20 research outputs found
Peroxiredoxin 2: a potential biomarker for early diagnosis of Hepatitis B Virus related liver fibrosis identified by proteomic analysis of the plasma
N′,2-Diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists
The development and maintenance of spatial patterns and the way they affect the dynamics of populations and ecosystems is a key issue in ecology. Since each individual and each species experiences the environment on a unique range of scales, it is vital to determine the spatial scales across which organisms interact with each other and the structuring influence of their environments, which can be achieved by analyzing species’ distribution patterns. Here, the spatial variation in the distribution of <i>Scrobicularia plana</i> is described for 4 intertidal areas along the species’ distributional range. Spatial autocorrelation correlograms based on Moran’s coefficient reveal that while the Trondheim (Norway) population was randomly distributed, at Minho (Portugal), the Westerschelde, and the Wadden Sea (both in The Netherlands) populations were aggregated. Patch diameter varied from 150 to 1250 m, in Minho and Westerschelde, respectively; while in the Wadden Sea, patches of 4 to 10 km were detected. Comparisons of spatial patterns with those of other co-occurring bivalve species (<i>Abra tenuis</i>, <i>Cerastoderma edule</i>, and <i>Macoma balthica</i>) revealed that <i>S. plana</i>’s distribution was generally patchier. The distribution of <i>S. plana</i> was correlated with sediment type at Westerschelde and Trondheim, but not Minho. The observed differences in distribution patterns and their correlation with environmental factors reveal that spatial patterns of <i>S. plana</i> are site-specific rather than species-specific
Zr-89-Lumretuzumab PET Imaging before and during HER3 Antibody Lumretuzumab Treatment in Patients with Solid Tumors
Purpose: We evaluated biodistribution and tumor targeting of Zr-89-lumretuzumab before and during treatment with lumretuzumab, a human epidermal growth factor receptor 3 (HER3)targeting monoclonal antibody. Experimental Design: Twenty patients with histologically confirmed HER3-expressing tumors received Zr-89-lumretuzumab and underwent positron emission tomography (PET). In part A, (89)-Zr-lumretuzumab was given with additional, escalating doses of unlabeled lumretuzumab, and scans were performed 2, 4, and 7 days after injection to determine optimal imaging conditions. In part B, patients were scanned following tracer injection before (baseline) and after a pharmacodynamic (PD)-active lumretuzumab dose for saturation analysis. HER3 expression was determined immunohistochemically in skin biopsies. Tracer uptake was calculated as standardized uptake value (SUV). Results: Optimal PET conditions were found to be 4 and 7 days after administration of Zr-89-lumretuzumab with 100-mg unlabeled lumretuzumab. At baseline using 100-mg unlabeled lumretuzumab, the tumor SUVmax was 3.4(+/- 1.9) at 4 days after injection. SUVmean values for normal blood, liver, lung, and brain tissues were 4.9, 6.4, 0.9 and 0.2, respectively. Saturation analysis (n = 7) showed that 4 days after lumretuzumab administration, tumor uptake decreased by 11.9% (+/- 8.2), 10.0% (+/- 16.5), and 24.6% (+/- 20.9) at PD-active doses of 400, 800, and 1,600 mg, respectively, when compared with baseline. Membranous HER3 was completely downregulated in paired skin biopsies already at and above 400-mg lumretuzumab. Conclusions: PET imaging showed biodistribution and tumor-specific Zr-89-lumretuzumab uptake. Although, PD-active lumretuzumab doses decreased Zr-89-lumretuzumab uptake, there was no clear evidence of tumor saturation by PET imaging as the tumor SUV did not plateau with increasing doses. (C) 2017 AACR
Obinutuzumab (GA101) Monotherapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma or Mantle-Cell Lymphoma: Results From the Phase II GAUGUIN Study
Fluorometric evaluation of CYP3A4 expression using improved transgenic HepaRG cells carrying a dual-colour reporter for CYP3A4 and CYP3A7
Phase Ib Study of Lumretuzumab Plus Cetuximab or Erlotinib in Solid Tumor Patients and Evaluation of HER3 and Heregulin as Potential Biomarkers of Clinical Activity
AbstractPurpose: This study investigated the safety, clinical activity, and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas.Experimental Design: The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively. In both parts, patients received lumretuzumab doses from 400 to 2,000 mg plus cetuximab or erlotinib according to standard posology, respectively. The effect of HRG mRNA and HER3 mRNA and protein expression were investigated in a dedicated extension cohort of squamous non–small cell lung cancer (sqNSCLC) patients treated with lumretuzumab and erlotinib.Results: Altogether, 120 patients were treated. One dose-limiting toxicity (DLT) in the cetuximab part and two DLTs in the erlotinib part were reported. The most frequent adverse events were gastrointestinal and skin toxicities, which were manageable. The objective response rate (ORR) was 6.1% in the cetuximab part and 4.2% in the erlotinib part. In the sqNSCLC extension cohort of the erlotinib part, higher tumor HRG and HER3 mRNA levels were associated with a numerically higher disease control rate but not ORR.Conclusions: The toxicity profile of lumretuzumab in combination with cetuximab and erlotinib was manageable, but only modest clinical activity was observed across tumor types. In the sqNSCLC cohort, there was no evidence of meaningful clinical benefit despite enriching for tumors with higher HRG mRNA expression levels. Clin Cancer Res; 23(18); 5406–15. ©2017 AACR.</jats:p