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Lu S.,Sloan Kettering Cancer Center | Lu S.,Fudan University | Tan K.S.,Sloan Kettering Cancer Center | Kadota K.,Sloan Kettering Cancer Center | And 7 more authors.
Journal of Thoracic Oncology | Year: 2017

Introduction Spread through air spaces (STAS) is a recently recognized pattern of invasion in lung adenocarcinoma; however, it has not yet been characterized in squamous cell carcinoma (SCC). Methods We reviewed 445 resected stage I to III lung SCCs and investigated the clinical significance of STAS. Cumulative incidence of recurrence and lung cancer–specific death were evaluated by competing risks analyses and overall survival by Cox models. Results Of the total 445 patients, 336 (76%) were older than 65 years. Among the 273 patients who died, 91 (33%) died of lung cancer whereas the remaining ones died of competing events or unknown cause. STAS was observed in 132 patients (30%) and the frequency increased with stage. The cumulative incidences of any, distant, and locoregional recurrence as well as lung cancer–specific death were significantly higher in patients with STAS compared with in those without STAS, whereas there was no statistically significant difference in overall survival. In multivariable models for any recurrence and lung cancer–specific death, STAS was an independent predictor for both outcomes (p = 0.034 and 0.016, respectively). Conclusion STAS was present in one-third of resected lung SCCs. In competing risks analysis in a cohort in which three-fourths of the patients were elderly, STAS was associated with lung cancer–specific outcomes. Our findings suggest that STAS is one of the most prognostically significant histologic findings in lung SCC. © 2016 International Association for the Study of Lung Cancer

Kanaji N.,Kagawa UniversityKagawa | Sakai K.,Kagawa Prefectural Central HospitalKagawa | Ueda Y.,Kagawa Prefectural Central HospitalKagawa | Miyawaki H.,Kagawa Prefectural Central HospitalKagawa | And 6 more authors.
Lung Cancer | Year: 2017

Objectives Small cell lung cancer (SCLC) can be subgrouped into central and peripheral types according to the location of the primary lesion. However, the clinical differences between these two types remain unclear. This study compared their clinical features. Materials and methods Data on 231 patients with pathologically diagnosed SCLC were retrospectively subgrouped into central or peripheral types. Progression-free survival (PFS), overall survival (OS), treatments, responses to first-line therapy, and frequency of interstitial lung disease (ILD) were compared between the two groups. Results Of the 231 patients, 101 (44%) had central-type and 130 (56%) had peripheral-type SCLC. Peripheral-type SCLC was associated with a better performance status, higher frequency of ILD, and higher rate of limited disease stage. Patients with peripheral-type SCLC had a significantly longer OS than did those with central-type SCLC (median, 502 vs 370 days, respectively; p = 0.0186). Tumor location was not associated with PFS. PFS was poorer in patients with than without ILD (median, 143 vs 213 days, respectively; p = 0.0038), as was OS (median, 245 vs 545 days, respectively; p = 0.0014). Among patients without ILD, OS was longer in those with peripheral- than central-type tumors (median, 662 vs 421 days, respectively; p = 0.0074). Surgical resection was more often chosen for peripheral-type tumors, and this was one reason for the prolonged survival. There was no difference in the response to chemotherapy and/or radiotherapy between central- and peripheral-type SCLC. Multivariate analysis by a Cox proportional hazards model showed that male sex, a poor performance status, extensive disease, the presence of ILD, an elevated serum neuron-specific enolase concentration, and central-type SCLC were poor prognostic factors for OS. Conclusion Peripheral-type SCLC is associated with better OS and a higher frequency of ILD than is central-type SCLC. The presence of ILD is a poor prognostic factor for both PFS and OS. © 2017 Elsevier B.V.

