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BackgroundImmunological status in surgically resected specimens affects the outcome of ‘operable’ colorectal cancer patients. For example, a high number of tumor infiltrating lymphocytes, CD3+ cells, ... CD8+ cells, or CD45RO+ cells in a tumor is associated with improved prognosis. However, it has not been determined whether the immunological status in peripheral blood affects the outcome of ‘inoperable’ metastatic colorectal cancer (MCRC) patients. We investigated the impact of peripheral immunological status at pre-treatment on progression-free survival (PFS) of MCRC patients.MethodsPeripheral blood was prospectively collected from consecutive MCRC patients (n=40) before they received a first-line chemotherapy. The quantity of each of 25 immune subsets, including monocytic myeloid-derived suppressor cells (M-MDSC, defined as Lineage-CD14+CD11b+CD33+HLA-DRlow/-) and effector memory T cells (TEM, defined as CD3+CD4+ or CD8+CD45RA-CCR7-) was measured using multicolor-flow cytometry. The patients were divided into high (> median) and low (< median) groups based on the median value for each immune subset. PFS was compared between the two patient groups.ResultsOf the 25 immune subsets quantified, we identified a high quantity of M-MDSC, a low quantity of CD4+ TEM, or a low quantity of CD8+ TEM as adverse prognostic factors for PFS. Thus, patients with high M-MDSC, low CD4+ TEM or low CD8+ TEM had significantly shorter PFS than those with low M-MDSC, high CD4+ TEM, or high CD8+ TEM, respectively (p=0.004, 0.005, and 0.002, respectively). Ten (25%) patients had three adverse factors, 11 (27.5 %) patients had 2, 8 (20%) patients had one, and 11 (27.5%) patients had none. Patients were classified into two distinct prognostic groups based on the number of adverse factors that were present in each patient. The presence of 2 or 3 adverse factors (n=21, 52.5%) correlated with significantly shorter PFS compared to the presence of no or 1 adverse factor (n=19, 47.5%) (p=0.00001). In addition, multivariate analysis showed that the presence of 2 or 3 adverse factors was an independent poor prognostic factor for PFS (Hazard ratio, 10.2; 95% confidence interval, 2.9-35.9; p=0.0003) after adjustment for previously known prognostic factors.ConclusionsThese results suggest that peripheral immune status at pre-treatment impacts on the prognosis of MCRC patients treated with first-line chemotherapy. more

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We are developing a Compton telescope based on high-resolution Si and CdTe detectors for astrophysical observations in sub-MeV/MeV gamma-ray region. Recently, we constructed a prototype Compton ... telescope which consists of six layers of double-sided Si strip detectors (DSSDs) and CdTe pixel detectors to demonstrate the basic performance of this new technology. By irradiating the detector with gamma rays from radio isotope sources, we have succeeded in Compton reconstruction of images and spectra. The obtained angular resolution is 3.9°(FWHM) at 511 keV, and the energy resolution is 14 keV (FWHM) at the same energy. In addition to the conventional Compton reconstruction, i.e., drawing cones in the sky, we also demonstrated a full reconstruction by tracking Compton recoil electrons using the signals detected in successive Si layers. By irradiating 137Cs source, we successfully obtained an image and a spectrum of 662 keV line emission with this method. As a next step, development of larger DSSDs with a size of 4 cm × 4 cm is under way to improve the effective area of the Compton telescope. We are also developing a new low-noise analog ASIC to handle the increasing number of channels. Initial results from these two new technologies are presented in this paper as well. more

