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Joyce S Y Yau,
June K Y Li,
Vicki H K Tam,
L M Fung,
C K Yeung, K W Chan,
K M Lee,
K F Lee,
W S Cheung,
Vincent T F Yeung,
Y P Yuen,
W K Kwan
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ABSTRACT: To review the clinical manifestations of phaeochromocytoma in a Hong Kong Chinese population.
Retrospective review. SETTING. Five public hospitals in Hong Kong.
Seventeen patients with operated phaeochromocytoma between 1994 and 2003 were reviewed retrospectively.
Six patients (35%) were men, 11 (65%) were women. The mean age at presentation was 47 (range, 17-72) years. The diagnosis post-presentation was delayed by 1 to 132 months. Over 70% of the patients had hypertension. The most frequent symptoms were headache (53%), palpitations (53%), and sweating (41%); all these symptoms were present in 24% of the patients. Four (24%) had hereditary phaeochromocytoma/paraganglioma syndrome. The sensitivity of 24-hour urinary catecholamine measurements was 82%. Mean urinary adrenaline and noradrenaline concentrations were respectively 7- and 8-fold greater than the upper reference limits. Computed tomography and metaiodobenzylguanidine scintigraphy were the most widely used means for tumour localisation (sensitivity, 100% and 87% respectively). Approximately 65% of the patients had intra-adrenal tumours; 53% were on right side, 18% were bilateral. All the patients were prescribed phenoxybenzamine (dosage range, 20-120 mg/day) preoperatively. Two thirds of the patients had improved blood pressure 1 year after the operation. No malignancy was reported after a mean follow-up period of 7 years.
Our series of patients with phaeochromocytomas commonly had a high frequency of normotension and extra-adrenal tumours. A high index of clinical suspicion and appropriate biochemical investigations are necessary to make the diagnosis, especially for patients manifesting adrenal incidentaloma and extra-adrenal lesion.
Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine 08/2010; 16(4):252-6.
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ABSTRACT: To determine donor human leukocyte antigen (HLA) from renal allograft biopsies in transplant recipients whose donor HLA phenotype is not known.
Renal allograft biopsies were obtained from seven renal transplant recipients when indicated for allograft dysfunction or proteinuria. DNA was extracted fresh from allograft specimens, and HLA typing was performed with polymerase chain reaction-specific sequence primers (PCR-SSP) and polymerase chain reaction-sequence-specific oligonucleotides (PCR-SSO).
HLA typing of the seven renal allograft biopsies was composed of both recipient and donor HLA phenotypes, allowing the determination of the donor HLA and the degree of HLA mismatching.
Deducing mismatched donor HLA antigens in renal allograft recipients enables detection of donor-specific antibodies, and the management of humoral rejection, and enables more appropriate selection of a donor organ should future retransplantation be required.
Clinical Transplantation 04/2010; 24(5):E178-81. · 1.67 Impact Factor
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H-F Yuen,
Y-T Chiu,
K-K Chan,
Y-P Chan,
C-W Chua,
C M McCrudden,
K-H Tang,
M El-Tanani,
Y-C Wong,
X Wang, K-W Chan
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ABSTRACT: Id-1 is overexpressed in and correlated with metastatic potential of prostate cancer. The role of Id-1 in this metastatic process was further analysed.
Conditioned media from prostate cancer cells, expressing various levels of Id-1, were used to stimulate pre-osteoclast differentiation and osteoblast mineralisation. Downstream effectors of Id-1 were identified. Expressions of Id-1 and its downstream effectors in prostate cancers were studied using immunohistochemistry in a prostate cancer patient cohort (N=110).
We found that conditioned media from LNCaP prostate cancer cells overexpressing Id-1 had a higher ability to drive osteoclast differentiation and a lower ability to stimulate osteoblast mineralisation than control, whereas conditioned media from PC3 prostate cancer cells with Id-1 knockdown were less able to stimulate osteoclast differentiation. Id-1 was found to negatively regulate TNF-beta and this correlation was confirmed in human prostate cancer specimens (P=0.03). Furthermore, addition of recombinant TNF-beta to LNCaP Id-1 cell-derived media blocked the effect of Id-1 overexpression on osteoblast mineralisation.
In prostate cancer cells, the ability of Id-1 to modulate bone cell differentiation favouring metastatic bone disease is partially mediated by TNF-beta, and Id-1 could be a potential therapeutic target for prostate cancer to bone metastasis.
British Journal of Cancer 12/2009; 102(2):332-41. · 5.04 Impact Factor
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ABSTRACT: To evaluate the efficacy of a fixed dose of radioactive iodine (131-I) in the treatment of thyrotoxicosis, and to identify risk factors associated with treatment failure.
Retrospective study.
Thyroid Clinic of a regional hospital in Hong Kong.
Patients receiving their first dose of radioactive iodine for the treatment of thyrotoxicosis during the inclusive period September 1999 to August 2004.
Relapse rate and time to relapse.
A total of 113 patients received a fixed dose of 5 mCi (185 MBq), 6 mCi (222 MBq), 8 mCi (296 MBq), and 10 mCi (370 MBq) 131-I in a proportion of 1:6:71:35. At 1 year, 42 (37%) of the patients had relapsed, of which 69% received a second 131-I dose. The median time to relapse after first receiving 131-I was 4 months. At 1 year, the remaining 71 (63%) of the patients were successfully treated; 46 (41%) were euthyroid, and 25 (22%) had became permanently hypothyroid. Basal free thyroxine level and goitre size were significantly associated with a relapse rate after a single dose of 131-I; larger goitres showed a trend towards high rates of relapse. Patients pretreated with propylthiouracil had a higher rate of relapse during the first year after radioactive iodine than those pretreated with carbimazole, but the difference was not significant when combined with other pretreatment variables.
A single fixed dose of radioactive iodine is a simple, safe, and effective treatment for hyperthyroidism. High basal free thyroxine concentration and large goitre size are associated with higher chance of relapse. Higher radioiodine doses may be considered to improve the cure rate.
Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine 09/2009; 15(4):267-73.
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ABSTRACT: The recent discovery of cancer stem cells (CSCs) has played a pivotal role in changing our view of carcinogenesis and chemotherapy. Based on this concept, CSCs are responsible for the formation and growth of neoplastic tissue and are naturally resistant to chemotherapy, explaining why traditional chemotherapies can initially shrink a tumor but fails to eradicate it in full, allowing eventual recurrence. Recently, we identified a CSC population in hepatocellular carcinoma (HCC) characterized by their CD133 phenotype. However, the molecular mechanism by which it escapes conventional therapies remains unknown. Here, we examined the sensitivity of these cells to chemotherapeutic agents (doxorubicin and fluorouracil) and the possible mechanistic pathway by which resistance may be regulated. Purified CD133+ HCC cells isolated from human HCC cell line and xenograft mouse models survived chemotherapy in increased proportions relative to most tumor cells which lack the CD133 phenotype; the underlying mechanism of which required the preferential expression of survival proteins involved in the Akt/PKB and Bcl-2 pathway. Treatment of CD133+ HCC cells with an AKT1 inhibitor, specific to the Akt/PKB pathway, significantly reduced the expression of the survival proteins that was normally expressed endogenously. In addition, treatment of unsorted HCC cells with both anticancer drugs in vitro significantly enriched the CD133+ subpopulation. In conclusion, our results show that CD133+ HCC cells contribute to chemoresistance through preferential activation of Akt/PKB and Bcl-2 cell survival response. Targeting of this specific survival signaling pathway in CD133+ HCC CSCs may provide a novel therapeutic model for the disease.
Oncogene 04/2008; 27(12):1749-58. · 6.37 Impact Factor
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ABSTRACT: Rapamycin is a potent immunosuppressive drug currently used mainly for rejection prophylaxis in renal transplantation. The aim of this study was to determine the effect of rapamycin treatment on the development of nephritis in lupus-prone New Zealand Black/White F1 (NZB/W F1) mice. Twelve-week-old female NZB/W F1 mice were treated with rapamycin (3 mg/kg body weight) or saline once daily by oral gavage for 20 weeks. The severity of nephritis was assessed by clinical and biochemical parameters, renal histology, immunohistochemistry and gene expression studies. Rapamycin treatment markedly reduced proteinuria, improved renal function, decreased serum anti-double stranded DNA antibody levels and diminished splenomegaly. Kidney sections from saline-treated mice showed marked mesangial proliferation, tubular dilation with protein cast deposition and interstitial inflammatory cell infiltration. Rapamycin-treated mice had near normal renal histology, with marked reduction in glomerular immune deposition and the infiltration by T cells, B cells and macrophages. Rapamycin treatment was associated with down-regulation of intra-renal expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein. We conclude that rapamycin is highly effective in preventing the development of nephritis in NZB/W F1 mice. The beneficial effects of rapamycin are mediated through inhibition of lymphoproliferation and reduced MCP-1 expression.
