On-target efficacy of vemurafenib drug-pellet treatment. (A) Representative images of Haematoxylin and Eosin (H&E) and immunofluorescence staining of BRAFV600E zebrafish melanoma samples treated with DMSO or vemurafenib drug pellets. Phospho-Erk1/2 staining in melanoma cells (M) is clearly visible in zoomed regions. Regressing melanomas have reduced phospho-Erk1/2 staining, and the response is varied in vemurafenib-resistant disease. Scale bars: 100 μm. DMSO-treated melanoma sample (week 3; DMSO treatment); melanoma regression sample (week 3; 200 mg/kg vemurafenib treatment); melanoma-resistant tumour A and B (week 10; 5-week 100 mg/kg vemurafenib treatment, followed by 5-week 200 mg/kg vemurafenib treatment). (B,C) Quantification of immunofluorescence staining intensity of phospho-Erk1/2 (B) and total Erk1/2 (C) from BRAFV600E zebrafish melanoma samples treated with DMSO, regressing on vemurafenib drug pellets and resistant to vemurafenib. The DMSO-treated samples were collected after 2 or 3 weeks of treatment (N=4 fish, n=5 lesions). The regressing samples were collected at week 3, 200 mg/kg vemurafenib treatment (N=4 fish, n=5 lesions). The resistant samples were collected at week 10, 5-week 200 mg/kg vemurafenib treatment escalation course following the initial 5-week 100 mg/kg vemurafenib treatment (N=3 fish, n=6 lesions). Data are mean±s.d.; multiple t-test with Sidak–Bonferroni correction. ns, not significant; **P<0.01; ****P<0.0001. Lesions from the same fish are indicated by the same colour.
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