地震発生帯における深部掘削孔を用いた長期計測

Large earthquakes occur frequently in subduction zones. Most earthquakes are generated in the seismogenic zone, a fairly limited area confined to the shallower regions of the subduction plate boundary. To understand the processes of earthquake generation, it is essential to monitor the physical and mechanical properties of the seismogenic zone over long periods. At present, there are no deep borehole observations of the seismogenic zone more than 3km below seafloor, because it has, until now, been impossible to penetrate to such depths below the sea floor. The Integrated Ocean Drilling Program (IODP), scheduled to begin in 2003, plans to drill boreholes beneath the ocean floor using a multiple-drilling platform operation. The IODP riser-quipped drilling ship (Chikyu) enables the emplacement of boreholes up to 0km beneath the ocean floor, and will provide opportunities to conduct long-term deep borehole observations in the seismogenic zone. Long-term borehole observations in the seismogenic zone are expected to require the development of advanced sampling, monitoring, and recording technology. Here, we discuss the scientific objectives, engineering and technical challenges, and experimental design for a deep borehole, long-term deepborehole monitoring system aimed at understanding the processes of earthquake generation in the seismogenic zone of subduction plate boundaries. We focus specifically on the relationships between environmental conditions in the deep subsurface, details of monitoring and recording, and design and implementation of scientific tools and programs

Arginase II expressed in cancer-associated fibroblasts indicates tissue hypoxia and predicts poor outcome in patients with pancreatic cancer.

An adequate level of arginine in the tissue microenvironment is essential for T cell activity and survival. Arginine levels are regulated by the arginine-catabolizing enzyme, arginase (ARG). It has been reported that arginase II (ARG2), one of two ARGs, is aberrantly expressed in prostate cancer cells, which convert arginine into ornithine, resulting in a lack of arginine that weakens tumor-infiltrating lymphocytes and renders them dysfunctional. However, immune suppression mediated by ARG2-expressing cancer cells in lung cancer has not been observed. Here we studied the expression of ARG2 in pancreatic ductal carcinoma (PDC) tissue clinicopathologically by examining over 200 cases of PDC. In contrast to prostate cancer, ARG2 expression was rarely demonstrated in PDC cells by immunohistochemistry, and instead ARG2 was characteristically expressed in α-smooth muscle actin-positive cancer-associated fibroblasts (CAFs), especially those located within and around necrotic areas in PDC. The presence of ARG2-expressing CAFs was closely correlated with shorter overall survival (OS; P  = 0.003) and disease-free survival (DFS; P  = 0.0006). Multivariate Cox regression analysis showed that the presence of ARG2-expressing CAFs in PDC tissue was an independent predictor of poorer OS (hazard ratio [HR]  = 1.582, P  = 0.007) and DFS (HR  = 1.715, P  = 0.001) in PDC patients. In addition to the characteristic distribution of ARG2-expressing CAFs, such CAFs co-expressed carbonic anhydrase IX, SLC2A1, or HIF-1α, markers of hypoxia, in PDC tissue. Furthermore, in vitro experiments revealed that cultured fibroblasts extracted from PDC tissue expressed the ARG2 transcript after exposure to hypoxia, which had arginase activity. These results indicate that cancer cell-mediated immune suppression through ARG2 expression is not a general event and that the presence of ARG2-expressing CAFs is an indicator of poor prognosis, as well as hypoxia, in PDC tissue

Identification of adipophilin as a potential plasma biomarker for colorectal cancer using label-free quantitative mass spectrometry and protein microarray.

[Background]: The aim of this study was to identify a new plasma biomarker for use in early detection of colorectal cancer.[Methods]: Using the combination of hollow fiber membrane (HFM)-based low-molecular weight protein enrichment and two-dimensional image converted analysis of liquid chromatography and mass spectrometry (2DICAL), we compared the plasma proteome of 22 colorectal cancer patients with those of 21 healthy controls. An identified biomarker candidate was then validated in two larger cohorts [validation-1 (n = 210) and validation-2 (n = 113)] using a high-density reverse-phase protein microarray. [Results]: From a total of 53, 009 mass peaks, we identified 103 with an area under curve (AUC) value of 0.80 or higher that could distinguish cancer patients from healthy controls. A peak that increased in colorectal cancer patients, with an AUC of 0.81 and P value of 0.0004 (Mann–Whitney U test), was identified as a product of the PLIN2 gene [also known as perilipin-2, adipose differentiation-related protein (ADRP), or adipophilin]. An increase in plasma adipophilin was consistently observed in colorectal cancer patients, including those with stage I or stage II disease (P < 0.0001, Welch's t test). Immunohistochemical analysis revealed that adipophilin is expressed primarily in the basal sides of colorectal cancer cells forming polarized tubular structures, and that it is absent from adjacent normal intestinal mucosae. [Conclusions]: Adipophilin is a plasma biomarker potentially useful for the detection of early-stage colorectal cancer. [Impact]: The combination of HFM and 2DICAL enables the comprehensive analysis of plasma proteins and is ideal for use in all biomarker discovery studies

ARG2 was expressed mostly in CAFs under hypoxic conditions.

<p>Histology of PDC tissue in low- (upper columns) and high-power view (lower columns). HE staining and immunohistochemistry for ARG2, CAIX, and SLC2A1 in serial tissue sections. Necrotic areas are surrounded by star marks in the upper HE photo and the rectangle (light blue) corresponds to the area of the lower column. Double immunostaining (the right-most columns) reveals that most of the granular ARG2 staining (brown) is present in spindle-shaped cells stained for CAIX (purple). Inset is a very high-power view.</p

Univariate and multivariate analyses of prognostic factors associated with disease-free survival in patients with ductal carcinoma of the pancreas.

<p>W/D, well differentiated tubular adenocarcinoma and papillary carcinoma; M/D, moderately differentiated.</p><p>tubular adenocarcinoma; P/D, poorly differentaited adenocarcinoma.</p>*<p>Classified according to the classification of pancreatic carcinoma of Japan Pancreas Society.</p

Kaplan-Meier survival curves.

<p>(A, C) Kaplan-Meier survival curve showing a comparison of overall survival between the presence (grades 1 and 2) and absence (grade 0) of ARG2 expression in stromal cells (<i>P</i>  = 0.003) in A and that among expression grades (grades 0 to 2) of ARG2 in stromal cells (grade 0 vs. grade 1, log-rank test, <i>P</i>  = 2.08; grade 0 vs. grade 2, <i>P</i><0.0001; grade 1 vs. grade 2, <i>P</i>  = 0.0009) in C. (B, D) Kaplan-Meier survival curve showing a comparison of disease-free survival between the presence (grades 1 and 2) and absence (grade 0) of ARG2 expression in stromal cells (<i>P</i>  = 0.0006) in B and that among expression grades (grades 0 to 2) of ARG2 in stromal cells (grade 0 vs. grade 1, <i>P</i>  = 0.069; grade 0 vs. grade 2, <i>P</i><0.0001; grade 1 vs. grade 2, <i>P</i>  = 0.013) in D. Black circle and white circle represent censoring and failure, respectively.</p

Correlation of expression of ARG2 in stromal cells with clinicopathological characteristics.

<p>W/D, well differentiated tubular adenocarcinoma and papillary carcinoma; M/D, moderately differentiated.</p><p>tubular adenocarcinoma; P/D, poorly differentaited adenocarcinoma.</p>*<p>Classified according to the classification of pancreatic carcinoma of Japan Pancreas Society.</p>**<p>Comparisons of qualitative variables are performed using the χ² test and otherwise Fisher’s exact test.</p>***<p>Total number of patients are 211 and otherwise 214.</p