• 1
    Maines MD. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 1988; 2: 255768.
  • 2
    Shibahara S. Regulation of heme oxygenase gene expression. Semin Hematol 1988; 25: 3706.
  • 3
    Baranano DE, Rao M, Ferris CD, Snyder SH. Biliverdin reductase: a major physiologic cytoprotectant. Proc Natl Acad Sci USA 2002; 99: 160938.
  • 4
    McCoubrey WK Jr, Huang TJ, Maines MD. Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem 1997; 247: 72532.
  • 5
    Motterlini R, Foresti R, Bassi R, Calabrese V, Clark JE, Green CJ. Endothelial heme oxygenase-1 induction by hypoxia. Modulation by inducible nitric oxide synthase and S-nitrosothiols. J Biol Chem 2000; 275: 1361320.
  • 6
    Mitani K, Fujita H, Fukuda Y, Kappas A, Sassa S. The role of inorganic metals and metalloporphyrins in the induction of haem oxygenase and heat-shock protein 70 in human hepatoma cells. Biochem J 1993; 290: 81925.
  • 7
    Keyse SM, Tyrrell RM. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenate. Proc Natl Acad Sci USA 1989; 86: 99103.
  • 8
    Hara E, Takahashi K, Takeda K, Nakayama M, Yoshizawa M, Fujita H, et al. Induction of heme oxygenase-1 as a response in sensing the signals evoked by distinct nitric oxide donors. Biochem Pharmacol 1999; 58: 22736.
  • 9
    Hartsfield SL, Alam J, Cook JL, Choi AMK. Regulation of heme oxygenase-1 gene expression in vascular smooth muscle cells by nitric oxide. Am J Physiol 1997; 273: L9808.
  • 10
    Jeney V, Balla J, Yachie A, Varga Z, Vercellotti GM, Eaton JW, Balla G. Pro-oxidant and cytotoxic effects of circulating heme. Blood 2002; 100: 87987.
  • 11
    Brouard S, Otterbein LE, Anrather J, Tobiasch E, Bach FH, Choi AMK, Soares MP. Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J Exp Med 2000; 192: 101526.
  • 12
    Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F, Eaton JW, Vercellotti GM. Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem 1992; 267: 1814853.
  • 13
    Lee TS, Chau LY. Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 2002; 8: 2406.
  • 14
    Sato K, Balla J, Otterbein L, Smith RN, Brouard S, Lin Y, Csizmadia E, Sevigny J, Robson SC, Vercellotti G, Choi AM, Bach FH, et al. Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants. J Immunol 2001; 166: 418596.
  • 15
    Wagner M, Cadetg P, Ruf R, Mazzucchelli L, Ferrari P, Redaelli CA. Heme oxygenase-1 attenuates ischemia/reperfusion-induced apoptosis and improves survival in rat renal allografts. Kidney Int 2003; 63: 156473.
  • 16
    Agarwal A, Balla J, Alam J, Croatt AJ, Nath KA. Induction of heme oxygenase in toxic renal injury: a protective role in cisplatin nephrotoxicity in the rat. Kidney Int 1995; 48: 1298307.
  • 17
    Tullius SG, Nieminen-Kelha M, Buelow R, Reutzel-Selke A, Martins PN, Pratschke J, Bachmann U, Lehmann M, Southard D, Iyer S, Schmidbauer G, Sawitzki B, et al. Inhibition of ischemia/reperfusion injury and chronic graft deterioration by a single-donor treatment with cobalt-protoporphyrin for the induction of heme oxygenase-1. Transplantation 2002; 74: 5918.
  • 18
    Doi K, Akaike T, Fujii S, Tanaka S, Ikebe N, Beppu T, Shibahara S, Ogawa M, Maeda H. Induction of haem oxygenase-1 by nitric oxide and ischaemia in experimental solid tumours and implications for tumour growth. Br J Cancer 1999; 80: 194554.
  • 19
    Doi K, Akaike T, Horie H, Noguchi Y, Fujii S, Beppu T, Ogawa M, Maeda H. Excessive production of nitric oxide in rat solid tumor and its implication in rapid tumor growth. Cancer 1996; 77: 1598604.
  • 20
    Wu J, Akaike T, Maeda H. Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger. Cancer Res 1998; 58: 15965.
  • 21
    Tanaka S, Akaike T, Fang J, Beppu T, Ogawa M, Tamura F, Miyamoto Y, Maeda H. Antiapoptotic effect of haem oxygenase-1 induced by nitric oxide in experimental solid tumour. Br J Cancer 2003; 88: 9029.
