Publications by authors named "Anskar Yu-Hung Leung"

18 Publications

  • Page 1 of 1

COVID-19 vaccines and risks of hematological abnormalities: Nested case-control and self-controlled case series study.

Am J Hematol 2022 04 9;97(4):470-480. Epub 2022 Feb 9.

Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong Special Administrative Region, China.

Several studies reported hematological abnormalities after vaccination against the coronavirus disease 2019 (COVID-19). We evaluated the association between COVID-19 vaccines (CoronaVac and BNT162b2) and hematological abnormalities. We conducted nested case-control and self-controlled case series analyses using the data from the Hong Kong Hospital Authority and the Department of Health, HKSAR. Outcomes of interest were thrombocytopenia, leukopenia, and neutropenia. Adjusted odds ratios (aORs), incidence rate ratios (IRRs), and 95% confidence intervals (CIs) were estimated using conditional logistic regression. In total, 1 643 419 people received COVID-19 vaccination (738 609 CoronaVac; 904 810 BNT162b2). We identified 457 and 422 cases after CoronaVac and BNT162b2 vaccination, respectively. For CoronaVac, the incidence of thrombocytopenia, leukopenia, and neutropenia was 2.51, 1.08, and 0.15 per 10 000 doses. For BNT162b2, the corresponding incidence was 1.39, 1.17, and 0.26 per 10 000 doses. The incidence per 10 000 COVID-19 cases were 1254, 2341, and 884, respectively. We only observed an increased risk of leukopenia following the second dose of BNT162b2 (aOR 1.58, 95% CI 1.24-2.02; day 0-14, IRR 2.21; 95% CI 1.59-3.08). There was no increased risk of any hematological abnormalities after CoronaVac vaccination. We observed an increased risk of leukopenia shortly after the second dose of BNT162b2. However, the incidence was much lower than the incidence following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. There was no association between CoronaVac and hematological abnormalities. The benefits of vaccination against COVID-19 still outweigh the risk of hematological abnormalities.
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http://dx.doi.org/10.1002/ajh.26478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011752PMC
April 2022

Follistatin is a novel therapeutic target and biomarker in FLT3/ITD acute myeloid leukemia.

EMBO Mol Med 2020 04 5;12(4):e10895. Epub 2020 Mar 5.

Division of Hematology, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Internal tandem duplication of Fms-like tyrosine kinase 3 (FLT3/ITD) occurs in about 30% of acute myeloid leukemia (AML) and is associated with poor response to conventional treatment and adverse outcome. Here, we reported that human FLT3/ITD expression led to axis duplication and dorsalization in about 50% of zebrafish embryos. The morphologic phenotype was accompanied by ectopic expression of a morphogen follistatin (fst) during early embryonic development. Increase in fst expression also occurred in adult FLT3/ITD-transgenic zebrafish, Flt3/ITD knock-in mice, and human FLT3/ITD AML cells. Overexpression of human FST317 and FST344 isoforms enhanced clonogenicity and leukemia engraftment in xenotransplantation model via RET, IL2RA, and CCL5 upregulation. Specific targeting of FST by shRNA, CRISPR/Cas9, or antisense oligo inhibited leukemic growth in vitro and in vivo. Importantly, serum FST positively correlated with leukemia engraftment in FLT3/ITD AML patient-derived xenograft mice and leukemia blast percentage in primary AML patients. In FLT3/ITD AML patients treated with FLT3 inhibitor quizartinib, serum FST levels correlated with clinical response. These observations supported FST as a novel therapeutic target and biomarker in FLT3/ITD AML.
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http://dx.doi.org/10.15252/emmm.201910895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136967PMC
April 2020

Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial.

Lancet Oncol 2019 07 4;20(7):984-997. Epub 2019 Jun 4.

The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.

