凋亡的調節者,而由第三型細胞凋亡酶自BAT3所切割出的CTF-131則誘發了細胞凋亡相關型態上的劇烈變化。
ABSTRACT
Ricin is a member of type II ribosome-inactivating protein (RIP) family. It is composed of a toxophoric A-chain (RTA) and a galactose-binding B-chain (RTB). In cells, the RTA is retrograde translocated to one of its target site, endoplasmic reticulum (ER). Then, the RTA uses its RNA N-glycosidase activity to specifically remove an adenine residue (A4324) from the 28S rRNA, and inhibits protein biosynthesis.
Several lines of evidence have shown that ricin induces cell death through two pathways: Inhibition of protein translation and inducing of apoptosis. A yeast two-hybrid screening using RTA catalytic mutant (E177Q, R180L) as bait is employed to identify RTA-binding proteins. Three clones are isolated during screening. Specific interactions between RTA and these clones are confirmed by yeast co-transformation and reporter assay. Nucleotide sequencing and data base analysis show that these clones encode partial Nrf3, hPLIC-2 and BAT3. Interestingly, they belong to the Ubiquitin-like protein family. The BAT3 is chosen as a major target in this study since 70 % of positive two-hybrid clones encode the same fragment of BAT3 (BAT3614-1044). The cDNA encoding BAT3614-1044 is sub-cloned in a mammalian expression vector and expressed in cells as N-terminal FLAG-tagged BAT3614-1044. The BAT3614-1044 displays both nuclear and cytoplasmic localization as revealed by immunocytochemistry and confocal microscopy. Ricin treatment causes cleavage of BAT3614-1044 and a cleaved fragment is generated. The cleavage is blocked by zVAD-fmk or zDEVD-fmk but not by calpain or serine protease inhibitor. Site-directed mutagenesis reveals that BAT3614-1044 is cleaved at the consensus caspase-3 cleavage site (DEQD1001↓G).
To further explore roles of BAT3 in ricin-triggered apoptosis, full-length BAT3 cDNA is cloned by EST mapping or direct PCR from Jurkat cDNA library. A BAG domain-truncated variant of BAT3 due to alternative splicing is also obtained. Ectopically expressed BAT3 is cleaved by caspase-3 during treatment with ricin. The cleavage of BAT3 is inhibited by zDEVD-fmk.
Endogenous BAT3 is also cleaved by ricin-induced caspase-3 and a C-terminal fragment with 131 amino acid residues is released (CTF-131). In caspase-3 deficient MCF-7 cells, BAT3 remains intact during treatment with ricin. BAT3 protein is localized in the nucleus, while CTF-131 is localized in the cytoplasm. By amino acid sequences analysis and site-specific mutagenesis, a novel nuclear localization signal in BAT3 is identified. Strikingly, the CTF-131 expressing cells display hallmarks of apoptosis including cell rounding, shrinkage, chromatin condensation and externalization of phosphatidylserine. CTF-�婿AG shows pronounced nuclear staining pattern and fails to induce apoptotic morphology, suggesting that BAG domain is important for CTF-131-induced morphological changes. Moreover, CTF-131 significantly disturbs the F-actin structure, which might be responsible for cell morphological changes. Over-expression of BAT3 inhibits ricin-induced cytochrome c release and apoptosis partly through up-regulation of endogenous Bcl-2. Silencing expression of endogenous BAT3 by antisense oligonucleotide treatment suppresses ricin-triggered apoptosis, suggesting that BAT3 is crucial for ricin-triggered cell death. In this study, human BAT3 is identified as a RTA-binding apoptotic regulator. Caspase-3 cleavage of BAT3 releases an active CTF-131, which induces apoptotic morphological changes.
TABLE of CONTENTS
PAGE

ABBREVIATIONS 1

ABSTRACT 6

摘要 8

OVERVIEW and RATIONALE 10

INTRODUCTION 11

MATERIALS and METHODS 14
Materials 14
Isolation of ricin genomic DNA 14
Purification of DNA from agarose gel 15
Transformation of E. coli competent cells with plasmids 15
Plasmid isolation from yeast 15
Protein extraction from yeast cells 16
Site-directed mutagenesis 16
Nucleotide sequencing 17
Yeast two-hybrid screening 17
Colony-lift filter assay 17
Yeast mating assay 18
Liquid culture assay for quantitative analysis of protein interaction in yeast 18
GST pull-down assay 19
Western-blotting 19
Expression of CTF-131 by baculovirus system and production of anti-CTF-131 polyclonal antibody 19
Expression vectors, cDNA cloning and mutants construction 20
Cell culture, transfection and cell death assays 20
Phallodin labeling of the F-actin 23
Fractionation of F-actin and G-actin 23
Immunofluorescence and confocal microscopy 23
Co-localization of ricin and endogenous BAT3 24
Measurement of caspases activities 24
Preparation of subcellular fractions 25
RT-PCR 25
Oligodeoxynucleotides used to inhibit endogenous BAT3 expression 25

