Development and Reproduction (한국발생생물학회지:발생과생식)

The Korean Society of Developmental Biology (한국발생생물학회)
권호 표지

The Suicide Gene Diphtheria Toxin A Based Therapy in Cancer Treatment

  • Nguyen.T.Q., Anh (Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University) ;
  • Jeong, Dong-Kee (Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University)
  • Received : 2012.08.08
  • Accepted : 2012.09.07
  • Published : 2012.09.30
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Abstract

Therapeutic cancer is a long lasting and turbulent history accompany with the milestones in surgical intervention, chemotherapy and radiotherapy. In the past decade, however, metastatic cancer still obstinately exists challenging the professional scientist. Beside the major forms of cancer treatment, Diphtheria toxin (DT) which is produced by a pathogenic strain of bacterium Corynebacterium diphtheria to shield themselves against the other dangerous organism, have been researched as a potential candidate to overcome the drawback such as non-specific, non-effect to drug resistant cancer cell and side effects when using chemotherapy and radiotherapy. In the context of suicide gene therapy, the DT expression under controlling of tissue-specific promoter will be targeted in cancer cell but defect in normal cell. The molecular mechanism, characteristic of DT-bases therapy and prominent achievements of preclinical and clinical studies for the past decade are summarized and discussed in this review.

Keywords

References

  1. Abdul-Ghani R, Ohana P, Matouk I, Ayesh S, Ayesh B, Laster M, Bibi O, Giladi H, Molnar-Kimber K, Sughayer MA, De Groot N, Hochberg A (2000) Use of transcriptional regulatory sequences of telomerase (hTER and hTERT) for selective killing of cancer cells. Mol Ther 2:539-544. https://doi.org/10.1006/mthe.2000.0196
  2. Amit D, Hochberg A (2010) Development of targeted therapy for bladder cancer mediated by a double promoter plasmid expressing diphtheria toxin under the control of H19 and IGF-P4 regulatory sequences. Journal of Translational Medicine 8:134. https://doi.org/10.1186/1479-5876-8-134
  3. Amit D, Tamir S, Birman T, Gofrit ON, Hochberg A (2011) Development of targeted therapy for bladder cancer mediated by a double promoter plasmid expressing diphtheria toxin under the control of IGF2-P3 and IGF2-P4 regulatory sequences. Int J ClinExp Med 4(2): 91-102.
  4. Anderson DG, Akinc A, Houssain N, Langer R (2005) Structure/property studies of polymeric gene delivery using a library of poly(b-amino esters). Mol Ther 11: 426-434. https://doi.org/10.1016/j.ymthe.2004.11.015
  5. Anderson GD, Akinc A, Houssain N, Langer R (2004) A polymer library approach to suicide gene therapy for cancer. PNAS 16028-16033.
  6. Ariel I, Sughayer M, Fellig Y, Pizov G, Ayesh S, Podeh D, Libdeh BA, Levy C, Birman T, Tykocinski ML (2000) The imprinted H19 gene is a marker of early recurrence in human bladder carcinoma. Mol Pathol 53:320-323. https://doi.org/10.1136/mp.53.6.320
  7. Ayesh B, Matouk I, Ohana P, Sughayer MA, Birman T, Ayesh S, Schneider T, de Groot N, Hochberg A (2003) Inhibition of tumor growth by DT-A expressed under the control of IGF2 P3 and P4 promoter sequences. Mol Ther 7:535-541. https://doi.org/10.1016/S1525-0016(03)00056-X
  8. Ayesh B, Matouk I, Ohana P, Sughayer MA, Birman T, Ayesh S, Schneider T, de Groot N, Hochberg A (2003) Inhibition of tumor growth by DT-A expressed under the control of IGF2 P3 and P4 promoter sequences. Molecular Therapy 7:4.
  9. Bae SK, Bae MH, Ahn MY, Son MJ, Lee YM, Bae MK, Lee OH, Park BC, Kim KW (1999) Egr-1 mediates transcriptional activation of IGF-II gene in response to hypoxia. Cancer Res 59:5989-5994.
