• 1
    Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med 1998; 339: 9005.
  • 2
    Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004; 56: 185229.
  • 3
    Ewer MS, Benjamin RS, Yeh JT. Cardiac complications. In: KufeD, BastR, HaitW, HongW, PollackR, WeichselbaumR, HollandJ, FreiE, eds. Cancer medicine, 7th edn. Hamilton, Ontario: Decker, 2005. 252541.
  • 4
    Kratz F, Warnecke A, Scheuermann K, Stockmar C, Schwab J, Lazar P, Druckes P, Esser N, Drevs J, Rognan D, Bissantz C, Hinderling C, et al. Probing the cysteine-34 position of endogenous serum albumin with thiol-binding doxorubicin derivatives. Improved efficacy of an acid-sensitive doxorubicin derivative with specific albumin-binding properties compared to that of the parent compound. J Med Chem 2002; 45: 552333.
  • 5
    Kratz F, Warnecke A, Schmid B, Chung DE, Gitzel M. Prodrugs of anthracyclines in cancer chemotherapy. Curr Med Chem 2006; 13: 477523.
  • 6
    Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 2000; 65: 27184.
  • 7
    Kratz F, Kauffmann HM, Ehling G, Unger C. Acute and repeat-dose toxicity studies of the (6-maleimidocaproyl) hydrazone derivative of doxorubicin (DOXO-EMCH), an albumin-binding prodrug of the anticancer agent doxorubicin. Hum Exp Toxicol, in press.
  • 8
    Unger C, Medinger M, Steinbild S, Drevs J, Häring B. Phase I dose-escalation and pharmacokinetic (PK) study of a (6-maleimidocaproyl) hydrazone derivative of doxorubicin (DOXO-EMCH) in patients with advanced cancers. Paper presented at the German Cancer Congress, Berlin, 2006.
  • 9
    Lebrecht D, Setzer B, Ketelsen UP, Haberstroh J, Walker UA. Time-dependent and tissue-specific accumulation of mtDNA and respiratory chain defects in chronic doxorubicin cardiomyopathy. Circulation 2003; 108: 24239.
  • 10
    Lebrecht D, Kokkori A, Ketelsen UP, Setzer B, Walker UA. Tissue-specific mtDNA lesions and radical-associated mitochondrial dysfunction in human hearts exposed to doxorubicin. J Pathol 2005; 207: 43644.
  • 11
    NIH office of laboratory animal welfare. Public health service policy on humane care and use of laboratory animals. Available at 2002.
  • 12
    Della Torre P, Podesta A, Pinciroli G, Iatropoulos MJ, Mazue G. Long-lasting effect of dexrazoxane against anthracycline cardiotoxicity in rats. Toxicol Pathol 1996; 24: 398402.
  • 13
    Silvestri G, Santorelli FM, Shanske S, Whitley CB, Schimmenti LA, Smith SA, DiMauro S. A new mtDNA mutation in the tRNA (Leu(UUR)) gene associated with maternally inherited cardiomyopathy. Hum Mutat 1994; 3: 3743.
  • 14
    Capaldi RA, Marusich MF, Taanman JW. Mammalian cytochrome-c oxidase: characterization of enzyme and immunological detection of subunits in tissue extracts and whole cells. Methods Enzymol 1995; 260: 11732.
  • 15
    Walker UA, Setzer B, Venhoff N. Increased long-term mitochondrial toxicity in combinations of nucleoside analogue reverse-transcriptase inhibitors. AIDS 2002; 16: 216573.
  • 16
    Hammond EL, Sayer D, Nolan D, Walker UA, Ronde A, Montaner JS, Cote HC, Gahan ME, Cherry CL, Wesselingh SL, Reiss P, Mallal S. Assessment of precision and concordance of quantitative mitochondrial DNA assays: a collaborative international quality assurance study. J Clin Virol 2003; 27: 97110.