RESULTS 27
Ricin triggers hallmarks of apoptosis 27
Cloning of the RTA cDNA 29
Isolation of RTA binding protein by yeast two-hybrid library screening 30
Mapping binding sites of RTAcm for interaction with BAT3614-1044 33
Cloning and expression of full-length BAT3 cDNA 34
Expression of His6-CTF-131 and generation of anti-CTF-131 polyclonal antibody 35
In vitro and in vivo interaction of ricin and BAT3 36
BAT3 is a novel caspase-3 37
Ricin is crucial for cleavage of BAT3 40
CTF-131 induces apoptotic morphologies 40
CTF-131 induces F-actin dissolution 42
Intracellular localization of BAT3 and its mutants 44
Over-expression of full-length BAT3 inhibits ricin-induced cytochrome c release and cell 45
Ectopic expression of BAT3 prevents ricin-triggered apoptosis 47
Over-expression of BAT3 elevates endogenous Bcl-2 protein 48
BAT3 is crucial for ricin-induced apoptosis 48

DISCUSSION 51
Intracellular localization and caspase-3 cleavage of BAT3 51
BAG-like domain of BAT3 54
The pathway of CTF-131-induced apoptotic morphological changes 55
BAT3, an inherent pro-apoptotic factor 56
Clinical applications of RTA in cancer therapy 56
A model for ricin-triggered programmed cell death 58

FIGURES and LEGENDS 60
Fig. 1. Ricin-induced apoptotic features 60
Fig. 2. Caspases activation in ricin-treated cells 61
Fig. 3. Ricin-triggered DNA fragmentation 62
Fig. 4. Isolation of genomic DNA of Ricinus communis and cloning of pAS2-1-RTAcm and pGEX-2T-RTA 63
Fig. 5. Examination of phenotypes of yeast transformants and expression of RTAcm in
Y190 yeast cells 64
Fig. 6. Schematic representation of the yeast two-hybrid screening and the pGAD10 vector 65
Fig. 7. Isolation of RTAcm-binding proteins by yeast two-hybrid screening 66
Fig. 8. Binding activity between RTAcm and BAT3614-1044 67
Fig. 9. Mapping binding sites of RTAcm for interaction with BAT3614-1044 69
Fig. 10. Cloning of full-length BAT3 71
Fig. 11. BAT3 and its various mutants used in this study 74
Fig. 12. Expression of His6-CTF-131 and production of anti-CTF-131 polyclonal antibody 75
Fig. 13. Interaction of Ricin with BAT3 76
Fig. 14. BAT3 is a novel caspase-3 substrate 77
Fig. 15. Endogenous BAT3 is a novel caspase-3 substrate 78
Fig. 16. Ricin is crucial for caspase-3 cleavage of BAT3 79
Fig. 17. Induction of apoptotic features by CTF-131 is independent of activation of caspases 80
Fig. 18. CTF-131 induces exposure of phosphatidylserine 81
Fig. 19. F-actin dissolution induced by CTF-131 82
Fig. 20. Intracellular localization of BAT3 and its mutants 83
Fig. 21. Over-expression of BAT3 prevents ricin-induced cytochrome c release 84
Fig. 22. Over-expression of BAT3 inhibits ricin-triggered apoptosis 85
Fig. 23. Over-expression of BAT3 up-regulates protein levels of endogenous Bcl-2 86
Fig. 24. BAT3 is crucial for ricin-induced apoptosis 87
Fig. 25. A model for ricin-triggered apoptosis 88

REFERENCES 89

PUBLICATIONS 100
REFERENCES

1.Lin JY, Tserng KY, and Tung TC. Purification of ricin from Ricinus communis. Taiwan Yi Xue Hui Za Zhi. 1970, 69(1): 48-52.
2.Ishiguro. M, Takahashi. T, Funatsu G, Hayashi. K, and Funatsu. M. Biochemical studies on ricin. I. Purification of ricin. J Biochem (Tokyo). 1964, 55:587-92.
3.Ishiguro. M, Takahashi. T, Hayashi. K, and Funatsu. M. Biochemical studies on ricin. II. Molecular weight and some physicochemical properties of crystalline ricin D. J Biochem (Tokyo). 1964, 56:325-7.
4.Lin JY, Liu K, Chen CC, and Tung TC. Effect of crystalline ricin on the biosynthesis of protein, RNA, and DNA in experimental tumor cells. Cancer Res. 1971, 31(7): 921-4.
5.Lin JY, Lin LT, Chen CC, Tserng KY, and Tung TC. The inhibitory effect of crystalline ricin in Ehrlich ascites tumor. Taiwan Yi Xue Hui Za Zhi. 1970, 69(1): 53-7.
6.Lin JY, Tserng KY, Chen CC, Lin LT, and Tung TC. Abrin and ricin: new anti-tumour substances. Nature. 1970, 227(255): 292-3.
7.Lin JY, Chang YC, Huang LY, and Tung TC. The cytotoxic effects of abrin and ricin on Ehrlich ascites tumor cells. Toxicon. 1973 Jul; 11(4): 379-81.
8.Tung TC, Lin JY, and Hsu CT. The mechanism of the anti-cancer activities of abrin and ricin. Taiwan Yi Xue Hui Za Zhi. 1974 Nov; 73(11): 682-4.
9.Hsu CT, Lin JY, and Tung TC. Further report on therapeutic effect of abrin and ricin on human cancers. Taiwan Yi Xue Hui Za Zhi. 1974, 73(9): 526-42.
10.Refsnes K, Olsnes S, and Pihl A. On the toxic proteins abrin and ricin. Studies of their binding to and entry into Ehrlich ascites cells. J Biol Chem. 1974, 249(11): 3557-62.
11.Olsnes S, and Pihl A. Different biological properties of the two constituent peptide chains of ricin, a toxic protein inhibiting protein synthesis. Biochemistry. 1973, 12(16): 3121-6.
