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Balis, Frank M., Cynthia Lester McCully, Christine M. Busch, Elizabeth Fox, and Katherine E. Warren. "Pharmacokinetics of the disialoganglioside, GD2, a circulating tumor biomarker for neuroblastoma, in nonhuman primates." Journal of Circulating Biomarkers 10 (December 3, 2021): 26–29. http://dx.doi.org/10.33393/jcb.2021.2329.
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Background: The ganglioside GD2 is a potential circulating tumor biomarker for the childhood cancer, neuroblastoma. Interpreting the levels of a circulating tumor biomarker depends in part on a knowledge of the biomarker’s clinical pharmacology. Background: The ganglioside GD2 is a potential circulating tumor biomarker for the childhood cancer neuroblastoma. Interpreting the levels of a circulating tumor biomarker depends in part on a knowledge of the biomarker’s clinical pharmacology. Methods: We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics of the C18 lipoform of GD2 in two nonhuman primates with indwelling subcutaneous CSF lateral ventricular reservoir systems. GD2 was quantified with a validated high-performance liquid chromatography (HPLC)/tandem mass spectrometry assay. GD2 was administered as a short intravenous infusion and frequent plasma and CSF samples were drawn over 72 hours. Results: GD2 plasma concentration declined monoexponentially with a half-life of 16 hours. Clearance was 0.0136 and 0.0131 L/h and volume of distribution (Vd) was 0.035 and 0.038 L/kg in the two animals. Vd was equivalent to plasma volume. Greater than 98% of GD2 in plasma is in a bound form consistent with its known association with lipoproteins and accounting for its limited volume of distribution. GD2 did not cross over from plasma into the CSF. Conclusions: The pharmacokinetic profile of GD2 is favorable for a circulating tumor biomarker. This study demonstrates the value of characterizing the clinical pharmacology of circulating biomarkers to better understand their clinical behavior.
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Mehta, Arpita I., Sally Ross, Mark S. Lowenthal, Vincent Fusaro, David A. Fishman, Emanuel F. Petricoin, and Lance A. Liotta. "Biomarker Amplification by Serum Carrier Protein Binding." Disease Markers 19, no. 1 (2003): 1–10. http://dx.doi.org/10.1155/2003/104879.
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Mass spectroscopic analysis of the low molecular mass (LMM) range of the serum/plasma proteome is a rapidly emerging frontier for biomarker discovery. This study examined the proportion of LMM biomarkers, which are bound to circulating carrier proteins. Mass spectroscopic analysis of human serum following molecular mass fractionation, demonstrated that the majority of LMM biomarkers exist bound to carrier proteins. Moreover, the pattern of LMM biomarkers bound specifically to albumin is distinct from those bound to non-albumin carriers. Prominent SELDI-TOF ionic species (m/z 6631.7043) identified to correlate with the presence of ovarian cancer were amplified by albumin capture. Several insights emerged: a) Accumulation of LMM biomarkers on circulating carrier proteins greatly amplifies the total serum/plasma concentration of the measurable biomarker, b) The total serum/plasma biomarker concentration is largely determined by the carrier protein clearance rate, not the unbound biomarker clearance rate itself, and c) Examination of the LMM species bound to a specific carrier protein may contain important diagnostic information. These findings shift the focus of biomarker detection to the carrier protein and its biomarker content.
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Lim, Yen Ying, Paul Maruff, Naoki Kaneko, James Doecke, Christopher Fowler, Victor L. Villemagne, Takashi Kato, et al. "Plasma Amyloid-β Biomarker Associated with Cognitive Decline in Preclinical Alzheimer’s Disease." Journal of Alzheimer's Disease 77, no. 3 (September 29, 2020): 1057–65. http://dx.doi.org/10.3233/jad-200475.
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Background: Using immunoprecipitation-mass spectrometry, we recently developed and validated a plasma composite biomarker for the assessment of amyloid-β (Aβ) levels. However, as yet, its relationship with clinical outcomes remains unclear. Objective: We aimed to examine the relationship between this plasma Aβ composite biomarker and cognitive function in cognitively normal older adults in two independent cohorts. Methods: Participants enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study and the National Centre for Geriatrics and Gerontology (NCGG) study had undergone Aβ neuroimaging using positron emission tomography (PET), cognitive assessments and provided blood samples. We derived a high-performance plasma Aβ composite biomarker by immunoprecipitation with mass-spectrometry. Results: Both continuous and categorical measures of the plasma Aβ composite biomarker were significantly related to decline in episodic memory and executive function. The magnitude of effects of the plasma Aβ composite on episodic memory and executive function were comparable to that observed for the effects of PET Aβ levels on these same outcome measures. Conclusion: Several plasma Aβ biomarkers have been developed, but none have yet been applied to investigate their relationship with cognitive outcomes. Our results have important implications for the use of this biomarker in the detection of at-risk individuals.
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Meng, Ran, and Xunming Ji. "Plasma Biomarker and Stroke." Cerebrovascular Diseases 32, no. 4 (2011): 406. http://dx.doi.org/10.1159/000331927.
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Yang, Chun-Ju, Hai Yan, Naimei Tang, Yi Zou, Yas Al-Hadeethi, Xiaochuan Xu, Hamed Dalir, and Ray T. Chen. "Ultra Sensitivity Silicon-Based Photonic Crystal Microcavity Biosensors for Plasma Protein Detection in Patients with Pancreatic Cancer." Micromachines 11, no. 3 (March 9, 2020): 282. http://dx.doi.org/10.3390/mi11030282.
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Defect-engineered photonic crystal (PC) microcavities were fabricated by UV photolithography and their corresponding sensitivities to biomarkers in patient plasma samples were compared for different resonant microcavity characteristics of quality factor Q and biomarker fill fraction. Three different biomarkers in plasma from pancreatic cancer patients were experimentally detected by conventional L13 defect-engineered microcavities without nanoholes and higher sensitivity L13 PC microcavities with nanoholes. 8.8 femto-molar (0.334 pg/mL) concentration of pancreatic cancer biomarker in patient plasma samples was experimentally detected which are 50 times dilution than ELISA in a PC microcavity with high quality factor and high analyte fill fraction.
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Vrba, Lukas, and Bernard W. Futscher. "DNA methylation changes in biomarker loci occur early in cancer progression." F1000Research 8 (December 16, 2019): 2106. http://dx.doi.org/10.12688/f1000research.21584.1.
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Tumor-specific DNA methylation can be used for cancer diagnostics and monitoring. We have recently reported a set of DNA methylation biomarkers that can distinguish plasma samples from lung cancer patients versus healthy controls with high sensitivity and specificity. Furthermore, the DNA methylation signal from the biomarker loci detected in plasma samples correlated with tumor size and decreased after surgical resection of lung tumors. In order to determine the timing of DNA methylation of these loci during carcinogenesis and thus the potential of the biomarkers to detect early stages of the disease we analyzed the DNA methylation of the biomarker loci in five precancerous conditions using available data from the GEO database. We found that the DNA methylation of the biomarker loci is gained early in carcinogenesis since most of the precancerous conditions already have biomarker loci hypermethylated. Moreover, these DNA methylation biomarkers are able to distinguish between precancerous lesions with malignant potential and those that stay benign where data is available. Taken together, the biomarkers have the potential to detect the earliest cancer stages; the only limitation to detection of cancer from plasma samples or other liquid biopsies is the timing when tumors start to shed enough DNA into body fluids.
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Vrba, Lukas, and Bernard W. Futscher. "DNA methylation changes in biomarker loci occur early in cancer progression." F1000Research 8 (February 14, 2020): 2106. http://dx.doi.org/10.12688/f1000research.21584.2.
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Tumor-specific DNA methylation can be used for cancer diagnostics and monitoring. We have recently reported a set of DNA methylation biomarkers that can distinguish plasma samples from lung cancer patients versus healthy controls with high sensitivity and specificity. Furthermore, the DNA methylation signal from the biomarker loci detected in plasma samples correlated with tumor size and decreased after surgical resection of lung tumors. In order to determine the timing of DNA methylation of these loci during carcinogenesis and thus the potential of the biomarkers to detect early stages of the disease we analyzed the DNA methylation of the biomarker loci in five precancerous conditions using available data from the GEO database. We found that the DNA methylation of the biomarker loci is gained early in carcinogenesis since most of the precancerous conditions already have biomarker loci hypermethylated. Moreover, these DNA methylation biomarkers are able to distinguish between precancerous lesions with malignant potential and those that stay benign where data is available. Taken together, the biomarkers have the potential to detect the earliest cancer stages; the only limitation to detection of cancer from plasma samples or other liquid biopsies is the timing when tumors start to shed enough DNA into body fluids.
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Ebadi, Maryam, and Vera C. Mazurak. "Potential Biomarkers of Fat Loss as a Feature of Cancer Cachexia." Mediators of Inflammation 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/820934.
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Fat loss is associated with shorter survival and reduced quality of life in cancer patients. Effective intervention for fat loss in cachexia requires identification of the condition using prognostic biomarkers for early detection and prevention of further depletion. No biomarkers of fat mass alterations have been defined for application to the neoplastic state. Several inflammatory cytokines have been implicated in mediating fat loss associated with cachexia; however, plasma levels may not relate to adipose atrophy. Zinc-α2-glycoprotein may be a local catabolic mediator within adipose tissue rather than serving as a plasma biomarker of fat loss. Plasma glycerol and leptin associate with adipose tissue atrophy and mass, respectively; however, no study has evaluated their potential as a prognostic biomarker of cachexia-associated fat loss. This review confirms the need for further studies to identify valid prognostic biomarkers to identify loss of fat based on changes in plasma levels of biomarkers.
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Dan, Kisoon, Ji Eun Lee, Dohyun Han, Sun Min Kim, Subeen Hong, Hyeon Ji Kim, and Kyo Hoon Park. "Proteomic identification of biomarkers in maternal plasma that predict the outcome of rescue cerclage for cervical insufficiency." PLOS ONE 16, no. 4 (April 15, 2021): e0250031. http://dx.doi.org/10.1371/journal.pone.0250031.
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Objective We sought to identify plasma protein biomarkers that are predictive of the outcome of rescue cerclage in patients with cervical insufficiency. Methods This retrospective cohort study included 39 singleton pregnant women undergoing rescue cerclage for cervical insufficiency (17–25 weeks) who gave plasma samples. Three sets of pooled plasma samples from controls (cerclage success, n = 10) and cases (cerclage failure, n = 10, defined as spontaneous preterm delivery at <33 weeks) were labeled with 6-plex tandem mass tag (TMT) reagents and analyzed by liquid chromatography-tandem mass spectrometry. Differentially expressed proteins between the two groups were selected from the TMT-based quantitative analysis. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was further used to verify the candidate proteins of interest in patients with cervical insufficiency in the final cohort (n = 39). Results From MRM-MS analysis of the 40 proteins showing statistically significant changes (P < 0.05) from the TMT-based quantitative analysis, plasma IGFBP-2, PSG4, and PGLYRP2 levels were found to be significantly increased, whereas plasma MET and LXN levels were significantly decreased in women with cerclage failure. Of these, IGFBP-2, PSG4, and LXN levels in plasma were independent of cervical dilatation. A multiple-biomarker panel was developed for the prediction of cerclage failure, using a stepwise regression procedure, which included the plasma IGFBP-2, PSG4, and LXN (area under the curve [AUC] = 0.916). The AUC for this multiple-biomarker panel was significantly greater than the AUC for any single biomarker included in the multi-biomarker model. Conclusions Proteomic analysis identified useful and independent plasma biomarkers (IGFBP-2, PSG4, and LXN; verified by MRM) that predict poor pregnancy outcome following rescue cerclage. Their combined analysis in a multi-biomarker panel significantly improved predictability.
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Collard, Harold R., Carolyn S. Calfee, Paul J. Wolters, Jin Woo Song, Sang-Bum Hong, Sandra Brady, Akitoshi Ishizaka, et al. "Plasma biomarker profiles in acute exacerbation of idiopathic pulmonary fibrosis." American Journal of Physiology-Lung Cellular and Molecular Physiology 299, no. 1 (July 2010): L3—L7. http://dx.doi.org/10.1152/ajplung.90637.2008.
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Little is known about the pathobiology of acute exacerbation of idiopathic pulmonary fibrosis (IPF), a condition that shares clinical and histopathological features with acute lung injury. Plasma biomarkers have been well studied in acute lung injury and have provided insight into the underlying disease mechanism. The objective of this study was to determine the plasma biomarker profile of acute exacerbation of IPF and compare this profile with that of stable IPF and acute lung injury. Plasma was collected from patients with stable IPF, acute exacerbation of IPF, and acute lung injury for measurement of biomarkers of cellular activity/injury (receptor for advanced glycation endproducts, surfactant protein D, KL-6, von Willebrand factor), systemic inflammation (IL-6), and coagulation/fibrinolysis (protein C, thrombomodulin, plasminogen activator inhibitor-1). Plasma from patients with acute exacerbation of IPF showed significant elevations in markers of type II alveolar epithelial cell injury and/or proliferation, endothelial cell injury, and coagulation. This profile differed from the biomarker profile in patients with acute lung injury. These findings support the hypothesis that type II alveolar epithelial cells are centrally involved in the pathobiology of acute exacerbation of IPF. Furthermore, they suggest that acute exacerbation of IPF has a distinct plasma biomarker profile from that of acute lung injury.
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Ji, Xu, Rie Takahashi, Yumiko Hiura, Go Hirokawa, Yasue Fukushima, and Naoharu Iwai. "Plasma miR-208 as a Biomarker of Myocardial Injury." Clinical Chemistry 55, no. 11 (November 1, 2009): 1944–49. http://dx.doi.org/10.1373/clinchem.2009.125310.
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Abstract Background: MicroRNAs (miRNAs) are endogenous small RNAs of 21–25 nucleotides that can pair with sites in 3′ untranslated regions in mRNAs of protein-coding genes to downregulate their expression. Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. We assessed the hypothesis that miRNAs may leak into the circulating blood from injured cells and thereby serve as biomarkers for identifying the injured cell type. Methods: We used isoproterenol-induced myocardial injury in rats as a model and miRNA array analyses to identify candidate miRNAs specifically produced in the ventricles of the heart. Individual miRNA concentrations were measured by real-time reverse-transcription PCR. Plasma cardiac troponin I (cTnI) concentrations were measured with an ELISA. Results: Array analyses revealed miR-208 to be produced exclusively in the heart, and we selected this miRNA as a possible biomarker of myocardial injury. Plasma concentrations of miR-208 increased significantly (P < 0.0001) after isoproterenol-induced myocardial injury and showed a similar time course to the concentration of cTnI, a classic biomarker of myocardial injury. Conclusions: The plasma concentration of miR-208 may be a useful indicator of myocardial injury. Our results suggest that profiling of circulating miRNAs may help identify promising biomarkers of various pathologic conditions.
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Sumathy, Dr S., Dr V. G. Karpaghavalli, and Dr G. Chitra Siva Sankari. "Role of Plasma Fibrinogen as a Biomarker in Chronic Obstructive Pulmonary Disease." Scholars Journal of Applied Medical Sciences 4, no. 7 (July 2016): 2649–52. http://dx.doi.org/10.21276/sjams.2016.4.7.73.
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Branco-de-Almeida, L. S., Y. Cruz-Almeida, Y. Gonzalez-Marrero, H. Huang, I. Aukhil, P. Harrison, S. M. Wallet, and L. M. Shaddox. "Local and Plasma Biomarker Profiles in Localized Aggressive Periodontitis." JDR Clinical & Translational Research 2, no. 3 (April 14, 2017): 258–68. http://dx.doi.org/10.1177/2380084417701898.
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Localized aggressive periodontitis (LAP) patients possess a systemic hyperinflammatory response after lipopolysaccharide stimulation. However, the levels of inflammatory and bone biomarkers in plasma, as well as possible associations between local and plasma biomarkers, are unknown in LAP. This cross-sectional study aimed to characterize gingival crevicular fluid (GCF) and plasma biomarker profiles in LAP patients, their healthy siblings (HS), and healthy unrelated controls (HC). Fifty-eight LAP subjects, 33 HS, and 49 HC (African Americans, aged 5 to 25 y) were included. Following collection of clinical parameters with GCF and plasma samples, levels of 16 inflammatory and bone resorption biomarkers were determined with Milliplex. Univariate and correlation analyses were performed among all clinical and laboratorial parameters. Discriminant analyses were used to investigate groups of biomarkers discriminating LAP from HS and HC in GCF and plasma. GCF levels of multiple cytokines and chemokines and RANKL:OPG ratio (receptor activator of nuclear factor kappa-B ligand:osteoprotegerin) were higher in LAP disease, most of which positively correlated with probing depth and attachment loss of sampled sites. A group of IL-12p40, IL-6, IL-12p70, IL-2, and MIP-1α discriminated LAP diseased sites from twheir healthy sites, as well as from HS and HC healthy sites. In plasma, only RANKL levels were increased in LAP versus controls, which positively correlated with the percentage of affected sites and deep/bleeding sites. A plasma inflammatory profile including MIP-1α, IL-8, IL-10, and INF-γ could significantly discriminate LAP patients from HS and HC. No correlations were found between GCF and plasma levels of biomarkers. In conclusion, an inflammatory profile including groups of specific biomarkers in GCF and plasma may significantly discriminate LAP from healthy individuals. The hyperinflammatory response previously found in the peripheral blood of LAP patients is dependent on lipopolysaccharide stimulation, apparently resulting mostly in local tissue destruction and changes in biomarker profile, with a slight influence in the systemic inflammatory profile ( ClinicalTrials.gov NCT01330719). Knowledge Transfer Statement: The results of this study can be possibly used by clinicians in the future as diagnostic tools for localized aggressive periodontitis. Thus, in the future, with proper consideration of cost, patient preference, chair-side feasibility and ultimately further studies validating the role of GCF markers for disease progression and response to treatment, this information could lead to more appropriate therapeutic decisions and the development of preventive approaches for susceptible patients.
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Kalabat, Dalia Y., Allison Vitsky, Wesley Scott, Erick Kindt, Kyle Hayes, Annette John-Baptiste, Wenhu Huang, and Amy H. Yang. "Identification and Evaluation of Novel MicroRNA Biomarkers in Plasma and Feces Associated with Drug-induced Intestinal Toxicity." Toxicologic Pathology 45, no. 2 (July 11, 2016): 302–20. http://dx.doi.org/10.1177/0192623316644992.
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Gastrointestinal toxicity is dose limiting with many therapeutic and anticancer agents. Real-time, noninvasive detection of markers of toxicity in biofluids is advantageous. Ongoing research has revealed microRNAs as potential diagnostic and predictive biomarkers for the detection of select organ toxicities. To study the potential utility of microRNA biomarkers of intestinal injury in a preclinical toxicology species, we evaluated 3 rodent models of drug-induced intestinal toxicity, each with a distinct mechanism of toxicity. MiR-215 and miR-194 were identified as putative intestinal toxicity biomarkers. Both were evaluated in plasma and feces and compared to plasma citrulline, an established intestinal injury biomarker. Following intestinal toxicant dosing, microRNA changes in feces and plasma were detected noninvasively and correlated with histologic evidence of intestinal injury. Fecal miR-215 and miR-194 levels increased, and plasma miR-215 decreased in a dose- and time-dependent manner. Dose-dependent decreases in plasma miR-215 levels also preceded and correlated positively with plasma citrulline modulation, suggesting miR-215 is a more sensitive biomarker. Moreover, during the drug-free recovery phase, plasma miR-215 returned to predose levels, supporting a corresponding recovery of histologic lesions. Despite limitations, this study provides preliminary evidence that select microRNAs have the potential to act as noninvasive, sensitive, and quantitative biomarkers of intestinal injury.
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Aguree, Sixtus, and Alison D. Gernand. "A methodology for examining the association between plasma volume and micronutrient biomarker mass and concentration in healthy eumenorrheic women." PeerJ 8 (December 21, 2020): e10535. http://dx.doi.org/10.7717/peerj.10535.
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Background Accurate estimation and interpretation of nutritional biomarker concentrations are important in nutritional research, clinical care, and public health surveillance. Plasma volume (PV) may affect the interpretation of plasma biomarkers but is rarely measured. We aimed to examine the association between plasma volume (PV) and micronutrient biomarker concentrations and mass as part of pilot work to develop methods. Methods Nine healthy women with regular menstrual cycles provided fasting blood samples to measure micronutrient biomarkers. Indocyanine green was injected, and five timed blood draws were taken from 2 to 5 min to measure PV. Visits were scheduled around menstrual cycle day 2. Retinol, 25-hydroxyvitamin D, riboflavin, alpha-tocopherol, zinc, copper, magnesium, manganese, cobalt, iron, and ferritin concentrations were measured in serum. Total circulating micronutrient biomarker mass was calculated from PV and concentration. Results The mean PV was 2067 ± 470 mL. PV correlated positively with concentration of iron (r = 0.87, P = 0.005); other correlations were weaker with p > 0.05. PV and total mass of retinol (r = 0.90), 25(OH)D (r = 0.75), zinc (r = 0.88), copper (r = 0.83), magnesium (r = 0.93), manganese (r = 0.72), and iron (r = 0.92) were strongly correlated (all p < 0.05). PV was positively correlated with circulating micronutrient mass for most biomarkers, implying that concentrations are maintained at different volumes of plasma. Larger studies are needed to further examine these relationships. Conclusion Though there appear to be some association between micronutrient biomarker mass and plasma volume, we are unable to draw a firm conclusion about any relationship from these results because of the small sample size. We consider these findings as a preliminary analysis to establish methods for future studies.
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Stege, Nienke M., Rudolf A. de Boer, Maarten P. van den Berg, and Herman H. W. Silljé. "The Time Has Come to Explore Plasma Biomarkers in Genetic Cardiomyopathies." International Journal of Molecular Sciences 22, no. 6 (March 14, 2021): 2955. http://dx.doi.org/10.3390/ijms22062955.
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For patients with hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM), screening for pathogenic variants has become standard clinical practice. Genetic cascade screening also allows the identification of relatives that carry the same mutation as the proband, but disease onset and severity in mutation carriers often remains uncertain. Early detection of disease onset may allow timely treatment before irreversible changes are present. Although plasma biomarkers may aid in the prediction of disease onset, monitoring relies predominantly on identifying early clinical symptoms, on imaging techniques like echocardiography (Echo) and cardiac magnetic resonance imaging (CMR), and on (ambulatory) electrocardiography (electrocardiograms (ECGs)). In contrast to most other cardiac diseases, which are explained by a combination of risk factors and comorbidities, genetic cardiomyopathies have a clear primary genetically defined cardiac background. Cardiomyopathy cohorts could therefore have excellent value in biomarker studies and in distinguishing biomarkers related to the primary cardiac disease from those related to extracardiac, secondary organ dysfunction. Despite this advantage, biomarker investigations in cardiomyopathies are still limited, most likely due to the limited number of carriers in the past. Here, we discuss not only the potential use of established plasma biomarkers, including natriuretic peptides and troponins, but also the use of novel biomarkers, such as cardiac autoantibodies in genetic cardiomyopathy, and discuss how we can gauge biomarker studies in cardiomyopathy cohorts for heart failure at large.
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Suh, Ji Hun, Min Chul Park, Peter C. Goughnour, Byung Soh Min, Sang Bum Kim, Woo Yong Lee, Yong Beom Cho, et al. "Plasma Lysyl-tRNA Synthetase 1 (KARS1) as a Novel Diagnostic and Monitoring Biomarker for Colorectal Cancer." Journal of Clinical Medicine 9, no. 2 (February 15, 2020): 533. http://dx.doi.org/10.3390/jcm9020533.
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Colorectal cancer (CRC) is one of the leading causes of world cancer deaths. To improve the survival rate of CRC, diagnosis and post-operative monitoring is necessary. Currently, biomarkers are used for CRC diagnosis and prognosis. However, these biomarkers have limitations of specificity and sensitivity. Levels of plasma lysyl-tRNA synthetase (KARS1), which was reported to be secreted from colon cancer cells by stimuli, along with other secreted aminoacyl-tRNA synthetases (ARSs), were analyzed in CRC and compared with the currently used biomarkers. The KARS1 levels of CRC patients (n = 164) plasma were shown to be higher than those of healthy volunteers (n = 32). The diagnostic values of plasma KARS1 were also evaluated by receiving operating characteristic (ROC) curve. Compared with other biomarkers and ARSs, KARS1 showed the best diagnostic value for CRC. The cancer specificity and burden correlation of plasma KARS1 level were validated using azoxymethane (AOM)/dextran sodium sulfate (DSS) model, and paired pre- and post-surgery CRC patient plasma. In the AOM/DSS model, the plasma level of KARS1 showed high correlation with number of polyps, but not for inflammation. Using paired pre- and post-surgery CRC plasma samples (n = 60), the plasma level of KARS1 was significantly decreased in post-surgery samples. Based on these evidence, KARS1, a surrogate biomarker reflecting CRC burden, can be used as a novel diagnostic and post-operative monitoring biomarker for CRC.
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Sims, Tasha Nicholle, Bo Gao, Robert Phillips, and Israel Lowy. "Potential predictive and prognostic biomarkers identified in baseline plasma samples from the VELOUR trial." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 638. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.638.
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638 Background: Biomarkers of resistance or susceptibility to vascular endothelial growth factor (VEGF) inhibition have not been validated. Ziv-aflibercept (ZALTRAP), a fusion protein that binds and neutralizes ligands of VEGFR1 and VEGFR2 (e.g., VEGFA, PLGF, and VEGFB), is approved for the treatment of metastatic colorectal cancer (mCRC) in combination with FOLFIRI in patients who have progressed after oxaliplatin therapy. We are currently analyzing plasma samples from VELOUR, the registration trial of FOLFIRI +/- ziv-aflibercept, in an effort to identify prognostic and predictive factors. Methods: VELOUR was a prospective, multicenter, multinational, randomized (1:1), double-blind, parallel-arm phase III study conducted in 1,226 patients. Retrospective analysis of circulating proteins from 553 baseline plasma samples was performed. Samples were analyzed for levels of 98 analytes using multiplex assays and ELISA. Biomarker values were dichotomized around the median value and analyzed with respect to overall survival (OS). Results: The biomarker study sub-population was similar to the overall VELOUR population. For OS, the hazard ratio (HR) was 0.809 in the plasma biomarker population vs. HR =0.817 in the overall VELOUR population. For PFS, the HR = 0.752 in the plasma biomarker population vs. HR = 0.758 in VELOUR. Patient demographics, including ECOG status, were similar between the groups. Several biomarkers were identified as potentially predictive or prognostic (or both) of OS, with a HR<0.7 (false discovery rate of 0.05 and interaction p < 0.10). No biomarker subset corresponded to worse OS with ziv-aflibercept treatment. Conclusions: Multiple potential prognostic and predictive biomarkers were identified in VELOUR and will be presented. These results are exploratory and require prospective studies for validation. Patient subsets with elevated expression of alternative angiogenic factors or increased pro-inflammatory markers may correlate with poor outcome overall, and in some cases are not improved by addition of ziv-aflibercept treatment. Further investigation of this dataset continues, including analysis of on-treatment plasma samples in a subset of patients.
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Al-Mshhdani, Basma A., Miranda D. Grounds, Peter G. Arthur, and Jessica R. Terrill. "A Blood Biomarker for Duchenne Muscular Dystrophy Shows That Oxidation State of Albumin Correlates with Protein Oxidation and Damage in Mdx Muscle." Antioxidants 10, no. 8 (August 3, 2021): 1241. http://dx.doi.org/10.3390/antiox10081241.
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Duchenne muscular dystrophy (DMD) is a severe X-linked muscle wasting disease with no cure. While the precise mechanisms of progressive dystropathology remain unclear, oxidative stress caused by excessive generation of oxidants is strongly implicated. Blood biomarkers that could track oxidant levels in tissues would be valuable to measure the effectiveness of clinical treatments for DMD; our research has focused on developing such biomarkers. One target of oxidants that has the potential to be harnessed as a clinical biomarker is the thiol side chain of cysteine 34 (Cys34) of the blood protein albumin. This study using the mdx mouse model of DMD shows that in plasma, albumin Cys34 undergoes thiol oxidation and these changes correlate with levels of protein thiol oxidation and damage of the dystrophic muscles. A comparison with the commonly used biomarker protein carbonylation, confirmed that albumin thiol oxidation is the more sensitive plasma biomarker of oxidative stress occurring in muscle tissue. We show that plasma albumin oxidation reflects muscle dystropathology, as increased after exercise and decreased after taurine treatment of mdx mice. These data support the use of albumin thiol oxidation as a blood biomarker of dystropathology to assist with advancing clinical development of therapies for DMD.
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Sharma, Gautam, Rahul Bijlani, Evangelos Litinas, Debra Hoppensteadt, Josephine Cunanan, Hussein Khan, Gautum Sharma, Inder Kaul, and Jawed Fareed. "Identification of Unique Biomarkers in Sepsis Associated Coagulopathy." Blood 118, no. 21 (November 18, 2011): 1237. http://dx.doi.org/10.1182/blood.v118.21.1237.1237.
