Issues

The cover features a micropictogram (80X magnification) of H & E staining of a paraffin-embedded liver section of a mouse that received metformin to reduce or prevent hepatocellular carcinogenesis. Metformin (given as 250 mg/kg of body weight in chow) inhibited hepatocellular carcinogenesis induced by the liver-specific carcinogen diethylnitrosamine (DEN) in C57BL/6J mice. Mice injected with DEN at 2 weeks of age were put on metformin or control chow after weaning. At 24 or 36 weeks post-DEN treatment, livertumor multiplicity and size were reduced significantly in metformin-fed versus control-fed mice. Representative H & E sections indicate that the pathology of tumors in metformin-fed (featured on the cover) and controlfed mice (not shown) were similar, despite the decrease in tumor formation. In the cover image, the prominent oval shape at the bottom is a blood vessel in the portal tract (with additional vascular spaces below it). Just above and left of this vessel, a hepatocellular tumor appears as a circular cluster of larger cells with enlarged nuclei and somewhat more basophilic cytoplasm. See articles by Bhalla et al. (beginning on page 544) and by Pollak and Gonzalez-Angulo (beginning on page 500) for more information.