Acetic acid-indigo carmine chromoendoscopy for delineating early gastric cancers: its usefulness according to histological type

<p>Abstract</p> <p>Background</p> <p>Endoscopic treatments, such as endoscopic submucosal dissection (ESD) and laparoscopic gastrectomy, are increasingly used to treat a subset of patients with early gastric cancer (EGC). To achieve successful outcomes, it is very important to accurately determine the lateral extent of the tumor. Therefore, we investigated the diagnostic performance of chromoendoscopy using indigo carmine dye added to acetic acid (AI chromoendoscopy) in delineating differentiated or undifferentiated adenocarcinomas in patients with EGC.</p> <p>Methods</p> <p>We prospectively included 151 lesions of 141 patients that had an endoscopic diagnosis of EGC. All the lesions were examined by conventional endoscopy and AI chromoendoscopy before ESD or laparoscopic gastrectomy. The border clarification between the lesion and the normal mucosa was classified as distinct or indistinct before and after AI chromoendoscopy.</p> <p>Results</p> <p>The borders of the lesions were distinct in 66.9% (101/151) with conventional endoscopy and in 84.1% (127/151) with AI chromoendoscopy (<it>P </it>< 0.001). Compared with conventional endoscopy, AI chromoendoscopy clarified the border in a significantly higher percentage of differentiated adenocarcinomas (74/108 [68.5%] vs 97/108 [89.8%], respectively, <it>P </it>< 0.001). However, the border clarification rate for undifferentiated adenocarcinomas did not differ between conventional endoscopy and AI chromoendoscopy (27/43 [62.8%] vs 30/43 [70.0%], respectively, <it>P </it>= 0.494).</p> <p>Conclusions</p> <p>AI chromoendoscopy is useful in determining the lateral extent of EGCs. However, its usefulness is reduced in undifferentiated adenocarcinomas.</p

Inertio-elastic focusing of bioparticles in microchannels at high throughput

Controlled manipulation of particles from very large volumes of fluid at high throughput is critical for many biomedical, environmental and industrial applications. One promising approach is to use microfluidic technologies that rely on fluid inertia or elasticity to drive lateral migration of particles to stable equilibrium positions in a microchannel. Here, we report on a hydrodynamic approach that enables deterministic focusing of beads, mammalian cells and anisotropic hydrogel particles in a microchannel at extremely high flow rates. We show that on addition of micromolar concentrations of hyaluronic acid, the resulting fluid viscoelasticity can be used to control the focal position of particles at Reynolds numbers up to Re≈10,000 with corresponding flow rates and particle velocities up to 50 ml min[superscript −1] and 130 m s[superscript −1]. This study explores a previously unattained regime of inertio-elastic fluid flow and demonstrates bioparticle focusing at flow rates that are the highest yet achieved.National Institute for Biomedical Imaging and Bioengineering (U.S.) (P41 BioMicroElectroMechanical Systems Resource Center)National Institute for Biomedical Imaging and Bioengineering (U.S.) (P41 EB002503)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Army Research Office (Institute for Collaborative Biotechnologies Grant W911NF-09-0001

The Function of Heterodimeric AP-1 Comprised of c-Jun and c-Fos in Activin Mediated Spemann Organizer Gene Expression

BACKGROUND:Activator protein-1 (AP-1) is a mediator of BMP or FGF signaling during Xenopus embryogenesis. However, specific role of AP-1 in activin signaling has not been elucidated during vertebrate development. METHODOLOGY/PRINCIPAL FINDINGS:We provide new evidence showing that overexpression of heterodimeric AP-1 comprised of c-jun and c-fos (AP-1(c-Jun/c-Fos)) induces the expression of BMP-antagonizing organizer genes (noggin, chordin and goosecoid) that were normally expressed by high dose of activin. AP-1(c-Jun/c-Fos) enhanced the promoter activities of organizer genes but reduced that of PV.1, a BMP4-response gene. A loss of function study clearly demonstrated that AP-1(c-Jun/c-Fos) is required for the activin-induced organizer and neural gene expression. Moreover, physical interaction of AP-1(c-Jun/c-Fos) and Smad3 cooperatively enhanced the transcriptional activity of goosecoid via direct binding on this promoter. Interestingly, Smad3 mutants at c-Jun binding site failed in regulation of organizer genes, indicating that these physical interactions are specifically necessary for the expression of organizer genes. CONCLUSIONS/SIGNIFICANCE:AP-1(c-Jun/c-Fos) plays a specific role in organizer gene expression in downstream of activin signal during early Xenopus embryogenesis

Frequent Long-Range Epigenetic Silencing of Protocadherin Gene Clusters on Chromosome 5q31 in Wilms' Tumor

Wilms' tumour (WT) is a pediatric tumor of the kidney that arises via failure of the fetal developmental program. The absence of identifiable mutations in the majority of WTs suggests the frequent involvement of epigenetic aberrations in WT. We therefore conducted a genome-wide analysis of promoter hypermethylation in WTs and identified hypermethylation at chromosome 5q31 spanning 800 kilobases (kb) and more than 50 genes. The methylated genes all belong to α-, β-, and γ-protocadherin (PCDH) gene clusters (Human Genome Organization nomenclature PCDHA@, PCDHB@, and PCDHG@, respectively). This demonstrates that long-range epigenetic silencing (LRES) occurs in developmental tumors as well as in adult tumors. Bisulfite polymerase chain reaction analysis showed that PCDH hypermethylation is a frequent event found in all Wilms' tumor subtypes. Hypermethylation is concordant with reduced PCDH expression in tumors. WT precursor lesions showed no PCDH hypermethylation, suggesting that de novo PCDH hypermethylation occurs during malignant progression. Discrete boundaries of the PCDH domain are delimited by abrupt changes in histone modifications; unmethylated genes flanking the LRES are associated with permissive marks which are absent from methylated genes within the domain. Silenced genes are marked with non-permissive histone 3 lysine 9 dimethylation. Expression analysis of embryonic murine kidney and differentiating rat metanephric mesenchymal cells demonstrates that Pcdh expression is developmentally regulated and that Pcdhg@ genes are expressed in blastemal cells. Importantly, we show that PCDHs negatively regulate canonical Wnt signalling, as short-interfering RNA–induced reduction of PCDHG@ encoded proteins leads to elevated β-catenin protein, increased β-catenin/T-cell factor (TCF) reporter activity, and induction of Wnt target genes. Conversely, over-expression of PCDHs suppresses β-catenin/TCF-reporter activity and also inhibits colony formation and growth of cancer cells in soft agar. Thus PCDHs are candidate tumor suppressors that modulate regulatory pathways critical in development and disease, such as canonical Wnt signaling