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Articles by M Fu
Total Records ( 4 ) for M Fu
  P. E Pergola , G Gartenberg , M Fu , M Wolfson , S Rao and P. Bowers
 

Background and objectives: In clinical practice, physicians often use once-weekly (QW) and biweekly (Q2W) dosing of epoetin alfa to treat anemia in patients with chronic kidney disease (CKD). Although the literature supports this practice, previous studies were limited by short treatment duration, lack of randomization, or absence of the approved three times per week (TIW) dosing arm. This randomized trial evaluated extended dosing regimens of epoetin alfa, comparing QW and Q2W to TIW dosing in anemic CKD subjects. The primary objective was to show that treatment with epoetin alfa at QW and Q2W intervals was not inferior to TIW dosing.

Design, setting, participants, & measurements: 375 subjects with stage 3 to 4 CKD were randomized equally to the three groups and treated for 44 wk; to explore the impact of changing from TIW to QW administration on hemoglobin (Hb) control and adverse events, subjects on TIW switched to QW after 22 wk. The Hb was measured weekly, and the dose of epoetin alfa was adjusted to achieve and maintain an Hb level of 11.0 to 11.9 g/dl.

Results: Both the QW and Q2W regimens met the primary efficacy endpoint. More subjects in the TIW group than in the QW and Q2W groups exceeded the Hb ceiling. Adverse events were similar across treatment groups and consistent with the morbidities of CKD patients.

Conclusions: Administration of epoetin alfa at QW and Q2W intervals are potential alternatives to TIW dosing for the treatment of anemia in stage 3 to 4 CKD subjects.

  P. E Pergola , G Gartenberg , M Fu , S Sun , M Wolfson and P. Bowers
 

Background and objectives: Extended-interval dosing of epoetin alfa (EPO) is commonly used to treat anemia in patients with chronic kidney disease (CKD). This study aimed to demonstrate that EPO dosed every 2 weeks (Q2W) and every 4 weeks (Q4W) was noninferior to once-weekly (QW) dosing.

Design, setting, participants, & measurements: 430 anemic subjects with stage 3 to 4 CKD receiving a stable QW dose of EPO were randomized 1:1:2 to QW, Q2W, and Q4W dosing for 36 weeks. Hemoglobin (Hb) was measured weekly, and the dose of EPO was adjusted to maintain an Hb level of 11.0 to 11.9 g/dl. The primary endpoint was change in Hb from baseline to the average of the last 12 weeks of treatment.

Results: Both the Q2W and Q4W dosing groups were noninferior to the QW group. The estimated difference of the mean change in Hb between Q2W and QW was –0.03 g/dl; and between Q4W and QW was –0.09 g/dl. From weeks 13 to 37, the mean percentage of weeks per subject with Hb 10.0 to 11.9 g/dl, inclusive, was 81% for QW, 81% for Q2W, and 75% for Q4W. Death occurred, respectively, in 4%, 3%, and 4%; thromboembolic vascular events occurred in 3%, 5%, and 3%; and serious adverse events occurred in 22%, 26%, and 26% of subjects.

Conclusions: Q2W and Q4W EPO dosing maintained Hb levels in subjects with stage 3 to 4 CKD. Deaths, thromboembolic vascular events, and serious adverse events were comparable across the dosing groups.

  Y Yang , X Li , L Cui , M Fu , A. B Rabie and D. Zhang
 

Mechanical stress induces human periodontal ligament (PDL) cells to express an osteoblastic phenotype in vitro. Core binding factor a1 (CBFA1) is a key regulator of osteoblast differentiation. This study was designed to investigate the role of CBFA1 in alveolar bone remodelling, specifically the expression of CBFA1 messenger RNA (mRNA) in human PDL cells under mechanical stress and its up- and downstream relationships with other bone remodelling markers. Cultured human PDL cells were exposed to mechanical stress. The expressions of CBFA1 and alkaline phosphatase (ALP), osteopontin (OPN), osteoprotegrin (OPG), and receptor activator nuclear factor kappa B ligand (RANKL) were detected before and after RNA interference (RNAi) of CBFA1. The data were analysed using a t-test and one-way analysis of variance.

After mechanical stress loading, CBFA1 mRNA expression was raised initially, followed by an increased expression of ALP and RANKL, decreased expression of OPG, and a change in OPN expression. After CBFA1 knock-down in human PDL cells by small hairpin (sh) RNA, the expression of ALP, OPN, OPG, and RANKL also changed. These findings suggest that in the present model system CBFA1 may play an important role in PDL-mediated bone remodelling in response to mechanical stimulation. Mechanical stress: CBFA1–ALP and OPG–PDL homeostasis may be one of the signal transduction pathways of human PDL cell differentiation under mechanical stress without exclusion of the involvement of other pathways.

  T Sun , M Fu , A. L Bookout , S. A Kliewer and D. J. Mangelsdorf
 

Differentiation of 3T3-L1 cells into adipocytes involves a highly orchestrated series of events including clonal expansion, growth arrest, and terminal differentiation. The mechanisms coordinating these different steps are not yet fully understood. Here we investigated whether microRNAs (miRNAs) play a role in this process. Microarray analysis was performed to detect miRNA expression during 3T3-L1 preadipocyte differentiation. Several miRNAs, including let-7, were up-regulated during 3T3-L1 adipogenesis. Ectopic introduction of let-7 into 3T3-L1 cells inhibited clonal expansion as well as terminal differentiation. The mRNA encoding high-mobility group AT-hook 2 (HMGA2), a transcription factor that regulates growth and proliferation in other contexts, was inversely correlated with let-7 levels during 3T3-L1 cell adipogenesis, and let-7 markedly reduced HMGA2 concentrations. Knockdown of HMGA2 inhibited 3T3-L1 differentiation. These results suggest that let-7 plays an important role in adipocyte differentiation and that it does so in part by targeting HMGA2, thereby regulating the transition from clonal expansion to terminal differentiation.

 
 
 
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