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Abstract : Auto-Analysis for Ki-67 Indices of Breast Cancer Using Specified Computer Software and a Virtual Microscopy
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Abstract: Ki-67 index is one of important markers that is correlated with chemotherapy response and prognosis of breast cancer patients. However, Ki-67 index is not easily provided and are limited by intra-observer error and potentially subjective decision making. We performed this study to develop an objective auto-analysis system to count Ki-67 indices. A total of185 invasive breast cancer cases were used. Immunohistochemical staining was performed using auto-stainer and MIB-1 antibody. The results were stored digitally by virtual microscopy and auto-analyzed by Genie/Aperio software (Vista, CA, USA). As for Ki-67 indices, a good correlation was observed between direct ocular observations and auto-analysis techniques (r = 0.94, p < 0.001). The index examined by auto-analysis was significantly correlated with nuclear atypia, mitotic counts, and nuclear grade of pT1 breast cancers. Auto-analysis of 5 high power fields was better correlated with nuclear grade than that of whole fields. Further, the Ki-67 index was better correlated with mitotic counts than with nuclear atypia.Auto-analysis can provide results concordant with those obtained by direct ocular observation in a short time. Auto-analysis is more likely to result in an objective observation and provide a means by which to standardize methods for immunohistochemical Ki-67 indices of breast cancer. Keywords: Breast cancer, Ki-67, auto-analysis, virtual microscopy, immunohistochemistry, prognosis, objective analysis, nuclear grade. Download Full Article |
Abstract : Exploring Time-Resolved Characterization of the Heterogeneity and Dynamics of Ligand-Receptor Interactions on Living Cells
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Abstract: The time-resolved interaction analysis was applied on living cells to extract detailed interaction characteristics of two therapeutic antibodies and natural ligand binding to the same receptor expressed on two different human carcinoma cell lines. The observed differences in the antibody binding characteristics and heterogeneity could be attributed both to differences in antibodies and cell lines. The stability of antibody binding to EGFR on cells is significantly higher than the binding stability to isolated EGFR. This higher stability can be of fundamental importance as it potentially shifts the drug-target residence time into a domain that is limiting in pharmacokinetics and hence is of importance for in vivo drug efficacy. EGF binding to its receptor was more heterogeneous and it was demonstrated for the first time that time-resolved interaction measurements in combination with Interaction Map analysis could be used to probe the dynamics of a ligand (protein) induced dimerization and/or oligomerization process. Keywords: Cetuximab, EGF receptor, Interaction Map, kinetics, panitumumab, tracer. Download Full Article |
Abstract : Nanoparticles and CNS Delivery of Therapeutic Agents in the Treatment of Primary Brain Tumors
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Abstract: Patients affected by malignant brain tumor present an extremely poor prognosis, notwithstanding improvements in surgery techniques and therapeutic protocols. Late diagnosis and the limitation of conventional therapies are major reasons for this unsolved clinical problem. The blood-brain barrier formed by a complex of endothelial cells, astrocyte and pericytes reduces notably the diffusion of a large number of therapeutic agents. Nanotechnology involves the design, synthesis, and characterization of materials and devices that have a functional organization in at least one dimension on the nanometer scale. The nanoparticles have emerged as potential vectors for brain delivery able to overcome the difficulties of modern strategies. Nanoparticles drug delivery systems can be, also, used to provide targeted delivery of drugs, improve bioavailability, sustains release of drugs for systemic delivery. Moreover, multi-functionality can be engineered into a single nanoplatform so that it can provide tumor-specific detection, treatment, and follow-up monitoring. In this study we will focus on the blood-brain barrier role and possibilities of its therapeutic overcoming. Recent studies of some kinds of nanoparticles systems in brain tumors treatment are summarized. Keywords: Blood-Brain Barrier,Brain Tumors, Glioma, Glioblastoma Multiforme, Nanoparticles. |
Abstract : 99mTc-Labeled Bevacizumab via HYNIC for Imaging of Melanoma
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Abstract: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumour-induced angiogenesis in several types, including melanoma. Bevacizumab, a monoclonal antibody anti-VEGF, could be used as an imaging tool in clinical studies. The aim of this study was to radiolabeled Bevacizumab with 99mTc and evaluate it in vivo imaging properties. Bevacizumab was derivatized with the activated ester succinimidyl-hydrazinonicotinamide hydrochloride (Suc-HYNIC) as a bifunctional coupling agent. A mixture of Tricine/SnCl2.2H2O was added to Bevacizumab-HYNIC and radiolabeled with 99mTcO4-. The radiochemical stability of the radiolabeled sntibody was assessed. Biodistribution studies and SPECT-CT imaging were evaluated in healthy and tumor-bearing C57BL/6J mice at 1, 4 and 24 h (n =5). We demonstrated that 99mTc-HYNIC-Bevacizumab was stable over 24 h in solution and serum. In vivo biodistribution studies revealed tumor-to-muscle ratios of 99mTc-HYNIC-Bevacizumab was 9.28, 17.19 and 8.51 at 1, 4 and 24 h p.i. SPECT/CT imaging of tumor-bearing C57BL/6J mice showed tumor selective uptake of 99mTc-HYNIC-Bevacizumab. 99mTc-HYNIC-Bevacizumab could become a potential radiopharmaceutical to evaluate the expression of vascular endothelial growth factor (VEGF) in solid tumors and could be seen as a clinic tool for the screening of solid tumors that might respond to the Bevacizumab chemotherapy. Keywords: Melanoma, Angiogenesis, Bevacizumab, HYNIC, organic synthesis, technetium-99m.Download Full Article |