12.Lord JM, Deeks E, Marsden CJ, Moore K, Pateman C, Smith DC, Spooner RA, Watson P, and Roberts LM. Retrograde transport of toxins across the endoplasmic reticulum membrane. Biochem Soc Trans. 200, (Pt 6): 1260-2.
13.Sandvig K, Grimmer S, Lauvrak SU, Torgersen ML, Skretting G, van Deurs B, and Iversen TG. Pathways followed by ricin and Shiga toxin into cells. Histochem Cell Biol. 2002, 117(2): 131-41.
14.Sandvig K, and van Deurs B. Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives. EMBO J. 2000, 19(22): 5943-50.
15.Gonatas NK, Steiber A, Kim SU, Graham DI, and Avrameas S. Internalization of neuronal plasma membrane ricin receptors into the Golgi apparatus. Exp Cell Res. 1975, 94(2): 426-31.
16.Feigenson ME, Schnebli HP, and Baggiolini M. Demonstration of ricin-binding sites on the outer face of azurophil and specific granules of rabbit polymorphonuclear leukocytes. J Cell Biol. 1975, 66(1): 183-8.
17.Sandvig K, Olsnes S, and Pihl A. Kinetics of binding of the toxic lectins abrin and ricin to surface receptors of human cells. J Biol Chem. 1976, 251(13): 3977-84.
18.Riccobono F, and Fiani ML. Mannose receptor dependent uptake of ricin A1 and A2 chains by macrophages. Carbohydr Res. 1996, 282(2): 285-92.
19.Cavallaro U, Nykjaer A, Nielsen M, and Soria MR. Alpha 2-macroglobulin receptor mediates binding and cytotoxicity of plant ribosome-inactivating proteins. Eur J Biochem. 1995, 232(1): 165-71.
20.Magnusson S, and Berg T. Endocytosis of ricin by rat liver cells in vivo and in vitro is mainly mediated by mannose receptors on sinusoidal endothelial cells. Biochem J. 1993, 291 ( Pt 3): 749-55
21.Brech A, Magnusson S, Stang E, Berg T, and Roos N. Receptor-mediated endocytosis of ricin in rat liver endothelial cells. An immunocytochemical study. Eur J Cell Biol. 1993, 60(1): 154-62.
22.van Deurs B, Pedersen LR, Sundan A, Olsnes S, and Sandvig K. Receptor-mediated endocytosis of a ricin-colloidal gold conjugate in vero cells. Intracellular routing to vacuolar and tubulo-vesicular portions of the endosomal system. Exp Cell Res. 1985, 159(2): 287-304.
23.Lin JY, Ju ST, Wu HL, and Tung TC. The binding of abrin and ricin by Ehrlich ascites tumor cells. Cancer Res. 1973, 33(11): 2688-91.
24.Lin JY, Pao CC, Ju ST, and Tung TC. Polyribosome disaggregation in rat liver following administration of the phytotoxic proteins, abrin and ricin. Cancer Res. 1972, 32(5): 943-7.
25.Sperti S, Montanaro L, Mattioli A, and Stirpe F. Inhibition by ricin of protein synthesis in vitro: 60 S ribosomal subunit as the target of the toxin. Biochem J. 1973, 136(3): 813-5.
26.Montanaro L, Sperti S, Mattioli A, Testoni G, and Stirpe F. Inhibition by ricin of protein synthesis in vitro. Inhibition of the binding of elongation factor 2 and of adenosine diphosphate-ribosylated elongation factor 2 to ribosomes. Biochem J. 1975, 146(1): 127-31.
27.Benson S, Olsnes S, Pihl A, Skorve J, and Abraham AK. On the mechanism of protein-synthesis inhibition by abrin and ricin. Inhibition of the GTP-hydrolysis site on the 60-S ribosomal subunit. Eur J Biochem. 1975, 59(2): 573-80.
28.Endo Y, and Tsurugi K. RNA N-glycosidase activity of ricin A-chain. Mechanism of action of the toxic lectin ricin on eukaryotic ribosomes. J Biol Chem. 1987, 262(17): 8128-30.
29.Endo Y, and and Tsurugi K. The RNA N-glycosidase activity of ricin A-chain. The characteristics of the enzymatic activity of ricin A-chain with ribosomes and with rRNA. J Biol Chem. 1988, 263(18): 8735-9.
30.Olsnes S, Refsnes K, and Pihl A. Mechanism of action of the toxic lectins abrin and ricin. Nature. 1974, 249(458): 627-31.
31.Morris KN, and Wool IG. Determination by systematic deletion of the amino acids essential for catalysis by ricin A chain. Proc Natl Acad Sci U S A. 1992, 89(11): 4869-73.
32.Munishkin A, and Wool IG. Systematic deletion analysis of ricin A-chain function. Single amino acid deletions. J Biol Chem. 1995, 270(51): 30581-7.
33.Olson MA. Ricin A-chain structural determinant for binding substrate analogues: a molecular dynamics simulation analysis. Proteins. 1997, 27(1): 80-95.
34.Day PJ, Ernst SR, Frankel AE, Monzingo AF, Pascal JM, Molina-Svinth MC, and Robertus JD. Structure and activity of an active site substitution of ricin-A chain. Biochemistry. 1996, 35(34): 11098-103.
35.Weston SA, Tucker AD, Thatcher DR, Derbyshire DJ, and Pauptit RA. X-ray structure of recombinant ricin A-chain at 1.8 A resolution. J Mol Biol. 1994, 244(4): 410-22.
36.Mlsna D, Monzingo AF, Katzin BJ, Ernst S, and Robertus JD. Structure of recombinant ricin-A chain at 2.3 A. Protein Sci. 1993, 2(3): 429-35.
