Combined inhibitors of angiogenesis and histone deacetylase: Efficacy in rat hepatoma

Table 1 Extrahepatic tumor burden and side effects in untreated and treated tumor-bearing rats (%)

	Control group (n = 12)	Monotherapy (n = 17)	Combination therapy (n = 24)	P value2
Tumor burden - pulmonary	83.3	82.4	70.8	0.586
Tumor burden - abdominal	91.7	100.0	66.7	0.013
Ascites	83.3	29.4	0.0	< 0.001
Behavior1	41.7	0.0	25.0	0.019
Loss of fur	16.7	41.2	66.7	0.015
Loss of weight (> 10% body weight)	0.0	47.1	79.2	< 0.001
Diarrhea	16.7	29.4	62.5	0.015

¹Reduced food consumption, isolation, stereotypic movements, apathia;

²P values for combined vs single therapy.

Table 2 Histological analysis of the tissue

	Control 1	PTK/ZK	MS-275	PTK/ZK MS-275	PTK/ZK MS-275 TAM cRA
PCNA pos. cell	44.2 ± 12.4	42.7 ± 9.4	43.7± 5.5	35.1 ± 3.6a	23.6 ± 3.8ac
TUNEL pos. cells	6.9 ± 4.4	11.8 ± 6.6a	12.2 ± 7.7a	18.4 ±5.5c	24.8 ± 10bc

^aP < 0.05 vs control 1;

^bP < 0.01 vs control 1;

^cP = 0.01 dual therapy vs quadruple therapy for TdT-mediated dUTP-biotin nick end labeling and proliferating cell nuclear antigen staining. PTK/ZK: PTK787/ZK222584; TAM: Tamoxifen; cRA: 9-cis-retinoic acid; PCNA: Proliferating cell nuclear antigen; TUNEL: TdT-mediated dUTP-biotin nick end labeling.