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Abstract Abstract 1237 Introduction: Disseminated Intravascular Coagulation represents a complex multi-factorial pathophysiological process in which protease disregulation along with other pathologic processes play an important role. The uncontrolled protease activities result in generation of several mediators which are not fully characterized. Biomarker profiling using protein chip array technology has been used in the identification of unique mediators in various diseases. Surface Enhanced Laser Desorption Ionisation(SELDI) is an ionization method in mass spectrometry that is used for the analysis of protein mixtures and correspondingly in the profiling of biomarkers in various diseases. Purpose: The purpose of this study was to profile and identify unique biomarkers in hospitalized patients with sepsis associated coagulopathy. Study design: There were 385 plasma samples included in this study. Baseline protein chip array profile in Molecular weight range of 0–200 kDa was carried out using SELDI technique employing gold chips. Plasma samples from normal humans (n=100) and pooled preparation from both the normal (NHP) and suspect liver disease/coagulopathy were utilized as controls. Results: Of the 385 baseline samples analyzed 371 patients (96.86%) exhibited the presence of a unique biomarker at 11.6 kDa. In addition down regulation of a biomarker at 56.4 kDa was also noted in 218 of patients (56.74%) In the normal human pooled plasma the 11.6 kDa peak was nearly absent. However in Pathological pooled plasma a distinct biomarker at 11.6 kDa with a much lower intensity was noted. Additional markers in baseline samples in 1–10 kDa range were also noted. Conclusions: These observations suggest that sepsis associated coagulopathy results in the generation of specific unique biomarker at 11.6kDa which requires further characterization. The downregulation of biomarker at 56.4 kDa and the apparent reduction levels during hospitalization require further investigations. Disclosures: No relevant conflicts of interest to declare.
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Chi, Shuhong, Jing Xue, Xiaodong Chen, Xiaoming Liu, and Yanhong Ji. "Correlation of plasma and urine Wnt5A with the disease activity and cutaneous lesion severity in patients with systemic lupus erythematosus." Immunologic Research 70, no. 2 (December 3, 2021): 174–84. http://dx.doi.org/10.1007/s12026-021-09253-w.
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AbstractReliable noninvasive biomarkers are needed to accurately assess disease activity and prognosis in patients with systemic lupus erythematosus (SLE). The purpose of this study was to investigate the clinical relevance of Wnt5A with disease activity and severity with cutaneous involvement in particular in SLE patients; its concentrations in plasma and urine were examined and analyzed. In the cross-sectional study, the clinical relevance of Wnt5A protein was evaluated in both plasma and urine of SLE patients and healthy cohorts using commercial enzyme-linked immunosorbent assays (ELISA). Significantly, more abundances of Wnt5A protein were determined in both of plasmas and urines of SLE patients compared to healthy cohorts (p < 0.0001), which were even higher in active disease (AD) SLE patients relative to low disease activity (LDA) SLE patients (p < 0.0001). Meanwhile, the ROC curve analysis demonstrated that the plasma and urine Wnt5A were potential candidate biomarkers for identifying the disease activity and severity in SLE patients. The discriminant function analysis further revealed that the plasma and urine Wnt5A were separated and distinct for AD SLE patients and healthy controls. In consistence, the disease severity was correlated with the plasma and urine Wnt5A as ascertained by CLASI activity score and the prevalence of serositis in SLE patients. These results suggest that Wnt5A, as a summary measure for different inflammatory processes, could be a potential biomarker for accessing the disease activity, and a noninvasive biomarker for evaluating the disease severity in terms of cutaneous involvement in SLE patients.
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Reitz, Katherine M., Danielle S. Gruen, Frances Guyette, Joshua B. Brown, Mark H. Yazer, Yoram Vodovotz, Pär I. Johanssen, et al. "Age of thawed plasma does not affect clinical outcomes or biomarker expression in patients receiving prehospital thawed plasma: a PAMPer secondary analysis." Trauma Surgery & Acute Care Open 6, no. 1 (February 2021): e000648. http://dx.doi.org/10.1136/tsaco-2020-000648.
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BackgroundPrehospital plasma administration during air medical transport reduces the endotheliopathy of trauma, circulating pro-inflammatory cytokines, and 30-day mortality among traumatically injured patients at risk of hemorrhagic shock. No clinical data currently exists evaluating the age of thawed plasma and its association with clinical outcomes and biomarker expression post-injury.MethodsWe performed a secondary analysis from the prehospital plasma administration randomized controlled trial, PAMPer. We dichotomized the age of thawed plasma creating three groups: standard-care, YOUNG (day 0–1) plasma, and OLD (day 2–5) plasma. We generated HRs and 95% CIs for mortality. Among all patients randomized to plasma, we compared predicted biomarker values at hospital admission (T0) and 24 hours later (T24) controlling for key difference between groups with a multivariable linear regression. Analyses were repeated in a severely injured subgroup.ResultsTwo hundred and seventy-one patients were randomized to standard-care and 230 to plasma (40% YOUNG, 60% OLD). There were no clinically or statistically significant differences in demographics, injury, admission vital signs, or laboratory values including thromboelastography between YOUNG and OLD. Compared with standard-care, YOUNG (HR 0.66 (95% CI 0.41 to 1.07), p=0.09) and OLD (HR 0.64 (95% CI 0.42 to 0.96), p=0.03) plasma demonstrated reduced 30-day mortality. Among those randomized to plasma, plasma age did not affect mortality (HR 1.04 (95% CI 0.60 to 1.82), p=0.90) and/or adjusted serum markers by plasma age at T0 or T24 (p>0.05). However, among the severely injured subgroup, OLD plasma was significantly associated with increased adjusted inflammatory and decreased adjusted endothelial biomarkers at T0.DiscussionAge of thawed plasma does not result in clinical outcome or biomarker expression differences in the overall PAMPer study cohort. There were biomarker expression differences in those patients with severe injury. Definitive investigation is needed to determine if the age of thawed plasma is associated with biomarker expression and outcome differences following traumatic injury.Level of evidenceII.
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Madsen, Marie T. B., Anne A. Bjerregaard, Jeremy D. Furtado, Thorhallur I. Halldorsson, Marin Ström, Charlotta Granström, Edward Giovannucci, and Sjurdur F. Olsen. "Comparisons of Estimated Intakes and Plasma Concentrations of Selected Fatty Acids in Pregnancy." Nutrients 11, no. 3 (March 6, 2019): 568. http://dx.doi.org/10.3390/nu11030568.
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The growing interest in potential health effects of long-chain polyunsaturated fatty acids (PUFAs) makes it important to evaluate the method used to assess the fatty acid intake in nutrition research studies. We aimed to validate the questionnaire-based dietary intake of selected PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), α-linolenic acid (ALA), linoleic acid (LA), and arachidonic acid (AA) within the Danish National Birth Cohort (DNBC), by comparing 345 women’s reported intake with concentration of plasma biomarkers. The applied questionnaire- and biomarker data reflect dietary intake from around the same time point in mid-pregnancy and relationships were investigated by use of Pearson and Spearman correlation and linear regression statistics. We demonstrated moderate but consistent adjusted correlations between dietary intake estimates and the corresponding plasma biomarker concentrations (differences in plasma concentration per 100 mg/day greater intake of 0.05 (95% CI: 0.02; 0.08)) and 0.05 (95% CI: 0.01; 0.08) percentage of total plasma fatty acids for EPA and DHA, respectively). The associations strengthened when restricting the analyses to women with ALA intake below the median intake. We found a weak correlation between the dietary intake of ALA and its plasma biomarker with a difference in plasma concentration of 0.07 (95% CI: 0.03; 0.10) percent of total plasma fatty acids per 1 g/day greater intake, while the dietary intake of LA and AA did not correlate with their corresponding biomarkers.
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Knesek, Michael John, Evangelos Litinas, Cafer Adiguzel, William Hopkinson, Debra Hoppensteadt, Michael Lassen, and Jawed Fareed. "Inflammatory Biomarker Profiling in Elderly Patients With Acute Hip Fracture Treated With Heparins." Clinical and Applied Thrombosis/Hemostasis 16, no. 1 (December 2, 2009): 42–50. http://dx.doi.org/10.1177/1076029609351876.
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Hip fracture is common in the elderly patients with associated high risk of venous thromboembolic complications. Pathogenic activation results in the generation of various surrogate markers in plasma. This study is designed to identify unique biomarkers in elderly patients with hip fracture using protein chip array enzyme-linked immunosorbent assay (ELISA) methods. Plasma from a randomized hip fracture study (PK-532; n = 341) treated with either enoxaparin (40 mg once daily) or unfractionated heparin (UFH; 5000 IU twice daily) were collected prior to and at 1, 3, 5, and 7 days. A total of 52 samples were analyzed using proteomic surface-enhanced laser desorption/ ionization-time of flight (SELDI-TOF) mass spectrometry to identify unique biomarkers in the molecular weight range of 0 to 150 kd. Twenty-nine healthy volunteer’s and pooled plasma from total hip replacement/total knee replacement patients with a unique biomarker at 11.9 kd were used as quality controls. In the 29 healthy individuals, the biomarker profile did not reveal the presence of any unique peak in comparison to the reference normal human plasma (NHP). Plasma obtained prior to surgery exhibits unique biomarkers in 4 of 52 (7.6%) of the samples. On day 1 postoperatively, 41 of 51 (80.3%) showed a distinct peak at 11.9 kd. On day 3, 43 of 49 (87.8%) patients showed the presence of this biomarker most often at its strongest intensity. In all, 22 of 44 (50%) showed this biomarker on day 5 and 4 of 23 (17.9%) on day 7. C-reactive protein (CRP), tumor necrosis factor α (TNF-α), and serum amyloid A were also increased after surgery. Tissue factor pathway inhibitor (TFPI) antigen levels were increased due to the treatment modalities.
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Lagatie, Ole, Emmanuel Njumbe Ediage, Dirk Van Roosbroeck, Stijn Van Asten, Ann Verheyen, Linda Batsa Debrah, Alex Debrah, et al. "Multimodal biomarker discovery for active Onchocerca volvulus infection." PLOS Neglected Tropical Diseases 15, no. 11 (November 29, 2021): e0009999. http://dx.doi.org/10.1371/journal.pntd.0009999.
