15 research outputs found

    Biomechanics of pressure ulcer in body tissues interacting with external forces during locomotion

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    2009-2010 > Academic research: refereed > Publication in refereed journalAuthor’s OriginalPublishe

    Proteasome inhibition alleviates prolonged moderate compression-induced muscle pathology

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    Author name used in this publication: Bee T TengAuthor name used in this publication: Eric W Tam2010-2011 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

    Azacytidine sensitizes acute myeloid leukemia cells to arsenic trioxide by up-regulating the arsenic transporter aquaglyceroporin 9

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    Abstract BACKGROUND: The therapeutic efficacy of arsenic trioxide (As2O3) in acute myeloid leukemia (AML) is modest, which is partly related to its limited intracellular uptake into the leukemic cells. As2O3 enters cells via the transmembrane protein aquaglyceroporin 9 (AQP9). Azacytidine, a demethylating agent that is approved for the treatment of AML, has been shown to have synergistic effect with As2O3. We tested the hypothesis that azacytidine might up-regulate AQP9 and enhances As2O3-mediated cytotoxicity in AML. METHODS: Arsenic-induced cytotoxicity, the expression of AQP9, and the intracellular uptake of As2O3 were determined in AML cell lines and primary AML cells with or without azacytidine pre-treatment. The mechanism of AQP9 up-regulation was then investigated by examining the expression of transcription factors for AQP9 gene and the methylation status of their gene promoters. RESULTS: As2O3-induced cytotoxicity in AML cell lines was significantly enhanced after azacytidine pre-treatment as a result of AQP9 up-regulation, leading to increased arsenic uptake and hence intracellular concentration. Blocking AQP9-mediated As2O3 uptake with mercury chloride abrogated the sensitization effect of azacytidine. AQP9 promoter does not contain CpG islands. Instead, azacytidine pre-treatment led to increased expression of HNF1A, a transcription activator of AQP9, through demethylation of HNF1A promoter. HNF1 knockdown abrogated azacytidine-induced AQP9 up-regulation and almost completely blocked intracellular As2O3 entry, confirming that azacytidine enhanced As2O3-mediated cell death via up-regulation of HNF1A and hence increased AQP9 and As2O3 intracellular concentration. Azacytidine sensitization to As2O3 treatment was re-capitulated also in primary AML samples. Finally, azacytidine did not enhance arsenic toxicity in a liver cell line, where HNF1A was largely unmethylated. CONCLUSIONS: Azacytidine sensitizes AML cells to As2O3 treatment, and our results provide proof-of-principle evidence that pharmacological up-regulation of AQP9 potentially expands the therapeutic spectrum of As2O3. Further clinical trial should evaluate the efficacy of azacytidine in combination with As2O3 in the treatment of AML.published_or_final_versio

    Toe tap test (TTT) for assessing people with chronic stroke

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    This Free Access journal suppl. entitled: Asia Pacific Stroke Conference 2016. Abstracts of the Annual Conference of the Asia Pacific Stroke Organization (APSO) Combined with Stroke Society of Australasia, Brisbane, Qld., Australia, July 14-17, 2016: AbstractsPoster Presentation: P173BACKGROUND AND RATIONALE: Impaired ankle control is common in stroke survivors (Ng & Hui-Chan 2012, 2013). Ankle control, including ankle dorsiflexion and plantarflexion, is important in regaining normal gait pattern after stroke. Indeed, ankle dorsiflexor strength was independently associated with the walking endurance (Ng & Hui-Chan 2013) and functional mobility (Ng & Hui-Chan2013) of stroke survivors. In order to reflect changes in ankle control during the rehabilitation process, a reliable, valid and comprehensive measurement tools for assessing ankle control are definitely needed. Toe tap test (TTT) was initially introduced as a simple toetapping test to determine speed of ankle control in healthy adults (Kent-Braun & Ng 1999). Each subject was required to sit with knee and hip at 90 degrees of flexion, and maintain their heel on floor. Then, subjects were instructed to tap the floor as rapid as possible for 10 seconds. The objectives of this study were to investigate: (1) the interrater and test-retest reliability, (2) the correlation of TTT counts with other measures of stroke-specific impairments (3) minimal detectable change (MDC) of TTT counts. METHODS: It was a cross-sectional study with 37 subjects with chronic stroke. The main outcome measured included: TTT counts, Fugl-Meyer Lower Extremity assessment (FMA-LE); ankle muscle strength; Five Times Sit-to-Stand Test (FTSTS) times; Berg Balance Scale (BBS) and Timed ‘Up and Go’ test (TUG) scores. RESULTS: Excellent intra-rater and test-retest reliability (ICC = 0.725–0.995)) of TTT counts were found. The TTT counts of paretic legs were significantly associated with FMA-LE, ankle dorsiflexor and plantarflexor strength, BBS score, FTSTS completion time and TUG score. The 95% MDC of TTT counts was 8.7 counts and 12.6 counts of the paretic and non-paretic legs, respectively. CONCLUSION: The TTT counts is a reliable and valid measurement tool for assessing the ankle control of subjects with chronic stroke.link_to_OA_fulltex

    Reliability and convergent validity of the five-step test in people with chronic stroke

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    2017-2018 > Academic research: refereed > Publication in refereed journal201807 bcrcVersion of RecordOthersHong Kong Polytechnic UniversityPublishe

    LDH is an adverse prognostic factor independent of ISS in transplant-eligible myeloma patients receiving bortezomib-based induction regimens

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    BACKGROUND: Serum lactate dehydrogenase (LDH) has been an adverse prognostic factor for myeloma but does not feature in the International Staging System (ISS). We examined if elevated serum LDH at diagnosis remains an adverse risk factor independent of ISS for survivals transplant-eligible myeloma patients receiving early/frontline bortezomib-based induction, followed by autologous stem cell transplantation (ASCT). PATIENTS: Seventy-seven transplant-eligible Chinese patients received three induction regimens [staged approach (N=25), PAD (N=19), VTD (N=33)], followed by ASCT and thalidomide maintenance. RESULTS: Five-year overall (OS) and event-free (EFS) survivals were 66.4% and 36.2%. There was no difference in demographics, CR/nCR rates post-induction or -ASCT, and survivals among patients induced by the three induction regimens. Elevated LDH was associated with male gender (p=0.006), ISS III (p=0.042) and serum β2-microglobulin (p=0.040). Univariate analysis showed that elevated LDH, ISS III, high β2-microglobulin and failure to attain CR/nCR post-ACST were risk factors adversely impacting both OS and EFS. Multivariate analysis showed that elevated LDH was the only factor impacting both OS (p=0.007) and EFS (p=0.008). CONCLUSION: In this uniformly treated cohort of transplant-eligible myeloma patients, elevated serum LDH is an adverse risk factor independent of ISS for both OS and EFS. Bortezomib-based induction/ASCT regimen had not abolished the adverse impact of elevated LDH. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved
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