「地球的市民性」を培うグローバル学習方法論研究 : イギリス地理教材を手がかりに

内容の要約広島大学(Hiroshima University)博士(教育学)Doctor of Philosophy in Educationdoctora

A dominant-negative FGF1 mutant (the R50E mutant) suppresses tumorigenesis and angiogenesis.

Fibroblast growth factor-1 (FGF1) and FGF2 play a critical role in angiogenesis, a formation of new blood vessels from existing blood vessels. Integrins are critically involved in FGF signaling through crosstalk. We previously reported that FGF1 directly binds to integrin αvβ3 and induces FGF receptor-1 (FGFR1)-FGF1-integrin αvβ3 ternary complex. We previously generated an integrin binding defective FGF1 mutant (Arg-50 to Glu, R50E). R50E is defective in inducing ternary complex formation, cell proliferation, and cell migration, and suppresses FGF signaling induced by WT FGF1 (a dominant-negative effect) in vitro. These findings suggest that FGFR and αvβ3 crosstalk through direct integrin binding to FGF, and that R50E acts as an antagonist to FGFR. We studied if R50E suppresses tumorigenesis and angiogenesis. Here we describe that R50E suppressed tumor growth in vivo while WT FGF1 enhanced it using cancer cells that stably express WT FGF1 or R50E. Since R50E did not affect proliferation of cancer cells in vitro, we hypothesized that R50E suppressed tumorigenesis indirectly through suppressing angiogenesis. We thus studied the effect of R50E on angiogenesis in several angiogenesis models. We found that excess R50E suppressed FGF1-induced migration and tube formation of endothelial cells, FGF1-induced angiogenesis in matrigel plug assays, and the outgrowth of cells in aorta ring assays. Excess R50E suppressed FGF1-induced angiogenesis in chick embryo chorioallantoic membrane (CAM) assays. Interestingly, excess R50E suppressed FGF2-induced angiogenesis in CAM assays as well, suggesting that R50E may uniquely suppress signaling from other members of the FGF family. Taken together, our results suggest that R50E suppresses angiogenesis induced by FGF1 or FGF2, and thereby indirectly suppresses tumorigenesis, in addition to its possible direct effect on tumor cell proliferation in vivo. We propose that R50E has potential as an anti-cancer and anti-angiogenesis therapeutic agent ("FGF1 decoy")

Characterization of an active LINE-1 in the naked mole-rat genome.

Naked mole-rats (NMRs, Heterocephalus glaber) are the longest-living rodent species. A reason for their long lifespan is pronounced cancer resistance. Therefore, researchers believe that NMRs have unknown secrets of cancer resistance and seek to find them. Here, to reveal the secrets, we noticed a retrotransposon, long interspersed nuclear element 1 (L1). L1s can amplify themselves and are considered endogenous oncogenic mutagens. Since the NMR genome contains fewer L1-derived sequences than other mammalian genomes, we reasoned that the retrotransposition activity of L1s in the NMR genome is lower than those in other mammalian genomes. In this study, we successfully cloned an intact L1 from the NMR genome and named it NMR-L1. An L1 retrotransposition assay using the NMR-L1 reporter revealed that NMR-L1 was active retrotransposon, but its activity was lower than that of human and mouse L1s. Despite lower retrotrasposition activity, NMR-L1 was still capable of inducing cell senescence, a tumor-protective system. NMR-L1 required the 3' untranslated region (UTR) for retrotransposition, suggesting that NMR-L1 is a stringent-type of L1. We also confirmed the 5' UTR promoter activity of NMR-L1. Finally, we identified the G-quadruplex structure of the 3' UTR, which modulated the retrotransposition activity of NMR-L1. Taken together, the data indicate that NMR-L1 retrotranspose less efficiently, which may contribute to the cancer resistance of NMRs

Genotoxicity of nano/microparticles in in vitro micronuclei, in vivo comet and mutation assay systems

