Increased growth and incidence of lymph node metastases due to the angiogenesis inhibitor AGM-1470.
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.
Hori
K
K
Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Li
H C
HC
Saito
S
S
Sato
Y
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001132:Arm; D001365:Axilla; D001835:Body Weight; D003510:Cyclohexanes; D003627:Data Interpretation, Statistical; D006801:Humans; D006965:Hyperplasia; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D051381:Rats; D012517:Sarcoma, Yoshida / Q000188:drug therapy* / Q000473:pathology; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol