Journal of Circulating Biomarkers最新文献

{"title":"Case report: Whole exome sequencing of circulating cell-free tumor DNA in a follicular thyroid carcinoma patient with lung and bone metastases.","authors":"Jianlu Song,&nbsp;Zhili Yang","doi":"10.1177/1849454418763725","DOIUrl":"https://doi.org/10.1177/1849454418763725","url":null,"abstract":"<p><p>Metastatic follicular thyroid carcinoma (FTC), unresectable or resistance to radioactive iodine, is associated with poor survival. It is believed that this kind of FTC is driven by mutated genes. However, what kind of changes of genome and underlying mechanisms are elusive. The aim of this article is to understand whether there are somatic mutations in circulating cell-free tumor DNA (cfDNA) in a FTC patient with lung and bone metastases. A 55-year-old woman was diagnosed with FTC with bone and lung metastases. Appropriate amounts of DNA were extracted from formalin-fixed, paraffin-embedded thyroid tumor, peripheral cell-free plasma, and peripheral blood leukocytes and then sequenced. The significance of DNA sequencing was evaluated. There were 13,519 common variants in both tissue DNA and cfDNA. Fifty-five somatic mutations were identified in tumor, with 5 of them nonsynonymous. Seventy-two somatic mutations were found in cfDNA, with 2 of them causing amino acid change. Sixteen common alterations existed in both samples, that is, 31.3% of all the tissue somatic mutations. This pilot study provided proof that cfDNA represents the genomic characteristics of FTC primary tissue DNA well, but also metastatic tumors. Further studies are needed to better prove the effectiveness of cfDNA in the field of thyroid cancer metastatic mechanism research and real-time monitoring.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"7 ","pages":"1849454418763725"},"PeriodicalIF":0.0,"publicationDate":"2018-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1849454418763725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35980942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlations of GDF-15 with sST2, MMPs, and worsening functional capacity in idiopathic dilated cardiomyopathy: Can we gain new insights into the pathophysiology?","authors":"Nandini Nair, Enrique Gongora","doi":"10.1177/1849454417751735","DOIUrl":"10.1177/1849454417751735","url":null,"abstract":"<p><p>Growth and differentiation factor-15 (GDF-15) has been implicated in fibrosis, inflammation, and ventricular remodeling. The role of GDF-15 in the regulation of cardiac remodeling in idiopathic dilated cardiomyopathy (DCM) remains poorly defined. This study attempts to analyze the molecular interactions between GDF-15 and markers of fibrosis as well as its positive correlations with worsening functional capacity. The study population consisted of 24 DCM patients and 8 control subjects. All DCM patients had normal coronary angiographic studies. Plasma levels of GDF-15, matrix metalloproteinase-2 (MMP2), MMP3, MMP9, tissue inhibitor of MMP 1 (TIMP1), and soluble suppression of tumorigenicity-2 protein (sST2) were determined by enzyme-linked immunosorbent assays. Brain Natriuretic Peptide (BNP) was measured as per core laboratory protocol assay at Scott and White Memorial Hospital core laboratory. Correlation analysis was performed between GDF-15 and each of the MMPs-MMP2, MMP3, MMP9, and TIMP as well as New York Heart Association (NYHA) class and echocardiographic parameters (left ventricular ejection fraction (LVEF) and left ventricular internal dimension in diastole (LVIDd)). LVEF and LVIDd were obtained by two-dimensional echocardiography. The protocol was approved by Scott and White Memorial Hospital Institutional Review Board (S&W IRB). Correlation analysis of control versus all DCM patients showed a strong correlation of GDF-15 with TIMP1 (<i>r</i> = 0.83, <i>p</i> < 0.0001) and weaker correlation with MMP3 (<i>r</i> = 0.41, <i>p</i> = 0.011) and MMP2 (<i>r</i> = 0.47, <i>p</i> = 0.003). MMP9 showed poor correlation with GDF-15 (<i>r</i> = 0.3036, <i>p</i> = 0.046). GDF-15 correlated negatively with MMP2/TIMP1 ratio (<i>r</i> = -0.47, <i>p</i> = 0.006). sST2 correlated strongly with GDF-15 (<i>r</i> = 0.7, <i>p</i> < 0.0001). GDF-15 correlated negatively with LVEF (<i>r</i> = -0.49, <i>p</i> = 0.004) and positively with LVIDd (<i>r</i> = 0.58, <i>p</i> = 0.0006). GDF-15 showed significant positive correlation with NYHA functional class (<i>r</i> = 0.71, <i>p</i> < 0.00001) and BNP (<i>r</i> = 0.86, <i>p</i> < 0.00001). Significant associations of GDF-15 with MMPs, sST2, LVIDd, LVEF, and NYHA class reported here for the first time in nonischemic dilated hearts may open up new avenues of investigations to better understand molecular mechanisms controlling cardiac remodeling. This study is limited by its small size and needs validation in larger populations.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"7 ","pages":"1849454417751735"},"PeriodicalIF":0.0,"publicationDate":"2018-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ab/bb/10.1177_1849454417751735.PMC5777561.