37.Gluck A, Endo Y, and Wool IG. The ribosomal RNA identity elements for ricin and for alpha-sarcin: mutations in the putative CG pair that closes a GAGA tetraloop. Nucleic Acids Res. 1994, 22(3): 321-4.
38.Wool IG, Gluck A, and Endo Y. Ribotoxin recognition of ribosomal RNA and a proposal for the mechanism of translocation. Trends Biochem Sci. 1992, 17(7): 266-9.
39.Robertus J. The structure and action of ricin, a cytotoxic N-glycosidase. Semin Cell Biol. 1991, 2(1): 23-30.
40.Stirpe F, Barbieri L, Battelli MG, Soria M, and Lappi DA. Ribosome-inactivating proteins from plants: present status and future prospects. Biotechnology (N Y). 1992, 10(4): 405-12.
41.Brigotti M, Rambelli F, Zamboni M, Montanaro L, and Sperti S. Effect of alpha-sarcin and ribosome-inactivating proteins on the interaction of elongation factors with ribosomes. Biochem J. 1989, 257(3): 723-7.
42.Roy CJ, Hale M, Hartings JM, Pitt L, and Duniho S.Impact of inhalation exposure modality and particle size on the respiratory deposition of ricin in BALB/c mice. Inhal Toxicol. 2003, 15(6): 619-38.
43.Bradberry SM, Dickers KJ, Rice P, Griffiths GD, and Vale JA. Ricin poisoning. Toxicol Rev. 2003; 22(1): 65-70.
44.Collins JA, Schandi CA, Young KK, Vesely J, and Willingham MC. Major DNA fragmentation is a late event in apoptosis. J Histochem Cytochem. 1997, 45(7): 923-34.
45.Hughes JN, Lindsay CD, and Griffiths GD. Morphology of ricin and abrin exposed endothelial cells is consistent with apoptotic cell death. Hum Exp Toxicol. 1996, 15(5): 443-51.
46.Baluna R, Coleman E, Jones C, Ghetie V, and Vitetta ES. The effect of a monoclonal antibody coupled to ricin A chain-derived peptides on endothelial cells in vitro: insights into toxin-mediated vascular damage. Exp Cell Res. 2000, 258(2): 417-24.
47.Sadakata N, Oda T, Komatsu N, and Muramatsu T. Effects of glutathione-related compounds on increased caspase-3 and caspase-6-like activities in ricin-treated U937 cells. Biosci Biotechnol Biochem. 2000, 64(1): 202-5.
48.Keppler-Hafkemeyer A, Brinkmann U, and Pastan I. Role of caspases in immunotoxin-induced apoptosis of cancer cells. Biochemistry. 1998, 37(48): 16934-42.
49.Komatsu N, Oda T, and Muramatsu T. Involvement of both caspase-like proteases and serine proteases in apoptotic cell death induced by ricin, modeccin, diphtheria toxin, and pseudomonas toxin. J Biochem (Tokyo). 1998, 124(5): 1038-44.
50.Higuchi S, Tamura T, and Oda T. Cross-Talk between the Pathways Leading to the Induction of Apoptosis and the Secretion of Tumor Necrosis Factor-alpha in Ricin-Treated RAW 264.7 Cells. J Biochem (Tokyo). 2003, 134(6): 927-33.
51.Brigotti M, Alfieri R, Sestili P, Bonelli M, Petronini PG, Guidarelli A, Barbieri L, Stirpe F, and Sperti S. Damage to nuclear DNA induced by Shiga toxin 1 and ricin in human endothelial cells. FASEB J. 2002, 16(3): 365-72.
52.Ghetie V, and Vitetta ES. Chemical construction of immunotoxins. Mol Biotechnol. 2001, 18(3): 251-68.
53.Schnell R, Borchmann P, Schulz H, and Engert A. Current strategies of antibody-based treatment in Hodgkin''s disease. Ann Oncol. 2002, 13 Suppl 1:57-66.
54.Fidias P, Grossbard M, and Lynch TJ Jr. A phase II study of the immunotoxin N901-blocked ricin in small-cell lung cancer. Clin Lung Cancer. 2002, 3(3): 219-22.
55.Schnell R, Borchmann P, Staak JO, Schindler J, Ghetie V, Vitetta ES, and Engert A. Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin''s lymphoma. Ann Oncol. 2003, 14(5): 729-36.
56.Szatrowski TP, Dodge RK, Reynolds C, Westbrook CA, Frankel SR, Sklar J, Stewart CC, Hurd DD, Kolitz JE, Velez-Garcia E, Stone RM, Bloomfield CD, Schiffer CA, and Larson RA. Lineage specific treatment of adult patients with acute lymphoblastic leukemia in first remission with anti-B4-blocked ricin or high-dose cytarabine: Cancer and Leukemia Group B Study 9311. Cancer. 2003, 97(6): 1471-80.
57.Smallshaw JE, Ghetie V, Rizo J, Fulmer JR, Trahan LL, Ghetie MA, and Vitetta ES. Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice. Nat Biotechnol. 2003, (4): 387-91.
58.Schnell R, Staak O, Borchmann P, Schwartz C, Matthey B, Hansen H, Schindler J, Ghetie V, Vitetta ES, Diehl V, and Engert A. A Phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4.dgA) in patients with refractory CD30+ Hodgkin''s and non-Hodgkin''s lymphoma. Clin Cancer Res. 2002, 8(6): 1779-86.
