Positivity for cancer stem cell markers, CD44 and CD133, is a useful biomarker for predicting the outcomes of patients with advanced gastric cancer

Background; The CD44 and CD133 expressions have been identified to be putative cancer stem cell (CSC) markers. Some reports have revealed a correlation between these CSC markers and a poor prognosis in the clinical setting. However, clinical impact of combined use of these markers has not been determinated in advanced gastric cancer.Methods; Specimens were obtained from 73 patients with gastric cancer with invasion beyond the muscularis (T3/4a) who underwent curative gastrectomy. Immunohistochemically, tumors with more than 5% CD44-positive cells or at least one CD133-positive cancer cell were regard as being CSC marker-positive.Results; Forty patients were CSC marker-positive. There were significant correlations between the CSC marker expression and the extent of lymphatic (p=0.04) and vessel invasion (p<0.001). The CSC marker-positive patients exhibitedpoor prognoses in both the overall (p=0.006) and disease-free survival analyses (p=0.019). Based on the results of the univariate analysis, the peritoneal CEA value, the extent of lymph node metastasis and CSC marker positivity were analyzed in the multivariate analysis. The results revealed that the extent of lymph node metastasis (p<0.001) and CSC marker positivity (p=0.04) were significant risk factors.Conclusion; CSC marker positivity is an independent prognostic factor in patients with T3/4a gastric cancer

The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin’s osmotic diuresis mechanism, patients’ serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (β1=−0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e’ tended to decrease (β1=−0.382, p=0.13, LRA). Compared to the baseline, E/e’ was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e’ group (E/e’≥10, n=34), E/e’ decreased significantly (β1=−0.63, p<0.05, LRA). ΔE/e’ was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e’ in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function

Draft Genome Sequence of Leishmania tarentolae Parrot Tar II, Obtained by Single-Molecule Real-Time Sequencing

Leishmania tarentolae is a protozoan parasite of lizards and is nonpathogenic to mammals. Genome information for the nonpathogenic species will facilitate an understanding of the pathology caused by species pathogenic to mammals. Here, we report resequencing of the L. tarentolae genome with a single-molecule real-time (SMRT) sequencer to provide a more complete genome assembly

Applying the "TANKYU Factor" to Improve Teaching in Multiple Subjects

本研究は，複数教科（国語・社会・数学・理科・英語）の教員によるチームで推進したものである。『探究ファクター』を適用した通常授業教材を開発・実施し，生徒アンケートのテキストマイニングを行うことで，教材開発に関する示唆を得ることができた。また，複数教科の教員による共同研究の進め方について，本実践をもとに検討した。This study was conducted by a team of teachers of several subjects (Japanese, Social Studies, athematics, Science, and English). We developed teaching plans for regular classes by applying the "TANKYU Factor" and obtained suggestions for developing teaching plans by text mining the student questionnaires. In addition, we discussed how to promote joint research by teachers of multiple subjects based on this practice

Chronological changes in the liver after temporary partial portal venous occlusion

AIM: To investigate time-dependent changes caused by temporal portal vein obstruction and subsequent reperfusion in the lobe with or without an occluded portal vein. METHODS: The portal vein (PV) of the anterior lobe of the liver of a male Wistar rat (8 wk-old) was obstructed (70%) for 12, 24, 36 and 48 h, respectively, and models were sacrificed at 48 h after reperfusion (each group: n = 10). The histological changes and the status of liver regeneration were compared between a liver biopsy performed on each lobe after temporary obstruction of the portal vein in the same rat liver, and the liver extracted at the time of sacrifice (48 h after reperfusion). RESULTS: With regard to the obstructed lobe, the liver weight/body weight ratio significantly decreased according to obstruction time. On the other hand, in the non-obstructed lobe, there were no significant differences within each group. The duration of PV occlusion did not seem to be strong enough to introduce liver weight increase. Stimulation of liver regeneration was brought about in the non-occluded lobe by 12-h occlusion, and was sustained even at 48 h after reperfusion. The obstructed lobe atrophied with the passage of time in the obstructed state. However, the proliferating-cell nuclear antigen labeling index also increased at 48 h after reperfusion, and a repair mechanism was observed. CONCLUSION: Temporary blood flow obstruction of the portal vein may become a significant trigger for liver regeneration, even with an obstruction of 12 h

Structure of HIV-2 Nef Reveals Features Distinct from HIV-1 Involved in Immune Regulation

The human immunodeficiency virus (HIV) accessory protein Nef plays a major role in establishing and maintaining infection, particularly through immune evasion. Many HIV-2-infected people experience long-term viral control and survival, resembling HIV-1 elite control. HIV-2 Nef has overlapping but also distinct functions from HIV-1 Nef. Here we report the crystal structure of HIV-2 Nef core. The di-leucine sorting motif forms a helix bound to neighboring molecules, and moreover, isothermal titration calorimetry demonstrated that the CD3 endocytosis motif can directly bind to HIV-2 Nef, ensuring AP-2-mediated endocytosis for CD3. The highly conserved C-terminal region forms a alpha-helix, absent from HIV-1. We further determined the structure of simian immunodeficiency virus (SIV) Nef harboring this region, demonstrating similar C-terminal a-helix, which may contribute to AP-1 binding for MHC-I downregulation. These results provide insights into the distinct pathogenesis of HIV-2 infection