The Drosophila large intestine is initially subdivided into dorsal and ventral domains with distinct cell types, and a one-cell-wide strand of boundary cells is induced between them. Here we show ... that cell identity and localization of the boundary cells are determined by the combined action of Delta, Notch, and engrailed genes. The prospective dorsal domain of the hindgut primordium expresses engrailed. Engrailed represses Delta, which is ubiquitously expressed throughout the prospective hindgut region in early blastodermal stages, in the dorsal domain, and thus generates a Delta-positive/negative prepattern. Expression of Engrailed protein determines the dorsal domain, while an Engrailed-negative (Delta-positive) region is differentiated into the ventral domain. Delta-positive ventral cells activate a Notch cascade in abutting dorsal cells, and thus induce their differentiation into boundary cells. Mis-expression of a constitutively active Notch intracellular domain causes the entire large intestine to develop as boundary cells. It was also found that the transducing activity of a transmembrane form of activated Notch, which requires further proteolytic processing to generate intracellular fragments, is suppressed in the Delta-positive domain. Delta acts in two distinct ways: it activates the Notch signaling pathway in adjacent Delta-negative cells, and, at the same time, autonomously blocks Notch signaling in Delta-positive cells by affecting Notch processing. more

背景.直視所見を有する病変には直視下で生検,擦過,洗浄などを施行し,診断を試みることが多いが,出血により十分な検査が施行できない場合がある.目的.ガイドシース挿入可能な直視所見を有する病変に対してEBUS-GS法を行い,その有効性と安全性について検討した.方法.2009年4月7日から2014年1月21日までに,名古屋大学附属病院で直視所見を有する病変に対してEBUS-GS併用気管支内生検を行った15症例(GS群)を対象とし,その診断率と安全性を検討した.また直視下で生検を行った27症例を直視生検群とし,比較検討を行った.結果.全15症例中, 14例(93.3%)で診断可能であり,重篤な合併症は認められなかった. GS群の病変部位は区域支が主であり(14例/15例93.3%),またGS群における診断率は直視生検群と比較し, 93.3%と85.2%で有意差は認めなかった.なお病変が粘膜下病変であるもしくは壊死組織に覆われている場合に,生検による病理組織診断が得られにくい傾向を認めた.生検回数はGS群,直視生検群でそれぞれ中央値9回(6〜12回)と7回(5〜9回)であり, GS群で有意に多かった(P=0.012).またGS/直視生検併用群6例を除いたGS群9例と直視生検群27例では,両群ともに止血剤の使用割合はほぼ同等であったが,検査後の発熱や低酸素血症などの合併症の割合は11.1%, 29.6%とGS群で少ない傾向にあり,また平均検査時間は43.9±15.8分, 57.6±14.9分と有意にGS群で短かった(P=0.024).結論.ガイドシースを挿入可能な直視所見を有する病変に対してEBUS-GS法は安全かつ十分な回数の生検が可能で,有用な方法であると考えられた.

Background. Although most cystic mediastinal diseases are benign, it should be noted that malignant tumor could appear as a cystic lesion. We report a case of mediastinal parathyroid cyst with a ... brown tumor of the rib, initially suspected to be a malignant tumor with bone metastasis. Case. A 63-year-old man was hospitalized because of dysphagia and hoarseness. A PET-CT showed a cystic mass in the upper mediastinum and an osteolytic lesion in the left rib accompanied with increased uptake of FDG. We performed EBUS-TBNA of the mediastinal mass and found no malignant findings. Blood examinations also revealed no abnormalities. Biopsy of the rib lesion revealed the possibility of a brown tumor due to hyperparathyroidism and blood examinations revealed a high blood parathyroid hormone. The mediastinal parathyroid cyst was resected and the bone lesion reduced in size. Conclusion. Ectopic mediastinal parathyroid cyst with rib brown tumor is very rare. When we see a tumorous legion with hypercalcemia, parathyroid hormone measurements would be performed to rule out ectopic parathyroid tumors. more

The gamma-ray spectrometer (GRS) of Japanese lunar polar orbiter SELENE uses a Ge detector for the first time on a lunar mission. This spectrometer will observe lunar gamma rays for 1 year or more to ... determine chemical composition over the entire lunar surface. For cooling the Ge detector, we adopted a Stirling cryocooler. The SELENE GRS flight model was completed and an energy resolution of 3.0 keV (FWHM) at 1.33 MeV was achieved. This paper describes the details of the detector-cryogenic system and its performance. more