Antitumor Effects of Angiogenesis Inhibitor O-(Chloroacetyl-Carbamoyl) Fumagillol (TNP-470) against Murine Renal Cell Carcinoma

No AccessJournal of UrologyInvestigative Urology1 May 1996Antitumor Effects of Angiogenesis Inhibitor O-(Chloroacetyl-Carbamoyl) Fumagillol (TNP-470) against Murine Renal Cell Carcinoma Tomoaki Fujioka, Michihiko Hasegawa, Kazunori Ogiu, Yasushi Matsushita, Masatsugu Sato, and Takashi Kubo Tomoaki FujiokaTomoaki Fujioka More articles by this author , Michihiko HasegawaMichihiko Hasegawa More articles by this author , Kazunori OgiuKazunori Ogiu More articles by this author , Yasushi MatsushitaYasushi Matsushita More articles by this author , Masatsugu SatoMasatsugu Sato More articles by this author , and Takashi KuboTakashi Kubo More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)66196-2AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The effect of 0-(chloroacetyl-carbamoyl) fumagillol (TNP-470) on tumor growth and metastasis is investigated. Materials and Methods: BALB/c mice were inoculated with the Renca murine tumor and graded doses of TNP-470 were given subcutaneously every other day beginning on day 1 and ending on day 9. Tumor angiogenesis was measured quantitatively by a colorimetric assay. Results: TNP-470 inhibited tumor growth and prolonged the life span of Renca-bearing mice in a dose-dependent manner. Body weight-loss was not observed in the mice given less than 30 mg./kg./day. When the treatment was delayed on day 6, TNP-470 did not inhibit tumor growth, pointing to the importance of the timing of drug administration in relation to disease stage. Tumor angiogenesis was inhibited 33 to 62 percent of the control level by TNP-470. Furthermore, TNP-470 reduced pulmonary and hepatic metastatic foci of intravenously inoculated Renca and of the tumor inoculated in the spleen. Conclusion: These data suggest that TNP-470 may be effective as a treatment of renal cell carcinoma, especially when micrometastases are involved. References 1 : Cancer statistics. CA Cancer J. Clin.1987; . Google Scholar 2 : Adjunctive treatment of renal cell carcinoma. Int. Adv. Surg. Oncol1983; 6: 309. Google Scholar 3 : Adoptive immunotherapy of urologic tumors. Cancer Treat. Res1989; 46: 213. Google Scholar 4 : Preparative cytoreductive surgery in patients with metastatic renal cell carcinoma treated with adoptive immunotherapy with interleukin-2 or interleukin-2 plus lymphokine activated killer cells. J. Urol1990; 144: 614. Link, Google Scholar 5 : Mechanisms of immunologic antitumor therapy: lessons from the laboratory and clinical applications. Hum. Immunol1990; 28: 198. Google Scholar 6 : Tumor angiogenesis: therapeutic implications. N. Engl. J. Med1971; 285: 1. Google Scholar 7 : Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene. Cell1989; 56: 345. Google Scholar 8 : How is blood vessel growth regulated in normal and neoplastic tissue?. Cancer Res1986; 46: 467. Google Scholar 9 : Tumor angiogenesis and metastasis-correlation in invasive breast carcinoma. N. Engl. J. Med1991; 324: 1. Google Scholar 10 : Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am. J. Pathol1993; 143: 401. Google Scholar 11 : Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumor growth. Nature1990; 348: 555. Google Scholar 12 : Cortisone inhibition of tumor angiogenesis measured by a quantitative colorimetric assay in mice. Cancer Chemother. Pharmacol1990; 26: 461. Google Scholar 13 : Cytostatic inhibition of endothelial cell growth by the angiogenesis inhibitor TNP-470 (AGM-1470). Br. J. Cancer1994; 69: 212. Google Scholar 14 : AGM-1470, a potent angiogenesis inhibitor, prevents the entry of normal but not transformed endothelial cells into the G sub 1 phase of the cell cycle. Cancer Res1994; 54: 2073. Google Scholar 15 : Potent anti-angiogenic action of AGM-1470: comparison to the fumagillin parent. Biochem. Biophys. Res. Commun1991; 174: 1070. Google Scholar 16 : Investigation of tumor angiogenesis in an Id mouse model: role of host-tumor interactions. J. Natl. Cancer Inst1988; 80: 849. Google Scholar 17 : Inhibitory effects of heparin plus cortisone acetate on endothelial cell growth both in cultures and in tumor masses. J. Natl. Cancer Inst1987; 78: 518. Google Scholar 18 : Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell1991; 64: 327. Crossref, Medline, Google Scholar 19 : Tumor interactions with the vasculature: angiogenesis and tumor metastasis. Biochim. Biophys. Acta1990; 1032: 89. Google Scholar 20 : Inhibition of tumor growth and metastasis of rodent tumor by the angiogenesis inhibitor 0-(chloroacetylcarbamoyl)fumagillol (TNP-470; AGM-1470). Cancer Res1993; 53: 4267. Google Scholar Department of Urology, Iwate Medical University School of Medicine, Iwate, Japan.© 1996 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byPRUTHI R, DERKSEN E and GASTON K (2018) Cyclooxygenase-2 as a Potential Target in the Prevention and Treatment of Genitourinary Tumors: A ReviewJournal of Urology, VOL. 169, NO. 6, (2352-2359), Online publication date: 1-Jun-2003.FUJIOKA T, HASEGAWA M, ISHIKURA K, MATSUSHITA Y, SATO M and TANJI S (2018) INHIBITION OF TUMOR GROWTH AND ANGIOGENESIS BY VITAMIN D3 AGENTS IN MURINE RENAL CELL CARCINOMAJournal of Urology, VOL. 160, NO. 1, (247-251), Online publication date: 1-Jul-1998.Campbell S (2018) ADVANCES IN ANGIOGENESIS RESEARCH: RELEVANCE TO UROLOGICAL ONCOLOGYJournal of Urology, VOL. 158, NO. 5, (1663-1674), Online publication date: 1-Nov-1997. Volume 155Issue 5May 1996Page: 1775-1778 Advertisement Copyright & Permissions© 1996 by American Urological Association, Inc.Metrics Author Information Tomoaki Fujioka More articles by this author Michihiko Hasegawa More articles by this author Kazunori Ogiu More articles by this author Yasushi Matsushita More articles by this author Masatsugu Sato More articles by this author Takashi Kubo More articles by this author Expand All Advertisement PDF downloadLoading ...