A combination of a DNA-chimera siRNA against PLK-1 and zoledronic acid suppresses the growth of malignant mesothelioma cells in vitro.

Although novel agents effective against malignant mesothelioma (MM) have been developed, the prognosis of patients with MM is still poor. We generated a DNA-chimeric siRNA against polo-like kinase-1 (PLK-1), which was more stable in human serum than the non-chimeric siRNA. The chimeric PLK-1 siRNA inhibited MM cell proliferation through the induction of apoptosis. Next, we investigated the effects of zoledronic acid (ZOL) on MM cells, and found that ZOL also induced apoptosis in MM cells. Furthermore, ZOL augmented the inhibitory effects of the PLK-1 siRNA. In conclusion, combining a PLK-1 siRNA with ZOL treatment is an attractive strategy against MM

Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid Loci

The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses

イマチニブ抵抗性BCR-ABL陽性白血病細胞におけるマルチターゲット型キナーゼ阻害剤AT9283の作用機序と有用性に関する検討

京都大学0048新制・課程博士博士(医科学)甲第15993号医科博第19号新制||医科||2(附属図書館)28572京都大学大学院医学研究科医科学専攻(主査)教授 髙折 晃史, 教授 武田 俊一, 教授 松岡 雅雄学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Growth inhibition of imatinib-resistant CML cells with the T315I mutation and hypoxia-adaptation by AV65 - a novel Wnt/β-catenin signaling inhibitor.

We investigated the effect of a novel Wnt/β-catenin signaling inhibitor, AV65 on imatinib mesylate (IM)-sensitive and -resistant human chronic myeloid leukemia (CML) cells in vitro. AV65 inhibited the proliferation of various CML cell lines including T315I mutation-harboring cells. AV65 reduced the expression of β-catenin in CML cells, resulting in the induction of apoptosis. Moreover, AV65 inhibited the proliferation of hypoxia-adapted primitive CML cells that overexpress β-catenin. The combination of AV65 with IM had a synergistic inhibitory effect on the proliferation of CML cells. These findings suggest that AV65 could be a novel therapeutic agent for the treatment of CML

Concomitant administration of diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) with pentavalent rotavirus vaccine in Japanese infants

Rotavirus is the leading cause of severe acute gastroenteritis in infants and young children. Most children are infected with rotavirus, and the health and economic burdens of rotavirus gastroenteritis on healthcare systems and families are considerable. In 2012 pentavalent rotavirus vaccine (RV5) and diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) were licensed in Japan. We examined the immunogenicity and safety of DTaP-sIPV when administrated concomitantly with RV5 in Japanese infants. A total of 192 infants 6 to 11 weeks of age randomized to Group 1 (N = 96) received DTaP-sIPV and RV5 concomitantly, and Group 2 (N = 96) received DTaP-sIPV and RV5 separately. Antibody titer to diphtheria toxin, pertussis antigens (PT and FHA), tetanus toxin, and poliovirus type 1, 2, and 3 were measured at 4 to 6 weeks following 3-doses of DTaP-sIPV. Seroprotection rates for all components of DTaP-sIPV were 100% in both groups, and the geometric mean titers for DTaP-sIPV in Group 1 were comparable to Group 2. Incidence of systemic AEs (including diarrhea, vomiting, fever, and nasopharyngitis) were lower in Group 1 than in Group 2. All vaccine-related AEs were mild or moderate in intensity. There were no vaccine-related serious AEs, no deaths, and no cases of intussusception during the study. Concomitant administration of DTaP-sIPV and RV5 induced satisfactory immune responses to DTaP-sIPV and acceptable safety profile. The administration of DTaP-sIPV given concomitantly with RV5 is expected to facilitate compliance with the vaccination schedule and improve vaccine coverage in Japanese infants

Practical studies on the relationship between physical activity and life rhythm of young children.

本研究は, 広島大学附属幼稚園に在籍する幼児の身体活動と生活リズムの関連性を明らかにすることを目的とする。特に日内の身体活動量から幼児の生活リズム・体温変動における身体活動に関する視座を得ることを本研究の目的とする。 方法として, 幼稚園に在籍する5歳児34名の保護者に対し16項目の質問紙調査を行った。質問紙調査にて生活リズム評価の該当数を求め, 5項目以上該当する幼児を生活リズム未確立群, 0から2項目該当する幼児を生活リズム確立群とした。また, 対象児として抽出した24名の幼児の腰に2軸加速度計を装着し身体活動を測定した。加えて同対象者に耳式体温計を用い体温測定を行った。 結果から, 生活リズムが未確立である幼児は総じて身体活動を行う機会が少なく, 特に幼稚園降園後の遊びの様子として, 身体を動かして活発に遊ぶよりも静かに遊ぶ傾向が示された。生活リズムの違いによる体温の比較では, 生活リズムが確立されていない幼児は体温の上昇が遅い時刻に移行することが明らかとなった。このことから, 幼稚園の在園時間における運動遊びが, 一日を通して「動かせない身体」を持つ幼児の健康や身体発達に有効に働くことが示唆された

Types of Messages to Outside Teachers from the Early Childhood Education and Care Conferences : Examination of the Possibilities of Network Construction with the Hiroshima University Attached Kindergarten and Neighboring Areas.

本研究の目的は,次の通りである。(1)広島大学附属幼稚園が実施するSICSの理念に基づく保育カンファレンスは,他の保育園の保育者に対して何をもたらすのかについて検討する。(2)広島大学附属幼稚園と外部の保育者が共に学ぶためのネットワーク構築の在り方について検討する。 本研究では,調査協力者として,A保育園における4名の保育者を対象に,グループ・インタビューを実施した。研究方法として,大谷(2011)による質的データ分析法を用いた。 研究の結果,次の点が見出された。(1)他の保育園の保育者は日頃,子どもの気持ちを理解することに困難を感じていた。(2)そうした保育者にとって,保育カンファレンスは,子どもの気持ちを理解する方法論を提示するとともに,保育観の再発見をもたらした。(3)保育カンファレンスは,外部の保育者と広島大学附属幼稚園の保育者が共に学び合うためのネットワーク構築に寄与していた。The purposes of this study are as follows: (1) to examine what early childhood education and care conferences based on the idea of SICS by the Hiroshima University Attached Kindergarten bring to the teachers of other daycare centers, and (2) to examine network construction between two groups of childcare professionals to learn together. The participants in this study are four teachers from a day care center; we conducted a group interview and performed qualitative data analysis (Otani 2011) on the participants' narratives. The results of this study are as follows: (1) the teachers regularly experienced difficulty in understanding children's feelings, (2) the conferences introduced a methodology to resolve this difficulty, which led the teachers to rediscover the philosophy of early childhood education and care, and (3) the conferences contributed to building a network between the two groups of childcare professionals to learn together