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| Digital slide: |
Case 8-1
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| Species: |
Rat |
| Strain/breeder: |
Crl:Wist Han, Charles River Company |
| Sex: |
Male |
| Age: |
Approx. 8 weeks (at start of dosing) |
| Study type: |
26 week oral |
| Treatment: |
Vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors A or B (100 mg/kg/day) |
| Animal status: |
Compound A: Animal emaciated at necropsy after 26 weeks of treatment
Compound B: Animal emaciated and poor general condition of the animal at necropsy after 26 weeks of treatment |
| Clinical findings: |
Compounds A or B : Broken/discolored teeth, reduced body weight gain and reduced food intake; increased white blood counts from week 4 onwards; increased levels of serum urea, creatinine and urine electrolytes as well as decreased creatinine clearance from week 14 onwards
Compound B: In addition, presence of leucocytes in the urine as well as increased volume and decreased specific gravity of the urine |
| Organ(s): |
Kidneys (Compounds A or B) |
Gross
finding(s): |
Compound A: Nothing abnormal detected
Compound B: Granulated surface of the kidneys with several yellow foci |
| Staining: |
H&E |
| Literature: |
| Matter A (2001) Tumor angiogenesis as a therapeutic target. DDT 6: 105-1024 | | Wood JM et al. (2000) PTK787/ZK222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Research 60: 2178-2189 |
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