Faculty Bibliography

BACKGROUND: In most studies, circulating biomarkers are usually assessed from a single sample, assuming that this single measurement represents the long-term biomarker status of the individual. Such an assumption is rarely tested although it may not be valid for all biomarkers. The objective of this study was to investigate the temporal reproducibility of a panel of cytokines and growth factors. METHODS: Thirty-five postmenopausal women with two annual visits and 30 premenopausal women with three annual visits were randomly selected from the participants in an existing prospective cohort. A total of 23 serum cytokines, nine growth factors and C-reactive protein (CRP) were measured using the Luminex xMap technology. In addition, for eight biomarkers, regular and high sensitivity (hs) assays were compared. RESULTS: The biomarkers with adequate (>60%) detection rates and acceptable (> or =0.55) intra-class correlation coefficients (ICCs) were: hsIL-1beta, IL-1RA, hsIL-2, hsIL-4, hsIL-5, hsIL-6, hsIL-10, IL-12p40, hsIL-12p70, hsTNF-alpha, TNF-R1, TNF-R2, CRP, HGF, NGF, and EGFR. The remaining biomarkers either had low temporal reproducibility or were undetectable in more than 40% of samples. CONCLUSIONS: The results suggest that 16 of the 41 biomarkers measured with Luminex technology showed sufficient sensitivity and temporal reproducibility in sera

OBJECTIVE: To describe physical symptoms in those local residents, local workers, and cleanup workers who were enrolled in a treatment program and had reported symptoms and exposure to the dust, gas, and fumes released with the destruction of the World Trade Center (WTC) on September 11, 2001. METHODS: Symptomatic individuals underwent standardized evaluation and subsequent treatment. RESULTS: One thousand eight hundred ninety-eight individuals participated in the WTC Environmental Health Center between September 2005 and May 2008. Upper and lower respiratory symptoms that began after September 11, 2001 and persisted at the time of examination were common in each exposure population. Many (31%) had spirometry measurements below the lower limit of normal. CONCLUSIONS: Residents and local workers as well as those with work-associated exposure to WTC dust have new and persistent respiratory symptoms with lung function abnormalities 5 or more years after the WTC destruction

In an 8-year review of ectopic pregnancy (EP) rates in donor egg recipients and standard patients undergoing in vitro fertilization-embryo transfer (IVF-ET) at a large university-based program, we report an EP rate of 0.6% in donor egg recipients and 0.9% in standard IVF patients, a difference that is not statistically significant. Donor egg recipients were found to have a significantly lower incidence of tubal disease compared with standard IVF patients; however, tubal disease was not found to be an independent risk factor for EP in our practice, perhaps owing to aggressive management of tubal disease

T-cell acute lymphoblastic leukaemia (T-ALL) is a blood malignancy afflicting mainly children and adolescents. T-ALL patients present at diagnosis with increased white cell counts and hepatosplenomegaly, and are at an increased risk of central nervous system (CNS) relapse. For that reason, T-ALL patients usually receive cranial irradiation in addition to intensified intrathecal chemotherapy. The marked increase in survival is thought to be worth the considerable side-effects associated with this therapy. Such complications include secondary tumours, neurocognitive deficits, endocrine disorders and growth impairment. Little is known about the mechanism of leukaemic cell infiltration of the CNS, despite its clinical importance. Here we show, using T-ALL animal modelling and gene-expression profiling, that the chemokine receptor CCR7 (ref. 5) is the essential adhesion signal required for the targeting of leukaemic T-cells into the CNS. Ccr7 gene expression is controlled by the activity of the T-ALL oncogene Notch1 and is expressed in human tumours carrying Notch1-activating mutations. Silencing of either CCR7 or its chemokine ligand CCL19 (ref. 6) in an animal model of T-ALL specifically inhibits CNS infiltration. Furthermore, murine CNS-targeting by human T-ALL cells depends on their ability to express CCR7. These studies identify a single chemokine-receptor interaction as a CNS 'entry' signal, and open the way for future pharmacological targeting. Targeted inhibition of CNS involvement in T-ALL could potentially decrease the intensity of CNS-targeted therapy, thus reducing its associated short- and long-term complications

There is a growing interest in the role that cancer biomarkers, metastasis-related molecules, and chemokines may play in the development and progression of various cancers. However, few studies have addressed the reliability of such biomarkers in healthy individuals over time. The objective of this study was to investigate the temporal reliability of multiple proteins in serum samples from healthy women who donated blood over successive years. Thirty five, postmenopausal women with two, repeated annual visits, and thirty, premenopausal women with three, repeated annual visits were randomly selected among eligible subjects from an existing, prospective cohort. Multiplexing Luminex xMAPTM technology was used to measure the levels of 55 serum proteins representing cancer antigens, chemokines, angiogenic and anti-angiogenic factors, proteases, adipokines, apoptotic molecules, and other markers in these women. The biomarkers with high detection rates (> 60%) and acceptable reliability (intraclass correlation coefficient, ICCs > or = 0.55) using xMAPTM method were: cancer antigens: AFP, CA 15-3, CEA, CA-125, SCC, SAA; growth factors/related molecules: ErbB2, IGFBP-1; proteases and adhesion molecules: MMP-1, 8, 9, sE-selectin, human kallikreins (KLK) 8,10, ICAM-1, VCAM-1, chemokines: fractalkine, MCP-1,2, RANTES, MIP-1alpha, MIP-1beta, Eotaxin, GRO-alpha, IP-10; inhibitors of angiogenesis: angiostatin and endostatin; adipokines leptin and resistin; apoptotic factor: Fas, and other proteins mesothelin, myeloperoxidase (MPO), and PAI-1. The rest of the biomarkers under investigation either had ICCs less than 0.55 or had low levels of detection (< 60%). These included cancer antigens: CA 19-9, CA 72-4, MICA, S100, TTR, ULBP1, ULBP2, ULBP3; proteases: MMP 2, 3, 7, 12, 13; chemokines: MCP-3, MIF, MIG; adipokines: leptin and resistin; apoptotic factors: FasL, DR5, Cyfra 21-1; and inhibitors of angiogenesis and other markers: thrombospondin and heat shock protein (HSP) 27. In conclusion, 34 out of the 55 biomarkers investigated were present in detectable levels in > 60% of the samples, and with an ICC > or = 0.55, indicating that a single serum measurement can be used in prospective epidemiological studies using the xMAPTM method