Expert consensus document:Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted

PET Tracers to Study Clinically Relevant Hepatic Transporters

Peer reviewedPostprin

Role of Organic Anion-Transporting Polypeptides (OATPs) in Cancer Therapy

The superfamily of organic anion-transporting polypeptides (OATPs, gene symbol SLCO) includes important transporters handling a variety of endogenous and xenobiotic substrates. Currently, 11 human OATPs are known and their substrates include endogenous hormones and their conjugates, anticancer drugs, and imaging agents. The contribution of OATPs to the in vivo disposition of these substrates has been extensively investigated. An accumulating body of evidence also indicates that the expression of some OATPs may be up- or downregulated in several types of cancers, suggesting potential pathogenic roles during the development and progression of cancer. Given that the role of OATPs in handling cancer therapeutics has been already covered by several excellent reviews, this review will focus on the recent progresses on the topic, in particular the role of OATPs in the disposition of anticancer drugs, the impact of OATP genetic variations on the function of OATPs, and the OATPs differentially expressed in cancer and their potential roles in cancer development, progression, and treatment

Transporter function and cyclic AMP turnover in normal colonic mucosa from patients with and without colorectal neoplasia

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of colorectal neoplasia is still unresolved but has been associated with alterations in epithelial clearance of xenobiotics and metabolic waste products. The aim of this study was to functionally characterize the transport of cyclic nucleotides in colonic biopsies from patients with and without colorectal neoplasia.</p> <p>Methods</p> <p>Cyclic nucleotides were used as model substrates shared by some OATP- and ABC-transporters, which in part are responsible for clearance of metabolites and xenobiotics from the colonic epithelium. On colonic biopsies from patients with and without colorectal neoplasia, molecular transport was electrophysiologically registered in Ussing-chamber set-ups, mRNA level of selected transporters was quantified by rt-PCR, and subcellular location of transporters was determined by immunohistochemistry.</p> <p>Results</p> <p>Of four cyclic nucleotides, dibuturyl-cAMP induced the largest short circuit current in both patient groups. The induced short circuit current was significantly lower in neoplasia-patients (p = 0.024). The observed altered transport of dibuturyl-cAMP in neoplasia-patients could not be directly translated to an observed increased mRNA expression of OATP4A1 and OATP2B1 in neoplasia patients. All other examined transporters were expressed to similar extents in both patient groups.</p> <p>Conclusions</p> <p>OATP1C1, OATP4A1, OATP4C1 seem to be involved in the excretory system of human colon. ABCC4 is likely to be involved from an endoplasmic-Golgi complex and basolateral location in goblet cells. ABCC5 might be directly involved in the turnover of intracellular cAMP at the basolateral membrane of columnar epithelial cells, while OATP2B1 is indirectly related to the excretory system. Colorectal neoplasia is associated with lower transport or sensitivity to cyclic nucleotides and increased expression of OATP2B1 and OATP4A1 transporters, known to transport PGE₂.</p