Background: Patients with relapsed or refractory FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia have a poor prognosis, including high frequency of relapse, poorer response to salvage therapy, and shorter overall survival than those with FLT3 wild-type disease. We aimed to assess whether single-agent quizartinib, an oral, highly potent and selective type II FLT3 inhibitor, improves overall survival versus salvage chemotherapy.

Methods: QuANTUM-R is a randomised, controlled, phase 3 trial done at 152 hospitals and cancer centres in 19 countries. Eligible patients aged 18 years or older with ECOG performance status 0-2 with relapsed or refractory (duration of first composite complete remission ≤6 months) FLT3-ITD acute myeloid leukaemia after standard therapy with or without allogeneic haemopoietic stem-cell transplantation were randomly assigned (2:1; permuted block size of 6; stratified by response to previous therapy and choice of chemotherapy via a phone-based and web-based interactive response system) to quizartinib (60 mg [30 mg lead-in] orally once daily) or investigator's choice of preselected chemotherapy: subcutaneous low-dose cytarabine (subcutaneous injection of cytarabine 20 mg twice daily on days 1-10 of 28-day cycles); intravenous infusions of mitoxantrone (8 mg/m per day), etoposide (100 mg/m per day), and cytarabine (1000 mg/m per day on days 1-5 of up to two 28-day cycles); or intravenous granulocyte colony-stimulating factor (300 μg/m per day or 5 μg/kg per day subcutaneously on days 1-5), fludarabine (intravenous infusion 30 mg/m per day on days 2-6), cytarabine (intravenous infusion 2000 mg/m per day on days 2-6), and idarubicin (intravenous infusion 10 mg/m per day on days 2-4 in up to two 28-day cycles). Patients proceeding to haemopoietic stem-cell transplantation after quizartinib could resume quizartinib after haemopoietic stem-cell transplantation. The primary endpoint was overall survival in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02039726, and follow-up is ongoing.

Findings: Between May 7, 2014, and Sept 13, 2017, 367 patients were enrolled, of whom 245 were randomly allocated to quizartinib and 122 to chemotherapy. Four patients in the quizartinib group and 28 in the chemotherapy group were not treated. Median follow-up was 23·5 months (IQR 15·4-32·3). Overall survival was longer for quizartinib than for chemotherapy (hazard ratio 0·76 [95% CI 0·58-0·98; p=0·02]). Median overall survival was 6·2 months (5·3-7·2) in the quizartinib group and 4·7 months (4·0-5·5) in the chemotherapy group. The most common non-haematological grade 3-5 treatment-emergent adverse events (within ≤30 days of last dose or >30 days if suspected to be a treatment-related event) for quizartinib (241 patients) and chemotherapy (94 patients) were sepsis or septic shock (46 patients [19%] for quizartinib vs 18 [19%] for chemotherapy), pneumonia (29 [12%] vs eight [9%]), and hypokalaemia (28 [12%] vs eight [9%]). The most frequent treatment-related serious adverse events were febrile neutropenia (18 patients [7%]), sepsis or septic shock (11 [5%]), QT prolongation (five [2%]), and nausea (five [2%]) in the quizartinib group, and febrile neutropenia (five [5%]), sepsis or septic shock (four [4%]), pneumonia (two [2%]), and pyrexia (two [2%]) in the chemotherapy group. Grade 3 QT prolongation in the quizartinib group was uncommon (eight [3%] by central reading, ten [4%] by investigator report); no grade 4 events occurred. There were 80 (33%) treatment-emergent deaths in the quizartinib group (31 [13%] of which were due to adverse events) and 16 (17%) in the chemotherapy group (nine [10%] of which were due to adverse events).

Interpretation: Treatment with quizartinib had a survival benefit versus salvage chemotherapy and had a manageable safety profile in patients with rapidly proliferative disease and very poor prognosis. Quizartinib could be considered a new standard of care. Given that there are only a few available treatment options, this study highlights the value of targeting the FLT3-ITD driver mutation with a highly potent and selective FLT3 inhibitor.

