Effect of rs2293347 Polymorphism in EGFR on the Clinical Efficacy of Gefitinib in Patients with Non-small Cell Lung Cancer

Background and objective Genetic variations of the epidermal growth factor receptor (EGFR) may alter the protein function and therapeutic efficacy of EGFR inhibitors. The aim of this study is to investigate the association between single nucleotide polymorphism rs2293347 in EGFR and the clinical outcome in patients with advanced non-small cell lung cancer (NSCLC) treated with gefitinib. Methods A total of 88 advanced NSCLC patients treated with gefitinib were analyzed in the present study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was conducted to analyze the genotype. The association study was performed between genotypes and clinical efficacy among 88 patients. Results rs2293347 was associated with the efficacy of gefitinib. The response rate for the rs2293347 GG was significantly higher than that for the GA or AA (71.4% vs 36.0%, P=0.002). rs2293347 GG genotype was also associated with longer progression-free survival compared with GA or AA genotype (10 months vs 3 months, P=0.005). No significant difference was shown on the overall survival (OS) (P=0.409). Conclusion rs2293347 polymorphism in exon 25 is associated with the clinical efficacy of gefitinib and may be a potential biomarker to predict the clinical outcome in advanced NSCLC patients treated with gefitinib

Extracellular matrix-derived mechanical force governs breast cancer cell stemness and quiescence transition through integrin-DDR signaling

The extracellular matrix (ECM) serves as signals that regulate specific cell states in tumor tissues. Increasing evidence suggests that extracellular biomechanical force signals are critical in tumor progression. In this study, we aimed to explore the influence of ECM-derived biomechanical force on breast cancer cell status. Experiments were conducted using 3D collagen, fibrinogen, and Matrigel matrices to investigate the role of mechanical force in tumor development. Integrin-cytoskeleton-AIRE and DDR-STAT signals were examined using RNA sequencing and western blotting. Data from 1358 patients and 86 clinical specimens were used for ECM signature-prognosis analysis. Our findings revealed that ECM-derived mechanical force regulated tumor stemness and cell quiescence in breast cancer cells. A mechanical force of ~45 Pa derived from the extracellular substrate activated integrin β1/3 receptors, stimulating stem cell signaling pathways through the cytoskeleton/AIRE axis and promoting tumorigenic potential and stem-like phenotypes. However, excessive mechanical force (450 Pa) could drive stem-like cancer cells into a quiescent state, with the removal of mechanical forces leading to vigorous proliferation in quiescent cancer stem cells. Mechanical force facilitated cell cycle arrest to induce quiescence, dependent on DDR2/STAT1/P27 signaling. Therefore, ECM-derived mechanical force governs breast cancer cell status and proliferative characteristics through stiffness alterations. We further established an ECM signature based on the fibrinogen/fibronectin/vitronectin/elastin axis, which efficiently predicts patient prognosis in breast cancer. Our findings highlight the vital role of ECM-derived mechanical force in governing breast cancer cell stemness/quiescence transition and suggest the novel use of ECM signature in predicting the clinical prognosis of breast cancer

Shape-Tailorable Graphene-Based Ultra-High-Rate Supercapacitor for Wearable Electronics

With the bloom of wearable electronics, it is becoming necessary to develop energy storage units, <i>e</i>.<i>g</i>., supercapacitors that can be arbitrarily tailored at the device level. Although gel electrolytes have been applied in supercapacitors for decades, no report has studied the shape-tailorable capability of a supercapacitor, for instance, where the device still works after being cut. Here we report a tailorable gel-based supercapacitor with symmetric electrodes prepared by combining electrochemically reduced graphene oxide deposited on a nickel nanocone array current collector with a unique packaging method. This supercapacitor with good flexibility and consistency showed excellent rate performance, cycling stability, and mechanical properties. As a demonstration, these tailorable supercapacitors connected in series can be used to drive small gadgets, <i>e</i>.<i>g</i>., a light-emitting diode (LED) and a minimotor propeller. As simple as it is (electrochemical deposition, stencil printing, <i>etc</i>.), this technique can be used in wearable electronics and miniaturized device applications that require arbitrarily shaped energy storage units

Germline mutation landscape of Chinese patients with familial breast/ovarian cancer in a panel of 22 susceptibility genes

