Fig. 3. Evidence that long acting anti-angiogenic drugs render tumors refractory to subsequent anti-angiogenic ASMase-mediated tumor sensitization. A. 1x106 MCA/129 fibrosarcoma cells were implanted into the right flank of sv129/BI6JAX mice and tumor volume was measured daily according to the formula of Kim et. al. When tumors reached an average of 100mm3, mice were treated with gemcitabine 240 mg/ kg i.p. twice at 4 day intervals (black arrows). Some mice received DC101 (1600 μg/mouse = full dose) at 8h and/or 1h before each gemcitabine treatment, as indicated. Data (meanąSEM) are collated from 5 mice/group (p<0.01 -8h & -1h DC101+Gem vs. -1h DC101+Gem). B. These data depict the individual tumor response profiles collated in A.