Radiosensitization of gliomas by intracellular generation of 5-fluorouracil potentiates prodrug activator gene therapy with a retroviral replicating vector.

A tumor-selective non-lytic retroviral replicating vector (RRV), Toca 511, and an extended-release formulation of 5-fluorocytosine (5-FC), Toca FC, are currently being evaluated in clinical trials in patients with recurrent high-grade glioma (NCT01156584, NCT01470794 and NCT01985256). Tumor-selective propagation of this RRV enables highly efficient transduction of glioma cells with cytosine deaminase (CD), which serves as a prodrug activator for conversion of the anti-fungal prodrug 5-FC to the anti-cancer drug 5-fluorouracil (5-FU) directly within the infected cells. We investigated whether, in addition to its direct cytotoxic effects, 5-FU generated intracellularly by RRV-mediated CD/5-FC prodrug activator gene therapy could also act as a radiosensitizing agent. Efficient transduction by RRV and expression of CD were confirmed in the highly aggressive, radioresistant human glioblastoma cell line U87EGFRvIII and its parental cell line U87MG (U87). RRV-transduced cells showed significant radiosensitization even after transient exposure to 5-FC. This was confirmed both in vitro by a clonogenic colony survival assay and in vivo by bioluminescence imaging analysis. These results provide a convincing rationale for development of tumor-targeted radiosensitization strategies utilizing the tumor-selective replicative capability of RRV, and incorporation of radiation therapy into future clinical trials evaluating Toca 511 and Toca FC in brain tumor patients

カンキョウ ハイリョ ショウヒン ノ フキュウ タイヨウ ト モーダル ミックス

環境配慮商品といえども、環境配慮の側面だけではその普及の過程は平坦とはいえない。環境負荷の大きい自動車を基軸として、環境配慮商品としての普及に向けた取り組みを整理しながら、モーダルミックスの示唆する環境配慮社会の構築の枠組みを探っていく。The diffusion of products may not be just a matter of dealing with environmentally conscious products. A review of the diffusion process, especially concerning cars, whose environmental burden can be considerable, would be appropriate in helping to find framework suggested by modal mix, leading to an environmentally conscious society

Plasma S100A12 Levels and Peripheral Arterial Disease in End-Stage Renal Disease

Background: S100A12 is an endogenous ligand of the receptor for advanced glycation end products (RAGE). Plasma S100A12 levels are high in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). Peripheral arterial disease (PAD) is common in HD patients and is associated with increased cardiovascular morbidity and mortality rates in this population. To date, however, no study has specifically assessed the relationship between plasma S100A12 and PAD in HD patients. Methods: We conducted a cross-sectional study of 152 HD patients in our affiliated hospital. We investigated PAD history and patient characteristics and quantified plasma S100A12 levels in all participants. Results: HD patients with PAD (n = 26; 21.9 [13.6–33.4] ng/ml) showed significantly higher plasma S100A12 levels than HD patients without PAD (n = 126; 11.8 [7.5–17.6]ng/ml; p Conclusion: These results suggest that plasma S100A12 levels are strongly associated with PAD prevalence in ESRD patients undergoing HD

Unified Total Synthesis, Stereostructural Elucidation, and Biological Evaluation of Sarcophytonolides

Sarcophytonolides are cembranolide diterpenes isolated from the soft corals of genus Sarcophyton. Unified total synthesis of sarcophytonolides C, E, F, G, H, and J and isosarcophytonolide D was achieved. The synthetic routes feature NaHMDS- or SmI2-mediated fragment coupling, alkoxycarbonylallylation, macrolactonization, and transannular ring-closing metathesis. These total syntheses led to the absolute configurational confirmation of sarcophytonolide H, elucidation of sarcophytonolides C, E, F, and G, and revision of sarcophytonolide J and isosarcophytonolide D. We also evaluated the antifouling activity and toxicity of the synthetic sarcophytonolides H and J and their analogues as well as the cytotoxicity of the synthetic sarcophytonolides and the key synthetic intermediates

男性看護師のキャリア発達に関する意識と行動

急性期病院に勤務する男性看護師７名に対するインタビューから、男性看護師のキャリア発達に関する意識と行動について検討した。その結果、【キャリア発達に対する消極性】【経験の蓄積と技術研鑽への意欲】【職場における役割の獲得】【専門性の追求】及び【看護職への価値形成】のカテゴリー、男性看護師の特性として【看護の幅を広げる】、【未発達な男性看護師の立場】及び【家族に対する責任】のカテゴリーが抽出された。家庭を経済的に支える責任を担っているという意識は、男性看護師を継続する意志につながっていた。また、資格取得に伴う経済的負担や看護師としての経験不足は、キャリア発達に対する消極性につながっていた

Subgroup Analysis Stratified by Baseline Pancreatic β-cell Function in a Japanese Study of Dulaglutide in Patients with Type 2 Diabetes

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