中国人群中miiRNA-21对肺癌诊断价值的Meta分析

目的 通过Meta系统分析评价中国人群中微小RNA-21(miRNA-21)对肺癌的诊断价值.方法 全面检索万方、CNKI、维普、PubMed、Embase数据库,日期从建库至2020年10月,筛选相关文献提取数据,采用QUA-DAS-2标准评估文献质量,再对提取数据行初步合并,以判定异质性和诊断效能,并通过回归分析、敏感性分析及亚组分析探讨异质性来源,最后以漏斗图评估是否存在发表偏倚.结果 共纳入11篇文献,其中病例组1113例,对照组1182例.合并灵敏度和特异度分别为0.76(95％CI:0.73～0.78)和0.75(95％CI:0.72～0.77),阳性似然比和阴性似然比分别为2.85(95％CI:2.54～3.20)和0.33(95％CI:0.28～0.37),诊断比值比(DOR)为9.16(95％CI:7.11～11.80),综合受试者工作特征(SROC)曲线的曲线下面积(AUC)为0.82.样本类型、内参类型及探针类型均可能是异质性来源.亚组分析显示,筛查组织样本、血清样本和SYBR探针时,miRNA-21对肺癌具有很高的诊断价值(DOR=10.61、9.46、9.71),而内参为U6的诊断价值较低(DOR=6.74).结论 中国人群中miRNA-21对肺癌的诊断价值较高,有较高的灵敏度和特异度,可作为一项提高肺癌诊断水平的良好指标.     

18F标记的PSMA PET/CT对前列腺癌区域淋巴结转移诊断价值的Meta分析

目的 系统评价¹⁸F标记的PSMA PET/CT对前列腺癌区域淋巴结转移的诊断价值。方法 检索2000年1月1日至2021年5月31日PubMed、Embase、Cochrane Library、Web of Science、中国知网(CNKI)、维普、万方数据库中应用¹⁸F标记的PSMA PET/CT诊断前列腺癌区域淋巴结转移和分期的研究。两名研究者独立筛选文献、提取数据及评价文献质量。使用Meta-disc1.4和Stata16.0软件对数据进行Meta分析。结果 共纳入8篇文献,包括754例前列腺癌患者的2101枚淋巴结。Meta分析显示,合并敏感度、合并特异性、合并阳性似然比、合并阴性似然比及诊断比值比分别为0.82(95%CI:0.61～0.93)、0.98(95%CI:0.91～1.00)、45.7(95%CI:9.0～231.3)、0.18(95%CI:0.07～0.45)、251(95%CI:34～1851)。综合受试者工作特征曲线下面积为0.97(95%CI:0.95～0.98)。结论 ¹⁸F标记的PS...     

窄带成像内镜对鼻咽癌诊断价值的Meta分析

目的 鼻咽癌是头颈部常见恶性肿瘤之一,由于其易于复发和早期转移,因此鼻咽癌的早期诊断是临床工作中亟待解决的问题.内镜检测技术一直是头颈恶性肿瘤的有效检查方法,但传统白光内镜技术难以检测早期粘膜下病变.窄带成像技术(narrow band imaging,NBI)是一种新型内镜显像技术,可以清晰显示早期癌变部位粘膜下的血管形态分布.本研究通过对比评价NBI内镜与传统白光内镜对鼻咽癌的诊断价值,为临床实践提供参考.方法 计算机检索PubMed、Cochrane Library、Ovid、Web of Science和中国知网数据库,并手工检索相关期刊,全面收集NBI方法诊断鼻咽癌的诊断性试验,检索时间截止到2016-01-31.由两位研究员根据纳入和排除标准独立筛选文献,提取资料并按诊断性试验准确性质量评价工具(QUADAS-2)评价质量,采用Stata 12.0软件进行Meta分析.结果 最终纳入5篇研究,包括804个研究对象.Meta分析结果显示,窄带成像内镜诊断鼻咽癌的合并灵敏度和特异度分别为0.84(95％CI为0.67～0.94)和0.94(95％CI为0.90～0.97),层次综合受试者工作特征曲线(hierarchical summary receive operating characteristic,HSROC)曲线下面积为0.95(95％CI为0.92～0.96).普通白光内镜诊断鼻咽癌的灵敏度和特异度分别为0.68(95％CI为0.59～0.76)和0.92(95％CI为0.62～0.99).结论 NBI相比普通白光内镜诊断鼻咽癌具有更高的诊断价值,可以作为临床诊断的辅助工具.     

