Antitumor effects induced by the combination of TNP-470 as an angiogenesis inhibitor and lentinan as a biological response modifier in a rabbit spontaneous liver metastasis model.
OBJECTIVE
An angiogenesis inhibitor, TNP-470 (TNP), has shown promising results in tumor dormancy therapy, and we have been studying its antitumor effects using a rabbit spontaneous liver metastasis model. However, because inhibition was observed only at the step of micrometastasis, we examined the effects of combining TNP in the same model with a nonspecific immunopotentiator, lentinan (LNT), as a biological response modifier.


METHODS
The model was established by the inoculation of VX-2 tumors into the colon, and colectomy was subsequently performed, including the primary tumor. Combination (TNP + LNT) effects were evaluated in terms of the number and volume of metastatic nodules, microvessel density (MVD), expression of proliferating cell nuclear antigen (PCNA), and apoptosis, using immunohistochemical staining with anti-CD31, anti-PCNA monoclonal antibody, and the TUNEL (in situ nick end-labeling) method, respectively.


RESULTS
Angiogenesis was significantly inhibited in the TNP + LNT group, and the apoptotic index was also significantly higher than in the TNP or LNT groups. The positive expression of PCNA in the VX2 cells was reduced in the LNT alone and TNP + LNT groups, but not in the TNP alone group.


CONCLUSIONS
These findings indicate that TNP-470 and lentinan could prove useful for preventing the development of metachronous liver metastases from colorectal cancers after curative resection.
Sano
Bun
B
Second Department of Surgery, Gifu University School of Medicine, Japan.
Sugiyama
Yasuyuki
Y
Kunieda
Katsuyuki
K
Sano
Jun
J
Saji
Shigetoyo
S
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D003110:Colonic Neoplasms / Q000473:pathology; D003510:Cyclohexanes; D005260:Female; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000556:secondary*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D011817:Rabbits; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D018709:Statistics, Nonparametric
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol