title: Intravenous paclitaxel against metastasis of human gastric tumors of diffuse type.
abstract: OBJECTIVE
  Gastric cancer is one of the leading cancerous diseases worldwide. It is diagnosed often at the advanced stage for which chemotherapy is the main treatment option. The prognosis remains poor for metastatic, especially the diffuse type, gastric cancers. We investigated the efficacy of intravenously administered paclitaxel treating metastases of locally disseminated gastric tumors of diffuse type.
  
  
  METHODS
  Transfection of green fluorescent proteins (GFP)-expressing plasmid into human gastric cancer MKN45 cells of diffuse type was performed, and MKN45-GFP cells constitutively expressing GFP were isolated. The MKN45-GFP cells were orthotopically inoculated into the mouse peritoneal cavity, and tumor growth and organ metastases were monitored. Liver metastases were harvested, re-inoculated, monitored for liver metastases again, and harvested for further inoculation. This in vivo selection procedure was repeated to isolate a subline with high metastatic abilities demonstrated by in vitro invasion abilities using Transwell((R)) system. By visualizing the GFP-expressing tumors, the effects of intravenously administered paclitaxel against the growing peritoneally disseminated and metastasized tumors in nude mice without laparotomy were measured.
  
  
  RESULTS
  An in vivo selected gastric cancer cell line MKN45-GFP-ip4 with high metastatic ability was established. Its invasion ability was inhibited by paclitaxel treatments in vitro. The growths of metastatic and intraperitoneally disseminated MKN45-GFP-ip4 tumors were significantly suppressed by intravenous paclitaxel treatments in nude mice.
  
  
  CONCLUSIONS
  We found that intravenous paclitaxel is active against the metastases of human gastric cancer of peritoneal diffuse type, which warrants further investigations on optimizing the perioperative regimens with intravenous paclitaxel therapy for gastric cancer in patients.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli, Taiwan.
authors.forename: Tsung-Fan
authors.initials: TF
authors.lastname: Tuan
authors.forename: Meng-Li
authors.initials: ML
authors.lastname: Tsai
authors.forename: Kai-Chia
authors.initials: KC
authors.lastname: Yeh
authors.forename: Hsin-Chieh
authors.initials: HC
authors.lastname: Huang
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Chung
authors.forename: Chen-Lung
authors.initials: CL
authors.lastname: Huang
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Han
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Min-Hsien
authors.initials: MH
authors.lastname: Wang
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Shen
authors.forename: Yiu-Kay
authors.initials: YK
authors.lastname: Lai
authors.forename: Wen-Sen
authors.initials: WS
authors.lastname: Lee
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Hwang
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D010537:Peritoneum / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014162:Transfection
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D049452:Green Fluorescent Proteins; D017239:Paclitaxel