Identification of MACC1 as a novel prognostic marker in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Metastasis-associated in colon cancer-1 (<it>MACC1</it>) is a newly identified gene that plays a role in colon cancer metastasis through upregulation of c-MET proto-oncogene (c-MET). However, the value of <it>MACC1 </it>as a potential biomarker for hepatocellular carcinoma (HCC) remains unknown.</p> <p>Methods</p> <p><it>MACC1 </it>mRNA expression in 128 HCC tissues was examined by quantitative polymerase chain reaction. To show the potential correlation of <it>MACC1 </it>and c-MET, c-MET was also analysed.</p> <p>Results</p> <p><it>MACC1 </it>was more highly expressed in HCC than in non-HCC tissues (<it>P </it>= 0.009). High <it>MACC1 </it>expression was significantly increased in cases with high alpha fetoprotein (AFP) (<it>P </it>= 0.025). A positive correlation was found between <it>MACC1 </it>and c-MET mRNAs (r = 0.235, <it>P </it>= 0.009). Both univariate and multivariate analyses revealed that <it>MACC1 </it>expression was associated with overall survival (OS) and disease-free survival (DFS). Moreover, stratified analysis showed that tumour-node-metastasis (TNM) stage I patients with high <it>MACC1 </it>levels had shorter OS and DFS than those with low <it>MACC1</it>.</p> <p>Conclusions</p> <p><it>MACC1 </it>may identify low- and high-risk individuals with HCC and be a valuable indicator for stratifying the prognosis of TNM stage I patients. <it>MACC1 </it>may serve as a novel biomarker for HCC.</p

Enhanced adsorption of sulfonamide antibiotics in water by modified biochar derived from bagasse

In this study, biochars derived from bagasse were prepared and their ability for the adsorption of four kinds of sulfonamide antibiotics (sulfamethoxazol, thiazole, methylpyrimidine, dimethylpyrimidine) was investigated. Results showed that the modified biochar can efficiently adsorb sulfonamides in water. The biochar obtained at 500oC and modified with 30% hydrogen peroxide was chosen as the adsorbent. Under optimum conditions, pH 4 and 35°C, great adsorption performance was exhibited in the adsorption process of the four sulfonamide antibiotics. The productivity of the modified biochar was ~ 89% compared to un-modified biochar which is ~31%. The successful preparation of biochar from bagasse indicates that it is a good way to reuse the resources. Besides the adsorption of antibiotics, the obtained material also has a great prospect in the removal of other pollutants

Metabolic Hijacking of Hexose Metabolism to Ascorbate Synthesis Is the Unifying Biochemical Basis of Murine Liver Fibrosis

We wished to understand the metabolic reprogramming underlying liver fibrosis progression in mice. Administration to male C57BL/6J mice of the hepatotoxins carbon tetrachloride (CCl4), thioacetamide (TAA), or a 60% high-fat diet, choline-deficient, amino-acid-defined diet (HF-CDAA) was conducted using standard protocols. Livers collected at different times were analyzed by gas chromatography&ndash;mass spectrometry-based metabolomics. RNA was extracted from liver and assayed by qRT-PCR for mRNA expression of 11 genes potentially involved in the synthesis of ascorbic acid from hexoses, Gck, Adpgk, Hk1, Hk2, Ugp2, Ugdh, Ugt1a1, Akr1a4, Akr1b3, Rgn and Gulo. All hepatotoxins resulted in similar metabolic changes during active fibrogenesis, despite different etiology and resultant scarring pattern. Diminished hepatic glucose, galactose, fructose, pentose phosphate pathway intermediates, glucuronic acid and long-chain fatty acids were compensated by elevated ascorbate and the product of collagen prolyl 4-hydroxylase, succinate and its downstream metabolites fumarate and malate. Recovery from the HF-CDAA diet challenge (F2 stage fibrosis) after switching to normal chow was accompanied by increased glucose, galactose, fructose, ribulose 5-phosphate, glucuronic acid, the ascorbate metabolite threonate and diminished ascorbate. During the administration of CCl4, TAA and HF-CDAA, aldose reductase Akr1b3 transcription was induced six- to eightfold, indicating increased conversion of glucuronic acid to gulonic acid, a precursor of ascorbate synthesis. Triggering hepatic fibrosis by three independent mechanisms led to the hijacking of glucose and galactose metabolism towards ascorbate synthesis, to satisfy the increased demand for ascorbate as a cofactor for prolyl 4-hydroxylase for mature collagen production. This metabolic reprogramming and causal gene expression changes were reversible. The increased flux in this pathway was mediated predominantly by increased transcription of aldose reductase Akr1b3

Automated whole slide image analysis for a translational quantification of liver fibrosis.

Current literature highlights the need for precise histological quantitative assessment of fibrosis which cannot be achieved by conventional scoring systems, inherent to their discontinuous values and reader-dependent variability. Here we used an automated image analysis software to measure fibrosis deposition in two relevant preclinical models of liver fibrosis, and established correlation with other quantitative fibrosis descriptors. Longitudinal quantification of liver fibrosis was carried out during progression of post-necrotic (CCl-induced) and metabolic (HF-CDAA feeding) models of chronic liver disease in mice. Whole slide images of picrosirius red-stained liver sections were analyzed using a fully automated, unsupervised software. Fibrosis was characterized by a significant increase of collagen proportionate area (CPA) at weeks 3 (CCl) and 8 (HF-CDAA) with a progressive increase up to week 18 and 24, respectively. CPA was compared to collagen content assessed biochemically by hydroxyproline assay (HYP) and by standard histological staging systems. CPA showed a high correlation with HYP content for CCl (r = 0.8268) and HF-CDAA (r = 0.6799) models. High correlations were also found with Ishak score or its modified version (r = 0.9705) for CCl and HF-CDAA (r = 0.9062) as well as with NASH CRN for HF-CDAA (r = 0.7937). Such correlations support the use of automated digital analysis as a reliable tool to evaluate the dynamics of liver fibrosis and efficacy of antifibrotic drug candidates in preclinical models

Clinical features and outcome of multiple primary malignancies involving hepatocellular carcinoma: A long-term follow-up study

Abstract Background The prolonged survival of individuals diagnosed with cancer has led to an increase in the number of secondary primary malignancies. We undertook to perform a definitive study to characterize and predict prognosis of multiple primary malignancies (MPM) involving hepatocellular carcinoma (HCC), due to the scarcity of such reports. Methods Clinicopathological data were analyzed for 68 MPM patients involving HCC, with 35 (target group) underwent curative liver resection. Additional 140 HCC-alone patients with hepatectomy were selected randomly during the same period as the control group. Results Of the 68 patients with extrahepatic primary malignancies (EHPM), 22 were diagnosed synchronously with HCC, and 46 metachronously. The most frequent EHPM was nasophargeal carcinoma, followed by colorectal and lung cancer. Univariate analysis demonstrated that synchronous (P = 0.008) and non-radical treatment for EHPM (P P = 0.607, P = 0.131, respectively). Conclusions Curative treatment is an independent predictive factor for OS and HCC-specific OS, and should been taken into account both for synchronous and metachronous patients. MPM patients involving HCC should not be excluded from radical resection for HCC.</p