Genomic analysis of recurrences and high-grade forms of polymorphous adenocarcinoma.

AIMS: Polymorphous adenocarcinoma (PAC) usually follows an indolent course, but some cases may show recurrences and high-grade features. The genetic events associated with recurrences and high-grade versions are yet to be defined. Our aim was to determine the genetic underpinning of recurrent PACs of the salivary gland and the repertoire of somatic genetic alterations in cases with high-grade histology. METHODS AND RESULTS: Four PACs from three patients, including one case with matching primary and recurrent tumours, one de-novo high-grade PAC, and a PAC that transformed to a high-grade tumour following multiple recurrences, were subjected to targeted sequencing (Memorial Sloan Kettering Mutation Profiling of Actionable Cancer Targets assay) or whole-exome sequencing. Both matching primary and recurrent tumours, and the de-novo high-grade PAC, harboured clonal PRKD1 E710D hotspot mutations, whereas the PAC that underwent high-grade transformation upon recurrence, which was wild-type for PRKD1, harboured a PRKD2 rearrangement. The PACs analysed here also harboured mutations targeting cancer genes such as PIK3CA, SETD2, ARID1A, and NOTCH2. A clonal decomposition analysis of the matching primary and recurrent PACs revealed that a minor subclone from the primary tumour became dominant in the recurrent tumour following a clonal selection evolutionary pattern. CONCLUSIONS: Our findings demonstrate that recurrent and high-grade PACs are underpinned by PRKD1 E710D hotspot mutations or PRKD2 rearrangements, and that recurrences of PACs may stem from the selection of pre-existing subclones in the primary tumour.

Ultimate eradication rate of Helicobacter pylori after first, second, or third-line therapy in Korea.

BACKGROUND AND AIMS: Resistance rates of Helicobacter pylori to clarithromycin, metronidazole, and quinolone are over 30% in South Korea. The aim of this prospective study was to evaluate the ultimate eradication rate of H. pylori after first, second, or third-line therapy in Korea. METHODS: A cohort of 2202 patients with H. pylori was treated with proton pump inhibitor (PPI)-based triple therapy for seven days. In case of treatment failure or recurrence, moxifloxacin-based triple therapy (MA) or bismuth-based quadruple therapy (QUAD) was randomly given. When the second-line treatment failed or H. pylori recurred, the unused MA or QUAD was used as a third-line treatment. RESULTS: Eighty-six patients had recurrence at least once during consecutive lines of treatments. Among 2116 patients (intention-to-treat [ITT]) without recurrence, 1644 (77.7%, per-protocol [PP]) completely followed our treatment flow. The ITT and PP rates of first-line treatment were 69.8% and 89.3%. After second line, they reached 78.4% (ITT) and 98.4% (PP). The "final" eradication rate up to third line treatment were 80.0% (1692/2116) and 99.8% (1641/1644), respectively. Resistance to clarithromycin showed significantly lower eradication rate (OR 0.358, P < 0.001) than those with susceptible strains in multivariate analysis. However in PP analysis, there was no significant difference in ultimate success rate regarding resistance pattern. CONCLUSION: Final success rate of PP was high, 99.8% in Korea in spite of high antibiotic resistance rates. However, high rate of refusal of further treatment and follow-up loss made ITT eradication rate low. Proper strategy to improve the treatment adherence is needed.

Salt-resistant homodimeric bactenecin, a cathelicidin-derived antimicrobial peptide.

The cathelicidin antimicrobial peptide bactenecin is a beta-hairpin molecule with a single disulfide bond and broad antimicrobial activity. The proform of bactenecin exists as a dimer, however, and it has been proposed that bactenecin is released as a dimer in vivo, although there has been little study of the dimeric form of bactenecin. To investigate the effect of bactenecin dimerization on its biological activity, we characterized the dimer's effect on phospholipid membranes, the kinetics of its bactericidal activity, and its salt sensitivity. We initially synthesized two bactenecin dimers (antiparallel and parallel) and two monomers (beta-hairpin and linear). Under oxidative folding conditions, reduced linear bactenecin preferentially folded into a dimer forming a ladder-like structure via intermolecular disulfide bonding. As compared to the monomer, the dimer had a greater ability to induce lysis of lipid bilayers and was more rapidly bactericidal. Interestingly, the dimer retained antimicrobial activity at physiological salt concentrations (150 mm NaCl), although the monomer was inactivated. This salt resistance was also seen with bactenecin dimer containing one intermolecular disulfide bond, and the bactenecin dimer appears to undergo multimeric oligomerization at high salt concentrations. Overall, dimeric bactenecin shows potent and rapid antimicrobial activity, and resists salt-induced inactivation under physiological conditions through condensation and oligomerization. These characteristics shed light on the features that a peptide would need to serve as an effective therapeutic agent.

Alternative mRNA polyadenylation can potentially affect detection of gene expression by affymetrix genechip arrays.

DNA microarrays have been widely used to examine gene expression. The Affymetrix GeneChip is one of the most commonly used platforms, employing DNA probes of 25 nucleotides designed to hybridise to different regions of target mRNA. The targeted region is often biased toward the 3' end of mRNA, which can lead to biases in detection. A large number of mammalian genes can undergo alternative polyadenylation under different cellular conditions. Multiple polyadenylation sites can lead to variable transcripts with different hybridisation properties. Here, we surveyed probes on human, mouse and rat GeneChip arrays and found that the detection of a significant proportion of mRNAs can potentially be affected by alternative polyadenylation. This could lead to inaccurate interpretation of GeneChip data when the changes of expression values actually result from alternative use of polyadenylation sites.

Assessment of waters and sediments impacted by drainage at the Young Dong coal mine site, South Korea.

INTRODUCTION: This study focused on the assessment of the geochemistry and hydrology of the Imgok Creek-Young Dong tributary for the design of a field coal mine drainage treatment system. METHODS AND RESULTS: Examination of this site showed that the pH was greatly lowered by the addition of the Young Dong water, except in the month of March. The alkalinity was also affected; the concentrations of iron, aluminum, and sulfate were elevated at sites below the confluence; of these, iron was particularly problematic. High iron concentrations were primarily restricted to the acid rock drainage (ARD) (YD-9) water sources, whereas high aluminum concentrations were seen in both the ARD and in some of the upstream water sources. The acidity was primarily due to ferrous and ferric iron with a lesser amount of aluminum acidity. Except for the sampling in March, the flow was dominated by the ARD. This hydrologic condition resulted from the loads of iron, aluminum, sulfate, and acidity, among other constituents, that were dominated by the ARD. CONCLUSION: Finally, treatment activities should primarily focus on the ARD and specifically seek to remove ferrous and ferric iron from the treatment system.

Dispersion and current-voltage characteristics of helical polyacetylene single fibers.

To study the transport properties of individual helical polyacetylene (PA) fibers, we developed a method to extract a single fiber from tightly entangled ropes of helical PA bulk film. After a few minutes of sonication of a piece of helical PA bulk film in an organic solution containing surfactant, a droplet of solution is deposited on the pre-pattened electrode under argon atmosphere. AFM images show that extracted helical PA fibers are typically 10 mum in length and 100-200 nm in diameter. We found that the helicity of bulk materials is conserved. We present the temperature dependencies of current-voltage characteristics of individual helical PA fibers doped with iodine.