Kagawa University

About: Kagawa University is a education organization based out in Takamatsu, Japan. It is known for research contribution in the topics: Cancer & Population. The organization has 6028 authors who have published 11918 publications receiving 224111 citations. The organization is also known as: Kagawa Daigaku.

A novel approach to adenine-induced chronic kidney disease associated anemia in rodents.

Abstract: To date, good experimental animal models of renal anemia are not available Therefore, the purpose of this study was to establish a novel approach to induce chronic kidney disease (CKD) with severe anemia by oral administration of adenine in rodents Adenine was administered to 6-week-old male C57BL/6 mice (25 and 50 mg/kg body weight) by oral gavage daily for 28 days Serum creatinine and BUN as well as hematocrit, hemoglobin (Hb) and plasma erythropoietin (EPO) levels were monitored to assess renal function and anemia, respectively Adenine at 25 mg/kg for 28 days slightly increased plasma creatinine levels, but did not induce anemia In contrast, 50 mg/kg of adenine daily for 28 days showed severe renal dysfunction (plasma creatinine 19 ± 010 mg/dL) and anemia (hematocrit 365 ± 10% and EPO 28 ± 24 pg/mL) as compared with vehicle-treated mice (04 ± 002 mg/dL, 496 ± 16% and 61 ± 40 pg/mL, respectively) At the end of experiment, level of Hb also significantly reduced in 50 mg/kg adenine administration group Remarkable histological changes of kidney tissues characterized by interstitial fibrosis and cystic appearance in tubules were observed in 50 mg/kg of adenine treatment group These results have demonstrated that oral dosing with adenine at 50 mg/kg for 28 days is suitable to induce a stable anemia associated with CKD in mice

Activated T-cell-mediated immunotherapy with a chimeric receptor against CD38 in B-cell non-Hodgkin lymphoma

Abstract: T-cell-mediated immunotherapy with a chimeric antigen receptor (CAR) is expected to become a powerful treatment for cancer. CD38, highly expressed in B-cell non-Hodgkin lymphoma (B-NHL) cells, is an attractive target in immunotherapy for B-NHL. We retrovirally transduced a T-cell line, Hut78, expressing little CD38, with an anti-CD38-CAR. Hut78 cells with the anti-CD38-CAR were cocultured with B-NHL cell lines bearing CD38 and also B-NHL cells from patients. Four days later most of the lymphoma cells were killed (the level of cytotoxicity was >95%). By contrast, there was undetectable cytotoxicity against CD38-negative cell lines. Then, we introduced the anti-CD38-CAR into human peripheral T cells. However, the recovery of viable cells was very low, presumably because of an autolytic reaction caused by the association of the anti-CD38-CAR with CD38 on the cell surface. The addition of an anti-CD38 antibody increased the yield of viable transduced T cell probably by blocking the autolytic reaction. We cocultured human peripheral T cells bearing anti-CD38-CAR with B-NHL cells. The median specific cytotoxicity was greater than 90%. These cells were injected 4 times into NOD/SCID mice, which were inoculated with B-NHL cells luciferase. Luciferase activity was not detectable even 30 days after the inoculation in 5 of 6 mice injected. By contrast, it increased in all of the mice injected with the mock vector-transduced T cell. In conclusion, T cell with the anti-CD38-CAR showed powerful cytotoxicity against B-NHL cells in vitro and in vivo. These findings may provide an important clue for improving the methodology of T-cell-mediated immunotherapy.

The profile of Japanese Association for Acute Medicine - out-of-hospital cardiac arrest registry in 2014-2015.

