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Articles by W Ma
Total Records ( 8 ) for W Ma
  W Ma , S. K Kang , H Hricak , S. R Gerst and J. Zhang
 

OBJECTIVE. The purpose of our study is to present the radiographic findings in a series of 16 patients with complications associated with intravesical bacille Calmette-Guérin (BCG) treatment of bladder cancer.

CONCLUSION. Intravesical BCG-related complications such as granulomatous disease may show imaging findings mimicking primary or metastatic tumors in patients with bladder cancer. Radiologists should consider this possibility when imaging abnormalities are encountered in bladder cancer patients treated with intravesical BCG so that appropriate management can be administered and unnecessary procedures avoided.

  E. J Kezirian , D. P White , A Malhotra , W Ma , C. E McCulloch and A. N. Goldberg
 

Objective  To determine the interrater reliability of drug-induced sleep endoscopy (DISE).

Design  Prospective cohort; blinded comparison.

Setting  Academic referral center.

Participants  Subjects with obstructive sleep apnea unable to tolerate positive airway pressure therapy.

Interventions  Drug-induced sleep endoscopy was performed with intravenous propofol infusion to achieve sedation, and the videoendoscopy recording was evaluated by 2 independent reviewers.

Main Outcome Measures  The following outcomes were measured: a global assessment of obstruction at the palate and/or hypopharynx; the degree of obstruction at the palate and hypopharynx; and the contribution of individual structures (palate, tonsils, tongue, epiglottis, and lateral pharyngeal walls) to obstruction.

Results  A total of 108 subjects underwent DISE examination. Diagnostic sleep studies demonstrated a mean (SD) apnea-hypopnea index of 39.6 (24.0). Three-quarters of the subjects demonstrated multilevel airway obstruction at the palate and hypopharynx, with a diversity of individual structures contributing to obstruction. The interrater reliability for the presence of obstruction at the palate and hypopharynx ( values, 0.76 and 0.79, respectively) was higher than for the degree of obstruction (weighted values, 0.60 and 0.44). The interrater reliability for the assessment of primary structures contributing to obstruction at the palate and hypopharynx (0.70 and 0.86) was higher than for the contributions of individual structures ( values, 0.42-0.71). The interrater reliability for evaluation of the hypopharyngeal structures was higher than for those of the palate region.

Conclusion  The interrater reliability of DISE is moderate to substantial.

Trial Registration  clinicaltrials.gov Identifier: NCT00695214

  J. Y Park , P. y Wang , T Matsumoto , H. J Sung , W Ma , J. W Choi , S. A Anderson , S. C Leary , R. S Balaban , J. G Kang and P. M. Hwang
 

Rationale: Exercise capacity is a physiological characteristic associated with protection from both cardiovascular and all-cause mortality. p53 regulates mitochondrial function and its deletion markedly diminishes exercise capacity, but the underlying genetic mechanism orchestrating this is unclear. Understanding the biology of how p53 improves exercise capacity may provide useful insights for improving both cardiovascular as well as general health.

Objective: The purpose of this study was to understand the genetic mechanism by which p53 regulates aerobic exercise capacity.

Methods and Results: Using a variety of physiological, metabolic, and molecular techniques, we further characterized maximum exercise capacity and the effects of training, measured various nonmitochondrial and mitochondrial determinants of exercise capacity, and examined putative regulators of mitochondrial biogenesis. As p53 did not affect baseline cardiac function or inotropic reserve, we focused on the involvement of skeletal muscle and now report a wider role for p53 in modulating skeletal muscle mitochondrial function. p53 interacts with Mitochondrial Transcription Factor A (TFAM), a nuclear-encoded gene important for mitochondrial DNA (mtDNA) transcription and maintenance, and regulates mtDNA content. The increased mtDNA in p53+/+ compared to p53–/– mice was more marked in aerobic versus glycolytic skeletal muscle groups with no significant changes in cardiac tissue. These in vivo observations were further supported by in vitro studies showing overexpression of p53 in mouse myoblasts increases both TFAM and mtDNA levels whereas depletion of TFAM by shRNA decreases mtDNA content.

Conclusions: Our current findings indicate that p53 promotes aerobic metabolism and exercise capacity by using different mitochondrial genes and mechanisms in a tissue-specific manner.

  W Ma , H Kantarjian , B Bekele , A. C Donahue , X Zhang , Z. J Zhang , S O`Brien , E Estey , Z Estrov , J Cortes , M Keating , F Giles and M. Albitar
 

Purpose: Cytogenetic abnormalities are currently the most important predictors of response and clinical outcome for patients with acute myeloid leukemia (AML) or advanced-stage myelodysplastic syndrome (MDS). Because clinical outcomes vary markedly within cytogenetic subgroups, additional biological markers are needed for risk stratification.

Experimental Design: We assessed the utility of measuring pretreatment proteasome chymotrypsin-like, caspase-like, and trypsin-like activities in plasma to predict response and survival of patients with AML (n = 174) or advanced-stage MDS (n = 52).

