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Poster PS6-09, 1st ICSU World Data System Conference: Global Data for Global Science (September 3-6, 2011, Kyoto, Japan

小児がん患者のQOL向上を目指した支持療法の最適化に関する研究

13301甲第4693号博士（薬学）金沢大学博士論文要旨Abstract 以下に掲載および掲載予定：1.Drug Metabolism and Disposition 44(1) pp.1-7 2016. ASPECT. 共著者：Fujita D, Saito Y, Nakanishi T, Tamai I 2.Japanese Journal of Clinical Oncology 46(9) pp.856-861 2016. OXFORD. 共著者：Saito Y, Kumamoto T, Makino Y, Tamai I, Ogawa C, Terakado H 3.Asia-Pacific Journal of Clinical Oncology WILEY. 共著者：Saito Y, Kumamoto T, Shiraiwa M, Sonoda T, Arakawa A, Hashimoto H, Tamai I, Ogawa C, Terakado

Green Tea-Derived Catechins Have Beneficial Effects on Cognition in the Pond Snail

Green tea has been used as a medicine in East Asia for thousands of years. Plant-derived compounds called flavanols, which are included in green tea, may have potentials to help maintain healthy brain function. In this chapter, we review the effects of flavanols, e.g. epicatechin (EpiC), on cognitive ability in the pond snail, Lymnaea stagnalis. In this decade, the Lukowiak’s group has tested the effects of EpiC on cognition ability in Lymnaea. In a Lymnaea model system, they showed that EpiC and EpiC-containing foods have a rapid and activity-dependent effect enhancing the formation of long-term memory (LTM) following operant conditioning of aerial respiratory behavior. In the last part of this chapter, we also introduce our study for the effects of EpiC on LTM formation in another model system in Lymnaea. This study showed that EpiC increases the persistence of LTM formed by classical conditioning of feeding behavior, and suggested that EpiC alters some electrophysiological properties of a neuron in the feeding system

Corticosterone Induces Rapid Spinogenesis via Synaptic Glucocorticoid Receptors and Kinase Networks in Hippocampus

BACKGROUND: Modulation of dendritic spines under acute stress is attracting much attention. Exposure to acute stress induces corticosterone (CORT) secretion from the adrenal cortex, resulting in rapid increase of CORT levels in plasma and the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrated the mechanisms of rapid effect (∼1 h) of CORT on the density and morphology of spines by imaging neurons in adult male rat hippocampal slices. The application of CORT at 100-1000 nM induced a rapid increase in the density of spines of CA1 pyramidal neurons. The density of small-head spines (0.2-0.4 µm) was increased even at low CORT levels (100-200 nM). The density of middle-head spines (0.4-0.5 µm) was increased at high CORT levels between 400-1000 nM. The density of large-head spines (0.5-1.0 µm) was increased only at 1000 nM CORT. Co-administration of RU486, an antagonist of glucocorticoid receptor (GR), abolished the effect of CORT. Blocking a single kinase, such as MAPK, PKA, PKC or PI3K, suppressed CORT-induced enhancement of spinogenesis. Blocking NMDA receptors suppressed the CORT effect. CONCLUSIONS/SIGNIFICANCE: These results imply that stress levels of CORT (100-1000 nM) drive the spinogenesis via synaptic GR and multiple kinase pathways

Outcomes and Prognosis of Neurological Decompression and Stabilization for Spinal Metastasis: Is Assessment with the Spinal Instability Neoplastic Score Useful for Predicting Surgical Results?

Study Design Retrospective study. Purpose To evaluate the efficacy of the Spinal Instability Neoplastic Score (SINS) in predicting surgical outcomes and survival. Patients were categorized into two groups according to the SINS, and their surgical outcomes and survival following decompression and stabilization were assessed. Overview of Literature Palliative surgery in patients with a life expectancy ≥3 months may effectively improve their overall condition in the long term. Currently, the effectiveness of the SINS for predicting surgical results and survival remains controversial. Methods This study included 44 patients who underwent decompression and stabilization for spinal metastases at Yokosuka Kyosai Hospital between 2008 and 2017. The patients were divided into two groups: stable (SINS ≤12) and unstable (SINS ≥13). Changes in the Frankel score and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) were compared between the two groups, and patient survival was evaluated according to the SINS, Tokuhashi score, and Katagiri score. Results The stable group (SINS range, 7–12) included 24 patients while the unstable group (SINS range, 13–16) included 20 patients. The Frankel score significantly improved from 2.8 to 3.6 in the stable group (p <0.001) and from 2.7 to 3.9 in the unstable group (p <0.001). The ECOG-PS significantly improved from 3.2 to 2.1 in the stable group (p <0.001) and from 3.0 to 1.8 in the unstable group (p <0.001). There was a statistically significant difference in median survival between the two groups. Conclusions All patients treated with palliative surgery showed favorable outcomes, as indicated by improved the Frankel score and ECOG-PS following surgery. However, median survival was significantly better in the stable group. The results of this study indicate that the SINS is appropriate for surgical decision making and may be used to predict survival

Helicobacter pylori and Gastric Mucosa-associated Lymphoid Tissue (MALT) Lymphoma: Updated Review of Clinical Outcomes and the Molecular Pathogenesis

In most H. pylori-positive patients, gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regress both endoscopically and histopathologically after H. pylori eradication, but no factors that can be predictive of the response to the eradication have been definitively identified, and there is little information on how to determine the optimal observation period before additional treatment can be started. Here, clinical studies dealing with the diagnosis and treatment of gastric MALT lymphomas and H. pylori published during the last 5 years were systematically reviewed, and studies identifying the molecular approaches involved in the pathogenesis were summarized. Most of the clinical studies indicate a favorable effect of H. pylori eradication on the clinical outcome of gastric MALT lymphomas. Some studies suggest the necessity of additional treatment in nonresponders to H. pylori eradication, while others suggest the adoption of a watch-and-wait strategy. The molecular characteristics of MALT lymphomas could play an important role in prognostic prediction and the selection of further therapeutic intervention after the eradication. This updated review of gastric MALT lymphomas illustrates the potential efficacy of H. pylori eradication in tumor remission, but further molecular characterization is necessary to establish the most suitable therapeutic strategy for patients who do not respond to eradication

Prenatal diagnosis of severe mitochondrial diseases caused by nuclear gene defects: a study in Japan

Prenatal diagnoses of mitochondrial diseases caused by defects in nuclear DNA (nDNA) or mitochondrial DNA have been reported in several countries except for Japan. The present study aimed to clarify the status of prenatal genetic diagnosis of mitochondrial diseases caused by nDNA defects in Japan. A comprehensive genomic analysis was performed to diagnose more than 400 patients, of which, 13 families (16 cases) had requested prenatal diagnoses. Eight cases diagnosed with wild type homozygous or heterozygous variants same as either of the heterozygous parents continued the pregnancy and delivered healthy babies. Another eight cases were diagnosed with homozygous, compound heterozygous, or hemizygous variants same as the proband. Of these, seven families chose to terminate the pregnancy, while one decided to continue the pregnancy. Neonatal- or infantile-onset mitochondrial diseases show severe phenotypes and lead to lethality. Therefore, such diseases could be candidates for prenatal diagnosis with careful genetic counseling, and prenatal testing could be a viable option for families