A combined biomarker panel shows improved sensitivity for the early detection of ovarian cancer allowing the identification of the most aggressive Type II tumours.

Background: There is an urgent need for biomarkers for the early detection of ovarian cancer (OC). The purpose of this study was to assess whether changes in serum levels of lecithin-cholesterol acyltransferase (LCAT), sex hormone-binding globulin (SHBG), glucoseregulated protein, 78 kDa (GRP78), calprotectin and insulin-like growth factor-binding protein 2 (IGFBP2) are observed before clinical presentation and to assess the performance of these markers alone and in combination with CA125 for early detection. Methods: This nested case–control study used samples from the United Kingdom Collaborative Trial of Ovarian Cancer Screening trial. The sample set consisted of 482 serum samples from 49 OC subjects and 31 controls, with serial samples spanning up to 7 years pre-diagnosis. The set was divided into the following: (I) a discovery set, which included all women with only two samples from each woman, the first ato14 months and the second at 432 months to diagnosis; and (ii) a corroboration set, which included all the serial samples from the same women spanning the 7-year period. Lecithin-cholesterol acyltransferase, SHBG, GRP78, calprotectin and IGFBP2 were measured using ELISA. The performance of the markers to detect cancers pre-diagnosis was assessed. Results: A combined threshold model IGFBP2 478.5 ng ml 1 : LCAT o8.831 mg ml 1 : CA125 435 Uml 1 outperformed CA125 alone for the earlier detection of OC. The threshold model was able to identify the most aggressive Type II cancers. In addition, it increased the lead time by 5–6 months and identified 26% of Type I subjects and 13% of Type II subjects that were not identified by CA125 alone. Conclusions: Combined biomarker panels (IGFBP2, LCAT and CA125) outperformed CA125 up to 3 years pre-diagnosis, identifying cancers missed by CA125, providing increased diagnostic lead times for Type I and Type II OC. The model identified more aggressive Type II cancers, with women crossing the threshold dying earlier, indicating that these markers can improve on the sensitivity of CA125 alone for the early detection of OC

Influence of murine hepatitis induced by D-(+)-galactosamine hydrochloride and lipopolysaccharide on gene expression of polyethylenimine/plasmid DNA polyplex

We investigated the influence of murine hepatitis induced by D-(+)-galactosamine and lipopolysaccharide (DGalN/LPS) on polyethylenimine (PEI)-mediated plasmid DNA (pDNA) delivery. pDNA encoding firefly luciferase was used as the model reporter gene. PEI was used as the non-viral vector because of its high gene expression and low toxicity. The activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice indicated the highest peaks at 12 h after D-GalN/LPS injection, then the activities of serum ALT and AST rapidly decreased. We determined luciferase activity in various organs of D-GalN/LPS-treated mice and control mice after an intravenous administration of PEI/pDNA complexes. High transgene expression was observed in the liver, spleen, and lung of both mice. Compared to the control mice, a significant increase of transgene expression was observed in the liver of D-GalN/LPS-treated mice after D-GalN/LPS injection. The transgene expression in the spleen and lung decreased at 6 and 12 h after D-GalN/LPS injection. In conclusion, we found that murine hepatitis induced by D-GalN/LPS injection can influence PEI-mediated pDNA delivery and its influence was different from that induced by CCl4 injection which was reported previously. These results demonstrated the necessity of considering the timing and dose of gene therapy according to the disease and its stage