Ricerc@Sapienza

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that may develop at any
level of the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar (pCCA) and
distal (dCCA) on the basis of its anatomical location. Notably, although these three CCA subtypes
have common features, they also have important inter- and intra-tumor differences that can
affect their pathogenesis and outcome. A unique feature of CCA is that it manifests in the hepatic

Background and Aims: Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by inflammation and bile duct fibrosis. Massive proliferation of biliary tree stem/progenitor cell (BTSC), expansion of peribiliary glands (PBG) and dysplasia were observed in PSC. Cholangiocarcinoma (CCA) frequently complicates the course of PSC. The aims of the present study were to evaluate the involvement of PBGs and BTSCs in CCA emerging in PSC patients.

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that could develop at any level from the biliary tree. CCA is currently classified into intrahepatic (iCCA), perihilar and distal on the basis of its anatomical location. Of note, these three CCA subtypes have common features but also important inter-tumor and intra-tumor differences that can affect the pathogenesis and outcome.

Human cholangiocarcinoma (CCA) is an aggressive tumour entity arising from the biliary tree, whose molecular pathogenesis remains largely undeciphered. Over the last decade, the advent of high-throughput and cell-based techniques has significantly increased our knowledge on the molecular mechanisms underlying this disease while, at the same time, unravelling CCA complexity.

Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly.

In normal human livers, EpCAMpos cells are mostly restricted in two distinct niches, which are (i) the bile ductules and (ii) the mucous glands present inside the wall of large intrahepatic bile ducts (the so-called peribiliary glands). These EpCAMpos cell niches have been proven to harbor stem/progenitor cells with great importance in liver and biliary tree regeneration and in the pathophysiology of human diseases. The EpCAMpos progenitor cells within bile ductules are engaged in driving regenerative processes in chronic diseases affecting hepatocytes or interlobular bile ducts.

Changes in single microRNA (MIR) expression have been associated with chemo-resistance in Biliary Tract Cancer (BTC). However, a global assessment of the dynamic role of the microRNome has never been performed to identify potential therapeutic targets that are functionally relevant in the BTC cell response to chemotherapy. APPROACH AND RESULTS: high-throughput-screening of 997 LNA-MIR-inhibitors was performed in 6 CCA cell lines treated with Cisplatin-Gemcitabine (CG) seeking changes in cell viability. Validation experiments were performed with miRvana probes.

Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with marked resistance to chemotherapeutics without therapies. The tumour microenvironment of iCCA is enriched of Cancer-Stem-Cells expressing Epithelial-to-Mesenchymal Transition (EMT) traits, being these features associated with aggressiveness and drug resistance. Treatment with the anti-diabetic drug Metformin, has been recently associated with reduced incidence of iCCA. We aimed to evaluate the anti-cancerogenic effects of Metformin in vitro and in vivo on primary cultures of human iCCA.

L’albero biliare è costituito da cellule epiteliali mature, i colangiociti, ed è suddiviso in dotti biliari intra ed extraepatici. I colangiociti facilitano la secrezione e la modificazione dei costituenti della bile e fungono da condotti di trasporto della bile nell’intestino. L’alterazione della normale funzione del colangiocita può portare allo sviluppo di molteplici patologie biliari, conosciute come colangiopatie.

Liver diseases are a major health concern and affect a large proportion of people worldwide. There are over 100 types of liver disorders, including cirrhosis, cholangiocarcinoma (CCA), hepatocellular carcinoma, and hepatitis. Despite the relevant number of people who are affected by liver diseases, and the increased awareness with regard to these disorders, the number of deaths corresponding to liver injury is expected to increase in the foreseeable future.