Sheung Tat Fan
University of Hong Kong
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Featured researches published by Sheung Tat Fan.
Hepatology | 2005
Tung-Yu Tsui; Chi-Keung Lau; Jian Ma; Xiaobing Wu; Yan-Qing Wang; Stefan Farkas; Ruian Xu; Hans J. Schlitt; Sheung Tat Fan
Liver fibrosis is the consequence of activation of hepatic stellate cells mediated by persistent or recurrent liver injury, where oxidative stress or inflammatory response resulting from immune cells and cytokines are involved. Targeting of hepatic stellate cells could be an important strategy for the therapy of liver fibrosis. In this study, we showed a tropism of recombinant adeno‐associated virus (rAAV, serotype 2) with high efficiency in transduction of a homeostatic gene, heme oxygenase‐1 (HO‐1), to activated stellate cells. The binding of rAAVs to stellate cells increased significantly after serum‐stimulated activation compared with quiescent status. Portal injection of rAAVs to normal or carbon tetrachloride (CCl4)‐induced liver fibrosis showed a distinct distribution of rAAV binding. The majority of injected rAAVs bound to the cells in fibrotic areas that were associated with higher expression levels of fibroblast growth factor receptor‐1α at 2 hours after administration. Isolation of different types of cells from CCl4‐induced fibrotic livers showed predominant expression of transgene in stellate cells after rAAV/HO‐1 administration on day 3 and remained stable for 12 weeks. In addition, HO‐1–transduced stellate cells showed reduced transcript levels of type 1 collagen and impaired proliferative ability compared with controls. With this approach, the severity of established micronodular cirrhosis was markedly reduced. In conclusion, these findings suggest a new approach for the treatment of liver fibrosis using adeno‐associated virus‐mediated gene transfer. (HEPATOLOGY 2005;42:335–342.)
Cancer Cell | 2008
Zhen Fan Yang; David W. Ho; Michael N. Ng; Chi Keung Lau; Wan Ching Yu; Patricia Ngai; Patrick Chu; Chi Tat Lam; Ronnie Tung-Ping Poon; Sheung Tat Fan
This study characterized cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) cell lines, tumor specimens, and blood samples. The CD90+ cells, but not the CD90(-) cells, from HCC cell lines displayed tumorigenic capacity. All the tumor specimens and 91.6% of blood samples from liver cancer patients bore the CD45(-)CD90+ population, which could generate tumor nodules in immunodeficient mice. The CD90+CD44+ cells demonstrated a more aggressive phenotype than the CD90+CD44(-) counterpart and formed metastatic lesions in the lung of immunodeficient mice. CD44 blockade prevented the formation of local and metastatic tumor nodules by the CD90+ cells. Differential gene expression profiles were identified in the CD45(-)CD90+ and CD45(-)CD90(-) cells isolated from tissue and blood samples from liver cancer patients and controls.
Cell | 2006
Lars Zender; Mona S. Spector; Wen Xue; Peer Flemming; Carlos Cordon-Cardo; John Silke; Sheung Tat Fan; John M. Luk; Michael Wigler; Gregory J. Hannon; David Mu; Robert Lucito; Scott Powers; Scott W. Lowe
The heterogeneity and instability of human tumors hamper straightforward identification of cancer-causing mutations through genomic approaches alone. Herein we describe a mouse model of liver cancer initiated from progenitor cells harboring defined cancer-predisposing lesions. Genome-wide analyses of tumors in this mouse model and in human hepatocellular carcinomas revealed a recurrent amplification at mouse chromosome 9qA1, the syntenic region of human chromosome 11q22. Gene-expression analyses delineated cIAP1, a known inhibitor of apoptosis, and Yap, a transcription factor, as candidate oncogenes in the amplicon. In the genetic context of their amplification, both cIAP1 and Yap accelerated tumorigenesis and were required to sustain rapid growth of amplicon-containing tumors. Furthermore, cIAP1 and Yap cooperated to promote tumorigenesis. Our results establish a tractable model of liver cancer, identify two oncogenes that cooperate by virtue of their coamplification in the same genomic locus, and suggest an efficient strategy for the annotation of human cancer genes.
