High baseline NLR was associated with worse OS for patients with early HCC; post-RFA NLR predicted not only OS, but also tumor recurrence.

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Effects of n-acetyl cysteine (NAC), s-ethyl cysteine (SEC), s-propyl cysteine (SPC) and cysteine on enzymes participating in biosynthesis of TAG and cholesterol, and antioxidant protection in liver from mice consuming a high-saturated fat diet was examined. The high-fat diet provided 70 % fat energy, in which saturated fat was 55 % of total fat. NAC, SEC, SPC or cysteine, each agent at 1 g/l, was directly added into the drinking water as a supplement for 4 weeks. Results showed high saturated fat significantly increased hepatic TAG and total cholesterol contents (P, 0·05) via enhancing the activity and mRNA expression of malic enzyme, fatty acid synthase and 3-hydroxy-3-methylglutaryl coenzyme A reductase (P,0·05). The intake of NAC, SEC or SPC significantly decreased TAG and total cholesterol levels (P,0·05) via lowering the activity and mRNA expression of these three lipogenic-related enzymes (P,0·05). NAC, SEC or SPC treatment also significantly suppressed high saturated fat-induced hepatic mRNA expression of sterol regulatory element-binding protein (SREBP)-1c and SREBP-2 (P, 0·05). High saturated fat decreased hepatic content of glutathione, and the activity of catalase and glutathione peroxidase (P,0·05). The intake of NAC, SEC or SPC significantly increased hepatic glutathione content (P, 0·05), restored the activity and mRNA expression of glutathione peroxidase, and alleviated the high saturated fat-induced oxidative stress (P,0·05). These results support that NAC, SEC and SPC are potent agents for affecting hepatic biosynthesis of TAG and cholesterol, and protecting liver against high saturated fat-associated oxidative damage.s-Ethyl cysteine: s-Propyl cysteine: Fatty acid synthase: HMG-CoA reductase: Sterol regulatory element-binding proteins: Glutathione peroxidase n-Acetyl cysteine (NAC), s-ethyl cysteine (SEC) and s-propyl cysteine (SPC) are three hydrophilic cysteine-containing compounds naturally formed in Allium plants such as garlic and onion 1,2 . Our previous study has observed that the intake of these three compounds effectively decreased high saturated fat-induced TAG and cholesterol accumulation in mice liver via reducing the activity of malic enzyme and fatty acid synthase (FAS), and the intake of these compounds also protected liver against high saturated fat-induced oxidative damage via enhancing glutathione peroxidase (GPx) activity 3 . In order to understand the molecular mechanism of these compounds, this present study examined the effects of these compounds on the mRNA expression of enzymes associated with biosynthesis of TAG and cholesterol, and anti-oxidative defence in mice liver.On the other hand, sterol regulatory element-binding proteins (SREBP) are important transcription factors responsible for fatty acid and cholesterol metabolism 4 . It is known that three forms of SREBP, SREBP-1a, SREBP-1c and SREBP-2, are expressed in organs such as liver, kidney and heart, in which SREBP-1c is more effective in modulating the expression of genes involved in fatty acid synthesis, whereas ...

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This study provided novel clinical findings regarding the status of oxidative stress and B vitamins in HCC patients. Plasma glutathione level may be a proper biomarker for evaluating oxidative status for HCC patients. Our data indicate that HCC patients might need B vitamins supplementation. The increased serum level of triglyceride and cholesterol might be a consequence of an impaired hepatic fat metabolism, and might be improved by a lower fat administration to these patients.

ENO1 (α-enolase) expression is significantly correlated with reduced survival and poor prognosis in many cancer types, including lung cancer. However, the function of ENO1 in carcinogenesis remains elusive. In this study, we found that high expression of ENO1 is present in metastatic lung cancer cell lines and malignant tumors and is associated with poor overall survival of patients with lung cancer. Knockdown of ENO1 decreased cancer cell proliferation and invasiveness, whereas overexpression of ENO1 enhanced these processes. Moreover, ENO1 expression promoted tumor growth in orthotopic models and enhanced lung tumor metastasis in tail-vein injection models. These effects were mediated by upregulation of mesenchymal markers N-cadherin and vimentin and the epithelial-to-mesenchymal transition regulator SLUG, along with concurrent downregulation of E-cadherin. Mechanistically, ENO1 interacted with hepatocyte growth factor receptor (HGFR) and activated HGFR and Wnt signaling via increased phosphorylation of HGFR and the Wnt coreceptor LRP5/6. Activation of these signaling axes decreased GSK3β activity via Src–PI3K–AKT signaling and inactivation of the β-catenin destruction complex to ultimately upregulate SLUG and β-catenin. In addition, we generated a chimeric anti-ENO1 mAb (chENO1-22) that can decrease cancer cell proliferation and invasion. chENO1-22 attenuated cancer cell invasion by inhibiting ENO1-mediated GSK3β inactivation to promote SLUG protein ubiquitination and degradation. Moreover, chENO1-22 prevented lung tumor metastasis and prolonged survival in animal models. Taken together, these findings illuminate the molecular mechanisms underlying the function of ENO1 in lung cancer metastasis and support the therapeutic potential of a novel antibody targeting ENO1 for treating lung cancer. Significance: This study shows that ENO1 promotes lung cancer metastasis via HGFR and WNT signaling and introduces a novel anti-ENO1 antibody for potential therapeutic use in lung cancer.