AROS Is a Significant Biomarker for Tumor Aggressiveness in Non-cirrhotic Hepatocellular Carcinoma

Despite a low risk of liver failure and preserved liver function, non-cirrhotic hepatocellular carcinoma (HCC) has a poor prognosis. In the current study, we evaluated an active regulator of SIRT1 (AROS) as a prognostic biomarker in non-cirrhotic HCC. mRNA levels of AROS were measured in tumor and non-tumor tissues obtained from 283 non-cirrhotic HCC patients. AROS expression was exclusively up-regulated in recurrent tissues from the non-cirrhotic HCC patients (P = 0.015) and also in tumor tissues irrespective of tumor stage (P < 0.001) or BCLC stage (P < 0.001). High mRNA levels of AROS were statistically significantly associated with tumor stage (P < 0.001), BCLC stage (P = 0.007), alpha fetoprotein (AFP) level (P = 0.013), microvascular invasion (P = 0.001), tumor size (P = 0.036), and portal vein invasion (P = 0.005). Kaplan-Meir curve analysis demonstrated that HCC patients with higher AROS levels had shorter disease-free survival (DFS) in both the short-term (P < 0.001) and long-term (P = 0.005) compared to those with low AROS. Cox regression analysis demonstrated that AROS is a significant predictor for DFS along with large tumor size, tumor multiplicity, vascular invasion, and poor tumor differentiation, which are the known prognostic factors. In conclusion, AROS is a significant biomarker for tumor aggressiveness in non-cirrhotic hepatocellular carcinoma.1122Ysciescopu

A monodisperse transmembrane α-helical peptide barrel

The fabrication of monodisperse transmembrane barrels formed from short synthetic peptides has not been demonstrated previously. This is in part because of the complexity of the interactions between peptides and lipids within the hydrophobic environment of a membrane. Here we report the formation of a transmembrane pore through the self-assembly of 35 amino acid α-helical peptides. The design of the peptides is based on the C-terminal D4 domain of the Escherichia coli polysaccharide transporter Wza. By using single-channel current recording, we define discrete assembly intermediates and show that the pore is most probably a helix barrel that contains eight D4 peptides arranged in parallel. We also show that the peptide pore is functional and capable of conducting ions and binding blockers. Such α-helix barrels engineered from peptides could find applications in nanopore technologies such as single-molecule sensing and nucleic-acid sequencing

Absence of an association of human polyomavirus and papillomavirus infection with lung cancer in China: a nested case–control study

BACKGROUND: Studies of human polyomavirus (HPyV) infection and lung cancer are limited and those regarding the association of human papillomavirus (HPV) infection and lung cancer have produced inconsistent results. METHODS: We conducted a nested case–control study to assess the association between incident lung cancer of various histologies and evidence of prior infection with HPyVs and HPVs. We selected serum from 183 cases and 217 frequency matched controls from the Yunnan Tin Miner’s Cohort study, which was designed to identify biomarkers for early detection of lung cancer. Using multiplex liquid bead microarray (LBMA) antibody assays, we tested for antibodies to the VP1 structural protein and small T antigen (ST-Ag) of Merkel cell, KI, and WU HPyVs. We also tested for antibodies against HPV L1 structural proteins (high-risk types 16, 18, 31, 33, 52, and 58 and low-risk types 6 and 11) and E6 and E7 oncoproteins (high risk types 16 and 18). Measures of antibody reactivity were log transformed and analyzed using logistic regression. RESULTS: We found no association between KIV, WUV, and MCV antibody levels and incident lung cancer (P-corrected for multiple comparisons >0.10 for all trend tests). We also found no association with HPV-16, 18, 31, 33, 52, and 58 seropositivity (P-corrected for multiple comparisons >0.05 for all). CONCLUSIONS: Future studies of infectious etiologies of lung cancer should look beyond HPyVs and HPVs as candidate infectious agents. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2381-3) contains supplementary material, which is available to authorized users

American ginseng suppresses Western diet-promoted tumorigenesis in model of inflammation-associated colon cancer: role of EGFR

