A novel anticancer treatment for xenoplanted human gastric cancer using polyamine antimetabolites in a low polyamine diet.
The aim of the present study was to evaluate a new anticancer treatment for gastrointestinal cancer, using a combination of polyamine antimetabolites, an anticancer agent and a low-polyamine state. Two polyamine antimetabolites, given as either 40 mg/kg of methylglyoxal-bis-guanylhydrazone (MGBG) or ethylglyoxal-bis-guanylhydrazone (EGBG) and a normal diet (ND), or 20 mg/kg of each drug and a low polyamine diet (LPD), together with 1,000 mg/kg of alphadifluoromethylornithine (DFMO) were administered ip to nude mice for six consecutive days. Mitomycin C (MMC) at 2 mg/kg was then given ip for 3 alternate days. The combination of MGBG or EGBG with DFMO plus MMC resulted in an enhanced antitumor efficacy on LPD. However, the combination which included EGBG was much more enhanced than that which included MGBG and there was no evidence of any tumor regrowth. Weight loss was minimal or nil in the mice given the combination with EGBG, but was evident in those given the combination with MGBG. These results led to the conclusion that in mice, the combined therapy of EGBG with DFMO plus MMC and LPD is a safe and effective regimen for the treatment of gastric cancer.
Shrestha
R D
RD
First Department of Surgery, School of Medicine, Chiba University, Japan.
Fujimoto
S
S
Okui
K
K
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D001835:Body Weight; D002455:Cell Division / Q000187:drug effects; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004032:Diet; D004359:Drug Therapy, Combination; D000518:Eflornithine / Q000032:analysis / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008935:Mitoguazone / Q000031:analogs & derivatives* / Q000032:analysis / Q000627:therapeutic use*; D016685:Mitomycin / Q000032:analysis / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D011073:Polyamines / Q000008:administration & dosage* / Q000032:analysis; D013274:Stomach Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology
D004273:DNA, Neoplasm; D011073:Polyamines; C041127:ethylglyoxal bis(guanylhydrazone); D016685:Mitomycin; D012437:Adenosylmethionine Decarboxylase; D008935:Mitoguazone; D000518:Eflornithine