<p>Abstract</p> <p>Background</p> <p>Recently, manufactured nano/microparticles such as fullerenes (C₆₀), carbon black (CB) and ceramic fiber are being widely used because of their desirable properties in industrial, medical and cosmetic fields. However, there are few data on these particles in mammalian mutagenesis and carcinogenesis. To examine genotoxic effects by C₆₀, CB and kaolin, an <it>in vitro </it>micronuclei (MN) test was conducted with human lung cancer cell line, A549 cells. In addition, DNA damage and mutations were analyzed by <it>in vivo </it>assay systems using male C57BL/6J or <it>gpt </it>delta transgenic mice which were intratracheally instilled with single or multiple doses of 0.2 mg per animal of particles.</p> <p>Results</p> <p>In <it>in vitro </it>genotoxic analysis, increased MN frequencies were observed in A549 cells treated with C₆₀, CB and kaolin in a dose-dependent manner. These three nano/microparticles also induced DNA damage in the lungs of C57BL/6J mice measured by comet assay. Moreover, single or multiple instillations of C₆₀and kaolin, increased either or both of <it>gpt </it>and Spi^-mutant frequencies in the lungs of <it>gpt </it>delta transgenic mice. Mutation spectra analysis showed transversions were predominant, and more than 60% of the base substitutions occurred at G:C base pairs in the <it>gpt </it>genes. The G:C to C:G transversion was commonly increased by these particle instillations.</p> <p>Conclusion</p> <p>Manufactured nano/microparticles, CB, C₆₀and kaolin, were shown to be genotoxic in <it>in vitro </it>and <it>in vivo </it>assay systems.</p

Fish oil-enriched nutrition combined with systemic chemotherapy for gastrointestinal cancer patients with cancer cachexia

Despite recent advances in chemotherapy for gastrointestinal cancer, a crucial factor related to poor prognosis is reduced tolerance to chemotherapy induced by cancer cachexia. Fish oil (FO)-derived eicosapentaenoic acid (EPA) modulates inflammation in patients with various malignancies; however, the impact of FO-enriched nutrition as a combined modality therapy on clinical outcomes remains controversial. We systemically analysed chronological changes in biochemical and physiological status using bioelectrical impedance analysis in 128 gastrointestinal cancer patients provided with or without FO-enriched nutrition during chemotherapy. Furthermore, we evaluated the clinical significance of FO-enriched nutrition and clarified appropriate patient groups that receive prognostic benefits from FO-enriched nutrition during treatment of gastrointestinal cancer. The control group showed significant up-regulation of serum CRP) levels and no significant difference in both skeletal muscle mass and lean body mass. In contrast, the FO-enriched nutrition group showed no changes in serum CRP concentration and significantly increased skeletal muscle mass and lean body mass over time. Furthermore, high CRP levels significantly correlated with reduced tolerance to chemotherapy, and FO-enriched nutrition improved chemotherapy tolerance and prognosis, particularly in gastrointestinal cancer patients with a modified Glasgow prognostic score (mGPS) of 1 or 2. We conclude that FO-enriched nutrition may improve the prognosis of patients with cancer cachexia and systemic inflammation (i.e., those with a mGPS of 1 or 2)

カイゴフクシシ ヨウセイ キョウイク ニオケル グループ ケンキュウ : ジュギョウ ジッセン ト ケンキュウ カダイ ノ ケイコウ

本研究は、グループ研究の形態で行う「卒業研究」の研究課題決定に関する授業実践の評価を行い、学生の研究課題の傾向から、今後の介護福祉士養成教育における教育的アプローチへの示唆を得ることを目的とした。結果、1)授業実践の評価として、グループ活動を促進するには「グループ学習のねらい」や「授業計画」を提示し、学生の準備を整えることが大切である。2)研究課題の傾向をみた結果、実習で得られた体験から問題意識を深め、自分の課題に向き合う姿勢を評価できた。一方、幅広い視点が持てるには2 年生課程における限界も示唆されたが、学生が現在捉えている関心に引きつけて社会的な視点がもてるような指導を行うことが大切である。3)カリキュラム改正により社会福祉系科目を含め、現在の介護福祉実践を形成してきた科目への比重が低下した。国が指定する教育内容は教育の前提条件であるため、現行カリキュラムの検証を行うとともに、介護福祉士養成教育の前提条件をどう作っていくかの課題があることを指摘した