298 research outputs found

    17世紀宗教詩のパラテクストに関する一考察

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    早大学位記番号:新8065早稲田大

    Long interspersed nuclear element-1 hypomethylation is a potential biomarker for the prediction of response to oral fluoropyrimidines in microsatellite stable and CpG island methylator phenotype-negative colorectal cancer

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    金沢大学がん研究所We investigated the clinical value of methylation of long interspersed nuclear element-1 (LINE-1) for the prognosis of colorectal cancer (CRC) and for the survival benefit from adjuvant chemotherapy with oral fluoropyrimidines. LINE-1 methylation in tumor DNA was measured by quantitative methylation-specific PCR in 155 samples of stage II and stage III CRC. The presence of microsatellite instability and CpG island methylator phenotype (CIMP) were assessed and 131 microsatellite stable/CIMP- cases were selected for survival analysis, of which 77 patients had received postoperative adjuvant chemotherapy with oral fluoropyrimidines. The CRC cell lines were used to investigate possible mechanistic links between LINE-1 methylation and effects of 5-fluorouracil (5-FU). High LINE-1 methylation was a marker for better prognosis in patients treated by surgery alone. Patients with low LINE-1 methylation who were treated with adjuvant chemotherapy survived longer than those treated by surgery alone, suggestive of a survival benefit from the use of oral fluoropyrimidines. In contrast, a survival benefit from chemotherapy was not observed for patients with high LINE-1 methylation. The CRC cell lines treated with 5-FU showed increased expression of LINE-1 mRNA. This was associated with upregulation of the phospho-histone H2A.X in cells with low LINE-1 methylation, but not in cells with high LINE-1 methylation. The 5-FU-mediated induction of phospho-histone H2A.X, a marker of DNA damage, was inhibited by knockdown of LINE-1. These results suggest that LINE-1 methylation is a novel predictive marker for survival benefit from adjuvant chemotherapy with oral fluoropyrimidines in CRC patients. This finding could be important for achieving personalized chemotherapy. © 2010 Japanese Cancer Association

    Long interspersed nuclear element 1 hypomethylation is a marker of poor prognosis in stage IA non-small cell lung cancer

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    金沢大学がん研究所Purpose: Global hypomethylation and the hypermethylation of gene promoter regions are common events in tumor DNA. The aim of this study was to evaluate the prognostic significance of both global hypomethylation and gene promoter hypermethylation in DNA from non-small cell lung cancer (NSCLC). Experimental Design: Genomic DNA was obtained from the tumor tissue of 379 NSCLC patients who underwent surgery. Methylation levels were measured by real-time PCR following bisulfite modification of DNA and were correlated with clinicopathologic parameters and patient prognosis. Methylation of long interspersed nuclear element 1 (LINE-1) was used as a surrogate marker for global methylation. Hypermethylation of the APC, CDH13, and RASSF1 promoter regions was also evaluated. Results: Tumor tissue showed significantly higher CDH13 and RASSF1 methylation levels compared with normal lung tissue, but lower LINE-1 methylation levels. APC, RASSF1, and LINE-1 methylation levels were significant prognostic factors in univariate analysis of an initial cohort of 234 cases. APC and LINE-1 methylation remained significant prognostic factors in multivariate analysis that included age, gender, smoking history, histologic type, and pathologic stage. LINE-1 methylation showed marginally significant prognostic value in stage IA and IB disease. Expansion of the study cohort to 364 cases revealed that LINE-1 methylation had significant prognostic value for stage IA NSCLC patients in multivariate analysis. Conclusions: LINE-1 hypomethylation was an independent marker of poor prognosis in stage IA NSCLC. Validation of this finding in additional tumor cohorts could have clinical relevance for the management of early-stage NSCLC. ©2010 AACR

    RVS for small lesion in hepatectomy

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    Background : Systemic chemotherapy can drastically downsize metastatic liver tumors and these small liver lesions could sometimes be difficult for surgeons to detect during hepatectomy. We assessed the usefulness of intraoperative real-time virtual sonography (RVS) with contrast-enhanced ultrasonography (CEUS) using ‘Sonazoid’ contrast agent (RVS-CEUS). Methods : We performed the intraoperative RVS-CEUS technique on 10 tumor lesions in six cases, which were scheduled for hepatic resection of < 10 mm in diameter in our liver metastases series. These lesions were preoperatively diagnosed by contrast enhanced-computed tomography (CE-CT) or Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (EOB-MRI). We assessed the detectability of a tumor with RVS-CEUS during surgery and compared it with that of preoperative CE-CT or EOB-MRI. Results : Detectability of RVS-CEUS for 10 small lesions was 90% (n = 9/10) and that of other preoperative modalities were 50% (n = 5/10, CE-CT) and 100% (n = 10/10, EOB-MRI). Minimum tumor size detected was 3.0 mm in diameter, and maximum depth of detection with RVS-CEUS was 43.5 mm ; these results could be an advantage when compared with other intraoperative diagnostic modalities. Conclusion : Intraoperative RVS-CEUS was useful for detecting small metastatic liver lesions after chemotherapy and could be an effective intraoperative diagnostic technique for hepatic resection of a size < 10 mm

    Initial In-Orbit Operation Result of Microsatellite HIBARI: Attitude Control by Driving Solar Array Paddles

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    We have developed a 50kg class microsatellite HIBARI . The mission of this satellite is to demonstrate a novel attitude control method for microsatellites which is called “Variable Shape Attitude Control (VSAC).” VSAC is a method using anti-torque by driving variable shape structures. HIBARI has four drivable solar array paddles, and will demonstrate VSAC. The development of HIBARI began in 2019, and it was injected into orbit in November 2021 under the Innovative Satellite Technology Demonstration Program led by JAXA. Currently, HIBARI has completed its critical phase and paddle deployment phase, and is conducting paddle drive experiments in orbit. In paddle drive experiments, the paddles are driven according to the command values, and the accompanying attitude change is confirmed. These results indicate that the satellite can generate angular velocities of 4 deg/s or more and achieve the target agile maneuver of 30deg in 10seconds, which is comparable to that of CMG for microsatellite

    Disconnectivity between Dorsal Raphe Nucleus and Posterior Cingulate Cortex in Later Life Depression

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    The dorsal raphe nucleus (DRN) has been repeatedly implicated as having a significant relationship with depression, along with its serotoninergic innervation. However, functional connectivity of the DRN in depression is not well understood. The current study aimed to isolate functional connectivity of the DRN distinct in later life depression (LLD) compared to a healthy age-matched population. Resting state functional magnetic resonance imaging (rsfMRI) data from 95 participants (33 LLD and 62 healthy) were collected to examine functional connectivity from the DRN to the whole brain in voxel-wise fashion. The posterior cingulate cortex (PCC) bilaterally showed significantly smaller connectivity in the LLD group than the control group. The DRN to PCC connectivity did not show any association with the depressive status. The findings implicate that the LLD involves disruption of serotoninergic input to the PCC, which has been suggested to be a part of the reduced default mode network in depression
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