Nonvolatile SRAM based on Phase Change

金沢大学大学院自然科学研究科電子情報科学金沢大学工学

Site‐specific methylation patterns of the GAL and GALR1/2 genes in head and neck cancer: Potential utility as biomarkers for prognosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136246/1/mc22577.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136246/2/mc22577_am.pd

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

Mutation Spectrum Induced by 8-Bromoguanine, a Base Damaged by Reactive Brominating Species, in Human Cells

To date, the types of mutations caused by 8-bromoguanine (8BrG), a major base lesion induced by reactive brominating species during inflammation, in human cells and the 8BrG repair system remain largely unknown. In this study, we performed a supF forward mutation assay using a shuttle vector plasmid containing a single 8BrG in three kinds of human cell lines and revealed that 8BrG in DNA predominantly induces a G → T mutation but can also induce G → C, G → A, and delG mutations in human cells. Next, we tested whether eight kinds of DNA glycosylases (MUTYH, MPG, NEIL1, OGG1, SMUG1, TDG, UNG2, and NTHL1) are capable of repairing 8BrG mispairs with any of the four bases using a DNA cleavage activity assay. We found that both the SMUG1 protein and the TDG protein exhibit DNA glycosylase activity against thymine mispaired with 8BrG and that the MUTYH protein exhibits DNA glycosylase activity against adenine mispaired with 8BrG. These results suggest that 8BrG induces some types of mutations, chiefly a G → T mutation, in human cells, and some DNA glycosylases are involved in the repair of 8BrG

A long-forgotten ‘dinosaur’ bone from a museum cabinet, uncovered to be a Japan\u27s iconic extinct mammal, Paleoparadoxia (Desmostylia, Mammalia)

Here, we report a new ‘discovery’ of a desmostylian fossil in the geological collection at a national university in Japan. This fossil was unearthed over 60 years ago and donated to the university. Owing to the original hand-written note kept with the fossil in combination with interview investigation, we were able to reach two equally possible fossil sites in the town of Tsuchiyu Onsen, Fukushima. Through the interviews, we learned that the fossil was discovered during construction of a debris flow barrier and that it was recognized as a ‘dinosaur’ bone among the locals and displayed in the Village Hall before/until the town experienced a fire disaster in 1954. As scientific findings, the fossil was identified to be a right femur of Paleoparadoxia (Desmostylia), which shows well-preserved muscle scars on the surface. The age was estimated to be 15.9 Ma or younger in zircon-dating. This study shows an excellent case that historical and scientific significances could be extracted from long-forgotten uncatalogued specimens as long as the original information is retained with the specimens

Abnormal Expressions of DNA Glycosylase Genes NEIL1, NEIL2, and NEIL3 Are Associated with Somatic Mutation Loads in Human Cancer

The effects of abnormalities in the DNA glycosylases NEIL1, NEIL2, and NEIL3 on human cancer have not been fully elucidated. In this paper, we found that the median somatic total mutation loads and the median somatic single nucleotide mutation loads exhibited significant inverse correlations with the median NEIL1 and NEIL2 expression levels and a significant positive correlation with the median NEIL3 expression level using data for 13 cancer types from the Cancer Genome Atlas (TCGA) database. A subset of the cancer types exhibited reduced NEIL1 and NEIL2 expressions and elevated NEIL3 expression, and such abnormal expressions of NEIL1, NEIL2, and NEIL3 were also significantly associated with the mutation loads in cancer. As a mechanism underlying the reduced expression of NEIL1 in cancer, the epigenetic silencing of NEIL1 through promoter hypermethylation was found. Finally, we investigated the reason why an elevated NEIL3 expression level was associated with an increased number of somatic mutations in cancer and found that NEIL3 expression was positively correlated with the expression of APOBEC3B, a potent inducer of mutations, in diverse cancers. These results suggested that the abnormal expressions of NEIL1, NEIL2, and NEIL3 are involved in cancer through their association with the somatic mutation load

Implantation of Liquid Nitrogen Frozen Tumor Tissue after Posterior Decompression and Stabilization for Metastatic Spinal Tumors

Study DesignA retrospective study.PurposeTo evaluate the immunity-enhancing effect of implantation of a liquid nitrogen-treated tumor.Overview of LiteratureWe have developed a new technique of implanting a tumor frozen in liquid nitrogen after posterior decompression and stabilization, with the aim of enhancing antitumor immunity in order to prolong the survival period of the patient. In the current study, the immunity-enhancing effect of this new technique has been evaluated.MethodsThe subjects were 19 patients in whom we had earlier performed decompression and stabilization between April 2011 and September 2013. The 19 subjects were divided into two groups, namely a frozen autologous tumor tissue implantation group (n=15; "implantation group"), which consisted of patients, who underwent implantation with autologous tumor tissue frozen in liquid nitrogen, and a control group (n=4), which consisted of patients, who did not undergo autologous cancer transplantation. To evaluate the immunity-enhancing effect of the protocol, plasma cytokines (interferon [IFN]-γ and interleukin [IL]-12) were analyzed before surgery and a month after surgery.ResultsThe mean rate of increase in IFN-γ was significantly higher in the implantation group (p=0.03). Regarding IL-12, no significant difference was observed between the groups, although the implantation group exhibited increased levels of IL-12 (p=0.22).ConclusionsDecompression and stabilization combined with autologous frozen tumor cell implantation can enhance cancer immunity in metastatic spinal tumor patients. It is hypothesized that this procedure might prevent local recurrence and prolong survival period

Surgical site infection after total en bloc spondylectomy: Risk factors and the preventive new technology

Background context Surgical site infection (SSI) associated with instruments remains a serious and common complication in patients who undergo total en bloc spondylectomy (TES). It is very important that the risk factors for SSI are known to prevent it.Purpose The purpose of the study was to identify independent risk factors for SSI after TES and evaluate the positive effect of iodine-supported spinal instruments in the prevention of SSI after TES.Study design This is a retrospective clinical study.Patient sample One hundred twenty-five patients who underwent TES for vertebral tumor were evaluated.Outcome measures Incidence rate of SSI, risk factors for SSI after TES, and safety of iodine-supported spinal instruments were the outcome measures.Methods Risk factors for SSI were analyzed using logistic regression. In recent 69 patients with iodine-supported spinal instruments, the thyroid hormone levels in the blood were examined to confirm if iodine from the implant influenced thyroid function. Postoperative radiological evaluations were performed regularly.Results The rate of SSI was 6.4% (8/125 patients). By multivariate logistic regression, combined anterior and posterior approach and nonuse of iodine-supported spinal instruments were associated with an increased risk of SSI. The rate of SSI without iodine-supported spinal instruments was 12.5%, whereas the rate with iodine-supported spinal instruments was 1.4%. This difference was statistically significant. There were no detected abnormalities of thyroid gland function with the use of iodine-supported instruments. Among the 69 patients with iodine-supported spinal instruments, 2 patients required additional surgery because of instrument failure. However, there were no obvious involvements with the use of iodine-supported spinal instruments.Conclusions This study identified combined anterior and posterior approach and nonuse of iodine-supported spinal instruments to be independent risk factors for SSI after TES. Iodine-supported spinal instrument was extremely effective for prevention of SSI in patients with compromised status, and it had no detection of cytotoxic or adverse effects on the patients