前列腺癌生物标志物的研究进展

前列腺癌(PCa)是一种发生于前列腺组织中的恶性肿瘤,是前列腺腺泡细胞异常无序生长的结果.PCa发病率具有明显的地理和种族差异,在欧美等发达国家和地区,是男性最常见的恶性肿瘤,病死率居各种癌症第2位[1];在亚洲,其发病率低于西方国家,但近年来随着人口老龄化及生活条件的改善,发病率呈迅速上升趋势[2];在我国,PCa在男性泌尿、生殖系统恶性肿瘤中发病率已跃居第3位,患者主要是老年人,严重影响着我国老年男性的晚年生活质量[3,4].PCa的生存率有赖于早期的诊断和治疗,生物标志物往往能先于其他手段如直肠指检(DRE)、超声等检出癌症,故寻找有效的生物标志物一直是研究的热点.现就PCa生物标志物研究进展作一综述.     

心脏生物标志物的研究进展

目前,越来越多的心脏生物标志物的应用为临床诊断提供了新的方法和思路,其与心血管疾病的病理生理学的密切联系使其成为倍受关注的诊断和预后的工具.具有高度敏感性、特异性的心脏生物标志物的研究已经成为-临床研究的热点,对于心血管疾病的诊断、预后判断已经显示出一定的价值.     

胃癌免疫治疗的相关生物标志物研究进展

目的 胃癌(Gastric cancer, GC)是我国常见恶性肿瘤,临床中,免疫治疗逐渐被用于治疗晚期胃癌,但治疗效果存在明显的个体差异,为了进一步预测免疫治疗效果,改善胃癌的预后,我们总结了目前和免疫治疗相关的生物标志物(包括PD-L1、微卫星不稳定性、EB病毒和肿瘤突变负荷等),综述了影响GC免疫治疗的潜在生物标志物及可能的机制。胃癌免疫相关标志物的分析和总结,可能为胃癌患者的免疫治疗的选择和疗效的预测提供一定的指导。     

心房颤动心房纤维化相关生物标志物研究进展

<正>心房颤动是目前临床最常见的心律失常疾病之一,其增加中老年血栓栓塞、心力衰竭发病及死亡率~[1],近年广泛受到关注。现有研究证实心房纤维化参与心房电机械重构,在心房颤动的发生发展中起到至关重要的作用~[2-3];应用MRI技术定量评估心房颤动心房纤维化程度高者,其心房颤动射频消融术后复发率上升~[4]。因此,心房纤维化程度是评估心房颤动发展的重要指标,筛选心房颤动心房纤维化特异性生物标志物,指导判断患者预后成为亟待解决的临床问题。近年心房纤     

胆汁淤积的生物标志物研究进展

<正>胆汁淤积概述胆汁的主要成分为胆汁酸,其由肝细胞合成并依次排入胆管、肠道。约95%的胆汁酸可在肠道被重吸收,形成胆汁酸的肠肝循环,维系胆汁酸的稳态^[1]。胆汁酸循环的各个环节受不同致病因素的影响,致使流入十二指肠的胆汁减少,从而引起胆汁淤积。胆汁淤积按发生部位可分为肝内胆汁淤积和肝外胆汁淤积。肝内胆汁淤积主要原因有药物、     

帕金森病相关外周血淋巴细胞生物标志物的研究进展

<正>目前临床中主要依据临床症状及对左旋多巴治疗的反应对帕金森病(PD)患者进行诊断,当PD患者出现明显或典型临床症状时,绝大多数患者纹状体多巴胺浓度一般已较正常水平降低80%以上,如果能从患者外周血中获取可以对PD诊断和治疗效果进行判断的有效生物标志物,这将会对PD的诊断及治疗产生重要意义,但至今尚无肯定的临床生物标志物。外周血容易获取,并可进行长期随访观察,且淋巴细胞上表达有多     

心肌间质纤维化相关生物标志物的研究进展

<正>全球目前约有1.25亿冠状动脉疾病(coronary artery disease, CAD)患者,心肌梗死(myocardial infarction,MI)导致的缺血性心肌病(ischemic cardiomyopathy,ICM)和心力衰竭(heart failure, HF)是死亡、反复住院的主要原因^[1]。尽管造成心力衰竭的根本原因通常是多因素且相互重叠的,缺血性心肌病仍是心力衰竭的最大单一因素^[1]。     

IgA肾病诊治相关的生物标志物

IgA肾病（IgAN）是目前世界范围内最常见的原发性肾小球疾病,是终末期肾衰竭的主要原因。多见于青壮年, 目前机制尚不明确,临床和病理改变多样,尚缺乏特效治疗手段。目前确诊仍有赖于肾活检,治疗上需要临床结合病 理改变进行个体化治疗。因此,寻找敏感、特异有效、无创的生物标志物用于诊断和预后评估是迫切需要的。文章将 从IgAN诊断、疾病进展和预后评估及治疗相关的血和尿生物标志物重点进行阐述。     