Kobayashi A.,Tokushima University | Tamura A.,Tokushima University | Ichihara T.,Kagawa UniversityKagawa | Minagawa T.,Tokushima University
Journal of Medical Investigation | Year: 2017

Purpose: The aim of this study was to clarify the changes in medication-taking behavior and related factors over time in patients with initial mild cerebral infarction up to 12 months after onset. Methods: Thirty-one patients with initial mild cerebral infarction were surveyed a total of four times: on admission to hospital, 3 months after onset, 6 months after onset, and 12 months after onset. Patients were surveyed regarding medication compliance, awareness of taking medication, perceived behavioral control, lifestyle risk factors, and subjective norms. Results: Medication compliance improved over time from the time of admission, but no changes were seen in awareness of taking medication. A cluster analysis based on changes in medication compliance over time revealed a “Persistently high compliance group” and a “Persistently low compliance group” for medication compliance. The health locus of control in the “Persistently high compliance group” was perceived as the result of chance and fate. Conclusions: Assessing the current state of medication compliance and the health locus of control during hospitalization permitted an understanding of patient characteristics, and indicated a need for recurrence prevention education and medication guidance tailored to each patient’s cognitive and behavioral characteristics. © 2017, University of Tokushima. All rights reserved.

Suzuki S.,Kagawa UniversityKagawa | Koshimizu H.,Japan Society for the Promotion of Science | Koshimizu H.,Japan National Institute of Advanced Industrial Science and Technology | Adachi N.,Kwansei Gakuin University | And 5 more authors.
Peptides | Year: 2017

Accumulating evidence suggests functional interaction between brain-derived neurotrophic factor (BDNF) and metabotropic glutamate receptor (mGluR) signaling pathways in the central nervous system (CNS). To date, eight subtypes of mGluRs, mGluR1–8, have been identified, and a previous study suggested that BDNF leads to down-regulation of GluR2 mRNA in rat cerebral cortical cultures. However, precise transcriptomic effects of BDNF on other mGluRs and their cellular significance on the BDNF signaling pathway remain largely unknown. In this study, we assessed the transcriptomic effects of BDNF on mGluR1–8 in primary cultures of rat cerebral cortical neurons, and transcriptomic impacts of mGluR(s) whose expression is regulated by BDNF, on BDNF target genes. Real-time quantitative PCR (RT-qPCR) revealed that stimulation of the cultures with 100 ng/mL BDNF led to marked reductions not only in the gene expression levels of mGluR2, but also in those of mGluR3, both of which belong to group II mGluRs (mGluR II). There were, on the other hand, no changes in the amounts of mGluR I (mGluR1 and 5) and III (mGluR4, 6, 7, and 8) mRNA. Further, 10 ng/mL of BDNF, which mainly activates the high-affinity BDNF receptor, TrkB, but not the low-affinity receptor, p75NTR, was able to induce down-regulation of mGluR II mRNA. The BDNF-induced suppression of mGluR II was not significantly attenuated in the presence of tetrodotoxin (TTX), a blocker for voltage-gated sodium channels. In addition, on stimulation with BDNF (100 ng/mL), no significant down-regulation of mGluR II mRNA was seen in cultured astrocytes, which only express the truncated form of TrkB. Finally, we assessed the transcriptomic effect of mGluR II on the expressions of BDNF target genes, BDNF and activity-regulated cytoskeleton-associated protein (Arc). LY404039, an mGluR II agonist, enhanced the BDNF-induced up-regulation of BDNF, but not Arc. On the other hand, LY341495, an mGluR II antagonist, down-regulated BDNF mRNA levels. Collectively, these observations demonstrated the detailed functional interaction between BDNF and mGluR II: Activation of mGluR II positively regulates self-induced BDNF expression, and, in turn, BDNF negatively regulates the gene expression of mGluR II in a neuronal activity-independent manner, in cortical neurons, but not in astrocytes. © 2017 Elsevier Inc.

