Biomarkers

Induced theta activity as a biomarker for alcoholism in long-term abstinent alcoholics

by Casey Gilmore

Casey S. Gilmore & George Fein. Under review.

Event-related, target stimulus-phase-locked (evoked) brain activity in both the time and time-frequency (TF) domains... more Event-related, target stimulus-phase-locked (evoked) brain activity in both the time and time-frequency (TF) domains (the P3b ERP; evoked theta oscillations) has been shown to be reduced in alcoholics. Recently, studies have suggested that there is alcohol-related information in the non-stimulus-phase-locked (induced) theta TF activity. We applied TF analysis to target stimulus event-related EEG recorded during an oddball task from 41 long-term abstinent alcoholics (LTAA) and 71 non-alcoholic controls (NAC) to investigate the relationship between P3b, evoked theta, and induced theta activity. Results showed that induced theta 1) was larger in LTAA compared to NAC, and 2) was sensitive to differences between LTAA and NAC groups that was independent of the differences accounted for by P3b amplitude or evoked theta. These findings suggest that increased induced theta may likely be a biomarker for the effects of alcohol abuse on brain function.

Application of Genomic and Proteomic Technologies in Biomarker Discovery

by Elana Fertig

EJ Fertig, R Slebos, and CH Chung. Application of Genomic and Proteomic Technologies in Biomarker Discovery. In: Govindan R, ed. 2012 ASCO Educational Book. Alexandria, VA: American Society of Clinical Oncology; 2012;377-382.

Overview: Sequencing of the human genome was completed in 2001. Building on the technology and experience of... more Overview: Sequencing of the human genome was completed in 2001. Building on the technology and experience of whole-exome sequencing, numerous cancer genomes have been sequenced, including head and neck squamous cell carcinoma (HNSCC) in 2011. Although DNA sequencing data reveals a complex genome with numerous mutations, the biologic interaction and clinical significance of the overall genetic aberrations are largely unknown. Comprehensive analyses of the tumors using genomics and proteomics beyond sequencing data can potentially accelerate the rate and number of biomarker discoveries to improve biology-driven classification of tumors for prognosis and patient selection for a specific therapy. In this review, we will summarize the current genomic and proteomic technologies, general biomarker-discovery paradigms using the technology and published data in HNSCC---including potential clinical applications and limitations.

Filingeri, D., Proia, P., Bianco, A., Schiera, G., Saladino, P., Pomara, F., Petrucci, M., Traina, M., Palma, A. (2011). Monitoring biomarkers during preseason preparation period in professional soccer players. Italian Journal Of Anatomy and Embryology. 116(2), 73.

by Davide Filingeri

Exercise intervention and inflammatory markers in coronary artery disease: a meta-analysis

by Walter Swardfager

Swardfager W, Herrmann N, Cornish S, Mazereeuw G, Marzolini S, Sham L, Lanctôt KL. Am Heart J 2012;163:666-676.e3

Background: Inflammatory activity plays a role in the development and progression of coronary artery disease (CAD),... more Background: Inflammatory activity plays a role in the development and progression of coronary artery disease (CAD), and exercise confers survival benefit. We performed a meta-analysis of changes in inflammatory biomarkers over the course of exercise interventions in patients with CAD.

Methods: We searched MEDLINE, Embase, the Cochrane Collaboration, AMED, and CINAHL for studies reporting peripheral inflammatory biomarker concentrations before and after exercise interventions of ≥2 weeks in patients with CAD. Data were summarized using standard mean differences (SMD) and 95% CIs.

Results: Twenty-three studies were included. Concentrations of C-reactive protein (CRP; SMD −0.345, 95% CI −0.444 to −0.246, n = 1,466, P < .001), interleukin 6 (SMD −0.546, 95% CI −0.739 to −0.353, n = 280, P < .001), fibrinogen (SMD −0.638, 95% CI −0.953 to −0.323, n = 247, P < .001), and vascular cell adhesion molecule 1 (SMD −0.413, 95% CI −0.778 to −0.048, n = 187, P = .027) were lower postintervention. Higher total cholesterol (B = −0.328, 95% CI −0.612 to −0.043, P = .026) and higher total/high-density lipoprotein cholesterol ratios (B = −0.250, 95% CI −0.425 to −0.076, P = .008) at baseline were associated with greater reductions in CRP. In controlled studies, follow-up concentrations of CRP (SMD −0.500, 95% CI −0.844 to −0.157, nexercise/control = 485/284, P = .004), and fibrinogen (SMD −0.544, 95% CI −1.058 to −0.030, nexercise/control = 148/100, P = .038) were lower in subjects who exercised compared with controls.