MOC-31在鉴别良恶性浆膜腔积液中诊断价值的Meta分析

目的 通过荟萃分析以确定MOC-31在鉴别良恶性浆膜腔积液中的诊断价值。方法检索国内外数据库,采用诊断性试验荟萃分析的标准方法对纳入文献进行系统评价,汇总各研究中MOC-31在鉴别良恶性浆膜腔积液的灵敏度、特异度、阳性似然比、阴性似然比及诊断优势比,并绘制总的受试者工作特征曲线（SROC）。结果 最终纳入16项独立研究进行荟萃分析,共1602例样本。MOC-31诊断恶性浆膜腔积液的灵敏度为0.90（95％CI：0.88～0.92）,特异度为0.98（95％CI：0.96～0.99）,阳性似然比为18.43（95％CI：11.38～29.84）,阴性似然比为0.11（95％CI：0.07～0.17）,诊断优势比为349.19（95％CI：138.73～878.95）。灵敏度与特异度交点最大值为0.96。结论 MOC-31在鉴别良恶性浆膜腔积液中的灵敏度与特异度较高,SROC曲线显示其诊断效率较高,具有较广阔的临床应用前景。     

配对盒基因1甲基化检测对宫颈癌诊断价值的Meta分析

目的采用Meta系统分析评价中国人群中配对盒基因1(PAX1)甲基化检测对宫颈癌的诊断价值。方法检索万方、中国知网、维普、PubMed、Embase数据库,筛选相关文献后提取数据,采用QUADAS-2标准对纳入文献进行质量评价,再对提取数据行初步合并,以判定异质性和诊断效能,进一步探讨异质性来源及亚组分析,最后以漏斗图评估是否存在发表偏倚。结果共纳入13篇文献,其中病例组336例,对照组1006例。合并灵敏度为0.89(95%CI:0.85~0.92),合并特异度为0.76(95%CI:0.73~0.79),阳性似然比为4.48(95%CI:3.10~6.49),阴性似然比为0.14(95%CI:0.08~0.25),诊断优势比为31.11(95%CI:18.89~51.22),综合受试者工作特征(SROC)曲线的曲线下面积(AUC)为0.92(95%CI:0.90~0.94)。亚组分析显示,PAX1甲基化在宫颈癌的诊断中,对行焦磷酸定量化检测和未手术及放化疗患者的诊断价值较高(诊断比值比=41.74、40.78)。Meta回归分析表明,高级别宫颈癌前病变患者在对照组中占比是潜在异质性来源。结论PAX1甲基化检测对宫颈癌的诊断价值较高,有较高的灵敏度和特异度,可作为一项提高宫颈癌诊断水平的良好指标。     

2006～2015年中国大肠癌筛查人群依从性的Meta分析

[目的]系统评价中国大肠癌筛查人群的依从性,为开展相关预防与控制工作提供基础数据.[方法]计算机检索中国生物医学文献数据库(光盘版)、中文期刊全文数据库(光盘版)、万方电子期刊、PubMed、EBSCO等数据库,并辅以参考文献追溯和手工检索方法,查找大肠癌初筛人群数量在5000～300 000人的研究文献,且采用的筛查方法为问卷调查与大便潜血检测(FOBT)进行初筛,发现高危人群再接受肠镜检查.检索时限为建库时间至2016年6月.由2位评价员按照纳入与排除标准独立筛选文献、提取资料和评价纳入研究的方法学质量后,采用R3.3.1软件进行Meta分析.[结果]最终纳入25篇文献,共827 904人接受初筛.Meta分析结果显示,问卷调查、FOBT、肠镜的依从率分别为56％ (95％CI:40％～72％,P＜0.0001)、50％ (95％CI:33％～67％,P＜0.0001)、44％ (95％CI:33％～56％,P＜0.0001).对肠镜依从率分层分析发现,农村地区肠镜依从率为64％(95％CI:52％～75％,P＜0.0001),高于城市地区33％ (95％CI:22％～45％,P＜0.0001);北方为44％(95％CI:27％～70％,P＜0.0001),略高于南方42％(95％CI:29％～55％,P＜0.0001);初筛人数≥10 000人的大样本研究依从率为49％(95％CI:34％～64％,P＜0.0001),高于小样本研究的35％(95％CI:16％～57％,P＜0.0001);与职工体检结合的大肠癌伺机性筛查的肠镜依从率为83％(95％CI:32％～98％,P＜0.0001),高于一般社区人群筛查的40％ (95％CI:29％～52％,P＜0.0001).[结论]中国大肠癌筛查人群依从性较低,因此需从筛查方式的选择、筛查流程设计、筛查过程的质量控制、健康宣传等多方面入手提高依从性.     