Lupus 02/2008; 17(4):305-13. · 2.34 Impact Factor
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ABSTRACT: Id protein family consists of four members namely Id-1 to Id-4. Different from other basic helix-loop-helix transcription factors, they lack the DNA binding domain. Id proteins have been shown to be dysregulated in many different cancer types and their prognostic value has also been demonstrated. Recently, Id-1 has been shown to be upregulated in oesophageal squamous cell carcinoma (ESCC). However, the prognostic implications of Id proteins in ESCC have not been reported. We examined the expression of the Id proteins in ESCC cell lines and clinical ESCC specimens and found that Id protein expressions were dysregulated in both the ESCC cell lines and specimens. By correlating the expression levels of Id proteins and the clinicopathological data of our patient cohort, we found that M1 stage tumours had significantly higher nuclear Id-1 expression (P=0.012) while high nuclear Id-1 expression could predict development of distant metastasis within 1 year of oesophagectomy (P=0.005). In addition, high levels of Id-2 expression in both cytoplasmic and nuclear regions predicted longer patient survival (P=0.041). Multivariate analysis showed that high-level expression of Id-2 in both cytoplasmic and nuclear regions and lower level of nuclear Id-1 expression were independent favourable predictors of survival in our ESCC patients. Our results suggest that Id-1 may promote distant metastasis in ESCC, and both Id-1 and Id-2 may be used for prognostication for ESCC patients.
British Journal of Cancer 12/2007; 97(10):1409-15. · 5.04 Impact Factor
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American Journal of Hematology 05/2007; 82(4):327-8. · 4.67 Impact Factor
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ABSTRACT: Development of metastasis is one of the main causes of prostatic cancer-related death. We have previously found that up-regulation of TWIST, a highly conserved basic helix-loop-helix transcription factor, in prostatic cancer cells can promote epithelial to mesenchymal transition through down-regulation of E-cadherin. The present study aimed to investigate the prognostic significance of TWIST and to correlate TWIST and E-cadherin expression in prostatic cancer specimens.
TWIST and E-cadherin expression was studied in 115 prostatic cancer specimens, eight cases of prostatic intraepithelial neoplasia and 37 cases of benign prostatic hyperplasia by immunohistochemistry. Increased cytoplasmic expression of TWIST was associated with malignant transformation of prostatic epithelium and histological progression of prostatic cancer, while nuclear TWIST expression was significant in predicting the metastatic potential of the primary prostatic cancer. In addition, high levels of TWIST expression were also significantly associated with aberrant E-cadherin expression.
These results suggest that TWIST may serve as a prognostic marker for high-grade prostatic cancer. In addition, up-regulation of TWIST in combination with aberrant E-cadherin expression in primary prostatic cancer specimens may predict development of distal metastatic disease.
Histopathology 04/2007; 50(5):648-58. · 3.08 Impact Factor
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ABSTRACT: LIM domain only 2 (LMO2) proteins are important regulators in determining cell fate and controlling cell growth and differentiation. This study has investigated LMO2 expression in human prostatic tissue specimens, prostate cancer cell lines, and xenografts; and has assessed the possible role and mechanism of LMO2 in prostate carcinogenesis. Immunohistochemical analysis on a tissue microarray consisting of 91 human prostate specimens, including normal, prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia, and invasive carcinoma, revealed that overexpression of LMO2 was significantly associated with advanced tumour stage, as measured by Gleason score (p = 0.012), as well as with the development of distant metastasis (p = 0.018). These data were supported by quantitative real-time PCR experiments, where LMO2 mRNA levels were found to be significantly higher in prostate tumour specimen than in normal epithelium (p = 0.037). The expression of LMO2 in cell lines and xenografts representing androgen-dependent (AD) and androgen-independent (AI) prostate cancer stages was further studied. Consistent with the in vivo data, LMO2 mRNA and protein were found to be overexpressed in the more aggressive AI cells (PC3, DU145, and AI CWR22 xenografts) compared with less aggressive AD cells (LNCaP and AD CWR22 xenografts). Furthermore, stable introduction of LMO2 into LNCaP cells conferred enhanced cell motility and invasiveness in vitro, accompanied by down-regulation of E-cadherin expression. Taken together, these findings provide the first evidence to support the hypothesis that LMO2 may play an important role in prostate cancer progression, possibly via repression of E-cadherin expression.
The Journal of Pathology 03/2007; 211(3):278-85. · 6.32 Impact Factor
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Histopathology 06/2006; 48(6):775-6. · 3.08 Impact Factor
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ABSTRACT: To determine the extent of Fas expression in oesophageal squamous cell carcinomas (ESCCs) from Chinese patients and to correlate Fas expression with clinicopathological prognostic parameters.
Clinicopathological data were collected from 58 patients with ESCC who underwent oesophagectomy and had no prior radiotherapy or chemotherapy. Immunostaining was performed on the primary tumours. Expression of Fas was correlated with patients' demographics, tumour characteristics and stage, R category of surgery, and patients' survival.