The New England Journal of Medicine | 1993
Sheung Tat Fan; Edward C. S. Lai; Francis P. T. Mok; Chung Mau Lo; Shu-Sen Zheng; John Wong
BACKGROUND Most patients with acute biliary pancreatitis have stones in the biliary tract or ampulla of Vater. Because these stones may be passed spontaneously soon after a patient is admitted to the hospital, the importance of early operative removal is not known. We tested the hypothesis that endoscopic papillotomy within 24 hours of admission decreased the incidence of complications in patients with acute biliary pancreatitis. METHODS We studied 195 patients with acute pancreatitis who were randomly assigned to one of two groups: 97 patients underwent within 24 hours after admission emergency endoscopic retrograde cholangiopancreatography (ERCP) followed by endoscopic papillotomy for ampullary and common-bile-duct stones, and 98 patients received initial conservative treatment and selective ERCP with or without endoscopic papillotomy only if their condition deteriorated. RESULTS One hundred twenty-seven patients ultimately proved to have biliary stones. Emergency ERCP with or without endoscopic papillotomy resulted in a reduction in biliary sepsis as compared with conservative treatment (0 of 97 patients vs. 12 of 98 patients, P = 0.001). The decrease in biliary sepsis occurred both in patients predicted to have mild pancreatitis (0 of 56 patients in the group that received emergency ERCP vs. 4 of 58 patients in the conservative-treatment group, P = 0.14) and in patients predicted to have severe pancreatitis (0 of 41 patients vs. 8 of 40 patients, P = 0.008). In all patients who had unrelenting biliary sepsis, persistent ampullary or common-bile-duct stones were identified. There were no major differences in the incidence of local complications (10 patients in the group that received emergency ERCP vs. 12 patients in the conservative-treatment group) or systemic complications (10 patients vs. 14 patients) of acute pancreatitis between the two groups, but the hospital mortality rate was slightly lower in the group undergoing emergency ERCP with or without endoscopic papillotomy (5 patients vs. 9 patients, P = 0.4). CONCLUSIONS Emergency ERCP with or without endoscopic papillotomy is indicated in the treatment of patients with acute pancreatitis.
Annals of Surgery | 1999
Sheung Tat Fan; Chung Mau Lo; Chi-Leung Liu; Chi-Ming Lam; Wk Yuen; Chun Yeung; John Wong
OBJECTIVE The authors report on the surgical techniques and protocol for perioperative care that have yielded a zero hospital mortality rate in 110 consecutive patients undergoing hepatectomy for hepatocellular carcinoma (HCC). The hepatectomy results are analyzed with the aim of further reducing the postoperative morbidity rate. SUMMARY BACKGROUND DATA In recent years, hepatectomy has been performed with a mortality rate of <10% in patients with HCC, but a zero hospital mortality rate in a large patient series has never been reported. At Queen Mary Hospital, Hong Kong, the surgical techniques and perioperative management in hepatectomy for HCC have evolved yearly into a final standardized protocol that reduced the hospital mortality rate from 28% in 1989 to 0% in 1996 and 1997. METHODS Surgical techniques were designed to reduce intraoperative blood loss, blood transfusion, and ischemic injury to the liver remnant in hepatectomy. Postoperative care was focused on preservation and promotion of liver function by providing adequate tissue oxygenation and immediate postoperative nutritional support that consisted of branched-chain amino acid-enriched solution, low-dose dextrose, medium-chain triglycerides, and phosphate. The pre-, intra-, and postoperative data were collected prospectively and analyzed each year to assess the influence of the evolving surgical techniques and perioperative care on outcome. RESULTS Of 330 patients undergoing hepatectomy for HCC, underlying cirrhosis and chronic hepatitis were present in 161 (49%) and 108 (33%) patients, respectively. There were no significant changes in the patient characteristics throughout the 9-year period, but there were significant reductions in intraoperative blood loss and blood transfusion requirements. From 1994 to 1997, the median blood transfusion requirement was 0 ml, and 64% of the patients did not require a blood transfusion. The postoperative morbidity rate remained the same throughout the study period. Complications in the patients operated on during 1996 and 1997 were primarily wound infections; the potentially fatal complications seen in the early years, such as subphrenic sepsis, biliary leakage, and hepatic coma, were absent. By univariate analysis, the volume of blood loss, volume of blood transfusions, and operation time were correlated positively with postoperative morbidity rates in 1996 and 1997. Stepwise logistic regression analysis revealed that the operation time was the only parameter that correlated significantly with the postoperative morbidity rate. CONCLUSION With appropriate surgical techniques and perioperative management to preserve function of the liver remnant, hepatectomy for HCC can be performed without hospital deaths. To improve surgical outcome further, strategies to reduce the operation time are being investigated.
