PURPOSE: Induction of apoptosis is a key factor in the response of @entity5 to chemotherapy. Laboratory studies have established many of the factors that regulate and execute apoptosis, but the significance of these in @entity1 @entity5 is poorly understood. Therefore, the relationship between key components of this machinery was examined in primary @entity1 @entity0 before and 24 h after the initiation of chemotherapy. EXPERIMENTAL DESIGN: Apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated nick end labeling assay, and proliferation was assessed using the anti-Ki67 antibody @entity1758 . Monospecific polyclonal antibodies were used for immunohistochemical detection of @entity588 , @entity589 , @entity9846 , activated (cleaved) @entity522 and 6, and cleaved @entity13779 ( @entity13779 ) using paraffin-embedded tissues. RESULTS: Before treatment, a significant correlation was found between apoptosis and proliferation (r = 0.64, P < 0.0001), between caspases 3 and 6 (r = 0.49, P = 0.004) and between cleaved @entity13779 and active caspases 3 (r = 0.66, P < 0.0001) or 6 (r = 0.47, P = 0.006). Before treatment, expression of inhibitor of apoptosis protein, @entity9846 , also correlated positively with cleaved @entity522 (r = 0.64, P < 0.0001), @entity8293 (r = 0.36, P = 0.04), and @entity13779 (r = 0.61, P = 0.0001). At 24 h after chemotherapy, significant increases in apoptosis and decreases in proliferation were observed, with the degree of increase in apoptosis inversely associated with decrease in proliferation. Chemotherapy-induced increases in @entity589 were correlated with increases in cleaved @entity13779 (r = 0.54, P = 0.0008), but no other variables showed significant change at 24 h after initiation of chemotherapy. CONCLUSION: The pretreatment biomarker relationships suggest parallel cleavage and activation of these executioner proteins in @entity0 and that @entity9846 may maintain cell survival in the face of caspase activation. The findings provide in vivo evidence in @entity1 @entity0 that chemotherapy induces an apoptotic program characterized by up-regulation of @entity589 and cleavage of caspase substrate @entity13779 .

Coordinate expression of apoptosis-associated proteins in @entity1 XXXX before and during chemotherapy.

@entity1 :: ('9606', 'Species') :: ['human'] @entity589 :: ('581', 'Gene') :: ['Bax'] @entity588 :: ('596', 'Gene') :: ['Bcl-2'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer', 'breast carcinomas'] @entity9846 :: ('331', 'Gene') :: ['XIAP'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumors'] @entity522 :: ('836', 'Gene') :: ['caspase 3'] @entity13779 :: ('1677', 'Gene') :: ['DNA Fragmentation Factor-40', 'DFF40'] @entity1758 :: ('57534', 'Gene') :: ['MIB-1'] @entity8293 :: ('839', 'Gene') :: ['caspase 6']
@entity0 :: (MESH:D001943,Disease) :: ['breast cancer']