The actuarial survival rates of all patients at two and five years after surgery were 48% and 14%, respectively. Fas expression was detected in 89.7% of ESCCs. Higher Fas expression recorded on a four point scale correlated with better tumour differentiation (p < 0.01), but not with other patient or tumour variables. Importantly, higher Fas expression was associated with better survival (p = 0.0317).
These findings suggest that Fas activated apoptosis is important in the pathogenesis of ESCC. This molecular pathway may be a potential therapeutic target for ESCC.
Journal of Clinical Pathology 01/2006; 59(1):101-4. · 2.31 Impact Factor
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ABSTRACT: Our goal was to define the spectrum of glomerular diseases in allograft kidneys and to correlate them with clinical parameters.
Eight hundred ninety-one renal graft biopsies and 43 graft nephrectomies from 1980 to 2004 were obtained from 442 allografts transplanted to 425 patients.
Glomerular diseases were diagnosed in 33% of kidney grafts. Indications for biopsy were baseline assessment (23 biopsies, 2.5%); renal dysfunction (790 biopsies, 88.7%); proteinuria (154 biopsies, 17.3%); hematuria (11 biopsies, 1.2%); and study protocol (four biopsies, 0.4%). The median time to take a biopsy was less than 8 months posttransplant. The mean time posttransplant when the biopsy diagnosis was made was 70 months for IgA nephropathy (IgAN); 66 months for transplant glomerulopathy (TG); 65 months for focal segmental glomerulosclerosis (FSG); 55 months for mesangiocapillary glomerulonephritis (MCGN); 45 months for membranous glomerulonephritis (GN); 49 months for mesangial proliferative GN; and 101 months for diabetic nephropathy. Recurrent glomerular disease was documented in 31 (7.0%) grafts. Specific glomerular diseases were diagnosed by biopsies in 106 (89.1%) of 119 proteinuric allografts.
Glomerulopathy was common in allografted kidneys. IgAN, TG, FSG, mesangial proliferative GN, and membranous GN were the majority. A higher proportion of grafts from donors related to the recipients than from unrelated donors showed IgAN (P < .05), suggesting that genetic factors might play a role in the pathogenesis of IgAN. Recurrence of glomerulopathy underlying ESRD was frequent for IgAN, FSG, and MCGN, but this was rarely seen in membranous GN.
Transplantation Proceedings 12/2005; 37(10):4293-6. · 1.00 Impact Factor
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Histopathology 01/2005; 45(6):648-51. · 3.08 Impact Factor
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Haematologica 08/2004; 89(7):ECR21. · 6.42 Impact Factor
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Haematologica 05/2004; 89(4):EIM08. · 6.42 Impact Factor
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Bone Marrow Transplantation 04/2004; 33(6):669-70. · 3.75 Impact Factor
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Histopathology 03/2004; 44(2):191-3. · 3.08 Impact Factor
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Betty But,
C W Chan,
Fredriech Chan, K W Chan,
Anna W F Cheng,
Patrick Cheung,
K L Choi,
C B Chow,
Francis C C Chow,
Creswell Eastman, [......],
S C Tiu,
H Y Tse,
Winnie Tse,
Gary Wong,
Shell Wong,
William Wong,
Vincent T F Yeung,
Rosie Young,
C M Yu,
Richard Yu
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ABSTRACT: This article reviews the available data on the study of iodine deficiency disorders in Hong Kong and to discuss the approach towards preventing such disorders in Hong Kong. The importance of iodine and iodine deficiency disorders is described, and the available data on the dietary iodine intake and urinary iodine concentration in different populations of Hong Kong are summarised and discussed. Dietary iodine insufficiency among pregnant women in Hong Kong is associated with maternal goitrogenesis and hypothyroxinaemia as well as neonatal hypothyroidism. Borderline iodine deficiency exists in the expectant mothers in Hong Kong. Women of reproductive age, and pregnant and lactating women should be made aware and educated to have an adequate iodine intake, such as iodised salt, as an interim measure. A steering group involving all stakeholders should be formed to advise on the strategy of ensuring adequate iodine intake, including universal iodisation of salt in Hong Kong. Continuous surveillance of iodine status in the Hong Kong population is necessary.
Hong Kong medical journal = Xianggang yi xue za zhi / Hong Kong Academy of Medicine 01/2004; 9(6):446-53.
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ABSTRACT: Urinary tract infection is a common complication after renal transplantation. The etiologies are diverse and the bacterial agents may sometimes be acquired during the hospital stay. We report a patient who developed Burkholderia cepacia urinary tract infection after renal transplantation. The bacteria showed in vivo resistance to all of the available antibiotics. A graft nephrectomy was eventually required to clear the infection. The consequence of some fastidious infection may be catastrophic and early recognition and treatment is necessary to optimize the treatment.
Transplant Infectious Disease 04/2003; 5(1):59-61. · 2.22 Impact Factor