Overexpression of RKIP mimics NO in tumor cells-induced sensitization to apoptosis. The induction of RKIP by NO was the result of the inhibition of the RKIP repressor, Snail, downstream of NF-kappa B. These findings established the presence of a dysregulated NF-kappa B/Snail/YY1/ RKIP circuitry in resistance and that treatment with NO modifies this loop in tumor cells in favor of the inhibition of tumor cell survival and the response to cytotoxic drugs. Noteworthy, the NF-kappa B/Snail/YY1/RKIP loop consists of gene products that regulate the
epithelial to mesenchymal Selleckchem INCB28060 transition (EMT) and, thus, tumor metastasis. Hence, we have found that treatment of metastatic cancer cell lines with DETANONOate inhibited the EMT phenotype, through both the inhibition of the metastasis-inducers, NF-kappa B and Snail and the induction of the metastasis-suppressor, Selleck GSK2245840 RKIP. Altogether, the above findings establish, for the first time, the dual role of high levels of NO in the sensitization of tumor cells to apoptotic stimuli as well as inhibition
of EMT. Hence, NO donors may be considered as novel potential therapeutic agents with dual roles in the treatment of patients with refractory cancer and in the prevention of the initiation of the metastatic cascade via EMT. (C) 2010 Elsevier Inc. All rights reserved.”
“Objective: The aim of this study was to assess the angiographic results of the radial artery as a coronary bypass conduit at long term (>5 years).
Methods: Radial artery grafts were controlled in 202 patients at 10.1 years by conventional angiography Methane monooxygenase (n = 79) and computed tomography (n = 123). Clinical or paraclinical evidence of ischemia was noted in 81 patients, whereas
121 patients were asymptomatic. Some 520 conduits were controlled: radial artery (n = 230), left internal thoracic artery (n = 190), right internal thoracic artery (n = 30), and veins (n = 70). Radial arteries were anastomosed to the right coronary (24%), marginal (58%), diagonal (16%), and left anterior descending (<1%) arteries, whereas left internal thoracic arteries were primarily anastomosed to the left anterior descending artery (95%). The mean number of antithrombotic and anti-anginal medications was 1.2 and 1.9 per patient, respectively.
Results: The ejection fraction was slightly decreased compared with its preoperative value (54% +/- 11% vs 57% +/- 9%; P = .009). Nine reoperations were required at 10.5 years for valve replacement (n = and isolated bypass (n = 1). Percutaneous intervention was performed in 48 patients (24%) at 7.6 years on a graft (28%) or a native coronary artery (72%). The 10-year patency of radial artery grafts was 83%, which was lower than the patency of left internal thoracic arteries (95%, P < .001) and similar to the patency of right internal thoracic arteries (87%, P = .66) and veins (81%, P = .50).