Organized proteomic heterogeneity in colorectal cancer liver metastases and implications for therapies

Andrei Turtoi, Arnaud Blomme, Delphine Debois, Joan Somja, David Delvaux, Georgios Patsos, Emmanuel Valentin, Olivier Peulen, Eugène Nzaramba Mutijima, Edwin Pauw, Philippe Delvenne, Olivier Detry, Vincent Castronovo – 6 July 2013 – Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach.

Biliary complications adversely affect patient and graft survival after liver retransplantation

C. Kristian Enestvedt, Saloni Malik, Peter P. Reese, Alexander Maskin, Peter S. Yoo, Sameh A. Fayek, Peter Abt, Kim M. Olthoff, Abraham Shaked – 2 July 2013 – Inferior outcomes are consistently observed for recipients of liver retransplantation (re‐LT) versus recipients of primary transplants. Few studies have examined the incidence and impact of biliary complications (BCs) on outcomes after re‐LT. The aim of this study was to compare patient and graft survival for re‐LT recipients with BCs (BC+) and re‐LT recipients without BCs (BC−).

Hepatic loss of survivin impairs postnatal liver development and promotes expansion of hepatic progenitor cells in mice

Dan Li, Jin Cen, Xiaotao Chen, Edward M. Conway, Yuan Ji, Lijian Hui – 28 June 2013 – Hepatocytes possess a remarkable capacity to regenerate and reconstitute the parenchyma after liver damage. However, in the case of chronic injury, their proliferative potential is impaired and hepatic progenitor cells (HPCs) are activated, resulting in a ductular reaction known as oval cell response. Proapoptotic and survival signals maintain a precise balance to spare hepatocytes and progenitors from hyperplasia and cell death during regeneration.

High‐fat and high‐sucrose (western) diet induces steatohepatitis that is dependent on fructokinase

Takuji Ishimoto, Miguel A. Lanaspa, Christopher J. Rivard, Carlos A. Roncal‐Jimenez, David J. Orlicky, Christina Cicerchi, Rachel H. McMahan, Manal F. Abdelmalek, Hugo R. Rosen, Matthew R. Jackman, Paul S. MacLean, Christine P. Diggle, Aruna Asipu, Shinichiro Inaba, Tomoki Kosugi, Waichi Sato, Shoichi Maruyama, Laura G. Sánchez‐Lozada, Yuri Y. Sautin, James O. Hill, David T. Bonthron, Richard J. Johnson – 28 June 2013 – Fructose intake from added sugars has been implicated as a cause of nonalcoholic fatty liver disease.

CD39 expression by hepatic myeloid dendritic cells attenuates inflammation in liver transplant ischemia‐reperfusion injury in mice

Osamu Yoshida, Shoko Kimura, Edwin K. Jackson, Simon C. Robson, David A. Geller, Noriko Murase, Angus W. Thomson – 28 June 2013 – Hepatic innate immune cells, in particular, interstitial dendritic cells (DCs), regulate inflammatory responses and may promote inherent liver tolerogenicity. After tissue injury, adenosine triphosphate (ATP) is released and acts as a damage‐associated molecular pattern that activates innate immune cells by pattern recognition receptors. CD39 (ectonucleoside triphosphate diphosphohydrolase‐1) rapidly hydrolyzes extracellular ATP to maintain physiological levels.

Cannabinoid receptor 2 counteracts interleukin‐17‐induced immune and fibrogenic responses in mouse liver

Adrien Guillot, Nabila Hamdaoui, Alexandra Bizy, Keve Zoltani, Rachid Souktani, Elie‐Serge Zafrani, Ariane Mallat, Sophie Lotersztajn, Fouad Lafdil – 28 June 2013 – Interleukin (IL)‐17 is a proinflammatory and fibrogenic cytokine mainly produced by T‐helper (Th)17 lymphocytes, together with the hepatoprotective and antifibrogenic cytokine, IL‐22. Cannabinoid receptor 2 (CB2) is predominantly expressed in immune cells and displays anti‐inflammatory and antifibrogenic effects.

First experience of high‐intensity focused ultrasound combined with transcatheter arterial embolization as local control for hepatoblastoma

Shan Wang, Chao Yang, Jun Zhang, Xiang‐ru Kong, Hui Zhu, Feng Wu, Zhibiao Wang – 28 June 2013 – The purpose of this study was to assess the effectiveness of high‐intensity focused ultrasound (HIFU) combined with transarterial chemoembolization (TACE) in treating pediatric hepatoblastoma. Twelve patients with initially unresectable hepatoblastoma were enrolled in the study. All patients received chemotherapy, TACE, and HIFU ablation. Follow‐up materials were obtained in all patients. The tumor response, survival rate, and complications were analyzed.

Overactivation of the TGF‐β pathway confers a mesenchymal‐like phenotype and CXCR4‐dependent migratory properties to liver tumor cells

Esther Bertran, Eva Crosas‐Molist, Patricia Sancho, Laia Caja, Judit Lopez‐Luque, Estanislao Navarro, Gustavo Egea, Raquel Lastra, Teresa Serrano, Emilio Ramos, Isabel Fabregat – 28 June 2013 – Transforming growth factor‐beta (TGF‐β) is an important regulatory suppressor factor in hepatocytes. However, liver tumor cells develop mechanisms to overcome its suppressor effects and respond to this cytokine by inducing other processes, such as the epithelial‐mesenchymal transition (EMT), which contributes to tumor progression and dissemination.

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