Conclusion: Exercise training is associated with reduced inflammatory activity in patients with CAD. C-reactive protein and fibrinogen have provided the strongest evidence. Higher baseline CRP and adverse baseline lipid profiles predicted greater reductions in CRP.

Absorption and Fluorescence Properties of Oligothiophene Biomarkers from Long-Range-Corrected Time-Dependent Density Functional Theory

by Bryan Wong

Physical Chemistry Chemical Physics, 11, 4498 (2009)

Performance of Aβ1-40, Aβ1-42, Total Tau, and Phosphorylated Tau as Predictors of Dementia in a Cohort of Patients with Mild Cognitive Impairment

by Paolo Eusebi

Parnetti L, Chiasserini D, Eusebi P, Giannandrea D, Bellomo G, De Carlo C, Padiglioni C, Mastrocola S, Lisetti V, Calabresi P.
J Alzheimers Dis. 2012 Jan 9. [Epub ahead of print]

Mild cognitive impairment (MCI) is a common condition in the elderly which may remain stable along time (MCI-MCI) or... more Mild cognitive impairment (MCI) is a common condition in the elderly which may remain stable along time (MCI-MCI) or evolve into Alzheimer's disease (MCI-AD) or other dementias. Cerebrospinal fluid (CSF) classical biomarkers, i.e., amyloid-β 1-42 (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) reflect the neuropathological changes taking place in AD brains, thus disclosing the disease in its prodromal phase. With the aim to evaluate the power of each biomarker and/or their combination in predicting AD progression, we have measured CSF Aβ1-40, Aβ1-42, t-tau, and p-tau in patients with AD, MCI-MCI, MCI-AD, and other neurological diseases without dementia (OND) followed up for four years. Aβ1-42 levels were significantly lower in AD and MCI-AD than in MCI-MCI. T-tau and p-tau levels were significantly increased in AD and MCI-AD versus OND and MCI-MCI. The Aβ1-42/Aβ1-40 ratio showed a significant decrease in AD and MCI-AD as compared to MCI-MCI. Both Aβ1-42/t-tau and Aβ1-42/p-tau ratios showed significantly decreased values in AD and MCI-AD with respect to OND and MCI-MCI. Aβ1-42/p-tau ratio was the best parameter for discriminating MCI-AD from MCI-MCI (sensitivity 81%, specificity 95%), being also correlated with the annual change rate in the Mini Mental State Examination annual change rate score (MMSE-ACR, rS = −0.71, p < 0.0001). Survival analysis showed that 81% of MCI with a low Aβ1-42/p-tau ratio (<1372) progressed to AD. The best model of logistic regression analysis retained Aβ1-42 and p-tau (sensitivity 75%, 95%CI: 70–80%; specificity 96%, 95%CI: 94–98%). We can conclude that Aβ1-42 and p-tau reliably predict conversion to AD in MCI patients.

A sandwich enzyme-linked immunosorbent assay for adducts of polycyclic aromatic hydrocarbons with human serum albumin

by (Jake) Ming Kei Chung

Strengthening of North American dust sources during the late Pliocene (2.7 Ma)

by David Naafs

Published in Earth and Planetary Science Letters

Here we present orbitally-resolved records of terrestrial higher plant leaf wax input to the North Atlantic over the... more Here we present orbitally-resolved records of terrestrial higher plant leaf wax input to the North Atlantic over the last 3.5 Ma, based on the accumulation of long-chain n-alkanes and n-alkanl-1-ols at IODP Site U1313. These lipids are a major component of dust, even in remote ocean areas, and have a predominantly aeolian origin in distal marine sediments. Our results demonstrate that around 2.7 million years ago (Ma), coinciding with the intensification of the Northern Hemisphere glaciation (NHG), the aeolian input of terrestrial material to the North Atlantic increased drastically. Since then, during every glacial the aeolian input of higher plant material was up to 30 times higher than during interglacials. The close correspondence between aeolian input to the North Atlantic and other dust records indicates a globally uniform response of dust
sources to Quaternary climate variability, although the amplitude of variation differs among areas. We argue that the increased aeolian input at Site U1313 during glacials is predominantly related to the episodic appearance of continental ice sheets in North America and the associated strengthening of glaciogenic dust sources. Evolutional spectral analyses of the n-alkane records were therefore used to determine the dominant
astronomical forcing in North American ice sheet advances. These results demonstrate that during the early Pleistocene North American ice sheet dynamics responded predominantly to variations in obliquity (41 ka), which argues against previous suggestions of precession-related variations in Northern Hemisphere ice sheets during the early Pleistocene.