  10. Bingle L, Singleton V, Bingle CD (2002) The putative ovarian tumour marker gene HE4 (WFDC2) is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms. Oncogene 21:2768-2773. https://doi.org/10.1038/sj.onc.1205363
  11. Breidenbach M, Rein DT, Everts M, Glasgow JN, Wang M, Passineau MJ, Alvarez RD, Korokhov N, Curiel DT (2005) Mesothelin-mediated targeting of adenoviral vectors for ovarian cancer gene therapy. Gene Therapy 12:187-193. https://doi.org/10.1038/sj.gt.3302404
  12. Cao GW, Qi ZT, Zhang XP, Miao XQ, Feng XH, Lu Y, Kuriyama S, Du P (1998) Gene therapy for human colorectal carcinoma using human CEA promoter controlled bacterial ADP-ribosylating toxin genes human CEA: PEA & DTA gene transfer. World J Gastroenterol 4:388-391. https://doi.org/10.3748/wjg.v4.i5.388
  13. Chiron MF, Frying CM, FitzGerald DJ (1994) Cleavage of pseudomonas exotoxin and diphtheria toxin by a furin-like enzyme prepared from beef liver. J Biol Chem 269:18167-18176.
  14. Choe S, Bennett MJ, Fujii G, Curmi PMG, Kantardjieff KA, Collier RJ, Eisenberg P (1992) The crystal structural of diphtheria toxin. Nature 357:216-222. https://doi.org/10.1038/357216a0
  15. Clements JA (1989) The glandular kallikrein family of enzymes: Tissue-specific expression and hormonal regulation. Endocrinol Rev 10:393-419. https://doi.org/10.1210/edrv-10-4-393
  16. Collier RJ (1975) Diphtheria toxin: Mode of action and structure, bacteriological reviews. American Society for Microbiology 39:54-85.
  17. Cooper MJ, Fischer M, Komitowski D, Shevelev A, Schulze E, Ariel I, Tykocinski ML, Miron S, Ilan J, de Groot N, Hochberg A (1996) Developmentally imprinted genes as markers for bladder tumor progression. J Urol 155(6):2120-2127. https://doi.org/10.1016/S0022-5347(01)66120-2
  18. Deng Q, Barbieri JT (2008) Molecular mechanism of the cytotoxicity of ADP-ribosylating toxins. Annu Rev Microbiol 62:271-288. https://doi.org/10.1146/annurev.micro.62.081307.162848
  19. Dinh P, Harnett P, Piccart-Gebhart MJ, Awada A (2008) New therapies for ovarian cancer: cytotoxics and molecularly targeted agents. Crit Rev Oncol Hematol 67: 103-112. https://doi.org/10.1016/j.critrevonc.2008.01.012
  20. Dixon CS, Kevin B, Knop F, Figg DW (2001) The control of prostate-specific antigen expression and gene regulation by pharmacological agents. Pharmacol Rev 53:73-91.
  21. Doherty A, Smith G, Banks L, Christmas T, Epstein RJ (1999) Correlation of the osteoblastic phenotype with prostate-specific antigen expression in metastatic prostate cancer: Implications for paracrine growth. J Pathol 188:278-281. https://doi.org/10.1002/(SICI)1096-9896(199907)188:3<278::AID-PATH358>3.0.CO;2-G
  22. Dugimont T, Curgy JJ, Wernert N, Delobelle A, Raes MB, Joubel A, Stehelin D, Coll J (1995) The H19 gene is expressed within both epithelial and stromal components of human invasive adenocarcinomas. Bio Cell 85:117-124. https://doi.org/10.1016/0248-4900(96)85272-5
  23. Engstrom W, Shokrai A, Otte K, Granerus M, Gessbo A, Bierke P, Madej A, Sjolund M, Ward A (1998) Transcriptional regulation and biological significance of the insulin like growth factor II gene. Cell Prolif 31:173-189.
