-GlcNAc transferase acts as a critical nutritional node for the control of liver homeostasis.

Background & Aims: -GlcNAcylation is a reversible post-translational modification controlled by the activity of two enzymes, -GlcNAc transferase (OGT) and -GlcNAcase (OGA). In the liver, -GlcNAcylation has emerged as an important regulatory mechanism underlying normal liver physiology and metabolic disease.

Methods: To address whether OGT acts as a critical hepatic nutritional node, mice with a constitutive hepatocyte-specific deletion of OGT (OGT) were generated and challenged with different carbohydrate- and lipid-containing diets.

In Vitro Cell Toxicity and Intracellular Uptake of Doxorubicin Exposed as a Solution or Liposomes: Implications for Treatment of Hepatocellular Carcinoma.

Cytostatic effects of doxorubicin in clinically applied doses are often inadequate and limited by systemic toxicity. The main objective of this in vitro study was to determine the anti-tumoral effect (IC) and intracellular accumulation of free and liposomal doxorubicin (DOX) in four human cancer cell lines (HepG2, Huh7, SNU449 and MCF7). The results of this study showed a correlation between longer DOX exposure time and lower IC values, which can be attributed to an increased cellular uptake and intracellular exposure of DOX, ultimately leading to cell death.

Exploring the Role of Endoplasmic Reticulum Stress in Hepatocellular Carcinoma through mining of the Human Protein Atlas.

Endoplasmic reticulum (ER) stress and actors of unfolded protein response (UPR) have emerged as key hallmarks of hepatocarcinogenesis. Numerous reports have shown that the main actors in the UPR pathways are upregulated in HCC and contribute to the different facets of tumor initiation and disease progression. Furthermore, ER-stress inducers and inhibitors have shown success in preclinical HCC models.

Targeting ER stress in the hepatic tumor microenvironment.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. It currently ranks as one of the most aggressive and deadly cancers worldwide, with an increasing mortality rate and limited treatment options. An important hallmark of liver pathologies, such as liver fibrosis and HCC, is the accumulation of misfolded and unfolded proteins in the lumen of the endoplasmic reticulum (ER), which induces ER stress and leads to the activation of the unfolded protein response (UPR).

Activated platelets contribute to the progression of hepatocellular carcinoma by altering the tumor environment.

Aim: Hepatocellular carcinoma (HCC) is a primary liver cancer that usually develops in a background of chronic liver disease and prolonged inflammation. A major contributor in the complex molecular pathogenesis of HCC is the highly intertwined cross-talk between the tumor and the surrounding stromal cells, such as hepatic stellate cells, endothelial cells, macrophages and other immune cells. These tumor-stroma interactions actively fuel tumor growth and modulate the hepatic microenvironment to benefit tumor invasion and disease progression.

Inhibiting P2Y12 in Macrophages Induces Endoplasmic Reticulum Stress and Promotes an Anti-Tumoral Phenotype.

The P2Y12 receptor is an adenosine diphosphate responsive G protein-coupled receptor expressed on the surface of platelets and is the pharmacologic target of several anti-thrombotic agents. In this study, we use liver samples from mice with cirrhosis and hepatocellular carcinoma to show that P2Y12 is expressed by macrophages in the liver. Using in vitro methods, we show that inhibition of P2Y12 with ticagrelor enhances tumor cell phagocytosis by macrophages and induces an anti-tumoral phenotype.

Inhibiting IRE1α-endonuclease activity decreases tumor burden in a mouse model for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a liver tumor that usually arises in patients with cirrhosis. Hepatic stellate cells are key players in the progression of HCC, as they create a fibrotic micro-environment and produce growth factors and cytokines that enhance tumor cell proliferation and migration. We assessed the role of endoplasmic reticulum (ER) stress in the cross-talk between stellate cells and HCC cells.

A Biomimetic Model for Liver Cancer to Study Tumor-Stroma Interactions in a 3D Environment with Tunable Bio-Physical Properties.

Hepatocellular carcinoma (HCC) is a primary liver tumor developing in the wake of chronic liver disease. Chronic liver disease and inflammation leads to a fibrotic environment actively supporting and driving hepatocarcinogenesis. Insight into hepatocarcinogenesis in terms of the interplay between the tumor stroma micro-environment and tumor cells is thus of considerable importance.

Fibrin fragment E potentiates TGF-β-induced myofibroblast activation and recruitment.

Fibrin is an essential constituent of the coagulation cascade, and the formation of hemostatic fibrin clots is central to wound healing. Fibrin clots are over time degraded into fibrin degradation products as the injured tissue is replaced by granulation tissue. Our goal was to study the role of the fibrin degradation product fragment E (FnE) in fibroblast activation and migration.

Liver Cancer Cell Lines Treated with Doxorubicin under Normoxia and Hypoxia: Cell Viability and Oncologic Protein Profile.

Hepatocellular carcinoma is often treated with a combination of doxorubicin and embolization, exposing it to high concentrations and hypoxia. Separation of the possible synergistic effect of this combination in vivo is difficult. Here, treatment with doxorubicin, under hypoxia or normoxia in different liver cancer cell lines, was evaluated.

Platelets as Key Factors in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a primary liver cancer that usually develops in the setting of chronic inflammation and liver damage. The hepatic microenvironment plays a crucial role in the disease development, as players such as hepatic stellate cells, resident liver macrophages (Kupffer cells), endothelial cells, extracellular matrix, and a variety of immune cells interact in highly complex and intertwined signaling pathways. A key factor in these cross-talks are platelets, whose role in cancer has gained growing evidence in recent years.

Anti-Stokes contribution to the SBS Stokes gain in remotely seeded bidirectional NG-PON systems.

We assess the importance of Stimulated Brillouin scattering (SBS) anti-Stokes wave on reflection tolerance in remotely seeded wavelength-division multiplexing passive optical networks (WDM PON). Experimental validation of the extended model for the externally seeded SBS is presented towards assessing the conditions in which the anti-Stokes contribution becomes relevant in the variant scenario of remotely carrier-seeded PON. We identify relevant operating conditions in which the latter can no longer be reliably neglected, and analyze the remote seed power budget implications of such contribution.