Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro

Sandra March, Elliot E. Hui, Gregory H. Underhill, Salman Khetani, Sangeeta N. Bhatia – 27 August 2009 – Liver sinusoidal endothelial cells (LSECs) differ, both structurally and functionally, from endothelial cells (ECs) lining blood vessels of other tissues. For example, in contrast to other ECs, LSECs possess fenestrations, have low detectable levels of platelet endothelial cell adhesion molecule 1 expression, and in rat tissue, they distinctively express a cell surface marker recognized by the SE‐1 antibody.

CD24 polymorphisms affect risk and progression of chronic hepatitis B virus infection

Dongling Li, Linghua Zheng, Lei Jin, Yuesu Zhou, Haiying Li, Junliang Fu, Ming Shi, Peishuang Du, Lizhong Wang, Hao Wu, Guo‐Yun Chen, Pan Zheng, Yang Liu, Fu‐Sheng Wang, Shengdian Wang – 27 August 2009 – T‐cell immunity to hepatitis B virus (HBV) is involved in both viral clearance and the pathogenesis of cirrhosis and hepatocellular carcinoma following chronic HBV infection. It is therefore of great interest to analyze whether genetic polymorphism of genes involved in the immune response may determine the outcomes of chronic HBV infection.

Long‐term reduction of jaundice in Gunn rats by nonviral liver‐targeted delivery of Sleeping Beauty transposon

Xia Wang, Debi P. Sarkar, Prashant Mani, Clifford J. Steer, Yong Chen, Chandan Guha, Voshavar Chandrasekhar, Arabinda Chaudhuri, Namita Roy‐Chowdhury, Betsy T. Kren, Jayanta Roy‐Chowdhury – 27 August 2009 – Asialoglycoprotein receptor (ASGPR)‐mediated endocytosis has been used to target genes to hepatocytes in vivo. However, the level and duration of transgene expression have been low because of lysosomal translocation and degradation of the DNA and lack of its integration into the host genome.

Oxidative stress induces anti‐hepatitis C virus status via the activation of extracellular signal‐regulated kinase

Masahiko Yano, Masanori Ikeda, Ken‐ichi Abe, Yoshinari Kawai, Misao Kuroki, Kyoko Mori, Hiromichi Dansako, Yasuo Ariumi, Shougo Ohkoshi, Yutaka Aoyagi, Nobuyuki Kato – 27 August 2009 – Recently, we reported that β‐carotene, vitamin D2, and linoleic acid inhibited hepatitis C virus (HCV) RNA replication in hepatoma cells. Interestingly, in the course of the study, we found that the antioxidant vitamin E negated the anti‐HCV activities of these nutrients. These results suggest that the oxidative stress caused by the three nutrients is involved in their anti‐HCV activities.

Renal dysfunction in chronic hepatitis B patients treated with adefovir dipivoxil

Nghi B. Ha, Nghiem B. Ha, Ruel T. Garcia, Huy N. Trinh, Andrew A. Vu, Huy A. Nguyen, Khanh K. Nguyen, Brian S. Levitt, Mindie H. Nguyen – 27 August 2009 – Renal dysfunction has been reported in patients treated with adefovir dipivoxil (ADV); however, its incidence and clinical importance may be underappreciated given the lack of long‐term follow‐up and data outside of a clinical trial setting.

Up‐regulated microRNA‐143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression

Xiaoying Zhang, Shanrong Liu, Tingsong Hu, Shupeng Liu, Ying He, Shuhan Sun – 29 July 2009 – It is increasingly clear that hepatocellular carcinoma (HCC) has a distinct microRNA (miRNA) expression profile that is involved in malignancy; however, little is known about how functional miRNA modulates the metastasis of hepatitis B virus (HBV)‐related HCC (HBV‐HCC). In the present study, we demonstrate that the levels of miRNA‐143 (miR‐143) are dramatically increased in metastatic HBV‐HCC of both p21‐HBx transgenic mice and HCC patients.

Rapamycin delays tumor development in murine livers by inhibiting proliferation of hepatocytes with DNA damage

Laura Elisa Buitrago‐Molina, Deepika Pothiraju, Jutta Lamlé, Silke Marhenke, Uta Kossatz, Kai Breuhahn, Michael P. Manns, Nisar Malek, Arndt Vogel – 29 July 2009 – In this study, everolimus (RAD001) was used to determine the role of mammalian target of rapamycin (mTOR) in hepatocarcinogenesis. We show that RAD001 effectively inhibits proliferation of hepatocytes during chronic liver injury. Remarkably, the ability of RAD001 to impair cell cycle progression requires activation of the DNA damage response; loss of p53 significantly attenuates the antiproliferative effects of mTOR inhibition.

Repair‐related activation of hedgehog signaling promotes cholangiocyte chemokine production

Alessia Omenetti, Wing‐Kin Syn, Youngmi Jung, Heather Francis, Alessandro Porrello, Rafal P. Witek, Steve S. Choi, Liu Yang, Marlyn J. Mayo, M. Eric Gershwin, Gianfranco Alpini, Anna Mae Diehl – 29 July 2009 – The mechanisms mediating hepatic accumulation of inflammatory cells in cholestatic liver disease remain enigmatic. Our thesis is that Hedgehog (Hh) pathway activation promotes hepatic accumulation of immune cells that interact with cholangiocytes.

S‐adenosylmethionine in the chemoprevention and treatment of hepatocellular carcinoma in a rat model

Shelly C. Lu, Komal Ramani, Xiaopeng Ou, Mark Lin, Victor Yu, Kwangsuk Ko, Ryan Park, Teodoro Bottiglieri, Hidekazu Tsukamoto, Gary Kanel, Samuel W. French, José M. Mato, Rex Moats, Edward Grant – 29 July 2009 – Hepatocellular carcinoma (HCC) remains a common cancer worldwide that lacks effective chemoprevention or treatment. Chronic liver disease often leads to impaired hepatic S‐adenosylmethionine (SAMe) biosynthesis, and mice with SAMe deficiency develop HCC spontaneously. SAMe is antiapoptotic in normal hepatocytes but proapoptotic in cancerous hepatocytes.

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