Funding: Daiichi Sankyo.
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http://dx.doi.org/10.1016/S1470-2045(19)30150-0DOI Listing
July 2019

Treatment of acute myeloid leukemia in the next decade - Towards real-time functional testing and personalized medicine.

Blood Rev 2017 11 4;31(6):418-425. Epub 2017 Aug 4.

Division of Haematology, Department of Medicine, The University of Hong Kong, Hong Kong, China.. Electronic address:

Information arising from next generation sequencing of leukemia genome has shed important light on the heterogeneous and combinatorial driver events in acute myeloid leukemia (AML). It has also provided insight into its intricate signaling pathways operative in the disease pathogenesis. These have also become biomarkers and targets for therapeutic intervention. Emerging evidence from in vitro drug screening has demonstrated its potential value in predicting clinical drug responses in specific AML subtypes. However, the best culture conditions and readouts have yet to be standardized and the drugs included in these screening exercises frequently revised in view of the rapid emergence of new therapeutic agents in the oncology field. Testing of leukemia cell functions, including BCL2 profiling, has also been used to predict treatment response to conventional chemotherapy and hypomethylating agents as well as BCL2 antagonist in small patient cohorts. These platforms should be integrated into future clinical trials to develop personalized treatment of AML.
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http://dx.doi.org/10.1016/j.blre.2017.08.001DOI Listing
November 2017

Transcriptome analysis reveals a ribosome constituents disorder involved in the RPL5 downregulated zebrafish model of Diamond-Blackfan anemia.

BMC Med Genomics 2016 Mar 9;9:13. Epub 2016 Mar 9.

CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.

Background: Diamond-Blackfan anemia (DBA) was the first ribosomopathy associated with mutations in ribosome protein (RP) genes. The clinical phenotypes of DBA include failure of erythropoiesis, congenital anomalies and cancer predisposition. Mutations in RPL5 are reported in approximately 9 ~ 21 % of DBA patients, which represents the most common pathological condition related to a large-subunit ribosomal protein. However, it remains unclear how RPL5 downregulation results in severe phenotypes of this disease.

Results: In this study, we generated a zebrafish model of DBA with RPL5 morphants and implemented high-throughput RNA-seq and ncRNA-seq to identify key genes, lncRNAs, and miRNAs during zebrafish development and hematopoiesis. We demonstrated that RPL5 is required for both primitive and definitive hematopoiesis processes. By comparing with other DBA zebrafish models and processing functional coupling network, we identified some common regulated genes, lncRNAs and miRNAs, that might play important roles in development and hematopoiesis.

Conclusions: Ribosome biogenesis and translation process were affected more in RPL5 MO than in other RP MOs. Both P53 dependent (for example, cell cycle pathway) and independent pathways (such as Aminoacyl-tRNA biosynthesis pathway) play important roles in DBA pathology. Our results therefore provide a comprehensive basis for the study of molecular pathogenesis of RPL5-mediated DBA and other ribosomopathies.
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http://dx.doi.org/10.1186/s12920-016-0174-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785739PMC
March 2016

Fluorescent Probe HKSOX-1 for Imaging and Detection of Endogenous Superoxide in Live Cells and In Vivo.

J Am Chem Soc 2015 Jun 19;137(21):6837-43. Epub 2015 May 19.

†Morningside Laboratory for Chemical Biology and Department of Chemistry, ‡School of Chinese Medicine, and §Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China.

Superoxide anion radical (O2(•-)) is undoubtedly the most important primary reactive oxygen species (ROS) found in cells, whose formation and fate are intertwined with diverse physiological and pathological processes. Here we report a highly sensitive and selective O2(•-) detecting strategy involving O2(•-) cleavage of an aryl trifluoromethanesulfonate group to yield a free phenol. We have synthesized three new O2(•-) fluorescent probes (HKSOX-1, HKSOX-1r for cellular retention, and HKSOX-1m for mitochondria-targeting) which exhibit excellent selectivity and sensitivity toward O2(•-) over a broad range of pH, strong oxidants, and abundant reductants found in cells. In confocal imaging, flow cytometry, and 96-well microplate assay, HKSOX-1r has been robustly applied to detect O2(•-) in multiple cellular models, such as inflammation and mitochondrial stress. Additionally, our probes can be efficiently applied to visualize O2(•-) in intact live zebrafish embryos. These probes open up exciting opportunities for unmasking the roles of O2(•-) in health and disease.
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http://dx.doi.org/10.1021/jacs.5b01881DOI Listing
June 2015

