Conventional colonoscopy can result in unnecessary biopsy or endoscopic resection due to its inability to distinguish adenomas from hyperplastic polyps. This study therefore evaluated the efficacy of ...high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) in discriminating colon adenoma from hyperplastic polyps.
This was a prospective multicenter study in patients undergoing AFI and NBI examinations. HRE, AFI, and NBI images were classified into two groups based on morphological characteristics, the predominant color intensities, and the visibility of meshed capillary vessels, respectively. Each of the endoscopic photographs were independently evaluated by a single endoscopist. The images were then assessed by three specialists and three residents, the latter having performed < 500 colonoscopies and < 30 NBI and AFI examinations. Diagnostic test statistics were calculated to compare the accuracy in differentiating colon adenoma from hyperplastic polyps for each method.
A total of 183 patients were enrolled in the study and 339 adenomas and 85 hyperplastic polyps were identified. AFI and NBI could distinguish adenoma from hyperplastic polyps with an accuracy of 84.9 % and 88.4 %, respectively, whereas HRE exhibited an accuracy of 75.9 %. In the 358 lesions in which the AFI diagnosis was consistent with that of NBI, the accuracy, sensitivity, and specificity were high, at 91.9 %, 92.7 %, and 92.9 %, respectively. During the study comparing specialists and residents, AFI and NBI dramatically improved the diagnostic accuracy of residents from 69.1 % to 86.1 % and 84.7 %, respectively.
Both AFI and NBI are considered to be feasible tools that can discriminate colon adenoma from hyperplastic polyps, and their use may be particularly beneficial for less-experienced endoscopists.
Background.
A biomarker that predicts bone metastasis based on a protein laboratory assay has not been demonstrated. Reverse‐phase protein array (RPPA) enables quantification of total and ...phosphorylated proteins, providing information about their functional status. The aim of this study was to identify bone‐metastasis‐related markers in patients with primary breast cancer using RPPA analysis.
Patients and Methods.
Tumor samples were obtained from 169 patients with primary invasive breast carcinoma who underwent surgery. The patients were categorized by whether they developed breast cancer bone metastasis (BCBM) during follow‐up. Clinical characteristics and protein expression by RPPA were compared and verified by leave‐one‐out cross‐validation.
Results.
Lymph node status (p = .023) and expression level of 22 proteins by RPPA were significantly correlated with BCBM in logistic regression analysis. These variables were used to build a logistic regression model. After filtering the variables through a stepwise algorithm, the final model, consisting of 8 proteins and lymph node status, had sensitivity of 30.0%, specificity of 90.5%, positive predictive value of 30.0%, and negative predictive value of 90.5% in the cross‐validation. Most of the identified proteins were associated with cell cycle or signal transduction (CDK2, CDKN1A, Rb1, Src, phosphorylated‐ribosomal S6 kinase, HER2, BCL11A, and MYH11).
Conclusion.
Our validated model, in which the primary tumor is tested with RPPA, can predict patients who are at low risk of developing BCBM and thus who likely would not benefit from receiving a bisphosphonate in the adjuvant setting. Clinical trials excluding these patients have the potential to clarify the benefit of bisphosphonates in the adjuvant setting.
摘要
背景。尚未证实可基于蛋白质实验室检测预测骨转移的生物标志物。反相蛋白质阵列 (RPPA) 可用来对总蛋白质和磷酸化蛋白质进行量化分析，提供有关其功能状态的信息。本研究的目的是利用 RPPA 分析确定原发性乳腺癌患者中的骨转移相关生物标志物。
患者与方法。肿瘤样本采集自接受手术的 169 名原发侵袭性乳腺癌患者。患者按在随访期间是否出现乳腺癌骨转移 (BCBM) 进行分类。对临床特征和蛋白质的 RPPA 表达进行了比较，并通过留一交叉验证法进行验证。
结果。淋巴结状态 (p = .023) 和 22 种蛋白质的 RPPA 表达与逻辑回归分析中的 BCBM 显著相关。这些变量被用来建立逻辑回归模型。通过逐步算法过滤变量后，该模型最终由 8 种蛋白质和淋巴结状态组成，其在交叉验证中的敏感度为 30.0%、特异性为 90.5%、阳性预测值为 30.0%、阴性预测值为 90.5%。识别出来的多数蛋白质与细胞周期或信号转导有关（CDK2、CDKN1A、Rb1、Src、磷酸化核糖体 S6 激酶、HER2、BCL11A 和 MYH11）。
结论。我们用 RPPA 检测原发性肿瘤的验证模型可以预测患者出现 BCBM 的风险低，因此可能无法得益于双膦酸盐辅助治疗。排除这些患者的临床试验有可能查明双磷酸盐辅助治疗的益处。The Oncologist 2014;19:909–914
The aim of this study was to use the reverse‐phase protein array to predict patients who are at low risk of developing bone metastasis from breast cancer. The model showed novel predictive potential. Patients with low assessed risk are unlikely to benefit from receiving a bisphosphonate in the adjuvant setting. Further clinical trials excluding these patients will clarify the benefit of bisphosphonates.