18FDG PET/PET-CT诊断局部复发性结直肠癌价值的系统评价

 目的
系统评价¹⁸FDG PET/PET-CT 诊断局部复发性结直肠癌的临床价值。
方法
计算机检索Pubmed、Embase、SCI、CBM和Medion数据库，检索时间截至2011年7月，搜集¹⁸FDG PET/PET-CT诊断局部复发性结直肠癌的文献。由2位研究者根据纳入与排除标准独立筛选文献、提取资料和评价质量后，采用Stata10.1软件deeks法绘制漏斗图，MetaDiSc1.4软件进行Meta分析，计算合并敏感度，特异性，阳性似然比，阴性似然比及诊断比。绘制SROC曲线，计算曲线下面积（AUC）与Q值。
结果
最终纳入22个研究。汇总SROC曲线下面积及Q值分别为0.978，0.933。Meta分析结果显示敏感度0.944 (95% CI：0.918~0.964, I²=0)、诊断比208.670 (95% CI：109.56~397.44, I²=23.5%) 和阴性似然比0.084 (95% CI：0.060~0.119, I²=0) 同质性较好，特异性和阳性似然比存在异质性。根据森林图直接合并同质研究和Meta回归分析后再行同质研究合并分别得到特异性和阳性似然比0.986 (95% CI：0.975~0.993,I²=15%)，34.903 (95% CI：21.321~57.126,I²=0)；0.981 (95% CI：0.968~0.989,I²=55.5%)，27.937 (95%CI：15.953~48.926,I²=25.5%)。
结论
¹⁸FDG PET/PET-CT可作为敏感度及特异性均较高的影像工具用于局部复发性结直肠癌的诊断。     

血清-NTx对肺癌、乳腺癌患者诊断骨转移及预后评价价值的Meta分析

目的 用Meta分析方法评估骨代谢标志物血清-NTx（Ⅰ型胶原交联氨基末端肽）对肺癌乳腺癌患者骨转移诊断和预后的价值。方法 利用计算机检索PubMed、Cochrane Library、EMBase、中国知网、万方和维普等数据库,收集涉及骨代谢标志物血清-NTx肺癌乳腺癌患者骨转移诊断及预后的临床研究,按文献纳入排除标准筛选文献,评价文献质量,提取数据资料,应用Stata 12.0软件进行Meta分析。结果 共纳入文献11篇,其中英文文献6篇,中文文献5篇,有关NTx对肺癌乳腺癌骨转移诊断研究8篇,预后研究2篇,1篇文献同时涉及诊断与预后的研究。共计1203例研究对象,肺癌患者726例,乳腺癌患者372例。诊断骨转移：合并灵敏度为76.5 ％ （95％CI： 61.5％～86.9％）,合并特异度为83.3％ （95％CI： 77.1％～ 88.1％）;总生存期的风险比（HR）：初治高血清-NTx者与低血清-NTx者比较,合并HR=1.208 （95％CI： 1.128～1.293,P＜0.05）。结论 NTx对肺癌乳腺癌患者诊断骨转移和评估预后具有较高的临床价值。     

