Therapeutic Applications of Nitric Oxide for Malignant Tumor in Animal Models and Human Studies

  • Hiroyasu Yasuda
  • Kazuhiro Yanagihara
  • Katsutoshi Nakayama
  • Tadashi Mio
  • Takahiko Sasaki
  • Masanori Asada
  • Mutsuo Yamaya
  • Masanori Fukushima
Part of the Cancer Drug Discovery and Development book series (CDD&D)


In cancer science, nitric oxide (NO) has been mainly discussed as an oncogenic molecule over the past decades. However, NO has recently been noted in cancer biology to be associated with cancer cell apoptosis, cancer cell cycle, cancer progression and metastasis, cancer angiogenesis, cancer chemoprevention, and a modulator for chemo/radio/immunotherapy. NO is produced and released from three different isoforms of NO synthase (NOS) and from exogenously administered NO donors in vivo. Over-expression of inducible NOS (iNOS) in cancer tissues is associated with an increase in microvascular density in tumor tissues and poor prognosis in patients with cancers. Recently, NO donors and iNOS transfer have been demonstrated to enhance the effects of cancer therapy including chemotherapy, radiotherapy, and immunotherapy for solid cancers, resulting in a prolonged survival time. In this chapter, we to discuss the recent animal experiments and clinical trials to develop these investigations for clinical applications.


Nitric oxide Nitric oxide synthase Cancer biology Cancer progression Metastasis Apoptosis Cell cycle Proliferation Chemoprevention Chemotherapy Radiotherapy Immunotherapy Animal experiment Clinical trial 



apoptosis-inducing factor


endothelial NOS


hypoxia-inducible factor-1 alpha


inducible NOS


Lewis lung carcinoma


nitric oxide


NO synthase


non-steroidal anti-inflammatory drug


non-small cell lung cancer


tumor necrosis factor


TNF-related apoptosis-inducing ligand


vascular endothelial growth factor


Yin–Yang 1



The chapter was supervised by Dr. K. Yanagihara and Prof. M. Fukushima. Dr. H. Yasuda was supported by a Grant-In-Aid for Scientific Research from the Ministry of Education, Science and Culture (17790524, 19689018) of the Japanese government and The Kanae Foundation for the Promotion of Medical Science.


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Copyright information

© Springer Science + Business Media, LLC 2010

Authors and Affiliations

  • Hiroyasu Yasuda
    • 1
  • Kazuhiro Yanagihara
    • 2
  • Katsutoshi Nakayama
    • 3
  • Tadashi Mio
    • 4
  • Takahiko Sasaki
    • 7
  • Masanori Asada
    • 5
  • Mutsuo Yamaya
    • 6
  • Masanori Fukushima
    • 2
  1. 1.Department of Clinical Application, Translational Research CenterTohoku UniversitySendaiJapan
  2. 2.Outpatient Oncology UnitKyoto University HospitalKyotoJapan
  3. 3.Department of Respiratory MedicineJikei University School of MedicineTokyoJapan
  4. 4.Department of Multidisciplinary Cancer TreatmentKyoto University School of MedicineKyotoJapan
  5. 5.Department of Geriatrics and Gerontology, Institute of Development, Aging and CancerTohoku UniversitySendaiJapan
  6. 6.Department of Advanced Preventive Medicine for Infectious DiseaseTohoku University School of MedicineSendaiJapan
  7. 7.Department of Respiratory MedicineTohoku University School of MedicineSendaiJapan

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