Systemic Therapy for Hepatocellular Carcinoma: Chinese Consensus-Based Interdisciplinary Expert Statements.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and causes many cancer-related deaths worldwide; in China, it is the second most prevalent cause of cancer deaths. Most patients are diagnosed clinically with advanced stage disease. Summary: For more than a decade, sorafenib, a small-molecular-weight tyrosine kinase inhibitor (SMW-TKI) was the only molecular targeted drug available with a survival benefit for the treatment of advanced HCC. With the development of novel TKIs and immune checkpoint inhibitors for advanced HCC, the management of patients has been greatly improved. However, though angiogenic-based targeted therapy remains the backbone for the systemic treatment of HCC, to date, no Chinese guidelines for novel molecular targeted therapies to treat advanced HCC have been established. Our interdisciplinary panel on the treatment of advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, pathologists, orthopedic surgeons, traditional Chinese medicine physicians, and interventional radiologists has reviewed the literature in order to develop updated treatment regimens. Key Messages: Panel consensus statements for the appropriate use of new molecular -targeted drugs including doses, combination therapies, adverse reaction management as well as efficacy evaluation, and predictions for treatment of advanced HCC with evidence levels based on published data are presented, thereby providing an overview of molecular targeted therapies for healthcare professionals.

LncRNA-URHC Functions as ceRNA to Regulate DNAJB9 Expression by Competitively Binding to miR-5007-3p in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is often diagnosed at a late stage, when the prognosis is poor. The regulation of long noncoding RNAs (lncRNAs) plays a crucial role in HCC. However, the precise regulatory mechanisms of lncRNA signaling in HCC remain largely unknown. Our study aims to investigate the underlying mechanisms of lncRNA (upregulated in hepatocellular carcinoma) URHC in HCC. OBJECTIVE: To study the in vivo and in vitro localization and biological effects of URHC on liver cancer cells. Through bioinformatics analysis, dual-luciferase reporter gene analysis and rescue experiments revealed the possible mechanism of URHC. METHODS: RT-qPCR, fluorescence in situ hybridization (FISH) staining, EdU, colony formation, and tumor xenograft experiments were used to identify localized and biological effects of URHC on HCC cells in vitro and in vivo. The bioinformatics analysis, dual-luciferase reporter assay, and rescue experiments revealed the potential mechanism of URHC. RESULTS: URHC silencing may inhibit the HCC cells' proliferation in vitro and in vivo. We found that URHC was mainly localized in the cytoplasm. The expression of miR-5007-3p was negatively regulated by URHC. And miR-5007-3p could reverse the effect of URHC in HCC cells. The expression of DNAJB9 was negatively regulated by miR-5007-3p but positively regulated by URHC. These suggestive of lncRNA-URHC positively regulated the level of DNAJB9 by sponging miR-5007-3p. CONCLUSION: Together, our study elucidated the role of URHC as a miRNA sponge in HCC and shed new light on lncRNA-directed diagnostics and therapeutics in HCC.

Wogonin alleviates liver injury in sepsis through Nrf2-mediated NF-κB signalling suppression.

Sepsis is a life-threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)- or caecal ligation and puncture (CLP)-induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro-inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti-oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti-oxidative enzymes including NQO-1, GST, HO-1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin-induced Nrf2 activation could suppress NF-κB-regulated up-regulation of pro-inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti-oxidative enzymes and inhibited NF-κB-regulated pro-inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.

The multifaceted mechanisms for coffee's anti-tumorigenic effect on liver.

Epidemiological studies have found an inverse association between coffee consumption and the risk of liver cancer. Animal data support such a chemopreventive effect of coffee. Substantial research has been devoted to the identification of coffee components that may be responsible for these beneficial effects. Based on the current available literature, three major components, i.e. coffee diterpenes cafestol and kahweol (C+K), caffeine and chlorogenic acid contribute to the beneficial effects. These components induce phase II detoxifying and antioxidant enzymes as well as inhibit the expression or decrease the activity of phase I activating enzymes thus prevent carcinogenesis. These components target different stages of a common pathway, Kelch-like ECH-associated protein 1 (Keap1)--NF-E2-related factor-2 (Nrf2)--antioxidant-responsive-element (ARE) signal pathway thus alter the ARE-dependent expression of genes needed in the anti-tumorigenic effects.