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Diethylnorspermine

Polyamine analogue treatment results in growth inhibition and sometimes in cell death. Therefore, polyamine analogues are considered in the treatment of cancer.  see Anti-Cancer Drugs: 2008,19(19):871-883

Developer:    Genzyme (Orphan Drug), University of Florida (Originator), Genzyme (Not Determined), Johns Hopkins University (Not Determined), Pfizer (Licensee), SunPharm (Licensee).

 1: Tummala R, Diegelman P, Hector S, Kramer DL, Clark K, Zagst P, Fetterly G, Porter CW, Pendyala L. Combination effects of platinum drugs and N (1), N (11) diethylnorspermine on spermidine/spermine N (1)-acetyltransferase, polyamines and growth inhibition in A2780 human ovarian carcinoma cells and their oxaliplatin and cisplatin-resistant variants. Cancer Chemother Pharmacol. 2010 May 5. [Epub ahead of print] PubMed PMID: 20443003.

2: Marverti G, Ligabue A, Guerrieri D, Paglietti G, Piras S, Costi MP, Farina D, Frassineti C, Monti MG, Moruzzi MS. Spermidine/spermine N1-acetyltranferase modulation by novel folate cycle inhibitors in cisplatin-sensitive and -resistant human ovarian cancer cell lines. Gynecol Oncol. 2010 May;117(2):202-10. Epub 2010 Jan 19. PubMed PMID: 20031193.

3: Pirinen E, Gylling H, Itkonen P, Yaluri N, Heikkinen S, Pietilä M, Kuulasmaa T, Tusa M, Cerrada-Gimenez M, Pihlajamäki J, Alhonen L, Jänne J, Miettinen TA, Laakso M. Activated polyamine catabolism leads to low cholesterol levels by enhancing bile acid synthesis. Amino Acids. 2010 Feb;38(2):549-60. Epub 2009 Dec 3. PubMed PMID: 19956992.

4: Pledgie-Tracy A, Billam M, Hacker A, Sobolewski MD, Woster PM, Zhang Z, Casero RA, Davidson NE. The role of the polyamine catabolic enzymes SSAT and SMO in the synergistic effects of standard chemotherapeutic agents with a polyamine analogue in human breast cancer cell lines. Cancer Chemother Pharmacol. 2010 May;65(6):1067-81. Epub 2009 Aug 30. PubMed PMID: 19727732; PubMed Central PMCID: PMC2840063.

5: Uimari A, Keinänen TA, Karppinen A, Woster P, Uimari P, Jänne J, Alhonen L. Spermine analogue-regulated expression of spermidine/spermine N1-acetyltransferase and its effects on depletion of intracellular polyamine pools in mouse fetal fibroblasts. Biochem J. 2009 Jul 29;422(1):101-9. PubMed PMID: 19473115.

6: Myhre L, Alm K, Johansson M, Oredsson SM. Normal-like breast cells, but not breast cancer cells, recovered from treatment with N',N''-diethylnorspermine. Anticancer Drugs. 2009 Apr;20(4):230-7. PubMed PMID: 19288605.

7: Stanic' I, Facchini A, Borzì RM, Stefanelli C, Flamigni F. The polyamine analogue N1,N11-diethylnorspermine can induce chondrocyte apoptosis independently of its ability to alter metabolism and levels of natural polyamines. J Cell Physiol. 2009 Apr;219(1):109-16. PubMed PMID: 19097065.

8: Johansson VM, Miniotis MF, Hegardt C, Jönsson G, Staaf J, Berntsson PS, Oredsson SM, Alm K. Effect of polyamine deficiency on proteins involved in Okazaki fragment maturation. Cell Biol Int. 2008 Dec;32(12):1467-77. Epub 2008 Aug 22. PubMed PMID: 18786645.

9: Holst CM, Staaf J, Jönsson G, Hegardt C, Oredsson SM. Molecular mechanisms underlying N1, N11-diethylnorspermine-induced apoptosis in a human breast cancer cell line. Anticancer Drugs. 2008 Oct;19(9):871-83. PubMed PMID: 18766001.

