Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients

<p>Abstract</p> <p>Background</p> <p>Germline mono-allelic promoter hypermethylation of the <it>MLH1 </it>or <it>MSH2 </it>gene in families with hereditary nonpolyposis colorectal cancer has recently been reported. The purpose of this study was to evaluate if germline promoter hypermethylation of the tumor suppressor gene <it>CDH1 </it>(<it>E-cadherin</it>) might cause predisposition to gastric cancer.</p> <p>Methods</p> <p>We prepared two groups of samples, a group of blood samples from 22 patients with familial gastric cancer or early-onset gastric cancer selected from among 39 patients, and a group of non-cancerous gastric tissue samples from 18 patients with sporadic gastric cancer showing loss of CDH1 expression selected from among 159 patients. We then investigated the allele-specific methylation status of the <it>CDH1 </it>promoter by bisulfite sequencing of multiple clones.</p> <p>Results</p> <p>Although there was a difference between the methylation level of the two alleles in some samples, there was no mono-allelic promoter hypermethylation in any of the samples.</p> <p>Conclusion</p> <p>These results suggest that germline mono-allelic hypermethylation of the <it>CDH1 </it>promoter is not a major predisposing factor for gastric cancer.</p

The CRKL gene encoding an adaptor protein is amplified, overexpressed, and a possible therapeutic target in gastric cancer

<p>Abstract</p> <p>Background</p> <p>Genomic DNA amplification is a genetic factor involved in cancer, and some oncogenes, such as <it>ERBB2</it>, are highly amplified in gastric cancer. We searched for the possible amplification of other genes in gastric cancer.</p> <p>Methods and Results</p> <p>A genome-wide single nucleotide polymorphism microarray analysis was performed using three cell lines of differentiated gastric cancers, and 22 genes (including <it>ERBB2</it>) in five highly amplified chromosome regions (with a copy number of more than 6) were identified. Particular attention was paid to the <it>CRKL</it> gene, the product of which is an adaptor protein containing Src homology 2 and 3 (SH2/SH3) domains. An extremely high <it>CRKL</it> copy number was confirmed in the MKN74 gastric cancer cell line using fluorescence <it>in situ</it> hybridization (FISH), and a high level of CRKL expression was also observed in the cells. The RNA-interference-mediated knockdown of CRKL in MKN74 disclosed the ability of CRKL to upregulate gastric cell proliferation. An immunohistochemical analysis revealed that CRKL protein was overexpressed in 24.4% (88/360) of the primary gastric cancers that were analyzed. The <it>CRKL</it> copy number was also examined in 360 primary gastric cancers using a FISH analysis, and <it>CRKL</it> amplification was found to be associated with CRKL overexpression. Finally, we showed that MKN74 cells with <it>CRKL</it> amplification were responsive to the dual Src/BCR-ABL kinase inhibitor BMS354825, likely via the inhibition of CRKL phosphorylation, and that the proliferation of MKN74 cells was suppressed by treatment with a CRKL-targeting peptide.</p> <p>Conclusion</p> <p>These results suggested that CRKL protein is overexpressed in a subset of gastric cancers and is associated with <it>CRKL</it> amplification in gastric cancer. Furthermore, our results suggested that CRKL protein has the ability to regulate gastric cell proliferation and has the potential to serve as a molecular therapy target for gastric cancer.</p

Moving Particle Semi-Implicit and Finite Element Method Coupled Analysis for Brain Shift Estimation

Neuronavigation is a computer-assisted technique for presenting three-dimensional images of a patient's brain to facilitate immediate and precise lesion localization by surgeons. Neuronavigation systems use preoperative medical images of patients. In neurosurgery, when the dura mater and arachnoid membrane are incised and the cerebrospinal fluid (CSF) drains out, the brain loses the CSF buoyancy and deforms in the direction of gravity, which is referred to as brain shift. This brain shift yields inaccurate neuronavigation. To reduce this inaccuracy, an intraoperative brain shift should be estimated. This paper proposes a dynamic simulation method for brain-shift estimation combining the moving-particle semi-implicit (MPS) method and the finite element method (FEM). The CSF was modeled using fluid particles, whereas the brain parenchyma was modeled using finite elements (FEs). Node particles were attached to the surface nodes of the brain parenchyma in the FE model. The interaction between the CSF and brain parenchyma was simulated using the repulsive force between the fluid particles and node particles. Validation experiments were performed using a gelatin block. The gelatin block was dipped into silicone oil, which was then gradually removed; the block deformation owing to the buoyancy loss was measured. The experimental deformation data were compared with the results of the MPS-FEM coupled analysis. The mean absolute error (MAE) between the simulated deformation and the average across the four experiments was 0.26 mm, while the mean absolute percentage error (MAPE) was 27.7%. Brain-shift simulations were performed using the MPS-FEM coupled analysis, and the computational cost was evaluated

2-Chloroalkoxy-Substituted Pentafluorinated Bistolanes as Novel Light-Emitting Liquid Crystals

In this study, we designed and synthesized novel pentafluorinated bistolane derivatives with 2-chloropentyl or 2-chlorohexyl flexible units as novel light-emitting liquid crystals (LELCs). By measuring the phase-transition behaviors, all derivatives were found to display liquid-crystalline (LC) phases during both heating and cooling processes. Among the novel bistolanes, the S- and R-configured derivatives exhibited a chiral nematic (N*) phase with a typical Grandjean optical texture. Interestingly, the chiral derivatives also exhibited a blue phase with a typical platelet texture in a narrow temperature range (2&#8211;4 &#176;C). Photophysical measurements revealed that the 2-chloroalkoxy-substituted pentafluorinated bistolanes exhibited intense photoluminescence (PL) both in solution and in crystalline phases. The PL characteristics, especially the maximum PL wavelength, were found to switch sensitively during the heating and cooling cycles depending on the molecular aggregates through the crystal (Cr) ⇄ N* phase transition. The 2-chloroalkoxy flexible units induced dynamic changes in the LC and PL properties, providing valuable insight into the potential of various LELCs as PL sensing materials