ISSN:
1573-7209
Keywords:
Anti-tumor action
;
complement
;
cytokines
;
endothelial cells
;
immunohistochemistry
;
polysaccharide
;
RT-PCR
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Group B streptococcus (GBS) isolated from human neonates diagnosed with sepsis and respiratory distress produces a polysaccharide exotoxin (CM101) which has been previously described as GBS toxin. CM101 infused i.v. into tumor-bearing mice causes rapid tumor neovascularitis, infiltration of inflammatory cells, inhibition of tumor growth and tumor apoptosis. CM101 has successfully completed phase I studies in refractory cancer patients with very encouraging results. We have now demonstrated a mechanism of action for CM101. Using a normal mouse tumor model, we have examined tumor and normal tissues which were harvested at 0, 5, 15, 30 and 60 min post-infusion of either CM101 or dextran. We present evidence that CM101 is rapidly (within the first 5 min) bound to the tumor neovasculature. Complement is activated by the alternative pathway (C3) and leukocytes start to infiltrate the tumor within the first 5 min. Through RT-PCR and immunohistochemical techniques, we demonstrate that proinflammatory cytokines, interleukin-6 and tumor necrosis factor (TNF)-α, are up-regulated in infiltrating leukocytes and TNF receptor 2 is up-regulated in the targeted tumor neovasculature. Combined, these events constitute possible explanations for the observed pathophysiology of tumor ablation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1009258801899
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