急性肾损伤早期诊断生物标志物研究进展

急性肾损伤(Acute kidney injury,AKI)可发生于各临床科室其临床经过常见并严重,ICU的重症患者AKI的发病率和死亡率更高。早期诊断对AKI的预后影响重大,能否找到临床实用的早期预测AKI的生物学标志物尽早采取干预措施是改善其预后的关键。本文就近年来研究的几种具有潜力的生物标志物作一综述。     

肿瘤标志物联合检测在乳腺癌早期诊断中的应用

目的：探讨肿瘤标志物癌胚抗原（CEA）、糖链抗原19-9（CA19-9）、糖链抗原15-3（CA15-3）联合检测在乳腺癌早期诊断中的应用价值。方法：检测87例乳腺癌患者,55例乳腺良性肿瘤患者和35例健康人血清中CEA、CA19-9、CA153等肿瘤标志物的水平及3种标志物不同组合对乳腺癌的阳性检出率。结果：乳腺癌患者3种肿瘤标志物显著高于正常对照组及乳腺良性肿瘤组（P〈0.01）。3项标志物不同组合对不同分期乳腺癌检出的敏感性均高于单项标志物。其中CEA＋CA199＋CA153组合的检出敏感性较其他组合均高,特别是对早期患者检出率明显提高。结论：CEA＋CA199＋CA153联合检测能提高乳腺癌的早期诊断率。     

肿瘤标志物联合检测在乳腺癌早期诊断中的应用

目的:探讨肿瘤标志物癌胚抗原(CEA)、糖链抗原19-9(CA19-9)、糖链抗原15-3(CA15-3)联合检测在乳腺癌早期诊断中的应用价值。方法:检测87例乳腺癌患者,55例乳腺良性肿瘤患者和35例健康人血清中CEA、CA19-9、CA153等肿瘤标志物的水平及3种标志物不同组合对乳腺癌的阳性检出率。结果:乳腺癌患者3种肿瘤标志物显著高于正常对照组及乳腺良性肿瘤组(P<0.01)。3项标志物不同组合对不同分期乳腺癌检出的敏感性均高于单项标志物。其中CEA+CA199+CA153组合的检出敏感性较其他组合均高,特别是对早期患者检出率明显提高。结论:CEA+CA199+CA153联合检测能提高乳腺癌的早期诊断率。     

阿尔茨海默病早期诊断的体液生物标志物

阿尔茨海默病(Alzheimer’s disease,AD)是目前发病率较高的神经退行性疾病,主要临床表现为不可逆的记忆力丧失与认知功能的衰退。AD起病隐秘,不易察觉,病程长达数十年,尚无有效治疗手段,因此AD早期的诊断与干预尤为重要;但是,当前AD早期诊断缺乏灵敏、简便的检测方案。体液(特别是血液)中的生物标志物受到了越来越多的关注,可能成为AD早期诊断的有效手段。现主要综述了与AD病理进程相关的脑脊液、血液、尿液中的生物标志物,并对其应用与前景做一展望。     

miRNA作为三阴乳腺癌潜在生物标志物的研究进展

三阴乳腺癌(triple-negative breast cancer,TNBC)是指雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)及人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-...     

脓毒症诊断的生物学标志物的研究进展

脓毒症是由致病微生物感染引发的全身炎症反应综合征(SIRS),合并血压降低且经快速液体复苏后血压仍不能恢复正常者称为脓毒性休克(Septic shock),其中一部分患者发展为多器官功能障碍综合症(MODS)。由于目前临床上仍缺乏早期敏感性诊断手段,脓毒症病死率居高不下。每10万人口中约50-300人会发生严重脓毒症,其短期死亡率达20%-25%,当发展为脓毒性休克时其死亡率达50%。随着分子生物学和现代生物技术的不断发展,人们发现多种生物标志物在脓毒症的早期诊断、病情及预后判断,疗效评估中发挥重要作用。因此深入了解脓毒症病理生理机制中不同生物标志物的意义及价值,对于脓毒症及其并发症的早期识别及干预,降低患者病死率及改善患者生活质量有积极意义。本文综述了近几年来对脓毒症的诊断和预后有一定价值的主要标志物及其应用。     