  • 17
    Schon EA, Rizzuto R, Moraes CT, Nakase H, Zeviani M, DiMauro S. A direct repeat is a hotspot for large-scale deletion of human mitochondrial DNA. Science 1989; 244: 3469.
  • 18
    Tuzgen S, Kaynar MY, Guner A, Gumustas K, Belce A, Etus V, Ozyurt E. The effect of epidural cooling on lipid peroxidation after experimental spinal cord injury. Spinal Cord 1998; 36: 6547.
  • 19
    Miller FJ,Jr, Gutterman DD, Rios CD, Heistad DD, Davidson BL. Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis. Circ Res 1998; 82: 1298305.
  • 20
    Lebrecht D, Setzer B, Rohrbach R, Walker UA. Mitochondrial DNA and its respiratory chain products are defective in doxorubicin nephrosis. Nephrol Dial Transplant 2004; 19: 32936.
  • 21
    Mansour AM, Drevs J, Esser N, Hamada FM, Badary OA, Unger C, Fichtner I, Kratz F. A new approach for the treatment of malignant melanoma: enhanced antitumor efficacy of an albumin-binding doxorubicin prodrug that is cleaved by matrix metalloproteinase 2. Cancer Res 2003; 63: 40626.
  • 22
    Warnecke A Kratz F. Maleimide-oligo(ethylene glycol) derivatives of camptothecin as albumin-binding prodrugs: synthesis and antitumor efficacy. Bioconjug Chem 2003; 14: 37787.
  • 23
    Cullinane C, Cutts SM, Panousis C, Phillips DR. Interstrand cross-linking by adriamycin in nuclear and mitochondrial DNA of MCF-7 cells. Nucleic Acids Res 2000; 28: 101925.
  • 24
    Keizer HG, Pinedo HM, Schuurhuis GJ, Joenje H. Doxorubicin (adriamycin): a critical review of free radical-dependent mechanisms of cytotoxicity. Pharmacol Ther 1990; 47: 21931.
  • 25
    Tewey KM, Rowe TC, Yang L, Halligan BD, Liu LF. Adriamycin induced DNA damage mediated by mammalian DNA topoisomerase II. Science 1984; 226: 4668.
  • 26
    Wiseman A, Attardi G. Reversible tenfold reduction in mitochondria DNA content of human cells treated with ethidium bromide. Mol Gen Genet 1978; 167: 5163.
  • 27
    Hopewel JW, Duncan R, Wilding D, Chakrabarti K. Preclinical evaluation of the cardiotoxicity of PK2: a novel HPMA copolymer-doxorubicin-galactosamine conjugate antitumour agent. Hum Exp Toxicol 2001; 20: 46170.
  • 28
    O'Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol 2004; 15: 4409.
  • 29
    Working PK, Newman MS, Sullivan T, Yarrington J. Reduction of the cardiotoxicity of doxorubicin in rabbits and dogs by encapsulation in long-circulating, pegylated liposomes. J Pharmacol Exp Ther 1999; 289: 112833.
  • 30
    Zeviani M, Gellera C, Antozzi C, Rimoldi M, Moramdi L, Villani F, Tiranti V, DiDonato S. Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNA leu (UUR). Lancet 1991; 338: 1437.
  • 31
    Cummings J, Willmott N, More I, Kerr DJ, Morrison JG, Kaye SB. Comparative cardiotoxicity and antitumour activity of doxorubicin (adriamycin) and 4′-deoxydoxorubicin and the relationship to in vivo disposition and metabolism in the target tissues. Biochem Pharmacol 1987; 36: 15216.
  • 32
    Childs AC, Phaneuf SL, Dirks AJ, Phillips T, Leeuwenburgh C. Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2:Bax ratio. Cancer Res 2002; 62: 45928.
  • 33
    Grandjean F, Bremaud L, Robert J, Ratinaud MH. Alterations in the expression of cytochrome c oxidase subunits in doxorubicin-resistant leukemia K562 cells. Biochem Pharmacol 2002; 63: 82331.