Notch pathway inhibition affects lung metastasis. A and B, a large tumor filled the entire eye 3 weeks after intravitreal injection of OCM1 cells treated with vehicle (DMSO), whereas only microscopic disease was present in most eyes receiving MRK003 at the time of xenograft initiation (original magnification 40× for both panels). C and D, higher magnification views showing solid sheets of melanoma cells in control eyes, but only focal tumor growth (D, arrows) following local MRK003 treatment (original magnification 400×). E, intraocular xenograft area was significantly reduced (P = 0.04) by combined local and systemic MRK003 treatment, whereas the changes in tumors treated locally alone was not significant. F and G, multiple melanoma metastases were identified in the lungs of 2 of 10 control animals (F, arrows), but none in the 20 mice treated with MRK003 (G, original magnification 200×). H and I, the metastatic tumor nodules were composed of cells with enlarged nuclei and prominent nucleoli (asterisks) as compared with normal adjacent bronchial cells (arrows, original magnification 1,000×). Immunostains for the MITF were positive in tumor cells (I).