Abstract
Using the rat tumour cell line LY80, a subline of Yoshida sarcoma, the effects of AGM-1470 on the growth of primary tumour and the incidence of regional lymph node metastasis were evaluated. AGM-1470 (30 mg kg(-1)) was administered subcutaneously or intravenously. Subcutaneous (s.c.) and intravenous (i.v.) injections were repeated for 8 days and 7 days respectively. Tumour growth of a primary region tended to be suppressed by AGM-1470. The s.c. tumours after sacrifice were much smaller in the AGM-1470-treated group (s.c. injection) than in the control groups. However, the growth of metastatic foci in the lymph nodes was prompted markedly by AGM-1470. All six of the AGM-1470-treated rats had developed swollen axillary lymph nodes and/or brachial lymph nodes on day 19 after tumour implantation (the 7th day after the last treatment) compared with one of six saline-injected rats and three of six vehicle-alone treated rats with swollen axillary lymph nodes. The weight of lymph nodes after sacrifice in the AGM-1470-treated rats was much heavier than that of the other two groups. Histological examination showed that in the AGM-1470-treated group, the cortex and the medulla of the axillary lymph nodes were almost entirely replaced by tumour cells while, in the vehicle alone group, a notable hyperplasia of the lymph nodes due to BT cell proliferation tended to be induced. In the saline group, although a slight hyperplasia of lymph nodes was observed, there were only a few lymph node metastases. In the case of i.v. injection of AGM-1470, similar results were obtained. It is thought that LY80 cells spread to regional lymph nodes at a comparatively early stage by some change or other in which AGM-1470 participated. From the present experiment, it is concluded that application of AGM-1470 alone to patients should be carried out with great caution.
Full text
PDF![1730](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d7/2223605/fa9dde9b9f7d/brjcancer00189-0020.png)
![1731](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d7/2223605/83e791ce45cc/brjcancer00189-0021.png)
![1732](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d7/2223605/f3e1896cb1b8/brjcancer00189-0022.png)
![1733](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d7/2223605/8d58d8eb9d9d/brjcancer00189-0023.png)
![1734](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39d7/2223605/196bdb919ada/brjcancer00189-0024.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Antoine N., Daukandt M., Heinen E., Simar L. J., Castronovo V. In vitro and in vivo stimulation of the murine immune system by AGM-1470, a potent angiogenesis inhibitor. Am J Pathol. 1996 Feb;148(2):393–398. [PMC free article] [PubMed] [Google Scholar]
- Ingber D., Fujita T., Kishimoto S., Sudo K., Kanamaru T., Brem H., Folkman J. Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth. Nature. 1990 Dec 6;348(6301):555–557. doi: 10.1038/348555a0. [DOI] [PubMed] [Google Scholar]
- Kurebayashi J, Kurosumi M, Dickson RB, Sonoo H. Angiogenesis Inhibitor O-(Chloroacetyl-carbamoyl) fumagillol (TNP-470) Inhibits Tumor Angiogenesis, Growth and Spontaneous Metastasis of MKL-4 Human Breast Cancer Cells in Female Athymic Nude Mice. Breast Cancer. 1994 Dec 30;1(2):109–115. doi: 10.1007/BF02967040. [DOI] [PubMed] [Google Scholar]
- Kusaka M., Sudo K., Fujita T., Marui S., Itoh F., Ingber D., Folkman J. Potent anti-angiogenic action of AGM-1470: comparison to the fumagillin parent. Biochem Biophys Res Commun. 1991 Feb 14;174(3):1070–1076. doi: 10.1016/0006-291x(91)91529-l. [DOI] [PubMed] [Google Scholar]
- McLeskey S. W., Zhang L., Trock B. J., Kharbanda S., Liu Y., Gottardis M. M., Lippman M. E., Kern F. G. Effects of AGM-1470 and pentosan polysulphate on tumorigenicity and metastasis of FGF-transfected MCF-7 cells. Br J Cancer. 1996 May;73(9):1053–1062. doi: 10.1038/bjc.1996.204. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pollard M. Thalidomide promotes metastasis of prostate adenocarcinoma cells (PA-III) in L-W rats. Cancer Lett. 1996 Mar 19;101(1):21–24. doi: 10.1016/0304-3835(95)04105-2. [DOI] [PubMed] [Google Scholar]
- Tanaka T., Konno H., Matsuda I., Nakamura S., Baba S. Prevention of hepatic metastasis of human colon cancer by angiogenesis inhibitor TNP-470. Cancer Res. 1995 Feb 15;55(4):836–839. [PubMed] [Google Scholar]
- Yamaoka M., Yamamoto T., Ikeyama S., Sudo K., Fujita T. Angiogenesis inhibitor TNP-470 (AGM-1470) potently inhibits the tumor growth of hormone-independent human breast and prostate carcinoma cell lines. Cancer Res. 1993 Nov 1;53(21):5233–5236. [PubMed] [Google Scholar]
- Yamaoka M., Yamamoto T., Masaki T., Ikeyama S., Sudo K., Fujita T. Inhibition of tumor growth and metastasis of rodent tumors by the angiogenesis inhibitor O-(chloroacetyl-carbamoyl)fumagillol (TNP-470; AGM-1470). Cancer Res. 1993 Sep 15;53(18):4262–4267. [PubMed] [Google Scholar]
- Yanase T., Tamura M., Fujita K., Kodama S., Tanaka K. Inhibitory effect of angiogenesis inhibitor TNP-470 on tumor growth and metastasis of human cell lines in vitro and in vivo. Cancer Res. 1993 Jun 1;53(11):2566–2570. [PubMed] [Google Scholar]