Table III:
Histological evidence of toxicity in mice following dose-escalation of sorafenib (S), quinacrine (Q), S/Q and doxorubicin.
| Organ/tissue | Vehicle (V) | Quinacrine (Q) | Sorafenib (S) | Q/S | Doxorubicin |
|---|---|---|---|---|---|
| Bone marrowa, ** | 0/5 (0) | 0/4 (0) | 0/5 (0) | 0/5 (0) | 3/5 (0.60) |
| GIb, ** | 0/5 (0) | 0/4 (0) | 0/5 (0) | 0/5 (0) | 4/5 (0.80) |
| Heartc | 2/5 (0.40) | 1/5 (0.20) | 0/5 (0) | 1/5 (0.20) | 0/5 (0) |
| Pancreas d, ** | 0/5 (0) | 0/4 (0) | 5/5 (1.00) | 4/5 (0.80) | 4/5 (0.80) |
| Liver | |||||
| Vaculation | 2/5 (0.40) | 3/4 (0.75) | 4/5 (0.80) | 4/5 (0.80) | 4/5 (0.80) |
| Glycogene | 2/5 (0.40) | 3/4 (0.75) | 4/5 (0.80) | 2/5 (0.40) | 3/5 (0.60) |
| Hydropic degeneration with basophilic stippling, centrilobular | 0/5 (0) | 2/4 (0.50) | 0/5 (0) | 2/5 (0.40) | 0/5 (0) |
| Lipid, centrilobular | 0/5 (0) | 0/5 (0) | 0/5 (0) | 0/5 (0) | 1/5 (0.20) |
| Kupffer cell hyperplasia, centrilobular | 0/5 (0) | 0/5 (0) | 0/5 (0) | 0/5 (0) | 1/5 (0.20) |
| Hepatocyte apoptosis, centrilobular | 0/5 (0) | 0/5 (0) | 0/5 (0) | 0/5 (0) | 1/5 (0.20) |
| Kidneyf | 0/5 (0) | 0/5 (0) | 0/5 (0) | 2/5 (0.40) | 0/4 (0) |
Characterized by the appearance of prominent congested sinusoids
Characterized by the appearance of villous blunting, crypt dilation, crypt hyperplasia, crypt abscesses and inflammation of lamina propria.
Characterized in (V) by one case of focal segmental medial mineralization in a small mural coronary artery and one case of mineralized necrotic cardiomyocytes affecting <0.1% of the myocardium. In (Q), one case characterized by a nodule of large macrophages and few mast cells between the left ventricle and atrium. In (Q/S), one case displayed several mineralized necrotic cardiomyocytes affecting <0.1% of the myocardium.
Characterized by the appearance of serositis of the pancreatic capsule; subacute or chronic, mild to moderate; necrotizing pancreatitis, subacute, minimal to moderate. This finding may be a result of the intra-peritoneal injection route of drug administration.
Diffuse, centrilobular, midzonal or peri-portal.
Characterized by the appearance of one (1) small focal chronic cortical infarct with a volume of <0.01%.
P<0.05 (Chi-square test).
P<0.01 (Chi-square test).