Multiplexed profiling of secreted proteins for the detection of potential space biomarkers.

by Winnok H. De Vos

B. Dieriks(1), W. De Vos(1), M. Ghardi, M. Moreels, R. Hennekam, J. Broers, S. Baatout and P. Van Oostveldt.
Molecular Medicine Reports 4, 17-23, 2011.
(1equal contribution, first author).

Space travel exposes astronauts to a plethora of potentially detrimental conditions, such as cosmic radiation and... more Space travel exposes astronauts to a plethora of potentially detrimental conditions, such as cosmic radiation and microgravity. As both factors are hard to simulate on Earth, present knowledge remains limited. However, this knowledge is of vital importance, making space flight experiments a necessity for determining the biological effects and the underlying biochemical processes, especially when keeping future long-term interplanetary missions in mind. Instead of estimating the long-term effects, which usually implicate severe endpoints (e.g., cancer) and which are often difficult to attribute, research has shifted to finding representative biomarkers for rapid and sensitive detection of individual radiosensitivity. In this context, an appealing set of candidate markers is the group of secreted proteins, as they exert an intercellular signaling function and are easy to assess. We screened a subset of secreted proteins in cells exposed to space travel by means of multiplex bead array analysis. To determine the cell-specific signatures of the secreted molecules, we compared the conditioned medium of normal fibroblast cells to fibroblasts isolated from a patient with Hutchinson-Gilford Progeria syndrome, which are known to have a perturbed nuclear architecture and DNA damage response. Out of the 88 molecules screened, 20 showed a significant level increase or decrease, with a differential response to space conditions between the two cell types. Among the molecules that were retained, which may prove to be valuable biomarkers, are apolipoprotein C-III, plasminogen activator inhibitor type 1, β-2-microglobulin, ferritin, MMP-3, TIMP-1 and VEGF.

Factors influencing the metabolite pattern of urinary arsenic following exposure via drinking water

by Giovanni Leonardi

Lindberg, A.L.; Goessler, W.; Leonardi, G.; Rahman, M.; Person, L.A.; Ekstrom, E.C.; Kumar, R.; Vahter, M.
Toxicology Letters, 2006; 164:S199-S200

Evidence for depression and schizophrenia in speech prosody

by Roi Kliper

Could the Health Decline of Prehistoric California Indians be Related to Exposure to Polycyclic Aromatic Hydrocarbons (PAHs) from Natural Bitumen?

by sebastian wärmländer

Immune biomarkers in relation to exposure to particulate matter: a cross-sectional survey in 17 cities of Central Europe

by Giovanni Leonardi

Multi-disciplinary evidence of the Holocene history of a cultivated floodplain area in the wetlands of northern Colombia

by Arnoud Boom

Utility of osteopontin as a biomarker in recurrent epithelial ovarian cancer

by K Brakora

Objective. Osteopontin (OPN) is overexpressed in tumors and serum of ovarian cancer patients and may serve as a... more Objective. Osteopontin (OPN) is overexpressed in tumors and serum of ovarian cancer patients and may serve as a biomarker. To evaluate the utility of serum osteopontin in monitoring disease status, we evaluated 234 serum samples from post-oophorectomy patients with ovarian cancer and 38 samples from healthy controls.

Methods. Serum samples were collected from 203 women with recurrent ovarian cancer and 31 newly diagnosed women participating in an experimental chemotherapeutic clinical trial. Controls included 11 young healthy women and 27 peri- or postmenopausal women without ovarian cancer. Samples were assayed for osteopontin using an enzyme-linked immunosorbent assay (ELISA) kit. Statistical analyses for group comparisons of biomarker distribution used the nonparametric Wilcoxon's rank sum test for two-group comparisons and the Kruskal–Wallis test for three-group comparisons.

