51 research outputs found

    Complete response to pembrolizumab in advanced hepatocellular carcinoma with microsatellite instability

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    Hepatocellular carcinoma (HCC) has limited systemic treatment options and a poor prognosis. The immune checkpoint inhibitor pembrolizumab was recently approved for the treatment of solid tumors with microsatellite instability (MSI). However, its clinical utility for the management of HCC remains to be clarified. Here, we present a case of unresectable HCC with MSI that showed an impressive response to pembrolizumab treatment. A 64-year-old man with chronic HCV infection was diagnosed with a large HCC. His severe liver dysfunction and poor performance status prevented any treatment option other than sorafenib. However, sorafenib failed after a few days due to the rapid progression of the tumor. Based on the finding of MSI in a biopsy specimen, immunotherapy using pembrolizumab was initiated. A dramatic improvement in his general condition and a reduction in tumor size were observed after the initiation of pembrolizumab treatment. Among a cohort of 50 consecutive patients with advanced HCC who were refractory to standard systemic therapy, MSI was found only in the present case. Immune checkpoint blockade therapy induced prominent anti-tumor effects in HCC with MSI. Screening for defects in DNA mismatch repair function may be warranted in HCC patients despite the low frequency of MSI

    Directly Probing Intermolecular Structural Change of a Core Fragment of β<sub>2</sub>‑Microglobulin Amyloid Fibrils with Low-Frequency Raman Spectroscopy

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    Amyloid fibrils, which are ordered aggregates of proteins or peptides, have attracted keen interest because their deposition causes serious human diseases. Despite many studies utilizing X-ray crystallography, solid-state NMR, and other methods, intermolecular interactions governing the fibril formation remain largely unclear. Here, we used low-frequency Raman (LFR) spectroscopy to investigate the intermolecular β-sheet structure of a core fragment of β<sub>2</sub>-microglobulin amyloid fibrils, β<sub>2</sub>m<sub>21–29</sub>, in aqueous buffer solutions. The LFR spectra (approximately 10–200 cm<sup>–1</sup>) of β<sub>2</sub>m<sub>21–29</sub> amyloid fibrils measured at different pH values (ranging from 6.8 to 8.0) revealed a broad-spectral pattern with a maximum at ∼80 cm<sup>–1</sup> below pH 7.2 and at ∼110 cm<sup>–1</sup> above pH 7.4. This observation is attributed to a pH-dependent structural change from an antiparallel to a parallel intermolecular β-sheet structure. Multivariate curve resolution–alternating least-squares (MCR–ALS) analysis enabled us to decompose the apparently monotonous LFR spectra into three distinctly different contributions: intermolecular vibrations of the parallel and antiparallel β-sheets and intramolecular vibrations of the peptide backbone. Peak positions of the obtained LFR bands not only exhibit a much more pronounced difference between the two β-sheets than the conventional amide I band, but they also suggest stronger intermolecular interaction, due presumably to the hydrophobic effect, in the parallel β-sheet than in the antiparallel β-sheet. The present results show that LFR spectroscopy in combination with the MCR–ALS analysis holds promise for real-time tracking of the intermolecular dynamics of amyloid fibril formation under physiological conditions

    Serum Bilirubin Concentration is Associated with Left Ventricular Remodeling in Patients with Type 2 Diabetes Mellitus: A Cohort Study

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    <p>Article full text</p> <p>The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s13300-018-0368-6"><b>here</b>.</a></p> <p>Provide enhanced content for this article</p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p>Other enhanced features include, but are not limited to:</p> <ul> <li>Slide decks</li> <li>Videos and animations</li> <li>Audio abstracts</li> <li>Audio slides</li> </ul

    A study of the curriculum development to cultivate decision making skill based on scientific evidences (2)

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    本年度は, これまでに蓄積されてきた研究成果を踏まえて, 小学校まで校種の枠を広げた授業実践および高等学校への連関を考慮した中学校理科の教材開発を行うことを目的に研究を進めた。小学校では, 自身の考えに科学的な根拠をもって問題解決ができる能力を育成することが, 中学校, 高等学校まで視野に入れた取り組みとして最も基礎となると考えられるため, 第5学年を対象とした「ものの溶け方」の単元において問題解決的な学習を取り入れた実践を行った。高等学校への連関を考慮した中学校理科の教材としては, 水がどれほど汚れているかを知る指標であるCODを取り入れた教材開発に取り組んだ。COD測定に使用する過マンガン酸カリウムは「高等学校化学」で必ず学習する重要度の高い物質である。ただ, 過マンガン酸カリウムは中学生にとっては馴染みがないため, まず, 高校生を対象に試行的に実施し, その結果を踏まえて中学校で実践可能な教材となりうるかどうか検討した。小学では児童の問題解決能力や科学的な思考力を高める実践となった。また, 高等学校での試行的実施では, 中学校において実践可能な教材であると判断できる結果が得られた
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