加权ceRNA网络筛选乳腺癌生物标志物

竞争性内源RNA (competing endogenous RNA, ceRNA)作为生物标志物和潜在的治疗靶点,在探究肿瘤的发病机制中,表现出了巨大的研究价值和临床应用前景。本文对乳腺癌ceRNA网络进行了系统的分析,首先通过差异分析获得差异miRNA、mRNA和lncRNA,其次利用网络的边聚集系数(edge clustering coefficient,ECC)和皮尔逊相关系数(Pearson correlation coefficient, PCC)计算ceRNA网络节点的权重,最后采用基于随机森林的逐步特征选择(stepwise feature selection based on random forest, SFS-RF)方法筛选出一组可作为乳腺癌生物标志物的RNA——LINC00466、CHL1-AS2和LINC00337,并利用GEO数据库验证了该组RNA对乳腺癌样本的识别情况。此外,通过GO和KEGG通路富集分析探索了该组RNA在乳腺癌中的生物学功能。结果显示:这些RNA作为生物标志物,在识别乳腺癌样本方面具有高精度和高效率等特性,在乳腺肿瘤细胞的增殖及遗传物质的合成等过程中具有重要生物学意义。     

阿尔茨海默病血浆和肠道菌群中生物标志物的研究进展

阿尔茨海默病(Alzheimer’s disease, AD)是一种常见的神经退行性疾病,在老年人中患病率高.但目前其发生机制尚不明确,而且缺乏便捷的早期诊断手段,因而难以在疾病早期进行干预和治疗.近几年,随着质谱、免疫学方法等新技术的发展,外周血Aβ、P-tau、外泌体、miRNA、肠道细菌等成为AD早期诊断及病情监测的潜在生物学标志物.本文就目前AD外周血生物标志物及AD相关肠道菌群生物标志物现况进行了综述,旨在为AD的早期诊断和预测疾病进展提供参考.     

临床试验进展：生物标志物助推临床开发决策

生物标志物对于疾病的鉴定、早期诊断和预防,以及治疗过程中的监控具有重要作用。寻找和发现有价值的生物标志物已成为目前研究的一个热点。汤森路透Cortellis 临床试验情报将生物标志物的发现与针对当前常见疾病的相关临床试验关联,提供描绘临床图景关键元素和当前趋势的专家分析,从而指导临床开发决策。     

血清多肿瘤标志物蛋白芯片检测在乳腺癌诊断中的价值

目的:探讨血清多肿瘤标志物蛋白芯片检测系统在乳腺癌诊断中的临床价值。方法:临床确诊的乳腺癌患者307例为乳腺癌组,非乳腺癌的其他恶性肿瘤患者495例为对照组。应用多肿瘤标志物蛋白芯片检测系统检测12种肿瘤标志物水平,评价血清肿瘤标志物的在乳腺癌组与对照组之间的差异。结果:CA153,CEA,Free-PSA这三项指标为诊断乳腺癌的独立相关因素(P<0.05),比较三项指标ROC曲线下面积可见,CA153对于鉴别乳腺癌准确性更高,其敏感性、特异性分别为78.92和56.14,女性乳腺癌患者Free-PSA可见明显升高,对乳腺癌有特殊提示意义,手术前后标志物CA199、CA242、Ferrin、CA125水平差异有统计学意义。结论:在临床常用的肿瘤标记物中,CA153,CEA,Free_PSA水平的升高与乳腺癌发生独立相关,其中CA153具有更高的诊断准确性,Free_PSA水平升高对乳腺癌的诊断有特别提示意义。     

Biomarkers in cancer screening,research and detection: present and future: a review

Biomarkers provide a powerful and dynamic approach to understanding the spectrum of malignancies with applications in observational and analytic epidemiology, randomized clinical trials, screening, diagnosis and prognosis. Defined as alterations in the constituents of tissues or body fluids, these markers offer a means for homogeneous classification of a disease and risk factor, and they can extend one's basic information about the underlying pathogenesis of disease. The goals in cancer research include finding biomarkers that can be used for the early detection of cancers, design individual therapies, and to identify underlying processes involved in the disease. Because so many myriad processes are involved in the diseased states, the goal is similar to ‘finding a needle in a haystack’. However, the development of many -omic technologies, such as genomics and proteomics, has allowed us to monitor a large number of key cellular pathways simultaneously. This has enabled the identification of biomarkers and signalling molecules associated with cell growth, cell death and cellular metabolism. These are also facilitating in monitoring the functional disturbance, molecular and cellular damage, and damage response. This brief review describes the development of biomarkers in cancer research and detection with emphasis on different proteomic tools for the identification and discovery of new biomarkers, different clinical assays to detect various biomarkers in different specimens, role of biomarkers in cancer screening and last but not the least, the challenges in this direction of cancer research.     

