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1.  Detection of Vulnerable Atherosclerotic Plaque and Prediction of Thrombosis Events in a Rabbit Model Using 18F-FDG -PET/CT 
PLoS ONE  2013;8(4):e61140.
Detection of vulnerable plaques could be clinically significant in the prevention of cardiovascular events. We aimed to compare Fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in vulnerable and stable plaques, and investigate the feasibility of predicting thrombosis events using Positron Emission Tomography/Computed Tomography (PET/CT) angiography.
Atherosclerosis was induced in 23 male New Zealand white rabbits. The rabbits underwent pharmacological triggering to induce thrombosis. A pre-triggered PET/CTA scan and a post-triggered PET/CTA scan were respectively performed. 18F-FDG uptake by the aorta was expressed as maximal standardized uptake value (SUVmax) and mean SUV (SUVmean). SUVs were measured on serial 7.5 mm arterial segments.
Thrombosis was identified in 15 of 23 rabbits. The pre-triggered SUVmean and SUVmax were 0.768±0.111 and 0.804±0.120, respectively, in the arterial segments with stable plaque, and 1.097±0.189 and 1.229±0.290, respectively, in the arterial segments with vulnerable plaque (P<0.001, respectively). The post-triggered SUVmean and SUVmax were 0.849±0.167 and 0.906±0.191, respectively in the arterial segments without thrombosis, and 1.152±0.258 and 1.294±0.313, respectively in the arterial segments with thrombosis (P<0.001, respectively). The values of SUVmean in the pre-triggered arterial segments were used to plot a receiver operating characteristic curve (ROC) for predicting thrombosis events. Area under the curve (AUC) was 0.898. Maximal sensitivity and specificity (75.4% and 88.5%, respectively) were obtained when SUVmean was 0.882.
Vulnerable and stable plaques can be distinguished by quantitative analysis of 18F-FDG uptake in the arterial segments in this rabbit model. PET/CT may be used for predicting thrombosis events and risk-stratification in patients with atherosclerotic disease.
PMCID: PMC3629173  PMID: 23613798
2.  Synergy between Proteasome Inhibitors and Imatinib Mesylate in Chronic Myeloid Leukemia 
PLoS ONE  2009;4(7):e6257.
Resistance developed by leukemic cells, unsatisfactory efficacy on patients with chronic myeloid leukemia (CML) at accelerated and blastic phases, and potential cardiotoxity, have been limitations for imatinib mesylate (IM) in treating CML. Whether low dose IM in combination with agents of distinct but related mechanisms could be one of the strategies to overcome these concerns warrants careful investigation.
Methods and Findings
We tested the therapeutic efficacies as well as adverse effects of low dose IM in combination with proteasome inhibitor, Bortezomib (BOR) or proteasome inhibitor I (PSI), in two CML murine models, and investigated possible mechanisms of action on CML cells. Our results demonstrated that low dose IM in combination with BOR exerted satisfactory efficacy in prolongation of life span and inhibition of tumor growth in mice, and did not cause cardiotoxicity or body weight loss. Consistently, BOR and PSI enhanced IM-induced inhibition of long-term clonogenic activity and short-term cell growth of CML stem/progenitor cells, and potentiated IM-caused inhibition of proliferation and induction of apoptosis of BCR-ABL+ cells. IM/BOR and IM/PSI inhibited Bcl-2, increased cytoplasmic cytochrome C, and activated caspases. While exerting suppressive effects on BCR-ABL, E2F1, and β-catenin, IM/BOR and IM/PSI inhibited proteasomal degradation of protein phosphatase 2A (PP2A), leading to a re-activation of this important negative regulator of BCR-ABL. In addition, both combination therapties inhibited Bruton's tyrosine kinase via suppression of NFκB.
These data suggest that combined use of tyrosine kinase inhibitor and proteasome inhibitor might be helpful for optimizing CML treatment.
PMCID: PMC2705802  PMID: 19606213

Results 1-2 (2)