10: Johansson VM, Oredsson SM, Alm K. Polyamine depletion with two different polyamine analogues causes DNA damage in human breast cancer cell lines. DNA Cell Biol. 2008 Sep;27(9):511-6. PubMed PMID: 18554080.

11: Myhre L, Alm K, Hegardt C, Staaf J, Jönsson G, Larsson S, Oredsson SM. Different cell cycle kinetic effects of N1,N11-diethylnorspermine-induced polyamine depletion in four human breast cancer cell lines. Anticancer Drugs. 2008 Apr;19(4):359-68. PubMed PMID: 18454046.

12: Stanic I, Cetrullo S, Facchini A, Stefanelli C, Borzì RM, Tantini B, Guarnieri C, Caldarera CM, Flamigni F. Effect of the polyamine analogue N1,N11-diethylnorspermine on cell survival and susceptibility to apoptosis of human chondrocytes. J Cell Physiol. 2008 Jul;216(1):153-61. PubMed PMID: 18231987.

13: Hector S, Tummala R, Kisiel ND, Diegelman P, Vujcic S, Clark K, Fakih M, Kramer DL, Porter CW, Pendyala L. Polyamine catabolism in colorectal cancer cells following treatment with oxaliplatin, 5-fluorouracil and N1, N11 diethylnorspermine. Cancer Chemother Pharmacol. 2008 Aug;62(3):517-27. Epub 2007 Nov 7. PubMed PMID: 17987291.

14: Jiang R, Choi W, Hu L, Gerner EW, Hamilton SR, Zhang W. Activation of polyamine catabolism by N1, N11-diethylnorspermine alters the cellular localization of mTOR and downregulates mTOR protein level in glioblastoma cells. Cancer Biol Ther. 2007 Oct;6(10):1644-8. Epub 2007 Jul 27. PubMed PMID: 17921698.

15: Holst CM, Johansson VM, Alm K, Oredsson SM. Novel anti-apoptotic effect of Bcl-2: prevention of polyamine depletion-induced cell death. Cell Biol Int. 2008 Jan;32(1):66-74. Epub 2007 Sep 1. PubMed PMID: 17920946.

16: Holst CM, Nevsten P, Johansson F, Carlemalm E, Oredsson SM. Subcellular distribution of spermidine/spermine N1-acetyltransferase. Cell Biol Int. 2008 Jan;32(1):39-47. Epub 2007 Sep 1. PubMed PMID: 17920945.

17: Beauchemin R, N'soukpoé-Kossi CN, Thomas TJ, Thomas T, Carpentier R, Tajmir-Riahi HA. Polyamine analogues bind human serum albumin. Biomacromolecules. 2007 Oct;8(10):3177-83. Epub 2007 Sep 22. PubMed PMID: 17887793; PubMed Central PMCID: PMC2548305.

18: Butcher NJ, Broadhurst GM, Minchin RF. Polyamine-dependent regulation of spermidine-spermine N1-acetyltransferase mRNA translation. J Biol Chem. 2007 Sep 28;282(39):28530-9. Epub 2007 Aug 9. PubMed PMID: 17690107.

19: Jiang R, Choi W, Khan A, Hess K, Gerner EW, Casero RA Jr, Yung WK, Hamilton SR, Zhang W. Activation of polyamine catabolism by N1,N11-diethylnorspermine leads to cell death in glioblastoma. Int J Oncol. 2007 Aug;31(2):431-40. PubMed PMID: 17611701.

