The techniques of proteomic analysis combined with tissue microarray provide us a dramatic tool for screening of LNM-associated proteins in cancer research. The increased expression of HSP-27, GST, and Annexin II, but decreased expression of L-FABP, suggests a significantly elevated incidence of LNM in CRC.

Epithelial-mesenchymal transition (EMT) is a critical step in the metastasis of hepatocellular carcinoma (HCC). BTB/POZ domain-containing protein 7 (BTBD7) regulates EMTassociated proteins implicated in HCC progression. However, the role(s) of BTBD7 in HCC have not been identified. Using highly metastatic HCC HCCLM3 cells, immortalized L02 hepatocytes, metastatic HCC animal models, and three independent cohorts of HCC patient specimens, we aimed to determine the involvement of BTBD7 in HCC metastasis. We show that BTBD7 messenger RNA and protein was highly expressed in HCC cells and tumor tissues, with such expression being associated with: enhanced cell motility, venous invasion, and poor prognosis. BTBD7 promoted HCC angiogenesis and metastasis in vitro and in vivo, but did not influence cell proliferation or colony formation. BTBD7 enhancement of HCC invasion and EMT phenotype occurred through activation of a RhoC-Rock2-FAK-signaling pathway, resulting in matrix metalloproteinase-2/9 production and microvessel formation. Applying a predictive risk score model, Cox regression analysis revealed that high BTBD7 expression integrated with high microvessel density was a powerful independent predictive factor of HCC clinical outcome. Conclusion: The present study identifies BTBD7 as a novel candidate prognostic factor and a potential therapeutic target of HCC. (HEPATOLOGY 2013; 57:2326-2337 H epatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Overall survival (OS) of HCC patients remains unsatisfactory because of a high incidence of recurrence and metastasis after hepatic resection. 1 Understanding the mechanisms of HCC recurrence and metastasis should improve HCC treatment and outcomes.Epithelial-mesenchymal transition (EMT) is an important physiological process contributing to HCC recurrence and metastasis. Expression of several EMTassociated genes is correlated with HCC recurrence and metastasis. HCCs with EMT features consistently exhibit more venous invasion, metastases, and a poorer prognosis than those without EMT characteristics. 2 Therefore, for the treatment of HCC, there exists significant clinical potential in targeting EMT-associated factors.Members of the BTB (bric-a-brac tramtrack broad complex) (also known as POZ) gene family, characterized by a conserved BTB/POZ protein-protein interaction motif, have been implicated in human cancer. 3,4 The promoter region of BTB/POZ domain-containing protein 7 (BTBD7) contains binding sites for notable transcription factors, including alpha-fetoprotein (AFP)-1, CAAT enhancer-binding protein beta, GATA,

AIMTo observe gene polymorphisms of TPMT and NUDT15, and compare their predictive value for azathioprine (AZA)-induced leukopenia in inflammatory bowel disease (IBD).METHODSThis study enrolled 219 patients diagnosed with IBD in Xiangya Hospital, Central South University, Changsha, China from February 2016 to November 2017. Peripheral blood of all patients was collected to detect their genotypes of TPMT and NUDT15 by pyrosequencing at the Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital. Eighty patients were treated with AZA according to the disease condition. During the first month, patients who received AZA underwent routine blood tests and liver function tests once a week. The endpoint of the study was leukopenia induced by AZA. By analyzing patient characteristics, genotypes and leukopenia induced by drug use, we found the risk factors associated with AZA-induced leukopenia.RESULTSThere were 219 patients with IBD (160 men and 59 women), including 39 who were confirmed with ulcerative colitis (UC), 176 with Crohn’s disease (CD) and 4 with undetermined IBD (UIBD). There were 44 patients (20.1%) with mutant genotype of NUDT15 (C/T); among them, 16 received AZA, and 8 (50%) developed leukopenia. There were 175 patients (79.7%) with wild genotype of NUDT15 (C/C); among them, 64 received AZA, and 11 (17.2%) developed leukopenia. A significant difference was found between NUDT15 C/T and its wild-type C/C (P = 0.004). There were only 3 patients with TPMT mutant genotype of A/G (1.4%) who participated in the research, and 1 of them was treated with AZA and developed leukopenia. The remaining 216 patients (98.6%) were found to bear the wild genotype of TPMT (A/A); among them, 79 patients received AZA, and 18 (22.8%) developed leukopenia, and there was no significant difference from those with A/G (P = 0.071). The frequency of TPMT mutation was 1.4%, and NUDT15 mutation rate was significantly higher and reached 20.1% (P = 0.000). Therefore, NUDT15 gene polymorphism was obviously a better biomarker than TPMT gene polymorphism in the prediction of AZA-induced leukopenia.CONCLUSIONMutation rate of NUDT15 in Chinese IBD patients is higher than that of TPMT. NUDT15 polymorphism is a better predictor for AZA-induced leukopenia than TPMT polymorphism.

Z, Tao L. Fluorofenidone attenuates hepatic fibrosis by suppressing the proliferation and activation of hepatic stellate cells.

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We investigate the association of MUC1 with castration-resistant prostate cancer (CRPC), bone metastasis, and PC recurrence. MUC1 expression was studied in patient-derived bone metastasis and CRPCs produced by prostate-specific PTEN−/− mice and LNCaP xenografts. Elevations in MUC1 expression occur in CRPC. Among nine patients with hormone-naïve bone metastasis, eight express MUC1 in 61% to 100% of PC cells. Utilizing cBioPortal PC genomic data, we organized a training (n = 300), testing (n = 185), and validation (n = 194) cohort. Using the Cox model, a nine-gene signature was derived, including eight genes from a MUC1-related network (APC, CTNNB1/β-catenin, GALNT10, GRB2, LYN, SIGLEC1, SOS1, and ZAP70) and FAM84B. Genomic alterations in these genes reduce disease-free survival (DFS) in the training (P = .00161), testing (P = .00699), entire (training + testing, P = 5.557e-5), and a validation cohort (P = 3.326e-5). The signature independently predicts PC recurrence [hazard ratio (HR) = 1.731; 95% confidence interval (CI): 1.104-2.712; P = .0167] after adjusting for known clinical factors and stratifies patients with high risk of PC recurrence using the median (HR 2.072; 95% CI: 1.245-3.450, P = .0051) and quartile 3 (HR 3.707, 95% CI: 1.949-7.052, P = 6.51e-5) scores. Several novel β-catenin mutants are identified in PCs leading to a rapid onset of death and recurrence. Genomic alterations in APC and CTNNB1/β-catenin reduce DFS in two independent PC cohorts (n = 485, P = .0369; n = 84, P = .0437). The nine-gene signature also associates with reductions in overall survival (P = .0458) and DFS (P = .0163) in melanoma patients (n = 367). MUC1 upregulation is associated with CRPC and bone metastasis. A nine-gene signature derived from a MUC1 network predicts PC recurrence.

AKF-PD treatment inhibits the progression of hepatic fibrosis by suppressing HSCs proliferation and activation via MAPK signalling pathway.

No abstract