三维超声对乳腺癌诊断价值的Meta分析

目的:采用Meta分析方法评价三维超声对乳腺癌的诊断价值.方法:检索CNKI、CBM、Wanfang Data和VIP数据库,筛选出三维超声诊断乳腺癌的诊断性试验,提取数据及采用QUADA工具进行质量评价,根据异质性大小选择随机或固定效应模型合并效应量,采用Deeks' 法评估发表偏倚并绘制漏斗图.结果:最终20项研究,共2 451个病灶纳入分析;Meta分析结果示敏感度、特异度、阳性似然比、阴性似然比、诊断比值比、受试者工作曲线下面积(AUC)和Q指数分别为87%、88%、6.77、0.14、53.26、0.94±0.01和0.88±0.02.结论:三维超声在乳腺癌诊断中有较高的敏感度和特异度,对判断乳腺肿瘤良恶性具有重要价值.     

影像学检查对卵巢上皮性癌治疗后复发诊断价值的Meta分析

目的 系统评价影像学检查（B 超、CT、MRI、PET/CT）对卵巢上皮性癌治疗后复发的诊断价值。方法 以计算机检索PubMed、Embase、Medline、Cochrane Library、EBMR、CBM、CJFD、CSJD 和清华同方等数据库。检索期限自建库至今,收集有关影像学检查（B 超、CT、MRI、PET/CT）诊断卵巢上皮性癌复发的诊断试验。根据诊断性试验准确性质量评价工具（QUADAS）评价文献质量并提取数据, Meta-Disc 1.4 版软件进行Meta 分析。结果 最终纳入研究的 CT 文献 8 篇,共 478 例患者;MRI 文献 4 篇,共 231 例患者;PET/CT 文献 15 篇,共 1 007 例患者。Meta分析结果显示：CT 检查对卵巢上皮性癌治疗后复发的诊断比值比为10.32（95% CI：4.93～21.62）,敏感性和特异性分别为 70%（95% CI：64%～75%）和 81%（95%CI：75%～86%）,阳性似然比和阴性似然比分别为 3.11（95%CI：2.30～4.19）和 0.35（95% CI：0.23～0.55）。MRI 检查对卵巢上皮性癌治疗后复发的诊断比值比为 55.90（95% CI：19.37～161.36）,敏感性和特异性分别为87%（95%CI：82%～92%）和 90%（95% CI：78%～97%）,阳性似然比和阴性似然比分别为 7.57（95%CI：3.31～17.33） 和 0.15（95% CI：0.06～0.39）。PET/CT 检查对卵巢上皮性癌治疗后复发的诊断比值比为 63.09（95%CI：26.29～151.43）,敏感性和特异性分别为 88%（95% CI：85%～91%）和 88%（95% CI：84%～91%）,阳性似然比和阴性似然比分别为 7.64（95% CI：2.56～22.86）和 0.13（95% CI：0.08～0.22）。结论 CT、MRI、PET/CT 检查在诊断卵巢上皮性癌治疗后复发有较高的敏感性和特异性,而 PET/CT 检查的敏感性高于 MRI 及 CT 检查。     

Farnesyltransferase inhibitors: antineoplastic properties, mechanisms of action, and clinical prospects

Farnesyltransferase (FTase) inhibitors are among the current wave of molecularly targeted anti-cancer agents being used to attack malignancy in a rational manner. A large body of preclinical data indicates that FTase inhibitors block cancer cell proliferation through both cytostatic and cytotoxic effects. Interestingly, FTase inhibitors have rather limited effects on normal cell function, suggesting that they may target unique aspects of cancer cell pathophysiology. The development of FTase inhibitors was predicated on the discovery that the Ras oncoproteins must be post-translationally modified to transform cells. However, recent work indicates that the anti-neoplastic effects of FTase inhibitors depend on altering the post-translational modifications of non-Ras proteins as well. In particular, a critical target protein that responds to FTase inhibition by blocking tumor cell growth is RhoB, an endosomal Rho protein that functions in receptor trafficking. In this review, we survey the biological foundations for the clinical development of FTase inhibitors, and consider some of the latest mechanistic studies that reveal how these agents affect cellular physiology.     