  24. Fogar P, Navaglia F, Basso D, Zambon CF, Moserle L, Indraccolo S, Stranges A, Greco E, Fadi E, Padoan A, Pantano G, Sanzari MC, Pedrazzoli S, Montecucco C, Plebani M (2010) Heat-induced transcription of diphtheria toxin A or its variants, CRM176 and CRM197: Implications for pancreatic cancer gene therapy. Canc Gene Ther 17:58-68. https://doi.org/10.1038/cgt.2009.48
  25. Gordon VL, Yang W, Browman ME, Choe S (1997) Crystal structure of the complex of diphtheria toxin with an extracellular fragment of its receptor. Molecular Cell 1:67-78. https://doi.org/10.1016/S1097-2765(00)80008-8
  26. Hahn H, Wojnowski L, Specht K, Kappler R, Calzada- Wack J, Potter D, Zimmer A, Muller U, Samson E, Quintanilla-Martinez L, Zimmer A (2000) Patched target Igf2 is indispensable for the formation of medulloblastoma and rhabdomyosar-coma. J Biol Chem 275:28341-28344. https://doi.org/10.1074/jbc.C000352200
  27. Hellstrom I, Hellstrom KE (2008) SMRP and HE4 as biomarkers for ovarian carcinoma when used alone and in combination with CA125 and/or each other. Adv Exp Med Biol 622:15-21.
  28. Hellstrom I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, Drescher C, Urban N, Hellstrom KE (2003) The He4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res 63:3695-3700.
  29. Holthuizen P, van der Lee FM, Ikejiri K, Yamamoto M, Sussenbach JS (1990) Identification and initial characterization of a fourth leader exon and promoter of the human IGF-II gene. Biochim Biophys Acta 1087:341-343. https://doi.org/10.1016/0167-4781(90)90010-Y
  30. Honjo T, Nishizuka Y, Kato I, Hayaishi O (1971) Adenosin diphosphate ribisylation of aminoacyl transferase II and inhibition of protein synthesis by diphtheria toxin. The Journal of Biological Chemistry 246:4251-4260.
  31. Huang YH, Zugates GT, Peng W, Holtz D, Dunton C, Green JJ, Hossain N, Chernick MR, Padera RF Jr, Langer R, Anderson DG, Sawicki JA (2009) Nanoparticledelivered suicide gene therapy effectively reduces ovarian tumor burden in mice. Cancer Res 69:6184-6191. https://doi.org/10.1158/0008-5472.CAN-09-0061
  32. Ilan Y, Jona VK, Sengupta K, Davidson A, Horwitz MS, Roy-Chowdhury N, Roy-Chowdhury J (1997) Transient immuno-suppression with FK506 permits long-term expression of therapeutic genes introduced into the liver using recombinant adenoviruses in the rat. Hepatology 26:949-956. https://doi.org/10.1002/hep.510260422
  33. Jia W, Qun Z (2005) Viral vectors for cancer gene therapy: viral dissemination and tumor targeting. Current Gene Therapy 5:133-142. https://doi.org/10.2174/1566523052997460
  34. Joeng HC, Brooke SJ, Eidels L (1998) Toxin binding site of the diphtheria toxin receptor: loss and gain of diphtheria toxin binding of monkey and mouse herapinbinding, epidermal growth factor-like growth factor precursors by reciprocal site-directed mutagenesis. Molecular Microbiology 29(5):1275-1284. https://doi.org/10.1046/j.1365-2958.1998.01015.x
  35. Kaul P, Silverman J, Shen WH, Blanke SR, Huynh PD, Finkelstein A, Collier RJ (1996) Roles of Glu 349 and Asp 352 in membrane insertion and translocation by diphtheria toxin. Protein Sci 5:6875.S-692.