<p>Abstract</p> <p>Background</p> <p>Western diets increase colon cancer risk. Epidemiological evidence and experimental studies suggest that ginseng can inhibit colon cancer development. In this study we asked if ginseng could inhibit Western diet (20% fat) promoted colonic tumorigenesis and if compound K, a microbial metabolite of ginseng could suppress colon cancer xenograft growth.</p> <p>Methods</p> <p>Mice were initiated with azoxymethane (AOM) and, two weeks later fed a Western diet (WD, 20% fat) alone, or WD supplemented with 250-ppm ginseng. After 1 wk, mice received 2.5% dextran sulfate sodium (DSS) for 5 days and were sacrificed 12 wks after AOM. Tumors were harvested and cell proliferation measured by Ki67 staining and apoptosis by TUNEL assay. Levels of EGF-related signaling molecules and apoptosis regulators were determined by Western blotting. Anti-tumor effects of intraperitoneal compound K were examined using a tumor xenograft model and compound K absorption measured following oral ginseng gavage by UPLC-mass spectrometry. Effects of dietary ginseng on microbial diversity were measured by analysis of bacterial 16S rRNA.</p> <p>Results</p> <p>Ginseng significantly inhibited colonic inflammation and tumorigenesis and concomitantly reduced proliferation and increased apoptosis. The EGFR cascade was up-regulated in colonic tumors and ginseng significantly reduced EGFR and ErbB2 activation and Cox-2 expression. Dietary ginseng altered colonic microbial diversity, and bacterial suppression with metronidazole reduced serum compound K following ginseng gavage. Furthermore, compound K significantly inhibited tumor xenograft growth.</p> <p>Conclusions</p> <p>Ginseng inhibited colonic inflammation and tumorigenesis promoted by Western diet. We speculate that the ginseng metabolite compound K contributes to the chemopreventive effects of this agent in colonic tumorigenesis.</p

Two distinct P-2 purinergic receptors, P-2Y and P-2U, are coupled to phospholipase C in mouse pineal gland tumor cells

We found that extracellular ATP can increase the intracellular Ca2+ concentration ([Ca2+](i)) in mouse pineal gland tumor (PGT-beta) cells. Studies of the [Ca2+](i) rise using nucleotides and ATP analogues established the following potency order: ATP, adenosine 5&apos;-O-(3-thiotriphosphate) greater than or equal to UTP > 2-chloro-ATP > 3&apos;-O-(4-benzoyl)benzoyl ATP, GTP greater than or equal to 2-methylthio ATP, adenosine 5&apos;-O-(2-thiodiphosphate) (ADP beta S) > CTP. AMP, adenosine, alpha,beta-methyleneadenosine 5&apos;-triphosphate, beta,gamma-methyleneadenosine 5&apos;-triphosphate, and UMP had little or no effect on the [Ca2+](i) rise. Raising the extracellular Mg2+ concentration to 10 mM decreases the ATP- and UTP-induced [Ca2+](i) rise, because the responses depend on the ATP(4-) and UTP4- concentrations, respectively. The P-2U purinoceptor-selective agonist UTP and the P-2Y purinoceptor-selective agonist ADP beta S induce inositol 1,4,5-trisphosphate generation in a concentration-dependent manner with maximal effective concentrations of similar to 100 mu M. In sequential stimulation, UTP and ADP beta S do not interfere with each other in raising the [Ca2+](i). Costimulation with UTP and ADP beta S results in additive inositol 1,4,5-trisphosphate generation to a similar extent as is achieved with ATP alone. Pretreatment with pertussis toxin inhibits the action of UTP and ATP by maximally 45-55%, whereas it has no effect on the ADP beta S response. Treatment with 1 mu M phorbol 12-myristate 13-acetate inhibits the ADP beta S-induced [Ca2+](i) rise more effectively than the ATP- and UTP-induced responses. These results suggest that P-2U and P-2Y purinoceptors coexist on PGT-beta cells and that both receptors are linked to phospholipase C.X1115sciescopu