Molecular targeting therapy using bevacizumab for peritoneal metastasis from gastric cancer.
OBJECTIVE
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.


CONCLUSIONS
Findings suggested that bevacizumab for inhibiting VEGF could suppress peritoneal dissemination from gastric cancer.
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.
Keishiro
K
Aoyagi
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.
Kikuo
K
Kouhuji
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.
Motoshi
M
Miyagi
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.
Junya
J
Kizaki
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.
Taro
T
Isobe
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.
Kousuke
K
Hashimoto
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.
Kazuo
K
Shirouzu
Bevacizumab; Gastric cancer; MKN-45P; Peritoneal metastasis; Vascular endothelial growth factor