Radiation-induced liver disease: current understanding and future perspectives

Although radiotherapy (RT) is used for the treatment of cancers, including liver cancer, radiation-induced liver disease (RILD) has emerged as a major limitation of RT. Radiation-induced toxicities in nontumorous liver tissues are associated with the development of numerous symptoms that may limit the course of therapy or have serious chronic side effects, including late fibrosis. Although the clinical characteristics of RILD patients have been relatively well described, the understanding of RILD pathogenesis has been hampered by a lack of reliable animal models for RILD. Despite efforts to develop suitable experimental animal models for RILD, current animal models rarely present hepatic veno-occlusive disease, the pathological hallmark of human RILD patients, resulting in highly variable results in RILD-related studies. Therefore, we introduce the concept and clinical characteristics of RILD and propose a feasible explanation for RILD pathogenesis. In addition, currently available animal models of RILD are reviewed, focusing on similarities with human RILD and clues to understanding the mechanisms of RILD progression. Based on these findings from RILD research, we present potential therapeutic strategies for RILD and prospects for future RILD studies. Therefore, this review helps broaden our understanding for developing effective treatment strategies for RILD.

Tumor necrosis factor-inducible gene 6 protein ameliorates chronic liver damage by promoting autophagy formation in mice

Tumor necrosis factor-inducible gene 6 protein (TSG-6) has recently been shown to protect the liver from acute damage. However, the mechanism underlying the effect of TSG-6 on the liver remains unclear. Autophagy is a catabolic process that targets cell components to lysosomes for degradation, and its functions are reported to be dysregulated in liver diseases. Here we investigate whether TSG-6 promotes liver regeneration by inducing autophagic clearance in damaged livers. Mice fed a methionine choline-deficient diet supplemented with 0.1% ethionine (MCDE) for 2 weeks were injected with TSG-6 (the M+TSG-6 group) or saline (the M+V group) and fed with MCDE for 2 additional weeks. Histomorphological evidence of injury and increased levels of liver enzymes were evident in MCDE-treated mice, whereas these symptoms were ameliorated in the M+TSG-6 group. Livers from this group contained less active caspase-3 and more Ki67-positive hepatocytic cells than the M+V group. The autophagy markers ATG3, ATG7, LC3-II, LAMP2A and RAB7 were elevated in the M+TSG-6 group compared with those in the M+V group. Immunostaining for LC3 and RAB7 and electron microscopy analysis showed the accumulation of autophagy structures in the M+TSG-6 group. TSG-6 also blocked both tunicamycin- and palmitate-induced apoptosis of hepatocytes and increased their viability by inducing autophagy formation in these cells. An autophagy inhibitor suppressed TSG-6-mediated autophagy in the injured hepatocytes and livers of MCDE-treated mice. These results therefore demonstrate that TSG-6 protects hepatocytes from damage by enhancing autophagy influx and contributes to liver regeneration, suggesting that TSG-6 has therapeutic potential for the treatment of liver diseases.

Factors Influencing Posttraumatic Growth in Survivors of Breast Cancer

PURPOSE: Posttraumatic growth (PTG) is defined as 'positive psychological change experienced as a result of a struggle with highly challenging life circumstances'. The purpose of this study was to identify the level of PTG and its correlates in Korean patients with breast cancer. METHODS: A sample of 120 participants was recruited from outpatients, who had successfully completed primary treatment of breast cancer at a university hospital., Data were collected from June to December, 2014 using Posttraumatic Growth Inventory, lllness Intrusiveness Rating Scale, Cancer Coping Questionnaire, Revised Life Orientation Test and The Multidimensional Scale of Perceived Social Support. RESULTS: Total score for the PTG was 79.18±17.54 in patients surviving breast cancer. Bivariate analyses indicated that PTG was positively associated with having a religion, perceived social support, greater optimism, cancer coping, and illness intrusiveness. Results of the regression analysis showed that cancer coping (β=.29, p=.001), optimism (β=0.28, p=.001) and illness intrusiveness (β=0.17, p=.037) were statistically significant in patients' PTG. CONCLUSION: The research findings show that the variables of cancer coping, optimism and illness intrusiveness significantly explain PTG and these psychological variables can be used to provide improvement in PTG for patients with breast cancer