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pubmed-article:14734449pubmed:abstractTextIn a recent study, we presented preliminary evidence for biological activity in a Phase I dose-finding study (15-600 mg/m(2)) of recombinant human endostatin in patients with refractory solid tumors. Here, we conducted additional biomarker analyses to correlate changes in tumor biology with dose. Experimental Design: Excisional tumor biopsies were obtained at baseline and after 56 days of endostatin therapy. Laser scanning cytometry (LSC) was used to quantify biomarker levels in whole tissue sections. Apoptosis in tumor cells (TCs) and tumor-associated endothelial cells (ECs) was quantified by fluorescent three-color anti-CD31/terminal deoxynucleotidyl transferase-mediated nick end labeling staining. Microvessel densities were measured by LSC-guided vessel contouring. Levels of tumor-associated EC BCL-2 and hypoxia-inducible factor 1alpha were determined by immunofluorescence and LSC quantification. The results, including tumor blood flow measured by positron emission tomography, were analyzed using a quadratic polynomial model.lld:pubmed
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pubmed-article:14734449pubmed:articleTitleQuantitative analysis of biomarkers defines an optimal biological dose for recombinant human endostatin in primary human tumors.lld:pubmed
pubmed-article:14734449pubmed:affiliationDepartment of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.lld:pubmed
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