title: Combined therapy with cyclophosphamide and DNA preparation inhibits the tumor growth in mice.
abstract: BACKGROUND
  When cyclophosphamide and preparations of fragmented exogenous genomic double stranded DNA were administered in sequence, the regressive effect on the tumor was synergic: this combined treatment had a more pronounced effect than cyclophosphamide alone. Our further studies demonstrated that exogenous DNA stimulated the maturation and specific activities of dendritic cells. This suggests that cyclophosphamide, combined with DNA, leads to an immune response to the tumors that were grafted into the subjects post treatment.
  
  
  METHODS
  Three-month old CBA/Lac mice were used in the experiments. The mice were injected with cyclosphamide (200 mkg per 1 kg body weight) and genomic DNA (of human, mouse or salmon sperm origin). The DNA was administered intraperitoneally or subcutaneously. After 23 to 60 days, one million tumor cells were intramuscularly grafted into the mice. In the final experiment, the mice were pre-immunized by subcutaneous injections of 20 million repeatedly thawed and frozen tumor cells. Changes in tumor growth were determined by multiplying the three perpendicular diameters (measured by caliper). Students' t-tests were used to determine the difference between tumor growth and average survival rate between the mouse groups and the controls.
  
  
  RESULTS
  An analysis of varying treatments with cyclophosphamide and exogenous DNA, followed by tumor grafting, provided evidence that this combined treatment had an immunizing effect. This inhibitory effect in mice was analyzed in an experiment with the classical immunization of a tumor homogenate. The strongest inhibitory action on a transplanted graft was created through the following steps: cyclophosphamide at 200 mg/kg of body weight administered as a pretreatment; 6 mg fragmented exogenous DNA administered over the course of 3 days; tumor homogenate grafted 10 days following the final DNA injection.
  
  
  CONCLUSIONS
  Fragmented exogenous DNA injected with cyclophosphamide inhibits the growth of tumors that are grafted to mice after this combined treatment.
authors.affiliation: Novosibirsk State University, Novosibirsk, Russia. _just_smile@mail.ru
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Alyamkina
authors.forename: Evgenia V
authors.initials: EV
authors.lastname: Dolgova
authors.forename: Anastasia S
authors.initials: AS
authors.lastname: Likhacheva
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Rogachev
authors.forename: Tamara E
authors.initials: TE
authors.lastname: Sebeleva
authors.forename: Valeriy P
authors.initials: VP
authors.lastname: Nikolin
authors.forename: Nelly A
authors.initials: NA
authors.lastname: Popova
authors.forename: Konstantin E
authors.initials: KE
authors.lastname: Orishchenko
authors.forename: Dmitriy N
authors.initials: DN
authors.lastname: Strunkin
authors.forename: Elena R
authors.initials: ER
authors.lastname: Chernykh
authors.forename: Stanislav N
authors.initials: SN
authors.lastname: Zagrebelniy
authors.forename: Sergei S
authors.initials: SS
authors.lastname: Bogachev
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Shurdov
references.citation: Trends Immunol. 2006 Nov;27(11):525-32
references.pmid: 16979939
references.citation: Cancer Res. 2001 May 1;61(9):3689-97
references.pmid: 11325840
references.citation: J Dermatol Sci. 2005 Aug;39(2):105-12
references.pmid: 15899580
references.citation: Nat Med. 2004 Sep;10(9):942-9
references.pmid: 15322536
references.citation: Mol Cancer Ther. 2006 Jun;5(6):1585-92
references.pmid: 16818518
references.citation: Cancer Res. 2007 Sep 1;67(17):7941-4
references.pmid: 17804698
references.citation: J Immunol. 2006 Mar 1;176(5):2722-9
references.pmid: 16493027
references.citation: Cancer Immunol Immunother. 2008 Jan;57(1):123-31
references.pmid: 17522861
references.citation: Cancer Res. 2005 Jul 15;65(14):6388-93
references.pmid: 16024642
references.citation: J Clin Oncol. 2005 Dec 10;23(35):8950-8
references.pmid: 16061910
references.citation: Blood. 2005 Sep 15;106(6):2018-25
references.pmid: 15914560
references.citation: Nat Med. 2007 Jan;13(1):54-61
references.pmid: 17187072
references.citation: J Exp Med. 1982 Apr 1;155(4):1063-74
references.pmid: 6460831
references.citation: Clin Cancer Res. 2003 Aug 1;9(8):3105-14
references.pmid: 12912962
references.citation: J Clin Invest. 2007 May;117(5):1184-94
references.pmid: 17476348
references.citation: J Immunol. 2005 Mar 1;174(5):2457-65
references.pmid: 15728447
references.citation: Annu Rev Immunol. 2005;23:275-306
references.pmid: 15771572
references.citation: Biochemistry (Mosc). 2008 May;73(5):555-61
references.pmid: 18605980
references.citation: Gene Ther. 1999 May;6(5):893-903
references.pmid: 10505115
references.citation: Cancer Res. 2005 Sep 15;65(18):8059-64
references.pmid: 16166275
references.citation: J Immunother. 2006 Jul-Aug;29(4):367-80
references.pmid: 16799332
references.citation: Blood. 2005 Apr 1;105(7):2862-8
references.pmid: 15591121
references.citation: Clin Cancer Res. 2004 May 15;10(10):3401-9
references.pmid: 15161695
references.citation: J Exp Med. 2005 May 16;201(10):1591-602
references.pmid: 15883172
references.citation: Vopr Onkol. 2006;52(3):336-40
references.pmid: 17191708
references.citation: Nat Rev Cancer. 2005 May;5(5):397-405
references.pmid: 15864281
references.citation: Eur J Cancer. 1996 Sep;32A(10):1712-8
references.pmid: 8983279
references.citation: Nature. 1974 Jun 14;249(458):654-6
references.pmid: 4275846
references.citation: Cancer Res. 1988 Mar 15;48(6):1671-5
references.pmid: 2830969
references.citation: Nat Rev Immunol. 2006 Apr;6(4):295-307
references.pmid: 16557261
references.citation: World J Gastroenterol. 2005 Feb 28;11(8):1220-4
references.pmid: 15754409
references.citation: Nature. 2007 Oct 18;449(7164):819-26
references.pmid: 17943118
references.citation: Eur J Immunol. 2004 Feb;34(2):336-44
references.pmid: 14768038
references.citation: Nat Immunol. 2006 Feb;7(2):131-7
references.pmid: 16424890
references.citation: Oncol Rep. 2006 Jul;16(1):141-6
references.pmid: 16786137