Antioxidant N-acetyl-L-cysteine increases engraftment of human hematopoietic stem cells in immune-deficient mice.

Blood 2014 Nov 6;124(20):e45-8. Epub 2014 Oct 6.

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China; Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Beijing, China;

Immunocompromised mice, such as the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, have been widely used to examine the self-renewal and differentiation potential of human hematopoietic stem cells (HSCs) in vivo. However, the efficiency of human HSC engraftment remains very low. Here, we report that NOD/SCID mice had higher levels of reactive oxygen species (ROS) in their bone marrow (BM) than other commonly used mouse strains (C57BL/6 and BALB/C). Treatment with the antioxidant N-acetyl-l-cysteine (NAC) decreased ROS levels in the BM of NOD/SCID mice. Furthermore, the NAC-treated mice displayed a significant increase in human HSC engraftment and multilineage hematopoietic differentiation in the mice. In comparison with the control mice, NAC-treated recipients displayed a 10.8-fold increase in hematopoietic engraftment in the injected tibiae. A beneficial effect of NAC for human hematopoietic engraftment was also observed in an additional immunodeficient mouse strain, namely NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NOD/SCID/γc(-/-) or NSG). Thus, this study uncovers a previously unappreciated negative effect of ROS on human stem cell engraftment in immunodeficient mice.
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http://dx.doi.org/10.1182/blood-2014-03-559369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231425PMC
November 2014

Systematic transcriptome analysis of the zebrafish model of diamond-blackfan anemia induced by RPS24 deficiency.

BMC Genomics 2014 Sep 4;15:759. Epub 2014 Sep 4.

Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

Background: Diamond-Blackfan anemia (DBA) is a class of human diseases linked to defective ribosome biogenesis that results in clinical phenotypes. Genetic mutations in ribosome protein (RP) genes lead to DBA phenotypes, including hematopoietic defects and physical deformities. However, little is known about the global regulatory network as well as key miRNAs and gene pathways in the zebrafish model of DBA.

Results: In this study, we establish the DBA model in zebrafish using an RPS24 morpholino and found that RPS24 is required for both primitive hematopoiesis and definitive hematopoiesis processes that are partially mediated by the p53 pathway. Several deregulated genes and miRNAs were found to be related to hematopoiesis, vascular development and apoptosis in RPS24-deficient zebrafish via RNA-seq and miRNA-seq data analysis, and a comprehensive regulatory network was first constructed to identify the mechanisms of key miRNAs and gene pathways in the model. Interestingly, we found that the central node genes in the network were almost all targeted by significantly deregulated miRNAs. Furthermore, the enforced expression of miR-142-3p, a uniquely expressed miRNA, causes a significant decrease in primitive erythrocyte progenitor cells and HSCs.

Conclusions: The present analyses demonstrate that the comprehensive regulatory network we constructed is useful for the functional prediction of new and important miRNAs in DBA and will provide insights into the pathogenesis of mutant rps24-mediated human DBA disease.
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http://dx.doi.org/10.1186/1471-2164-15-759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169864PMC
September 2014

Sox4you: a new player in C/EBPα leukemia.

Cancer Cell 2013 Nov;24(5):557-9

Leukaemia and Stem Cell Biology Section, Division of Cancer Studies, Department of Haematological Medicine, King's College London, London SE5 9NU, UK.

