Born Again: A Review of Harry Jaffa\u27s \u3cem\u3eA New Birth of Freedom\u3c/em\u3e and \u3cem\u3eCrisis of the House Divided\u3c/em\u3e

Through the publication of Crisis of the House Divided, Harry Jaffa made a critical contribution to the understanding of Abraham Lincoln, the Civil War, and the transcendent principles of the American regime. In his long-awaited A New Birth of Freedom, Jaffa builds upon his earlier work by expanding the scope of his study beyond the time period immediately preceding the Civil War to include the entire antebellum period in American history. This expansion leads to a thorough analysis of not only Abraham Lincoln but also of such important figures as Thomas Jefferson and John C. Calhoun. The author synthesizes Jaffa\u27s works, thereby enhancing their content by revealing the way in which each benefits from the other while remaining distinct in themselves. In addition, by focusing not only upon the books being reviewed, the author provides valuable insight into Jaffa\u27s own contributions to our understanding of the American regime

Telomerase reverse transcriptase (TERT) promoter mutation correlated with intratumoral heterogeneity in hepatocellular carcinoma.

10.1111/pin.12974Pathol Int709624-63

OATP1B3 expression is strongly associated with Wnt/β-catenin signalling and represents the transporter of gadoxetic acid in hepatocellular carcinoma.

BACKGROUND & AIMS: In the current era of emerging molecular targeted drugs, it is necessary to identify before treatment the specific subclass to which a tumour belongs. Gadoxetic acid is a liver-specific contrast agent that is preferentially taken up by hepatocytes. Therefore, gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) should provide precise molecular information about hepatocellular carcinomas (HCCs). The aim of this study was to investigate the transporters of gadoxetic acid in HCC comprehensively and to analyse the molecular regulatory mechanism of such transporters. METHODS : Expression levels of transporters, transcriptional factors and Wnt target genes in clinical samples were examined by quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry. LiCl treatment of the HCC cell line KYN-2 was conducted in vitro to assess the effects of Wnt signalling activity. RESULTS: Comprehensive analyses of transporter mRNAs and protein expressions revealed that the organic anion transporting polypeptide 1B3 (OATP1B3) had the strongest correlation with tumour enhancement in hepatobiliary-phase images of EOB-MRI. Association analysis with OATP1B3 expression revealed significant correlation with the expression of Wnt/β-catenin target genes. Further, LiCl treatment induced OATP1B3 mRNA expression in KYN-2 cells, indicating a strong association between OATP1B3 expression and Wnt/β-catenin signalling. The sensitivity and specificity to predict Wnt/β-catenin-activated HCC using tumour enhancement in EOB-MRI were 78.9% and 81.7%, respectively. CONCLUSIONS: OATP1B3 was confirmed as the most important transporter mediating HCC enhancement in EOB-MRI. OATP1B3 expression showed a strong association with the expression of Wnt/β-catenin target genes, therefore, OATP1B3-upregulated HCC likely represents a specific subclass of Wnt/β-catenin-activated HCC