• 1
    Maeda H, Konno T. Metamorphosis of neocarzinostatin to SMANCS: chemistry, pharmacology and clinical effect of the first prototype anticancer polymer therapeutic. In: Maeda H, Edo K, Ishida N, eds. Neocarzinostatin: The Past, Present, and Future of an Anticancer Drug. Tokyo: Springer-Verlag, 1997; 22767.
  • 2
    Maeda H, Takeshita J, Kanamaru R. A lipophilic derivative of neocarzinostatin. A polymer conjugation of an antitumor protein antibiotic. Int J Pept Protein Res 1979; 14: 817.
  • 3
    Maeda H, Ueda M, Morinaga T, Matsumoto T. Conjugation of poly (styrene-co-maleic acid) derivatives to the antitumor protein neocarzinostatin: pronounced improvements in pharmacological properties. J Med Chem 1985; 28: 45561.
  • 4
    Maeda H, Takeshita J, Kanamaru R, Sato H, Khatoh J, Sato H. Antimetastatic and antitumor activity of a derivative of neocarzinostatin: an organic solvent- and water-soluble polymer-conjugated protein. Gann 1979; 70: 6016.
  • 5
    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.
  • 6
    Maeda H, Matsumura Y. Tumoritropic and lymphotropic principles of macromolecular drugs. Crit Rev Ther Drug Carrier Syst 1989; 6: 193210.
  • 7
    Takeshita J, Maeda H, Kanamaru R. In vitro mode of action, pharmacokinetics, and organ specificity of poly(maleic acid-styrene)-conjugated neocarzinostatin, SMANCS. Gann 1982; 73: 27884.
  • 8
    Maeda H, Matsumoto T, Konno T, Iwai K, Ueda M. Tailor-making of protein drugs by polymer conjugation for tumor targeting: a brief review on Smancs. J Protein Chem 1984; 3: 18193.
  • 9
    Kobayashi A, Oda T, Maeda H. Protein binding of macromolecular anticancer agent SMANCS: characterization of poly(styrene-co-maleic acid) derivatives as an albumin binding ligand. J Bioact Compat Polym 1988; 3: 31933.
  • 10
    Oka K, Miyamoto Y, Matsumura Y et al. Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation. Pharmaceut Res 1990; 7: 85255.
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    Miyamoto Y, Oda T, Maeda H. Comparison of the cytotoxic effects of the high- and low-molecular-weight anticancer agents on multidrug-resistant Chinese hamster ovary cells in vitro. Cancer Res 1990; 50: 157175.
  • 12
    Noguchi Y, Wu J, Duncan R 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.
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    Seymour LW, Miyamoto Y, Maeda H et al. Influence of molecular weight on passive tumour accumulation of a soluble macromolecular drug carrier. Eur J Cancer 1995; 31: 76670.
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    Maeda H, Seymour LW, Miyamoto Y. Conjugates of anticancer agents and polymers: advantages of macromolecular therapeutics in vivo. Bioconj Chem 1992; 3: 35162.
  • 15
    Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics. J Control Release 2000; 65: 27184.
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    Maeda H, Matsumura Y, Kato H. Purification and identification of [hydroxprolyl3]bradykinin in ascitic fluid from a patient with gastric cancer. J Biol Chem 1988; 263: 1605154.
  • 17
    Maeda H, Noguchi Y, Sato K, Akaike T. Enhanced vascular permeability in solid tumor is mediated by nitric oxide and inhibited by both new nitric oxide scavenger and nitric oxide synthase inhibitor. Jpn J Cancer Res 1994; 85: 33134.
  • 18
    Maeda H, Wu J, Okamoto T, Maruo K, Akaike T. Kallikrein-kinin in infection and cancer. Immunopharmacology 1999; 43: 11528.
  • 19
    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.
  • 20
    Wu J, Akaike T, Hayashida K, Okamoto T, Okuyama A, Maeda H. Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinase. Jpn J Cancer Res 2001; 92: 43951.
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    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.
  • 22
    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 Cont Release 2001; 74: 4761.
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    Kaminishi H, Cho T, Itoh T et al. Vascular permeability enhancing activity of Porphyromonas gingivalis protease in guinea pigs. FEMS Microbiol Lett 1993; 114: 10914.