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The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that 17 million people are infected worldwide, the majority of them living in Africa. Today there are no non-invasive tests available that can detect ongoing infection, and that can be used for effective monitoring of elimination programs. In addition, to enable pharmacodynamic studies with novel macrofilaricide drug candidates, surrogate endpoints and efficacy biomarkers are needed but are non-existent. We describe the use of a multimodal untargeted mass spectrometry-based approach (metabolomics and lipidomics) to identify onchocerciasis-associated metabolites in urine and plasma, and of specific lipid features in plasma of infected individuals (O. volvulus infected cases: 68 individuals with palpable nodules; lymphatic filariasis cases: 8 individuals; non-endemic controls: 20 individuals). This work resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine (CCG) as biomarker for O. volvulus. During the targeted validation study, metabolite-specific cutoffs were determined (inosine: 34.2 ng/ml; hypoxanthine: 1380 ng/ml; CCG: 29.7 ng/ml) and sensitivity and specificity profiles were established. Subsequent evaluation of these biomarkers in a non-endemic population from a different geographical region invalidated the urine metabolite CCG as biomarker for O. volvulus. The plasma metabolites inosine and hypoxanthine were confirmed as biomarkers for filarial infection. With the availability of targeted LC-MS procedures, the full potential of these 2 biomarkers in macrofilaricide clinical trials, MDA efficacy surveys, and epidemiological transmission studies can be investigated.
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Majumder, Mousumi, Kingsley Chukwunonso Ugwuagbo, Sujit Maiti, Peeyush K. Lala, and Muriel Brackstone. "Pri-miR526b and Pri-miR655 Are Potential Blood Biomarkers for Breast Cancer." Cancers 13, no. 15 (July 30, 2021): 3838. http://dx.doi.org/10.3390/cancers13153838.
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We reported that two microRNAs, miR526b and miR655, are oncogenic in breast cancer (BC). Overexpression of these two miRNAs in poorly metastatic BC cells promotes aggressive BC phenotypes in vitro and in vivo. High expression of each miRNA was associated with poor patient survival. In this pilot biomarker study, we report for the first time that miRNA precursor RNAs (pri-miRNAs) are robust and sensitive biomarkers for BC, detectable in both human blood plasma and biopsy tissues. Pri-miRNA detection and quantification do not require a special enrichment procedure, thus reducing specimen quantity. Blood plasma samples from 90 malignant tumor-bearing patients and 20 benign lesion-bearing participants (control) were analyzed for pri-miRNA expression with a quantitative real-time polymerase chain reaction. Results revealed that normalized expressions of plasma pri-miR526b and pri-miR655 are significantly upregulated in malignancy compared to benign plasmas (p = 0.002 and p = 0.03, respectively). Both pri-miRNAs showed more prominent results to distinguish stage I plasmas from benign plasmas (p = 0.001 for pri-miR526b and p = 0.0001 for pri-miR655). We have also validated pri-miRNA expression in independent tumor bank tissues, showing significant upregulation of both pri-miRNAs in BC; thus, pri-miRNAs are robust markers. The diagnostic relevance of pri-miRNAs was computed with the area under the curve (AUC). Pri-miR526b is a sensitive biomarker to distinguish cancer from control plasmas (sensitivity of 86%; AUC = 71.47%, p = 0.0027) with a positive predictive value of 88.89%; however, pri-miR655 did not show significant sensitivity. Furthermore, pri-miR526b could also significantly distinguish tumors as early as stage I from control (sensitivity of 75%; AUC = 72.71%, p = 0.0037). Therefore, pri-miR526b can be used as an early diagnostic biomarker. The expression of both pri-miRNAs was significantly high in ER-positive and HER2-negative subgroups of BC; hence, these biomarkers might play a role in the management of endocrine therapy designs. Additionally, with a case–control cohort study, we identified that high expression of pri-miR526b in the blood is also a risk factor associated with breast cancer (OR = 4.3, CI = 1.39–13.34, p = 0.01). Pri-miRNAs could be considered novel breast cancer blood biomarkers.
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Naveed, Muhammad, Shamsa Mubeen, Abeer Khan, Sehrish Ibrahim, and Bisma Meer. "Plasma Biomarkers: Potent Screeners of Alzheimer’s Disease." American Journal of Alzheimer's Disease & Other Dementias® 34, no. 5 (May 9, 2019): 290–301. http://dx.doi.org/10.1177/1533317519848239.
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Alzheimer’s disease (AD), a neurological disorder, is as a complex chronic disease of brain cell death that usher to cognitive decline and loss of memory. Its prevalence differs according to risk factors associated with it and necropsy performs vital role in its definite diagnosis. The stages of AD vary from preclinical to severe that proceeds to death of patient with no availability of treatment. Biomarker may be a biochemical change that can be recognized by different emerging technologies such as proteomics and metabolomics. Plasma biomarkers, 5-protein classifiers, are readily being used for the diagnosis of AD and can also predict its progression with a great accuracy, specificity, and sensitivity. In this review, upregulation or downregulation of few plasma proteins in patients with AD has also been discussed, when juxtaposed with control, and thus serves as potent biomarker in the diagnosis of AD.
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Kim, Hyeon-Young, Hyeon-Seong Lee, In-Hyeon Kim, Youngbae Kim, Moongi Ji, Songjin Oh, Doo-Young Kim, Wonjae Lee, Sung-Hwan Kim, and Man-Jeong Paik. "Comprehensive Targeted Metabolomic Study in the Lung, Plasma, and Urine of PPE/LPS-Induced COPD Mice Model." International Journal of Molecular Sciences 23, no. 5 (March 2, 2022): 2748. http://dx.doi.org/10.3390/ijms23052748.
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(1) Background: Progression of chronic obstructive pulmonary disease (COPD) leads to irreversible lung damage and inflammatory responses; however, biomarker discovery for monitoring of COPD progression remains challenging. (2) Methods: This study evaluated the metabolic mechanisms and potential biomarkers of COPD through the integrated analysis and receiver operating characteristic (ROC) analysis of metabolic changes in lung, plasma, and urine, and changes in morphological characteristics and pulmonary function in a model of PPE/LPS-induced COPD exacerbation. (3) Results: Metabolic changes in the lungs were evaluated as metabolic reprogramming to counteract the changes caused by the onset of COPD. In plasma, several combinations of phenylalanine, 3-methylhistidine, and polyunsaturated fatty acids have been proposed as potential biomarkers; the α-aminobutyric acid/histidine ratio has also been reported, which is a novel candidate biomarker for COPD. In urine, a combination of succinic acid, isocitric acid, and pyruvic acid has been proposed as a potential biomarker. (4) Conclusions: This study proposed potential biomarkers in plasma and urine that reflect altered lung metabolism in COPD, concurrently with the evaluation of the COPD exacerbation model induced by PPE plus LPS administration. Therefore, understanding these integrative mechanisms provides new insights into the diagnosis, treatment, and severity assessment of COPD.
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Ou, Ya-Nan, Hao Hu, Zuo-Teng Wang, Wei Xu, Lan Tan, and Jin-Tai Yu. "Plasma neurofilament light as a longitudinal biomarker of neurodegeneration in Alzheimer’s disease." Brain Science Advances 5, no. 2 (June 2019): 94–105. http://dx.doi.org/10.1177/2096595820902582.
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Objective: To examine whether plasma neurofilament light (NFL) might be a potential longitudinal biomarker for Alzheimer’s disease (AD). Methods: A total of 835 individuals from the Alzheimer’s Disease Neuroimaging Initiative were involved. Correlations of the rate of change in plasma NFL with cerebrospinal fluid biomarkers, cognition, and brain structure were investigated. Cox proportional hazards models were used to assess the associations between quartiles of plasma NFL and the risk of AD conversion. Results: Participants were further divided into β amyloid-positive (Aβ+) versus β amyloid-negative (Aβ−), resulting in five biomarker group combinations, which are CN Aβ−, CN Aβ+, MCI Aβ−, MCI Aβ+ and AD Aβ+. Plasma NFL concentration markedly increased in the five groups longitudinally ( p < 0.001) with the greatest rate of change in AD Aβ+ group. The rate of change in plasma NFL was associated with cognitive deficits and neuroimaging hallmarks of AD over time ( p < 0.005). Compared with the bottom quartile, the top quartile of change rate was associated with a 5.41-fold increased risk of AD (95% CI = 1.83−16.01) in the multivariate model. Conclusion: Our finding implies the potential of plasma NFL as a longitudinal noninvasive biomarker in AD.
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Lee, Kam-Fai, Ming-Ming Tsai, Chung-Ying Tsai, Chung-Guei Huang, Yu-Hsiang Ou, Ching-Chuan Hsieh, Hsi-Lung Hsieh, Chia-Siu Wang, and Kwang-Huei Lin. "DEK Is a Potential Biomarker Associated with Malignant Phenotype in Gastric Cancer Tissues and Plasma." International Journal of Molecular Sciences 20, no. 22 (November 13, 2019): 5689. http://dx.doi.org/10.3390/ijms20225689.
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Gastric cancer (GC) is the second most widespread cause of cancer-related mortality worldwide. The discovery of novel biomarkers of oncoproteins can facilitate the development of therapeutic strategies for GC treatment. In this study, we identified novel biomarkers by integrating isobaric tags for relative and absolute quantitation (iTRAQ), a human plasma proteome database, and public Oncomine datasets to search for aberrantly expressed oncogene-associated proteins in GC tissues and plasma. One of the most significantly upregulated biomarkers, DEK, was selected and its expression validated. Our immunohistochemistry (IHC) (n = 92) and quantitative real-time polymerase chain reaction (qRT-PCR) (n = 72) analyses disclosed a marked increase in DEK expression in tumor tissue, compared with paired nontumor mucosa. Importantly, significantly higher preoperative plasma DEK levels were detected in GC patients than in healthy controls via enzyme-linked immunosorbent assay (ELISA). In clinicopathological analysis, higher expression of DEK in both tissue and plasma was significantly associated with advanced stage and poorer survival outcomes of GC patients. Data from receiver operating characteristic (ROC) curve analysis disclosed a better diagnostic accuracy of plasma DEK than carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), and C-reactive protein (CRP), highlighting its potential as an effective plasma biomarker for GC. Plasma DEK is also more sensitive in tumor detection than the other three biomarkers. Knockdown of DEK resulted in inhibition of GC cell migration via a mechanism involving modulation of matrix metalloproteinase MMP-2/MMP-9 level and vice versa. Our results collectively support plasma DEK as a useful biomarker for making diagnosis and prognosis of GC patients.