Biomarkers in cancer screening, research and detection: present and future: a review

Biomarkers provide a powerful and dynamic approach to understanding the spectrum of malignancies with applications in observational and analytic epidemiology, randomized clinical trials, screening, diagnosis and prognosis. Defined as alterations in the constituents of tissues or body fluids, these markers offer a means for homogeneous classification of a disease and risk factor, and they can extend one's basic information about the underlying pathogenesis of disease. The goals in cancer research include finding biomarkers that can be used for the early detection of cancers, design individual therapies, and to identify underlying processes involved in the disease. Because so many myriad processes are involved in the diseased states, the goal is similar to 'finding a needle in a haystack'. However, the development of many -omic technologies, such as genomics and proteomics, has allowed us to monitor a large number of key cellular pathways simultaneously. This has enabled the identification of biomarkers and signalling molecules associated with cell growth, cell death and cellular metabolism. These are also facilitating in monitoring the functional disturbance, molecular and cellular damage, and damage response. This brief review describes the development of biomarkers in cancer research and detection with emphasis on different proteomic tools for the identification and discovery of new biomarkers, different clinical assays to detect various biomarkers in different specimens, role of biomarkers in cancer screening and last but not the least, the challenges in this direction of cancer research.     

磷酸化蛋白质组学在三阴性乳腺癌诊治研究中的进展

三阴性乳腺癌是乳腺癌中恶性程度最高的亚型,其治疗仍以化疗为主,但容易出现耐药,且患者预后较差。随着蛋白质组学技术的发展,磷酸化蛋白质组学研究取得了长足的进步,并在肿瘤发生发展机制和诊治研究中得到了广泛的应用。同样,磷酸化蛋白质组学在三阴性乳腺癌的发生发展、靶向治疗和耐药机制研究等方面也发挥着重要作用。本文主要对目前磷酸化蛋白质组学在三阴性乳腺癌中的研究进展进行综述,旨在为基于磷酸化蛋白质组学的三阴性乳腺癌发生发展机制和诊治研究提供指导和帮助。     

Proteomics for early detection of colorectal cancer: recent updates

Introduction: Colorectal cancer (CRC) is a common type of cancer with a relatively poor survival rate. The survival rate of patients could be improved if CRC is detected early. Biomarkers associated with early stages of tumor development might provide useful tools for the early diagnosis of colorectal cancer.

Areas covered: Online searches using PubMed and Google Scholar were performed using keywords and with a focus on recent proteomic studies. The aim of this review is to highlight the need for biomarkers to improve the detection rate of early CRC and provide an overview of proteomic technologies used for biomarker discovery and validation. This review will also discuss recent proteomic studies which focus on identifying biomarkers associated with the early stages of CRC development.

Expert commentary: A large number of CRC biomarkers are increasingly being identified by proteomics using diverse approaches. However, the clinical relevance and introduction of these markers into clinical practice cannot be determined without a robust validation process. The size of validation cohorts remains a major limitation in many biomarker studies.     

Biomarkers for prostate cancer

The detection of prostate cancer using a blood test has by many standards changed the face of the disease. Despite this tremendous success, there are limitations attributed to the use of prostate specific antigen (PSA) as a means to screen and detect prostate cancer. PSA, as its name implies, is not specific for prostate cancer and as such is often found elevated in other prostatic diseases/symptoms associated with the aging male. Clearly, more specific marker(s) that could identify which individuals actually have prostate cancer and differentiate them from those without the disease would be of tremendous value. The search for more accurate and clinically useful biomarkers of prostate cancer has been extensive. This has focused on individual markers, as well as groups of markers. Included among these are PSA isoforms, pathological indicators and stains, nucleic acids and others. This article highlights the discovery of PSA as a first blood‐based biomarker for prostate cancer detection, as well as other molecular biomarkers and their potential application in detection of the disease. J. Cell. Biochem. 108: 3–9, 2009. © 2009 Wiley‐Liss, Inc.     

A monoclonal antibody driven biodiagnostic system for the quantitative screening of breast cancer

A prospective clinical parametric study comprising women afflicted by breast cancer and otherwise healthy participants was undertaken. The mean plasmatic concentration of putative leucine amino peptidase and nucleoside diphosphate phosphotransferase enzymatic complex in breast cancer cases was significantly elevated [43.9 +/- 2.8 microg ml(-1) (n = 9)] when compared to those found in otherwise healthy women [8.07 +/- 0.14 microg ml(-1) (n = 8)]. Women without images compatible with any tumours (n = 13) had a mean concentration of 10.77 +/- 1.49 microg ml(-1). The mean value obtained in women with fibroadenomas was 10.15 +/- 0.81 microg ml(-1) (n = 6) and with cystic fibrosis mastopathy 8.75 +/- 0.28 microg ml(-1) (n = 7). The efficacy of a tandem quantitative biodiagnostic system as a parametric screening tool for the early detection of breast cancer is underlined, raising the possibility of increasing the cost effectiveness of current imaging non-parametric technologies.     