Although CEBPA mutations are among the most common genetic abnormalities in acute myeloid leukemia (AML), the transformation mechanism remains largely obscure. In this issue of Cancer Cell, Zhang and colleagues report that SOX4 is a direct target and crucial mediator of C/EBPα mutants in AML, revealing a potential therapeutic avenue.
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http://dx.doi.org/10.1016/j.ccr.2013.10.016DOI Listing
November 2013

CFTR mediates bicarbonate-dependent activation of miR-125b in preimplantation embryo development.

Cell Res 2012 Oct 5;22(10):1453-66. Epub 2012 Jun 5.

The Chinese University of Hong Kong - Zhejiang University Joint Laboratory for Human Reproduction and Related Diseases, Hong Kong, China.

Although HCO(3)(-) is known to be required for early embryo development, its exact role remains elusive. Here we report that HCO(3)(-) acts as an environmental cue in regulating miR-125b expression through CFTR-mediated influx during preimplantation embryo development. The results show that the effect of HCO(3)(-) on preimplantation embryo development can be suppressed by interfering the function of a HCO(3)(-)-conducting channel, CFTR, by a specific inhibitor or gene knockout. Removal of extracellular HCO(3)(-) or inhibition of CFTR reduces miR-125b expression in 2 cell-stage mouse embryos. Knockdown of miR-125b mimics the effect of HCO(3)(-) removal and CFTR inhibition, while injection of miR-125b precursor reverses it. Downregulation of miR-125b upregulates p53 cascade in both human and mouse embryos. The activation of miR-125b is shown to be mediated by sAC/PKA-dependent nuclear shuttling of NF-κB. These results have revealed a critical role of CFTR in signal transduction linking the environmental HCO(3)(-) to activation of miR-125b during preimplantation embryo development and indicated the importance of ion channels in regulation of miRNAs.
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http://dx.doi.org/10.1038/cr.2012.88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463266PMC
October 2012

Utility of FDG PET/CT in the assessment of myeloid sarcoma.

AJR Am J Roentgenol 2012 May;198(5):1175-9

Department of Diagnostic Radiology, Queen Mary Hospital, University of Hong Kong, Hong Kong.

Objective: Myeloid sarcoma (MS) is a rare extramedullary manifestation of acute myeloid leukemia that often presents during remission or disease relapse. With awareness of this clinical entity and the appropriate clinical history, MS can be detected despite its nonspecific radiologic features.

Conclusion: This article highlights the utility of (18)F-FDG PET/CT, which has high sensitivity in detecting early MS and provides a systemic overview of tumor burden, and its potential role in monitoring of treatment response.
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http://dx.doi.org/10.2214/AJR.11.7743DOI Listing
May 2012

Post-genome wide association studies and functional analyses identify association of MPP7 gene variants with site-specific bone mineral density.

Hum Mol Genet 2012 Apr 13;21(7):1648-57. Epub 2011 Dec 13.

Department of Medicine, The University of Hong Kong, Hong Kong, China.

Our previous genome-wide association study (GWAS) in a Hong Kong Southern Chinese population with extreme bone mineral density (BMD) scores revealed suggestive association with MPP7, which ranked second after JAG1 as a candidate gene for BMD. To follow-up this suggestive signal, we replicated the top single-nucleotide polymorphism rs4317882 of MPP7 in three additional independent Asian-descent samples (n= 2684). The association of rs4317882 reached the genome-wide significance in the meta-analysis of all available subjects (P(meta)= 4.58 × 10(-8), n= 4204). Site heterogeneity was observed, with a larger effect on spine than hip BMD. Further functional studies in a zebrafish model revealed that vertebral bone mass was lower in an mpp7 knock-down model compared with the wide-type (P= 9.64 × 10(-4), n= 21). In addition, MPP7 was found to have constitutive expression in human bone-derived cells during osteogenesis. Immunostaining of murine MC3T3-E1 cells revealed that the Mpp7 protein is localized in the plasma membrane and intracytoplasmic compartment of osteoblasts. In an assessment of the function of identified variants, an electrophoretic mobility shift assay demonstrated the binding of transcriptional factor GATA2 to the risk allele 'A' but not the 'G' allele of rs4317882. An mRNA expression study in human peripheral blood mononuclear cells confirmed that the low BMD-related allele 'A' of rs4317882 was associated with lower MPP7 expression (P= 9.07 × 10(-3), n= 135). Our data suggest a genetic and functional association of MPP7 with BMD variation.
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http://dx.doi.org/10.1093/hmg/ddr586DOI Listing
April 2012

Angiogenic efficacy of simplified 2-herb formula (NF3) in zebrafish embryos in vivo and rat aortic ring in vitro.

J Ethnopharmacol 2012 Jan 26;139(2):447-53. Epub 2011 Nov 26.

Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong Special Administrative Region.

Ethnopharmacological Relevance: Diabetic foot ulceration results in high risk of lower extremity amputation, and represents a significant health care expenditure worldwide. Radix Astragali (RA) and Radix Rehmanniae (RR) are widely used Chinese medicinal herbs in treating diabetes, and have shown positive effects in enhancing wound healing in diabetic foot ulcer animal model.

Materials And Methods: The angiogenic efficacy of NF3, a simplified 2-herb formula consisting of RA and RR in 2:1 ratio, was investigated. Median lethal concentration (LC50) and median effective concentration (EC50) were determined by treating zebrafish embryos with different concentrations of NF3 from 20 hpf to 72 hpf. The angiogenic activity of NF3 was examined in zebrafish embryos in vivo and by rat aortic ring assay in vitro. Cell cycle analysis of endothelial cells induced by NF3 was analyzed by flow cytometry using transgenic zebrafish Tg(fli1:EGFP). Real-time PCR was used to analyze mRNA expression profiles of selected genes involved in VEGF, FGF and MAPK pathways.

Results: NF3 enhanced blood vessel formation as indicated by extra growth of intersegmental vessels in zebrafish embryos, and increased microvessels formation in rat aortic ring. NF3 also enhanced endothelial cells proliferation as shown by increased percentage of cells accumulating in S phase and G2/M phase of the cell cycle. NF3 exposure significantly induced up-regulation of VEGF-A, Flk-1, fgf1 and bRaf expression in zebrafish embryos.

Conclusions: Our results demonstrated that NF3 was effective in promoting angiogenesis in zebrafish embryos and by rat aortic ring assay, which provided scientific basis to support the use of NF3 as potential therapeutics in treating diabetic foot ulceration.
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http://dx.doi.org/10.1016/j.jep.2011.11.031DOI Listing
January 2012

Utility of 18F-FDG PET/CT in identifying terminal ileal myeloid sarcoma in an asymptomatic patient.

Am J Hematol 2011 Dec 28;86(12):1036-7. Epub 2011 Jul 28.

Department of Diagnostic Radiology, University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong.

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http://dx.doi.org/10.1002/ajh.22077DOI Listing
December 2011

Characterization of Sry-related HMG box group F genes in zebrafish hematopoiesis.

Exp Hematol 2011 Oct 1;39(10):986-998.e5. Epub 2011 Jul 1.

Division of Haematology and Bone Marrow Transplantation, Department of Medicine, Queen Mary Hospital, University of Hong Kong, China.

Objective: The roles of Sry-related HMG box (Sox) genes in zebrafish hematopoiesis are not clearly defined. In this study, we have characterized the sequence homology, gene expression, hematopoietic functions, and regulation of sox genes in F group (SoxF) in zebrafish embryos.

Materials And Methods: Expression of zebrafish SoxF genes were analyzed by whole-mount in situ hybridization, reverse transcription polymerase chain reaction, and real-time reverse transcription polymerase chain reaction of erythroid cells obtained from Tg(gata1:GFP) embryos by fluorescence-activated cell sorting. Roles of SoxF genes were analyzed in zebrafish embryos using morpholino knockdown and analyzed by whole-mount in situ hybridization and real-time reverse transcription polymerase chain reaction. Embryo patterning and vascular development were analyzed.