心力衰竭生物标志物的研究进展

随着人们对心力衰竭病理生理过程的认识逐步加深,多种生物学指标的改变对于心力衰竭诊断和预后的价值不断被发现。在其发生和发展过程中,机体通过心肌牵张、基质重塑、肌细胞损伤、氧化应激、炎症反应、神经激素激活和肾功能不全等途径发挥重要作用,现从不同途径分析几种可能运用于临床诊断和评估患者预后的生物标志物,并对其近年的研究现状做一综述。     

糖尿病肾病生物标志物研究进展

糖尿病肾病(DN)是造成终末期肾病(ESRD)的主要原因之一,众多因素参与并调控了DN的发生发展.目前临床上反应DN的生物标志物主要为尿白蛋白(UA1b),其具有明显的缺陷,因此筛选早期DN生物标志物的研究有助于更好地理解DN的发生及进展机制,从而更好地指导治疗.本文就DN生物标志物研究的最新进展进行介绍.     

Circulating microRNAs as stable blood-based markers for cancer detection

Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small ( approximately 22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.     

胃癌肿瘤标志物研究进展

胃癌肿瘤标志物在胃癌的诊断、治疗及预后判断中发挥重要作用.此文概述胃癌发生发展过程中的分子生物学改变,列出可能用于预测胃癌的肿瘤标志物及其在临床中的应用.     

Discovery and horizontal follow-up of an autoantibody signature in human prostate cancer

In response to an urgent need for improved diagnostic and predictive serum biomarkers for management of metastatic prostate cancer, we used phage display fingerprinting to analyze sequentially acquired serum samples from a patient with advancing prostate cancer. We identified a peptide ligand, CTFAGSSC, demonstrating an increased recovery frequency over time. Serum antibody reactivity to this peptide epitope increased in the index patient, in parallel with development of deteriorating symptoms. The antigen mimicking the peptide epitope was identified as alpha-2–Heremans–Schmid glycoprotein, also known as fetuin-A. Metastatic prostate cancer cell lines and bone metastasis samples displayed robust fetuin-A expression, and we demonstrated serum immune reactivity to fetuin-A with concomitant development of metastatic castrate-resistant disease in a large cohort of prostate cancer patients. Whereas fetuin-A is an established tumor antigen in several types of cancer, including breast cancer, glioblastoma, and pancreas cancer, this report is to our knowledge the first study implicating fetuin-A in prostate cancer and indicating that autoantibodies specific for fetuin-A show utility as a prognostic indicator for prostate cancer patients prone to progress to metastatic disease.Prostate cancer accounts for nearly 27,000 deaths annually, with end-stage bone metastases representing a leading cause of morbidity and mortality (1). The introduction of diagnostic serum biomarkers into clinical practice, such as prostate-specific antigen (PSA), has greatly improved early detection of the disease (2). However, the lack of reliable methods for prediction of progression beyond early-stage disease and the paucity of treatment options for patients with bone metastasis results in many patients with localized disease subjected to aggressive treatment with sequelae including incontinence and impotence (3). Thus, identification of biomarkers to improve the accuracy of clinical assessment and stratification of patients needing conservative versus aggressive treatment would constitute a major advance in the management of this disease.Antibodies specific for tumor-associated antigens are detectable in the serum of cancer patients and have been studied as diagnostic and prognostic markers (4). Simultaneous quantification of autoantibodies and PSA was proposed as a new approach to improve diagnosis and prognosis of prostate cancer (5). After autoantibodies against Huntingtin interacting protein-1 were identified in prostate cancer patients, combining serum reactivity with PSA values led to a screening discrimination with 97% specificity (6).Using combinatorial peptide phage libraries, we developed a fingerprinting method based on targeting of circulating tumor-associated antibodies isolated from cancer patients (7, 8). Specific autoantibodies and their cognate tumor-associated antigens have been characterized, e.g., GRP78 for prostate cancer (9), HSP90 for ovarian cancer (8), ubiquilin 1 in lung cancer (10), and annexin XI-A in breast cancer (11). In addition, phage-based screening approaches have been developed for high-throughput profiling of immunogenic antigens for prostate cancer (12).In this study, we analyzed clinically annotated serum samples obtained from an index patient at time points from his initial diagnosis, presenting with androgen-dependent, localized prostate cancer, until his death with androgen-independent metastatic multifocal bone disease 7 y after the initial banked serum sample. A unique peptide, CTFAGSSC, was identified, for which autologous serum IgG showed increasing reactivity. We identified alpha-2–Heremans–Schmid glycoprotein (AHSG, also known as fetuin-A) as the putative protein corresponding to the peptide mimic. We demonstrated increased serum antibody reactivity to fetuin-A during progression of disease in the index patient, as well as strong serum reactivity in a large cohort of metastatic prostate cancer patients. Reactivity to fetuin-A, identified years before the onset of metastatic disease in the index patient, indicates that serum antibodies constitute potential predictive biomarkers for metastatic prostate cancer and might facilitate relevant early treatment decisions.     

