Human PLAU/uPA ELISA Kit

BackgroundDetecting small nodules that are grossly unidentifiable remains a major challenge in liver resection for cancer. Novel developments in navigation surgery, especially indocyanine green (ICG)-based fluorescence imaging, are making a clear breakthrough in addressing this issue. ICG is almost routinely administered during the preoperative stage in hepatobiliary surgery. However, its full potential has yet to be realized, partly because there are no precise guidelines regarding the optimal dose or timing of ICG injections before liver surgery. The main goal of this study was to design an algorithm for the management of ICG injections to achieve optimal liver staining results.MethodsTwenty-seven consecutive, unselected patients undergoing liver resection for cancer were enrolled and underwent preoperative liver function assessment by the LiMON test. Extra ICG i.v. injections at different doses and timings were performed. In vivo intraoperative analysis of the stain detected by near-infrared fluorescence imaging of the liver and ex vivo analysis of each resected nodule was performed and compared to the pathological analysis.Results(i) The success rate of ICG injections in terms of liver staining was 92.6%; (ii) in the absence of or with 7 or more days from a previous ICG injection, the best dose to inject before the operation was 0.2mg/kg, and the best timing was between 24 and 48h before the scheduled surgery; and (iii) the ICG fluorescence patterns observed in the tumors were total fluorescence staining (41% of the cases), partial fluorescence staining (15%), rim fluorescence staining surrounding the tumor (30%), and no staining (15%).ConclusionsThis study is a building block for the characterization of liver nodules and the search for additional surface lesions undetected by preoperative radiological work-upa crucial task for the successful treatment of liver cancer at an early stage using a safe, minimally invasive, and inexpensive technique.

BACKGROUND & AIMS: Hepatitis C virus (HCV) co-opts the very-low-density lipoprotein pathway for morphogenesis, maturation, and secretion, and circulates as lipoviroparticles (LVPs). We investigated the functions and underlying mechanisms of the lipid-associated TM6SF2 protein in modulating LVP formation and the HCV life cycle. METHODS: We knocked down or overexpressed TM6SF2 in hepatic cells and examined HCV infection, measuring viral RNA and protein levels and infectious LVP titers. The density of secreted LVPs was evaluated by iodixanol gradient assay. We measured levels and patterns of TM6SF2 in liver biopsies from 73 patients with chronic hepatitis C, livers of HCV-infected humanized Alb-uPA/SCID/beige mice, and HCV-infected Huh7.5.1 cells. RESULTS: TM6SF2 knockdown in hepatocytes reduced viral RNA and infectious viral particle secretion without affecting HCV genome replication, translation, or assembly. Overexpression of TM6SF2 reduced intracellular levels of HCV RNA and infectious LVPs, and conversely increased their levels in the culture supernatants. In HCV-infected cells, TM6SF2 overexpression resulted in production of more infectious LVPs in the lower-density fractions of supernatant. HCV infection increased TM6SF2 expression in cultured cells, humanized livers of mice, and liver tissues of HCV patients. TM6SF2 messenger RNA levels correlated positively with HCV RNA levels in liver biopsies from patients. SREBF2 appears to mediate the ability of HCV to increase the expression of TM6SF2 in hepatic cells. CONCLUSIONS: In studies of cells, mice and human liver tissues, we found TM6SF2 is required for maturation, lipidation, and secretion of infectious LVPs. HCV, in turn, up-regulates expression of TM6SF2 to facilitate productive infection.