Male NOD/SCID/IL-2Rgnull mice more efficiently support human HCC progression than syngeneic female mice. (Top panels) HCC tumors grow faster and have a higher volume in male than female NSG recipients. PLC/PRF-5 and SNU-387 derived from female patients and HepG2, HUH7, SNU-475, and a primary HCC derived from male patients (105 cells/20μL) were injected orthotopically in the subsera of the liver of 8-week-old male and female NSG mice. (A) HUH7 tumor growth was monitored by weekly detection of human α-fetoprotein (AFP) secreted specifically by tumor cells in the plasma by a chemoluminescent particles immunoassay (CMIA) and analyzed in an ARCHITECT optical system (Abbott Laboratories). Results are mean ± SD (female n = 10, males n = 15). (B) Human AFP levels at sacrifice reveals that hepatic tumors are larger in all HCC cells lines tested and in a primary HCC culture. SNU-387 and SNU-475 were found to be not tumorigenic in this animal model. (Bottom panels) Ventral views of the orthotopic TGL-HUH7 tumor model. Tumor progression was followed using the IVIS Imaging System (Xenogen) weekly. A strong statistical association between mean bioluminescence and plasma AFP (in mg/mL) was found (R2 = 0.914).