Abstract: Aim To describe the registry design of the Japanese Association for Acute Medicine - out-of-hospital cardiac arrest (JAAM-OHCA) Registry as well as its profile on hospital information, patient and emergency medical service characteristics, and in-hospital procedures and outcomes among patients with OHCA who were transported to the participating institutions. Methods The special committee aiming to improve the survival after OHCA by providing evidence-based therapeutic strategies and emergency medical systems from the JAAM has launched a multicenter, prospective registry that enrolled OHCA patients who were transported to critical care medical centers or hospitals with an emergency care department. The primary outcome was a favorable neurological status 1 month after OHCA. Results Between June 2014 and December 2015, a total of 12,024 eligible patients with OHCA were registered in 73 participating institutions. The mean age of the patients was 69.2 years, and 61.0% of them were male. The first documented shockable rhythm on arrival of emergency medical services was 9.0%. After hospital arrival, 9.4% underwent defibrillation, 68.9% tracheal intubation, 3.7% extracorporeal cardiopulmonary resuscitation, 3.0% intra-aortic balloon pumping, 6.4% coronary angiography, 3.0% percutaneous coronary intervention, 6.4% targeted temperature management, and 81.1% adrenaline administration. The proportion of cerebral performance category 1 or 2 at 1 month after OHCA was 3.9% among adult patients and 5.5% among pediatric patients. Conclusions The special committee of the JAAM launched the JAAM-OHCA Registry in June 2014 and continuously gathers data on OHCA patients. This registry can provide valuable information to establish appropriate therapeutic strategies for OHCA patients in the near future.

11C-Acetate PET in the Evaluation of Brain Glioma: Comparison with 11C-Methionine and 18F-FDG-PET

Abstract: The aim of the study is to retrospectively investigate the usefulness of 11C-acetate (ACE)-positron emission tomography (PET) for evaluation of brain glioma, in comparison with 11C-methionine (MET) and 2-deoxy-2-18F-fluoro-d-glucose (FDG). Fifteen patients with brain glioma referred to initial diagnosis were examined with ACE, MET, and FDG-PET. Five patients had low-grade gliomas (grade II), three had anaplastic astrocytomas (grade III), and seven had glioblastomas (grade IV). PET results were evaluated by visual and semiquantitative analysis. For semiquantitative analysis, the standardized uptake value (SUV) and tumor to contralateral normal gray matter (T/N) ratio were calculated. The sensitivity for detection of high-grade gliomas was calculated using visual analysis. Sensitivities of ACE, MET, and FDG were 90%, 100%, and 40%, respectively. ACE and MET T/N ratios were significantly higher than that of FDG. ACE and FDG SUV in high-grade gliomas were significantly higher than that in low-grade gliomas. No significant differences were observed using MET. ACE PET is a potentially useful radiotracer for detecting brain gliomas and differentiating high-grade gliomas.

Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT.

Abstract: The sensitivity to 5-fluorouracil (5-FU) has been reported to be associated with target molecule thymidylate synthase (TS), fluoropyrimidine-metabolising enzymes such as orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD). We performed an immunohistochemical study on the clinical significance of TS, OPRT, and DPD expression using 151 resected non-small-cell lung cancer (NSCLC) patients postoperatively treated with a combination of tegafur and uracil (UFT). Eighty-two carcinomas were TS-positive, 105 carcinomas were OPRT-positive, 68 carcinomas were DPD-positive. No correlation was observed in the HSCORE between the TS and OPRT expression (r=0.203), between the TS and DPD expression (r=0.098), or between the OPRT and DPD expression (r=0.074). Regarding the survival of NSCLC patients treated with UFT, the 5-year survival rate of patients with TS-negative tumours was significantly higher than that with TS-positive tumours (P=0.0133). The 5-year survival rate of patients with OPRT-positive stage II to III tumours was significantly higher than that with OPRT-negative stage II to III tumours (P=0.0145). In addition, the 5-year survival rate of patients with DPD-negative tumours was also significantly higher than that with DPD-positive tumours (P=0.0004). A Cox multivariate regression analysis revealed the TS status (hazard ratio 2.663; P=0.0003), OPRT status (hazard ratio 2.543; P=0.0005), and DPD status (hazard ratio 2.840; P<0.0001) to all be significant prognostic factors for the survival of resected NSCLC patients postoperatively treated with UFT.