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    Kaminishi H, Hamatake H, Cho T et al. Activation of blood clotting factors by microbial proteinases. FEMS Microbiol Lett 1994; 121: 32732.
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    Kaminishi H, Miyaguchi H, Tamaki T et al. Degradation of humoral host defense by Candida albicans proteinase. Infect Immun 1995; 63: 98488.
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    Matsumoto K, Yamamoto T, Kamata R, Maeda H. Pathogenesis of serratial infection: activation of the Hageman factor-prekallikrein cascade by serratial protease. J Biochem 1984; 96: 73949.
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    Kamata R, Yamamoto T, Matsumoto K, Maeda H. A serratial protease causes vascular permeability reaction by activation of the Hageman factor-dependent pathway in guinea pigs. Infect Immun 1985; 48: 74753.
  • 28
    Molla A, Yamamoto T, Akaike T, Miyoshi S, Maeda H. Activation of Hageman factor and prekallikrein and generation of kinin by various microbial proteinases. J Biol Chem 1989; 264: 1058994.
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    Maeda H. Role of microbial proteases in pathogenesis. Microbiol Immunol 1996; 40: 68599.
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    Maeda H. Microbial proteinases and pathogenesis of infection. In: Creighton TE, ed. Wiley Encyclopedia of Molecular Medicine. New York: John Wiley & Sons, 2002; 4: 266368.
  • 31
    Maruo K, Akaike T, Inada Y, Ohkubo I, Ono T, Maeda H. Effect of microbial and mite proteases on low and high molecular weight kininogens. J Biol Chem 1993; 268: 1771115.
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    Matsumura Y, Kimura M, Yamamoto T, Maeda H. Involvement of the kinin-generating cascade in enhanced vascular permeability in tumor tissue. Jpn J Cancer Res 1988; 79: 132734.
  • 33
    Matsumura Y, Maruo K, Kimura M, Yamamoto T, Konno T, Maeda H. Kinin-generating cascade in advanced cancer patients and in vitro study. Jpn J Cancer Res 1991; 82: 73241.
  • 34
    Matsumura Y, Kimura M, Kato H, Yamamoto T, Maeda H. Quantification, isolation and structural determination of bradykinin and hydroxyprolyl-bradykinin in tumor ascites. Adv Exp Med Biol 1989; 247A: 58792.
  • 35
    Bhoola K, Ramsaroop R, Plendl J, Cassim B, Dlamini Z, Naicker S. Kallikrein and kinin receptor expression in inflammation and cancer. Biol Chem 2001; 382: 7789.
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    Figueroa CD, Ehrenfeld P, Bhoola KD. Kinin receptors as targets for cancer therapy. Expert Opin Ther Targets 2012; 16: 299312.
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    Oda T, Akaike T, Hamamoto T, Suzuki F, Hirano T, Maeda H. Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymer-conjugated SOD. Science 1989; 244: 97476.
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    Akaike T, Ando M, Oda T et al. Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice. J Clin Invest 1990; 85: 73945.
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    Maeda H, Akaike T. Oxygen free radicals as pathogenic molecules in viral diseases. Proc Soc Exp Biol Med 1991; 198: 72127.
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    Maeda H. Paradigm shift in microbial pathogenesis: an alternative to the Koch-Pasteur paradigm on the new millennium. In: ed. Arai S, Kurume University School of Medicine. Abstr. in the Proceedings of the 13th International Congress for Mycoplasmology; 14–19 July 2000, Fukuoka, Japan.
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    Yoshitake J, Akaike T, Akuta T et al. Nitric oxide as an endogenous mutagen for Sendai virus without antiviral activity. J Virol 2004; 78: 870919.
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    Akaike T, Maeda H. Nitric oxide and virus infection. Immunology 2000; 101: 3008.
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    Akaike T, Maeda H. Pathophysiological effects of high-output production of nitric oxide. In: Ignarro LJ, ed. Nitric Oxide. San Diego: Academic Press, 2000; 73345.
  • 47
    Akaike T, Okamoto S, Sawa T et al. 8-Nitroguanosine formation in viral pneumonia and its implication for pathogenesis. Proc Natl Acad Sci USA 2003; 100: 68590.
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    Akaike T, Fujii S, Kato A et al. Viral mutation accelerated by nitric oxide production during infection in vivo. FASEB J 2000; 14: 144754.