Pharmacological screening and transcriptomic functional analyses identify a synergistic interaction between dasatinib and olaparib in triple-negative breast cancer

Identification of druggable vulnerabilities is a main objective in triple-negative breast cancer (TNBC), where no curative therapies exist. Gene set enrichment analyses (GSEA) and a pharmacological evaluation using a library of compounds were used to select potential druggable combinations. MTT and studies with semi-solid media were performed to explore the activity of the combinations. TNBC cell lines (MDAMB-231, BT549, HS-578T and HCC3153) and an additional panel of 16 cell lines were used to assess the activity of the two compounds. Flow cytometry experiments and biochemical studies were also performed to explore the mechanism of action. GSEA were performed using several data sets (GSE21422, GSE26910, GSE3744, GSE65194 and GSE42568), and more than 35 compounds against the identified functions were evaluated to discover druggable opportunities. Analyses done with the Chou and Talalay algorithm confirmed the synergy of dasatinib and olaparib. The combination of both agents significantly induced apoptosis in a caspase-dependent manner and revealed a pleotropic effect on cell cycle: Dasatinib arrested cells in G0/G1 and olaparib in G2/M. Dasatinib inhibited pChk1 and induced DNA damage measured by pH2AX, and olaparib increased pH3. Finally, the effect of the combination was also evaluated in a panel of 18 cell lines representative of the most frequent solid tumours, observing a particularly synergism in ovarian cancer. Breast cancer, triple negative, dasatinib, olaparib, screening.     

Hypofractionated radiation therapy for early breast cancer: Follow up of a new treatment standard

AimTo assess the oncological outcomes of patients with early breast cancer treated with breast-conserving surgery and adjuvant hypofractionated radiation therapy.Methods and MaterialThis retrospective analysis included all patients ≥50 year of age with T1-2 N0 M0 breast cancer treated at our Radiation Oncology Unit between 2008 and 2011. Whole-breast radiation therapy was delivered to a dose of 42.5 Gy in 16 fractions, without boost. The primary outcome was local control.Results212 patients were identified. With a median follow up of 60 months, we found 3% local recurrence and 5.3% regional and/or distant recurrences. At the moment of data analysis, 17 patients had died. Out of 5 local recurrences, 2 had previously had a distant recurrence, both of them died. The other three were still alive at the last follow up. These results are comparable to those observed in Phase III trials that use this fractionation scheme.ConclusionsThe results obtained with this retrospective analysis are comparable to those obtained in large randomized trials. This data also supports the use of hypofractionated radiation therapy in Latin America. Hypofractionated radiation therapy for early breast cancer patients should be the standard adjuvant treatment.     

Organizational challenges to equity in the delivery of services within a new personalized risk-based approach to breast cancer screening

Emerging evidence opens new possibilities to improve current breast cancer mammography screening programs. One promising avenue is to tailor mammography screening according to individual risk. However, some factors could challenge the implementation of such approach, specifically its potential impact on the equitable delivery of services. This study aims to identify the barriers and facilitators to the equitable delivery of services within a future integration of a personalized approach in the Québec screening program. We then propose different means to address them. We conducted 16 semi-structured interviews with stakeholders with a role in the management, implementation or assessment of the Québec screening program. The barriers and facilitators identified by respondents were regrouped in two themes: 1) Reproduction of social inequities, and 2) Amplification of regional disparities in access to services. We consider that fostering inclusion through communication strategies and relying on electronic communication technologies could help in addressing these issues.     

microRNAs in breast cancer: regulatory roles governing the hallmarks of cancer

A large number of etiological factors and the complexity of breast cancers present challenges for prevention and treatment. Recently, the emergence of microRNAs (miRNAs) as cancer biomarkers has added an extra dimension to the ‘molecular signatures’ of breast cancer. Bioinformatic analyses indicate that each miRNA can regulate hundreds of target genes and could serve functionally as ‘oncogenes’ or ‘tumour suppressor’ genes, and co‐ordinate multiple cellular processes relevant to cancer progression. A number of studies have shown that miRNAs play important roles in breast tumorigenesis, metastasis, proliferation and differentiation of breast cancer cells. This review provides a comprehensive overview of miRNAs with established functional relevance in breast cancer, their established target genes and resulting cellular phenotype. The role and application of circulating miRNAs in breast cancer is also discussed. Furthermore, we summarize the role of miRNAs in the hallmarks of breast cancer, as well as the possibility of using miRNAs as potential biomarkers for detection of breast cancer.