Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-28T17:10:59.707Z Has data issue: false hasContentIssue false
  • English
  • Français

Primary study in experimental antiangiogenic therapy of nasopharyngeal carcinoma with AGM-1470 (TNP-470)

Published online by Cambridge University Press:  29 June 2007

Chao-nan Qian ,
Hua-Qing Min ,
Han-liang Lin ,
Ming-Huang Hong  and
Yan-li Ye
Chao-nan Qian*
Affiliation:
Department of Nasopharyngeal Carcinoma, Tumor Hospital, Cancer Center, Sun Yat-sen University of Medical Sciences, (SUMS), Guangzhou, P.R. of China.
Hua-Qing Min
Affiliation:
Department of Nasopharyngeal Carcinoma, Tumor Hospital, Cancer Center, Sun Yat-sen University of Medical Sciences, (SUMS), Guangzhou, P.R. of China.
Han-liang Lin
Affiliation:
Department of Pathology, Tumor Hospital, Cancer Center, Sun Yat-sen University of Medical Sciences, (SUMS), Guangzhou, P.R. of China.
Ming-Huang Hong
Affiliation:
Department of Nasopharyngeal Carcinoma, Tumor Hospital, Cancer Center, Sun Yat-sen University of Medical Sciences, (SUMS), Guangzhou, P.R. of China.
Yan-li Ye
Affiliation:
Department of Animal Laboratory of the Cancer Center, Tumor Hospital, Cancer Center, Sun Yat-sen University of Medical Sciences, (SUMS), Guangzhou, P.R. of China.
*
Address for correspondence: Chao-nan Qian, M.D., Department of Nasopharyngeal Carcinoma, Tumor Hospital, Sun Yat-sen University of Medical Sciences, 651 Dongfeng East Road, Guangzhou 510060, P. R. of China. Fax: +86-20-87754506 E-mail: gzqcnan@publicl.guangzhou.gd.cn
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective

To evaluate the efficacy of the angiogenesis inhibitor AGM-1470 for the experimental treatment of nasopharyngeal carcinoma (NPC).

Methods

A NPC human tumour model was built by tumour-bearing nude mice using the NPC cell line CNE-2. Twenty-one BALB/c nude mice bearing CNE-2 xenografts were randomized into a treatment group and a control group. In the treatment group, AGM-1470 was injected 30 mg/kg subcutaneously every other day; while the vehicle (three per cent ethanol solution in 0.9 per cent saline) was given to the mice in control group. Tumour volumes and animal weights were measured every third day. Autopsy was performed after 18 days of treatment. The tumour tissue as well as the murine tissues of heart, kidney, and liver in each mouse were removed for formalin fixation and routine HE staining. Pathological evaluation was performed in these tissues.

Results

There was a significant difference in tumour volume between the two groups at day 9 of treatment and this increased thereafter. At day 15 of treatment, the tumour volume was 4251 ± 559 mm3 (n = 10) in the control group versus 3122 ± 967 mm3 (n = 11) in the AGM-1470 treated group (p = 0.004); and T:C ratio (mean tumour volume of treated/mean tumour volume of control) was 0.73, resulting in a 27 per cent decrease in tumour growth. Central necrosis and consequential shrinkage of tumours occurred in both groups at the end of experiment. Physical toxicity and histological toxicity of heart, liver, and kidney did not result from AGM-1470 therapy.

Conclusions

AGM-1470 suppresses the growth of the human NPC cell line CNE-2. Treatment by AGM-1470 has no physical nor histological toxicity. Angiogenesis inhibitors may be effective in the treatment of the local lesion of NPC.

Keywords

Nasopharyngeal neoplasmsCarcinomaNeovasculanzation inhibition, treatment
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 112 , Issue 9 , September 1998 , pp. 849 - 853
Copyright
Copyright © JLO (1984) Limited 1998

