Comparative effects of a recombinant and a mutein type of granulocyte colony stimulating factor on the growth of Meth-A fibrosarcoma with 5-fluorouracil chemotherapy.
The present study was designed to evaluate the effects of a recombinant human G-CSF (rhG-CSF) and a mutein G-CSF (KW-2228) on leucopenia and tumor growth in mice treated with 5-fluorouracil (5-FU). In normal mice, the number of leucocytes (white blood cell, WBC) reached the peak 12 hours after a single injection of either type of G-CSF and decreased to the normal level after 24 hours. Daily administration induced a continuous increase in the WBC count, however, administrations at intervals did not. Meth-A fibrosarcoma was subcutaneously inoculated into the backs of syngeneic BALB/c mice. The mice were treated with 5-FU alone or with G-CSFs. Chemotherapy with 5-FU alone resulted in leucopenia and an insignificant inhibition of tumor growth. The conjunctive administration of G-CSFs with 5-FU resulted in a significantly augmented inhibition of tumour growth, and leukopenia was not seen. This augmenting effect was more prominent with KW-2228. These results suggest that in 5-FU chemotherapy G-CSFs may be beneficial in restoring the number of leucocytes from leucopenic state and in augmenting the tumor inhibitory effect. Furthermore, KW-2228 may be more beneficial than the natural type rhG-CSF.
Nio
Y
Y
First Department of Surgery, Kyoto University, Faculty of Medicine, Japan.
Shiraishi
T
T
Tsubono
M
M
Morimoto
H
H
Tseng
C C
CC
Kawabata
K
K
Masai
Y
Y
Fukumoto
M
M
Tobe
T
T
D000595:Amino Acid Sequence; D000818:Animals; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D005472:Fluorouracil / Q000627:therapeutic use* / Q000633:toxicity; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D007970:Leukopenia / Q000139:chemically induced / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000494:pharmacology
D007155:Immunologic Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C072115:nartograstim; D005472:Fluorouracil