59.Saggioro D, Acquasaliente L, Daprai L, and Chieco-Bianchi L. Inhibition of Apoptosis by Human T-Lymphotropic Virus Type-1 Tax Protein. Ann N Y Acad Sci. 2003, (1010): 591-597.
60.Lay S, Prehaud C, Dietzschold B, and Lafon M. Glycoprotein of Nonpathogenic Rabies Viruses Is a Major Inducer of Apoptosis in Human Jurkat T Cells. Ann N Y Acad Sci. 2003, (1010): 577-581.
61.Castedo M, Perfettini JL, Andreau K, Roumier T, Piacentini M, and Kroemer G. Mitochondrial apoptosis induced by the HIV-1 envelope. Ann N Y Acad Sci. 2003, (1010): 19-28.
62.James CO, Huang MB, Khan M, Garcia-Barrio M, Powell MD, and Bond VC. Extracellular Nef protein targets CD4+ T cells for apoptosis by interacting with CXCR4 surface receptors. J Virol. 2004, 78(6): 3099-109.
63.Brune W, Menard C, Heesemann J, and Koszinowski UH. A ribonucleotide reductase homolog of cytomegalovirus and endothelial cell tropism. Science. 2001, 291(5502): 303-5.
64.Swingler S, Brichacek B, Jacque JM, Ulich C, Zhou J, and Stevenson M. HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infection. Nature. 2003, 424(6945): 213-9.
65.White K, Grether ME, Abrams JM, Young L, Farrell K, and Steller H. Genetic control of programmed cell death in Drosophila. Science. 1994, 264(5159): 677-83.
66.Thress K, Henzel W, Shillinglaw W, and Kornbluth S. Scythe: a novel reaper-binding apoptotic regulator. EMBO J. 1998, 17(21): 6135-43.
67.Thress K, Evans EK, and Kornbluth S. Reaper-induced dissociation of a Scythe-sequestered cytochrome c-releasing activity. EMBO J. 1999, 18(20): 5486-93.
68.Banerji J, Sands J, Strominger JL, and Spies T. A gene pair from the human major histocompatibility complex encodes large proline-rich proteins with multiple repeated motifs and a single ubiquitin-like domain. Proc Natl Acad Sci U S A. 1990, 87(6): 2374-8.
69.Manchen ST, and Hubberstey AV. Human Scythe contains a functional nuclear localization sequence and remains in the nucleus during staurosporine-induced apoptosis. Biochem Biophys Res Commun. 2001, 287(5): 1075-82.
70.Briknarova K, Takayama S, Homma S, Baker K, Cabezas E, Hoyt DW, Li Z, Satterthwait AC, and Ely KR. BAG4/SODD protein contains a short BAG domain. J Biol Chem. 2002, 277(34): 31172-8.
71.Thress K, Song J, Morimoto RI, and Kornbluth S. Reversible inhibition of Hsp70 chaperone function by Scythe and Reaper. EMBO J. 2001, 20(5):1033-41.
72.Kulms D, and Schwarz T. Molecular mechanisms involved in UV-induced apoptotic cell death. Skin Pharmacol Appl Skin Physiol. 2002, 15(5): 342-7.
73.Breckenridge DG, Germain M, Mathai JP, Nguyen M, and Shore GC. Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene. 2003, 22(53): 8608-18.
74.Takeda K, Matsuzawa A, Nishitoh H, and Ichijo H. Roles of MAPKKK ASK1 in stress-induced cell death. Cell Struct Funct. 2003, 28(1): 23-9.
75.Mills JC, Stone NL, and Pittman RN. Extranuclear apoptosis. The role of the cytoplasm in the execution phase. J Cell Biol. 1999, 146(4): 703-8.
76.Martelli AM, Zweyer M, Ochs RL, Tazzari PL, Tabellini G, Narducci P, and Bortul R. Nuclear apoptotic changes: an overview. J Cell Biochem. 82(4): 634-46.
77.Earnshaw WC. Nuclear changes in apoptosis. Curr Opin Cell Biol. 1995, 7(3): 337-43.
78.Koopman G, Reutelingsperger CP, Kuijten GA, Keehnen RM, Pals ST, and van Oers MH. Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood. 1994, 84(5): 1415-20.
79.Vermes I, Haanen C, Steffens-Nakken H, and Reutelingsperger C. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods. 1995, 184(1): 39-51.
80.Martin SJ, Reutelingsperger CP, McGahon AJ, Rader JA, van Schie RC, LaFace DM, and Green DR. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J Exp Med. 1995,182(5): 1545-56.
81.van Engeland M, Ramaekers FC, Schutte B, and Reutelingsperger CP. A novel assay to measure loss of plasma membrane asymmetry during apoptosis of adherent cells in culture. Cytometry. 1996, 24(2): 131-9.
82.Kagan VE, Borisenko GG, Serinkan BF, Tyurina YY, Tyurin VA, Jiang J, Liu SX, Shvedova AA, Fabisiak JP, Uthaisang W, and Fadeel B. Am J Physiol Lung Cell Mol Physiol. 2003, 285; L1-L17.
83.Ferri KF, and Kroemer G. Organelle-specific initiation of cell death pathways. Nat Cell Biol. 2001, 3(11): E255-63.
84.Meier P, Finch A, and Evan G. Apoptosis in development. Nature. 2000, 407(6805): 796-801.
85.Hengartner MO. The biochemistry of apoptosis. Nature. 2000, 407(6805): 770-6.
86.Adams JM, and Cory S. Apoptosomes: engines for caspase activation. Curr Opin Cell Biol. 2002, 14(6): 715-20.
