Original Article
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World J Crit Care Med. Nov 4, 2013; 2(4): 48-55
Published online Nov 4, 2013. doi: 10.5492/wjccm.v2.i4.48
Molecular targeting therapy using bevacizumab for peritoneal metastasis from gastric cancer
Keishiro Aoyagi, Kikuo Kouhuji, Motoshi Miyagi, Junya Kizaki, Taro Isobe, Kousuke Hashimoto, Kazuo Shirouzu
Keishiro Aoyagi, Kikuo Kouhuji, Motoshi Miyagi, Junya Kizaki, Taro Isobe, Kousuke Hashimoto, Kazuo Shirouzu, Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
Author contributions: Aoyagi K was responsible for writing and revising the full text original article in response to an invitation from an editorial office member of the WJCCM; Kouhuji K instructed the research and clinical work; Miyagi M established the high potential peritoneal dissemination cell line MKN-45P; Kizaki J cultured the two cell lines and measured the concentration of various cytokines; Isobe T performed the in vivo study on the peritoneal dissemination model using nude mice; Hasimoto K performed the pathological study on the intra-abdominal tumor of nude mice; and Professor Shirouzu K, Chair of the Department of Surgery, provided useful critique and advice for our research.
Correspondence to: Keishiro Aoyagi, Assistant Professor, Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. keishiro@med.kurume-u.ac.jp
Telephone: +81-942-353311 Fax: +81-942-340709
Received: May 2, 2013
Revised: June 5, 2013
Accepted: July 4, 2013
Published online: November 4, 2013
Abstract

AIM: To clarify the significance of vascular endothelial growth factor (VEGF) in peritoneal metastasis from gastric cancer, using the gastric cancer cell line MKN-45 compared with the high potential peritoneal dissemination gastric cancer cell line MKN-45P.

METHODS: The supernatant of culture medium of MKN-45 cells or MKN-45P cells was collected and the concentrations were measured of various cytokines, matrix metalloproteinases, growth factor and angiogenic factors, including VEGF. We performed an initial pilot study to explore whether bevacizumab, a humanized monoclonal antibody against VEGF, had any suppressive effect on the peritoneal dissemination from gastric cancer in an experimental nude mouse model of peritoneal metastasis.

RESULTS: The concentrations of interleukin-6 (IL-6), IL-8, VEGF and matrix metalloproteinase-2 protein in the culture supernatant were each significantly higher than each of those for MKN-45. In the in vivo study, the volume of ascites and the mitotic index were significantly lower in the therapy group than in the non-therapy group. The survival curve of the therapy group was significantly higher than that of the non-therapy group. These results suggested that VEGF was correlated with peritoneal metastasis from gastric cancer.

CONCLUSION: Findings suggested that bevacizumab for inhibiting VEGF could suppress peritoneal dissemination from gastric cancer.

Keywords: Gastric cancer, Peritoneal metastasis, Vascular endothelial growth factor, MKN-45P, Bevacizumab