PubMed | Kagawa University, Sher-e-Bangla Agricultural University and Kagawa UniversityKagawa
Type: | Journal: Frontiers in plant science | Year: 2016

The present study investigates the regulatory role of exogenous calcium (Ca) in developing salt stress tolerance in rice seedlings. Hydroponically grown 13-day-old rice (Oryza sativa L. cv. BRRI dhan47) seedlings were exposed to 200 mM NaCl alone and combined with 2 mM CaCl2 and 2 mM ethylene glycol tetraacetic acid (EGTA, a Ca scavenger) for 3 days. The salt stress caused growth inhibition, chlorosis and water shortage in the rice seedlings. The salt-induced stress disrupted ion homeostasis through Na(+) influx and K(+) efflux, and decreased other mineral nutrient uptake. Salt stress caused oxidative stress in seedlings through lipid peroxidation, loss of plasma membrane integrity, higher reactive oxygen species (ROS) production and methylglyoxal (MG) formation. The salt-stressed seedlings supplemented with exogenous Ca recovered from water loss, chlorosis and growth inhibition. Calcium supplementation in the salt-stressed rice seedlings improved ion homeostasis by inhibition of Na(+) influx and K(+) leakage. Exogenous Ca also improved ROS and MG detoxification by improving the antioxidant defense and glyoxalase systems, respectively. On the other hand, applying EGTA along with salt and Ca again negatively affected the seedlings as EGTA negated Ca activity. It confirms that, the positive responses in salt-stressed rice seedlings to exogenous Ca were for Ca mediated improvement of ion homeostasis, antioxidant defense and glyoxalase system.

Itoh K.,Tokushima Bunri University | Ishihara Y.,Hiroshima UniversityHiroshima | Komori R.,Tokushima Bunri University | Nochi H.,Tokushima Bunri University | And 6 more authors.
Brain Research | Year: 2016

Our previous study showed that treatment with levetiracetam (LEV) after status epilepticus (SE) termination by diazepam might prevent the development of spontaneous recurrent seizures via the inhibition of neurotoxicity induced by brain edema events. In the present study, we determined the possible molecular and cellular mechanisms of LEV treatment after termination of SE. To assess the effect of LEV against the brain alterations after SE, we focused on blood-brain barrier (BBB) dysfunction associated with angiogenesis and brain inflammation. The consecutive treatment of LEV inhibited the temporarily increased BBB leakage in the hippocampus two days after SE. At the same time point, the LEV treatment significantly inhibited the increase in the number of CD31-positive endothelial immature cells and in the expression of angiogenic factors. These findings suggested that the increase in neovascularization led to an increase in BBB permeability by SE-induced BBB failure, and these brain alterations were prevented by LEV treatment. Furthermore, in the acute phase of the latent period, pro-inflammatory responses for epileptogenic targets in microglia and astrocytes of the hippocampus activated, and these upregulations of pro-inflammatory-related molecules were inhibited by LEV treatment. These findings suggest that LEV is likely involved in neuroprotection via anti-angiogenesis and anti-inflammatory activities against BBB dysfunction in the acute phase of epileptogenesis after SE. © 2016 Elsevier B.V.

Kuboi T.,Shikoku Medical Center for Children and Adults | Okazaki K.,Shikoku Medical Center for Children and Adults | Kusaka T.,Kagawa UniversityKagawa | Shimada A.,Tokushima University
Pediatrics International | Year: 2015

Congenital dacryocystocele is a relatively rare type of nasolacrimal duct obstruction that may induce respiratory distress during the early neonatal period. We encountered a case of bilateral congenital dacryocystoceles with intranasal cysts in a premature infant delivered at 34 weeks of gestation. The patient developed symptoms of respiratory failure immediately after birth, but no ophthalmologic symptoms. Treatment with nasal continuous positive airway pressure via a nasal mask, instead of a nasal prong, effectively relieved the symptoms. Early diagnosis and appropriate treatment are critical for infants with nasal obstruction. © 2015 Japan Pediatric Society.

