Increased growth and incidence of lymph node metastases due to the angiogenesis inhibitor AGM-1470

Br J Cancer. 1997;75(12):1730-4. doi: 10.1038/bjc.1997.296.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / adverse effects*
  • Arm
  • Axilla
  • Body Weight
  • Cyclohexanes
  • Data Interpretation, Statistical
  • Humans
  • Hyperplasia
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Lymph Nodes / pathology
  • Lymphatic Metastasis* / pathology
  • Male
  • O-(Chloroacetylcarbamoyl)fumagillol
  • Rats
  • Sarcoma, Yoshida / drug therapy*
  • Sarcoma, Yoshida / pathology
  • Sesquiterpenes / administration & dosage
  • Sesquiterpenes / adverse effects*
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Antibiotics, Antineoplastic
  • Cyclohexanes
  • Sesquiterpenes
  • O-(Chloroacetylcarbamoyl)fumagillol