Previous studies from our laboratory have demonstrated that particulate
glucan is efficacious in the
therapy of a syngeneic murine
reticulum cell sarcoma (M5706), which specifically metastasizes from its primary site to the liver. The present study was undertaken to examine the therapeutic efficacy of a newly developed soluble
glucan, in combination with
cyclophosphamide in the treatment of hepatic metastatic disease. Male C57Bl/6J mice were injected subcutaneously on Day 0 with 1 x 10(4)
sarcoma cells.
Glucan (200 mg per kg i.v.),
cyclophosphamide (45 mg per kg i.p.) or
glucan and
cyclophosphamide were administered beginning on Day 20, when hepatic
metastases were evident, and continued at 3-day intervals up to Day 50. Combined
therapy with
glucan and
cyclophosphamide resulted in reduction of hepatic metastatic lesions on Day 36, compared to control. Survival data revealed that the combination of
glucan and
cyclophosphamide significantly (p less than 0.001) extended median survival time and the time to 100% mortality in an additive fashion, when compared to either
therapy alone.
Glucan-
cyclophosphamide therapy was also effective in decreasing primary
tumor weight to a level that was significantly (p less than 0.05) less than when
therapy was initiated. In vitro studies revealed that Kupffer cell tumoricidal activity against
sarcoma was increased (p less than 0.05) following
glucan and
cyclophosphamide.
Glucan and
cyclophosphamide also enhanced bone marrow proliferation and splenocyte response to
mitogens in vitro. Additionally,
glucan was observed to exert a direct
cytostatic effect on
sarcoma in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)