20: Pirinen E, Kuulasmaa T, Pietilä M, Heikkinen S, Tusa M, Itkonen P, Boman S, Skommer J, Virkamäki A, Hohtola E, Kettunen M, Fatrai S, Kansanen E, Koota S, Niiranen K, Parkkinen J, Levonen AL, Ylä-Herttuala S, Hiltunen JK, Alhonen L, Smith U, Jänne J, Laakso M. Enhanced polyamine catabolism alters homeostatic control of white adipose tissue mass, energy expenditure, and glucose metabolism. Mol Cell Biol. 2007 Jul;27(13):4953-67. Epub 2007 May 7. PubMed PMID: 17485446; PubMed Central PMCID: PMC1951486.

21: Oredsson SM, Alm K, Dahlberg E, Holst CM, Johansson VM, Myhre L, Söderstjerna E. Inhibition of cell proliferation and induction of apoptosis by N(1),N(11)-diethylnorspermine-induced polyamine pool reduction. Biochem Soc Trans. 2007 Apr;35(Pt 2):405-9. PubMed PMID: 17371287.

22: Allen WL, McLean EG, Boyer J, McCulla A, Wilson PM, Coyle V, Longley DB, Casero RA Jr, Johnston PG. The role of spermidine/spermine N1-acetyltransferase in determining response to chemotherapeutic agents in colorectal cancer cells. Mol Cancer Ther. 2007 Jan;6(1):128-37. PubMed PMID: 17237273.

23: Nair SK, Verma A, Thomas TJ, Chou TC, Gallo MA, Shirahata A, Thomas T. Synergistic apoptosis of MCF-7 breast cancer cells by 2-methoxyestradiol and bis(ethyl)norspermine. Cancer Lett. 2007 Jun 8;250(2):311-22. Epub 2006 Dec 20. PubMed PMID: 17184909; PubMed Central PMCID: PMC1899838.

24: Niiranen K, Keinänen TA, Pirinen E, Heikkinen S, Tusa M, Fatrai S, Suppola S, Pietilä M, Uimari A, Laakso M, Alhonen L, Jänne J. Mice with targeted disruption of spermidine/spermine N1-acetyltransferase gene maintain nearly normal tissue polyamine homeostasis but show signs of insulin resistance upon aging. J Cell Mol Med. 2006 Oct-Dec;10(4):933-45. PubMed PMID: 17125596.

25: Choi W, Proctor L, Xia Q, Feng Y, Gerner EW, Chiao PJ, Hamilton SR, Zhang W. Inactivation of IkappaB contributes to transcriptional activation of spermidine/spermine N(1)-acetyltransferase. Mol Carcinog. 2006 Sep;45(9):685-93. PubMed PMID: 16637064.

26: Emanuele E, Martinelli V, Politi P. Potential usefulness of N1,N11-diethylnorspermine to prevent suicidal behaviour. Med Hypotheses. 2006;67(1):192. Epub 2006 Apr 3. PubMed PMID: 16580785.

27: Pledgie A, Huang Y, Hacker A, Zhang Z, Woster PM, Davidson NE, Casero RA Jr. Spermine oxidase SMO(PAOh1), Not N1-acetylpolyamine oxidase PAO, is the primary source of cytotoxic H2O2 in polyamine analogue-treated human breast cancer cell lines. J Biol Chem. 2005 Dec 2;280(48):39843-51. Epub 2005 Oct 5. PubMed PMID: 16207710.

28: Minchin RF, Knight S, Arulpragasam A, Fogel-Petrovic M. Concentration-dependent effects of N1, N11-diethylnorspermine on melanoma cell proliferation. Int J Cancer. 2006 Jan 15;118(2):509-12. PubMed PMID: 16052528.

29: Royo M, Fitzpatrick PF. Mechanistic studies of mouse polyamine oxidase with N1,N12-bisethylspermine as a substrate. Biochemistry. 2005 May 10;44(18):7079-84. PubMed PMID: 15865452; PubMed Central PMCID: PMC1635011.

30: Qutob SS, Proulx D, Mesak FM, Ng CE. Effects of N1, N13-diethylnorspermine (DENSPM) and X-radiation treatment on human colorectal tumor clones with varying X-radiation and drug responses. Radiat Res. 2005 Apr;163(4):357-63. PubMed PMID: 15799689.

