Therapeutic effects of novel anti-tumor reagent, apoptosis inducing nucleosides from CD57+HLA-DRbright natural suppressor cell line on human gastric carcinoma-bearing SCID mice.
To further provide scientific evidence before clinical application, the anti-tumor effects of apoptosis inducing nucleosides (AINs) released from CD57+HLA-DRbright natural suppressor (CD57.DR-NS) cell line on human gastric carcinoma (GCIY)-bearing severe combined immunodeficiency (SCID) mice were examined by monitoring tumor cell growth and change of body weight of mice. The results obtained evidenced that AINs strongly induced apoptosis in the tumor tissues in SCID mice with decrease of tumor size and without loss of body weight. We found that peak 5 and peak 6 (P5 and P6) components among six components (AINs) isolated from CD57.DR-NS cell cultures by high performance liquid chromatography (HPLC) are the most effective. The anti-tumor effective dosage of P5, P6 and their mixture, P5+P6, were obtained in dose-dependent manner. Thus, the most effective method of administration of AINs for tumor regression without exhaustion was established in the present study. Corresponding to the previous study that AINs could generate apoptosis in malignant cells while lacking the toxicity in normal cells, the results obtained in the present preclinical experiments suggested anti-tumor efficacy of AINs with possible refrainment from side-effects in clinical trials.
Jin
Aishun
A
Department of Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Qi
Yunlong
Y
Mori
Etsuko
E
Guo
Maowu
M
Takasaki
Seiichi
S
Mori
Tsuneatsu
T
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017209:Apoptosis; D001835:Body Weight / Q000187:drug effects*; D018959:CD57 Antigens / Q000276:immunology / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005467:Floxuridine / Q000627:therapeutic use; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009705:Nucleosides / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D018959:CD57 Antigens; D006684:HLA-DR Antigens; D009705:Nucleosides; D005467:Floxuridine; C025034:doxifluridine