Mediatory Summary Generation: Summary-Passage Extraction for Information Credibility on the Web

PACLIC 23 / City University of Hong Kong / 3-5 December 200

Targeting critical kinases and anti-apoptotic molecules overcomes steroid resistance in MLL-rearranged leukaemia.

BACKGROUND: Acute lymphoblastic leukaemia with mixed lineage leukaemia gene rearrangement (MLL-ALL) frequently affects infants and is associated with a poor prognosis. Primary refractory and relapsed disease due to resistance to glucocorticoids (GCs) remains a substantial hurdle to improving clinical outcomes. In this study, we aimed to overcome GC resistance of MLL-ALL. METHODS: Using leukaemia patient specimens, we performed bioinformatic analyses to identify target genes/pathways. To test inhibition of target pathways in vivo, we created pre-clinical therapeutic mouse patient-derived xenograft (PDX)-models by transplanting human MLL-ALL leukaemia initiating cells (LIC) into immune-deficient NSG mice. Finally, we conducted B-cell lymphoma-2 (BCL-2) homology domain 3 (BH3) profiling to identify BH3 peptides responsible for treatment resistance in MLL-leukaemia. FINDINGS: Src family kinases (SFKs) and Fms-like tyrosine kinase 3 (FLT3) signaling pathway were over-represented in MLL-ALL cells. PDX-models of infant MLL- ALL recapitulated GC-resistance in vivo but RK-20449, an inhibitor of SFKs and FLT3 eliminated human MLL-ALL cells in vivo, overcoming GC-resistance. Further, we identified BCL-2 dependence as a mechanism of treatment resistance in MLL-ALL through BH3 profiling. Furthermore, MLL-ALL cells resistant to RK-20449 treatment were dependent on the anti-apoptotic BCL-2 protein for their survival. Combined inhibition of SFKs/FLT3 by RK-20449 and of BCL-2 by ABT-199 led to substantial elimination of MLL-ALL cells in vitro and in vivo. Triple treatment combining GCs, RK-20449 and ABT-199 resulted in complete elimination of MLL-ALL cells in vivo. INTERPRETATION: SFKs/FLT3 signaling pathways are promising targets for treatment of treatment-resistant MLL-ALL. Combined inhibition of these kinase pathways and anti-apoptotic BCL-2 successfully eliminated highly resistant MLL-ALL and demonstrated a new treatment strategy for treatment-resistant poor-outcome MLL-ALL. FUNDING: This study was supported by RIKEN (RIKEN President\u27s Discretionary Grant) for FI, Japan Agency for Medical Research and Development (the Basic Science and Platform Technology Program for Innovative Biological Medicine for FI and by NIH CA034196 for LDS. The funders had no role in the study design, data collection, data analysis, interpretation nor writing of the report

Human NK cell development in hIL-7 and hIL-15 knockin NOD/SCID/IL2rgKO mice.

The immune system encompasses acquired and innate immunity that matures through interaction with microenvironmental components. Cytokines serve as environmental factors that foster functional maturation of immune cells. Although NOD/SCID/IL2rgKO (NSG) humanized mice support investigation of human immunity in vivo, a species barrier between human immune cells and the mouse microenvironment limits human acquired as well as innate immune function. To study the roles of human cytokines in human acquired and innate immune cell development, we created NSG mice expressing hIL-7 and hIL-15. Although hIL-7 alone was not sufficient for supporting human NK cell development in vivo, increased frequencies of human NK cells were confirmed in multiple organs of hIL-7 and hIL-15 double knockin (hIL-7xhIL-15 KI) NSG mice engrafted with human hematopoietic stem cells. hIL-7xhIL-15 KI NSG humanized mice provide a valuable in vivo model to investigate development and function of human NK cells

地方環境税としての産業廃棄物税について

1 はじめに / 2 産廃税の分類 / 3 インセンティブ効果に着目した4タイプの産廃税の比較 / 4 産廃税の広域調整問題 / 5 広域調整可能なハイブリッド型産廃税 : 福岡県「資源循環促進税 （仮称）」構想 / 6 まと

産業廃棄物税の排出抑制効果の部分均衡分析

1　はじめに / 2　産廃処理の状況と産廃税の諸タイプ / 3　産廃税の部分均衡モデル / 4　ハイブリッド型産廃税：TypeD / 5　複数地域の産廃税課税による総排出抑制効果 / 6　おわり

Abstract and Assessment of Doctoral Theses(2005)

Principles of Innovation Uncertainty Management and the IUM Model(イノベーションの不確実性マネジメントの原理とモデル)[Klasen]公共財供給の経済分析 : 選挙と政治献金の経済モデル[金崎]環境規制と汚染者の有限責任問題の経済分析[境]研究開発活動と内生的成長に関する理論分析 : マクロ動学モデルによる分析[片桐]台湾パソコン産業の発展とグローバル生産ネットワーク : 学習という観点から[中原]A REVIEW OF THE KNOWLEDGE MANAGEMENT MODEL BASED ON AN EMPIRICAL SURVEY OF KOREAN EXPERTS(韓国専門家実証調査による知識経営モデル考察)[朴]金融機関と金融行政の効率性の経済分析[下田]分散共分散変動モデルによる現物資産価格変動のリスクヘッジ[森田]産業廃棄物税の研究 : わが国における分権的環境政策の観点から[金子]アメリカにおけるミクロ社会経済分析の方法的形成とわが国への適用[伊藤]新規株式公開（IPO）制度と利益マネジメント : 新規公開企業の業績・株価動向を中心に[松本]私立大学のガバナンス : 統治と意思決定の仕組み[平山