31: Holst CM, Oredsson SM. Comparison of three cytotoxicity tests in the evaluation of the cytotoxicity of a spermine analogue on human breast cancer cell lines. Toxicol In Vitro. 2005 Apr;19(3):379-87. Epub 2004 Dec 24. PubMed PMID: 15713545.

32: Balabhadrapathruni S, Santhakumaran LM, Thomas TJ, Shirahata A, Gallo MA, Thomas T. Bis(ethyl)norspermine potentiates the apoptotic activity of the pure antiestrogen ICI 182780 in breast cancer cells. Oncol Rep. 2005 Jan;13(1):101-8. PubMed PMID: 15583809.

33: Choi W, Gerner EW, Ramdas L, Dupart J, Carew J, Proctor L, Huang P, Zhang W, Hamilton SR. Combination of 5-fluorouracil and N1,N11-diethylnorspermine markedly activates spermidine/spermine N1-acetyltransferase expression, depletes polyamines, and synergistically induces apoptosis in colon carcinoma cells. J Biol Chem. 2005 Feb 4;280(5):3295-304. Epub 2004 Nov 16. PubMed PMID: 15546879.

34: Hector S, Porter CW, Kramer DL, Clark K, Prey J, Kisiel N, Diegelman P, Chen Y, Pendyala L. Polyamine catabolism in platinum drug action: Interactions between oxaliplatin and the polyamine analogue N1,N11-diethylnorspermine at the level of spermidine/spermine N1-acetyltransferase. Mol Cancer Ther. 2004 Jul;3(7):813-22. PubMed PMID: 15252142.

35: Gabrielson E, Tully E, Hacker A, Pegg AE, Davidson NE, Casero RA Jr. Induction of spermidine/spermine N1-acetyltransferase in breast cancer tissues treated with the polyamine analogue N1, N11-diethylnorspermine. Cancer Chemother Pharmacol. 2004 Aug;54(2):122-6. Epub 2004 May 8. PubMed PMID: 15138709.

36: Wolff AC, Armstrong DK, Fetting JH, Carducci MK, Riley CD, Bender JF, Casero RA Jr, Davidson NE. A Phase II study of the polyamine analog N1,N11-diethylnorspermine (DENSpm) daily for five days every 21 days in patients with previously treated metastatic breast cancer. Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):5922-8. PubMed PMID: 14676116.

37: Chen Y, Kramer DL, Jell J, Vujcic S, Porter CW. Small interfering RNA suppression of polyamine analog-induced spermidine/spermine n1-acetyltransferase. Mol Pharmacol. 2003 Nov;64(5):1153-9. PubMed PMID: 14573765.

38: Chen Y, Kramer DL, Li F, Porter CW. Loss of inhibitor of apoptosis proteins as a determinant of polyamine analog-induced apoptosis in human melanoma cells. Oncogene. 2003 Aug 7;22(32):4964-72. PubMed PMID: 12902979.

39: Bayes M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2003 Jun;25(5):387-408. PubMed PMID: 12851663.

40: Chen Y, Alm K, Vujcic S, Kramer DL, Kee K, Diegelman P, Porter CW. The role of mitogen-activated protein kinase activation in determining cellular outcomes in polyamine analogue-treated human melanoma cells. Cancer Res. 2003 Jul 1;63(13):3619-25. PubMed PMID: 12839950.

41: McCloskey DE, Pegg AE. Properties of the spermidine/spermine N1-acetyltransferase mutant L156F that decreases cellular sensitivity to the polyamine analogue N1, N11-bis(ethyl)norspermine. J Biol Chem. 2003 Apr 18;278(16):13881-7. Epub 2003 Feb 10. PubMed PMID: 12578836.

42: Niiranen K, Pietilä M, Pirttilä TJ, Järvinen A, Halmekytö M, Korhonen VP, Keinänen TA, Alhonen L, Jänne J. Targeted disruption of spermidine/spermine N1-acetyltransferase gene in mouse embryonic stem cells. Effects on polyamine homeostasis and sensitivity to polyamine analogues. J Biol Chem. 2002 Jul 12;277(28):25323-8. Epub 2002 May 8. PubMed PMID: 12000764.

43: Hahm HA, Ettinger DS, Bowling K, Hoker B, Chen TL, Zabelina Y, Casero RA Jr. Phase I study of N(1),N(11)-diethylnorspermine in patients with non-small cell lung cancer. Clin Cancer Res. 2002 Mar;8(3):684-90. PubMed PMID: 11895896.

44: Hegardt C, Johannsson OT, Oredsson SM. Rapid caspase-dependent cell death in cultured human breast cancer cells induced by the polyamine analogue N(1),N(11)-diethylnorspermine. Eur J Biochem. 2002 Feb;269(3):1033-9. PubMed PMID: 11846806.

45: Alhonen L, Räsänen TL, Sinervirta R, Parkkinen JJ, Korhonen VP, Pietilä M, Jänne J. Polyamines are required for the initiation of rat liver regeneration. Biochem J. 2002 Feb 15;362(Pt 1):149-53. PubMed PMID: 11829751; PubMed Central PMCID: PMC1222371.

46: Bergeron RJ, Wiegand J, Fannin TL. Control of irritable bowel syndrome with polyamine analogs: a structure-activity study. Dig Dis Sci. 2001 Dec;46(12):2615-23. PubMed PMID: 11768250.

47: Chen Y, Kramer DL, Diegelman P, Vujcic S, Porter CW. Apoptotic signaling in polyamine analogue-treated SK-MEL-28 human melanoma cells. Cancer Res. 2001 Sep 1;61(17):6437-44. PubMed PMID: 11522638.

48: Suppola S, Heikkinen S, Parkkinen JJ, Uusi-Oukari M, Korhonen VP, Keinänen T, Alhonen L, Jänne J. Concurrent overexpression of ornithine decarboxylase and spermidine/spermine N(1)-acetyltransferase further accelerates the catabolism of hepatic polyamines in transgenic mice. Biochem J. 2001 Sep 1;358(Pt 2):343-8. PubMed PMID: 11513732; PubMed Central PMCID: PMC1222066.

49: Bergeron RJ, Müller R, Huang G, McManis JS, Algee SE, Yao H, Weimar WR, Wiegand J. Synthesis and evaluation of hydroxylated polyamine analogues as antiproliferatives. J Med Chem. 2001 Jul 19;44(15):2451-9. PubMed PMID: 11448227.

50: Streiff RR, Bender JF. Phase 1 study of N1-N11-diethylnorspermine (DENSPM) administered TID for 6 days in patients with advanced malignancies. Invest New Drugs. 2001;19(1):29-39. PubMed PMID: 11291831.

51: Korhonen VP, Niiranen K, Halmekytö M, Pietilä M, Diegelman P, Parkkinen JJ, Eloranta T, Porter CW, Alhonen L, Jänne J. Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. Mol Pharmacol. 2001 Feb;59(2):231-8. PubMed PMID: 11160858.

52: Vujcic S, Halmekyto M, Diegelman P, Gan G, Kramer DL, Janne J, Porter CW. Effects of conditional overexpression of spermidine/spermine N1-acetyltransferase on polyamine pool dynamics, cell growth, and sensitivity to polyamine analogs. J Biol Chem. 2000 Dec 8;275(49):38319-28. PubMed PMID: 10978316.

53: Bergeron RJ, Merriman RL, Olson SG, Wiegand J, Bender J, Streiff RR, Weimar WR. Metabolism and pharmacokinetics of N1,N11-diethylnorspermine in a Cebus apella primate model. Cancer Res. 2000 Aug 15;60(16):4433-9. PubMed PMID: 10969789.

