Circulating stem cell–like epithelial cell adhesion molecule–positive tumor cells indicate poor prognosis of hepatocellular carcinoma after curative resection

Yun‐Fan Sun, Yang Xu, Xin‐Rong Yang, Wei Guo, Xin Zhang, Shuang‐Jian Qiu, Ruo‐Yu Shi, Bo Hu, Jian Zhou, Jia Fan – 23 November 2012 – Epithelial cell adhesion molecule–positive (EpCAM+) hepatocellular carcinoma (HCC) cells may constitute a tumor‐initiating subpopulation in tumorigenic cell lines and HCC specimens. In the present study, EpCAM+ circulating tumor cells (CTCs) were identified prospectively in HCC patients undergoing curative resection, and the prognostic significance and their stem cell–like characteristics were investigated further.

Oxidative stress plays a major role in chlorpromazine‐induced cholestasis in human HepaRG cells

Sébastien Anthérieu, Pamela Bachour‐El Azzi, Julie Dumont, Ziad Abdel‐Razzak, Christiane Guguen‐Guillouzo, Bernard Fromenty, Marie‐Anne Robin, André Guillouzo – 23 November 2012 – Drugs induce cholestasis by diverse and still poorly understood mechanisms in humans. Early hepatic effects of chlorpromazine (CPZ), a neuroleptic drug known for years to induce intrahepatic cholestasis, were investigated using the differentiated human hepatoma HepaRG cells.

Discrete nature of EpCAM+ and CD90+ cancer stem cells in human hepatocellular carcinoma

Taro Yamashita, Masao Honda, Yasunari Nakamoto, Masayo Baba, Kouki Nio, Yasumasa Hara, Sha Sha Zeng, Takehiro Hayashi, Mitsumasa Kondo, Hajime Takatori, Tatsuya Yamashita, Eishiro Mizukoshi, Hiroko Ikeda, Yoh Zen, Hiroyuki Takamura, Xin Wei Wang, Shuichi Kaneko – 23 November 2012 – Recent evidence suggests that hepatocellular carcinoma (HCC) is organized by a subset of cells with stem cell features (cancer stem cells; CSCs). CSCs are considered a pivotal target for the eradication of cancer, and liver CSCs have been identified by the use of various stem cell markers.

Macrophage migration inhibitory factor contributes to ethanol‐induced liver injury by mediating cell injury, steatohepatitis, and steatosis

Mark A. Barnes, Megan R. McMullen, Sanjoy Roychowdhury, Sorana G. Pisano, Xiuli Liu, Abram B. Stavitsky, Richard Bucala, Laura E. Nagy – 23 November 2012 – Macrophage migration inhibitory factor (MIF), a multipotent protein that exhibits both cytokine and chemotactic properties, is expressed by many cell types, including hepatocytes and nonparenchymal cells. We hypothesized that MIF is a key contributor to liver injury after ethanol exposure.

Placental stem cell correction of murine intermediate maple syrup urine disease

Kristen J. Skvorak, Kenneth Dorko, Fabio Marongiu, Veysel Tahan, Marc C. Hansel, Roberto Gramignoli, K. Michael Gibson, Stephen C. Strom – 23 November 2012 – There is improved survival and partial metabolic correction of a mouse intermediate maple syrup urine disease (iMSUD) model after allogenic hepatocyte transplantation, confirming that a small number of enzyme‐proficient liver‐engrafted cells can improve phenotype. However, clinical shortages of suitable livers for hepatocyte isolation indicate a need for alternative cell sources.

Enhancement of tumor‐associated antigen‐specific T cell responses by radiofrequency ablation of hepatocellular carcinoma

Eishiro Mizukoshi, Tatsuya Yamashita, Kuniaki Arai, Hajime Sunagozaka, Teruyuki Ueda, Fumitaka Arihara, Takashi Kagaya, Taro Yamashita, Kazumi Fushimi, Shuichi Kaneko – 23 November 2012 – Radiofrequency ablation (RFA) is one of the treatments for hepatocellular carcinoma (HCC) and is known to enhance host immune response. However, the epitopes to which enhanced immune responses occur, the impact on patient prognosis, and the functions and phenotype of T cells induced are still unclear.

Chronic intermittent hypoxia aggravates intrahepatic endothelial dysfunction in cirrhotic rats

Manuel Hernández‐Guerra, Zaida Adrián de Ganzo, Yanira González‐Méndez, Eduardo Salido, Pedro Abreu, Miguel Moreno, Vanesa Felipe, Beatriz Abrante, Enrique Quintero – 23 November 2012 – Chronic intermittent hypoxia (CIH) occurs with obstructive sleep apnea syndrome (OSAS) and provokes systemic endothelial dysfunction, which is associated with oxidative stress and low nitric oxide (NO) bioavailability. Cirrhotic livers exhibit intrahepatic endothelial dysfunction, which is characterized by an impaired endothelium‐dependent response to vasodilators and hyperresponse to vasoconstrictors.

Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States

Donghee Kim, W. Ray Kim, Hwa Jung Kim, Terry M. Therneau – 23 November 2012 – The clinical and public health significance of nonalcoholic fatty liver disease (NAFLD) is not well established. We investigated the long‐term effect of NAFLD on mortality. This analysis utilized the National Health and Nutrition Examination Survey conducted in 1988‐1994 and subsequent follow‐up data for mortality through December 31, 2006. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other known liver diseases.

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