Annals of Surgery | 2002
Ronnie Tung-Ping Poon; Sheung Tat Fan; Chung Mau Lo; Chi Leung Liu; John Wong
ObjectiveTo evaluate the survival results and pattern of recurrence after resection of potentially transplantable small hepatocellular carcinomas (HCC) in patients with preserved liver function, with special reference to the implications for a strategy of salvage transplantation. Summary Background DataPrimary resection followed by transplantation for recurrence or deterioration of liver function has been recently suggested as a rational strategy for patients with HCC 5 cm or smaller and preserved liver function. However, there are no published data on transplantability after HCC recurrence or long-term deterioration of liver function after resection of small HCC in Child-Pugh class A patients. Such data are critical in determining the feasibility of salvage transplantation. MethodsFrom a prospective database of 473 patients with resection of HCC between 1989 and 1999, 135 patients age 65 years or younger had Child-Pugh class A chronic liver disease (chronic hepatitis or cirrhosis) and transplantable small HCC (solitary ≤5 cm or two or three tumors ≤3 cm). Survival results were analyzed and the pattern of recurrence was examined for eligibility for salvage transplantation based on the same criteria as those of primary transplantation for HCC. ResultsOverall survival rates at 1, 3, 5, and 10 years were 90%, 76%, 70%, and 35%, respectively, and the corresponding disease-free survival rates were 74%, 50%, 36%, and 22%. Cirrhosis and oligonodular tumors were predictive of worse disease-free survival. Patients with concomitant oligonodular tumors and cirrhosis had a 5-year overall survival rate of 48% and a disease-free survival rate of 0%, which were significantly worse compared with other subgroups. At a median follow-up of 48 months, 67 patients had recurrence and 53 (79%) of them were considered eligible for salvage transplantation. Decompensation from Child-Pugh class A to B or C without recurrence occurred in only six patients. ConclusionsFor Child-Pugh class A patients with small HCC, hepatic resection is a reasonable first-line treatment associated with a favorable 5-year overall survival rate. A considerable proportion of patients may survive without recurrence for 5 or even 10 years; among those with recurrence, the majority may be eligible for salvage transplantation. These data suggest that primary resection and salvage transplantation may be a feasible and rational strategy for patients with small HCC and preserved liver function. Primary transplantation may be a preferable option for the subset of patients with oligonodular tumors in cirrhotic liver in view of the poor survival results after resection.