Results: All three enzymatic activities were significantly (P < 0.001) increased in the plasma of patients with AML and MDS compared with normal controls. Both chymotrypsin-like and caspase-like activities, but not trypsin-like activity, correlated with outcome. Chymotrypsin-like and caspase-like activities, but not trypsin-like activity, predicted response in univariate analysis (P = 0.002). However, only chymotrypsin-like activity was independent predictor of response from age grouping (<70 versus ≥70 years), cytogenetics, and blood urea nitrogen in multivariate analysis. Similarly, both chymotrypsin-like and caspase-like activities, but not trypsin-like activity, were predictors of overall survival in univariate analysis (P < 0.0001), but only chymotrypsin-like activity was independent of cytogenetics, age, performance status, blood urea nitrogen, and β2-microglobulin in multivariate Cox regression models. Chymotrypsin-like activity was also a strong independent predictor of survival in patients with intermediate karyotype (n = 124).

Conclusions: Measuring plasma chymotrypsin-like activity may provide a powerful biomarker for risk stratification in patients with AML and advanced-stage MDS, including those with normal karyotype.

  D. r Xie , Q Yang , D. l Chen , Z. m Jiang , Z. f Bi , W Ma and Y. d. Zhang
  Objective

Previous meta-analyses showed a survival advantage with gemcitabine (GEM)-based combinations over GEM in advanced pancreatic cancer. Therefore, it would be valuable to explore the specific active regimens based on a subgroup meta-analysis.

Methods

Updated data by comprehensive search of the literature from databases and conference proceedings. Subgroup meta-analysis compared GEM with GEM-based doublets chemotherapy in terms of 6-month overall survival (OS) and 1-year OS.

Results

Eighteen randomized controlled trials with 4237 patients were included, which were divided into five subgroups: GEM/capecitabine, GEM/cisplatin, GEM/5-fluorouracil, GEM/irinotecan and GEM/oxaliplatin. In each subgroup, risk ratios (RRs) for 6-month OS were 0.85 (P = 0.04), 0.99 (P = 0.88), 0.95 (P = 0.46), 1.03 (P = 0.77) and 0.80 (P = 0.001), respectively, and RRs for 1-year OS were 0.94 (P = 0.14), 0.99 (P = 0.75), 0.96 (P = 0.19), 1.00 (P = 0.97) and 0.93 (P = 0.05), respectively. A meta-analysis of the trials with adequate information on performance status (PS) was performed in four trials with 1325 patients. Patients with a good PS did not show a survival benefit when receiving combination chemotherapy. RRs for 6-month and 1-year OS were 0.82 (P = 0.18) and 0.93 (P = 0.08). In contrast, application of combination chemotherapy to patients with a poor PS appeared to be harmful. RRs were 1.17 (P = 0.04) for 6-month OS and 1.09 (P = 0.04) for 1-year OS.

Conclusions

The meta-analysis indicated a significant survival benefit when GEM was either combined with capcitabine or oxaliplatin. On the basis of a preliminary subgroup analysis, pancreatic cancer patients with a poor PS appeared to have a worse survival benefit from GEM-based cytotoxic doublets.

  S Hu , G Yao , X Guan , Z Ni , W Ma , E. M Wilson , F. S French , Q Liu and Y. Zhang
 

Epididymal function depends on androgen signaling through the androgen receptor (AR), although most of the direct AR target genes in epididymis remain unknown. Here we globally mapped the AR binding regions in mouse caput epididymis in which AR is highly expressed. Chromatin immunoprecipitation sequencing indicated that AR bound selectively to 19,377 DNA regions, the majority of which were intergenic and intronic. Motif analysis showed that 94% of the AR binding regions harbored consensus androgen response elements enriched with multiple binding motifs that included nuclear factor 1 and activator protein 2 sites consistent with combinatorial regulation. Unexpectedly, AR binding regions showed limited conservation across species, regardless of whether the metric for conservation was based on local sequence similarity or the presence of consensus androgen response elements. Further analysis suggested the AR target genes are involved in diverse biological themes that include lipid metabolism and sperm maturation. Potential novel mechanisms of AR regulation were revealed at individual genes such as cysteine-rich secretory protein 1. The composite studies provide new insights into AR regulation under physiological conditions and a global resource of AR binding sites in a normal androgen-responsive tissue.

  R Salcedo , A Worschech , M Cardone , Y Jones , Z Gyulai , R. M Dai , E Wang , W Ma , D Haines , C O'hUigin , F. M Marincola and G. Trinchieri
 

Signaling through the adaptor protein myeloid differentiation factor 88 (MyD88) promotes carcinogenesis in several cancer models. In contrast, MyD88 signaling has a protective role in the development of azoxymethane (AOM)/dextran sodium sulfate (DSS) colitis-associated cancer (CAC). The inability of Myd88–/– mice to heal ulcers generated upon injury creates an altered inflammatory environment that induces early alterations in expression of genes encoding proinflammatory factors, as well as pathways regulating cell proliferation, apoptosis, and DNA repair, resulting in a dramatic increase in adenoma formation and progression to infiltrating adenocarcinomas with frequent clonal mutations in the β-catenin gene. Others have reported that toll-like receptor (Tlr) 4–deficient mice have a similar susceptibility to colitis to Myd88-deficient mice but, unlike the latter, are resistant to CAC. We have observed that mice deficient for Tlr2 or Il1r do not show a differential susceptibility to colitis or CAC. However, upon AOM/DSS treatment Il18–/– and Il18r1–/– mice were more susceptible to colitis and polyp formation than wild-type mice, suggesting that the phenotype of Myd88–/– mice is, in part, a result of their inability to signal through the IL-18 receptor. This study revealed a previously unknown level of complexity surrounding MyD88 activities downstream of different receptors that impact tissue homeostasis and carcinogenesis.

 
 
 
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