Inhibition of motility and invasiveness of renal cell carcinoma induced by short interfering RNA transfection of β1,4GalNAc transferase

AbstractHuman renal cell carcinoma (RCC) has been characterized by remarkable changes in ganglioside composition. TOS1 cells, typical of metastatic RCC, are characterized by predominance of GM2 as monosialoganglioside, and β1,4GalNAc disialyl-Lc4 (RM2 antigen) as disialoganglioside [J. Biol. Chem. 276 (2001) 16695]. In order to observe the functional role of gangliosides in RCC malignancy, TOS1 cells were transfected with short interfering RNA (siRNA) based on open reading frame sequence of β1,4GalNAc transferase (β1,4GalNAc-T), and its disordered sequence of siRNA (dsiRNA) as control. In siRNA transfectant, β1,4GalNAc-T mRNA level and GM2 expression were greatly reduced, whereby GM3 expression appeared. In contrast, RM2 antigen level was unchanged, even though it has the same β1,4GalNAc epitope at the terminus. dsiRNA transfectant showed no change of β1,4GalNAc-T mRNA and did not express GM3. Concomitant with reduction of GM2 and appearance of GM3, siRNA transfectant showed greatly reduced motility and invasiveness, although growth rate was unaltered. Both transfectants with siRNA and dsiRNA expressed the same level of tetraspanin CD9. Since CD9/GM3 complex is known to reduce integrin-dependent motility and invasiveness [Biochemistry 40 (2001) 6414], it is plausible that motility and invasiveness of siRNA transfectant of TOS1 cells may be reduced by enhanced formation of such complex

放射線被ばくの現状と課題 : 救急災害医療の立場から

わが国における過去の放射線被ばく事故は、当時の救急医療体制が十分整備されておらず、被ばく者に対する初期救急災害医療において多くの問題があった。今回、緊急被ばくについて救急災害医療の視点から、過去のJOC社東海事業所臨界事故および東日本大震災に伴う東京電力福島第一原発事故における急性放射線症候群の事例について着目し検証した。それらの問題点と課題を抽出し、今後の放射線被ばく事故時における緊急救急医療体制のあり方について考察した。とくに、緊急被ばく医療体制のあり方においては、危機管理体制の整備と情報を共有する新しい総合的な体制作りを注視した。すなわち、今後準備とサーベイランス（監視）の2 つの戦略を構築していくことが重要であると考えた。journal articl

Acquired resistance of leukemic cells to AraC is associated with the upregulation of aldehyde dehydrogenase 1 family member A2.

The elucidation of drug resistance mechanisms is important in the development of clinical therapies for the treatment of leukemia. To study the drug resistance mechanisms, protein expression profiles of 1-β-D-arabinofuranosylcytosine (AraC)-sensitive K562 (K562S) cells and AraC-resistant K562 (K562AC) cells were compared using two-dimensional fluorescence difference gel electrophoresis. In a comparison of protein expression profiles, 2073 protein spots were found to be altered, and 15 proteins of them were remarkably altered. These proteins were identified by mass spectrometry. The most differently expressed proteins were aldehyde dehydrogenase 1 family member A2 (ALDH1A2) and vimentin. Both proteins were verified using reverse transcriptase polymerase chain reaction and Western blot analysis. ALDH1A2 protein was found to be effective in AraC resistance. ALDH1A2 knock-down induced sensitivity to AraC treatment in K562AC cells, and ALDH1A2 overexpressed K562S cells acquired the AraC resistance. Furthermore, the findings also suggest that ALDH1A2 expression is increased after the appearance of AraC resistance in clinical cases. These results will be helpful in understanding the mechanism of AraC resistance

新型コロナウイルス感染における PCR 検査の意義に関する考察 ─ 最近の文献からのエビデンス ─

新型コロナウイルス（SARS-CoV-2）による新型コロナウイルス感染症（COVID-19）は，1 年半以上も世界中で感染が拡大し続け，長期化して未だ終息させることが困難な状況にある。世界的に本症を確実に診断する手法として，遺伝子核酸増幅検査がパンデミック当初から導入され，標準検査として現在に至っている。今回，その中で本症における診 断的意義が高いとされるPCR（polymerase chain reaction）検査について着目し，その意義に関する文献を検索し，根拠に基づく医療（EBM）の手法によりエビデンスを抽出し分析した。とくに，感度および特異度における精度を比較した。これらの検索の結果，PCR 検査の感度は90% 以上であること，唾液を材料としても鼻咽頭検体と精度が同等で あることなど，ガイドラインに有用なエビデンスが得られていることが明らかになった。 PCR 検査の臨床診断としての意義は標準検査として汎用され，公衆衛生の観点からも無症状者に対する検査実施の意義が明らかとなった