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除染廃棄物の焼却灰 容積減らす新施設完成

福島県内の除染廃棄物を燃やして出る、汚染の程度が高い灰の容積を減らすための新しい施設が、福島第一原発の周辺にある中間貯蔵施設の用地に完成しました。

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Dual inhibition of canonical and non-canonical NF-κB pathways demonstrates significant anti-tumor activities in multiple myeloma.

著者 Fabre C , Mimura N , Bobb K , Kong SY , Gorgun G , Cirstea D , Hu Y , Minami J , Ohguchi H , Zhang J , Meshulam J , Carrasco R , Tai YT , Richardson PG , Hideshima T , Anderson KC
Clin Cancer Res.2012 Jul 17 ; ():.
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Medical Oncology, Dana-Farber Cancer Institute.

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PURPOSE: NF-κB transcription factor plays a key role in the pathogenesis of multiple myeloma (MM) in the context of the bone marrow (BM) microenvironment. Both canonical and non-canonical pathways contribute to total NF-κB activity. Recent studies have demonstrated a critical role for the non-canonical pathway: selective inhibitors of the canonical pathway present a limited activity, mutations of the non-canonical pathway are frequent, and bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-κB activity. Experimental design: MM cell lines, primary patient cells, and the human MM xenograft murine model were used to examine the biologic impact of dual inhibition of both canonical and non-canonical NF-κB pathways. RESULTS: We show that PBS-1086 induces potent cytotoxicity in MM cells, but not in peripheral blood mononuclear cells. PBS-1086 overcomes the proliferative and anti-apoptotic effects of the BM milieu, associated with inhibition of NF-κB activity. Moreover, PBS-1086 strongly enhances the cytotoxicity of bortezomib in bortezomib-resistant MM cell lines and patient MM cells. PBS-1086 also inhibits osteoclastogenesis through an inhibition of RANKL-induced NF-κB activation. Finally, in a xenograft model of human MM in the BM milieu, PBS-1086 shows significant in vivo anti-MM activity and prolongs host survival, associated with apoptosis and inhibition of both NF-κB pathways in tumor cells. CONCLUSIONS: Our data demonstrate that PBS-1086 is a promising dual inhibitor of the canonical and non-canonical NF-κB pathways. Our preclinical study therefore provides the framework for clinical evaluation of PBS-1086 in combination with bortezomib for the treatment of MM and related bone lesions.
PMID: 22806876 [PubMed - as supplied by publisher]
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