BACKGROUND:Lidocaine has been widely used to relieve acute pain and chronic refractory pain effectively by both systemic and local administration. Numerous studies reported that lidocaine affects ...several pain signaling pathways as well as voltage-gated sodium channels, suggesting the existence of multiple mechanisms underlying pain relief by lidocaine. Some extracellular adenosine triphosphate (ATP) receptor subunits are thought to play a role in chronic pain mechanisms, but there have been few studies on the effects of lidocaine on ATP receptors. We studied the effects of lidocaine on purinergic P2X3, P2X4, and P2X7 receptors to explore the mechanisms underlying pain-relieving effects of lidocaine.
METHODS:We investigated the effects of lidocaine on ATP-induced currents in ATP receptor subunits, P2X3, P2X4, and P2X7 expressed in Xenopus oocytes, by using whole-cell, two-electrode, voltage-clamp techniques.
RESULTS:Lidocaine inhibited ATP-induced currents in P2X7, but not in P2X3 or P2X4 subunits, in a concentration-dependent manner. The half maximal inhibitory concentration for lidocaine inhibition was 282 ± 45 μmol/L. By contrast, mepivacaine, ropivacaine, and bupivacaine exerted only limited effects on the P2X7 receptor. Lidocaine inhibited the ATP concentration–response curve for the P2X7 receptor via noncompetitive inhibition. Intracellular and extracellular N-(2,6-dimethylphenylcarbamoylmethyl) triethylammonium bromide (QX-314) and benzocaine suppressed ATP-induced currents in the P2X7 receptor in a concentration-dependent manner. In addition, repetitive ATP treatments at 5-minute intervals in the continuous presence of lidocaine revealed that lidocaine inhibition was use-dependent. Finally, the selective P2X7 receptor antagonists Brilliant Blue G and AZ11645373 did not affect the inhibitory actions of lidocaine on the P2X7 receptor.
CONCLUSIONS:Lidocaine selectively inhibited the function of the P2X7 receptor expressed in Xenopus oocytes. This effect may be caused by acting on sites in the ion channel pore both extracellularly and intracellularly. These results help to understand the mechanisms underlying the analgesic effects of lidocaine when it is administered locally at least.
The structure and interactions of different (Li salt + glyme) mixtures, namely equimolar mixtures of lithium bis(trifluoromethylsulfonyl)imide, nitrate or trifluoroacetate salts combined with either ...triglyme or tetraglyme molecules, are probed using Molecular Dynamics simulations. structure factor functions, calculated from the MD trajectories, confirmed the presence of different amounts of lithium-glyme solvates in the aforementioned systems. The MD results are corroborated by
S
(
q
) functions derived from diffraction and scattering data (HEXRD and SAXS/WAXS). The competition between the glyme molecules and the salt anions for the coordination to the lithium cations is quantified by comprehensive aggregate analyses. Lithium-glyme solvates are dominant in the lithium bis(trifluoromethylsulfonyl)imide systems and much less so in systems based on the other two salts. The aggregation studies also emphasize the existence of complex coordination patterns between the different species (cations, anions, glyme molecules) present in the studied fluid media. The analysis of such complex behavior is extended to the conformational landscape of the anions and glyme molecules and to the dynamics (solvate diffusion) of the bis(trifluoromethylsulfonyl)imide plus triglyme system.
