Effect of angiogenesis inhibitor TNP-470 on the progression of human gastric cancer xenotransplanted into nude mice

Abstract

The effect of an angiogenesis inhibitor, TNP-470, on primary tumor growth, liver metastasis and peritoneal dissemination of gastric cancer was investigated by means of an orthotopic xenotransplanted model of 2 human gastric cancers, MT-2 and MT-5. TNP-470 showed a significant inhibitory effect on the growth of primary tumors after orthotopic transplantation of both xenografts when given at a dose of 30 mg/kg on alternate days from day 7 after transplantation (early treatment). However, growth of the MT-2 primary tumor was not inhibited by administration from day 14 after transplantation (late treatment). Liver metastasis was prevented significantly by early treatment of TNP-470. In particular, early treatment of MT-2 completely inhibited the development of macroscopic foci in the liver and was significantly more effective than late treatment. Peritoneal dissemination also was inhibited. Thus, TNP-470 was revealed to have strong inhibitory activity not only on primary tumors and liver metastases but also against peritoneal dissemination. These results suggest that this agent may provide a new approach to the treatment of gastric cancer. Int.

p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer

“…The predictive value of MVD has also been suggested in other studies in which a higher MVD was associated with the development of distant metastases (Tanigawa et al, 1996) or bone marrow micrometastases (Maehara et al, 1998). Similarly, experimental studies using antiangiogenic agents, such as TNP-470, have shown effectiveness in decreasing tumour proliferative activity and inhibiting the development of liver and peritoneal metastases (Kanai et al, 1997;Yoshikawa et al, 2000). These findings reinforce the relationship between tumour angiogenesis and the spread of metastases.…”

Anti‐angiogenic Treatment for Peritoneal Dissemination of Pancreas Adenocarcinoma: A Study Using TNP‐470

“…Test mice (n=4) were killed, and disseminated nodules on the mesentery were evaluated on the 28th day. In the TNP-short-treatment group, TNP-470 at 30 mg/kg was administered every other day beginning on day 14 and continuing through day 28, with the day of 1×10 7 PCI inoculation being day 0. Test mice (n=5) were killed and disseminated nodules on the mesentery were evaluated on the 28th day.…”

“…However, its importance in the establishment and growth of peritoneal dissemination remains largely unknown, as very few studies have been conducted. 7) The peritoneal implants of pancreas adenocarcinoma patients are histologically composed of a proliferation of carcinoma cells accompanied by desmoplastic stromal reaction with neovascularization. Thus, inhibition of tumor angiogenesis might suppress peritoneal implants, as in the case of hematogenous metastatic nodules.…”

Antitumor Effect of a Neutralizing Antibody to Vascular Endothelial Growth Factor on Liver Metastasis of Endocrine Neoplasm

“…We have previously reported the therapeutic effect of an angiogenesis inhibitor on the liver metastasis of human gastrointestinal malignancies. [4][5][6] In the present study, the therapeutic effect of vascular endothelial cell growth factor neutralizing monoclonal antibody (VEGFAb) on the liver metastasis of EN-1 was investigated by using a liver metastatic model, with the aim of developing a novel therapy for endocrine neoplasm. …”