  36. Kawamoto K, Onodera H, Kan S, Kondo S, Imamura M (1999) Possible paracrine mechanism of insulin-like growth factor-2 in the development of liver metastases from colorectal carcinoma. Cancer 85:18-25. https://doi.org/10.1002/(SICI)1097-0142(19990101)85:1<18::AID-CNCR3>3.0.CO;2-4
  37. Kondo M, Suzuki H, Ueda R, Osada H, Takagi K, Takahashi T (1995) Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene 10:1193-1198.
  38. Kunitomi M, Takayama E, Suzuki S, Yasuda T, Tsutsui K, Nagaike K, Hiroi S, Tadakuma T (2000) Selective inhibition of hepatoma cells using diphtheria toxin A under the control of the promoter/enhancer region of the human alpha-fetoprotein gene. Jpn J Canc Res 91: 343-350. https://doi.org/10.1111/j.1349-7006.2000.tb00951.x
  39. Lambotte P, Falmagne P, Capiau C, Zanen J, Ruysschaert JM, Dirkx J (1980) Primary structure of diphtheria toxin fragment B: structural similarities with lipid-binding domains. The Journal of Cell Biology 87:837-840. https://doi.org/10.1083/jcb.87.3.837
  40. Latham JP, Searle PF, Mautner V, James ND (2000) Prostatespecific antigen promoter/enhancer driven gene therapy for prostate cancer: construction and testing of a tissuespecific adenovirus vector. Cancer Res 60:334-341.
  41. Lee EJ, Jameson JL (2002) Cell-specific cre-mediated activation of the diphtheria toxin gene in pituitary tumor cells: potential for cytotoxic gene therapy. Human Gene Ther 13:533-542. https://doi.org/10.1089/10430340252809829
  42. Lee YI, Lee S, Das GC, Park US, Park SM, Lee YI (2000) Activation of the insulin-like growth factor II transcription by afiatoxin B1 induced p53 mutant 249 is caused by activation of transcription complexes; implications for a gain-of-function during the formation of hepatocellular carcinoma. Oncogene 19:3717-3726. https://doi.org/10.1038/sj.onc.1203694
  43. Lemichez E, Bomsel M, Devilliers G, vanderSpek J, Murphy JR, Lukianov EV, Olsnes S, Boquet P (1997) Menbrane translocation of diphtheria toxin fragment A exploits early to late endosome trafficking machinery. MolMicrobiol 23:445-457.
  44. Li Y, McCadden J, Ferrer F, Kruszewski M, Carducci M, Simons J, Rodriguez R (2002) Prostate-specific expression of the diphtheria toxin A chain (DT-A): Studies of inducibility and specificity of expression of prostatespecific antigen promoter-driven DT-A Adenovira-mediated gene transfer. Cancer Res 62:2576-2582.
  45. Lidor YJ, Lee WE, Nilson JH, Maxwell IH, Su LJ, Brand E, Glode LM (1997) In vitro expression of the diphtheria toxin A-chain gene under the control of human chorionic gonadotropin gene promoters as a means of directing toxicity to ovarian cancer cell lines. Am J Obstet Gynecol 177:579-585. https://doi.org/10.1016/S0002-9378(97)70149-2
  46. Lustig-Yariv O, Schulze E, Komitowski D, Erdmann V, Schneider T, de Groot N, Hochberg A (1997) The expression of the imprinted genes H19 and IGF-2 in choriocarcinoma cell lines. Is H19 a tumor suppressor gene? Oncogene 15:169-177. https://doi.org/10.1038/sj.onc.1201175
  47. Martin V, Cortes ML, de Felipe P, Farsetti A, Calcaterra NB, Izquierdo M (2000) Cancer gene therapy by thyroid hormone-mediated expression of toxin genes. Canc Res 60:3218-3224.
  48. Maxwell F, Maxwell IH, Glode LM (1986) Regulated expression of a diphtheria toxin A-chain gene transfected into human cells: possible strategy for inducing cancer cell suicide. Cancer Res 46:4660-4664.
  49. Maxwell F, Maxwell IH, Glode LM (1987) Cloning, sequence determination, and expression in transfected cells of the coding sequence for the tox 176 attenuated diphtheria toxin chain. MolCel Bio 7:1576-1579.
  50. Maxwell IH, Glode LM, Maxwell F (1991) Expression of the diphtheria toxin A-chain coding sequence under the control of promoters and enhancers from immunoglobulin genes as a means of directing toxicity to B-lymphoid cells. Canc Res 51:4299-4304.
  51. Mineo R, Fichera E, Liang SJ, Fujita-Yamaguchi Y (2000) Promoter usage for insulin-like growth factor-II in cancerous and benign human breast, prostate, and bladder tissues, and confirmation of a 10th exon. Biochem Biophys Res Commun 268(3):886-892. https://doi.org/10.1006/bbrc.2000.2225
  52. Mitamura T, Umata T, Nakano F, Shishido Y, Toyoda T, Itai A, Kimura H, Mekada E (1997) Structure-function analysis of the diphtheria toxin receptor toxin binding site by site-directed mutagenesis. The Journal of Biological Chemistry 272:27084-27090. https://doi.org/10.1074/jbc.272.43.27084
  53. Mizrahi A, Czerniak A, Levy T, Amiur S, Gallula J, Matouk I, Abu-lail R, Sorin V, Birman T, de Groot N, Hochberg A, Ohana P (2009) Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences. Journal of Translational Medicine 7:69. https://doi.org/10.1186/1479-5876-7-69
  54. Mizrahi A, Czerniak A, Ohana P, Amiur S, Gallula J, Matouk I, Abu-Lail R, Birman T, Hochberg A, Levy T (2010) Treatment of ovarian cancer ascites by intraperitoneal injection of diphtheria toxin A chain-H19 vector: A case report. J Med Case Rep 4:228. https://doi.org/10.1186/1752-1947-4-228
  55. Morimoto H, Bonavida B (1992) Diphtheria toxin and Pseudomonas A toxin-mediated apoptosis. ADP ribosylation of elongation factor-2 is required for DNA fragmentation and cell lysis and synergy with tumor necrosis factor-alpha. J Immunol 149:2089-2094.
  56. Murayama Y, Tadakuma T, Kunitomi M, Kumai K, Tsutsui K, Yasuda T, Kitajima M (1999) Cell-specific expression of the diphtheria toxin A-chain coding sequence under the control of the upstream region of the human alphafetoprotein gene. J Surg Oncol 70:145-149. https://doi.org/10.1002/(SICI)1096-9098(199903)70:3<145::AID-JSO1>3.0.CO;2-O
  57. Ohana P, Bibi O, Matouk I, Levy C, Birman T, Ariel I, Schneider T, Ayesh S, Giladi H, Laster M, de Groot N, Hochberg A (2002) Use of H19 regulatory sequences for targeted gene therapy in cancer. Int J Cancer 98: 645-650. https://doi.org/10.1002/ijc.10243
  58. Pachnis V, Brannan CI, Tilghman SM (1988) The structure and expression of a novel gene activated in early mouse embryogenesis. EMBOJ 7:673-681.
  59. Pagter-Holthuizen P, Jansen M, Kammen RA, van Schaik FM, Sussenbach JS (1988) Differential expression of the human insulin-like growth factor II gene. Characterization of the IGF-II mRNAs and an mRNA encoding a putative IGF-II-associated protein. Biochim Biophys Acta 950:282-295. https://doi.org/10.1016/0167-4781(88)90124-8
  60. Pagter-Holthuizen P, Jansen M, van Schaik FM, van der Kammen R, Oosterwijk C, Van den Brande JL, Sussenbach JS (1987) The human insulin-like growth factor II gene contains two development-specific promoters. FEBS Lett 214:259-264. https://doi.org/10.1016/0014-5793(87)80066-2
  61. Paulus W, Baur I, Oberee DM, Breakefield XO, Reeves SA (1997) Regulated expression of the diphtheria toxin A gene in human glioma cells using prokaryotic transcriptional control elements. J Neurosurg 87:89-95. https://doi.org/10.3171/jns.1997.87.1.0089
  62. Pavelic K, Bukovic D, Pavelic J (2002) The role of insulinlike growth factor 2 and its receptors in human tumors. Mol Med 8:771-780.
