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(Chest. 1998;114:1668-1675.)
© 1998 American College of Chest Physicians

Vascular Endothelial Growth Factor Increased by Pulmonary Surgery Accelerates the Growth of Micrometastases in Metastatic Lung Cancer

Yoshimasa Maniwa MD1; Masayoshi Okada MD1; Noboru Ishii MD1; and Kazue Kiyooka MD1

1 From the Department of Surgery Division II, Kobe University School of Medicine, Kobe, Japan

Yoshimasa Maniwa, MD, Department of Surgery Division II, Kobe University School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650, Japan; e-mail: rk3y-mnw{at}asahi-net.or.jp

Background: The use of surgery for metastatic lung cancer has been established recently and the indications have been extended to multiple and bilateral lung metastases. However, in some patients, secondary lung metastasis appears soon after the first pulmonary surgery, making curative treatment very difficult. Postoperative weakness of tumor angiogenesis suppression mechanisms seems to play an important role in the recurrence of lung metastases. To verify this hypothesis, we performed a clinical and an experimental study.

Results and conclusion: The clinical study revealed that serum vascular endothelial growth factor (VEGF), also known as vascular permeability factor, increased after pulmonary surgery. The experimental study showed that VEGF played an important role in the rapid growth of dormant micrometastases of the lung. These results suggested that the postoperative increase of VEGF disrupted angiogenesis suppression and induced the growth of dormant micrometastases early in the postoperative period. It was also demonstrated that this effect of VEGF on micrometastases was abolished by AGM-1470, an angiogenesis inhibitor. In conclusion, postoperative treatment with AGM-1470 might inhibit the early recurrence of malignant tumors.

Key Words: angiogenesis inhibitor • lung metastasis • metastatic lung cancer • vascular endothelial growth factor • vascular permeability factor

Submitted on November 26, 1997
Accepted on April 20, 1998




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