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Park, Jung Eun, Tamil Iniyan Gunasekaran, Yeong Hee Cho, Seong-Min Choi, Min-Kyung Song, Soo Hyun Cho, Jahae Kim, et al. "Diagnostic Blood Biomarkers in Alzheimer’s Disease." Biomedicines 10, no. 1 (January 13, 2022): 169. http://dx.doi.org/10.3390/biomedicines10010169.
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Potential biomarkers for Alzheimer’s disease (AD) include amyloid β1–42 (Aβ1–42), t-Tau, p-Tau181, neurofilament light chain (NFL), and neuroimaging biomarkers. Their combined use is useful for diagnosing and monitoring the progress of AD. Therefore, further development of a combination of these biomarkers is essential. We investigated whether plasma NFL/Aβ1–42 can serve as a plasma-based primary screening biomarker reflecting brain neurodegeneration and amyloid pathology in AD for monitoring disease progression and early diagnosis. We measured the NFL and Aβ1–42 concentrations in the CSF and plasma samples and performed correlation analysis to evaluate the utility of these biomarkers in the early diagnosis and monitoring of AD spectrum disease progression. Pearson’s correlation analysis was used to analyse the associations between the fluid biomarkers and neuroimaging data. The study included 136 participants, classified into five groups: 28 cognitively normal individuals, 23 patients with preclinical AD, 22 amyloid-negative patients with amnestic mild cognitive impairment, 32 patients with prodromal AD, and 31 patients with AD dementia. With disease progression, the NFL concentrations increased and Aβ1–42 concentrations decreased. The plasma and CSF NFL/Aβ1–42 were strongly correlated (r = 0.558). Plasma NFL/Aβ1–42 was strongly correlated with hippocampal volume/intracranial volume (r = 0.409). In early AD, plasma NFL/Aβ1–42 was associated with higher diagnostic accuracy than the individual biomarkers. Moreover, in preclinical AD, plasma NFL/Aβ1–42 changed more rapidly than the CSF t-Tau or p-Tau181 concentrations. Our findings highlight the utility of plasma NFL/Aβ1–42 as a non-invasive plasma-based biomarker for early diagnosis and monitoring of AD spectrum disease progression.
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Lin, Xiaobo, Susan B. Racette, Lina Ma, Michael Wallendorf, Catherine Anderson Spearie, and Richard E. Ostlund. "Plasma Biomarker of Dietary Phytosterol Intake." PLOS ONE 10, no. 2 (February 10, 2015): e0116912. http://dx.doi.org/10.1371/journal.pone.0116912.
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Geyer, Philipp E., Lesca M. Holdt, Daniel Teupser, and Matthias Mann. "Revisiting biomarker discovery by plasma proteomics." Molecular Systems Biology 13, no. 9 (September 2017): 942. http://dx.doi.org/10.15252/msb.20156297.
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Thorsen, Stine, Irina Gromova, Ib Christensen, Simon Fredriksson, Claus Andersen, Hans Nielsen, Jan Stenvang, and José Moreira. "Gel-Based Proteomics of Clinical Samples Identifies Potential Serological Biomarkers for Early Detection of Colorectal Cancer." International Journal of Molecular Sciences 20, no. 23 (December 2, 2019): 6082. http://dx.doi.org/10.3390/ijms20236082.
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The burden of colorectal cancer (CRC) is considerable—approximately 1.8 million people are diagnosed each year with CRC and of these about half will succumb to the disease. In the case of CRC, there is strong evidence that an early diagnosis leads to a better prognosis, with metastatic CRC having a 5-year survival that is only slightly greater than 10% compared with up to 90% for stage I CRC. Clearly, biomarkers for the early detection of CRC would have a major clinical impact. We implemented a coherent gel-based proteomics biomarker discovery platform for the identification of clinically useful biomarkers for the early detection of CRC. Potential protein biomarkers were identified by a 2D gel-based analysis of a cohort composed of 128 CRC and site-matched normal tissue biopsies. Potential biomarkers were prioritized and assays to quantitatively measure plasma expression of the candidate biomarkers were developed. Those biomarkers that fulfilled the preset criteria for technical validity were validated in a case-control set of plasma samples, including 70 patients with CRC, adenomas, or non-cancer diseases and healthy individuals in each group. We identified 63 consistently upregulated polypeptides (factor of four-fold or more) in our proteomics analysis. We selected 10 out of these 63 upregulated polypeptides, and established assays to measure the concentration of each one of the ten biomarkers in plasma samples. Biomarker levels were analyzed in plasma samples from healthy individuals, individuals with adenomas, CRC patients, and patients with non-cancer diseases and we identified one protein, tropomyosin 3 (Tpm3) that could discriminate CRC at a significant level (p = 0.0146). Our results suggest that at least one of the identified proteins, Tpm3, could be used as a biomarker in the early detection of CRC, and further studies should provide unequivocal evidence for the real-life clinical validity and usefulness of Tpm3.
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Khan, OH, and S. Agnihotri. "P.097 Metabolomic and lipidomic profiling of high and low grade gliomas - a matched serum and tissue clinical study." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 46, s1 (June 2019): S39. http://dx.doi.org/10.1017/cjn.2019.192.
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Background: It is well understood that gliomas require vast supply of energy to proliferate, invade and spread. We wished to identify novel biomarkers by comparing normal brain and plasma to high and low grade gliomas using newer techniques in laser ionization mass spectroscopy - precision metabolomics and lipidomics. Methods: Single center IRB approved tissue bank of “normal” brain and plasma (n=6) and IDH wild-type GBM tissue and plamsa (n=29), IDH mutant GBM tissue and plamsa (n=6), Low grade glioma (n=4) tissue and plamsa were analyzed for over 2000 endogenous metbolites and complex lipids. Unbiased clustering and Random Forest plots and pathway analysis were performed with appropriate statsitical analysis (significance p < 0.05). Results: IDH mutant GBM had higher levels of 2-HG, however, plasma 2-HG did not reflect IDH genotype. Changes in glucose and fatty acid utilization were observed in IDH WT and mutant gliomas compared to normal brain tissue. Lipidomics of plasma and tissue of normal and gliomas did not reveal a biomarker reaching statistical significance. Conclusions: We will continue to investigate if plasma and tissue biomarkers including hypotaurine, methionine, branched chain amino acid catabolites and pregnonolone can be used to predict tumor progression, response to treatment and clinical outcomes.
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Jayson, Gordon C., Cong Zhou, Laura Hope Horsley, Kalena Marti, Danielle Shaw, Nerissa Mescallado, Andrew R. Clamp, et al. "Inter-tumor validation, through advanced MRI and circulating biomarkers, of plasma Tie2 as the vascular response biomarker for bevacizumab." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 11521. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.11521.
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11521 Background: VEGF inhibitor (VEGFi) use is compromised by lack of predictive/ response biomarkers. Previously, we identified plasma Tie2 (pTie2) as a vascular response biomarker (VRB) for bevacizumab (bev) in ovarian cancer (OC). Here, we applied dynamic contrast-enhanced MRI (DCE-MRI) and circulating biomarkers in colorectal cancer (CRC), to validate pTie2 as the first tumor VRB. Methods: Seventy patients were recruited, with untreated, mCRC and ≥1 lesion of 3-10cm diameter for DCE-MRI. Patients received bev 10mg/kg for 2 weeks to elicit a biomarker response and then FOLFOX6/bev until progressive disease (PD) Thirteen circulating and 6 imaging biomarkers were measured before and during treatment and at PD. Unsupervised correlation analysis identified bev-induced biomarker correlations. Biomarkers were evaluated by clustered parameter-time course studies to determine their epithelial or vascular origin. Clinical significance was determined by relating the biomarker data to tumor 3D volumetric change assessed by MRI and PFS. The emergent vascular biomarker signal was modelled with epithelial biomarkers to assess the independent contribution of the vascular compartment to PD. Results: Bev induced significant correlations between pTie2, Ang2 and Ktrans. Cluster analysis of Tie2 concentration-time course curves showed that pTie2 reflected tumor Ktransbut not CK18, an epithelial antigen, i.e. changes in pTie2 reflected tumor vascular biology Patients who had the greatest area under the pTie2-time curve had tumors with high Ktransand/or low pVEGFR2, pre-treatment. They also had the greatest reduction in tumor volume and longest PFS. Fusion of pTie2 and CK18 data significantly improved modelling of PD. Conclusions: Bev impacts tumor vasculature causing proportional changes in pTie2. Information from pTie2 adds clinical value to that derived from the epithelial compartment. Thus (i) pTie2 is the first vascular response biomarker for bev and probably all VEGFi and (ii) demonstration of separate vascular and epithelial compartments in ovarian and CRC validates the vascular compartment as a target. This work identifies the first assay that could optimise use of VEGFi. Clinical trial information: 2009-011377-33.
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Rosenberg-Hasson, Yael, Tiffany C. Ho, Tamara D. Simon, Jing Liang, Serena Chang, Iris Herschmann, Ian H. Gotlib, and Holden T. Maecker. "Biomarker Trends: Luminex & Olink, Dried Blood Spots & Plasma." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 159.4. http://dx.doi.org/10.4049/jimmunol.204.supp.159.4.
