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BMC Pharmacology and Toxicology

Open Access

The world's first clinical randomized trial of atrial natriuretic peptide for preventing cancer recurrence following lung cancer surgery

  • Takashi Nojiri1, 2Email author,
  • Hiroshi Hosoda3,
  • Takeshi Tokudome1,
  • Toru Kimura1, 2,
  • Meinoshin Okumura2 and
  • Kenji Kangawa1
BMC Pharmacology and Toxicology201516(Suppl 1):A72

Published: 2 September 2015


Most patients suffering from cancer die of metastatic disease. Surgical removal of solid tumors is performed as an initial attempt to cure patients if the primary tumor meets surgical indications. However, it is possible that surgical trauma itself influences the development of early recurrence. First, resection handling of the tumor can provoke detachment of tumor cells. Second, surgical trauma provokes the severe inflammatory reaction. Vascular inflammation is considered to render the endothelium adhesive to circulating tumor cells thereby allowing the metastasis of tumor cells. We have previously reported that administration of atrial natriuretic peptide (ANP) during the perioperative period reduces inflammatory response and has a prophylactic effect on postoperative cardiopulmonary complications in lung cancer surgery. Here we demonstrate that cancer recurrence after curative surgery was significantly lower in ANP-treated patients than in control patients (surgery alone). ANP is known to bind specifically to guanylyl cyclase-A (GC-A) receptor. In mouse models, we found that metastasis of GC-A–non-expressing tumor cells (i.e., B16 mouse melanoma cells) to the lung was increased in vascular endothelium-specificGC-A knockout mice and decreased in vascular endothelium-specific GC-A transgenic mice compared with control mice. ANP inhibited the adhesion of cancer cells to human pulmonary artery endothelial cells by suppressing the E-selectin expression that is promoted by inflammation. These results suggest that ANP prevents cancer metastasis by inhibiting the adhesion of tumor cells to inflamed endothelial cells. Thus, we have planned to start a multicenter randomized clinical trial to examine the use of perioperative administration of ANP for the prevention of cancer recurrence after lung cancer surgery in this year. In the near future, we want to expand the adaptation of ANP for various types of cancer surgery.

Authors’ Affiliations

Department of Biochemistry, National Cerebral and Cardiovascular Center Research Institute
Department of General Thoracic Surgery, Osaka University Graduate School of Medicine
Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center Research Institute


© Nojiri et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.