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35773261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Journal of Circulating Biomarkers</i> looks forward after being indexed in PubMed Central.","authors":"Winston Patrick Kuo","doi":"10.1177/1849454417745757","DOIUrl":"https://doi.org/10.1177/1849454417745757","url":null,"abstract":"Abstract non disponibile","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"6 ","pages":"1849454417745757"},"PeriodicalIF":0.0,"publicationDate":"2017-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1849454417745757","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35681954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of aerobic and anaerobic exercises on circulating soluble-Klotho and IGF-I in young and elderly adults and in CAD patients.","authors":"Moran S Saghiv, D Ben Sira, E Goldhammer, M Sagiv","doi":"10.1177/1849454417733388","DOIUrl":"10.1177/1849454417733388","url":null,"abstract":"<p><p>Different studies support the notion that chronic aerobic exercises training can influence the circulating levels of soluble-Klotho (s-Klotho) and insulin-like growth factor 1 (IGF-I). The effects of s-Klotho include improving the quality of life, alleviating the negative impact of age on the body's work capacity, and possibly increasing longevity. This review provides an overview of the latest findings in this field of research in humans. The different modes of dynamic exercise and their impact on circulating levels of s-Klotho and IGF-I in young adult athletes, untrained young adults, trained healthy older adults, untrained healthy older adults, and coronary artery disease (CAD) patients are reviewed and discussed. Together these findings suggest that long-lasting (chronic) aerobic exercise training is probably one of the antiaging factors that counteract the aging and CAD process by increasing the circulating s-Klotho and lowering the IGF-I levels. However, following anaerobic exercise training the opposite occurs. The exact metabolic and physiological pathways involved in the activity of these well-trained young and master sportsmen should be further studied and elucidated. The purpose of this review was to provide a clarification regarding the roles of s-Klotho and intensities and durations of different exercise on human health.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"6 ","pages":"1849454417733388"},"PeriodicalIF":0.0,"publicationDate":"2017-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fd/95/10.1177_1849454417733388.PMC5644364.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35557863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mildly elevated serum total bilirubin is negatively associated with hemoglobin A1c independently of confounding factors among community-dwelling middle-aged and elderly persons.","authors":"Ryuichi Kawamoto, Daisuke Ninomiya, Kensuke Senzaki, Teru Kumagi","doi":"10.1177/1849454417726609","DOIUrl":"10.1177/1849454417726609","url":null,"abstract":"<p><p>Abnormally high glycated hemoglobin (Hb) (HbA1c) is significantly associated with oxidative stress and an increased risk of cardiovascular disease (CVD). Serum total bilirubin (T-B) may have a beneficial role in preventing oxidative changes and be a negative risk factor of CVD. Limited information is available on whether serum T-B is an independent confounding factor of HbA1c. The study subjects were 633 men aged 70 ± 9 (mean ± standard deviation (SD)) years and 878 women aged 70 ± 8 years who were enrolled consecutively from among patients aged ≥40 years through a community-based annual check-up process. We evaluated the relationship between various confounding factors including serum T-B and HbA1c in each gender. Multiple linear regression analysis pertaining to HbA1c showed that in men, serum T-B (<i>β</i> = -0.139) as well as waist circumference (<i>β</i> = 0.099), exercise habit (<i>β</i> = 0.137), systolic blood pressure (SBP) (<i>β</i> = 0.076), triglycerides (<i>β</i> = 0.087), and uric acid (<i>β</i> = -0.123) were significantly and independently associated with HbA1c, and in women, serum T-B (<i>β</i> = -0.084) as well as body mass index (<i>β</i> = 0.090), smoking status (<i>β</i> = -0.077), SBP (<i>β</i> = 0.117), diastolic blood pressure (DBP) (<i>β</i> = -0.155), low-density lipoprotein cholesterol (<i>β</i> = 0.074), prevalence of antidyslipidemic medication (<i>β</i> = 0.174), and uric acid (<i>β</i> = 0.090) were also significantly and independently associated with HbA1c. Multivariate-adjusted serum HbA1c levels were significantly high in subjects with the lowest serum T-B levels in both genders. Serum T-B is an independent confounding factor for HbA1c among community-dwelling middle-aged and elderly persons.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"6 ","pages":"1849454417726609"},"PeriodicalIF":0.0,"publicationDate":"2017-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c8/9a/10.1177_1849454417726609.PMC5599010.