Figure 7.

Inactivation of Met results in the sustained regression of HCC. (a and b) Doxycycline dramatically reduces tumor burden within 1 mo. A moribund tumor-bearing mouse (lower) with enlarged abdomen before doxycycline treatment and the control littermate (upper; panel a). Substantial shrinkage of the tumor was evident after 1-mo treatment with doxycycline (b). (c–f) Gross pathology of HCC regression. Moribund tumor-bearing mice together with their wild-type littermates received doxycycline in their diet. Normal adult liver (c), HCC-containing liver before doxycycline treatment (d), HCC-containing liver after 20 d of doxycycline treatment (e), and liver of a previously HCC-bearing mouse after 4 mo of doxycycline treatment (f). The white arrows indicate normal liver tissue and black arrows point to the involuting residual mass. (g–j) Histology of liver with regressed tumors. Light microscopy of hematoxylin and eosin–stained liver sections from a previously tumor-bearing mouse treated for 4 mo with doxycycline. The majority of liver appeared normal (g), although a residual nodule was evident (h–j). The center of the residual mass was composed mainly of necrotic and calcified tissues (h). The border of normal liver (upper) and the involuted residue (lower) is marked by the white arrowheads in panel i. The border at higher magnification showed extensive infiltration of inflammatory cells (j). The arrows point to neutrophils and the arrowheads point to brown pigmented macrophages.