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Abstract Biomarker discovery is at the forefront of understanding disease etiology, diagnosis and emerging treatments. One of the hurdles is to compare data generated by different platforms and technologies. Measurements of common biomarkers between vendors is another challenge which increases as we multiplex and generate more complex data. We address both these aspects concentrating on two major platforms: Luminex and Olink, in serum and cerebrospinal fluid samples. We find that among 30 overlapping cytokines and chemokines, about 20 display similar trends across these two platforms with comparable sensitivity. A few cytokines had differential and reduced sensitivity in one of these platforms emphasizing the need for improved biomarker detection. Our analysis offers a simple method to compare the data from the two platforms. In addition, we demonstrate the use of Dried Blood Spots as a reliable source for generating multiplex data. We compare plasma and DBS samples and observe similar trends for four out of the six cytokines analyzed, specifically: IL-1b, IFN-g, IL-6 and TNF-a. We discuss limitations of this approach and the need to analyze additional biomarkers in both matrices.
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Khan, Mostafa J., Heather Desaire, Oscar L. Lopez, M. Ilyas Kamboh, and Renã A. S. Robinson. "Why Inclusion Matters for Alzheimer’s Disease Biomarker Discovery in Plasma." Journal of Alzheimer's Disease 79, no. 3 (February 2, 2021): 1327–44. http://dx.doi.org/10.3233/jad-201318.
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Background: African American/Black adults have a disproportionate incidence of Alzheimer’s disease (AD) and are underrepresented in biomarker discovery efforts. Objective: This study aimed to identify potential diagnostic biomarkers for AD using a combination of proteomics and machine learning approaches in a cohort that included African American/Black adults. Methods: We conducted a discovery-based plasma proteomics study on plasma samples (N = 113) obtained from clinically diagnosed AD and cognitively normal adults that were self-reported African American/Black or non-Hispanic White. Sets of differentially-expressed proteins were then classified using a support vector machine (SVM) to identify biomarker candidates. Results: In total, 740 proteins were identified of which, 25 differentially-expressed proteins in AD came from comparisons within a single racial and ethnic background group. Six proteins were differentially-expressed in AD regardless of racial and ethnic background. Supervised classification by SVM yielded an area under the curve (AUC) of 0.91 and accuracy of 86%for differentiating AD in samples from non-Hispanic White adults when trained with differentially-expressed proteins unique to that group. However, the same model yielded an AUC of 0.49 and accuracy of 47%for differentiating AD in samples from African American/Black adults. Other covariates such as age, APOE4 status, sex, and years of education were found to improve the model mostly in the samples from non-Hispanic White adults for classifying AD. Conclusion: These results demonstrate the importance of study designs in AD biomarker discovery, which must include diverse racial and ethnic groups such as African American/Black adults to develop effective biomarkers.
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Kikkeri, Kruthika, Dan Wu, and Joel Voldman. "A sample-to-answer electrochemical biosensor system for biomarker detection." Lab on a Chip 22, no. 1 (2022): 100–107. http://dx.doi.org/10.1039/d1lc00910a.
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We interfaced with a painless blood collection device and integrated on-chip blood-to-plasma separation with an electronic bead-based biomarker detection assay to enable true sample-to-answer detection of biomarkers.
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Weber, Daniel G., Katarzyna Gawrych, Swaantje Casjens, Alexander Brik, Martin Lehnert, Dirk Taeger, Beate Pesch, et al. "Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant Mesothelioma." Disease Markers 2017 (2017): 1–15. http://dx.doi.org/10.1155/2017/9280170.
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The use of circulating microRNAs as biomarkers has opened new opportunities for diagnosis of cancer because microRNAs exhibit tumor-specific expression profiles. The aim of this study was the identification of circulating microRNAs in human plasma as potential biomarkers for the diagnosis of malignant mesothelioma. For discovery, TaqMan Low Density Array Human MicroRNA Cards were used to analyze 377 microRNAs in plasma samples from 21 mesothelioma patients and 21 asbestos-exposed controls. For verification, individual TaqMan microRNA assays were used for quantitative real-time PCR in plasma samples from 22 mesothelioma patients and 44 asbestos-exposed controls. The circulating miR-132-3p showed different expression levels between mesothelioma patients and asbestos-exposed controls. For discrimination, sensitivity of 86% and specificity of 61% were calculated. Circulating miR-132-3p in plasma was not affected by hemolysis and no impact of age or smoking status on miR-132-3p levels could be observed. For the combination of miR-132-3p with the previously described miR-126, sensitivity of 77% and specificity of 86% were calculated. The results of this study indicate that miR-132-3p might be a new promising diagnostic biomarker for malignant mesothelioma. It is indicated that the combination of miR-132-3p with other individual biomarkers improves the biomarker performance.
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Peng, Liyuan, David I. Cantor, Canhua Huang, Kui Wang, Mark S. Baker, and Edouard C. Nice. "Tissue and plasma proteomics for early stage cancer detection." Molecular Omics 14, no. 6 (2018): 405–23. http://dx.doi.org/10.1039/c8mo00126j.
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The pursuit of novel and effective biomarkers is essential in the struggle against cancer, which is a leading cause of mortality worldwide. Here we discuss the relative advantages and disadvantages of the most frequently used proteomics techniques, concentrating on the latest advances and application of tissue and plasma proteomics for novel cancer biomarker discovery.
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Sheinerman, Kira S., Vladimir G. Tsivinsky, Laila Abdullah, Fiona Crawford, and Samuil R. Umansky. "Plasma microRNA biomarkers for detection of mild cognitive impairment: Biomarker Validation Study." Aging 5, no. 12 (December 22, 2013): 925–38. http://dx.doi.org/10.18632/aging.100624.
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Takahari, Daisuke, Takeru Wakatsuki, Tetsuo Mashima, Takashi Ichimura, Keisho Chin, Mariko Ogura, Izuma Nakayama, et al. "Plasma biomarker analysis of ramucirumab in Japanese patients with advanced gastric cancer: Preliminary results." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 72. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.72.
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72 Background: Ramucirumab, anti-VEGFR2 receptor antibody, showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use; however, no validated biomarker has been available until today. The aim of this study is 1) to reveal the dynamics of plasma biomarkers, 2) to assess the associations between these baseline levels or dynamics and efficacy. Methods: Plasma samples were collected at three points: base line, day 8, and after disease progression. Nine kinds of plasma biomarker involved in angiogenesis were measured by means of ELISA. Progression-free survival (PFS) was estimated using Kaplan-Meier methods and compared using the log-rank test. Comparisons of plasma biomarker levels were performed using Mann-Whitney-U test. Results: Samples were collected from 35 patients. Among them, 25 patients were evaluated when analyzed and 6 patients showed disease progression at the first evaluation. In VEGF-A and PlGF, plasma biomarker levels of day 8 were dramatically elevated in all patients; Day8/ baseline ratios were 18.1 folds in VEGF-A and 19.3 folds in PlGF. On the other hand, Day8/ baseline ratio of VEGFR1 and NRP1 were 0.7 and 0.8, respectively. The others appeared to show variable change at day 8. In survival analysis, lower than median Day8/ baseline ratios of VEGF-A were significantly associated with longer PFS with 6.3 months in < median vs. 2.4 months in ≥ median (p = 0.004). In addition, patients with disease progression at the first evaluation by CT showed higher Day8/ baseline ratios of VEGF-C, Angiopoietin 1, and lower baseline NRP1 levels than those of patients with non-disease progression. Conclusions: Dramatic changes of biomarker levels at day 8 were observed among patients in each biomarker. These changes in VEGF-A, C, and Angiopoietin-1 may be candidate predictive marker of ramucirumab in Japanese patients with gastric cancer.
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Ahmed, N., and P. J. Thornalley. "Quantitative screening of protein biomarkers of early glycation, advanced glycation, oxidation and nitrosation in cellular and extracellular proteins by tandem mass spectrometry multiple reaction monitoring." Biochemical Society Transactions 31, no. 6 (December 1, 2003): 1417–22. http://dx.doi.org/10.1042/bst0311417.
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Glycation of proteins forms fructosamines and AGEs (advanced glycation end products). Oxidative and nitrosative stress leads to the formation of oxidative and nitrosative modifications. The modified amino acid residues formed in these processes are biomarkers of protein damage: some are risk markers and some may be risk factors for disease development. We developed a method for the concurrent quantitative measurement of 16 biomarkers indicative of protein glycation, oxidation and nitrosation damage using LC-MS/MS (LC with tandem MS detection). Underivatized analytes were detected free in physiological fluids and in enzymatic hydrolysates of cellular and extracellular proteins. Hydroimidazolones were the most important glycation biomarkers, and methionine sulphoxide was the most important oxidative biomarker quantitatively; 3-nitrotyrosine was the biomarker of nitrosation. Quantitative screening showed high levels of AGEs in cellular protein and moderate levels in protein of blood plasma. Levels of 3-nitrotyrosine were typically 100-fold lower than this. The major glycation adducts in blood plasma had high renal clearances in normal healthy human subjects, whereas methionine sulphoxide and 3-nitrotyrosine had low renal clearances due to further metabolism. Physiological AGEs in blood plasma were eliminated from the circulation in the kidney and not in the liver. LC-MS/MS peptide mapping was also used to locate the protein biomarkers. These studies reveal that advanced glycation is a significant modification of cellular and extracellular protein. The enzymatic defences against glycation, antioxidants and proteasomal protein degradation inside cells are probable factors regulating biomarker levels of cellular protein.
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Escudier, Bernard J., Camillo Porta, Matthew Squires, Cezary Szczylik, Christian K. Kollmannsberger, Bohuslav Melichar, Sun Young Rha, et al. "Biomarker analysis from a phase III trial (GOLD) of dovitinib (Dov) versus sorafenib (Sor) in patients with metastatic renal cell carcinoma after one prior VEGF pathway–targeted therapy and one prior mTOR inhibitor therapy." Journal of Clinical Oncology 32, no. 4_suppl (February 1, 2014): 473. http://dx.doi.org/10.1200/jco.2014.32.4_suppl.473.