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Al-Sarraf, M., McLaughlin, P. W. (1995) Nasopharyngeal carcinoma: choice of treatment. International Journal of Radiation Oncology Biology and Physics 33(3): 761–763.CrossRefGoogle ScholarPubMed
Antoine, N., Greimers, R., De Roanne, C., Kusaka, M., Heinen, E., Simar, L. J., Castronovo, V. (1994) AGM-1470, a potent angiogenesis inhibitor, prevents the entry of normal but not transformed endothelial cells into the G1 phase of the cell cycle. Cancer Research 54(8): 2073–2076.Google Scholar
Brem, H., Folkman, J. (1993) Analysis of experimental antiangiogenic therapy. Journal of Pediatric Surgery 28(3): 445–451.CrossRefGoogle ScholarPubMed
Brem, H., Ingber, D., Blood, C. H., Bradley, D., Urioste, S., Folkman, J. (1991) Suppression of tumor metastasis by angiogenesis inhibition. Surgical Forum 42: 439–441.Google Scholar
Castronovo, V., Belotti, D. (1996) TNP-470 (AGM-1470): Mechanisms of action and early clinical development. European Journal of Cancer 32A(14): 2520–2527.CrossRefGoogle ScholarPubMed
Cvitkovic, E., Grange, G. R. L., Temple, S. (1994) Neoadjuvant chemotherapy (NACY) with Epirubicin (EPI), Cisplatin (CDDP), Bleomycin (BLEO) (BEC) in undifferentiated nasopharyngeal cancer (UNCT): Preliminary results of an international Phase III Trial. Proceedings of the American Society of Clinical Oncology 13: 283.Google Scholar
Editorial (1991) Exploiting angiogenesis. Lancet 337(8735): 208–209.CrossRefGoogle Scholar
Fandi, A., Altun, M., Azli, N., Armand, J. P., Cvitkovic, E. (1994) Nasopharyngeal cancer: epidemiology, staging and treatment. Seminars in Oncology 21(3): 382–397.Google ScholarPubMed
Folkman, J. (1972) Tumor angiogenesis: therapeutic implications. New England and Journal of Medicine 285: 1182–1186.Google Scholar
Fox, S. B., Gatter, K. C., Harris, A. L. (1996) Tumor angiogenesis. Journal of Pathology 179: 232–237.3.0.CO;2-A>CrossRefGoogle Scholar
Fujioka, T., Hasegawa, M., Ogiu, K., Matsushita, Y., Sato, M., Kubo, T. (1996) Antitumor effects of angiogenesis inhibitor O-(chloroacetyl-carbamoyl) fumagillol (TNP-470) against murine renal cell carcinoma. Journal of Urology 155(5): 1775–1778.CrossRefGoogle Scholar
Hwang, H. N. (1983) Nasopharyngeal carcinoma in the People's Republic of China: incidence, treatment and survival rates. Radiology 149: 305–309.CrossRefGoogle ScholarPubMed
Ingber, D., Fujita, T., Kishimoto, S., Sudo, K., Kanamaru, T., Brem, H., Folkman, J. (1990) Synthetic analogue of fumagillin that inhibit angiogenesis and suppress tumor growth Nature 348(6301): 555–557.CrossRefGoogle Scholar
Kato, T., Sato, K., Kakinuma, H., Matsuda, Y. (1994) Enhanced suppression of tumor growth by combination of angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470) and cytotoxic agents in mice. Cancer Research 54(19): 5143–5147.Google Scholar
Kusaka, M., Sudo, K., Fujita, T., Marui, S., Itoh, F., Ingber, D., Folkman, J. (1991) Potent anti-angiogenic action of AGM-1470: comparison of the fumagillin parent. Biochemical Biophysical Research Communications 174: 1070–1076.CrossRefGoogle ScholarPubMed
Kusaka, M., Sudo, K., Matsutani, E., Kozai, Y., Marui, S., Fujita, T., Ingber, D., Folkman, J. (1994) Cytostatic inhibition of endothelial cell growth by the angiogenesis inhibitor TNP-470 (AGM-1470). British Journal of Cancer 69: 212–216.CrossRefGoogle Scholar
Kwong, D., Sham, J., Choy, D. (1994) The effect of locoregional control on distant metastatic dissemination in carcinoma of the nasopharynx: an analysis of 1301 patients. International Journal of Radiation Oncology Biology and Physics 30(5): 1029–1036.CrossRefGoogle ScholarPubMed