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    Kuwahara H, Kariu T, Fan J, Maeda H. Generation of drug-resistant mutants of Helicobacter pylori in the presence of peroxynitrite, a derivative of nitric oxide, at pathophysiological concentration. Microbiol Immunol 2009; 52: 17.
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    Kuwahara H, Kanazawa A, Wakamatsu D et al. Antioxidative and antimutagenic activities of 4-vinyl-2,6-dimethoxyphenol (canolol) isolated from canola oil. J Agric Food Chem 2004; 52: 438087.
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    Maeda H, Akaike T. Nitric oxide and oxygen radicals in infection, inflammation, and cancer. Biochemistry (Moscow) 1998; 63: 100717.
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    Sawa T, Akaike T, Ichimori K et al. Superoxide generation mediated by 8-nitroguanosine, a highly redox-active nucleic acid derivative. Biochem Biophys Res Commun 2003; 311: 3006.
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    Sato K, Akaike T, Kojima Y, Ando M, Nagao M, Maeda H. Evidence of direct generation of oxygen free radicals from heterocyclic amines by NADPH/cytochrome P-450 reductase in vitro. Jpn J Cancer Res 1992; 83: 12049.
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    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.
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    Kanazawa A, Sawa T, Akaike T, Maeda H. Dietary lipid peroxidation products and DNA damage in colon carcinogenesis. Eur J Lipid Sci Technol 2002; 104: 43947.
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    Maeda H, Sato K, Akaike T. Superoxide radical generation from heterocyclic amines. In: Adamson RH, Gustafsson JA, Ito N et al. eds. Heterocyclic Amines in Cooked Foods: Possible Human Carcinogens. Proceedings of the 23rd International Symposium of the Princess Takamatsu Cancer Research Fund, Tokyo. Princeton, NJ: Princeton Scientific Publishing Co., 1995; 10312.
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    Tanaka T, Maeda M, Kohno H et al. Inhibition of azoxymethane-induced colon carcinogenesis in male F344 rats by the citrus limonoids obacunone and limonin. Carcinogenesis 2001; 22: 19398.
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    Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 2003; 3: 76880.
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    Iwai K, Maeda H, Konno T. Use of oily contrast medium for selective drug targeting to tumor: enhanced therapeutic effect and X-ray image. Cancer Res 1984; 44: 211521.
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    Maeda H. Tumor-selective delivery of macromolecular drugs via the EPR effect: background and future prospects. Bioconjug Chem 2010; 21: 797802.
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    Konno T, Maeda H, Yokoyama I et al. Use of a lipid lymphographic agent, lipiodol, as a carrier of high molecular weight antitumor agent, SMANCS, for hepatocellular carcinoma. Cancer Chemother 1982; 9: 200515 (in Japanese).
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    Konno T, Maeda H, Iwai K et al. Effect of arterial administration of high-molecular-weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma: a preliminary report. Eur J Cancer Clin Oncol 1983; 19: 105365.
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    Konno T, Maeda H, Iwai K et al. Selective targeting of anti-cancer drug and simultaneous image enhancement in solid tumors by arterially administered lipid contrast medium. Cancer 1984; 54: 236774.
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    Maki S, Konno T, Maeda H. Image enhancement in computerized tomography for sensitive diagnosis of liver cancer and semiquantitation of tumor selective drug targeting with oily contrast medium. Cancer 1985; 56: 75157.
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    Konno T, Maeda H. Targeting chemotherapy of hepatocellular carcinoma. In: Okuda K, Ishak KG, eds. Neoplasms of the Liver. Tokyo, Berlin, Heidelberg, New York: Springer-Verlag, 1987; 34352.
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    Kobayashi M, Imai K, Sugihara S, Maeda H, Konno T, Yamanaka H. Tumor-targeted chemotherapy with lipid contrast medium and macromolecular anticancer drug (SMANCS) for renal cell carcinoma. Urology 1991; 37: 28894.
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    Tsuchiya K, Uchida T, Kobayashi M. Long-term survival rate after tumor-targeted chemotherapy with the macromolecular anticancer drug SMANCS in lipid contrast medium for renal cell carcinoma: preoperative therapy for nonmetastatic cases. Urology 2000; 55: 495500.
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    Maeda H. Macromolecular therapeutics in cancer treatment: the EPR effect and beyond. J Control Release 2012; 164: 13844.
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