Targeting tumor vasculature with homing peptides from phage display

Tumor vasculature expresses a number of molecular markers at much lower levels than those seen in the blood vessels of normal tissues, and in some cases, such markers are undetectable. The presence of these markers relates to angiogenesis; the same markers are shared by all blood vessels undergoing angiogenesis. The endothelial cells, pericytes and smooth muscle cells, and the vascular extracellular matrix in angiogenic vessels can each express such markers. Molecularly, they represent vascular growth factor receptors, cell adhesion proteins and their receptors. Screening of phage display libraries for peptides that home to tumor vasculature when injected into mice has recently provided a new tool for analyzing the distinguishing features of tumor vasculature. Tumor-homing peptides isolated in this manner, as well as an antibody against a form of fibronectin expressed in tumor blood vessels, have been found to serve as targeting devices to concentrate drugs and other therapeutic materials to tumors in in vivo models. Such a targeting strategy can therefore potentially improve the efficacy of drugs and reduce their side effects.     

Identification of EBV transforming genes by recombinant EBV technology

Epstein-Barr virus (EBV) is able to infect primary B-lymphocytes but usually does not proceed to replicate more virions. Instead, EBV persists as an incomplete virus and expresses 12 gene products that transform the growth of these cells into continuously proliferating lymphoblastoid cell lines. Because EBV is associated with several human malignancies, there is intense interest in delineating the molecular functions of these EBV gene products in transformation. This review focuses on the recombinant EBV technologies that have been developed to introduce specific mutations into EBV and test the functions of these EBV genes in primary B-lymphocyte growth transformation.     

Matrix metalloproteinases in tumor invasion and metastasis

Extensive work on the mechanisms of tumor invasion and metastasis has identified matrix metalloproteinases (MMPs) as key players in the events that underlie tumor dissemination. Studies using natural and synthetic MMP inhibitors, as well as tumor cells transfected with cDNAs encoding the MMPs characterized thus far have provided compelling evidence that MMP activity can induce or enhance tumor survival, invasion and metastasis. Because of the ability of MMPs to degrade extracellular matrix (ECM) proteins, the principal mechanism whereby MMPs promote tumor development has been thought to be the proteolytic breakdown of tissue barriers to invasion and the associated facilitation of circulating tumor cell extravasation. However, recent evidence stemming from the use of novel experimental approaches indicates that MMPs do not play a major role in the process of extravasation itself. Rather, they appear to promote intravasation (the process of penetrating the circulation following invasion of blood vessels) and regulate the relationship between tumor cells and host tissue stroma subsequent to extravasation. In addition, the discoveries that a growing number of proteolytically active MMPs may localize to the cell surface in association with adhesion receptors, and that MMP substrates include latent cytokines and growth factors, provide a new conceptual framework for the mechanisms whereby MMPs influence tumor behavior.     

New aspects of integrin signaling in cancer

Members of the integrin family of cell adhesion receptors influence several important aspects of cancer cell behavior, including motility and invasiveness, cell growth, and cell survival. Engagement of integrins with extracellular matrix (ECM) proteins can activate members of the Rho-family of small GTPases; conversely, Rho- and Ras-family proteins can influence the ability of integrins to bind their ligands. These events impinge on the control of cell motility, and ultimately on invasive and metastatic behavior. Integrin engagement with ECM also has important effects on cell survival, particularly for cells of epithelial origin. In some cases, specific integrins have selective effects on the efficiency of signal transduction in cell survival pathways.     

Role of LMP1 in immune control of EBV infection

The Epstein-Barr virus (EBV) encoded latent membrane protein (LMP1) plays a crucial role in the long-term persistence of this virus within the cells of the immune system. Not only is this protein critical for the transformation of resting B cells by EBV, it also displays pleiotropic effects on various cellular proteins expressed in the host cell. These include up-regulation of expression of B cell activation antigens, adhesion molecules and various components of the antigen processing pathway. Here we discuss how LMP1 acts like an expression 'switch' which, depending on the stage of EBV infection, manoeuvres various pathways that either modulate the immune system towards or against its survival.     