54: Schipper RG, Deli G, Deloyer P, Lange WP, Schalken JA, Verhofstad AA. Antitumor activity of the polyamine analog N(1), N(11)-diethylnorspermine against human prostate carcinoma cells. Prostate. 2000 Sep 1;44(4):313-21. PubMed PMID: 10951496.

55: McCloskey DE, Pegg AE. Altered spermidine/spermine N1-acetyltransferase activity as a mechanism of cellular resistance to bis(ethyl)polyamine analogues. J Biol Chem. 2000 Sep 15;275(37):28708-14. PubMed PMID: 10887189.

56: Alhonen L, Parkkinen JJ, Keinanen T, Sinervirta R, Herzig KH, Jänne J. Activation of polyamine catabolism in transgenic rats induces acute pancreatitis. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8290-5. PubMed PMID: 10880565; PubMed Central PMCID: PMC26940.

57: Alm K, Berntsson PS, Kramer DL, Porter CW, Oredsson SM. Treatment of cells with the polyamine analog N, N11-diethylnorspermine retards S phase progression within one cell cycle. Eur J Biochem. 2000 Jul;267(13):4157-64. PubMed PMID: 10866819.

58: Davidson NE, Hahm HA, McCloskey DE, Woster PM, Casero RA Jr. Clinical aspects of cell death in breast cancer: the polyamine pathway as a new target for treatment. Endocr Relat Cancer. 1999 Mar;6(1):69-73. Review. PubMed PMID: 10732790.

59: Shah N, Antony T, Haddad S, Amenta P, Shirahata A, Thomas TJ, Thomas T. Antitumor effects of bis(ethyl)polyamine analogs on mammary tumor development in FVB/NTgN (MMTVneu) transgenic mice. Cancer Lett. 1999 Nov 1;146(1):15-23. PubMed PMID: 10656605.

60: McCloskey DE, Woster PM, Casero RA Jr, Davidson NE. Effects of the polyamine analogues N1-ethyl-N11-((cyclopropyl)methyl)-4,8-diazaundecane and N1-ethylN-11-((cycloheptyl)methyl)-4,8-diazaundecane in human prostate cancer cells. Clin Cancer Res. 2000 Jan;6(1):17-23. PubMed PMID: 10656427.

61: Bergeron RJ, Müller R, Bussenius J, McManis JS, Merriman RL, Smith RE, Yao H, Weimar WR. Synthesis and evaluation of hydroxylated polyamine analogues as antiproliferatives. J Med Chem. 2000 Jan 27;43(2):224-35. PubMed PMID: 10649978.

62: Antony T, Thomas T, Shirahata A, Thomas TJ. Selectivity of polyamines on the stability of RNA-DNA hybrids containing phosphodiester and phosphorothioate oligodeoxyribonucleotides. Biochemistry. 1999 Aug 17;38(33):10775-84. PubMed PMID: 10451373.

63: Rojiani AM, Williams LS, Valenstein EJ. Chemotherapy for pancreatic cancer: a neuroimaging clinicopathologic correlation. J Neuroimaging. 1999 Jul;9(3):165-70. PubMed PMID: 10436759.

64: Gabrielson EW, Pegg AE, Casero RA Jr. The induction of spermidine/spermine N1-acetyltransferase (SSAT) is a common event in the response of human primary non-small cell lung carcinomas to exposure to the new antitumor polyamine analogue N1,N11-bis(ethyl)norspermine. Clin Cancer Res. 1999 Jul;5(7):1638-41. PubMed PMID: 10430062.

65: Giuseppina Monti M, Ghiaroni S, Barbieri D, Franceschi C, Marverti G, Moruzzi MS. 2-deoxy-d-ribose-induced apoptosis in HL-60 cells is associated with the cell cycle progression by spermidine. Biochem Biophys Res Commun. 1999 Apr 13;257(2):460-5. PubMed PMID: 10198235.

66: Alhonen L, Pietilä M, Halmekytö M, Kramer DL, Jänne J, Porter CW. Transgenic mice with activated polyamine catabolism due to overexpression of spermidine/spermine N1-acetyltransferase show enhanced sensitivity to the polyamine analog, N1, N11-diethylnorspermine. Mol Pharmacol. 1999 Apr;55(4):693-8. PubMed PMID: 10101027.

67: Kramer DL, Vujcic S, Diegelman P, Alderfer J, Miller JT, Black JD, Bergeron RJ, Porter CW. Polyamine analogue induction of the p53-p21WAF1/CIP1-Rb pathway and G1 arrest in human melanoma cells. Cancer Res. 1999 Mar 15;59(6):1278-86. PubMed PMID: 10096560.

68: Basu HS, Dreckschmidt N, Tu L, Chanbusarakum L. Polyamine analog bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) enhances simian virus 40 late gene expression. Cancer Chemother Pharmacol. 1999;43(4):336-40. PubMed PMID: 10071986.

69: Kramer DL, Vujcic S, Diegelman P, White C, Black JD, Porter CW. Polyamine analogue-mediated cell cycle responses in human melanoma cells involves the p53, p21, Rb regulatory pathway. Biochem Soc Trans. 1998 Nov;26(4):609-14. Review. PubMed PMID: 10047792.

70: Suppola S, Pietilä M, Parkkinen JJ, Korhonen VP, Alhonen L, Halmekytö M, Porter CW, Jänne J. Overexpression of spermidine/spermine N1-acetyltransferase under the control of mouse metallothionein I promoter in transgenic mice: evidence for a striking post-transcriptional regulation of transgene expression by a polyamine analogue. Biochem J. 1999 Mar 1;338 ( Pt 2):311-6. PubMed PMID: 10024505; PubMed Central PMCID: PMC1220055.

71: Bergeron RJ, Weimar WR, Müller R, Zimmerman CO, McCosar BH, Yao H, Smith RE. Effect of polyamine analogues on hypusine content in JURKAT T-cells. J Med Chem. 1998 Sep 24;41(20):3901-8. PubMed PMID: 9748365.

72: Kramer DL, Black JD, Mett H, Bergeron RJ, Porter CW. Lysosomal sequestration of polyamine analogues in Chinese hamster ovary cells resistant to the S-adenosylmethionine decarboxylase inhibitor, CGP-48664. Cancer Res. 1998 Sep 1;58(17):3883-90. PubMed PMID: 9731498.

73: Marverti G, Piccinini G, Ghiaroni S, Barbieri D, Quaglino D, Moruzzi MS. N1,N12-bis(ethyl)spermine effect on growth of cis-diamminedichloroplatinum(II)-sensitive and -resistant human ovarian-carcinoma cell lines. Int J Cancer. 1998 Sep 25;78(1):33-40. PubMed PMID: 9724091.

74: Penning LC, Schipper RG, Vercammen D, Verhofstad AA, Denecker T, Beyaert R, Vandenabeele P. Sensitization of tnf-induced apoptosis with polyamine synthesis inhibitors in different human and murine tumour cell lines. Cytokine. 1998 Jun;10(6):423-31. PubMed PMID: 9632528.

75: Zagaja GP, Shrivastav M, Fleig MJ, Marton LJ, Rinker-Schaeffer CW, Dolan ME. Effects of polyamine analogues on prostatic adenocarcinoma cells in vitro and in vivo. Cancer Chemother Pharmacol. 1998;41(6):505-12. PubMed PMID: 9554596.

76: Ha HC, Yager JD, Woster PA, Casero RA Jr. Structural specificity of polyamines and polyamine analogues in the protection of DNA from strand breaks induced by reactive oxygen species. Biochem Biophys Res Commun. 1998 Mar 6;244(1):298-303. PubMed PMID: 9514920.

77: Felschow DM, Mi Z, Stanek J, Frei J, Porter CW. Selective labelling of cell-surface polyamine-binding proteins on leukaemic and solid-tumour cell types using a new polyamine photoprobe. Biochem J. 1997 Dec 15;328 ( Pt 3):889-95. PubMed PMID: 9396735; PubMed Central PMCID: PMC1219001.

