This Tutorial Review summarizes recent examples of electrophilic activation of allenes with particular focus on analogies and differences between Lewis and Brønsted acid activation of these versatile ...substrates. The aim of this article is to present a general overview of the possibilities offered to chemists using complementary modes of catalysis and to emphasize advantages and limitations of each approach, thereby providing a means to expand the scope of this powerful synthetic methodology.
This review focuses on electrophilic activation of allenes by an acid. Key mechanistic features are presented together with recent synthetic applications.
Worldwide epidemics of metabolic diseases, including liver steatosis, are associated with an increased frequency of malignancies, showing the highest positive correlation for liver cancer. The ...heterogeneity of liver cancer represents a clinical challenge. In liver, the transcription factor PPARgamma promotes metabolic adaptations of lipogenesis and aerobic glycolysis under the control of Akt2 activity, but the role of PPARgamma in liver tumorigenesis is unknown. Here we have combined preclinical mouse models of liver cancer and genetic studies of a human liver biopsy atlas with the aim of identifying putative therapeutic targets in the context of liver steatosis and cancer. We have revealed a protumoral interaction of Akt2 signaling with hepatocyte nuclear factor 1alpha (HNF1alpha) and PPARgamma, transcription factors that are master regulators of hepatocyte and adipocyte differentiation, respectively. Akt2 phosphorylates and inhibits HNF1alpha, thus relievingthe suppression of hepatic PPARgamma expression and promoting tumorigenesis. Finally, we observed that pharmacological inhibition of PPARgamma is therapeutically effective in a preclinical murine model of steatosis-associated liver cancer. Taken together, our studies in humans and mice reveal that Akt2 controls hepatic tumorigenesis through crosstalk between HNF1alpha and PPARgamma.
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