Telomerase and human tumorigenesis

Human cancer cells, unlike their normal counterparts, have shed the molecular restraints to limited cell growth and are immortal. Exactly how cancer cells manage this at the molecular level is beginning to be understood. Human cells must overcome two barriers to cellular proliferation. The first barrier, referred to as senescence, minimally involves the p53 and Rb tumor-suppressor pathways. Inactivation of these pathways results in some extension of lifespan. However, inactivation of these pathways is insufficient for immortalization. As normal cells undergo repeated rounds of DNA replication, their telomeres shorten due to the inability of traditional DNA polymerases to completely replicate the end of the chromosomal DNA. This shortening continues until the cells reach a second proliferative block referred to as crisis, which is characterized by chromosomal instability, end-to-end fusions, and cell death. Stabilization of the telomeric DNA through either telomerase activation or the activation of the alternative mechanism of telomere maintenance (ALT) is essential if the cells are to survive and proliferate indefinitely. Conversely, loss of telomere stabilization by an already-immortalized cell results in loss of immortality and cell death. Together this indicates that telomere maintenance is a critical component of immortality. In this review we attempt to describe our current understanding of the role of telomere maintenance in senescence, crisis, and tumorigenesis.     

ABCG2在肺癌中表达的定量研究

目的 观察ABCG2在肺癌和癌周肺组织的表达,从量化角度阐明其在肺癌组织中表达的病理学意义.方法 常规石蜡包埋、HE切片确诊,用免疫组化SP法检测ABCG2在肺癌和癌周肺组织的定位和表达,用LeicaQ500MC图像分析系统对其表达强度进行定量分析,并用表达的阳性单位(positive unit PU)反映其表达强度.结果 ABCG2蛋白在肺癌和癌周正常肺组织中的表达主要定位在细胞质和细胞膜.在癌周正常肺组织的支气管和细支气管上皮呈弥漫表达,腺上皮呈灶性表达;肺鳞癌和肺腺癌弥漫或大片表达,肺鳞癌表达的PU值高于肺腺癌(P＜0.001),肺大细胞癌和肺小细胞癌不表达,PU值接近于零.癌周肺组织表达的PU值高于各型肺癌(P＜0.05).ABCG2蛋白表达的PU值在肺癌原发灶和转移灶之间无差别(P＞0.05),且与肺癌患者的性别、年龄、转移和TNM分期未见明显相关性(P＞0.05),与肺癌分化程度有关(P＜0.001).分化程度越高,PU值越高,但高分化肺癌和癌周肺组织的表达PU值差异无显著性(P＞0.05).结论 ABCG2蛋白表达程度与肺癌类型及分化程度具有相关性,可能成为判断其指标之一.     

腹部压块对膈肌运动影响的研究

目的 :研究腹部压块对膈肌运动的影响。方法 :选择拟行立体适形放疗患有肺癌或肝脏肿瘤的患者 2 0例。按治疗体位仰卧于体部立体放疗定位负压袋内 ,待患者呼吸平稳后 ,将灯光野的中心点置于膈顶运动的最低点 ,在膈肌运动至最高位时拍摄照片 ,测量膈肌运动的最大幅度 ;然后 ,将心形腹部压块放置于患者剑突下 ,并用定位框架的腹带交叉固定 ,按压程度以不引起患者呼吸困难或其他不适为标准 ,5min后按上述方法再次测量膈肌运动的最大幅度。结果 :2 0例患者未加腹部压块的运动幅度为0 6 2～ 2 6 7cm ,平均 (1 4± 0 6 4)cm ,加腹部压块后的膈肌运动幅度为 0 2 8～ 2 0 8cm ,平均 (1 0±0 5 5 )cm ,加腹部压块后膈肌运动幅度平均减小 (0 4± 0 34)cm ,P =0 0 0 0。加腹部压块后 90 % (18/2 0 )的患者膈肌运动幅度受到不同程度的限制 ,但有 10 % (2 /2 0 )的患者膈肌运动幅度增加。结论 :腹部压块可使大部分患者膈肌运动的幅度减小 ,但少部分患者例外 ,即腹部压块并不能使所有膈肌周围肿瘤的照射容积减少。建议在制定放射治疗计划前应预先进行测量和评价     

Post-translational regulation of COX2 activity by FYN in prostate cancer cells

While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity.