Enhancing bevacizumab efficacy in a colorectal tumor mice model using dextran-coated albumin nanoparticles.

Bevacizumab is a monoclonal antibody (mAb) that prevents the growth of new blood vessels and is currently employed in the treatment of colorectal cancer (CRC). However, like other mAb, bevacizumab shows a limited penetration in the tumors, hampering their effectiveness and inducing adverse reactions. The aim of this work was to design and evaluate albumin-based nanoparticles, coated with dextran, as carriers for bevacizumab in order to promote its accumulation in the tumor and, thus, improve its antiangiogenic activity.

MicroRNA-506 promotes primary biliary cholangitis-like features in cholangiocytes and immune activation.

Unlabelled: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena targeting intrahepatic bile duct cells (cholangiocytes). Although its etiopathogenesis remains obscure, development of antimitochondrial autoantibodies against pyruvate dehydrogenase complex E2 is a common feature. MicroRNA (miR) dysregulation occurs in liver and immune cells of PBC patients, but its functional relevance is largely unknown.

The challenge of targeting cancer stem cells to halt metastasis.

Despite a continuing debate about the existence of cancer stem cells (CSCs), recent discoveries have provided further support for their existence and their roles in drug resistance, cancer recurrence and metastasis. CSC characteristics, such as self-renewal and tumour initiation, and supporting cellular processes, particularly the epithelial-to-mesenchymal transition, are attracting a great deal of attention from cancer researchers as they offer opportunities for discovering novel therapeutic targets for future drug development. However, the identification of potential CSC targets presents clear obstacles due to a lack of truly specific CSC markers and the reality of CSC plasticity, making this task a significant challenge.

SOX17 regulates cholangiocyte differentiation and acts as a tumor suppressor in cholangiocarcinoma.

Background & Aims: Cholangiocarcinoma (CCA) is a biliary malignancy linked to genetic and epigenetic abnormalities, such as hypermethylation of SOX17 promoter. Here, the role of SOX17 in cholangiocyte differentiation and cholangiocarcinogenesis was studied.

Methods: SOX17 expression/function was evaluated along the differentiation of human induced pluripotent stem cells (iPSC) into cholangiocytes, in the dedifferentiation process of normal human cholangiocytes (NHC) in culture and in cholangiocarcinogenesis.

Post-translational regulation of the type III inositol 1,4,5-trisphosphate receptor by miRNA-506.

The type III isoform of the inositol 1,4,5-trisphosphate receptor (InsP3R3) is apically localized and triggers Ca(2+) waves and secretion in a number of polarized epithelia. However, nothing is known about epigenetic regulation of this InsP3R isoform. We investigated miRNA regulation of InsP3R3 in primary bile duct epithelia (cholangiocytes) and in the H69 cholangiocyte cell line, because the role of InsP3R3 in cholangiocyte Ca(2+) signaling and secretion is well established and because loss of InsP3R3 from cholangiocytes is responsible for the impairment in bile secretion that occurs in a number of liver diseases.

TMPRSS4: an emerging potential therapeutic target in cancer.

Altered expression and activity of proteases is a key event in cancer, particularly in relation to invasion, modification of the extracellular matrix and metastasis. The transmembrane protease, serine 4 (TMPRSS4) is closely related to other cancer-associated proteases, such as hepsin, TMPRSS2 and matriptase. We review in this study up-to-date information about expression, role, regulation and clinical relevance of TMPRSS4 in cancer.

Functional crosstalk between the adenosine transporter CNT3 and purinergic receptors in the biliary epithelia.

Background & Aims: Both hepatocytes and cholangiocytes release ATP into the bile, where it acts as a potent autocrine/paracrine stimulus that activates biliary secretory mechanisms. ATP is known to be metabolized into multiple breakdown products, ultimately yielding adenosine. However, the elements implicated in the adenosine-dependent purinergic regulation of cholangiocytes are not known.

Linezolid-induced lactic acidosis in two liver transplant patients with the mitochondrial DNA A2706G polymorphism.

Mitochondrial toxicity has been recently suggested to be the underlying mechanism of long-term linezolid-associated toxicity in patients with 16S rRNA genetic polymorphisms. Here, we report for the first time two cases of lactic acidosis due to long-term linezolid exposure in liver transplant recipients who presented an A2706G mitochondrial DNA polymorphism.

Inhibition of metalloprotease hyperactivity in cystic cholangiocytes halts the development of polycystic liver diseases.

Objective: Polycystic liver diseases (PCLDs) are genetic disorders characterised by progressive bile duct dilatation and/or cyst development. Their pathogenesis is a consequence of hyperproliferation, hypersecretion and microRNA alterations in cholangiocytes. Here we evaluate the role of matrix metalloproteases (MMPs) in the hepatic cystogenesis of PCLDs.

Primers on molecular pathways - ion channels: key regulators of pancreatic physiology.

Ion transport across the cellular plasma membrane is important in almost every physiological process. This phenomenon is driven by the coordinated action of carriers, pumps and channels, which move ions in and out the cells and between different organelles. Ion channels are transmembrane proteins that provide a continuous aqueous pore through which ions can selectively move.