The structure and interactions of different (lithium salt plus glyme) equimolar mixtures are probed by Molecular Dynamics simulations.
Exotic nuclei are characterized by having a number of neutrons (or protons) in excess relative to stable nuclei. Their shell structure, which represents single-particle motion in a nucleus1,2, may ...vary due to nuclear force and excess neutrons3–6, in a phenomenon called shell evolution7. This effect could be counterbalanced by collective modes causing deformations of the nuclear surface8. Here, we study the interplay between shell evolution and shape deformation by focusing on the magnetic moment of an isomeric state of the neutron-rich nucleus 75Cu. We measure the magnetic moment using highly spin-controlled rare-isotope beams and achieve large spin alignment via a two-step reaction scheme9 that incorporates an angular-momentum-selecting nucleon removal. By combining our experiments with numerical simulations of many-fermion correlations, we find that the low-lying states in 75Cu are, to a large extent, of single-particle nature on top of a correlated 74Ni core. We elucidate the crucial role of shell evolution even in the presence of the collective mode, and within the same framework we consider whether and how the double magicity of the 78Ni nucleus is restored, which is also of keen interest from the perspective of nucleosynthesis in explosive stellar processes.The magnetic moment of the neutron-rich exotic 75Cu nucleus is measured using rare isotope beams with a high spin alignment, clarifying how the evolution of the nuclear shell and the shape deformations are connected.
Reverse phase protein array (RPPA) analysis, allows investigation of potential targets at the functional protein level,. We identified TNBC subtypes at the protein level using RPPA and compared them ...with mRNA molecular subtypes (TNBCtype, TNBCtype-4, and PAM50) that is unique in its availability of both RPPA and mRNA analyses.
We classified the samples from 80 TNBC patients using both k-means and hierarchical consensus clustering analysis and performed Ingenuity Pathway Analysis. We also investigated whether we could reproduce the mRNA molecular subtypes using the RPPA dataset.
Both clustering methods divided all samples into 2 clusters that were biologically the same. The top canonical pathways included inflammation, hormonal receptors, and MAPK signaling pathways for the first cluster "inflammation and hormonal-related (I/H) subtype" and the GADD45, DNA damage, and p53 signaling pathways for the second cluster "DNA damage (DD)-related subtype". Further k-means cluster analysis identified 5 TNBC clusters. Comparison between sample classification using the 5 RPPA-based k-means cluster subtypes and 6 gene-expression-based TNBCtype molecular subtypes showed significant association between the 2 classifications (p = 0.017).
The I/H and DD subtypes identified by RPPA advance our understanding of TNBC's heterogeneity from the functional proteomic perspective.
PurposeThis paper explores the moderating effects of four personal cultural orientations or PCOs (independence, interdependence, risk aversion and ambiguity intolerance) on the relationships among ...counterfeit proneness, subjective norms, ethical judgments, product evaluation and purchase intentions for counterfeit products.Design/methodology/approachA field study with 840 consumers in Hong Kong using a self-administered structured questionnaire is used to test all the hypotheses.FindingConsumers with high (low) scores on interdependence (independence) show stronger positive effects of counterfeit proneness on subjective norms and its effects on the counterfeit evaluation and purchase intentions. In contrast, consumers with high (low) scores on independence (interdependence) show stronger positive effects of counterfeit proneness on ethical judgments and its effects on counterfeit evaluation and purchase intentions. Consumers with higher scores on risk aversion and ambiguity intolerance show negative moderating effects on most of the relationships in the unified conceptual framework.Research limitations/implicationsThe authors collected data in Hong Kong, which is predominantly Chinese in culture. Hence, future research in other parts of the world with more diverse cultural values would help test the validity and generalizability of the results.Practical implicationsThe findings would be useful for managers of genuine brands to learn more about the process that explains deliberate counterfeit purchase behavior.Originality/valueThe authors extend the unified conceptual framework for deliberate counterfeit purchase behavior by incorporating four PCOs to explore cultural differences in the socio-psychological decision-making process underlying this behavior.
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