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Saint Paul, MN, United States

Choueiri T.K.,Harvard University | Figueroa D.J.,Glaxosmithkline | Fay A.P.,Harvard University | Signoretti S.,Harvard University | And 9 more authors.
Clinical Cancer Research | Year: 2015

Purpose: The interaction of programmed death-1 ligand (PDL1) with its receptor (PD-1) on T cells inactivates antitumor immune responses. PD-L1 expression has been associated with poor outcomes in renal cell carcinoma (RCC) but has not been investigated in advanced RCC patients receiving VEGF-targeted therapy. Experimental Design: Formalin-fixed paraffin-embedded specimens were collected at baseline from patients in the COMPARZ trial. Tumor cell PD-L1 expression by IHC was evaluated using Hscore (HS). Dual PD-L1/CD68 staining was used to differentiate PD-L1 tumor expression from tumor-associated macrophages. Intratumor CD8-positive T cells were quantified morphometrically. Associations between biomarkers and survival were investigated using the log-rank test. Results: HS data were available from 453 of 1, 110 patients. Sixty-four percent of patients had negative PD-L1 expression (HS =0). Patients with HS > 55 (n =59, 13%) had significantly shorter overall survival (OS) than those with HS ≤ 55 in both pazopanib and sunitinib arms (median 15.1 vs. 35.6 and 15.3 vs. 27.8 months, respectively, P =0.03). In both arms, median OS was shortest in patients with HS > 55 and intratumor CD8-positive T-cell counts > 300 (9.6 and 11.9 months with pazopanib and sunitinib, respectively). Median OS in patients with HS ≤ 55 and CD8-positive T-cell counts ≤ 300 was 36.8 and 28.0 months with pazopanib and sunitinib, respectively. Progression-free survival results were similar to OS results. Conclusions: Increased tumor cell PD-L1, or PD-L1 plus tumor CD8-positive T-cell counts, were associated with shorter survival in patients with metastatic RCC receiving VEGF-targeted agents. These findings may have implications for future design of randomized clinical trials in advanced RCC. Clin Cancer Res; 21(5); 1071-7. © 2014 AACR. Source


Joseph A.,University of Minnesota | Spector L.,University of Minnesota | Wickham K.,University of Minnesota | Janis G.,MedTox Laboratories | And 3 more authors.
American Journal of Public Health | Year: 2013

Objectives. We assessed tobacco smoke exposure (TSE), defined according to detection of cotinine, in dried blood spots collected fromchildren for lead screening. Methods. Dried blood spots collected from a national sample of 1541 Black and White children and submitted to a commercial laboratory for lead analysis were analyzed for cotinine. We used an anonymous administrative data set including information on children's characteristics to conduct univariate and multivariate analyses. Results. Cotinine was detected in 61% of dried blood spots; 17% of samples had cotinine levels above 3 nanograms per gram. Median cotinine levels were significantly higher among Black than White children (0.66 ng/g vs 0.30 ng/g) and among Medicaid recipients (0.94 ng/g vs < 0.3 ng/g). In multivariate analyses, significant increases in cotinine levels were associated with Black (vs White) race, older age, Medicaid coverage, higher state smoking rate, and higher average winter temperature. Detectable cotinine levels were significantly associated with higher lead levels. Conclusions. TSE is highly prevalent among children undergoing lead screening, and exposure levels are greater among Black children and children on Medicaid. TSE may contribute to lead exposure. Concurrent lead screening and biological screening for TSE may be a feasible approach to increasing childhood TSE detection. Source


Lowes S.,Advion BioServices Inc. | Jersey J.,Agilux Laboratories | Shoup R.,AIT Bioscience | Garofolo F.,Algorithme Pharma Inc. | And 34 more authors.
Bioanalysis | Year: 2012

The Global CRO Council for Bioanalysis (GCC) was formed in September 2010. Since then, the representatives of the member companies come together periodically to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. The 4th GCC Closed Forum brought together experts from bioanalytical CROs to share and discuss recent issues in regulated bioanalysis, such as the impact of coadministered drugs on stability, some differences between European Medicines Agency and US FDA bioanalytical guidance documents and lessons learned following recent Untitled Letters. Recent 483s and agency findings, as well as issues on method carryover, were also part of the topics discussed. © 2012 Future Science Ltd. Source


Lowes S.,Advion BioServices Inc. | Jersey J.,Agilux Laboratories | Shoup R.,AIT Bioscience | Garofolo F.,Algorithme Pharma Inc. | And 40 more authors.
Bioanalysis | Year: 2011

The Global CRO Council (GCC) for Bioanalysis was formed in an effort to bring together many CRO leaders to openly discuss bioanalysis and the regulatory challenges unique to the outsourcing industry. © 2011 Future Science Ltd. Source


Lowes S.,Quintiles | Boterman M.,ABL | Doig M.,ABS Laboratories | Breda M.,Accelera | And 86 more authors.
Bioanalysis | Year: 2012

An open letter written by the Global CRO Council for Bioanalysis (GCC) describing the GCC survey results on stability data from co-administered and co-formulated drugs was sent to multiple regulatory authorities on 14 December 2011. This letter and further discussions at different GCC meetings led to subsequent recommendations on this topic of widespread interest within the bioanalytical community over the past 2 years. © 2012 Future Science Ltd. Source

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