87.Ravagnan L, Roumier T, and Kroemer G. Mitochondria, the killer organelles and their weapons. J Cell Physiol. 2002, 192(2): 131-7.
88.Turk B, Stoka V, Rozman-Pungercar J, Cirman T, Droga-Mazovec G, Oresic K, and Turk V. Apoptotic pathways: involvement of lysosomal proteases. Biol Chem. 2002, 383(7-8): 1035-44.
89.Karran L, and Dyer MJ. Proteolytic cleavage of molecules involved in cell death or survival pathways: a role in the control of apoptosis? Crit Rev Eukaryot Gene Expr. 2001; 11(4): 269-77.
90.Sartorius U, Schmitz I, and Krammer PH. Molecular mechanisms of death-receptor-mediated apoptosis. Chembiochem. 2001, 2(1): 20-9.
91.Zimmermann KC, Bonzon C, and Green DR. The machinery of programmed cell death. Pharmacol Ther. 2001, 92(1): 57-70.
92.Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA, Roy S, Vaillancourt JP, Chapman KT, and Nicholson DW. A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem. 1997, 272(29): 17907-11.
93.Li H, Zhu H, Xu CJ, and Yuan J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell. 1998, 94(4): 491-501.
94.Luo X, Budihardjo I, Zou H, Slaughter C, and Wang X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell. 1998, 94(4): 481-90.
95.Chien CT, Bartel PL, Sternglanz R, and Fields S. The two-hybrid system: a method to identify and clone genes for proteins that interact with a protein of interest. Proc Natl Acad Sci U S A. 1991, 88(21):9578-82.
96.Morris KN, and Wool IG. Analysis of the contribution of an amphiphilic alpha-helix to the structure and to the function of ricin A chain. Proc Natl Acad Sci U S A. 1994, 91(16): 7530-3.
97.Kim Y, and Robertus JD. Analysis of several key active site residues of ricin A chain by mutagenesis and X-ray crystallography. Protein Eng. 1992, 5(8): 775-9.
98.Halling KC, Halling AC, Murray EE, Ladin BF, Houston LL, and Weaver RF. Genomic cloning and characterization of a ricin gene from Ricinus communis. Nucleic Acids Res. 1985, 13(22): 8019-33.
99.Shimada A. PCR-based site-directed mutagenesis. Methods Mol Biol. 1996; 57:157-65.
100.Natarajan K, Meyer MR, Jackson BM, Slade D, Roberts C, Hinnebusch AG, and Marton MJ. Transcriptional profiling shows that Gcn4p is a master regulator of gene expression during amino acid starvation in yeast. Mol Cell Biol. 2001, 21(13): 4347-68.
101.Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, and Klenk DC. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 150(1): 76-85. Erratum in: Anal Biochem 1987, 163(1): 279.
102.Janicke RU, Sprengart ML, Wati MR, and Porter AG. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem. 1998, 273(16): 9357-60.
103.Zhu H, Fearnhead HO, and Cohen GM. An ICE-like protease is a common mediator of apoptosis induced by diverse stimuli in human monocytic THP.1 cells. FEBS Lett. 1995, 374(2): 303-8.
104.Fraser AG, and Evan GI. Identification of a Drosophila melanogaster ICE/CED-3-related protease, drICE. EMBO J. 1997, 16(10): 2805-13.
105.Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, and Yuan J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature. 2000, 403(6765): 98-103.
106.Mashima T, Naito M, Noguchi K, Miller DK, Nicholson DW, and Tsuruo T. Actin cleavage by CPP-32/apopain during the development of apoptosis. Oncogene. 1997, 14(9): 1007-12.
107.Seimiya H, Mashima T, Toho M, and Tsuruo T. c-Jun NH2-terminal kinase-mediated activation of interleukin-1beta converting enzyme/CED-3-like protease during anticancer drug-induced apoptosis. J Biol Chem. 1997,272(7): 4631-6
108.Breitschopf K, Haendeler J, Malchow P, Zeiher AM, and Dimmeler S. Posttranslational modification of Bcl-2 facilitates its proteasome-dependent degradation: molecular characterization of the involved signaling pathway. Mol Cell Biol. 2000, 20(5): 1886-96.
109.Raftopoulou M, and Hall A. Cell migration: Rho GTPases lead the way. Dev Biol. 2004, 265(1): 23-32.
110.Burridge K, and Wennerberg K. Rho and Rac take center stage. Cell. 2004, 116(2): 167-79.
111.Guan KL, and Rao Y. Signalling mechanisms mediating neuronal responses to guidance cues. Nat Rev Neurosci. 2003, 4(12): 941-56.
112.Lengsfeld AM, Low I, Wieland T, Dancker P, and Hasselbach W. Interaction of phalloidin with actin. Proc Natl Acad Sci U S A. 1974, 71(7): 2803-7.
113.Low I, Dancker P, and Wieland T. Stabilization of F-actin by phalloidin. Reversal of the destabilizing effect of cytochalasin B. FEBS Lett. 1975, 54(2): 263-5.
114.Wang Q, Xie Y, Du QS, Wu XJ, Feng X, Mei L, McDonald JM, and Xiong WC. Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin. J Cell Biol. 2003, 160(4): 565-75.
115.Henderson S, Rowe M, Gregory C, Croom-Carter D, Wang F, Longnecker R, Kieff E, and Rickinson A. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell. 1991, 65(7): 1107-15.
116.Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, and Wang X Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science. 1997, 275(5303): 1129-32.
