Effects of recombinant human endostatin on a human neuroblastoma xenograft.
New antitumor agents must be added to the current neuroblastoma treatment regimens to improve the clinical results. We investigated whether recombinant human endostatin (rhEndostatin), an antiangiogenic agent, is effective against human neuroblastoma in the human neuroblastoma xenograft model designated TNB9. When tumors on the back of nude mice grew to a weight of 90-95 mg, rhEndostatin 10 mg/kg/day was administered subcutaneously every day for 10 consecutive days. Mean relative tumor weight in mice administered rhEndostatin (n=5) was significantly less than that in controls (n=12) on days 2, 4, and 6 after the start of administration (p<0.01 on day 2, p<0.05 on days 4 and 6), and regression of tumor growth (TRW<1.0) was marked on day 2. The maximum inhibition rate (MIR) by rhEndostatin was 46.4%, indicating inefficacy, but it may not be appropriate to apply Battelle Columbus Laboratories criteria to this experimental model because rhEndostatin is a protein. After day 8, tumors in the experimental group increased in weight and were not statistically significantly different from those in controls. Recombinant human endostatin was used in tumors in the arterial system of the mouse in this experiment because eventually rhEndostatin, not recombinant mouse endostatin, may be used to treat advanced neuroblastoma in the clinical setting. The results show that there is little cross-reactivity of rhEndostatin with the human and mouse models and indicate that rhEndostatin could become an effective agent for the treatment of human neuroblastoma.
Kuroiwa
M
M
Department of Surgery, Gunma Children's Medical Center, Hokkitsu, Seta-gun, Gunma 377-8577, Japan.
Ikeda
H
H
Hongo
T
T
Tsuchida
Y
Y
Hirato
J
J
Kaneko
Y
Y
Suzuki
N
N
Obana
K
K
Makino
S I
SI
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000627:therapeutic use*; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003094:Collagen