95 results on '"Ng, Margaret H L"'
Search Results
52. 4q loss is potentially an important genetic event in MM tumorigenesis: identification of a tumor suppressor gene regulated by promoter methylation at 4q13.3, platelet factor 4
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Cheng, Suk Hang, primary, Ng, Margaret H. L., additional, Lau, Kin Mang, additional, Liu, Herman S. Y., additional, Chan, Joyce C. W., additional, Hui, Angela B. Y., additional, Lo, Kwok Wai, additional, Jiang, Hua, additional, Hou, Jian, additional, Chu, Raymond W., additional, Wong, Wai Shan, additional, Chan,, Natalie P. H., additional, and Ng, Ho Keung, additional
- Published
- 2006
- Full Text
- View/download PDF
53. Association of Human‐Leukocyte‐Antigen Class I (B*0703) and Class II (DRB1*0301) Genotypes with Susceptibility and Resistance to the Development of Severe Acute Respiratory Syndrome
- Author
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Ng, Margaret H. L., primary, Lau, Kin‐Mang, additional, Li, Libby, additional, Cheng, Suk‐Hang, additional, Chan, Wing Y., additional, Hui, Pak K., additional, Zee, Benny, additional, Leung, Chi‐Bon, additional, and Sung, Joseph J. Y., additional
- Published
- 2004
- Full Text
- View/download PDF
54. Aberrant p15 promoter methylation in adult and childhood acute leukemias of nearly all morphologic subtypes: potential prognostic implications
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Wong, Ivy H. N., primary, Ng, Margaret H. L., additional, Huang, Dolly P., additional, and Lee, Joseph C. K., additional
- Published
- 2000
- Full Text
- View/download PDF
55. Association between HLA-B*1502 Allele and Antiepileptic Drug-Induced Cutaneous Reactions in Han Chinese.
- Author
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Man, Celeste B. L., Kwan, Patrick, Baum, Larry, Yu, Evelyn, Lau, K. M., Cheng, Alice S. H., and Ng, Margaret H. L.
- Subjects
ANTICONVULSANTS ,CARBAMAZEPINE ,PHENYTOIN ,LAMOTRIGINE ,GENETIC polymorphisms ,DRUG side effects - Abstract
A previous study conducted in Taiwan found a 100% association between HLA-B*1502 allele and carbamazepine-induced Steven s-Johnson syndrome (SJS) in Han Chinese subjects, with an extremely high odds ratio compared with carbamazepine-tolerant subjects (odds ratio = 2,504). We examined this association in 24 Hong Kong Han Chinese subjects who had cutaneous adverse reactions induced by different antiepileptic drugs (AEDs). They were matched with 48 AED-tolerant controls. HLA-B*1502 was associated with severe cutaneous reactions (SCR) induced by AEDs, which included carbamazepine, phenytoin, and lamotrigine (p = 0.001, odds ratio = 17.6), but was not associated with maculopapular exanthema (MPE) (p = 0.32). Further studies in larger samples of ethnically matched subjects should be conducted to confirm the findings. Identification of genetic polymorphisms predisposing to development of AED-induced SCR offers the possibility of avoiding these high-risk drugs in genetically susceptible individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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56. Hematocrit, Independent of Chronic Kidney Disease, Predicts Adverse Cardovascular Outcomes in Chinese Patients With Type 2 Diabetes.
- Author
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Tong, Peter C. Y., Kong, Alice P. S., Wing-Yee So, Ng, Margaret H. L., Xilin Yang, Ng, Maggie C. Y., Ma, Ronald C. W., Chung-Shun Ho, Lam, Christopher W. K., Chun-Chung Chow, Cockram, Clive S., and Chan, Juliana C. N.
- Subjects
HEMATOCRIT ,CHRONIC kidney failure ,KIDNEY diseases ,TYPE 2 diabetes ,CARDIOVASCULAR diseases ,DIABETES - Abstract
OBJECTIVE -- Anemia and chronic kidney disease (CKD) are risk factors for cardiovascular diseases in diabetes. We examined the association between hematocrit, stratified by the presence of CKD, and cardiovascular events in a cohort of Chinese subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS -- A total of 3,983 patients who underwent assessment for diabetes complications were recruited. Subjects were categorized into five groups. Group I included subjects with hematocrit below the normal sex-specific range. The cutoff points for groups II-V were selected to represent the distribution of the hematocrit for each sex. CKD was defined by the estimated glomerular filtration rate <60 ml/min per 1.73 m². Cardiovascular events were defined as cardiovascular mortality and morbidity, including new onset of myocardial infarction, acute coronary syndrome, revascularization, heart failure, and stroke requiring hospitalization. RESULTS -- A total of 294 subjects (7.4%) developed cardiovascular events during the median of 36.4 months. The rate of cardiovascular events was highest in subjects with low hematocrit (group I, 18.6%) compared with group V (3.4%, P < 0.001). The multivariate-adjusted hazard ratio for cardiovascular events diminished with increasing hematocrit (group I, 1.0; group II, 0.73 [95% CI 0.51-1.04]; group III, 0.57 [0.39-0.83]; group IV, 0.61 [0.39-0.95]; and group V, 0.36 [0.17-0.79]). After stratifying by the presence of CKD, the previously observed reduction in the risk of developing cardiovascular events with increasing hematocrit was abolished in the cohort with CKD but persisted in the non-CKD cohort. CONCLUSIONS -- In Chinese subjects with type 2 diabetes, low levels of hematocrit and the presence of CKD are associated with increased risk of developing adverse cardiovascular events. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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57. Identification of TPO Receptors on Central Nervous System -- A Preliminary Report.
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YANG Mo, XIA Wen-Jie, LI, Karen, PONG Nga-Hin, CHIK Ki-Wai, LI Chi-Kong, NG, Margaret H. L., NG Ho-Keung, FUNG Kwok-Pui, and FOK Tai-Fai
- Published
- 2004
58. 4q loss is potentially an important genetic event in MM tumorigenesis: identification of a tumor suppressor gene regulated by promoter methylation at 4q13.3, platelet factor 4
- Author
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Cheng, Suk Hang, Ng, Margaret H. L., Lau, Kin Mang, Liu, Herman S. Y., Chan, Joyce C. W., Hui, Angela B. Y., Lo, Kwok Wai, Jiang, Hua, Hou, Jian, Chu, Raymond W., Wong, Wai Shan, Chan, Natalie P. H., and Ng, Ho Keung
- Abstract
In this study, we have elucidated the chromosomal imbalances in the multistep pathogenesis and delineated several critical tumor suppressor gene (TSG) loci in multiple myeloma (MM). By using comparative genomic hybridization, allelotyping, and multicolor interphase fluorescence in situ hybridization, 5 MM cell lines and bone marrow CD138+ plasma cells from 88 Chinese patients with monoclonal gammopathy of undetermined significance (MGUS) and early and advanced stages of MM were investigated. In all MGUS and MM samples, chromosome copy number abnormalities were detected. A higher number of chromosomal imbalances and specific genetic alterations are involved in MGUS to MM transition (−6q, +3p, and +1p) and MM progression (+2p and +9q). In addition to −13q, we first found high frequencies (42% to 46%) of −4q involving high percentages (70% to 74%) of clonal plasma cells in both MGUS and MM, suggesting that inactivation of TSG in this region is also a potentially critical genetic event in MM tumorigenesis. By high-resolution allelotyping, we defined a common deletion region on 4q13.3 and found that a candidate TSG, platelet factor 4, was frequently silenced by promoter hypermethylation in MM (15 of 28) and MM cell lines (5 of 5). These data have opened up a new approach in the molecular targeting therapy and provide novel insights into MM tumorigenesis.
- Published
- 2007
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59. Preclinical evaluation of the PI3K inhibitor BEZ235 in nasopharyngeal carcinoma cell lines
- Author
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Ma, Brigette B., Vivian Lui, Ho, Kakiu, Lau, Cecilia P. Y., Ng, Margaret H. L., Cheng, Suk-Hang, Tsang, Chi-Man, Tsao, Sai-Wah, Shi, Michael, Hui, Edwin P., and Chan, Anthony T. C.
60. FNDC3B is another novel partner fused to RARA in the t(3;17)(q26;q21) variant of acute promyelocytic leukemia.
- Author
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Chi Keung Cheng, Wang, Angela Z., Wong, Terry H. Y., Wan, Thomas S. K., Cheung, Joyce S., Raghupathy, Radha, Chan, Natalie P. H., and Ng, Margaret H. L.
- Subjects
- *
ACUTE promyelocytic leukemia , *RETINOIC acid receptors , *FIBRONECTINS - Published
- 2017
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61. Secreted-frizzled related protein 1 is a transcriptional repression target of the t(8;21) fusion protein in acute myeloid leukemia.
- Author
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Chi Keung Cheng, Libby Li, Suk Hang Cheng, Kitty Ng, Chan, Natalie P. H., Ip, Rosalina K. L., Wong, Raymond S. M., Shing, Matthew M. K., Chi Kong Li, and Ng, Margaret H. L.
- Subjects
- *
ACUTE myeloid leukemia , *TRANSCRIPTION factors , *HEMATOPOIESIS , *METHYLATION , *MESSENGER RNA - Abstract
Secreted-frizzled related proteins (SFRPs) are modulators of the Wnt signaling pathway that is closely involved in normal and malignant hematopoiesis. Epigenetic deregulation of Wnt modulators leading to aberrant signaling has been reported in adult patients with acute myeloid leukemia (AML), but its occurrence in childhood patients with AML and the role of individual modulators are unclear. In this study, we examined SFRP1, SFRP2, SFRP4, and SFRP5 promoter methylation in 83 patients with AML (59 children and 24 adults) and found preferential SFRP1 methylation and mRNA down-regulation in the prognostically favorable subgroup of AML with t(8;21) translocation. Among the 4 genes, SFRP1 methylation independently predicted prolonged event-free and relapse-free survivals in childhood patients with nonacute promyelocytic leukemia with nonadverse cytogenetics. Mechanistically, we further demonstrated that RUNX1-ETO, the t(8;21) fusion product, specifically bound the SFRP1 promoter and repressed its transcription via a consensus RUNX binding site. In t(8;21)-leukemia cells, SFRP1 selectively inhibited canonical Wnt signaling and cellular proliferation that were associated with concomitant down-regulation of Wnt/β-catenin target genes, including CCND1 and MYC. Taken together, we identified SFRP1 as a transcriptional repression target of the t(8;21) fusion protein and demonstrated a novel mechanism of Wnt activation in a specific subtype of AML. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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62. Sirtuin 1 Is Upregulated in a Subset of Hepatocellular Carcinomas where It Is Essential for Telomere Maintenance and Tumor Cell Growth.
- Author
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Chen, Juan, Bin Zhang, Wong, Nathalie, Lo, Anthony W. I., Ka-Fai To, Chan, Anthony W. H., Ng, Margaret H. L., Ho, Cecilia Y. S., Suk-Hang Cheng, Lai, Paul B. S., Jun Yu, Ho-Keung Ng, Ming-Tat Ling, Ai-Long Huang, Xue-Fei Cai, and Ko, Ben C. B.
- Subjects
- *
LIVER cancer , *CANCER treatment , *DOXORUBICIN , *CELL proliferation , *REVERSE transcriptase ,TUMOR prognosis - Abstract
Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. Treatment of HCC is complicated by the fact that the disease is often diagnosed at an advanced stage when it is no longer amenable to curative surgery, and current systemic chemotherapeutics are mostly inefficacious. Sirtuin 1 (SIRT1) is a class III histone deacetylase that is implicated in gene regulations and stress resistance. In this study, we found that SIRT1 is essential for the tumorigenesis of HCC. We showed that although SIRT1 was expressed at very low levels in normal livers, it was overexpressed in HCC cell lines and in a subset of HCC. Tissue microarray analysis of HCC and adjacent nontumoral liver tissues revealed a positive correlation between the expression levels of SIRT1 and advancement in tumor grades. Downregulation of SIRT1 consistently suppressed the proliferation of HCC cells via the induction of cellular senescence or apoptosis. SIRT1 silencing also caused telomere dysfunction--induced foci and nuclear abnormality that were clearly associated with reduced expressions of telomerase reverse transcriptase (TERT), and PTOP, which is a member of the shelterin complex. Ectopic expression of either TERT or PTOP in SIRT1-depleted cells significantly restored cell proliferation. There was also a positive correlation between the level of induction of SIRT1 and PTOP in human HCC. Finally, SIRT1-silencing sensitized HCC cells to doxorubicin treatment. Together, our findings reveal a novel function for SIRT1 in telomere maintenance of HCC, and they rationalize the clinical exploration of SIRT1 inhibitors for HCC therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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63. Platelet dropping, bleeding and new treatment requirements in ITP patients after inactivated COVID-19 vaccination.
- Author
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Zhan XY, Chen H, Kong H, Meng T, Ye J, Liu Y, Ng MHL, Li L, Zhang Y, Huang J, Peng Q, Chen C, He Y, and Yang M
- Subjects
- Humans, Chronic Disease, Hemorrhage etiology, Retrospective Studies, Vaccination, COVID-19 prevention & control, COVID-19 complications, COVID-19 Vaccines adverse effects, Purpura, Thrombocytopenic, Idiopathic therapy, Purpura, Thrombocytopenic, Idiopathic complications
- Abstract
Significant decreases in platelet counts and ITP relapses have been documented in ITP patients receiving COVID-19 mRNA vaccines; however, the effect of the inactivated COVID-19 vaccine on ITP patients remains unclear. The present study aimed to investigate the impact of inactivated COVID-19 vaccines on ITP patients, with a focus on platelet dropping events, bleeding events/scores, and the requirement of a new round of treatment. A total of 118 ITP patients, with 97 chronic ITP and 21 persistent ITP, who received inactivated COVID-19 immunization were investigated retrospectively. Following vaccination (within 1 month), ITP patients reported platelet dropping (31.36 %), new bleeding events (22.88 %), increases in bleeding scores (23.73 %), and new treatment requirements (22.03 %). Among them, persistent ITP patients with disease duration of 3-12 months had higher ratios of the above adverse events (71.43 %, 57.14 %, 61.90 % and 71.43 %, respectively) than chronic ITP patients with duration > 1 year (22.68 %, 15.46 %, 15.46 % and 11.34 %, respectively); patients' disease duration was negatively correlated with platelet dropping events and new treatment requirements. Furthermore, logistic regression analysis also supported the above findings, revealing that persistent ITP patients had 9.40-9.70, 7.24-10.08, and 27.17-28.51 times incidence of having platelet dropping events, new bleeding events, and new treatment requirements after vaccination, respectively, when compared to chronic ITP patients. In conclusion, the present study demonstrates that after receiving inactivated COVID-19 vaccines, ITP patients may experience platelet dropping, which may lead to new bleeding events and the requirement of a new round of treatment for ITP recurrence. As a result, platelet level monitoring is crucial for ITP patients during the vaccination, especially those with persistent ITP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2023
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64. Pharmacogenomic Profiling of Pediatric Acute Myeloid Leukemia to Identify Therapeutic Vulnerabilities and Inform Functional Precision Medicine.
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Wang H, Chan KYY, Cheng CK, Ng MHL, Lee PY, Cheng FWT, Lam GKS, Chow TW, Ha SY, Chiang AKS, Leung WH, Leung AYH, Wang CC, Zhang T, Zhang XB, So CC, Yuen YP, Sun Q, Zhang C, Xu Y, Cheung JTK, Ng WH, Tang PM, Kang W, To KF, Lee WYW, Wong RSM, Poon ENY, Zhao Q, Huang J, Chen C, Yuen PMP, Li CK, Leung AWK, and Leung KT
- Subjects
- Child, Adult, Humans, Pharmacogenetics, Gene Expression Profiling methods, Transcriptome, Precision Medicine methods, Leukemia, Myeloid, Acute drug therapy
- Abstract
Despite the expanding portfolio of targeted therapies for adults with acute myeloid leukemia (AML), direct implementation in children is challenging due to inherent differences in underlying genetics. Here we established the pharmacologic profile of pediatric AML by screening myeloblast sensitivity to approved and investigational agents, revealing candidates of immediate clinical relevance. Drug responses ex vivo correlated with patient characteristics, exhibited age-specific alterations, and concorded with activities in xenograft models. Integration with genomic data uncovered new gene-drug associations, suggesting actionable therapeutic vulnerabilities. Transcriptome profiling further identified gene-expression signatures associated with on- and off-target drug responses. We also demonstrated the feasibility of drug screening-guided treatment for children with high-risk AML, with two evaluable cases achieving remission. Collectively, this study offers a high-dimensional gene-drug clinical data set that could be leveraged to research the unique biology of pediatric AML and sets the stage for realizing functional precision medicine for the clinical management of the disease., Significance: We conducted integrated drug and genomic profiling of patient biopsies to build the functional genomic landscape of pediatric AML. Age-specific differences in drug response and new gene-drug interactions were identified. The feasibility of functional precision medicine-guided management of children with high-risk AML was successfully demonstrated in two evaluable clinical cases. This article is highlighted in the In This Issue feature, p. 476., (©2022 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2022
- Full Text
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65. An Evaluation for the Causes of Reduced Hb A 2 and the Molecular Characterization of HBD Variants in Hong Kong.
- Author
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Chan NCN, Wong THY, Cheng KCK, Chan NPH, and Ng MHL
- Subjects
- Hemoglobin A2 genetics, Heterozygote, Hong Kong epidemiology, Humans, Mutation, alpha-Thalassemia diagnosis, alpha-Thalassemia epidemiology, alpha-Thalassemia genetics, beta-Thalassemia diagnosis, beta-Thalassemia epidemiology, beta-Thalassemia genetics, delta-Globins genetics
- Abstract
Prenatal screening of β-thalassemia (β-thal) carriers is based on the hallmark phenotype of microcytosis and raised Hb A
2 . The unanticipated birth of β-thal major (β-TM) offspring to β-thal carriers who were misdiagnosed during prenatal screening have been reported. A subset of these resulted from the masked phenotype due to the coinheritance of HBD variants. In a broader sense, the causes of reduced Hb A2 in thalassemia screening, the prevalence and spectrum of HBD variants in Hong Kong remain to be characterized. Over a 13-month period, a total of 2982 samples were referred for thalassemia screening. Surplus samples with reduced Hb A2 levels (2.0%) were evaluated. HBD variations were assessed by direct sequencing. Sixty-six samples were tested. Hb H disease, HBD variants, α-thalassemia (α-thal) trait and iron deficiency were detected in 40 (60.6%), 12 (18.2%), eight (12.1%) and seven (10.6%) samples, respectively. Seven samples carried more than one of the mentioned conditions. The cause remained elusive in seven samples. Thirteen HBD variants were detected and two were recurrent, including HBD : c.-127T>C [-77 (T>C)] and HBD : c.314G>A (Hb Chori-Burnaby). A novel nonsense variant HBD : c.262C>T [codon 87 (C>T)] was detected in cis with HBD : c.-127T>C. Overall, the prevalence of HBD variants was 0.4%. This study advanced our understanding of the causes of reduced Hb A2 in clinical practice and identified hereditary disorders of α- and δ-globin genes as the prevailing causes. It established the landscape of HBD variations in our locality and highlighted the pitfall of phenotypic screening of β-thal carriers.- Published
- 2021
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66. t(1;22)(p13;q13) Acute Megakaryoblastic Leukemia Complicated by Hepatic Fibrosis: Antifibrosis Therapy?
- Author
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Feng J, Leung AWK, Cheng FWT, Lam GKS, Chow TTW, Ng MHL, Chu WCW, Chan NPH, and Li CK
- Subjects
- Antioxidants therapeutic use, Child, Preschool, Drug Therapy, Combination, Female, Humans, Infant, Newborn, Keratolytic Agents therapeutic use, Leukemia, Megakaryoblastic, Acute complications, Leukemia, Megakaryoblastic, Acute genetics, Leukemia, Megakaryoblastic, Acute pathology, Liver Cirrhosis complications, Liver Cirrhosis genetics, Liver Cirrhosis pathology, Prognosis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 22 genetics, Leukemia, Megakaryoblastic, Acute drug therapy, Liver Cirrhosis drug therapy, Translocation, Genetic, Tretinoin therapeutic use, alpha-Tocopherol therapeutic use
- Abstract
Background: There is no established effective treatment for patients with t(1;22)(p13;q13) acute megakaryoblastic leukemia (AMKL) and hepatic fibrosis., Observation: Here we report the outcomes of 2 t(1;22)(p13;q13) AMKL patients with hepatic fibrosis. One patient died from liver failure despite the control of leukemia. The other patient was successfully treated with reduced-intensity chemotherapy and antifibrosis therapy with tretinoin and α-tocopheryl acetate, the hepatic fibrosis resolved and leukemia was in remission for 3 years., Conclusions: Reduced-intensity chemotherapy plus antifibrosis therapy with tretinoin and α-tocopheryl acetate could be a treatment option for these patients with t(1;22)(p13;q13) AMKL and hepatic fibrosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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67. A novel F11 mutation in a Chinese paediatric patient with severe factor XI deficiency.
- Author
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Leung PY, Li CK, Cheng CK, Ng MHL, and Chan NCN
- Subjects
- Child, China, Factor XI genetics, Heterozygote, Humans, Mutation, Mutation, Missense, Pedigree, Factor XI Deficiency genetics
- Abstract
Competing Interests: Declaration of competing interest The authors stated that they had no interests which might be perceived as posing a conflict or bias.
- Published
- 2020
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68. Rapid detection of chromosomal translocation and precise breakpoint characterization in acute myeloid leukemia by nanopore long-read sequencing.
- Author
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Au CH, Ho DN, Ip BBK, Wan TSK, Ng MHL, Chiu EKW, Chan TL, and Ma ESK
- Subjects
- Female, High-Throughput Nucleotide Sequencing, Humans, Karyotyping, Middle Aged, Neoplasm, Residual genetics, Leukemia, Myeloid, Acute genetics, Nanopores, Translocation, Genetic genetics, Whole Genome Sequencing methods
- Abstract
Detection of chromosomal translocation is a key component in diagnosis and management of acute myeloid leukemia (AML). Targeted RNA next-generation sequencing (NGS) is emerging as a powerful and clinically practical tool, but it depends on expression of RNA transcript from the underlying DNA translocation. Here, we show the clinical utility of nanopore long-read sequencing in rapidly detecting DNA translocation with exact breakpoints. In a newly diagnosed patient with AML, conventional karyotyping showed translocation t(10;12)(q22;p13) but RNA NGS detected NUP98-NSD1 fusion transcripts from a known cryptic translocation t(5;11)(q35;p15). Rapid PCR-free nanopore whole-genome sequencing yielded a 26,194 bp sequencing read and revealed the t(10;12) breakpoint to be DUSP13 and GRIN2B in head-to-head configuration. This translocation was then classified as a passenger structural variant. The sequencing also yielded a 20,709 bp sequencing read and revealed the t(5;11) breakpoint of the driver NUP98-NSD1 fusion. The identified DNA breakpoints also served as markers for molecular monitoring, in addition to fusion transcript expression by digital PCR and sequence mutations by NGS. We illustrate that third-generation nanopore sequencing is a simple and low-cost workflow for DNA translocation detection., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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69. Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells.
- Author
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Cheng CK, Wong THY, Yung YL, Chan NCN, and Ng MHL
- Subjects
- Animals, Cell Line, Tumor, Core Binding Factor Alpha 2 Subunit genetics, Gene Editing methods, Gene Expression Regulation, Neoplastic, Gene Silencing, Humans, Mice, RNA, Guide, CRISPR-Cas Systems genetics, Ribonucleoproteins metabolism, CRISPR-Cas Systems, Core Binding Factor Alpha 2 Subunit metabolism, Leukemia, Myeloid, Acute metabolism
- Abstract
The bulk of the human genome (~98%) is comprised of non-coding sequences. Cis-regulatory elements (CREs) are non-coding DNA sequences that contain binding sites for transcriptional regulators to modulate gene expression. Alterations of CREs have been implicated in various diseases including cancer. While promoters and enhancers have been the primary CREs for studying gene regulation, very little is known about the role of silencer, which is another type of CRE that mediates gene repression. Originally identified as an adaptive immunity system in prokaryotes, CRISPR/Cas9 has been exploited to be a powerful tool for eukaryotic genome editing. Here, we present the use of this technique to delete an intronic silencer in the human RUNX1 gene and investigate the impacts on gene expression in OCI-AML3 leukemic cells. Our approach relies on electroporation-mediated delivery of two preassembled Cas9/guide RNA (gRNA) ribonucleoprotein (RNP) complexes to create two double-strand breaks (DSBs) that flank the silencer. Deletions can be readily screened by fragment analysis. Expression analyses of different mRNAs transcribed from alternative promoters help evaluate promoter-dependent effects. This strategy can be used to study other CREs and is particularly suitable for hematopoietic cells, which are often difficult to transfect with plasmid-based methods. The use of a plasmid- and virus-free strategy allows simple and fast assessments of gene regulatory functions.
- Published
- 2019
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70. Prevalence and Clinicopathologic Significance of BRAF V600E Mutation in Chinese Multiple Myeloma Patients.
- Author
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Cheung CHY, Cheng CK, Lau KM, Ip RKL, Chan NCN, Tam THC, Wong RSM, Raghupathy R, Chan NPH, and Ng MHL
- Subjects
- Adult, Aged, Aged, 80 and over, Asian People, Biomarkers, Tumor, China epidemiology, DNA Mutational Analysis, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multiple Myeloma epidemiology, Multiple Myeloma mortality, Prevalence, ras Proteins genetics, Amino Acid Substitution, Multiple Myeloma genetics, Multiple Myeloma pathology, Mutation, Proto-Oncogene Proteins B-raf genetics
- Abstract
Background: Previous studies in Western countries demonstrated BRAF V600E mutation only in a small subset of multiple myeloma (MM) patients. However, the prevalence and clinicopathologic significances of this mutation remain unclear in Chinese MM patients., Patients and Methods: We studied diagnostic bone marrow samples from 205 Chinese MM patients by allele-specific PCR to detect BRAF V600E mutation and by high-resolution melting assay to detect KRAS and NRAS mutations. The mutations were confirmed by independent assays., Results: BRAF V600E mutation was found in 9.3% of the cases, the highest prevalence hitherto reported. In addition, the mutation was significantly associated with hypercalcemia and a male predominance but not with aggressive extramedullary diseases or a high serum creatinine level as reported in Western studies. Importantly, BRAF V600E mutation was an adverse prognostic factor for overall survival in younger MM patients by subgroup analysis. Concurrent analysis of RAS mutations highlighted differential alteration spectrum of RAS signaling between Chinese and Western MM, which may suggest a unique myeloma-related genetic profile in Chinese patients., Conclusion: Our study revealed a higher prevalence of BRAF V600E mutation in Chinese MM patients. The associated prognostic impacts on younger patients could be beneficial to risk stratification and potential application of BRAF-targeted therapies in Chinese MM management. This is the first large-scale study revealing the prevalence and clinicopathologic significances of BRAF V600E mutation in Chinese myeloma., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
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71. Next-generation sequencing and molecular cytogenetic characterization of ETV6-LYN fusion due to chromosomes 1, 8 and 12 rearrangement in acute myeloid leukemia.
- Author
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Ma ESK, Wan TSK, Au CH, Ho DN, Ma SY, Ng MHL, and Chan TL
- Subjects
- Adult, Chromosome Aberrations, High-Throughput Nucleotide Sequencing methods, Humans, In Situ Hybridization, Fluorescence, Leukemia, Myeloid, Acute pathology, Male, ETS Translocation Variant 6 Protein, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, Pair 12 genetics, Chromosomes, Human, Pair 8 genetics, Gene Rearrangement, Leukemia, Myeloid, Acute genetics, Oncogene Proteins, Fusion genetics, Proto-Oncogene Proteins c-ets genetics, Repressor Proteins genetics, src-Family Kinases genetics
- Abstract
In a newly diagnosed patient with acute myeloid leukemia (AML) and complex cytogenetics and negative for gene mutations associated with myeloid neoplasms, RNA sequencing by next-generation sequencing (NGS) through a large cancer-related gene panel showed ETV6-LYN leukemic fusion transcript. Breakpoint analysis of the NGS reads showed fusion of exon 5 of the ETV6 gene to exon 8 of the LYN gene. Metaphase fluorescence in situ hybridization (FISH) inferred a four-break rearrangement of three chromosomes, namely 1, 8 and 12. First, there was a balanced translocation t(1;12)(p13;p13.2) in which the ETV6 was split between der(1) and der(12). Second, an inverted insertion of 8q12.1~q24.21 into 1p13 occurred, thus bringing ETV6 and LYN into juxtaposition in the correct 5' to 3' orientation to produce an in-frame chimeric fusion gene on der(1). Notwithstanding two previous reports of ETV6-LYN fusion in myeloproliferative neoplasms (MPN), we report the first case of this fusion in AML and hence broaden its disease association. We also illustrate the clinical utility of NGS based detection of gene fusion in the setting of complex karyotype or cryptic aberration, since this method does not require a priori knowledge of the translocation partner and exact breakpoints to guide the application of appropriate primers or probes., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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- View/download PDF
72. First Report of Hb Kent [β37(C3)Trp→Cys (TGG>TGC) HBB: c.114G>C] in a Chinese Family.
- Author
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Chan NCN, Chow KH, Leung RFY, Tang SSH, Chiu MFW, Lie R, Cheng KCK, Lau KM, Chan NPH, and Ng MHL
- Subjects
- Adult, Amino Acid Substitution, Asian People, China, Family, Female, Hemoglobins, Abnormal metabolism, Humans, Male, Hemoglobins, Abnormal genetics, Mutation, Missense
- Abstract
We report a novel HBB: c.114G>C mutation in a Chinese family. This mutation resulted in a β37(C3)Trp→Cys amino acid substitution and was synonymous with Hb Kent, a hemoglobin (Hb) variant that was reported exclusively in patients of European descent. Though Hb Kent has a normal oxygen affinity and molecular stability, it has a characteristic dual variant appearance on cellulose acetate electrophoresis (CAE) and high performance liquid chromatography (HPLC) caused by the posttranslational modification of cysteine. We also report the phenotypic expression of this variant when coinherited with the Southeast Asian (- -
SEA ) double α-globin gene deletion.- Published
- 2017
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73. Chromosome Preparation for Myeloid Malignancies.
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Hui EK, Wan TS, and Ng MH
- Subjects
- Bone Marrow pathology, Bone Marrow Cells metabolism, Bone Marrow Cells pathology, Cell Count, Cells, Cultured, Humans, Chromosome Aberrations, Cytogenetic Analysis methods, Myeloproliferative Disorders diagnosis, Myeloproliferative Disorders genetics
- Abstract
Many cases of myeloid malignancies are associated with recurring cytogenetic aberrations. Chromosomal analysis can aid in diagnosis, predict prognosis, and disclose subsequent clonal evolution. Three different cell culture methods: direct harvest, nonsynchronized culture, and synchronized culture are usually prepared if the nucleated cell counts in marrow blood are sufficient. Synchronized culture is the first choice of method in myeloid malignancies, whereas the direct method can be omitted if the cell count is low. The aseptic culture technique is strictly followed until harvesting procedure. For synchronized culture, uridine and fluorodeoxyuridine are added as blocking reagents and released by thymidine on the following day. Harvesting steps of the cultures involved colcemid exposure, hypotonic treatment, and Carnoy's fixation. The cells are then ready for slide making and banding for chromosomal analysis.
- Published
- 2017
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74. Chromosome Recognition.
- Author
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Wan TS, Hui EK, and Ng MH
- Subjects
- Chromosome Aberrations, Chromosome Banding, Chromosomes, Human, Humans, Metaphase, Neoplasms diagnosis, Neoplasms genetics, Cytogenetic Analysis methods, Karyotype, Karyotyping
- Abstract
Chromosomal analysis of human cells serves to characterize aberrations of chromosome number and structure. Individual chromosome can be identified precisely by recognition of its morphological characteristics and staining patterns according to specific landmarks, regions, and bands as described in the ideogram. Since the quality of metaphases obtained from malignant cells is generally poor for karyotyping, a practical and accurate chromosome recognition training guide is mandatory for a trainee or newly employed cytogenetic technologist in a cancer cytogenetics laboratory. The most distinguishable bands for each chromosome are described in detail in this chapter with an aim to facilitate quick and accurate karyotyping in cancers. This is an indispensable chromosome recognition guide used in a cancer cytogenetics laboratory.
- Published
- 2017
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75. A Multi-locus Approach to Characterization of Major Quantitative Trait Loci Influencing Hb F Regulation in Chinese β-thalassemia Carriers.
- Author
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Chan NC, Lau KM, Cheng KC, Chan NP, and Ng MH
- Subjects
- Adult, Asian People, DNA, Intergenic genetics, Female, GTP-Binding Proteins genetics, HSP70 Heat-Shock Proteins genetics, Humans, Male, Models, Statistical, Peptide Elongation Factors genetics, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-myb genetics, Fetal Hemoglobin metabolism, Heterozygote, Quantitative Trait Loci, beta-Thalassemia genetics
- Abstract
Genetic association studies showed that Hb F is under the influence of major quantitative trait loci (QTL) in β-thalassemia (β-thal) carriers. Single nucleotide polymorphisms (SNPs) at three major QTLs, BCL11A, HBS1L-MYB intergenic region and XmnI-HBG2 were individually validated in univariate models. However, their relative effect sizes on Hb F regulation are unknown. We genotyped 99 Chinese β-thal carriers for the three major QTLs and performed genetic association studies using three different statistical models, including mass univariate analysis, multivariate linear regression and partial least square regression structural equation modeling (PLS-SEM). Performances of the three models were compared and effect sizes of the three QTLs in a multivariate model were assessed. Traditional mass univariate analysis and multivariate linear regression showed limited statistical power in our small cohort and the latter was constrained by multicollinearity. Partial least structural equation modeling showed significant positive associations of each QTL (p <0.05) with Hb F regulation, together explained 34.4% of variance. The HBS1L-MYB intergenic region polymorphism (HMIP) demonstrated the highest effect on Hb F prediction with effect size f
2 0.294. PLS-SEM offered a statistically powerful multivariate model for multi-locus genetic association studies. We reproduced findings of previous studies with a much smaller cohort and demonstrated HMIP as the strongest regulator of Hb F in Chinese β-thal carriers.- Published
- 2016
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76. Hb Tarrant [α126(H9)Asp→Asn; HBA2: c.379G > A (or HBA1)] in a Chinese Family as a Cause of Familial Erythrocytosis.
- Author
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Ip KL, So JC, Law MF, Wong RS, Tam HC, and Ng MH
- Subjects
- Asian People, Clinical Laboratory Techniques methods, Humans, Molecular Diagnostic Techniques, Pedigree, Polycythemia etiology, Hemoglobins, Abnormal, Polycythemia congenital, Polycythemia genetics
- Abstract
Hb Tarrant [α126(H9)Asp→Asn; HBA2: c.379G > A (or HBA1)], is a rare high oxygen affinity hemoglobin (Hb) variant that causes erythrocytosis, previously described in a few Mexican-American families. Here we report the first Chinese family with this Hb variant presenting with unexplained familial erythrocytosis. No evidence of hemolysis was seen. A locally adapted approach to the diagnostic process in clinical laboratories is discussed. Molecular analysis has an important role in confirmation of the diagnosis. Proper identification of this rare but clinically significant Hb variant is helpful for family counseling and will help to guide appropriate management of absolute erythrocytosis.
- Published
- 2016
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77. Preclinical evaluation of the mTOR-PI3K inhibitor BEZ235 in nasopharyngeal cancer models.
- Author
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Ma BB, Lui VW, Hui CW, Lau CP, Wong CH, Hui EP, Ng MH, Cheng SH, Tsao SW, Tsang CM, Cheung CS, Ho K, and Chan AT
- Subjects
- Animals, Antineoplastic Agents pharmacology, Carcinoma, Cell Cycle, Cell Line, Tumor, Cell Survival, Cisplatin pharmacology, Enzyme Activation, Female, Humans, Inhibitory Concentration 50, MAP Kinase Signaling System, Mice, Mice, Nude, Nasopharyngeal Carcinoma, Nasopharyngeal Neoplasms genetics, Neoplasm Transplantation, Paclitaxel pharmacology, Phosphoinositide-3 Kinase Inhibitors, TOR Serine-Threonine Kinases antagonists & inhibitors, Gene Expression Regulation, Neoplastic, Imidazoles pharmacology, Nasopharyngeal Neoplasms metabolism, Phosphatidylinositol 3-Kinases metabolism, Quinolines pharmacology, TOR Serine-Threonine Kinases metabolism
- Abstract
The dual PI3K-mTOR inhibitor BEZ235 was evaluated in preclinical models of nasopharyngeal carcinoma (NPC). The IC50 value of BEZ235 for growth was in the nanomolar range in vitro, induce G1 cycle arrest and apoptosis, and inhibited AKT and mTOR signaling in most NPC cell lines. No synergistic effect was observed when BEZ235 was combined with chemotherapy. BEZ235 increased MAPK activation in vitro but not in vivo. A daily schedule was more effective than a weekly schedule on tumor growth and inhibition of downstream mTOR signaling in vivo. The activity of BEZ235 maybe independent of the PIK3CA amplification and mutation status., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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78. SIRT2 overexpression in hepatocellular carcinoma mediates epithelial to mesenchymal transition by protein kinase B/glycogen synthase kinase-3β/β-catenin signaling.
- Author
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Chen J, Chan AW, To KF, Chen W, Zhang Z, Ren J, Song C, Cheung YS, Lai PB, Cheng SH, Ng MH, Huang A, and Ko BC
- Subjects
- Adult, Aged, Apoptosis, Cell Movement, Cell Proliferation, Female, Gene Silencing, Glycogen Synthase Kinase 3 metabolism, Glycogen Synthase Kinase 3 beta, Hep G2 Cells, Humans, Male, Middle Aged, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction, beta Catenin metabolism, Carcinoma, Hepatocellular metabolism, Epithelial-Mesenchymal Transition, Liver Neoplasms metabolism, Sirtuin 2 metabolism
- Abstract
Unlabelled: Sirtuin 1 (SIRT1) has been implicated in telomere maintenance and the growth of hepatocellular carcinoma (HCC). Nevertheless, the role of other sirtuins in the pathogenesis of HCC remains elusive. We found that sirtuin 2 (SIRT2), another member of the sirtuin family, also contributes to cell motility and invasiveness of HCC. SIRT2 is up-regulated in HCC cell lines and in a subset of human HCC tissues (23/45). Up-regulations of SIRT2 in primary HCC tumors were significantly correlated with the presence of microscopic vascular invasion (P = 0.001), a more advanced tumor stage (P = 0.004), and shorter overall survival (P = 0.0499). Functional studies by short hairpin RNA-mediated suppression of SIRT2 expression in HCC cell lines revealed significant inhibition of motility and invasiveness. Depletion of SIRT2 also led to the regression of epithelial-mesenchymal transition (EMT) phenotypes, whereas the ectopic expression of SIRT2 in the immortalized hepatocyte cell line L02 promoted cell motility and invasiveness. Mechanistic studies revealed that SIRT2 regulates the deacetylation and activation of protein kinase B, which subsequently impinges on the glycogen synthase kinase-3β/β-catenin signaling pathway to regulate EMT., Conclusions: Our findings have uncovered a novel role for SIRT2 in HCC metastasis, and provide a rationale to explore the use of sirtuin inhibitors in HCC therapy. (HEPATOLOGY 2013;)., (Copyright © 2013 American Association for the Study of Liver Diseases.)
- Published
- 2013
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79. A polymorphism in the 3'-untranslated region of the NPM1 gene causes illegitimate regulation by microRNA-337-5p and correlates with adverse outcome in acute myeloid leukemia.
- Author
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Cheng CK, Kwan TK, Cheung CY, Ng K, Liang P, Cheng SH, Chan NP, Ip RK, Wong RS, Lee V, Li CK, Yip SF, and Ng MH
- Subjects
- Adult, Aged, Female, Genotype, Humans, Male, Middle Aged, Nucleophosmin, Young Adult, 3' Untranslated Regions, Gene Expression Regulation, Leukemic, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute mortality, MicroRNAs genetics, Nuclear Proteins genetics, Polymorphism, Genetic
- Abstract
Nucleophosmin, encoded by NPM1, is a haploinsufficient suppressor in hematologic malignancies. NPM1 mutations are mostly found in acute myeloid leukemia patients with normal karyotype and associated with favorable prognosis. A polymorphic nucleotide T deletion with unknown significance is present in the NPM1 3'-untranslated region. Here, we showed that the homozygous nucleotide T deletion was associated with adverse outcomes and could independently predict shortened survival in patients with de novo acute myeloid leukemia. Mechanistically, we demonstrated that the nucleotide T deletion created an illegitimate binding NPM1 for miR-337-5p, which was widely expressed in different acute myeloid leukemia subtypes and inhibited NPM1 expression. Accordingly, NPM1 levels were found to be significantly reduced and correlated with miR-337-5p levels in patients carrying a homozygous nucleotide T-deletion genotype. Together, our findings uncover a microRNA-mediated control of NPM1 expression that contributes to disease heterogeneity and suggest additional prognostic values of NPM1 in acute myeloid leukemia.
- Published
- 2013
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80. Platelet factor 4 induces cell apoptosis by inhibition of STAT3 via up-regulation of SOCS3 expression in multiple myeloma.
- Author
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Liang P, Cheng SH, Cheng CK, Lau KM, Lin SY, Chow EY, Chan NP, Ip RK, Wong RS, and Ng MH
- Subjects
- Cell Line, Tumor, Gene Expression Regulation, Neoplastic drug effects, Gene Silencing, Humans, Interleukin-6 pharmacology, Low Density Lipoprotein Receptor-Related Protein-1 metabolism, Multiple Myeloma mortality, Multiple Myeloma pathology, Neovascularization, Pathologic, Phosphorylation drug effects, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, Signal Transduction drug effects, Suppressor of Cytokine Signaling 3 Protein, Apoptosis drug effects, Apoptosis genetics, Multiple Myeloma genetics, Multiple Myeloma metabolism, Platelet Factor 4 pharmacology, STAT3 Transcription Factor antagonists & inhibitors, Suppressor of Cytokine Signaling Proteins genetics
- Abstract
Platelet factor 4 (PF4) is an angiostatic chemokine that suppresses tumor growth and metastasis. We previously revealed frequent transcriptional silencing of PF4 in multiple myeloma, but the functional roles of this chemokine are still unknown. We studied the apoptotic effects of PF4 on myeloma cell lines and primary myeloma in vitro, and investigated the involved signaling pathway. The in vivo effects were also studied using a mouse model. PF4 not only suppressed myeloma-associated angiogenesis, but also inhibited growth and induced apoptosis in myeloma cells. We found that PF4 negatively regulated STAT3 and concordantly inhibited constitutive and interleukin-6-induced phosphorylation of STAT3, and down-regulated the expression of STAT3 target genes (Mcl-1, survivin and VEGF). Overexpression of constitutively activated STAT3 could rescue PF4-induced apoptotic effects. Furthermore, we found that PF4 induced the expression of SOCS3, a STAT3 inhibitor, and gene silencing of SOCS3 abolished its ability to inhibit STAT3 activation, suggesting a critical role of SOCS3 in PF4-induced STAT3 inhibition. Knockdown of LRP1, a putative PF4 receptor, could also abolish PF4-induced apoptosis and STAT3 inhibition. Finally, the tumor growth inhibitory effect of PF4 was confirmed by in vivo mouse models. Immunostaining of rabbit bone xenografts from PF4-treated mice showed induction of apoptosis of myeloma cells and inhibition of angiogenesis, which was associated with suppression of STAT3 activity. Together, our preclinical data indicate that PF4 may be a potential new targeting agent for the treatment of myeloma.
- Published
- 2013
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81. A novel 19q13 nucleolar zinc finger protein suppresses tumor cell growth through inhibiting ribosome biogenesis and inducing apoptosis but is frequently silenced in multiple carcinomas.
- Author
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Cheng Y, Liang P, Geng H, Wang Z, Li L, Cheng SH, Ying J, Su X, Ng KM, Ng MH, Mok TS, Chan AT, and Tao Q
- Subjects
- Animals, COS Cells, Chlorocebus aethiops, CpG Islands, DNA Methylation genetics, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Gene Silencing, HCT116 Cells, Humans, Ribosomes metabolism, Apoptosis genetics, Cell Proliferation, Nuclear Proteins genetics, Nuclear Proteins metabolism, Zinc Fingers genetics
- Abstract
Epigenetic disruption of tumor suppressor genes is frequently involved in tumorigenesis. We identified a novel 19q13 KRAB domain-containing zinc finger protein, ZNF545/ZFP82, broadly expressed in normal tissues but downregulated in multiple tumor cell lines. The ZNF545 promoter contains a CpG island, which is frequently methylated in cell lines. The transcriptional silencing of ZNF545 could be reversed by pharmacologic or genetic demethylation, indicating direct epigenetic silencing. ZNF545 was also frequently methylated in multiple primary tumors of nasopharyngeal, esophageal, lung, gastric, colon, and breast, but rarely in normal epithelial tissues and paired normal tissues. ZNF545 is located in the nucleus and mainly sequestered in nucleoli, functioning as a repressor. ZNF545 is able to repress NF-κB and AP-1 signaling pathways, whereas ectopic expression of ZNF545 in silenced tumor cells significantly inhibited their growth and induced apoptosis. Functional studies showed that ZNF545 was involved in ribosome biogenesis through inhibiting the activity of rDNA promoter and decreasing cellular protein translation efficiency. Thus, we identified ZNF545 as a novel tumor suppressor inducing tumor cell apoptosis, repressing ribosome biogenesis and target gene transcription. The tumor-specific methylation of ZNF545 could be an epigenetic biomarker for cancer diagnosis., (Mol Cancer Res; 10(7); 925-36. ©2012 AACR.)
- Published
- 2012
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82. A pale Chinese boy with recurrent painful digital swelling.
- Author
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Cheng FW, Leung WK, Lee V, Ng MH, Chu WC, Huen KF, Shing MK, and Li CK
- Subjects
- Child, Fingers, Humans, Male, Pallor etiology, Recurrence, Pain etiology, Sickle Cell Trait complications, beta-Thalassemia complications
- Abstract
Thalassaemia is the most common haemoglobinopathy in the Chinese population. However, recurrent painful digital swelling is not a typical manifestation of this well-known hereditary condition. We describe a case of co-inheritance of beta-thalassaemia and sickle cell trait in a Chinese family and a child who suffered from sickle cell/beta-thalassaemia with recurrent dactylitis. This report highlights awareness of this rare condition in the Chinese population, since acute manifestations can be life-threatening and mimic other emergency conditions. Prompt management can prevent further complications and avoid unnecessary interventions due to delay in diagnosis. A detailed family history and examination of the patient's peripheral blood smear is crucial to reach a correct diagnosis.
- Published
- 2012
83. Familial aggregation of narcolepsy.
- Author
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Wing YK, Chen L, Lam SP, Li AM, Tang NL, Ng MH, Cheng SH, Ho CK, Mok V, Leung HW, Lau A, Chan MH, Chan HS, and Chan PS
- Subjects
- Adolescent, Adult, Child, Female, Histocompatibility Testing, Humans, Male, Narcolepsy diagnosis, Polysomnography, Prevalence, Risk Factors, Young Adult, Family, Family Health statistics & numerical data, HLA-DQ beta-Chains genetics, Narcolepsy epidemiology, Narcolepsy genetics
- Abstract
Objectives: To determine the familial aggregation of narcolepsy from perspectives of clinical symptomatology, polysomnographic data, and human leukocyte antigen (HLA) typing., Methods: This was a Family study at the University-affiliated hospital. The participants were narcolepsy probands and their first degree relatives, and, also, age and sex matched unrelated healthy controls. Interventions were not applicable., Measurements and Results: All study subjects underwent structured interviews, overnight polysomnography followed by a multiple sleep latency test (MSLT), and HLA typing. Altogether, 33 probands and 81 first degree relatives (response rate 65%) were recruited. Among the relatives, 12.3% were diagnosed with narcolepsy and 39.5% had narcolepsy spectrum as defined by unexplained abnormal MSLT (shortened MSL and SOREMP) results. The relative risk of narcolepsy in first degree relatives was 361.8. Familial aggregation of narcolepsy symptoms, excessive daytime sleepiness, HLA status, abnormal MSLT, and nocturnal polysomnographic findings were observed., Conclusions: The familial risk of narcolepsy among first degree relatives is much higher than previously reported. There exists a spectrum of narcolepsy features among relatives, ranging from full clinical tetrads to asymptomatic abnormal MSLT findings., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2011
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84. KRAB zinc finger protein ZNF382 is a proapoptotic tumor suppressor that represses multiple oncogenes and is commonly silenced in multiple carcinomas.
- Author
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Cheng Y, Geng H, Cheng SH, Liang P, Bai Y, Li J, Srivastava G, Ng MH, Fukagawa T, Wu X, Chan AT, and Tao Q
- Subjects
- Animals, Apoptosis genetics, COS Cells, Cell Growth Processes genetics, Chlorocebus aethiops, DNA Methylation, DNA-Binding Proteins biosynthesis, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Knockout Techniques, Gene Silencing, HCT116 Cells, Humans, I-kappa B Kinase genetics, Inhibitor of Differentiation Protein 1 genetics, NF-kappa B antagonists & inhibitors, NF-kappa B metabolism, Neoplasms, Multiple Primary metabolism, Neoplasms, Multiple Primary pathology, Promoter Regions, Genetic, STAT3 Transcription Factor genetics, STAT5 Transcription Factor genetics, Signal Transduction, Transcription Factor AP-1 antagonists & inhibitors, Transcription Factor AP-1 metabolism, Transcription Factors biosynthesis, DNA-Binding Proteins genetics, Genes, Tumor Suppressor, Neoplasms, Multiple Primary genetics, Transcription Factors genetics
- Abstract
Zinc finger transcription factors are involved broadly in development and tumorigenesis. Here, we report that the little studied zinc finger transcription factor ZNF382 functions as a tumor suppressor in multiple carcinomas. Although broadly expressed in normal tissues, ZNF382 expression was attenuated in multiple carcinoma cell lines due to promoter CpG methylation. ZNF382 was also frequently methylated in multiple primary tumors (nasopharyngeal, esophageal, colon, gastric, and breast). Ectopic expression of ZNF382 in silenced tumor cells significantly inhibited their clonogenicity and proliferation and induced apoptosis. We further found that ZNF382 inhibited NF-kappaB and AP-1 signaling and downregulated the expression of multiple oncogenes including MYC, MITF, HMGA2, and CDK6, as well as the NF-kappaB upstream factors STAT3, STAT5B, ID1, and IKBKE, most likely through heterochromatin silencing. ZNF382 could suppress tumorigenesis through heterochromatin-mediated silencing, as ZNF382 was colocalized and interacted with heterochromatin protein HP1 and further changed the chromatin modifications of ZNF382 target oncogenes. Our data show that ZNF382 is a functional tumor suppressor frequently methylated in multiple carcinomas., ((c)2010 AACR.)
- Published
- 2010
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85. Reverse phase protein array identifies novel anti-invasion mechanisms of YC-1.
- Author
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Hong B, Lui VW, Hui EP, Lu Y, Leung HS, Wong EY, Cheng SH, Ng MH, Mills GB, and Chan AT
- Subjects
- Carcinoma drug therapy, Carcinoma pathology, Cell Line, Tumor, Cell Proliferation drug effects, Checkpoint Kinase 1, Checkpoint Kinase 2, Down-Regulation, Gene Expression Regulation, Neoplastic physiology, Humans, Nasopharyngeal Neoplasms drug therapy, Nasopharyngeal Neoplasms pathology, Neoplasm Invasiveness, Poly(ADP-ribose) Polymerases metabolism, Protein Kinases metabolism, Protein Serine-Threonine Kinases metabolism, S Phase drug effects, Antineoplastic Agents pharmacology, Furans pharmacology, Indazoles pharmacology, Neoplasm Proteins metabolism, Protein Array Analysis methods
- Abstract
YC-1 has recently been demonstrated to have potent anti-invasion and anti-metastatic activity in several cancer models, in addition to its anti-proliferation activity. However, the mechanism underlying its anti-invasion/anti-metastatic activity is largely unknown. Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer in Southeast Asia. Here, we demonstrated that YC-1 inhibited invasiveness and proliferation of NPC cells, with the latter being accompanied by PARP cleavage, S-phase arrest and activation of Chk1/Chk2. We aimed at identifying novel anti-invasion mechanisms of YC-1 in NPC by a functional proteomic platform, the reverse phase protein array (RPPA). Our study revealed for the first time that multiple invasion-related signaling proteins (beta-catenin, caveolin, Src and EGFR), as well as several growth-related proteins (AMPKalpha, phospho-acetyl-CoA carboxylase (p-ACC), HER-2 and mTOR), which were previously un-described signaling proteins altered by YC-1, were found to be down-modulated by YC-1 in NPC cells. We hypothesized that YC-1-mediated downregulation of these invasion proteins contributed to its anti-invasion activity in NPC cells. Overexpression of EGFR, activated Src or caveolin, but not beta-catenin reversed the inhibitory effects of YC-1 on NPC cell invasion, with EGFR and activated Src having additional effects on rescuing NPC cells from YC-1-mediated growth inhibition. In summary, we have identified several novel anti-invasion mechanisms of YC-1 that could impact NPC, and possibly other cancers as well., (Copyright 2009. Published by Elsevier Inc.)
- Published
- 2010
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86. Alisol B, a novel inhibitor of the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase pump, induces autophagy, endoplasmic reticulum stress, and apoptosis.
- Author
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Law BY, Wang M, Ma DL, Al-Mousa F, Michelangeli F, Cheng SH, Ng MH, To KF, Mok AY, Ko RY, Lam SK, Chen F, Che CM, Chiu P, and Ko BC
- Subjects
- Animals, Antineoplastic Agents pharmacology, Cells, Cultured, Drug Screening Assays, Antitumor, Endoplasmic Reticulum pathology, Enzyme Inhibitors pharmacology, HeLa Cells, Humans, Inhibitory Concentration 50, Mice, Models, Biological, Unfolded Protein Response drug effects, Apoptosis drug effects, Autophagy drug effects, Cholestenones pharmacology, Endoplasmic Reticulum drug effects, Sarcoplasmic Reticulum Calcium-Transporting ATPases antagonists & inhibitors, Stress, Physiological drug effects
- Abstract
Emerging evidence suggests that autophagic modulators have therapeutic potential. This study aims to identify novel autophagic inducers from traditional Chinese medicinal herbs as potential antitumor agents. Using an image-based screen and bioactivity-guided purification, we identified alisol B 23-acetate, alisol A 24-acetate, and alisol B from the rhizome of Alisma orientale as novel inducers of autophagy, with alisol B being the most potent natural product. Across several cancer cell lines, we showed that alisol B-treated cells displayed an increase of autophagic flux and formation of autophagosomes, leading to cell cycle arrest at the G(1) phase and cell death. Alisol B induced calcium mobilization from internal stores, leading to autophagy through the activation of the CaMKK-AMPK-mammalian target of rapamycin pathway. Moreover, the disruption of calcium homeostasis induces endoplasmic reticulum stress and unfolded protein responses in alisol B-treated cells, leading to apoptotic cell death. Finally, by computational virtual docking analysis and biochemical assays, we showed that the molecular target of alisol B is the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase. This study provides detailed insights into the cytotoxic mechanism of a novel antitumor compound.
- Published
- 2010
- Full Text
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87. Role of 'atypical pathogens' among adult hospitalized patients with community-acquired pneumonia.
- Author
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Lui G, Ip M, Lee N, Rainer TH, Man SY, Cockram CS, Antonio GE, Ng MH, Chan MH, Chau SS, Mak P, Chan PK, Ahuja AT, Sung JJ, and Hui DS
- Subjects
- Aged, Aged, 80 and over, Anti-Bacterial Agents therapeutic use, Chlamydophila Infections diagnosis, Chlamydophila Infections epidemiology, Community-Acquired Infections diagnosis, Community-Acquired Infections epidemiology, Female, Hong Kong epidemiology, Humans, Male, Middle Aged, Pneumonia, Bacterial diagnosis, Pneumonia, Bacterial epidemiology, Pneumonia, Mycoplasma diagnosis, Pneumonia, Mycoplasma epidemiology, Prevalence, Prognosis, Prospective Studies, Retrospective Studies, Severity of Illness Index, Chlamydophila Infections microbiology, Chlamydophila pneumoniae pathogenicity, Community-Acquired Infections microbiology, Mycoplasma pneumoniae pathogenicity, Pneumonia, Bacterial microbiology, Pneumonia, Mycoplasma microbiology
- Abstract
Background and Objective: Agents such as Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila are recognized as important causes of community-acquired pneumonia (CAP) worldwide. This study examined the role of these 'atypical pathogens' (AP) among adult hospitalized patients with CAP., Methods: A prospective, observational study of consecutive adult CAP (clinico-radiological diagnosis) patients hospitalized during 2004-2005 was conducted. Causal organisms were determined using cultures, antigen testing and paired serology. Clinical/laboratory/radiological variables and outcomes were compared between different aetiologies, and a clinical prediction rule for AP was constructed., Results: There were 1193 patients studied (mean age 70.8 +/- 18.0 years, men 59.3%). Causal organisms were identified in 468 (39.2%) patients: 'bacterial' (48.7%), 'viral' (26.9%), 'AP' (28.6%). The AP infections comprised Mycoplasma or Chlamydophila pneumoniae (97.8%) and co-infection with bacteria/virus (30.6%). The majority of AP infections involved elderly patients (63.4%) with comorbidities (41.8%), and more than one-third of patients were classified as 'intermediate' or 'high' risk CAP on presentation (pneumonia severity index IV-V (35.1%); CURB-65 2-5 (42.5%)). Patients with AP infections had disease severities and outcomes similar to patients with CAP due to other organisms (oxygen therapy 29.1% vs 29.8%; non-invasive ventilation 3.7% vs 3.3%; admission to the intensive care unit 4.5% vs 2.7%; length of hospitalization 6 day vs 7 day; 30-day mortality: 2.2% vs 6.0%; overall P > 0.05). Age <65 years, female gender, fever > or =38.0 degrees C, respiratory rate <25/min, pulse rate <100/min, serum sodium >130 mmol/L, leucocyte count <11 x 10(9)/L and Hb < 11 g/dL were features associated with AP infection, but the derived prediction rule failed to reliably discriminate CAP caused by AP from bacterial CAP (area under the curve 0.75)., Conclusions: M. pneumoniae and C. pneumoniae as single/co-pathogens are important causes of severe pneumonia among older adults. No reliable clinical indicators exist, so empirical antibiotic coverage for hospitalized CAP patients may need to be considered.
- Published
- 2009
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88. Thrombopoietin levels increased in patients with severe acute respiratory syndrome.
- Author
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Yang M, Ng MH, Li CK, Chan PK, Liu C, Ye JY, and Chong BH
- Subjects
- Antigens, CD34 biosynthesis, Enzyme-Linked Immunosorbent Assay methods, Hematopoietic Stem Cells cytology, Humans, Megakaryocytes cytology, Microscopy, Fluorescence, Models, Biological, Regression Analysis, Severe acute respiratory syndrome-related coronavirus metabolism, Severe Acute Respiratory Syndrome virology, Stem Cells, Thrombocytopenia blood, Thrombocytopenia genetics, Transforming Growth Factor beta immunology, Gene Expression Regulation, Severe Acute Respiratory Syndrome blood, Thrombopoietin biosynthesis
- Abstract
Hematological changes in patients with Severe Acute Respiratory Syndrome (SARS) are common and frequently include thrombocytopenia. Using a ELISA method, we found an increase in thrombopoietin (TPO) levels in the plasma of convalesced SARS patients (290+/-53 pg/ml) and active SARS patients (251+/-23 pg/ml) comparing to that from normal control patients (228+/-17 pg/ml). In addition, the plasma from active SARS patients had an inhibitory effect on CFU-MK formation, which could be neutralized by anti-TGF-beta antibodies. In the experiment to determine whether SARS-CoV can directly infect hematopoietic stem cells and megakaryocytic cells, incubation of the cells with SARS-CoV did not show active infection. Our findings of increased TPO levels in the plasma of SARS patients provide a possible explanation for the genesis of thrombocytosis, which frequently develops from thrombocytopenia in SARS patients.
- Published
- 2008
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89. Use of cefoperazone still needs a caution for bleeding from induced vitamin K deficiency.
- Author
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Wong RS, Cheng G, Chan NP, Wong WS, and NG MH
- Subjects
- Aged, 80 and over, Anti-Bacterial Agents administration & dosage, Blood Coagulation drug effects, Blood Coagulation Factors analysis, Blood Component Transfusion, Cefoperazone administration & dosage, Female, Hematuria blood, Hematuria drug therapy, Hematuria urine, Humans, Infusions, Intravenous, Plasma, Vitamin K administration & dosage, Vitamin K Deficiency blood, Vitamin K Deficiency therapy, Vitamin K Deficiency urine, Anti-Bacterial Agents adverse effects, Cefoperazone adverse effects, Hematuria complications, Vitamin K Deficiency etiology
- Published
- 2006
- Full Text
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90. Thrombocytopenia in patients with severe acute respiratory syndrome (review).
- Author
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Yang M, Ng MH, and Li CK
- Subjects
- Hematopoietic Stem Cells immunology, Hematopoietic Stem Cells virology, Humans, Lymphocyte Count, Lymphopenia etiology, Lymphopenia immunology, Lymphopenia virology, Purpura, Thrombocytopenic, Idiopathic etiology, Purpura, Thrombocytopenic, Idiopathic virology, Severe Acute Respiratory Syndrome complications, Purpura, Thrombocytopenic, Idiopathic immunology, Severe acute respiratory syndrome-related coronavirus immunology, Severe Acute Respiratory Syndrome immunology
- Abstract
Severe Acute Respiratory Syndrome (SARS) has been recognized as a new human infectious disease caused by a novel coronavirus (SARS-CoV). Hematological changes in patients with SARS were common, including notably lymphopenia and thrombocytopenia. While the former is the result of decreases in CD4+ or CD8+ T-lymphocytes related to the onset of disease or use of glucocorticoids, the latter may involve a number of potential mechanisms. Although the development of autoimmune antibodies or immune complexes triggered by viral infection may play a significant role in inducing thrombocytopenia, SARS-CoV may also directly infect hematopoietic stem/progenitor cells, megakaryocytes and platelets inducing their growth inhibition and apoptosis. Moreover, the increased consumption of platelets and/or the decreased production of platelets in the damaged lungs are a potential alternative mechanism that can contribute to thrombocytopenia in severe critical pulmonary conditions, which has been rarely revealed and will be discussed.
- Published
- 2005
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91. Identification of TPO receptors on central nervous system-a preliminary report.
- Author
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Yang M, Xia WJ, Li K, Pong NH, Chik KW, Li CK, Ng MH, Ng HK, Fung KP, and Fok TF
- Subjects
- Animals, Apoptosis drug effects, Cell Line, Cell Proliferation drug effects, Erythropoietin pharmacology, Humans, Mice, Neurons drug effects, Receptors, Thrombopoietin, Thrombopoietin pharmacology, Brain Chemistry, Neoplasm Proteins analysis, Oncogene Proteins analysis, Proto-Oncogene Proteins analysis, Receptors, Cytokine analysis
- Abstract
To identify the expression of thrombopoietin (TPO) receptors (c-mpl) on central nervous system (CNS) and to evaluate the role of TPO on neural cell proliferation and protection, immunohistochemical staining, RT-PCR, MTT, and annexin-V methods were used in this study. The results showed the expression of TPO receptor on human CNS and murine neural cells. C-mpl mRNA was identified in human cerebral hemispheres and cerebellum, and mouse neural cell line C17.2 by RT-PCR. C-mpl was also confirmed in human cerebral hemispheres by immunohistostaining with con-focal microscopy. Furthermore, TPO had a stimulating effect on the growth of in vitro neural cell C17.2 by MTT assay. The anti-apoptotic effect of TPO on C17.2 cells was also demonstrated by staining with annexin-V and PI. In conclusion, the first evidence showed the expression of TPO receptor c-mpl in central nervous system. Moreover, the effect of TPO on neural cell proliferation and anti-apoptosis was also demonstrated on in vitro neural cells.