Lee, A. W. M., Poon, Y. F., Foo, W., Law, S. C. K., Cheung, F. K., Chan, D. K. K., Tung, S. Y., Thaw, M., Ho, J. H. C. (1992) Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976–1985: overall survival and patterns of failure. International Journal of Radiation Oncology Biology and Physics 23(2): 26–270.CrossRefGoogle ScholarPubMed
Li, Z. Q., Pan, Q. C., Chen, J. J. (1983) Clinic of NPC and experimental research, Technological Publication Press, Guangdong, pp 12–74.Google Scholar
O'Reilly, M. S., Brem, H., Folkman, J. (1995) Treatment of murine hemangioendotheliomas with the angiogenesis inhibitor AGM-1470. Journal of Pediatric Surgery 30(2): 325–330.CrossRefGoogle ScholarPubMed
Qian, C. N., Min, H. Q., Liang, X. M., Zheng, S. S., Lin, H. L. (1998) Primary study of neovasculature correlating with metastatic nasopharyngeal carcinoma using computer image analysis (in press).Google Scholar
Roychowdhury, D. F., Tseng, Jr. A., Fu, K. K., Weinberg, V., Weidher, N. (1996) New prognostic factors in nasopharyngeal carcinoma: tumour angiogenesis and C-erbB2 expression. Cancer 77(8): 1419–1426.3.0.CO;2-7>CrossRefGoogle ScholarPubMed
Scott, P. A. E., Harris, A. L. (1994) Current approaches to targeting cancer using antiangiogenesis therapies. Cancer Treatment Reviews 20: 393–412.CrossRefGoogle ScholarPubMed
Tanaka, T., Konno, H., Matsuda, I., Nakamura, S., Baba, S. (1995) Prevention of hepatic metastasis of human colon cancer by angiogenesis inhibitor TNP-470. Cancer Research 55(4): 836–839.Google ScholarPubMed
Tao, H. Q., Lin, Y. J. (1996) Microvessel density of tumor is a prognostic factor of malignancies. Journal of Practical Oncology (China) 10(2): 73–75.Google Scholar
Teicher, B. A., Dupuis, N. P., Robinson, M. F., Emi, Y., Goff, D. A. (1995) Antiangiogenic treatment (TNP-470/minocyclin) increases tissue levels of anticancer drugs in mice bearing Lewis lung carcinoma. Oncology Research 7(5): 237–243.Google ScholarPubMed
Voest, E. E. (1996) Inhibitors of angiogenesis in a clinical perspective. Anti-Cancer Drugs 7: 723–727.CrossRefGoogle ScholarPubMed
Yamamoto, T., Sudo, K., Fujita, T. (1994) Significant inhibition of endothelial cell growth in tumor vasculature by an angiogenesis inhibitor, TNP-470 (AGM-1470). Anticancer Research 14: 1–4.Google Scholar
Yamaoka, M., Yamamoto, T., Ikeyama, S., Sudo, K., Fujita, T. (1993) Angiogenesis inhibitor TNP-470 (AGM-1470) potently inhibits the tumour growth of hormone-independent human breast and prostate carcinoma cell lines. Cancer Research 53: 5233–5236.Google ScholarPubMed
Yanase, T., Tamura, M., Fujita, K., Kodama, S., Tanaka, K. (1993) Inhibitory effect of angiogenesis inhibitor TNP-470 on tumor growth and metastasis of human cell lines in vitro and in vivo. Cancer Research 53(11): 2566–2570.Google ScholarPubMed
Yano, T., Tanase, M., Watanabe, A., Sawada, H., Yamada, Y., Shino, Y., Nakano, H., Ohnishi, T. (1995) Enhancement effect of an anti-angiogenic agent, TNP-470 on hyperthermia-induced growth suppression of human esophageal and gastric cancers transplantable to nude mice. Anticancer Research 15: 1355–1358.Google ScholarPubMed
Yazaki, T., Takamiya, Y., Costello, P. C., Mineta, T., Menon, A. G., Rabkin, S. D., Martuza, R. L. (1995) Inhibition of angiogenesis and growth of human non-malignant and malignant meningiomas by TNP-470. Journal of Neurooncology 23(1): 23–29.CrossRefGoogle ScholarPubMed
Zhang, S. Z. H., Gao, X. K., Zeng, Y. (1983) Cytogenetic study on an epithelial cell line derived from poorly differentiated nasopharyngeal carcinoma. International Journal of Cancer 31: 587–590.Google Scholar