Disseminated intravascular coagulation as the presenting sign of metastatic prostate cancer

Disseminated intravascular coagulation (DIC) is an acquired coagulation disorder that may occur in a wide variety of clinical conditions. Suspicion of DIC should lead to a differential diagnosis that includes primary fibrinolysis and other bleeding diatheses such as thrombocytopenias of diverse etiology. Confirmation of the diagnosis of DIC should always prompt a search for an underlying medical disorder, including sepsis, severe trauma, solid and hematological malignancies, obstetrical complications, and vascular disorders. Here, we describe an unusual case of acute bleeding and DIC as the presenting manifestation of metastatic prostate cancer in a 60-year-old man. Treatment with a luteinizing hormone-releasing hormone (LHRH) agonist and a short course of an antiandrogen, together with supportive measures (i.e., clotting factors, heparin, and platelets), led to normalization of all coagulation parameters within 1 week, and to clinical improvement and decline in the serum level of prostate-specific antigen (PSA). We discuss the pathogenesis, differential diagnosis, and association of DIC with prostate cancer along with the management of this condition.     

Disseminated intravascular coogulation as the presenting sign of metastatic prostate cancer

Disseminated intravascular coagulation (DIC) is an acquired coagulation disorder that may occur in a wide variety of clinical conditions. Suspicion of DIC should lead to a differential diagnosis that includes primary fibrinolysis and other bleeding diatheses such as thrombocytopenias of diverse etiology. Confirmation of the diagnosis of DIC should always prompt a search for an underlying medical disorder, including sepsis, severe trauma, solid and hematological malignancies, obstetrical complications, and vascular disorders. Here, we describe an unusual case of acute bleeding and DIC as the presenting manifestation of metastatic prostate cancer in a 60-year-old man. Treatment with a luteinizing hormone-releasing hormone (LHRH) agonist and a short course of an antiandrogen, together with supportive measures (i.e., clotting factors, heparin, and platelets), led to normalization of all coagulation parameters within 1 week, and to clinical improvement and decline in the serum level of prostate-specific antigen (PSA). We discuss the pathogenesis, differential diagnosis, and association of DIC with prostate cancer along with the management of this condition. None of the authors have any conflicts of interest to declare.     

长链非编码RNA在癌症中的研究进展

长链非编码RNA(lncRNA)在癌症中扮演重要的角色。基因组关联研究已经发现,大量的lncRNA与各种类型的癌症相关。lncRNA的表达和突变能够促进肿瘤的形成和转移。lncRNA可能具有肿瘤抑制和促进致癌作用。因为lncRNA的基因组表达具有多样性和特异性,所以,lncRNA被认定可以作为新的肿瘤分子标志物和治疗靶点。本文结合国内外最新报道,对lncRNA在癌症中的研究进展作一综述。     

Treatment decisions for localized prostate cancer

OBJECTIVE: To identify what factors men consider important when choosing treatment for prostate cancer, and to assess why men reject watchful waiting as a treatment option. PARTICIPANTS: One hundred two consecutive men with newly diagnosed localized prostate cancer identified from hospital and community-based urology practice groups. MEASUREMENTS: Patients were asked open-ended questions about likes and dislikes of all treatments considered, how they chose their treatment, and reasons for rejecting watchful waiting. The interviews were conducted in person, after the men had made a treatment decision but before they received the treatment. MAIN RESULTS: The most common reasons for liking a treatment were removal of tumor for radical prostatectomy (RP) (n=15), evidence for external beam radiation (EBRT) (n=6), and short duration of therapy for brachytherapy (seeds) (n=25). The most frequently cited dislikes were high risk of incontinence for RP (n=46), long duration of therapy for EBRT (n=29), and lack of evidence for seeds (n=16). Only 12 men chose watchful waiting. Fear of future consequences, cited by 64% (n=90) of men, was the most common reason to reject watchful waiting. CONCLUSION: In discussing treatment options for localized prostate cancer, clinicians, including primary care providers, should recognize that patients’ decisions are often based on specific beliefs regarding each therapy’s intrinsic characteristics, supporting evidence, or pattern of complications. Even if patients do not recall a physician recommendation against watchful waiting, this option may not be chosen because of fear of future consequences. Presented in part at the 1998 annual meeting of the Society for General Internal Medicine. The opinions expressed herein are solely those of the authors and do not represent the views of the Department of Defense, the Department of the Navy, or the Department of Veterans Affairs. Dr. Holmboe completed this work as a Fellow in the Robert Wood Johnson Clinical Scholars program, Yale University School of Medicine. Dr. Concato is supported by a Career Development Award from the VA Health Services Research and Development Service.     

血清肿瘤标志物在肺癌早期诊断中的应用现状及研究进展

肺癌是目前最常见的恶性肿瘤之一,其5年生存率不足14％。提高肺癌患者生存率的关键在于早期诊断。血清肿瘤标志物作为有效的诊断方法倍受临床关注。本文综述了目前肺癌血清标志物研究现状和进展。