Antitumor effects of human recombinant macrophage colony-stimulating factor against rat brain tumors.
The tumoricidal effects of M-CSF were examined using two subcutaneously-transplanted rat brain tumor cell lines, 9L and T9 gliomas. In rats treated with high-dose M-CSF (16 million U/kg administered for 4 days a week for 3 weeks), 9L glioma growth was inhibited by 81.9% following subcutaneous (s.c.) injection and by 70.5% after intraperitoneal (i.p.) injection and T9 glioma growth was inhibited by 69.2% after i.p. injection. After short-term treatment with high-dose M-CSF (32 million U/kg administered s.c. for 6 consecutive days, 9L glioma growth was inhibited by 82.1%. All these inhibitory effects differed significantly compared with the respective untreated control groups. However, treatment with low-dose M-CSF (1.6 million U/kg administered s.c. for 4 days a week for 3 weeks) showed no significant effects against 9L and T9 glioma growth compared with the untreated controls. No significant effects of M-CSF against cell proliferation, measured as PCNA expression, were observed in any group. Significant hematopoietic effects on the leukocyte counts were observed only in the groups treated with high dose M-CSF. These results suggest that M-CSF at a high dose which produces hematopoietic effects on peripheral leukocytes inhibits the growth of gliomas. This inhibitory effect may have been due to a tumoricidal mechanism of M-CSF that depended on the production or release of some hematopoietic soluble factors, but was independent of PCNA expression by the tumors.
Matsuoka
T
T
Department of Neurosurgery, School of Medicine, Hiroshima University, Japan.
Uozumi
T
T
Kurisu
K
K
Maeda
H
H
Kawamoto
K
K
Monden
S
S
D000818:Animals; D001932:Brain Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D002455:Cell Division; D017690:Cell Transplantation; D005260:Female; D005910:Glioma / Q000097:blood / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007958:Leukocyte Count; D016173:Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D009368:Neoplasm Transplantation; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000627:therapeutic use
D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor