胆管癌の予後と腫瘍部位及び病理組織型との関連に関する研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 赤林 朗, 東京大学教授 小池 和彦, 東京大学教授 長谷川 潔, 東京大学准教授 大庭 幸治, 東京大学准教授 槇野 陽介University of Tokyo(東京大学

In-situ mechanical weakness of subducting sediments beneath a plate boundary décollement in the Nankai Trough

© 2018, The Author(s). The study investigates the in-situ strength of sediments across a plate boundary décollement using drilling parameters recorded when a 1180-m-deep borehole was established during International Ocean Discovery Program (IODP) Expedition 370, Temperature-Limit of the Deep Biosphere off Muroto (T-Limit). Information of the in-situ strength of the shallow portion in/around a plate boundary fault zone is critical for understanding the development of accretionary prisms and of the décollement itself. Studies using seismic reflection surveys and scientific ocean drillings have recently revealed the existence of high pore pressure zones around frontal accretionary prisms, which may reduce the effective strength of the sediments. A direct measurement of in-situ strength by experiments, however, has not been executed due to the difficulty in estimating in-situ stress conditions. In this study, we derived a depth profile for the in-situ strength of a frontal accretionary prism across a décollement from drilling parameters using the recently established equivalent strength (EST) method. At site C0023, the toe of the accretionary prism area off Cape Muroto, Japan, the EST gradually increases with depth but undergoes a sudden change at ~ 800 mbsf, corresponding to the top of the subducting sediment. At this depth, directly below the décollement zone, the EST decreases from ~ 10 to 2 MPa, with a change in the baseline. This mechanically weak zone in the subducting sediments extends over 250 m (~ 800–1050 mbsf), corresponding to the zone where the fluid influx was discovered, and high-fluid pressure was suggested by previous seismic imaging observations. Although the origin of the fluids or absolute values of the strength remain unclear, our investigations support previous studies suggesting that elevated pore pressure beneath the décollement weakens the subducting sediments. [Figure not available: see fulltext.]

Rebecca Goodale wrote illustrated books as a child, and as an adult creates and

Rebecca Goodale wrote illustrated books as a child, and as an adult creates and exhibits book art. She once wanted to be a research biologist and now draws from nature, as with her current series, Threatened and Endangered. She describes how she made her series, Draw Bridge, at the beginning of her career while living by a bridge in Portland. She teaches art at the University of Southern Maine. She recently discovered she has to move from her longtime studio

低温オーブントラッピングキャピラリーガスクロマトグラフィーによるヒト全血中アセトニトリル及びプロピオニトリルの高感度分析

We have developed a simple and sensitive method for determining acetonitrile and propionitrile in human whole blood using capillary gas chromatography (GC) with cryogenic oven trapping. After heating 0.5 ml of a whole blood sample containing both nitriles and 0.5 ml of distilled water in a 7-ml vial at 75℃ for 15 min, 5 ml of the headspace vapor was drawn into a 10-ml syringe and injected to GC with a flame thermionic detector. A sharp peak was obtained for acetonitrile at -10℃ of the initial oven temperature. The extraction efficiencies for acetonitrile and propionitrile were 0.27 and 0.40%, respectively. For quantitation of acetonitrile, propionitrile was used as internal standard, and vise versa. The calibration curves for both compounds gave good linearity in the range of 0.2-6 μg/ml whole blood. The detection limits (signal to noise ratio = 3) were 0.05μg/ml for acetonitrile and 0.01μg/ml for propionitrile. The coefficients of intra-day variations were 1.0% at 0.4μg/ml and 1.7% at 2μg/ml for acetonitrile; 7.1% at 0.4μg/m1 and 1.0 % at 2μg/ml for propionitrile. This method can be applicable for determining these nitriles in whole blood samples in acute and chronic intoxication cases.rights:日本法中毒学会rights:本文データは日本法中毒学会の許諾のもと掲載しています

Volume–Outcome Relationship in Cancer Survival Rates: Analysis of a Regional Population-Based Cancer Registry in Japan

Background: There is limited data on the relationship between hospital volumes and outcomes with respect to cancer survival in Japan. The primary objective of this study was to evaluate the effect of hospital volume on cancer survival rate using a population-based cohort database. Methods: Using the Kanagawa cancer registry, propensity score matching was employed to create a dataset for each cancer type by selecting 1:1 matches for cases from high- and other-volume hospitals. The 5-year survival rate was estimated and the hazard ratio (HR) for hospital volume was calculated using a Cox proportional hazard model. Additional analyses were performed limited to cancer patients who underwent surgical operation, chemotherapy, and other treatments in each tumor stage and at the time of diagnosis. Results: The number of cases with complete data, defined as common cancers (prostate, kidney, bladder, esophagus, stomach, liver, pancreas, colon, breast, and lung), was 181,039. Adjusted HR differed significantly among hospital volume categories for the most common cancers except bladder, and the trends varied according to cancer type. The HR ranged from 0.76 (95%CI, 0.74–0.79) for stomach cancer to 0.85 (0.81–0.90) for colon cancer. Conclusions: This study revealed that a relationship may exist between hospital volume and cancer survival in Japan

Targeted phototherapy for malignant pleural mesothelioma: near-infrared photoimmunotherapy targeting podoplanin

Malignant pleural mesothelioma (MPM) has extremely limited treatment despite a poor prognosis. Moreover, molecular targeted therapy for MPM has not yet been implemented; thus, a new targeted therapy is highly desirable. Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer therapy that combines the specificity of antibodies for targeting tumors with toxicity induced by the photoabsorber after exposure to NIR-light. In this study, we developed a new phototherapy targeting podoplanin (PDPN) for MPM with the use of both NIR-PIT and an anti-PDPN antibody, NZ-1. An antibody-photosensitizer conjugate consisting of NZ-1 and phthalocyanine dye was synthesized. In vitro NIR-PIT-induced cytotoxicity was measured with both dead cell staining and luciferase activity on various MPM cell lines. In vivo NIR-PIT was examined in both the flank tumor and orthotopic mouse model with in vivo real-time imaging. In vitro NIR-PIT-induced cytotoxicity was NIR-light dose dependent. In vivo NIR-PIT led to significant reduction in both tumor volume and luciferase activity in a flank model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). The PDPN-targeted NIR-PIT resulted in a significant antitumor effect in an MPM orthotopic mouse model (p < 0.05, NIR-PIT group versus NZ-1-IR700 group). This study suggests that PDPN-targeted NIR-PIT could be a new promising treatment for MPM

Insulin Acts through FOXO3a to Activate Transcription of Plasminogen Activator Inhibitor Type 1

Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of fibrinolysis. PAI-1 levels are elevated in type 2 diabetes, and this elevation correlates with macro- and microvascular complications of diabetes. However, the mechanistic link between insulin and up-regulation of PAI-1 is unclear. Here we demonstrate that overexpression of Forkhead-related transcription factor (Fox)O1, FoxO3a, and FoxC1 augment insulin’s ability to activate the PAI-1 promoter. In addition, insulin treatment promotes the phosphorylation of nuclear and cytoplasmic Fox03a and an increase of cytoplasmic Fox03a. In contrast, insulin treatment led to the accumulation of phospho-Fox01 only in the cytoplasm. Furthermore, insulin also increased the ability of chimeric LexA-FoxO1, LexA-FoxO3a, and LexA-FoxC1 proteins to increase the activity of a LexA reporter, suggesting that the effect of insulin on FoxO3a was direct. Using small interfering RNA to specifically deplete each of the Fox transcription factors tested, we demonstrate that only reduction of FoxO3a inhibits insulin-increased PAI-1-Luc expression and PAI-1 mRNA accumulation. Finally, chromatin immunoprecipitation assays confirm the presence of FoxO3a on the PAI-1 promoter. These results suggest that FoxO3a mediates insulin-increased PAI-1 gene expression