  63. Peng W, Anderson DG, Bao Y, Padera RF Jr, Langer R, Sawicki JA (2007) Nano-particulate delivery of suicide DNA to murine prostate and prostate tumors. The Prostate 67:855-862. https://doi.org/10.1002/pros.20576
  64. Peng W, Chen J, Huang YH, Sawicki JA (2005) Tightlyregulated suicide gene expression kills PSA-expressing prostate tumor cells. Gene Therapy 12:1573-1580. https://doi.org/10.1038/sj.gt.3302580
  65. Peng W, Verbitsky A, Bao Y, Sawicki JA (2002) Regulated expression of diphtheria toxin in prostate cancer cells. Mol Ther 6:537-545. https://doi.org/10.1006/mthe.2002.0694
  66. Poirier F, Chan CT, Timmons PM, Robertson EJ, Evans MJ, Rigby PW (1991) The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo. Development (Cambridge, U.K.) 113(4):1105-1114.
  67. Rachmilewitz J, Goshen R, Ariel I, Schneider T, de Groot N, Hochberg A (1992) Parental imprinting of the human H19 gene. FEBS Lett 309:25-85. https://doi.org/10.1016/0014-5793(92)80731-U
  68. Robert J (2006) Immunotoxins for target cancer therapy. The AAPS Journal 8(3):Article 63.
  69. Robinson DF, Maxwell IH (1995) Suppression of single and double nonsense mutations introduced into the diphtheria toxin A-chain gene: a potential binary system for toxin gene therapy. Hum Gene Ther 6:137-143. https://doi.org/10.1089/hum.1995.6.2-137
  70. Rodriguez R, Lim HY, Bartkowski LM, Simons JW (1998) Identification of diphtheria toxin via screening as a potent cell cycle and p53-independent cytotoxin for human prostate cancer therapeutics. Prostate 34:259-269. https://doi.org/10.1002/(SICI)1097-0045(19980301)34:4<259::AID-PROS3>3.0.CO;2-C
  71. Rolf JM, Garidin HM, Eidels L (1990) Localization of the diphtheria toxin receptor-binding domain to the carboxylterminal $M_I{\approx}6000$ region of the toxin. J Biol Chem 265:7331-7337.
  72. Rosen DG, Wang L, Atkinson JN, Yu Y, Lu KH, Diamandis EP, Hellstrom I, Mok SC, Liu J, Bast RC Jr (2005) Potential markers that complement expression of CA125 in epithelial ovarian cancer. Gynecol Oncol 99:267-277. https://doi.org/10.1016/j.ygyno.2005.06.040
  73. Rothfels H, Paschen A, Schadendorf D (2003) Evaluation of combined gene regulatory elements for transcriptional targeting of suicide gene expression to malignant melanoma. Exp Dermatol 12:799-810. https://doi.org/10.1111/j.0906-6705.2003.00093.x
  74. Schenk-Braat EA, Bangma CH (2005) Immunotherapy for superficial bladder cancer. Cancer Immunol Immunother 54:414-423. https://doi.org/10.1007/s00262-004-0621-x
  75. Shapira A, Benhar I (2010) Toxin-based therapeutic approaches. Toxins 2:2519-2583. https://doi.org/10.3390/toxins2112519
  76. Shi CX, Hitt M, Ng P, Graham FL (2002) Superior tissuespecific expression from tyrosinase and prostate-specific antigen promoters/enhancers in helper-dependent compared with first-generation adenoviral vectors. Hum Gene Ther 13:211-224. https://doi.org/10.1089/10430340252769743
  77. Shirakawa T, Ko SC, Gardner TA, Cheon J, Miyamoto T, Gotoh A, Chung LW, Kao C (1998) In vitro suppression of osteosarcoma pulmonary mestatasis with intravenous osteocalcin promoter-based toxic gene therapy. Cancer Gene Ther 5:274-280.
