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1.  Overexpression of Aurora-C interferes with the spindle checkpoint by promoting the degradation of Aurora-B 
Cell Death & Disease  2014;5(3):e1106-.
The chromosomal passenger complex (CPC) plays a pivotal role in controlling accurate chromosome segregation and cytokinesis during cell division. Aurora-B, one of the chromosomal passenger proteins, is important for the mitotic spindle assembly checkpoint (SAC). Previous reports noted that Aurora-C is predominantly expressed in male germ cells and has the same subcellular localization as Aurora-B. Increasing evidence indicates that Aurora-C is overexpressed in many somatic cancers, although its function is uncertain. Our previous study showed that the aberrant expression of Aurora-C increases the tumorigenicity of cancer cells. Here, we demonstrate that overexpressed Aurora-C displaces the centromeric localization of CPCs, including INCENP, survivin, and Aurora-B. When cells were treated with nocodazole to turn on SAC, both the Aurora-B protein stability and kinase activity were affected by overexpressed Aurora-C. As a result, the activation of spindle checkpoint protein, BubR1, and phosphorylation of histone H3 and MCAK were also eliminated in Aurora-C-overexpressing cells. Thus, our results suggest that aberrantly expressed Aurora-C in somatic cancer cells may impair SAC by displacing the centromeric localization of CPCs.
PMCID: PMC3973241  PMID: 24603334
Aurora-C; Aurora-B; spindle assembly checkpoint; chromosomal passenger proteins
2.  A positive feedback loop between EBP2 and c-Myc regulates rDNA transcription, cell proliferation, and tumorigenesis 
Liao, P | Wang, W | Shen, M | Pan, W | Zhang, K | Wang, R | Chen, T | Chen, Y | Chen, H | Wang, P
Cell Death & Disease  2014;5(1):e1032-.
The oncoprotein c-Myc is a key transcription factor with essential functions in the nucleolus (NO) to regulate ribosomal RNA (rRNA) synthesis, ribosome biogenesis, and cell proliferation. Yet, the mechanism that regulates the distribution and function of nucleolar c-Myc is still not completely understood. In this study, we identified nucleolar protein ENBA1 binding protein 2 (EBP2) as a novel functional binding partner of c-Myc. We found that coexpression of EBP2 markedly relocalized c-Myc from the nucleus to the NO, whereas depletion of EBP2 reduced the nucleolar distribution of c-Myc. Further study indicated that EBP2 is a direct binding partner of c-Myc and can block the degradation of c-Myc in a FBW7 (F-box and WD repeat domain containing 7)-independent manner. Moreover, EBP2 is a transcriptional target of c-Myc. c-Myc can bind to the promoter of EBP2 and positively regulate the EBP2 expression. Both protein and mRNA levels of EBP2 are upregulated in lung cancer samples and positively correlated with c-Myc expression. Functionally, EBP2 promotes c-Myc-mediated rRNA synthesis and cell proliferation. Collectively, our study indicates that EBP2 is a novel binding partner of c-Myc that regulates the function of nucleolar c-Myc, cell proliferation, and tumorigenesis via a positive feedback loop.
PMCID: PMC4040698  PMID: 24481446
c-Myc; EBP2; translocation; rDNA; lung cancer
3.  High STOP-Bang score indicates a high probability of obstructive sleep apnoea 
BJA: British Journal of Anaesthesia  2012;108(5):768-775.
The STOP-Bang questionnaire is used to screen patients for obstructive sleep apnoea (OSA). We evaluated the association between STOP-Bang scores and the probability of OSA.
After Institutional Review Board approval, patients who visited the preoperative clinics for a scheduled inpatient surgery were approached for informed consent. Patients answered STOP questionnaire and underwent either laboratory or portable polysomnography (PSG). PSG recordings were scored manually. The BMI, age, neck circumference, and gender (Bang) were documented. Over 4 yr, 6369 patients were approached and 1312 (20.6%) consented. Of them, 930 completed PSG, and 746 patients with complete data on PSG and STOP-Bang questionnaire were included for data analysis.
The median age of 746 patients was 60 yr, 49% males, BMI 30 kg m−2, and neck circumference 39 cm. OSA was present in 68.4% with 29.9% mild, 20.5% moderate, and 18.0% severe OSA. For a STOP-Bang score of 5, the odds ratio (OR) for moderate/severe and severe OSA was 4.8 and 10.4, respectively. For STOP-Bang 6, the OR for moderate/severe and severe OSA was 6.3 and 11.6, respectively. For STOP-Bang 7 and 8, the OR for moderate/severe and severe OSA was 6.9 and 14.9, respectively. The predicted probabilities for moderate/severe OSA increased from 0.36 to 0.60 as the STOP-Bang score increased from 3 to 7 and 8.
In the surgical population, a STOP-Bang score of 5–8 identified patients with high probability of moderate/severe OSA. The STOP-Bang score can help the healthcare team to stratify patients for unrecognized OSA, practice perioperative precautions, or triage patients for diagnosis and treatment.
PMCID: PMC3325050  PMID: 22401881
mass screening; obstructive/ep (epidemiology); polysomnography; prospective studies; questionnaires; sleep apnoea; snoring/di (diagnosis); snoring/ep (epidemiology)
4.  Mesenchymal stem cell as salvage treatment for refractory chronic GVHD 
Bone Marrow Transplantation  2010;45(12):1732-1740.
Refractory chronic GVHD (cGVHD) is an important complication after allogeneic hematopoietic SCT and is prognostic of poor outcome. MSCs are involved in tissue repair and modulating immune responses in vitro and in vivo. From April 2005 to October 2008, 19 patients with refractory cGVHD were treated with MSCs derived from the BM of volunteers. The median dose of MSCs was 0.6 × 106 cells per kg body weight. Fourteen of 19 patients (73.7%) responded well to MSCs, achieving a CR (n=4) or a PR (n=10). The immunosuppressive agent could be tapered to less than 50% of the starting dose in 5 of 14 surviving patients, and five patients could discontinue immunosuppressive agents. The median duration between MSC administration and immunosuppressive therapy discontinuation was 324 days (range, 200–550 days). No patients experienced adverse events during or immediately after MSC infusion. The 2-year survival rate was 77.7% in this study. Clinical improvement was accompanied by the increasing ratio of CD5+CD19+/CD5−CD19+ B cells and CD8+CD28−/CD8+CD28+ T cells. In conclusion, transfusion of MSCs expanded in vitro, irrespective of the donor, might be a safe and effective salvage therapy for patients with steroid-resistant, cGVHD.
PMCID: PMC3035976  PMID: 20818445
mesenchymal stem cell; refractory; chronic GVHD; transplantation

Results 1-4 (4)