117.Kluck RM, Bossy-Wetzel E, Green DR, and Newmeyer DD. The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science. 1997, 275(5303): 1132-6.
118.Heikkila R, Schwab G, Wickstrom E, Loke SL, Pluznik DH, Watt R, and Neckers LM. A c-myc antisense oligodeoxynucleotide inhibits entry into S phase but not progress from G0 to G1. Nature. 1987, 328(6129): 445-9.
119.Gupta KC. Antisense oligodeoxynucleotides provide insight into mechanism of translation initiation of two Sendai virus mRNAs. J Biol Chem. 1987, 262(16): 7492-6.
120.Dean NM, and Bennett CF. Antisense oligonucleotide-based therapeutics for cancer. Oncogene. 2003, 22(56): 9087-96.
121.Opalinska JB, and Gewirtz AM. Therapeutic potential of antisense nucleic acid molecules. Sci STKE. 2003, 206: pe47.
122.Day PJ, Owens SR, Wesche J, Olsnes S, Roberts LM, and Lord JM. An interaction between ricin and calreticulin that may have implications for toxin trafficking. J Biol Chem. 2001, 276(10): 7202-8.
123.Alami M, Taupiac MP, and Beaumelle B. Ricin-binding proteins along the endocytic pathway: the major endosomal ricin-binding protein is endosome-specific. Cell Biol Int. 1997, 21(3): 145-50.
124.Vater CA, Bartle LM, Leszyk JD, Lambert JM, and Goldmacher VS. Ricin A chain can be chemically cross-linked to the mammalian ribosomal proteins L9 and L10e. J Biol Chem. 1995, 270(21): 12933-40.
125.Roncuzzi L, and Gasperi-Campani A. DNA-nuclease activity of the single-chain ribosome-inactivating proteins dianthin 30, saporin 6 and gelonin. FEBS Lett. 1996, 392(1): 16-20.
126.Nicolas E, Beggs JM, Haltiwanger BM, and Taraschi TF. A new class of DNA glycosylase/apurinic/apyrimidinic lyases that act on specific adenines in single-stranded DNA. J Biol Chem. 1998, 273(27): 17216-20.
127.Brigotti M, Alfieri R, Sestili P, Bonelli M, Petronini PG, Guidarelli A, Barbieri L, Stirpe F, and Sperti S. Damage to nuclear DNA induced by Shiga toxin 1 and ricin in human endothelial cells. FASEB J. 2002, 16(3): 365-72.
128.Iborra FJ, Jackson DA, and Cook PR. Coupled transcription and translation within nuclei of mammalian cells. Science. 2001, 293(5532): 1139-42.
129.Katsuda K, Kataoka M, Uno F, Murakami T, Kondo T, Roth JA, Tanaka N, and Fujiwara T. Activation of caspase-3 and cleavage of Rb are associated with p16-mediated apoptosis in human non-small cell lung cancer cells. Oncogene. 2002, 21(13): 2108-13.
130.Smith GC, d''Adda di Fagagna F, Lakin ND, and Jackson SP. Cleavage and inactivation of ATM during apoptosis. Mol Cell Biol. 1999, 19(9): 6076-84.
131.Faleiro L, and Lazebnik Y. Caspases disrupt the nuclear-cytoplasmic barrier. J Cell Biol. 2000, 151(5): 951-9.
132.Takemoto K, Nagai T, Miyawaki A, and Miura M. Spatio-temporal activation of caspase revealed by indicator that is insensitive to environmental effects. J Cell Biol. 2003, 160(2): 235-43.
133.Breitschopf K, Haendeler J, Malchow P, Zeiher AM, and Dimmeler S. Posttranslational modification of Bcl-2 facilitates its proteasome-dependent degradation: molecular characterization of the involved signaling pathway. Mol Cell Biol. 2000, 20(5): 1886-96.
134.Takayama S, Bimston DN, Matsuzawa S, Freeman BC, Aime-Sempe C, Xie Z, Morimoto RI, and Reed JC. BAG-1 modulates the chaperone activity of Hsp70/Hsc70. EMBO J. 1997, 16(16): 4887-96.
135.Levee MG, Dabrowska MI, Lelli JL Jr, and Hinshaw DB. Actin polymerization and depolymerization during apoptosis in HL-60 cells. Am J Physiol. 1996, 271(6 Pt 1): C1981-92.
136.Keller H, Rentsch P, and Hagmann J. Differences in cortical actin structure and dynamics document that different types of blebs are formed by distinct mechanisms. Exp Cell Res. 2002, 277(2): 161-72.
137.Usatyuk PV, and Natarajan V. Role of mitogen-activated protein kinases in 4-hydroxy-2-nonenal-induced actin remodeling and barrier function in endothelial cells. J Biol Chem. 2004, 279(12): 11789-97.
138.Cabado AG, Leira F, Vieytes MR, Vieites JM, and Botana LM. Cytoskeletal disruption is the key factor that triggers apoptosis in okadaic acid-treated neuroblastoma cells. Arch Toxicol. 78(2): 74-85.
139.Liu T, Bauskin AR, Zaunders J, Brown DA, Pankurst S, Russell PJ, and Breit SN. Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells. Cancer Res. 2003,63(16): 5034-40
140.Kook S, Kim do H, Shim SR, Kim W, Chun JS, and Song WK. Caspase-dependent cleavage of tensin induces disruption of actin cytoskeleton during apoptosis. Biochem Biophys Res Commun. 2003, 303(1): 37-45.