  • 22
    Sahoo SK, Sawa T, Fang J, Tanaka S, Miyamoto Y, Akaike T, Maeda H. Pegylated zinc protoporphyrin: a water-soluble heme oxygenase inhibitor with tumor-targeting capacity. Bioconjug Chem 2002; 13: 10318.
  • 23
    Fang J, Sawa T, Akaike T, Akuta T, Sahoo SK, Khaled G, Hamada A, Maeda H. In vivo antitumor activity of pegylated zinc protoporphyrin: targeted inhibition of heme oxygenase in solid tumor. Cancer Res 2003; 63: 356774.
  • 24
    Maines MD, Abrahamsson PA. Expression of heme oxygenase-1 (HSP32) in human prostate: normal, hyperplastic, and tumor tissue distribution. Urology 1996; 47: 72733.
  • 25
    Hara E, Takahashi K, Tominaga T, Kumabe T, Kayama T, Suzuki H, Fujita H, Yoshimoto T, Shirato K, Shibahara S. Expression of heme oxygenase and inducible nitric oxide synthase mRNA in human brain tumors. Biochem Biophys Res Commun 1996; 224: 1538.
  • 26
    Tsuji MH, Yanagawa T, Iwasa S, Tabuchi K, Onizawa K, Bannai S, Toyooka H, Yoshida H. Heme oxygenase-1 expression in oral squamous cell carcinoma as involved in lymph node metastasis. Cancer Lett 1999; 138: 539.
  • 27
    Goodman AI, Choudhury M, da Silva JL, Schwartzman ML, Abraham NG. Overexpression of the heme oxygenase gene in renal cell carcinoma. Proc Soc Exp Biol Med 1997; 214: 5461.
  • 28
    Lin F, Girotti AW. Hyperresistance of leukemia cells to photodynamic inactivation after long-term exposure to hemin. Cancer Res 1996; 56: 463643.
  • 29
    Konorev EA, Kotamraju S, Zhao H, Kalivendi S, Joseph J, Kalyanaraman B. Paradoxical effects of metalloporphyrins on doxorubicin-induced apoptosis: scavenging of reactive oxygen species versus induction of heme oxygenase-1. Free Radic Biol Med 2002; 33: 98897.
  • 30
    Fang J, Sawa T, Akaike T, Maeda H. Tumor-targeted delivery of PEG-conjugated D-amino acid oxidase for antitumor therapy via enzymatic generation of hydrogen peroxide. Cancer Res 2002; 62: 313843.
  • 31
    GreensteinJP eds. Biochemistry of cancer, 2nd ed. New York: Academic Press, 1954. 653p
  • 32
    Sato K, Ito K, Kohara H, Yamaguchi Y, Adachi K, Endo H. Negative regulation of catalase gene expression in hepatoma cells. Mol Cell Biol 1992; 12: 252533.
  • 33
    Hasegawa Y, Takano T, Miyauchi A, Matsuzuka F, Yoshida H, Kuma K, Amino N. Decreased expression of glutathione peroxidase mRNA in thyroid anaplastic carcinoma. Cancer Lett 2002; 182: 6974.
  • 34
    Yamanaka N, Deamer D. Superoxide dismutase activity in WI-38 cell cultures: effects of age, trypsinization and SV-40 transformation. Physiol Chem Phys Med NMR 1974; 6: 95106.
  • 35
    Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Methods 1983; 65: 5563.
  • 36
    Royall JA, Ischiropoulos H. Evaluation of 2′, 7′-dichlorofluorescin and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells. Arch Biochem Biophys 1993; 302: 34855.
  • 37
    Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C. 1995. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labeled annexin V. J Immunol Methods 1995; 184: 3951.
  • 38
    Hall R, Malia RG. Basic haematological practice. In: HallR, MaliaRG. Medical laboratory haematology, 2nd ed. Oxford, England: Butterworth-Heinemann Ltd., 1991: 914, 101–4.
  • 39
    Negoescu A, Lorimier P, Labat-Moleur F, Drouet C, Robert C, Guillermet C, Brambilla C, Brambilla E. In situ apoptotic cell labeling by the TUNEL method: improvement and evaluation on cell preparations. J Histochem Cytochem 1996; 44: 95968.
  • 40
    Aust SD, Morehouse LA, Thomas CE. Role of metals in oxygen radical reactions. J Free Radic Biol Med 1985; 1: 325.
  • 41
    Hildeman DA, Mitchell T, Kappler J, Marrack P. T cell apoptosis and reactive oxygen species. J Clin Invest 2003; 111: 57581.
  • 42
    Das UN. A radical approach to cancer. Med Sci Monit 2002; 8: RA7992.
  • 43
    Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol 1999; 57: 72741.
  • 44
    Hsiang YH, Lihou MG, Liu LF. Arrest of replication forks by drug-stabilized topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin. Cancer Res 1989; 49: 507782.
  • 45
    Simizu S, Takada M, Umezawa K, Imoto M. Requirement of caspase-3(-like) protease-mediated hydrogen peroxide production for apoptosis induced by various anticancer drugs. J Biol Chem 1998; 273: 269007.
  • 46
    Powis G. Free radical formation by antitumor quinones. Free Radic Biol Med 1989; 6: 63101.
  • 47
    Van Maanen JMS, Retel J, de Vries J, Pinedo HM. Mechanism of action of antitumor drug etoposide: a review. J Natl Cancer Inst 1988; 80: 152633.
  • 48
    Sato K, Akaike T, Suga M, Ando M, Maeda H. Generation of free radicals from neocarzinostatin mediated by NADPH/cytochrome P-450 reductase via activation of enediyne chromophore. Biochem Biophys Res Commun 1994; 205: 171623.
  • 49
    Djavaheri-Mergny M, Wietzerbin J, Besancon F. 2-Methoxyestradiol induces apoptosis in Ewing sarcoma cells through mitochondrial hydrogen peroxide production. Oncogene 2003; 22: 255867.
  • 50
    Suzuki S, Higuchi M, Proske RJ, Oridate N, Hong WK, Lotan R. Implication of mitochondria-derived reactive oxygen species, cytochrome c and caspase-3 in N-(4-hydroxyphenyl)retinamide-induced apoptosis in cervical carcinoma cells. Oncogene 1999; 18: 63807.
  • 51
    Sawa T, Wu J, Akaike T, Maeda H. Tumor-targeting chemotherapy by a xanthine oxidase-polymer conjugate that generates oxygen-free radicals in tumor tissue. Cancer Res 2000; 60: 66671.
  • 52
    Hellman S. Principles of radiation therapy. In: deVitaVTJr, HellmanS, RosenbergSA. Cancer: principles and practice of oncology, 2nd ed. Philadelphia (PA): Lippincott, 1985: 22755.
  • 53
    Poss KD, Tonegawa S. Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci USA 1997; 94: 1091924.
  • 54
    Matsumura Y, Maeda H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 1986; 46: 638792.
  • 55
    Maeda H. SMANCS and polymer-conjugated macromolecular drugs: advantages in cancer chemotherapy. Adv Drug Deliv Rev 2001; 46: 16985.
  • 56
    Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 2001; 41: 189207.
  • 57
    Maeda H, Sawa T, Konno T. Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J Control Release 2001; 74: 4761.
  • 58
    Fang J, Sawa T, Maeda H. Factors and mechanism of “EPR” effect and the enhanced antitumor effects of macromolecular drugs including SMANCS. Adv Exp Med Biol 2003; 519: 2949.
  • 59
    Muggia FM. Doxorubicin-polymer conjugates: further demonstration of the concept of enhanced permeability and retention. Clin Cancer Res 1999; 5: 78.
  • 60
    Duncan R. The dawning era of polymer therapeutics. Nat Rev Drug Discov 2003; 2: 34760.
  • 61
    Noguchi Y, Wu J, Duncan R, Strohalm J, Ulbrich K, Akaike T, et al. Early phase tumor accumulation of macromolecules: a great difference in clearance rate between tumor and normal tissues. Jpn J Cancer Res 1998; 89: 30714.
  • 62
    Seymour LW, Miyamoto Y, Maeda H, Brereton M, Stroalm J, Ulbrich K, Duncan R. Influence of molecular weight on passive tumour accumulation of a soluble macromolecular drug carrier. Eur J Cancer 1995; 31A: 76670.
  • 63
    Klotz T, Bloch W, Volberg C, Engelmann U, Addicks K. Selective expression of inducible nitric oxide synthease in human prostate carcinoma. Cancer 1998; 82: 1897903.
  • 64
    Ellie E, Loiseau H, Lafond F, Arsaut J, Demotes-Mainard J. Differential expression of inducible nitric oxide synthase mRNA in human brain tumours. Neuroreport 1995; 7: 2946.
  • 65
    Chen YK, Hsue SS, Lin LM. Increased expression of inducible nitric oxide synthase for human buccal squamous-cell carcinoma: immunohistochemical, reverse transcription-polymerase chain reaction (RT-PCR) and in situ RT-PCR studies. Head Neck 2002; 24: 92532.
  • 66
    Hofesth LJ, Hussain SP, Wogan GN, Harris CC. Nitric oxide in cancer and chemoprevention. Free Radic Biol Med 2003; 34: 95568.