CD44 standard isoform is involved in maintenance of cancer stem cells of a hepatocellular carcinoma cell line

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Cancer stem cells (CSCs) have attracted attention as a novel therapeutic target for cancer because they play important roles in the development and aggravation of cancer. CD44 is expressed as a standard isoform (CD44s) and several variant isoforms. CD44v is a major isoform expressed on CSCs of a variety of tumors and has been extensively studied. However, HCC tissues dominantly express CD44s, whose function in CSCs remains unclear. In the present study, we investigated the roles of CD44s in CSCs of HCC. Knock-out of the CD44 gene in HuH7 HCC cells on which only CD44s is expressed resulted in decreased spheroid formation and increased drug sensitivity. The expression of CSC marker genes, including CD133 and EpCAM, was significantly downregulated in the spheroids of CD44-deficient cells compared with those in the spheroids of HuH7 cells. In addition, CD44 deficiency impaired antioxidant capacity, concomitant with downregulation of glutathione peroxidase 1 (GPX1) and thioredoxin. Because GPX1 uses the reduced form of glutathione (GSH) to regenerate oxidized cellular components, GSH levels were significantly increased in the CD44-deficient cells. We also found that NOTCH3 and its target genes were downregulated in the spheroids of CD44-deficient cells. NOTCH3 expression in HCC tissues was significantly increased compared with that in adjacent nontumor liver tissues and was correlated with CD44 expression. These results suggest that CD44s is involved in maintenance of CSCs in a HCC cell line, possibly through the NOTCH3 signaling pathway

マイクロ波CTマンモグラフィの開発

24個の固定ダイポールアンテナを用いて三次元マイクロ波CT実験を行い，スーパーコンピュータを用いてForward-Backward Time Stepping（FBTS）法によるCT計算を行った．その結果得られた知見は，FBTS法が雑音に強いこと，及び計算の初期設定やキャリブレーション設定が精度向上に重要なことである．また計算モデル化が容易な広帯域平面アンテナの開発も行った．これらの知見を生かし，FBTS法マイクロ波CTマンモグラフィ装置の概念設計を行った

Decomposition of the Superwind in M82

We present new optical images ($B$, $V$, and H$\alpha$) of the archetypical starburst/superwind galaxy M82 obtained with the 8.2 m Subaru Telescope to reveal new detailed structures of the superwind-driven nebula and the high-latitude dark lanes. The emission-line nebula is decomposed into (1) a ridge-dominated component comprising numerous filament/loop sub-structures whose overall morphology appears as a pair of narrow cylinders, and (2) a diffuse component extended over much wider opening angle from the nucleus. We suggest that these two components have different origins. The ridge-dominated component appears as a pair of cylinders rather than a pair of cones. Since this morphological property is similar to that of hot plasma probed by soft X-ray, this component seems to surround the hot plasma. On the other hand, the diffuse component may arise from dust grains which scatter stellar light from the galaxy. Since inner region of this component is seen over the prominent ^^ ^^ X"-shaped dark lanes streaming out from the nuclear region and they can be reproduced as a conical distribution of dust grains, there seems to be a dusty cold outflow as well as the hot one probed by soft X-ray and shock-excited optical emission lines. If this is the case, the presence of such high-latitude dust grains implies that neutral gaseous matter is also blown out during the course of the superwind activity.Comment: 12 pages, 6 figures. Accepted for publication in PAS

Cytokine-Based Log-Scale Expansion of Functional Murine Dendritic Cells

BACKGROUND: Limitations of the clinical efficacy of dendritic cell (DC)-based immunotherapy, as well as difficulties in their industrial production, are largely related to the limited number of autologous DCs from each patient. We here established a possible breakthrough, a simple and cytokine-based culture method to realize a log-scale order of functional murine DCs (>1,000-fold), which cells were used as a model before moving to human studies. METHODOLOGY/PRINCIPAL FINDINGS: Floating cultivation of lineage-negative hematopoietic progenitors from bone marrow in an optimized cytokine cocktail (FLT3-L, IL-3, IL-6, and SCF) led to a stable log-scale proliferation of these cells, and a subsequent differentiation study using IL-4/GM-CSF revealed that 3-weeks of expansion was optimal to produce CD11b+/CD11c+ DC-like cells. The expanded DCs had typical features of conventional myeloid DCs in vitro and in vivo, including identical efficacy as tumor vaccines. CONCLUSIONS/SIGNIFICANCE: The concept of DC expansion should make a significant contribution to the progress of DC-based immunotherapy

Conceptual Design of Rapid Circular Particle Accelerator Using High-Gradient Resonant Cavities with Fixed Frequency

A new high-energy particle accelerator with static combined type of magnetic field and high-gradient resonant cavities is introduced for muon acceleration up to 300 MeV and proton acceleration up to 400 MeV. The accelerator concept is expected to realize Mpps-class rapid cycling high-energy particle acceleration in circular particle accelerators. Conceptual designs of the circular accelerator are discussed with an emphasis on short lifetime particles. The fundamental concept of particle acceleration and the related practical issues, which should be discussed when designing the accelerators, are described as well

Tokyo Guidelines 2018 diagnostic criteria and severity grading of acute cholecystitis (with videos)

The Tokyo Guidelines 2013 (TG13) for acute cholangitis and cholecystitis were globally disseminated and various clinical studies about the management of acute cholecystitis were reported by many researchers and clinicians from all over the world. The 1st edition of the Tokyo Guidelines 2007 (TG07) was revised in 2013. According to that revision, the TG13 diagnostic criteria of acute cholecystitis provided better specificity and higher diagnostic accuracy. Thorough our literature search about diagnostic criteria for acute cholecystitis, new and strong evidence that had been released from 2013 to 2017 was not found with serious and important issues about using TG13 diagnostic criteria of acute cholecystitis. On the other hand, the TG13 severity grading for acute cholecystitis has been validated in numerous studies. As a result of these reviews, the TG13 severity grading for acute cholecystitis was significantly associated with parameters including 30-day overall mortality, length of hospital stay, conversion rates to open surgery, and medical costs. In terms of severity assessment, breakthrough and intensive literature for revising severity grading was not reported. Consequently, TG13 diagnostic criteria and severity grading were judged from numerous validation studies as useful indicators in clinical practice and adopted as TG18/TG13 diagnostic criteria and severity grading of acute cholecystitis without any modification. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also include

TG18 management strategies for gallbladder drainage in patients with acute cholecystitis: Updated Tokyo Guidelines 2018 (with videos)

Since the publication of the Tokyo Guidelines in 2007 and their revision in 2013, appropriate management for acute cholecystitis has been more clearly established. Since the last revision, several manuscripts, especially for alternative endoscopic techniques, have been reported; therefore, additional evaluation and refinement of the 2013 Guidelines is required. We describe a standard drainage method for surgically high-risk patients with acute cholecystitis and the latest developed endoscopic gallbladder drainage techniques described in the updated Tokyo Guidelines 2018 (TG18). Our study confirmed that percutaneous transhepatic gallbladder drainage should be considered the first alternative to surgical intervention in surgically high-risk patients with acute cholecystitis. Also, endoscopic transpapillary gallbladder drainage or endoscopic ultrasound-guided gallbladder drainage can be considered in high-volume institutes by skilled endoscopists. In the endoscopic transpapillary approach, either endoscopic naso-gallbladder drainage or gallbladder stenting can be considered for gallbladder drainage. We also introduce special techniques and the latest outcomes of endoscopic ultrasound-guided gallbladder drainage studies. Free full articles and mobile app of TG18 are available at: . Related clinical questions and references are also include