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473 Background: In the GOLD trial, Dov did not improve progression-free survival (PFS) or overall survival (OS) over Sor. An exploratory objective of the study was to investigate plasma and tumor biomarkers to predict outcome. Methods: Plasma samples were obtained longitudinally throughout the study, and biomarkers were assessed by immunoassay. Primary archival tumor samples were assessed by immunohistochemistry. Log-rank tests, stratified by baseline MSKCC risk group, for difference in Kaplan-Meier curves between biomarker category (low/high based on </≥ median baseline values) within treatment arm were performed. Hazard ratios (HRs) were estimated from Cox proportional hazards models. Results: Plasma samples were available from 561 patients (Dov, n = 281; Sor, n = 280), and tumor samples were available from 341 patients (Dov, n = 181; Sor, n = 160). Baseline plasma biomarker levels were not predictive of Dov or Sor PFS or OS. However, strong prognostic effects, particularly for OS, were observed. High baseline cKIT and low baseline FGF2, HGF, PlGF, sVEGFR1, VEGFA, and VEGFD were associated with better OS for both Dov and Sor (Table). Changes from baseline in a number of plasma biomarkers were observed following treatment with Dov and Sor, consistent with VEGFR/FGFR inhibitory effects. Prognostic effects were also observed for low FGFR2 (PFS) and low FGF2 (OS) expression in archival tumors. Conclusions: Baseline plasma biomarkers are prognostic but not predictive in the third-line setting. Clinical trial information: NCT01223027. [Table: see text]
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Japp, Nicole C., Joshua J. Souchek, Aaron R. Sasson, Michael A. Hollingsworth, Surinder K. Batra, and Wade M. Junker. "Tumor Biomarker In-Solution Quantification, Standard Production, and Multiplex Detection." Journal of Immunology Research 2021 (September 1, 2021): 1–12. http://dx.doi.org/10.1155/2021/9942605.
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The diagnosis and monitoring of cancer have been facilitated by discovering tumor “biomarkers” and methods to detect their presence. Yet, for certain cancers, we still lack sensitive and specific biomarkers or the means to quantify subtle concentration changes successfully. The identification of new biomarkers of disease and improving the sensitivity of detection will remain key to changing clinical outcomes. Patient liquid biopsies (serum and plasma) are the most easily obtained sources for noninvasive analysis of proteins that tumor cells release directly and via extracellular microvesicles and tumor shedding. Therefore, an emphasis on creating reliable assays using serum/plasma and “direct, in-solution” ELISA approaches has built an industry centered on patient protein biomarker analysis. A need for improved dynamic range and automation has resulted in the application of ELISA principles to paramagnetic beads with chemiluminescent or fluorescent detection. In the clinical testing lab, chemiluminescent paramagnetic assays are run on automated machines that test a single analyte, minimize technical variation, and are not limited by serum sample volumes. This differs slightly from the R&D setting, where serum samples are often limiting; therefore, multiplexing antibodies to test multiple biomarkers in low serum volumes may be preferred. This review summarizes the development of historical biomarker “standards”, paramagnetic particle assay principles, chemiluminescent or fluorescent biomarker detection advancements, and multiplexing for sensitive detection of novel serum biomarkers.
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Janssen, Joëlle J. E., Bart Lagerwaard, Arie G. Nieuwenhuizen, Xavier Escoté, Núria Canela, Josep M. del Bas, Vincent C. J. de Boer, and Jaap Keijer. "Single and Joined Behaviour of Circulating Biomarkers and Metabolic Parameters in High-Fit and Low-Fit Healthy Females." International Journal of Molecular Sciences 24, no. 4 (February 20, 2023): 4202. http://dx.doi.org/10.3390/ijms24044202.
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Biomarkers are important in the assessment of health and disease, but are poorly studied in still healthy individuals with a (potential) different risk for metabolic disease. This study investigated, first, how single biomarkers and metabolic parameters, functional biomarker and metabolic parameter categories, and total biomarker and metabolic parameter profiles behave in young healthy female adults of different aerobic fitness and, second, how these biomarkers and metabolic parameters are affected by recent exercise in these healthy individuals. A total of 102 biomarkers and metabolic parameters were analysed in serum or plasma samples from 30 young, healthy, female adults divided into a high-fit (V̇O2peak ≥ 47 mL/kg/min, N = 15) and a low-fit (V̇O2peak ≤ 37 mL/kg/min, N = 15) group, at baseline and overnight after a single bout of exercise (60 min, 70% V̇O2peak). Our results show that total biomarker and metabolic parameter profiles were similar between high-fit and low-fit females. Recent exercise significantly affected several single biomarkers and metabolic parameters, mostly related to inflammation and lipid metabolism. Furthermore, functional biomarker and metabolic parameter categories corresponded to biomarker and metabolic parameter clusters generated via hierarchical clustering models. In conclusion, this study provides insight into the single and joined behavior of circulating biomarkers and metabolic parameters in healthy females, and identified functional biomarker and metabolic parameter categories that may be used for the characterisation of human health physiology.
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Lele, Abhijit V., Bhunyawee Alunpipatthanachai, Qian Qiu, Crystalyn Clark-Bell, Arraya Watanitanon, Anne Moore, Randall M. Chesnut, William Armstead, and Monica S. Vavilala. "Plasma Levels, Temporal Trends and Clinical Associations between Biomarkers of Inflammation and Vascular Homeostasis after Pediatric Traumatic Brain Injury." Developmental Neuroscience 41, no. 3-4 (2019): 177–92. http://dx.doi.org/10.1159/000502276.
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Expression of inflammatory (interleukin-6 [IL-6]) and vascular homeostatic (angiopoietin-2 [AP-2], endothelin-1 [ET-1], endocan-2 [EC-2]) biomarkers in pediatric traumatic brain injury (TBI) was examined in this prospective, observational cohort study of 28 children hospitalized with mild, moderate, and severe TBI by clinical measures (age, sex, Glasgow Coma Scale score [GCS], Injury Severity Score [ISS], and cerebral autoregulation status). Biomarker patterns suggest an inverse relationship between GCS and AP-2, GCS and IL-6, ISS and ET-1, but a direct relationship between GCS and ET-1 and ISS and AP-2. Biomarker patterns suggest an inverse relationship between AP-2 and ET-1, AP-2 and EC-2, but a direct relationship between AP-2 and IL-6, IL-6 and EC-2, and IL-6 and ET-1. Plasma concentrations of inflammatory and vascular homeostatic biomarkers suggest a role for inflammation and disruption of vascular homeostasis during the first 10 days across the severity spectrum of pediatric TBI. Although not statistically significant, without impact on cerebral autoregulation, biomarker patterns suggest a relationship between inflammation and alterations in vascular homeostasis. The large variation in biomarker levels within TBI severity and age groups, and by sex suggests other contributory factors to biomarker expression.
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Trirahmanto, Addin, Hariyono Winarto, Aria Kekalih, and Ferry Sandra. "Plasma MicroRNA-200c as A Prognostic Biomarker for Epithelial Ovarian Cancer." Indonesian Biomedical Journal 11, no. 3 (December 3, 2019): 267–72. http://dx.doi.org/10.18585/inabj.v11i3.761.
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BACKGROUND: Ovarian cancer is the 8th most prevalent cancer in women in the world. Current biomarker prognosis for ovarian cancer has numerous limitations, thus new biomarkers are needed. MicroRNAs (miRs) are considered as potential biomarkers in ovarian cancer as they are stable in blood. One candidate is miR-200c, the main regulator in epithelial transition to the mesenchyme. The aim of this study is to determine the role of miR-200c as prognostic biomarker for epithelial ovarian cancer (EOC).METHODS: This is a prospective cohort study conducted at Dr. Sardjito Central General Hospital in Yogyakarta from September 2015 to July 2018. Sampling was done using consecutive sampling method. Forty plasma samples of EOC subjects were included in this study. miR-200c expression was quantified using Reverse Transcriptase Quantitative Quantitative Polymerase Chain Reaction (RTqPCR) with miR-16 as the reference gene.RESULTS: The expression of miR-200c was significantly higher in the group of subjects with preoperative CA-125 levels >500 U/mL (p=0.009) than the group of subjects with preoperative CA-125 levels <500 U/mL. Subjects with higher miR-200c expression had lower survival rate than subjects with lower miR-200c expression, although not statistically significant.CONCLUSION: The miR-200c could be a promising biomarker for EOC. Further studies with larger sample sizes are needed to clarify the prognostic value of miR200c.KEYWORDS: miR-200c, epithelial ovarian cancer, prognosis, overall survival
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Muñoz, Colleen X., Evan C. Johnson, Laura J. Kunces, Amy L. McKenzie, Michael Wininger, Cory L. Butts, Aaron Caldwell, et al. "Impact of Nutrient Intake on Hydration Biomarkers Following Exercise and Rehydration Using a Clustering-Based Approach." Nutrients 12, no. 5 (April 30, 2020): 1276. http://dx.doi.org/10.3390/nu12051276.
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We investigated the impact of nutrient intake on hydration biomarkers in cyclists before and after a 161 km ride, including one hour after a 650 mL water bolus consumed post-ride. To control for multicollinearity, we chose a clustering-based, machine learning statistical approach. Five hydration biomarkers (urine color, urine specific gravity, plasma osmolality, plasma copeptin, and body mass change) were configured as raw- and percent change. Linear regressions were used to test for associations between hydration markers and eight predictor terms derived from 19 nutrients merged into a reduced-dimensionality dataset through serial k-means clustering. Most predictor groups showed significant association with at least one hydration biomarker: (1) Glycemic Load + Carbohydrates + Sodium, (2) Protein + Fat + Zinc, (3) Magnesium + Calcium, (4) Pinitol, (5) Caffeine, (6) Fiber + Betaine, and (7) Water; potassium + three polyols, and mannitol + sorbitol showed no significant associations with any hydration biomarker. All five hydration biomarkers were associated with at least one nutrient predictor in at least one configuration. We conclude that in a real-life scenario, some nutrients may serve as mediators of body water, and urine-specific hydration biomarkers may be more responsive to nutrient intake than measures derived from plasma or body mass.