- Published
- 2004
92. Childhood acute myeloid leukemia with CBFbeta-MYH11 rearrangement: study of incidence, morphology, cytogenetics, and clinical outcomes of Chinese in Hong Kong.
- Author
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Chan NP, Wong WS, Ng MH, Tsang KS, Lau TT, Leung Y, Chik KW, Shing MM, and Li CK
- Subjects
- Adolescent, Bone Marrow pathology, Child, Child, Preschool, Chromosomes, Human, Pair 16, Female, Humans, Infant, Leukemia, Myeloid, Acute epidemiology, Leukemia, Myeloid, Acute pathology, Male, RNA, Messenger analysis, Recurrence, Remission Induction, Reverse Transcriptase Polymerase Chain Reaction, Survival Rate, Transcription Factor AP-2, Chromosome Aberrations, DNA-Binding Proteins genetics, Leukemia, Myeloid, Acute genetics, Myosin Heavy Chains genetics, Transcription Factors genetics
- Abstract
We analyzed 43 consecutive cases of pediatric acute myeloid leukemia (AML) for the presence of the CBFbeta-MYH11 rearrangement using molecular techniques in a regional hospital in Hong Kong. Five cases (11.6%), 3 girls and 2 boys, ranging in age from 8 months to 14 years old, were found positive for the CBFbeta-MYH11 rearrangement. Morphologically, they were FAB M2 or M4 with or without eosinophilia (Eo). Typical M4Eo was observed in only one case. The molecular findings were in complete concordance with cytogenetic data, which revealed inv(16)(p13q22) in all and also gains of chromosome 4, 8, 22, and Y in one patient. Clinically, all 5 patients achieved complete remission after chemotherapy with favorable outcomes except for the patient with infantile AML, who relapsed 11 months after diagnosis, underwent cord blood transplantation, and was in second remission. This is the first clinicopathological study and documentation of the incidence of CBFbeta-MYH11 in childhood AML of Chinese in Hong Kong., (Copyright 2004 Wiley-Liss, Inc.)
- Published
- 2004
- Full Text
- View/download PDF
93. A prospective, randomized, placebo-controlled study of the dose effect of oral estradiol on bone mineral density in postmenopausal Chinese women.
- Author
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Haines CJ, Yim SF, Chung TK, Lam CW, Lau EW, Ng MH, Chin R, and Lee DT
- Subjects
- Asian People, Estrogen Replacement Therapy, Female, Humans, Middle Aged, Osteoporosis, Postmenopausal ethnology, Prospective Studies, Bone Density drug effects, Estradiol therapeutic use, Osteoporosis, Postmenopausal drug therapy
- Abstract
Objectives: One of the long-term consequences of estrogen deficiency in postmenopausal women is an increased risk of osteoporosis. Fractures of the hip and lumbar spine are associated with considerable morbidity and mortality. Estrogen replacement therapy reduces the risk of osteoporosis, but there is no clear agreement on the most appropriate doses to be used. The aim of this study was to compare changes in bone mineral density (BMD) measurements using conventional and lower dose estradiol., Methods: A prospective, randomized, placebo-controlled 12-month study of the effect of 1 and 2 mg estradiol on BMD in 152 hysterectomized postmenopausal Chinese women with no contraindication to the use of estrogen replacement therapy., Results: Over 12 months, spinal BMD in placebo treated patients decreased by a mean of 2% from baseline (-0.02+/-0.03 g/cm(2)) while it increased by 2% in the 1 mg (0.02+/-0.03 g/cm(2)) and 3% in the 2 mg group (0.03+/-0.03 g/cm(2)). Mean changes in BMD over 12 months in the hip were -0.02+/-0.02 g/cm(2) (-2%), 0.01+/-0.02 g/cm(2) (+1%) and 0.01+/-0.03 g/cm(2) (+1%) in the placebo, 1 and 2 mg estradiol groups, respectively (P<0.05). Relative to placebo, increases in BMD in both 1 and 2 mg groups were statistically significant for both spine and hip (P<0.05). However, there was no significant difference in the increase in BMD between the 1 and 2 mg doses for either lumbar spine or hip (P=0.82, 0.53, respectively)., Conclusion: The results of our study show that a 1 mg dose of oral estradiol is effective in preventing bone loss in postmenopausal Chinese women.
- Published
- 2003
- Full Text
- View/download PDF
94. Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis.
- Author
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Wong RS, Wu A, To KF, Lee N, Lam CW, Wong CK, Chan PK, Ng MH, Yu LM, Hui DS, Tam JS, Cheng G, and Sung JJ
- Subjects
- Blood Coagulation physiology, Critical Care, Female, Hematologic Diseases blood, Hemoglobins analysis, Humans, Lymphocyte Count, Lymphopenia blood, Lymphopenia virology, Male, Multivariate Analysis, Neutropenia blood, Neutropenia virology, Platelet Count, Retrospective Studies, Severe Acute Respiratory Syndrome blood, Thrombocytopenia virology, Hematologic Diseases virology, Severe Acute Respiratory Syndrome complications
- Abstract
Objectives: To evaluate the haematological findings of patients with severe acute respiratory syndrome (SARS)., Design: Analysis of the demographic, clinical, and laboratory characteristics of patients with SARS., Setting: Prince of Wales Hospital, Hong Kong. Subjects All patients with a diagnosis of SARS between 11 March and 29 March 2003 who had no pre-existing haematological disorders., Main Outcome Measures: Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed to examine factors associated with adverse outcome., Results: 64 male and 93 female patients were included in this study. The most common findings included lymphopenia in 153 (98%) of the 157 patients, neutrophilia in 129 (82%), thrombocytopenia in 87 patients (55%), followed by thrombocytosis in 77 (49%), and isolated prolonged activated partial thromboplastin time in 96 patients (63%). The haemoglobin count dropped by more than 20 g/l from baseline in 95 (61%) patients. Four patients (2.5%) developed disseminated intravascular coagulation. Lymphopenia was shown in haemato-lymphoid organs at postmortem examination. Multivariate analysis showed that advanced age and a high concentration of lactate dehydrogenase at presentation were independent predictors of an adverse outcome. Subsets of peripheral blood lymphocytes were analysed in 31 patients. The counts of CD4 positive and CD8 positive T cells fell early in the course of illness. Low counts of CD4 and CD8 cells at presentation were associated with adverse outcomes., Conclusions: Abnormal haematological variables were common among patients with SARS. Lymphopenia and the depletion of T lymphocyte subsets may be associated with disease activity.
- Published
- 2003
- Full Text
- View/download PDF
95. A prospective, randomized, placebo-controlled study of the dose effect of oral oestradiol on menopausal symptoms, psychological well being, and quality of life in postmenopausal Chinese women.
- Author
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Haines CJ, Yim SF, Chung TK, Lam CW, Lau EW, Ng MH, Chin R, and Lee DT
- Subjects
- China, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Prospective Studies, Anxiety, Depression, Estradiol administration & dosage, Estrogen Replacement Therapy, Menopause psychology, Postmenopause, Quality of Life
- Abstract
Objectives: Hypoestrogenism occurring in association with the menopause may result in the development of vasomotor symptoms and it may also have a detrimental effect on psychological well being and quality of life (QOL). The aims of this study were to measure menopausal symptoms, mood and QOL in postmenopausal Chinese women and to assess the effect of different doses of oestrogen on these outcome indicators., Methods: A prospective, randomized, placebo-controlled study of the effect of 1 and 2 mg oestradiol on menopausal symptoms, anxiety and depressive symptoms, and QOL in 152 postmenopausal women over a 12 month study period. Menopausal symptoms were measured using a modified Kupperman's scale. Anxiety and depressive symptoms and QOL were measured using the Hospital Anxiety and Depression Scales and a modification of the World Health Organization Quality of Life questionnaire, respectively., Results: Baseline scoring of vasomotor symptoms in our population was low whilst QOL scoring was relatively high. Over 12 months, after adjustment for differences in baseline scoring, there was a significant reduction in menopausal symptom scores in the 2 mg oestradiol group compared with placebo but not in the 1 mg group. There were no statistically significant changes in levels of anxiety and depression or QOL in either the 1 or the 2 mg group compared with placebo., Conclusions: These results suggest that relatively few Chinese women will be expected to benefit from hormone replacement in terms of either QOL or mood. In addition, the overall benefit of treatment for vasomotor symptoms will be less for a given number of Chinese women than for Caucasians. Therefore, when considering the reasons for prescribing hormone replacement therapy in this population, protection against osteoporosis will for most women be the prime consideration.
- Published
- 2003
- Full Text
- View/download PDF
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