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35428139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of kallikrein-2 biomarkers (free-hK2 and pro-hK2) for predicting prostate cancer progression-free survival.","authors":"Anatilde Gonzalez Guerrico,&nbsp;David Hillman,&nbsp;Jeffery Karnes,&nbsp;Brian Davis,&nbsp;Steven Gaston,&nbsp;George Klee","doi":"10.1177/1849454417720151","DOIUrl":"https://doi.org/10.1177/1849454417720151","url":null,"abstract":"<p><p>Free human kallikrein 2 (free-hK2) and hK2 pro-form (pro-hK2) have been found to be increased in tumor tissues and serum from patients with prostate cancer. We established semiautomatic assays for free-hK2 and pro-hK2 using a research version of the Beckman Coulter ACCESS2 system. Serum samples from a cohort of 189 men undergoing radical prostatectomy for known high-risk disease were assayed for Prostate-Specific Antigen (PSA), free-PSA, free-hK2, and pro-hK2. Univariate Cox regression and multivariate models were used to predict both Gleason scores and progression-free survival (PFS). Free-hk2 levels ≥80 ng/L were predictive of both Gleason scores ≥7 (<i>p</i> = 0.04) and PFS (<i>p</i> = 0.03). PSA ≥8.0 µg/L also was predictive of PFS (<i>p</i> = 0.02). However, neither % free-PSA nor pro-hK2, when treated as continuous or cutoff variables were associated with Gleason score or PFS. Multivariable models showed that clinical stage T1c versus T2/T3, Gleason score ≥7, and PSA ≥8.0 µg/L or clinical stage T1c versus T2/T3, Gleason scores ≥7, and free-hK2 ≥80 ng/L were among the best models predicting PFS. Both free-hK2 and PSA in conjunction with clinical stage and Gleason score are good predictors of PFS in prostate cancer.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"6 ","pages":"1849454417720151"},"PeriodicalIF":0.0,"publicationDate":"2017-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1849454417720151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35428137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel method for the isolation of extracellular vesicles and RNA from urine.","authors":"Anna Markowska,&nbsp;R Scott Pendergrast,&nbsp;J Stephen Pendergrast,&nbsp;P Shannon Pendergrast","doi":"10.1177/1849454417712666","DOIUrl":"https://doi.org/10.1177/1849454417712666","url":null,"abstract":"<p><p>The discovery of urinary extracellular biomarkers has been impeded by the lack of efficient methods for the isolation of extracellular vesicles (EVs: exosomes and microvesicles) and extracellular nucleic acid (RNA and DNA) from urine. Ultracentrifugation (UC), considered the gold standard for vesicle isolation from many biofluids, is efficacious but laborious, and, like most commercially available methods, is unable to isolate enough material from small volumes for protein or RNA-based biomarker discovery. We have developed a novel precipitation method for the isolation of EVs and nucleic acids from urine. The method, which is now commercially available, takes less than 30 min and does not require polyethylene glycol. Transmission electron microscopy and Nanosight particle analysis confirm that the method isolates intact vesicles with a similar size, shape, and number to UC. Immunoblot analysis of preparations made from a variety of urine samples demonstrates that the method isolates multiple vesicle protein markers more efficiently than other commercial kits, especially from more diluted samples. Bioanalyzer, quantitative reverse transcription polymerase chain reaction, and array analysis show that the method is extremely efficient at the isolation of extracellular miRNAs. The Ymir Genomics EV and Extracellular RNA Isolation Kits offer an efficient and rapid alternative to UC and other commercial kits.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"6 ","pages":"1849454417712666"},"PeriodicalIF":0.0,"publicationDate":"2017-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1849454417712666","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35427692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The signature of circulating microparticles in heart failure patients with metabolic syndrome.","authors":"Alexander E Berezin,&nbsp;Alexander Kremzer,&nbsp;Tatyana Berezina,&nbsp;Yu Martovitskaya","doi":"10.1177/1849454416663659","DOIUrl":"https://doi.org/10.1177/1849454416663659","url":null,"abstract":"<p><p>The role of pattern of circulating endothelial cell-derived microparticles, platelet-derived microparticles (PMPs), and monocyte-derived microparticles (MMPs) in metabolic syndrome (MetS) patients with chronic heart failure (CHF) is not still understood. The aim of the study was to investigate a pattern of circulating microparticles (MPs) in MetS patients with CHF in relation to neurohumoral and inflammatory activation. The study retrospectively involved 101 patients with MetS and 35 healthy volunteers. Biomarkers