Results. Osteopontin values ranged from 25 to 1463 ng/ml for patients and 25 to 617 ng/ml for controls. Mean patient levels were lower than mean control levels (74 ng/ml vs. 147 ng/ml, respectively, P = 0.0006). Serum osteopontin levels correlated with recurrent disease versus remission (68 ng/ml vs. 34 ng/ml, P = 0.0034), presence of ascites versus absence (71 ng/ml vs. 53 ng/ml, P = 0.0002), and bulky disease vs. nonbulky disease (75 ng/ml vs. 38 ng/ml, P = 0.0005). CA-125 values yielded the same trends with greater statistical difference.

Conclusions. These results demonstrate that serum osteopontin concentrations in post-oophorectomy patients with recurrent ovarian cancer are not greater than in healthy controls. Nevertheless, within this heterogeneous patient population, the values do correlate with bulk of disease. The potential utility of this assay in monitoring women with CA-125 negative disease is worthy of exploration.

Richard D. Pancost, Sarah Pressley, Joanna M. Coleman, Liane G. Benning and B. W. Mountain (2005) Lipid biomolecules in silica sinters: indicators of microbial biodiversity Environmental Microbiology 7(1), 66–77.

by Liane G. Benning

Serum leptin: A marker of prostate cancer irrespective of obesity

by Vivekanand Jha

Co-authored with Singh SK, Grifson JJ, Mavuduru RS, Agarwal MM, Mandal AK,
Cancer Biomark. 2010 Jan 1;7(1):11-5.

Introduction: High expression of leptin receptors have been observed in the prostate cancer in various clinical... more Introduction: High expression of leptin receptors have been observed in the prostate cancer in various clinical studies; however the association of serum leptin with carcinoma prostate remains unresolved. We studied association, between serum leptin and carcinoma prostate in Asian (Indian) population and its association with obesity. Material and methods: 30 prospective cases of cancer prostate and 30 age matched controls were included in this study. Body mass index (BMI) was estimated and categorized in 4 groups by WHO criteria. Waist hip ratio (WHR) was calculated and divided into three groups. Serum leptin was estimated by sandwich ELISA technique (DRG leptin ELISA kit, Marburg, Germany). Results: Both the groups were comparable for age, WHR and BMI. Serum leptin was significantly higher in patients with cancer prostate as compared to controls (median 14.18 ng/ml vs. 1.63 ng/ml; p< 0.001). The level of leptin was found to have positive correlation with BMI and WHR in controls (r=0.485, p=0.007; r=0.314, p=0.091, respectively) however, no correlation was observed in patients with cancer prostate (r=0.071, p=0.711; r=0.067, p=0.725, respectively). There was no correlation between leptin and PSA. The serum leptin level was not related to the Gleason's score and stage of the carcinoma. Conclusions: This study shows that Prostate cancer is associated with raised serum leptin which is independent of obesity and serum PSA. It hints the role of leptin in pathogenesis of this tumor. It may not be a surrogate marker of aggressiveness. For validation, further studies including a large patient population is required.

Decreased glutathione content and glutathione S-transferase activity in red blood cells of coal miners with early stages of pneumoconiosis.

by Chris Evelo

C T Evelo, R P Bos, P J Borm (1993)  Decreased glutathione content and glutathione S-transferase activity in red blood cells of coal miners with early stages of pneumoconiosis.  Br J Ind Med 50: 7. 633-636 Jul

Blood samples of miners heavily exposed to coal dust were examined for changes in glutathione S-transferase (GST)... more Blood samples of miners heavily exposed to coal dust were examined for changes in glutathione S-transferase (GST) activity. Decreased GST activity was found in red blood cells of subjects with early stages of coal workers' pneumoconiosis (International Labour Office classification 0/1-1/2) when compared with control miners. At further progression of coal workers' pneumoconiosis (> or = 2/1), the activity of GST was not different from controls. In the same group with moderate coal workers' pneumoconiosis a decrease in GSH in red blood cells occurred. Decreases in GST activity in early stages of coal workers' pneumoconiosis, as well as the decreases in glutathione peroxidase (GPx) activity and in GSH concentrations reported earlier, may originate from damage caused by reactive oxygen species. These changes might imply an impairment of the detoxification capacity for electrophilic and oxidative compounds during this stage of the disease.