The 150 most important questions in cancer research and clinical oncology series:questions 50-56

Since the beginning of 2017,Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology,which sparkle diverse thoughts,interesting communications,and potential collaborations among researchers all over the world.In this article,seven more questions are presented as followed.Question 50.When tumor cells spread from primary site to distant sites,are they required to be "trained" or "armed" in the bone marrow niche prior to colonizing soft tissues? Question 51.Are there tipping points during cancer progression which can be identified for manipulation? Question 52.Can we replace molecular biomarkers by network biomarkers? Question 53.Are conventional inhibitors of key cellular processes such as cell proliferation and differentiation more effective than targeted chemotherapeutics that antagonize the downstream cell signaling network via cell-surface receptors such as epidermal growth factor receptor (EGFR),vascular endothelial growth factor receptor (VEGFR) and c-Met,or intraceilular receptors such as androgen receptor (AR) and estrogen receptor (ER),by drugs like erlotinib,sunitinib and cabozantinib,or enzalutamide and tomoxifen? Question 54.How can we robustly identify the candidate causal event of somatic genome alteration (SGA) by using computational approach? Question 55.How can we systematically reveal the immune evasion mechanism exploited by each tumor and utilize such information to guide targeted therapy to restore immune sensitivity? Question 56.Can the nasopharyngeal carcinoma (NPC) patients with sarcomatoid carcinoma (SC) subtype benefit from more specific targeted therapy?     

Anterior T-Wave Inversion in Young White Athletes and Nonathletes: Prevalence and Significance

Background

Anterior T-wave inversion (ATWI) on electrocardiography (ECG) in young white adults raises the possibility of cardiomyopathy, specifically arrhythmogenic right ventricular cardiomyopathy (ARVC). Whereas the 2010 European consensus recommendations for ECG interpretation in young athletes state that ATWI beyond lead V₁ warrants further investigation, the prevalence and significance of ATWI have never been reported in a large population of asymptomatic whites.

体外研究基牙位置和树脂粘接面积对金属丝-复合树脂夹板刚度的影响

目的 通过体外模型探讨改变基牙位置和树脂粘接面积对牙外伤金属丝- 复合树脂夹板刚度的影响.方法 建立体外外伤牙模型,将11、21 牙槽窝扩大模拟外伤牙,分别以12/22 和13/23 为基牙,用0.8mm 不锈钢丝对11、21 进行金属丝- 树脂夹板固定.根据基牙位置和树脂粘接面积不同,实验共分4 组:组1 以13、23 为基牙,树脂粘接面积为2mm×2mm;组2~ 组4 以12、22 为基牙,树脂粘接面积分别为2mm×2mm,3mm×3mm、4mm×4mm.使用万能材料试验机测量夹板固定前后水平和垂直向牙动度,比较各组别固定前后的牙动度差异,及各组别间牙动度差异.结果 ①各组固定后水平和垂直向牙动度均明显大于正常牙动度(P<0.05),夹板固定后水平向牙动度11 为0.36~0.72mm,21 为0.35~0.56mm,11 和21 垂直向牙动度为0.11~0.30mm.②基牙位置对夹板固定后牙动度无明显影响(P>0.05).③随着数值粘接面积的增大,组3 和组4 的夹板固定后水平向牙动度较组2 明显减小(P<0.05).结论 在体外模型上,外伤牙双侧相隔一个牙位固定并不显著影响夹板的刚度;树脂粘接面积的增大可明显影响外伤牙固定后的水平向牙动度,但对垂直向牙动度的影响则较小.     

两种评价面部三维表面数据不对称度方法的比较

目的：比较两种利用数字化技术三维定量确定人面部对称度的方法。方法：利用FaceScan三维激光扫描仪,获取20名受试者面部三维表面数据,将数据导入逆向工程软件Imageware 13.0和Geomagic 12,以YZ平面为镜像平面对其进行镜像,将本体和镜像图像利用迭代最近点算法（interactive closest point,ICP）和普氏分析法（Procrustes analysis,PA）重合,分别提取其正中矢状面,计算21个解剖标志点到正中矢状面的距离和不对称度,并进行比较分析。结果：对20个受试样本21个测量值进行配对t检验,得到t=1.346,P=0.193。结论：对于无明显不对称研究对象而言,ICP算法和PA算法都可以得到其正中矢状面,但是两种算法求得的正中矢状面之间无明显差异。     

简述V～ing Form

在英语语法中,V~ingForm既是重点又是难点。在以前的语法体系中,这种形式分成动名词和现在分词两个概念,但在当今流行的语法体系中,不再有这样的分法。现代英语注重语言的实际运用,而淡化语法,所以不必要专门抽时间去讲解枯燥无味的语法规则,只需在语言运用中渗透语法规则,用简易的归纳性语言讲清问题。     