Results: All members, except sox17, contained a putative β-catenin binding site. sox7 and 18 expressed primarily in the vasculature. sox17 expressed in the intermediate cell mass and its knockdown significantly reduced primitive erythropoiesis at 18 hours post-fertilization (hpf). Definitive hematopoiesis was unaffected. Concomitant sox7 and sox18 knockdown disrupted vasculogenesis and angiogenesis, but not hematopoiesis. sox32 knockdown delayed medial migration of hematopoietic and endothelial progenitors at 18 hpf and abolished cmyb expression at the caudal hematopoietic tissue at 48 hpf. These defects could be prevented by delaying its knockdown using a caged sox32 morpholino uncaged at 10 hpf. Knockdown of SoxF genes significantly upregulated their own expression and that of sox32 also upregulated sox18 expression.

Conclusions: sox17 helped to maintain primitive hematopoiesis, whereas sox7 and sox18 regulated angiogenesis and vasculogenesis. sox32 affected both vascular and hematopoietic development through its effects on medial migration of the hematopoietic and endothelial progenitors.
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http://dx.doi.org/10.1016/j.exphem.2011.06.010DOI Listing
October 2011

The angiogenic effects of Angelica sinensis extract on HUVEC in vitro and zebrafish in vivo.

J Cell Biochem 2008 Jan;103(1):195-211

Institute of Chinese Medical Sciences, University of Macau, Av. Padre Tomás Pereira S.J., Taipa, Macao, China.

Angiogenesis plays an important role in a wide range of physiological processes such as wound healing and fetal development. Many diseases are associated with imbalances in regulation of angiogenesis, in which it is either excessive or there is insufficient blood vessel formation. Angelica sinensis (AS), commonly used in the prescriptions of Chinese medicine, is a potential candidate for curing such diseases. However, biological effects of AS on angiogenesis and underlying mechanisms are yet to be fully elucidated. This investigation describes the angiogenic effects of AS extract on human endothelial cells (HUVEC) in vitro and zebrafish in vivo. The extract was demonstrated, by XTT assay and microscopic cell counting, to stimulate the proliferation of HUVEC; in addition, flow cytometry analysis indicated that the extract increased the percentage of HUVEC in the S phase. The wound healing migration assay illustrated that a dramatic increase in migration could be measured in AS extract-treated HUVEC. Meanwhile, the number of invaded cells and the mean tube length were significantly increased in AS extract treatment groups. The extract was also demonstrated to promote changes in subintestinal vessels (SIVs) in zebrafish, one feature of angiogenesis. In addition, AS extract was found by real-time PCR to enhance vascular endothelial growth factor (VEGF) mRNA expression. In a bead-based immunoassay, higher levels of p38 and JNK 1/2 expression were also observed in effusions compared with control cells. All results suggest that Angelica sinensis extract can promote angiogenesis, and that the angiogenic effects involve p38 and JNK 1/2 phosphorylation.
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http://dx.doi.org/10.1002/jcb.21403DOI Listing
January 2008

Quantification of adenovirus in the lower respiratory tract of patients without clinical adenovirus-related respiratory disease.

Clin Infect Dis 2005 May 4;40(10):1541-4. Epub 2005 Apr 4.

Department of Medicine, University of Hong Kong, Hong Kong.

Adenovirus in bronchoalveolar lavage fluid samples from 50 patients without adenovirus-related illness was quantified. In 49 patients, adenovirus was found (median load, 3.3 x 10(3) copies/microg of DNA). The adenovirus load was inversely related to lymphocyte count (Pearson correlation coefficient r = -0.311; P = .03) and was significantly greater in immunosuppressed patients than in immunocompetent patients (5.1 x 10(3) vs. 2.0 x 10(3) copies/microg of DNA; P = .028).
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http://dx.doi.org/10.1086/429627DOI Listing
May 2005
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