 Abstract Genetic testing for germline mutations in BRCA1/2 of patients with breast cancer (BC) is part of routine patient care. However, BRCA1/2 mutations account only for a fraction of familial BC. A custom panel of 22 gene sequencing was performed on each patient. Among the 481 female patients, 135 patients were detected to carry pathogenic (P)/likely pathogenic (LP) mutations (28.1%), which corresponded to 12 different cancer predisposition genes [14.6% (70/481) on BRCA1 gene, 5.0% (24/481) on BRCA2 gene, 8.5% (41/481) on non‐BRCA1/2 genes]. Moreover, 24.7% (119/481) of patients had mutation of unknown significance (VUS) in these genes. The most common (8/481) pathogenic mutation is BRCA1 c.5470_5477del, while BRIP1 2392 C > T of patients was detected. All the mutations detected were mainly seen in the homologous recombinant repair pathway. Compared to BRCA2 mutation, BRCA1 mutation is higher in younger female patients (P < 0.01). Some pathogenic mutations were detected in the patients’ familiy members without the past history of tumor and 92 novel mutations were detected (31 on BRCA including 2 P, 16 LP, 13 VUS; 61 on non‐BRCA1/2 including 9 LP, 52 VUS). The detection rate of BRCA1/2 mutations was higher in patients with three or more cancer family members than those with one or two. However, the difference was not statistically different. The results suggest that multigene panel testing can increase mutation detection rate for high‐risk BC patients. Detailed family history can help to categorize new mutations

Integrated computation model of lithium-ion battery subject to nail penetration

The nail penetration of lithium-ion batteries (LIBs) has become a standard battery safety evaluation method to mimic the potential penetration of a foreign object into LIB, which can lead to internal short circuit with catastrophic consequences, such as thermal runaway, fire, and explosion. To provide a safe, time-efficient, and cost-effective method for studying the nail penetration problem, an integrated computational method that considers the mechanical, electrochemical, and thermal behaviors of the jellyroll was developed using a coupled 3D mechanical model, a 1D battery model, and a short circuit model. The integrated model, along with the sub-models, was validated to agree reasonably well with experimental test data. In addition, a comprehensive quantitative analysis of governing factors, e.g., shapes, sizes, and displacements of nails, states of charge, and penetration speeds, was conducted. The proposed computational framework for LIB nail penetration was first introduced. This framework can provide an accurate prediction of the time history profile of battery voltage, temperature, and mechanical behavior. The factors that affected the behavior of the jellyroll under nail penetration were discussed systematically. Results provide a solid foundation for future in-depth studies on LIB nail penetration mechanisms and safety design. (C) 2016 Elsevier Ltd. All rights reserved

レーザー駆動中性子源の宇宙核物理学への応用 -放射化法による広いエネルギー領域における中性子数の測定-

大強度レーザーを用いて陽子と重陽子を加速して、Beに照射して中性子を生成した。10-20MeVの高エネルギーの中性子を金属試料に照射し、（n,2n)反応で生成された放射性同位体のβ崩壊によるγ線を計測する手法に、中性子の飛行時間計測法から得たエネルギー分布を組み合わせることで中性子の量を評価した。日本物理学会　2021年秋季大

Binding Model for the Interaction of Anticancer Arylsulfonamides with the p300 Transcription Cofactor

Hypoxia inducible factors (HIFs) are transcription factors that activate expression of multiple gene products and promote tumor adaptation to a hypoxic environment. To become transcriptionally active, HIFs associate with cofactors p300 or CBP. Previously, we found that arylsulfonamides can antagonize HIF transcription in a bioassay, block the p300/HIF-1α interaction, and exert potent anticancer activity in several animal models. In the present work, KCN1-bead affinity pull down, ¹⁴C-labeled KCN1 binding, and KCN1-surface plasmon resonance measurements provide initial support for a mechanism in which KCN1 can bind to the CH1 domain of p300 and likely prevent the p300/HIF-1α assembly. Using a previously reported NMR structure of the p300/HIF-1α complex, we have identified potential binding sites in the p300-CH1 domain. A two-site binding model coupled with IC₅₀ values has allowed establishment of a modest ROC-based enrichment and creation of a guide for future analogue synthesis

The Development of Laser-Driven Epithermal Neutron Source for Resonance Spectral DiagnosticsⅡ

大強度レーザーをターゲットに集光させ、陽子と重陽子を加速し、直後に配置したBeターゲットに照射することで短パルスで中性子を生成した。さらに、小型の減速材をBeターゲットに近接させることで効果的に熱外中性子を生成した。この熱外中性子を用いて共鳴計測の試験を行った。日本物理学会第77回年次大

レーザー駆動熱外中性子源による中性子共鳴吸収計測

大阪大学レーザー科学研究所の大強度レーザーLFEXを水素を含むターゲットに集光し数十MeVの陽子を加速し、近接したBeターゲットに陽子を照射し核反応で中性子を生成した。この中性子にモデレーターを設置して時間分解能の劣化を抑えつつ中性子を部分的に減速させた。この中性子パルスを用いて金属ターゲットを透過後に飛行時間計測法で中性子のエネルギースペクトルを計測した。物質の種類によって固有の中性子共鳴吸収エネルギーがあり分析可能である。本手法で中性子共鳴吸収を計測した。日本物理学会　第76回年次大