  78. Showalter SL, Huang YH, Witkiewicz A, Costantino CL, Yeo CJ, Green JJ, Langer R, Anderson DG, Sawicki JA, Brody JR (2008) Nanoparticulate delivery of diphtheria toxin DNA effectively kills Mesothelin expressing pancreatic cancer cells. Canc Biol Ther 7:1584-1590. https://doi.org/10.4161/cbt.7.10.6562
  79. Siegel R, Ward E, Brawley O, Jemal A (2011) The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. Cancer J Clin 61:212-236. https://doi.org/10.3322/caac.20121
  80. Smaldone MC, Davies BJ (2010) BC-819, a plasmid comprising the H19 gene regulatory sequences and diphtheria toxin A, for the potential target therapy of cancers. Curr Opin Mol Ther 12(5):607-616.
  81. Smith TA, White BD, Gardner JM, Kaleko M, McClelland A (1996) Transient immunosuppression permits successful repetitive intravenous administration of an adenovirus vector. Gene Ther 3:496-502.
  82. Sohda T, Yun K, Iwata K, Soejima H, Okumura M (1996) Increased expression of insulin-like growth factor 2 in hepatocellular carcinoma is primarily regulated at the transcriptional level. Lab Invest 75:307-311.
  83. Strauss N, Hendee ED (1959) The effectof diphtheria toxin on the metabolism of HeLa cells. J Exp Medm 109: 144-163.
  84. Sutkowski DM, Goode RL, Baniel J, Teater C, Cohen P, McNulty AM, Hsiung HM, Becker GW, Neubauer DL (1999) Growth regulation of prostatic stromal cells by prostate-specific antigen. J Natl Cancer Inst 91:1663-1669. https://doi.org/10.1093/jnci/91.19.1663
  85. Thomas CE, Ehrhardt A, Kay AM (2004) Progress and problems with the use of viral vectors for gene therapy. Nature Reviews 4:346-358.
  86. Thorburm A, Thorburm J, Frankel AE (2004) Induction of apoptosis by tumor cell- targeted toxins. Apoptosis 9: 19-25. https://doi.org/10.1023/B:APPT.0000012118.95548.88
  87. Tsuneoka M, Nakayama K, Hatsuzawa K, Komada M, Kitamura N, Mekada E (1993) Evidence for involvement of furin in cleavage and activation of diphtheria toxin. J Biol Chem 268:26461-26465.
  88. Wang CY, Li F, Yang Y, Guo HY, Wu CX, Wang S (2006) Recombinant baculovirus containing the diphtheria toxin a gene for malignant glioma therapy. Cancer Res 66:5798-5806. https://doi.org/10.1158/0008-5472.CAN-05-4514
  89. Wilson BA, Blanke SR, Reich KA, Collier RJ (1994) Active-site mutations of diphtheria toxin. Tryptophan 50 is a major determinant of NAD affinity. J Biol Chem 269:23296-23301.
  90. Yamaizumi M, Mekada E, Uchida T, Okada Y (1978) One molecule of diphtheria toxin fragment a introduced into a cell can kill the cell. Cell 15:245-250. https://doi.org/10.1016/0092-8674(78)90099-5
  91. Ye X, Robinson MB, Pabin C, Batshaw ML, Wilson JM (2000) Transient depletion of CD4 lymphocyte improves efficacy of repeated administration of recombinant adenovirus in the ornithine transcarbamylase deficient sparse fur mouse. Gene Ther 7:1761-1767. https://doi.org/10.1038/sj.gt.3301299
  92. Zheng ZY, Chen D, Chan J, Yu D, Ko E, Pang S (2003) Regression of prostate cancer xenografts by a lentiviral vector specifically expressing diphtheria toxin A. Cancer Gene Therapy 10:764-770. https://doi.org/10.1038/sj.cgt.7700629