were measured at baseline of the study. The results of the study have shown that numerous circulating PMPs- and MMPs in subjects with MetS (with or without CHF) insufficiently distinguished from level obtained in healthy volunteers. We found elevated level of CD31+/annexin V+ MPs in association with lower level of CD62E+ MPs. Therefore, we found that biomarkers of biomechanical stress serum N-terminal brain natriuretic peptide and inflammation (high-sensitive C-reactive protein ,osteoprotegerin) remain statistically significant predictors for decreased CD62E+ to CD31+/annexin V+ ratio in MetS patients with CHF. In conclusion, decreased CD62E+ to CD31+/annexin V+ ratio reflected that impaired immune phenotype of MPs may be discussed as a surrogate marker of CHF development in MetS population.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"5 ","pages":"1849454416663659"},"PeriodicalIF":0.0,"publicationDate":"2016-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1849454416663659","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35427688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microvesicles shed from fibroblasts act as metalloproteinase carriers in a 3-D collagen matrix.","authors":"Valentina Laghezza Masci,&nbsp;Anna Rita Taddei,&nbsp;Gabriella Gambellini,&nbsp;Franco Giorgi,&nbsp;Anna Maria Fausto","doi":"10.1177/1849454416663660","DOIUrl":"https://doi.org/10.1177/1849454416663660","url":null,"abstract":"<p><p>This study shows that fibroblasts migrating into a collagen matrix release numerous microvesicles into the surrounding medium. By spreading in regions of the matrix far distant from cells of origin, microvesicles carry metalloproteinase 9 (MMP-9) to act upon the collagen fibrils. As a result, the collagen matrix is gradually transformed from a laminar to a fibrillar type of architecture. As shown by western blots and gelatin zymography, MMP-9 is secreted as a 92 kDa precursor and activated upon release of 82 kDa product into the culture medium. Activation is more efficient under three-dimensional than in two-dimensional culturing conditions. While MMP-9 labeling is associated with intraluminal vesicles clustered inside the microvesicles, the microvesicle's integrin β1 marker is bound to the outer membrane. The intraluminal vesicles are recruited from the cortical cytoplasm and eventually released following uploading inside the microvesicle. Here, we propose that fusion of the intraluminal vesicles with the outer microvesicle's membrane could work as a mechanism controlling the extent to which MMP-9 is first activated and then released extracellularly.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"5 ","pages":"1849454416663660"},"PeriodicalIF":0.0,"publicationDate":"2016-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1849454416663660","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35427689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel blood test to predict neoplastic activity in healthy patients and metastatic recurrence after primary tumor resection.","authors":"Mohamed Abdouh,&nbsp;Dana Hamam,&nbsp;Vincenzo Arena,&nbsp;Manuel Arena,&nbsp;Hussam Alamri,&nbsp;Goffredo Orazio Arena","doi":"10.1177/1849454416663661","DOIUrl":"https://doi.org/10.1177/1849454416663661","url":null,"abstract":"<p><p>We reported that single oncosuppressor-mutated (SOM) cells turn malignant when exposed to cancer patients' sera. We tested the possibility to incorporate this discovery into a biological platform able to detect cancer in healthy individuals and to predict metastases after tumor resection. Blood was drawn prior to tumor resection and within a year after surgery. Blood samples from healthy individuals or metastatic patients were used as negative and positive controls, respectively. Patients at risk for cancer were included in the screening cohort. Once treated, cells were injected into nonobese diabetic/severe combined immunodeficiency mice to monitor tumor growth. All samples of sera coming from metastatic patients transformed SOM cells into malignant cells. Four samples from screened patients transformed SOM cells. Further clinical tests done on these patients showed the presence of early cancerous lesions despite normal tumor markers. Based on the xenotransplants size, we were able to predict metastasis in three patients before diagnostic tests confirmed the presence of the metastatic lesions. These data show that this serum-based platform has potentials to be used for cancer screening and for identification of patients at risks to develop metastases regardless of the Tumor Node Metastasis (TNM) stage or tumor markers level.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"5 ","pages":"1849454416663661"},"PeriodicalIF":0.0,"publicationDate":"2016-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1849454416663661","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35428135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}