Thus, in these two situations

immunodeficiency impairs clearance of senescent cell, contributing to the accumulation of oncogene-induced selleck products preneoplastic cells. Interestingly, cirrhosis patients with impaired liver function also have a well-known immune deficiency that could overcome OIS and promote tumor initiation. In parallel, the high rate of hepatocyte death and senescence observed in advanced cirrhosis could induce a compensative proliferation of liver stem cells or surviving hepatocytes that accumulate genetic alterations and promote HCC formation. In this line, studies of a large cohort of cirrhosis patients should focus on the prevalence of senescence markers in liver biopsy in order to further elucidate its link with HCC development. Finally, HRAS mutations, like other mutations of the RAS family, are very rare events in human hepatocarcinogenesis.9 Consequently, the work of Zender and collaborators could open new hypotheses on the role of OIS in the prevention of liver tumor initiation induced by frequent oncogene activation, such as activating mutations of β-catenin. To conclude, this elegant work enriches the interaction between immunity, inflammation, and initiation of liver

tumorogenesis. It supports the crucial role of the immune system as a guardian against oncogene-driven find more tumorigenesis. We thank Isabelle Desitter for critical reading of the article. “
“Hepatectomy is a standard therapy that allows liver cancer patients to achieve long-term survival. Preceding hepatectomy, portal vein embolization (PVE) is frequently performed to increase the remnant liver size and reduce complications. Although the clinical importance of PVE is widely accepted, molecular mechanisms by which PVE leads to compensatory

hypertrophy of nonembolized lobes remain elusive. We hypothesized that NF-E2-related factor 2 (Nrf2), a master regulator of cytoprotection, 上海皓元 promotes compensatory liver hypertrophy after PVE. To address this hypothesis, we utilized three mouse lines and the portal vein branch ligation (PVBL) technique, which primarily induces the redistribution of the portal bloodstream in liver in a manner similar to PVE. PVBL was conducted in Kelch-like ECH-associated protein 1 (Keap1) conditional knockout (Keap1-CKO) mice in which Nrf2 is constitutively activated, along with Nrf2-deficient (Nrf2-KO) mice. We found that hypertrophy of nonligated lobes after PVBL was enhanced and limited in Keap1-CKO and Nrf2-KO mice, respectively, compared to wild-type mice. In Keap1-CKO mice, Nrf2 activity was increased, consistent with transient activation of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway, and reactive hepatocyte proliferation was significantly prolonged after PVBL.