Functional and molecular characterization of adenosine transport at the rat inner blood-retinal barrier

取得学位 : 博士（医学）, 学位授与番号 : 医博甲第1839号, 学位授与年月日 : 平成19年3月22日, 学位授与大学 : 金沢大学, 主査教授 : 宮本 謙一, 副査教授 : 杉山 和久, 濱田 潤一

Phase I study of combined therapy with vorinostat and gefitinib to treat BIM deletion polymorphism-associated resistance in EGFR-mutant lung cancer (VICTROY-J) : a study protocol

The BIM deletion polymorphism is reported to be associated with poor outcomes of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) treated with EGFR-TKIs, including gefitinib. We have shown that a histone deacetylase inhibitor, vorinostat, can epigenetically restore BIM function and apoptosis sensitivity to EGFR-TKIs in EGFR-mutant NSCLC cells with BIM deletion polymorphisms. The purpose of this study is to determine the feasibility of combined treatment of vorinostat with gefitinib in BIM deletion polymorphism positive EGFR-mutant NSCLC patients. BIM deletion polymorphism positive EGFR mutant NSCLC patients treated with at least one EGFR-TKI and one regimen of chemotherapy are being recruited to this study. Vorinostat (200-400mg) will be administered orally once daily on days 1-7, and gefitinib 250 mg orally once daily on days 1-14. With a fixed dose of gefitinib, the dose of vorinostat will be escalated following a conventional 3+3 design. The primary endpoint is to define the maximum tolerated dose (MTD) of vorinostat combined with 250 mg of gefitinib. This is the first phase I study of combined therapy with vorinostat and gefitinib for NSCLC patients double selected for an EGFR mutation and BIM deletion polymorphism

Phase I/II study of alectinib in lung cancer with RET fusion gene : study protocol

Background : The rearranged during transfection (RET) fusion gene was discovered as a driver oncogene in 1-2% of non-small cell lung cancers (NSCLCs). Alectinib is an approved anaplastic lymphoma kinase (ALK) inhibitor that may also be effective for RET fusion-positive NSCLC. Methods/Design : RET fusion-positive NSCLC patients treated with at least one regimen of chemotherapy are being recruited. In step 1, alectinib (600 or 450 mg, twice daily) will be administered following a 3+3 design. The primary endpoint is safety. In step 2, alectinib will be administered at the recommended dose (RD) defined by step 1. The primary endpoint is the response rate of RET inhibitor treatment-naïve patients. Conclusion : This is the first study to investigate the safety and preliminary efficacy of alectinib in RET fusion-positive NSCLC patients. If successful, alectinib treatment may lead to substantial and important changes in the management of NSCLC with RET fusion genes

The “otemori” shift of group decision making : Are groups more selfish than individuals?

“Otemori” is a Japanese term referring to a kind of selfish behavior. A person incharge demonstrates otemori by making a decision or an arrangement that suitshimself/herself or his/her peers. For example, CEOs or members of an assembly tend toraise their own salary too much. In an experiment, participants were assigned totwo-person groups (dyads). At first they read a questionnaire and made an individualdecision about the amount of their own salary and their co-partner’s salary. This wasfollowed by a discussion within each group that led to a salary decision by consensus.Results indicate that only groups of peers, as opposed to groups of strangers,demonstrate the otemori shift. Peer groups set higher salaries than individuals do whensetting their own salaries, but not when setting their co-partner’s salaries. This isregarded as the otemori shift of group decision making. Groups composed of strangersdo not demonstrate this otemori shift. This suggests that groups are more selfish thanindividuals if they are composed of peers

Incidence and risk factors of neonatal hypoglycemia after ritodrine therapy in premature labor: a retrospective cohort study

Abstract Background Ritodrine hydrochloride (RD), a β2-adrenergic agonist, is widely used as a tocolytic medication to suppress premature labor, but can cause neonatal hypoglycemia, a potentially severe side effect. We examined the incidence and risk factors of neonatal hypoglycemia following maternal intravenous administration of RD. Methods This was a retrospective study of neonates, who had birth weight of ≥2000 g and were delivered at 36 weeks gestation or later in Kanazawa University Hospital from August 2013 to July 2016. We defined neonatal hypoglycemia as blood glucose level < 50 mg/dL. Neonates who were delivered without maternal intravenous RD or who were delivered 8 days or more after stopping maternal RD or who received oral RD were defined as the RD non-administration group, while those delivered within 7 days after stopping maternal RD were defined as the RD intravenous administration group. We examined the incidence and risk factors of RD-induced neonatal hypoglycemia by comparing these two groups. Results We enrolled 603 neonates in this study; 504 (83.6%) showed no neonatal hypoglycemia, while 99 (16.4%) exhibited neonatal hypoglycemia. The incidence of neonatal hypoglycemia was significantly higher (61.7%; 58/94) in the RD intravenous administration group than in the RD non-administration group (8.1%; 41/509) (p < 0.001). Binomial logistic regression analysis in the RD intravenous administration group showed that maternal age over 35 years (AOR: 3.385; 95% CI, 1.082–10.588, p = 0.036) and the interval to delivery from stopping intravenous administration of RD (AOR: 0.974; 95% CI, 0.953–0.996, p = 0.020) were independent factors associated with neonatal hypoglycemia. The cut-off value of the interval to predict the incidence of neonatal hypoglycemia was about 6 h (sensitivity 82.8%, specificity 63.9%). Conclusions The incidence of neonatal hypoglycemia was significantly increased by maternal intravenous administration of RD. We newly identified maternal age (over 35 years) and the interval to delivery from stopping intravenous administration of RD (within 6 h) as independent risk factors for neonatal hypoglycemia following maternal intravenous administration of RD. In cases with these risk factors, careful blood glucose monitoring is recommended for early detection and treatment of neonatal hypoglycemia