78: Alhonen L, Karppinen A, Uusi-Oukari M, Vujcic S, Korhonen VP, Halmekytö M, Kramer DL, Hines R, Jänne J, Porter CW. Correlation of polyamine and growth responses to N1,N11-diethylnorspermine in primary fetal fibroblasts derived from transgenic mice overexpressing spermidine/spermine N1-acetyltransferase. J Biol Chem. 1998 Jan 23;273(4):1964-9. PubMed PMID: 9442032.

79: Mi Z, Kramer DL, Miller JT, Bergeron RJ, Bernacki R, Porter CW. Human prostatic carcinoma cell lines display altered regulation of polyamine transport in response to polyamine analogs and inhibitors. Prostate. 1998 Jan 1;34(1):51-60. PubMed PMID: 9428388.

80: Kramer DL, Fogel-Petrovic M, Diegelman P, Cooley JM, Bernacki RJ, McManis JS, Bergeron RJ, Porter CW. Effects of novel spermine analogues on cell cycle progression and apoptosis in MALME-3M human melanoma cells. Cancer Res. 1997 Dec 15;57(24):5521-7. PubMed PMID: 9407962.

81: Dorhout B, Kingma AW, de Hoog E, Muskiet FA. Simultaneous determination of polyamines, N-acetylated polyamines and the polyamine analogues BE-3-3-3 and BE-4-4-4-4 by capillary gas chromatography with nitrogen-phosphorus detection. J Chromatogr B Biomed Sci Appl. 1997 Oct 24;700(1-2):23-30. PubMed PMID: 9390711.

82: Keithly JS, Zhu G, Upton SJ, Woods KM, Martinez MP, Yarlett N. Polyamine biosynthesis in Cryptosporidium parvum and its implications for chemotherapy. Mol Biochem Parasitol. 1997 Sep;88(1-2):35-42. PubMed PMID: 9274865.

83: Sharma A, Glaves D, Porter CW, Raghavan D, Bernacki RJ. Antitumor efficacy of N1,N11-diethylnorspermine on a human bladder tumor xenograft in nude athymic mice. Clin Cancer Res. 1997 Aug;3(8):1239-44. PubMed PMID: 9815805.

84: Fogel-Petrovic M, Kramer DL, Vujcic S, Miller J, McManis JS, Bergeron RJ, Porter CW. Structural basis for differential induction of spermidine/spermine N1-acetyltransferase activity by novel spermine analogs. Mol Pharmacol. 1997 Jul;52(1):69-74. PubMed PMID: 9224814.

85: Basu HS, Smirnov IV, Peng HF, Tiffany K, Jackson V. Effects of spermine and its cytotoxic analogs on nucleosome formation on topologically stressed DNA in vitro. Eur J Biochem. 1997 Jan 15;243(1-2):247-58. PubMed PMID: 9030746.

86: Creaven PJ, Perez R, Pendyala L, Meropol NJ, Loewen G, Levine E, Berghorn E, Raghavan D. Unusual central nervous system toxicity in a phase I study of N1N11 diethylnorspermine in patients with advanced malignancy. Invest New Drugs. 1997;15(3):227-34. PubMed PMID: 9387045.

87: Jeffers L, Church D, Basu H, Marton L, Wilding G. Effects of the polyamine analogues BE-4-4-4-4, BE-3-7-3, and BE-3-3-3 on the proliferation of three prostate cancer cell lines. Cancer Chemother Pharmacol. 1997;40(2):172-9. PubMed PMID: 9182840.

88: Bergeron RJ, Weimar WR, Wu Q, Feng Y, McManis JS. Polyamine analogue regulation of NMDA MK-801 binding: a structure-activity study. J Med Chem. 1996 Dec 20;39(26):5257-66. PubMed PMID: 8978854.

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