Clinical features and mutation status of EGFR, KRAS, BRAF, EML4-ALK and ROS1 between surgical resection samples and non surgical resection samples in lung cancer.

BACKGROUND: Target therapy is the first-line treatment in lung cancer. The testing of driver gene mutations is crucial for decision of treatment. Many lung cancer patients are in advanced grade, and lose the chance of operation. METHODS: The tissue used to perform mutation testing is only from biopsy. In order to analysis the difference between surgical resection samples (SRSs) and non-surgical resection samples (NSRSs), 1,357 surgical tissues and 145 biopsy samples histopathologically diagnosed with lung cancer were collected to detect the mutation status of EGFR, KRAS, BRAF, EML4-ALK and ROS1 in this study. RESULTS: There were no significant differences of age, gender, and histological type between the two group patients we collected; however, the significant difference was present in grade. More early stage patients were in the surgical group, but more advanced stage lung cancer patients were in non surgical group. In the mutation analysis, we also found no significant differences in all driver genes we detected between the two groups. CONCLUSIONS: Both surgical resection samples and biopsy samples could be used to perform the testing the driver gene mutation.

Rat hepatocyte culture model of macrosteatosis: effect of macrosteatosis induction and reversal on viability and liver-specific function.

BACKGROUND & AIMS: A common cause of liver donor ineligibility is macrosteatosis. Recovery of such livers could enhance donor availability. Living donor studies have shown diet-induced reduction of macrosteatosis enables transplantation. However, cadaveric liver macrosteatotic reduction must be performed ex vivo within hours. Towards this goal, we investigated the effect of accelerated macrosteatosis reduction on hepatocyte viability and function using a novel system of macrosteatotic hepatocytes. METHODS: Hepatocytes isolated from lean Zucker rats were cultured in a collagen sandwich, incubated for 6 days in fatty acid-supplemented medium to induce steatosis, and then switched for 2 days to medium supplemented with lipid metabolism promoting agents. Intracellular lipid droplet size distribution and triglyceride, viability, albumin and urea secretion, and bile canalicular function were measured. RESULTS: Fatty acid-supplemented medium induced microsteatosis in 3 days and macrosteatosis in 6 days, the latter evidenced by large lipid droplets dislocating the nucleus to the cell periphery. Macrosteatosis significantly impaired all functions tested. Macrosteatosis decreased upon returning hepatocytes to standard medium, and the rate of decrease was 4-fold faster with supplemented agents, yielding 80% reduction in 2 days. Viability of macrosteatosis reduced hepatocytes was similar to control lean cells. Accelerated macrosteatotic reduction led to faster recovery of urea secretion and bile canalicular function, but not of albumin secretion. CONCLUSIONS: Macrosteatosis reversibly decreases hepatocyte function and supplementary agents accelerate macrosteatosis reduction and some functional restoration with no effect on viability. This in vitro model may be useful to screen agents for macrosteatotic reduction in livers before transplantation.