多元点振荡空间力学分析对胰岛素抵抗数值诊断的探讨

目的探讨评价胰岛素抵抗程度的科学、简便方法,目的在于筛选治疗或改善胰岛素抵抗的新药。方法血糖,胰岛素及 C 肽的检测分别采用日立7060型全自动生化分析仪及美国 DPC 公司 IMMUHE 全自动化学发光免疫分析仪。有关数据的统计学处理,使用 SPSS(Statistics Package of Social Science)11.0 for Windows 软件包。在这项研究中,首先把血糖,胰岛素,C肽及参与血糖与胰岛素互相作用的各因子分别视为若干个单元。其每个单元中的元素(如:血糖这一单元在不同时点检测的值 a_1,a_2,a_3,……的各个 a 称之为元素)在任意时刻的检测值,均应视为多因子彼此互相作用的结果。结果当 G_0,I_0,C_0,y_1,y_2,y_3…,X_1,X_2,X_3…其相互作用处于平衡时,即相互作用力等于1的状态下,多元振荡点的空间作用力必然交于一点。结论 G_0/I_0·C_0(1式),糖负荷后时点 t,肘静脉血糖(G_t),胰岛素(I_t),C 肽(C_t)其相互作用的空间力点为:G_t/G_0·C_t/C_0·I_0/I_t(2式)。1式,2式可分别表达空腹及糖负荷后胰岛素抵抗的程度。     

Multiple aspects of the interaction of biomacromolecules with inorganic surfaces

The understanding of the mechanisms involved in the interaction of biological systems with inorganic materials is of interest in both fundamental and applied disciplines. The adsorption of proteins modulates the formation of biofilms onto surfaces, a process important in infections associated to medical implants, in dental caries, in environmental technologies. The interaction with biomacromolecules is crucial to determine the beneficial/adverse response of cells to foreign inorganic materials as implants, engineered or accidentally produced inorganic nanoparticles. A detailed knowledge of the surface/biological fluids interface processes is needed for the design of new biocompatible materials. Researchers involved in the different disciplines face up with similar difficulties in describing and predicting phenomena occurring at the interface between solid phases and biological fluids. This review represents an attempt to integrate the knowledge from different research areas by focussing on the search for determinants driving the interaction of inorganic surfaces with biological matter.     

Stable expression and functional characterization of a human nicotinic acetylcholine receptor with α6β2 properties: discovery of selective antagonists

BACKGROUND AND PURPOSE

Despite growing evidence that inhibition of α6β2-containing (α6β2*) nicotinic acetylcholine receptors (nAChRs) may be beneficial for the therapy of tobacco addiction, the lack of good sources of α6β2*-nAChRs has delayed the discovery of α6β2-selective antagonists. Our aim was to generate a cell line stably expressing functional nAChRs with α6β2 properties, to enable pharmacological characterization and the identification of novel α6β2-selective antagonists.

EXPERIMENTAL APPROACH

Different combinations of the α6, β2, β3, chimeric α6/3 and mutant β3^V273S subunits were transfected in human embryonic kidney cells and tested for activity in a fluorescent imaging plate reader assay. The pharmacology of rat immune-immobilized α6β2*-nAChRs was determined with ¹²⁵I-epibatidine binding.

KEY RESULTS

Functional channels were detected after co-transfection of α6/3, β2 and β3^V273S subunits, while all other subunit combinations failed to produce agonist-induced responses. Stably expressed α6/3β2β3^V273S-nAChR pharmacology was unique, and clearly distinct from α4β2-, α3β4-, α7- and α1β1δε-nAChRs. Antagonist potencies in inhibiting α6/3β2β3^V273S-nAChRs was similar to their binding affinity for rat native α6β2*-nAChRs. Agonist affinities for α6β2*-nAChRs was higher than their potency in activating α6/3β2β3^V273S-nAChRs, but their relative activities were equivalent. Focussed set screening at α6/3β2β3^V273S-nAChRs, followed by cross-screening with the other nAChRs, led to the identification of novel α6β2-selective antagonists.

CONCLUSIONS AND IMPLICATIONS

We generated a mammalian cell line stably expressing nAChRs, with pharmacological properties similar to native α6β2*-nAChRs, and used it to identify novel non-peptide, low molecular weight, α6β2-selective antagonists. We also propose a pharmacophore model of α6β2 antagonists, which offers a starting point for the development of new smoking cessation agents.     

喜炎平注射液足三里穴位封闭联合常规疗法治疗秋季腹泻83例临床观察

目的 观察喜炎平注射液足三里穴位封闭联合常规疗法治疗秋季腹泻的临床疗效.方法 将166例秋季腹泻患儿随机分为2组,对照组83例予蒙脱石散、枯草杆菌二联活菌颗粒及甘草锌口服,治疗组83例在对照组常规治疗基础上予喜炎平注射液足三里穴位封闭治疗.结果 治疗组总有效率95.18％,对照组总有效率79.52％,2组总有效率比较...