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Abstract Background α-Enolase (ENO1) is a key glycolytic enzyme implicated in the development of many human cancers including breast cancer. Increased expression of ENO1 has recently been reported in estrogen (ER)-positive human breast cancer patients. The present study examined the expression of ENO1 and assessed its significance in canine mammary carcinoma. Results Immunohistochemical staining was employed to investigate the expression of ENO1 in 82 cases of canine mammary tumor (32 benign tumors and 50 carcinomas). Quantification of immunohistochemistry was carried out using Quick score and the results showed cytoplasmic ENO1 overexpression in 9 of the 50 carcinomas (18%). Overexpression of ENO1 correlated significantly with shorter cause-specific survival (P = 0.019), but was not associated with ER positivity in canine mammary carcinoma. Conclusions Our findings suggest that overexpression of ENO1 may be used as a prognostic marker for poor outcome in canine mammary carcinoma.

The development of rapid and sensitive methods for the detection of immunogenic tumor-associated antigen is important not only for understanding their roles in cancer immunology but also for the development of clinical diagnostics, [alpha]-Enolase (ENO1), a p48 molecule, is widely distributed in a variety of tissues, whereas [gamma]-enolase (ENO2) and [beta]-enolase (ENO3) are found exclusively in neuron/neuroendocrine and muscle tissues, respectively. Because ENO1 has been correlated with small cell lung cancer, nonsmall cell lung cancer, and head and neck cancer, it can be used as a potential diagnostic marker for lung cancer. In this study, we developed a simple, yet novel and sensitive, electrochemical sandwich immunosensor for the detection of ENO1; it operates through physisorption of anti-ENO1 monoclonal antibody on polyethylene glycol-modified disposable screen-printed electrode as the detection platform, with polyclonal secondary anti-ENO1-hagged, gold nanoparticle (AuNP) congregates as electrochemical signal probes. The immunorecognition of the sample ENO1 by the congregated AuNP@antibody occurred on the surface of the electrodes; the electrochemical signal from the bound AuNP congregates was obtained after oxidizing them in 0.1 M HCl at 1.2 V for 120 s, followed by the reduction of Au[Cl.sup.4] in square wave voltammetry (SWV) mode. The resulting sigmoidally shaped dose--response curves possessed a linear dynamic working range from [10.sup.-8] to [10.sup.-12] g/mL. This AuNP congregate-based assay provides an amplification approach for detecting ENO1 at trace levels, leading to a detection limit as low as 11.9 fg (equivalent to 5 [micro]L of a 2.38 pg/mL solution). 10.1021/ac1001959

1. Introduction Atherosclerosis is a chronic inflammatory disease. The recruitment of inflammatory cells is an essential step in the development and progression of the disease. It is well documented that [...], Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1) is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8), a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-α-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-α stimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-α induced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis. Copyright © 2009 Chaur-Jong Hu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Gastrointestinal stromal tumor (GIST) is a type of KIT‐driven cancer. KIT gene mutations are found in approximately 80% of GISTs, and most of these mutations occur in exon 9 and exon 11. Imatinib has been successfully used as a first‐line treatment for advanced GIST, with a significant improvement in progression‐free survival (PFS) and overall survival. However, disease progression might develop due to primary or secondary resistance to imatinib. Sunitinib and regorafenib have been approved as second‐ and third‐line treatments for advanced GIST patients, with median PFS values of 6.8 and 4.8 months, respectively. However, these relatively modest improvements in PFS underscore the need for more effective KIT inhibitors. BPR1J373 is a multitargeted kinase inhibitor that has been shown to inhibit the proliferation of KIT‐driven acute myeloid leukemia cells in vitro and in vivo. In this study, we found that BPR1J373 inhibited proliferation and induced apoptosis by targeting KIT in GIST cells with KIT gene mutations. BPR1J373 also induced cell cycle arrest and senescent change in KIT‐mutant GIST48 cells, probably by targeting aurora kinase A. In the KIT‐null COS‐1 cell‐based system, BPR1J373 effectively inhibited KIT with single or double mutations of KIT developed in GIST. The antiproliferative effect was also consistently evident in GIST430 tumor‐grafted mice. The results suggest that BPR1J373 could be a potential anticancer drug for GIST and deserves further investigation for clinical applications. Our study shows that BPR1J373 effectively inhibits the proliferation of KIT‐mutated gastrointestinal stromal tumor in vitro and in vivo. It is a potential anticancer drug and deserves further investigation for its applications in clinical use. [ABSTRACT FROM AUTHOR]