- 作者列表："Wang J","Guo X
OBJECTIVES:The Cancer Genome Atlas Research Network identified 4 novel protein expression-defined subgroups in patients with lower-grade gliomas (LGGs). The RPPA3 subtype had high levels of Epidermal Growth Factor Receptor and Human epidermal growth factor receptor-2, further increasing the chances for targeted therapy. In this study, we aimed to explore the relationships between magnetic resonance features and reverse phase protein array (RPPA) subtypes (R1-R4). METHODS:Survival estimates for the Cancer Genome Atlas cohort were generated using the Kaplan-Meier method and time-dependent receiver operating characteristic curves. A total of 153 patients with LGG with brain magnetic resonance imaging from The Cancer Imaging Archive were retrospectively analyzed. Least absolute shrinkage and selection operator algorithm was used to reduce the feature dimensions of the RPPA3 subtype. RESULTS:A total of 51 (33.3%) RPPA1 subtype, 42 (27.4) RPPA2 subtype, 19 (12.4%) RPPA3 subtype, and 38 (24.8%) RPPA4 subtype were identified. On multivariate logistic regression analysis, subventricular zone involvement [odds ratio (OR), 0.370; P = 0.006; 95% confidence interval (CI), 0.181-0.757) was associated with RPPA1 subtype [area under the curve (AUC), 0.598]. Volume of 60 cm3 or greater (OR, 5.174; P < 0.001; 95% CI, 2.182-12.267) was associated with RPPA2 subtype (AUC, 0.684). Proportion contrast-enhanced tumor greater than 5% (OR, 4.722; P = 0.010; 95% CI, 1.456-15.317), extranodular growth (OR, 5.524; P = 0.010; 95% CI, 1.509-20.215), and L/CS ratio equal to or greater than median (OR, 0.132; P = 0.003; 95% CI, 0.035-0.500) were associated with RPPA3 subtype (AUC, 0.825). Proportion contrast-enhanced tumor greater than 5% (OR, 0.206; P = 0.005; 95% CI, 0.068-0.625) was associated with RPPA4 subtype (AUC, 0.638). For the prediction of RPPA3 subtype, the nomogram showed good discrimination, with an AUC of 0.825 (95% CI, 0.711-0.939) and was well calibrated. The RPPA3 subtype was associated with shortest mean overall survival (RPPA3 subtype vs other: 613 vs 873 days; P < 0.05). The time-dependent receiver operating characteristic curves for the RPPA3 subtype was 0.72 (95% CI, 0.60-0.84) for survival at 1 year. Decision curve analysis indicated that prediction for the RPPA3 model was clinically useful. CONCLUSIONS:The RPPA3 subtype is an unfavorable prognostic biomarker for overall survival in patients with LGG. Radiogenomics analysis of magnetic resonance features can predict the RPPA subtype preoperatively and may be of clinical value in tailoring the management strategies in patients with LGG.
目的: 癌症基因组图谱研究网络在低级别胶质瘤 (LGGs) 患者中发现了4个新的蛋白表达确定的亚组。RPPA3亚型具有高水平的表皮生长因子受体和人表皮生长因子受体-2，进一步增加了靶向治疗的机会。在这项研究中，我们旨在探讨磁共振特征和反相蛋白阵列 (RPPA) 亚型之间的关系 (R1-R4)。 方法: 使用Kaplan-Meier方法和时间依赖性接受者操作特征曲线生成癌症基因组图谱队列的存活估计。回顾性分析来自癌症影像档案的153例LGG患者的脑磁共振成像。使用最小绝对收缩和选择算子算法来减小RPPA3亚型的特征维度。 结果: 共鉴定了51 (33.3%) 个RPPA1亚型、42 (27.4) 个RPPA2亚型、19 (12.4%) 个RPPA3亚型和38 (24.8%) 个RPPA4亚型。在多变量logistic回归分析中，心室下区受累 [比值比 (OR)，0.370; P = 0.006; 95% 置信区间 (CI)，0.181-0.757) 与RPPA1亚型 [曲线下面积 (AUC)，0.598] 相关。60立方厘米或更大的体积 (or，5.174; P < 0.001; 95% CI，2.182-12.267) 与RPPA2亚型相关 (AUC，0.684)。对比增强肿瘤比例大于5% (OR，4.722; P = 0.010; 95% CI，1.456-15.317)，结节外生长 (OR，5.524; P = 0.010; 95% CI，1.509-20.215)，L/CS比值等于或大于中位数 (or，0.132; P = 0.003; 95% CI，0.035-0.500)与RPPA3亚型相关 (AUC，0.825)。对比增强肿瘤比例大于5% (OR，0.206; P = 0.005; 95% CI，0.068-0.625) 与RPPA4亚型相关 (AUC，0.638)。对于RPPA3亚型的预测，列线图显示出良好的区分度，AUC为0.825 (95% CI，0.711-0.939)，并且校准良好。RPPA3亚型与最短平均总生存期相关 (RPPA3亚型vs其他: 613 vs 873天; P <0.05)。RPPA3亚型的时间依赖性受试者工作特征曲线为1年生存率的0.72 (95% CI，0.60-0.84)。决策曲线分析表明RPPA3模型的预测在临床上是有用的。 结论: RPPA3亚型是LGG患者总生存期的不良预后生物标志物。磁共振特征的放射基因组学分析可以在术前预测RPPA亚型，并可能对LGG患者定制管理策略具有临床价值。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.