141.Kim JA, Mitsukawa K, Yamada MK, Nishiyama N, Matsuki N, and Ikegaya Y. Cytoskeleton disruption causes apoptotic degeneration of dentate granule cells in hippocampal slice cultures. Neuropharmacology. 2002, 42(8): 1109-18.
142.Kulms D, Dussmann H, Poppelmann B, Stander S, Schwarz A, and Schwarz T. Apoptosis induced by disruption of the actin cytoskeleton is mediated via activation of CD95 (Fas/APO-1). Cell Death Differ. 2002, 9(6): 598-608.
143.Hubberstey A, Yu G, Loewith R, Lakusta C, and Young D. Mammalian CAP interacts with CAP, CAP2, and actin. J Cell Biochem. 1996, 61(3): 459-66.
144.Moriyama K, and Yahara I. Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin turnover. J Cell Sci. 2002, 115(Pt 8): 1591-601.
145.Hubberstey AV, and Mottillo EP. Cyclase-associated proteins: CAPacity for linking signal transduction and actin polymerization. FASEB J. 2002, 16(6): 487-99.
146.Baum B, and Perrimon N. Spatial control of the actin cytoskeleton in Drosophila epithelial cells. Nat Cell Biol. 2001, 3(10): 883-90.
147.Stevenson VA, and Theurkauf WE. Actin cytoskeleton: putting a CAP on actin polymerization. Curr Biol. 2000, 10(19): R695-7.
148.Baum B, Li W, and Perrimon N. A cyclase-associated protein regulates actin and cell polarity during Drosophila oogenesis and in yeast. Curr Biol. 2000, 10(16): 964-73.
149.Benlali A, Draskovic I, Hazelett DJ, and Treisman JE. act up controls actin polymerization to alter cell shape and restrict Hedgehog signaling in the Drosophila eye disc. Cell. 2000, 101(3): 271-81.
150.Freeman NL, and Field J. Mammalian homolog of the yeast cyclase associated protein, CAP/Srv2p, regulates actin filament assembly. Cell Motil Cytoskeleton. 2000, 45(2): 106-20.
151.Zelicof A, Protopopov V, David D, Lin XY, Lustgarten V, and Gerst JE. Two separate functions are encoded by the carboxyl-terminal domains of the yeast cyclase-associated protein and its mammalian homologs. Dimerization and actin binding. J Biol Chem. 1996, 271(30): 18243-52.
152.Freeman NL, Lila T, Mintzer KA, Chen Z, Pahk AJ, Ren R, Drubin DG, and Field J. A conserved proline-rich region of the Saccharomyces cerevisiae cyclase-associated protein binds SH3 domains and modulates cytoskeletal localization. Mol Cell Biol. 1996, 16(2): 548-56.
153.Freeman NL, Chen Z, Horenstein J, Weber A, and Field J. An actin monomer binding activity localizes to the carboxyl-terminal half of the Saccharomyces cerevisiae cyclase-associated protein. J Biol Chem. 1995, 270(10): 5680-5.
154.Chien J, Staub J, Hu SI, Erickson-Johnson MR, Couch FJ, Smith DI, Crowl RM, Kaufmann SH, and Shridhar V. A candidate tumor suppressor HtrA1 is downregulated in ovarian cancer. Oncogene. 2004, 23(8): 1636-44.
155.Frasca F, Vella V, Aloisi A, Mandarino A, Mazzon E, Vigneri R, and Vigneri P. p73 tumor-suppressor activity is impaired in human thyroid cancer. Cancer Res. 2003, 63(18): 5829-37.
156.Igney FH, and Krammer PH. Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer. 2002, 2(4): 277-88.
157.Ozaki T, Hanaoka E, Naka M, Nakagawara A, and Sakiyama S. Cloning and characterization of rat BAT3 cDNA. DNA Cell Biol. 1999, 18(6): 503-12.
158.Tomblyn MR, and Tallman MS. New developments in antibody therapy for acute myeloid leukemia. Semin Oncol. 2003, 30(4): 502-8.
159.Villamor N, Montserrat E, and Colomer D. Mechanism of action and resistance to monoclonal antibody therapy. Semin Oncol. 2003, 30(4): 424-33.
160.von Mehren M, Adams GP, and Weiner LM. Monoclonal antibody therapy for cancer. Annu Rev Med., 54:343-69.
161.Ohtomo T, Kawata H, Sekimori Y, Shimizu K, Kishima H, Moriuchi S, Miyao Y, Akamatsu K, and Tsuchiya M. A humanized single-chain Fv fragment with high targeting potential against human malignant gliomas. Anticancer Res. 1998, 18(6A): 4311-5.
162.Carter P. Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer. 2001, 1(2): 118-29.
163.Vitetta ES. Immunotoxins and vascular leak syndrome. Cancer J. 2000; 6 Suppl 3:S218-24.
164.Soler-Rodriguez AM, Ghetie MA, Oppenheimer-Marks N, Uhr JW, and Vitetta ES. Ricin A-chain and ricin A-chain immunotoxins rapidly damage human endothelial cells: implications for vascular leak syndrome. Exp Cell Res. 1993, 206(2):227-34
165.Baluna R, Rizo J, Gordon BE, Ghetie V, and Vitetta ES. Evidence for a structural motif in toxins and interleukin-2 that may be responsible for binding to endothelial cells and initiating vascular leak syndrome. Proc Natl Acad Sci U S A. 1999, 96(7):3957-62.
166.Miller, J. H. (1972) Experiments in Molecular Genetics, pp. 352-355, Cold Spring Harbor Laboratory Press, Plainview, NY
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