Fujiwara S.,Kagawa UniversityKagawa | Toyama Y.,Takamatsu Redcross HospitalKagawa | Miyashita T.,Kagawa UniversityKagawa | Osaki Y.,Osaka Medical Center And Research Institute For Maternal and Child Health | And 4 more authors.
Auris Nasus Larynx | Year: 2016

Objective The aim of the study is to evaluate the usefulness of multislice computed tomography (MSCT) using multiplanar reconstruction (MPR) in obtaining preoperative information on the ossicular lesions of middle ear diseases by comparing the ossicular findings of MPR images with the operative findings. Methods Sixty-two ears and 10 ears with preoperative middle ear diseases underwent 4- and 64-detector row CT of the temporal bone in Kagawa University Hospital, respectively. MPR images of three ossicles were created at the planes parallel to the long axis of ossicles. Results The findings of the three ossicles in MPR images were compatible with their operative findings in approximately 91% of 72 ears with various middle ear diseases. There was no significant difference in the coincidence rate of both findings between 4- and 64-detector row CT scanners. The ears with no soft tissue shadows around the ossicles had the coincidence rate of 96–100% in each ossicular part, whereas the coincidence rate was lower in the ears with soft tissue shadows around the ossicles. Conclusion MPR imagings of the ossicles provide accurate preoperative information on the ossicular lesions in middle ear diseases. The 4-detector CT is still a useful device for imaging of the ossicles. © 2015 Elsevier Ireland Ltd

Hoque T.S.,Bangladesh Agricultural University | Hossain M.A.,Bangladesh Agricultural University | Mostofa M.G.,Bangabandhu Sheikh Mujibur Rahman Agricultural University | Burritt D.J.,University of Otago | And 2 more authors.
Frontiers in Plant Science | Year: 2016

The oxygenated short aldehyde methylglyoxal (MG) is produced in plants as a by- product of a number of metabolic reactions, including elimination of phosphate groups from glycolysis intermediates dihydroxyacetone phosphate and glyceraldehyde 3- phosphate. MG is mostly detoxified by the combined actions of the enzymes glyoxalase I and glyoxalase II that together with glutathione make up the glyoxalase system. Under normal growth conditions, basal levels of MG remain low in plants; however, when plants are exposed to abiotic stress, MG can accumulate to much higher levels. Stress-induced MG functions as a toxic molecule, inhibiting different developmental processes, including seed germination, photosynthesis and root growth, whereas MG, at low levels, acts as an important signaling molecule, involved in regulating diverse events, such as cell proliferation and survival, control of the redox status of cells, and many other aspects of general metabolism and cellular homeostases. MG can modulate plant stress responses by regulating stomatal opening and closure, the production of reactive oxygen species, cytosolic calcium ion concentrations, the activation of inward rectifying potassium channels and the expression of many stress-responsive genes. MG appears to play important roles in signal transduction by transmitting and amplifying cellular signals and functions that promote adaptation of plants growing under adverse environmental conditions. Thus, MG is now considered as a potential biochemical marker for plant abiotic stress tolerance, and is receiving considerable attention by the scientific community. In this review, we will summarize recent findings regarding MG metabolism in plants under abiotic stress, and evaluate the concept of MG signaling. In addition, we will demonstrate the importance of giving consideration to MG metabolism and the glyoxalase system, when investigating plant adaptation and responses to various environmental stresses. © 2016 Hoque, Hossain, Mostofa, Burritt, Fujita and Tran.

Ashida Y.,Ehime University | Yanagita R.C.,Kagawa UniversityKagawa | Takahashi C.,Kagawa UniversityKagawa | Kawanami Y.,Kagawa UniversityKagawa | Irie K.,Kyoto University
Bioorganic and Medicinal Chemistry | Year: 2016

Aplysiatoxin (ATX) is a naturally occurring tumor promoter isolated from a sea hare and cyanobacteria. ATX binds to, and activates, protein kinase C (PKC) isozymes and shows anti-proliferative activity against human cancer cell lines. Recently, ATX has attracted attention as a lead compound for the development of novel anticancer drugs. In order to predict the binding mode between ATX and protein kinase Cδ (PKCδ) C1B domain, we carried out molecular docking simulation, atomistic molecular dynamics simulation in phospholipid membrane environment, and structure–activity study on a simple acyclic analog of ATX. These studies provided the binding model where the carbonyl group at position 27, the hydroxyl group at position 30, and the phenolic hydroxyl group at position 20 of ATX were involved in intermolecular hydrogen bonding with the PKCδ C1B domain, which would be useful for the rational design of ATX derivatives as anticancer lead compounds. © 2016 Elsevier Ltd

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