Recombinant human (rhu) macrophage colony-stimulating factor (M-CSF) was evaluated, alone or in combination with local hyperthermia (LH), for their antitumor effects in mice inoculated with B16a melanoma cells. Several tumor related parameters and other hematopoietic and immunologic parameters were evaluated 5 weeks after subcutaneous (s.c.) inoculation of tumor cells into the right limbs of C57BL/6J male mice. RhuM-CSF was administered at 20 μg/injection, s.c., twice a day for 5 days/week for 2 weeks beginning 6 days after tumor cell inoculation and LH (43 ± 0.2°C) was given for 30 min twice/week for 2 weeks. Combined therapy prolonged survival of mice and caused significant inhibition of tumor growth, as measured by the volume or size of primary tumor, number and size of lung metastases, and chromatin fragment (CF) formation in tumor bearing mice, while treatment with M-CSF or LH alone had less or no effect. Combined therapy also resulted in increased numbers of splenic T-lymphocytes and the ratio of T-helper/suppressor cells, restoration of natural killer (NK) cell activity, increased numbers of peritoneal macrophages and their erythrophagocytosis capacity, and increased release or production of tumor necrosis factor (TNF)-α, but not interleukin (IL)-1α or IL-6. These results add to previous evidence that M-CSF might be a relevant therapeutic agent in combination with other therapies in the treatment of certain malignant diseases.
|Original language||English (US)|
|Number of pages||14|
|Journal||International Journal of Hematology|
|State||Published - Jan 1 1993|
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