Type I insulin-like growth factor as a liver reserve assessment tool in hepatocellular carcinoma

Reham Abdel-Wahab,1,2 Samir Shehata,2 Manal M Hassan,1 Mouhammed A Habra,3 Ghazaleh Eskandari,4 Peggy T Tinkey,5 Jennifer Mitchell,5 Ju-Seog Lee,6 Hesham M Amin,4,7 Ahmed O Kaseb11Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Clinical Oncology, Assiut University Hospital, Assiut, Egypt; 3Department of Endocrinology, 4Department of Hematopathology, 5Department of Veterinary Medicine and Surgery, 6Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 7Graduate School of Biomedical Sciences, Houston, TX, USAAbstract: Chronic liver diseases (CLDs) encompass a wide range of illnesses, including nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and viral hepatitis. Deterioration of liver capacity, with subsequent progression into cirrhosis and hepatocellular carcinoma (HCC), ultimately leads to a further decrease in the hepatic reserve. The Child–Turcotte–Pugh scoring system is the standard tool for assessing underlying liver reserve capacity in routine practice and in clinical trials of CLD and HCC. In this review, we highlight the clinical significance of insulin-like growth factor-I (IGF-I) and the growth hormone (GH) signaling pathway in HCC. IGF-I could be a marker for liver reserve capacity in CLDs and HCC in clinical practice. This approach could improve the risk assessment and stratifications of patients on the basis of their underlying liver reserve, either before active treatment in routine practice or before they are enrolled in clinical trials.Keywords: IGF-I, growth hormone, chronic liver diseas

A new experimental rat model of osteosarcoma established by intrafemoral tumor cell inoculation, useful for biology and therapy investigations

Satisfactory experimental models for preclinical cancer studies must follow several criteria: (1) reproducibility of the method used to induce the tumor and (2) clinical, pathological and kinetic similarity with the corresponding human tumors. We developed a model of osteosarcoma locally induced by the intrafemoral injection of osteosarcoma (OSR) cells in Sprague-Dawley rats. This method yields nearly 80% of bone tumors at the injection site. These tumors double their volume fairly slowly (in approximately 20 days) and lung metastases occur in 96% of the animals. The OSR cell-induced tumor is characterized by a direct production of mineralized matrix by the tumor cells themselves, as revealed by histochemical analysis. The microarchitectural parameters which were quantified by a microscanner show an increased trabecular bone volume (+238%) when OSR cells were injected in the femur, as compared to controls injected with vehicle. Osteoblastic markers such as alkaline phosphatase, osteopontin, osteocalcin and bone sialoprotein were expressed by the tumor in vivo, whereas the initially injected OSR cells did not express some of these markers, suggesting that OSR cells reacquired an osteoblastic phenotype in a favorable environment. The clinical, radiological and histological data show that this model shares high similarities with the osteocondensing forms of osteosarcoma in humans