Temporal reliability of cytokines and growth factors in EDTA plasma

Background. Cytokines are involved in the development of chronic diseases, including cancer. It is important to evaluate the temporal reproducibility of cytokines in plasma prior to conducting epidemiologic studies utilizing these markers. Findings. We assessed the temporal reliability of CRP, 22 cytokines and their soluble receptors (IL-1α, ILβ-1, IL-1RA, IL-2, sIL-2R, IL-4, IL-5, IL-6, sIL-6R, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, TNFα, sTNF-R1, sTNF-R2, IFNα, IFNγ) and eight growth factors (GM-CSF, EGF, bFGF, G-CSF, HGF, VEGF, EGFR, ErbB2) in repeated EDTA plasma samples collected an average of two years apart from 18 healthy women (age range: 42-62) enrolled in a prospective cohort study. We also estimated the correlation between serum and plasma biomarker levels using 18 paired clinical samples from postmenopausal women (age range: 75-86). Twenty-six assays were able to detect their analytes in at least 70% of samples. Of those 26 assays, we observed moderate to high intra-class correlation coefficients (ICCs)(ranging from 0.53-0.89) for 22 assays, and low ICCs (0-0.47) for four assays. Serum and plasma levels were highly correlated (r > 0.6) for most markers, except for seven assays (r < 0.5). Conclusions. For 22 of the 31 biomarkers, a single plasma measurement is a reliable estimate of a woman's average level over a two-year period. © 2010 Clendenen et al; licensee BioMed Central Ltd

Happiness economics

There is enough evidence to be confident that individuals are able and willing to provide a meaningful answer when asked to value on a finite scale their satisfaction with their own lives, a question that psychologists have long and often posed to respondents of large questionnaires. Without taking its limitations and criticisms too lightly, some economists have been using thismeasure of self-reported satisfaction as a proxy for utility so as to contribute to a better understanding of individuals' tastes and hopefully behavior. By means of satisfaction questions we can elicit information on individual likes and dislikes over a large set of relevant issues, such as income, working status and job amenities, the risk of becoming unemployed, inflation, and health status. This information can be used to evaluate existing ideas from a new perspective, understand individual behavior, evaluate and design public policies, study poverty and inequality, and develop a preference based valuation method. In this article I first critically assess the pros and cons of using satisfaction variables, and then discuss its main applications

Circulating mediators of inflammation and immune activation in AIDS-related non-Hodgkin lymphoma

Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries. An elevated risk of developing NHL persists among HIV-infected individuals in comparison to the general population despite the advent of effective antiretroviral therapy. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods: This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male subjects diagnosed with high-grade B-cell NHL. Controls were matched to each case from among participating HIV-positive males who did not develop any malignancy. Matching criteria included time HIV+ or since AIDS diagnosis, age, race and CD4+ cell count. Sera were tested for 161 serum biomarkers using multiplexed beadbased immunoassays. Results: A subset of 17 biomarkers, including cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators was identified to be significantly altered in A-NHL cases in comparison to controls. Many of the biomarkers included in this subset were positively correlated with HIV viral load. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions: These findings support the current hypothesis that A-NHL develops in the context of persistent immune stimulation and inflammation. Further analysis of the biomarkers identified in this report should enhance our ability to diagnose, monitor and treat this disease. © 2014 Nolen et al

Phase II biomarker trial of a multimarker diagnostic for ovarian cancer

The primary hypothesis to be tested in this study was that the diagnostic performance (as assessed by the area under the receiver operator characteristic curve, AUC) of a multianalyte panel to correctly identify women with ovarian cancer was significantly greater than that for CA-125 alone

Evaluation of midkine and anterior gradient 2 in a multimarker panel for the detection of ovarian cancer

The aims of this study were: to characterise and compare plasma concentrations of midkine (MDK) in normal healthy women with concentrations observed in women with ovarian cancer; and to establish and compare the performance of MDK with that of anterior gradient 2 protein (AGR2) and CA125 in the development of multi-analyte classification algorithms for ovarian cancer. Median plasma concentrations of immunoreactive MDK, AGR2 and CA125 were significantly greater in the case cohort (909 pg/ml, 765 pg/ml and 502 U/ml, respectively n = 46) than in the control cohort (383 pg/ml, 188 pg/ml and 13 U/ml, respectively n = 61) (p < 0.001). The area under the receiver operator characteristic curve (AUC) for MDK and AGR2 was not significantly different (0.734 ± 0.046 and 0.784 ± 0.049, respectively, mean ± SE) but were both significantly less than the AUC for CA125 (0.934 ± 0.030, p < 0.003). When subjected to stochastic gradient boosted logistic regression modelling, the AUC of the multi-analyte panel (MDK, AGR2 and CA125, 0.988 ± 0.010) was significantly greater than that of CA125 alone (0.934 ± 0.030, p = 0.035). The sensitivity and specificity of the multi-analyte algorithm were 95.2 and 97.7%, respectively. Within the study cohort, CA125 displayed a sensitivity and specificity of 87.0 and 94.6%, respectively. The data obtained in this study confirm that both MDK and AGR2 individually display utility as biomarkers for ovarian cancer and that in a multi-analyte panel significantly improve the diagnostic utility of CA125 in symptomatic women

Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Ginger (<it>Zingiber officinale </it>Rosc) is a natural dietary component with antioxidant and anticarcinogenic properties. The ginger component [6]-gingerol has been shown to exert anti-inflammatory effects through mediation of NF-κB. NF-κB can be constitutively activated in epithelial ovarian cancer cells and may contribute towards increased transcription and translation of angiogenic factors. In the present study, we investigated the effect of ginger on tumor cell growth and modulation of angiogenic factors in ovarian cancer cells <it>in vitro</it>.</p> <p>Methods</p> <p>The effect of ginger and the major ginger components on cell growth was determined in a panel of epithelial ovarian cancer cell lines. Activation of NF-κB and and production of VEGF and IL-8 was determined in the presence or absence of ginger.</p> <p>Results</p> <p>Ginger treatment of cultured ovarian cancer cells induced profound growth inhibition in all cell lines tested. We found that <it>in vitro</it>, 6-shogaol is the most active of the individual ginger components tested. Ginger treatment resulted in inhibition of NF-kB activation as well as diminished secretion of VEGF and IL-8.</p> <p>Conclusion</p> <p>Ginger inhibits growth and modulates secretion of angiogenic factors in ovarian cancer cells. The use of dietary agents such as ginger may have potential in the treatment and prevention of ovarian cancer.</p

Do serum biomarkers really measure breast cancer?

Background Because screening mammography for breast cancer is less effective for premenopausal women, we investigated the feasibility of a diagnostic blood test using serum proteins. Methods This study used a set of 98 serum proteins and chose diagnostically relevant subsets via various feature-selection techniques. Because of significant noise in the data set, we applied iterated Bayesian model averaging to account for model selection uncertainty and to improve generalization performance. We assessed generalization performance using leave-one-out cross-validation (LOOCV) and receiver operating characteristic (ROC) curve analysis. Results The classifiers were able to distinguish normal tissue from breast cancer with a classification performance of AUC = 0.82 ± 0.04 with the proteins MIF, MMP-9, and MPO. The classifiers distinguished normal tissue from benign lesions similarly at AUC = 0.80 ± 0.05. However, the serum proteins of benign and malignant lesions were indistinguishable (AUC = 0.55 ± 0.06). The classification tasks of normal vs. cancer and normal vs. benign selected the same top feature: MIF, which suggests that the biomarkers indicated inflammatory response rather than cancer. Conclusion Overall, the selected serum proteins showed moderate ability for detecting lesions. However, they are probably more indicative of secondary effects such as inflammation rather than specific for malignancy.United States. Dept. of Defense. Breast Cancer Research Program (Grant No. W81XWH-05-1-0292)National Institutes of Health (U.S.) (R01 CA-112437-01)National Institutes of Health (U.S.) (NIH CA 84955

Intravenous and isolated limb perfusion delivery of wild type and a tumor-selective replicating mutant vaccinia virus in nonhuman primates

In this study we examine the safety, feasibility, and biodistribution of a tumor-selective mutant vaccinia ( vvDD) and wild-type WR ( vF13) vaccinia after delivery via intradermal or intravenous infection or isolated limb perfusion ( ILP) in rhesus macaques. By intradermal inoculation, 10(6) PFU of vvDD caused a minimal skin reaction whereas vF13 caused marked erythema and necrosis with a peak indurated area of 108 cm(2). By intravenous delivery, vvDD caused no clinical symptoms of viremia and no viral recovery from tissues, serum, saliva, urine, or feces. In contrast, vF13 caused symptoms of lethargy, anorexia, fever, and signs of viremia. Delivery of vF13 via ILP resulted in numerous cutaneous pox lesions localized solely to the perfused limb with high viral recovery in the perfused skin and muscle. ILP with vvDD resulted in no visible pox lesions and no clinical signs or symptoms of viremia. No long-term toxicity was identified after ILP with 10(9) PFU of vvDD, and no virus was recovered from any tissue, serum, saliva, urine, or fecal sample. These results suggest that vvDD appears to be safe in primates, and thus vvDD should be further investigated for clinical trial in human cancer patients