Annals of Surgery | 2000
Ronnie Tung-Ping Poon; Sheung Tat Fan; John Wong
OBJECTIVE To evaluate the current knowledge on the risk factors for recurrence, efficacy of adjuvant therapy in preventing recurrence, and the optimal management of recurrence after resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA The long-term prognosis after resection of HCC remains unsatisfactory as a result of a high incidence of recurrence. Prevention and effective management of recurrence are the most important strategies to improve the long-term survival results. METHODS A review of relevant English articles was undertaken based on a Medline search from January 1980 to July 1999. RESULTS Pathologic factors indicative of tumor invasiveness such as venous invasion, presence of satellite nodules, large tumor size, and advanced pTNM stage, are the best-established risk factors for recurrence. Active hepatitis activity in the nontumorous liver and perioperative transfusion also appear to enhance recurrence. Recent molecular research has identified tumor biologic factors such as the proliferative and angiogenic activities of the tumor as new risk factors for recurrence. There is a lack of convincing evidence for the efficacy of neoadjuvant or adjuvant therapy in preventing recurrence. Retrospective studies suggested that postoperative hepatic arterial chemotherapy might improve disease-free survival, but results were conflicting. For the management of postoperative recurrence, studies have consistently indicated that surgical resection should be the treatment of choice for localized recurrence, be it in the liver remnant or extrahepatic organs. Transarterial chemoembolization and percutaneous ethanol injection are widely used to prolong survival in patients with unresectable intrahepatic recurrence, and combined therapy with these two modalities may offer additional benefit. CONCLUSIONS Knowledge of the risk factors for postoperative recurrence provides a basis for logical approaches to prevention. Minimal surgical manipulation of tumors to prevent tumor cell dissemination, avoidance of perioperative blood transfusion, and suppression of chronic hepatitis activity in the liver remnant are strategies that may be useful in preventing recurrence. The efficacy of postoperative adjuvant regional chemotherapy deserves further evaluation. New concepts on the influence of tumor biologic factors such as angiogenic activity on recurrence of HCC suggest a potential role of novel approaches such as antiangiogenesis for adjuvant therapy in the future. Currently, the most realistic approach in prolonging survival after resection of HCC is early detection and aggressive management of recurrence. Randomized trials are needed to define the roles of various treatment modalities for recurrence and the benefit of multimodality therapy.
Hepatology International | 2009
Shiv Kumar Sarin; A. Kumar; John Almeida; Yogesh Chawla; Sheung Tat Fan; Hitendra Garg; H. Janaka de Silva; Saeed Hamid; Rajiv Jalan; Piyawat Komolmit; George K. K. Lau; Qing Liu; Kaushal Madan; Rosmawati Mohamed; Qin Ning; Salimur Rahman; Archana Rastogi; Stephen M. Riordan; Puja Sakhuja; Didier Samuel; Samir Shah; Barjesh Chander Sharma; Praveen Sharma; Yasuhiro Takikawa; Babu Ram Thapa; Chun-Tao Wai; Man-Fung Yuen
The Asian Pacific Association for the Study of the Liver (APASL) set up a working party on acute-on-chronic liver failure (ACLF) in 2004, with a mandate to develop consensus guidelines on various aspects of ACLF relevant to disease patterns and clinical practice in the Asia-Pacific region. Experts predominantly from the Asia–Pacific region constituted this working party and were requested to identify different issues of ACLF and develop the consensus guidelines. A 2-day meeting of the working party was held on January 22–23, 2008, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and subsequently presented at the Annual Conference of the APASL at Seoul, Korea, in March 2008. The consensus statements along with relevant background information are presented in this review.
Cancer | 2000
Ronnie Tung-Ping Poon; Sheung Tat Fan; Irene Oi-Lin Ng; Chung-Mau Lo; Chi-Leung Liu; John Wong
Recent studies have shown that the prognosis of recurrent hepatocellular carcinoma (HCC) after resection was dependent on the time of recurrence. The current study investigated whether early and late intrahepatic recurrences were associated with different risk factors and prognostic factors.
Journal of Clinical Oncology | 2001
Ronnie Tung-Ping Poon; Sheung Tat Fan; John Wong
PURPOSE Angiogenesis, a process fundamental to tumor growth, is regulated by angiogenic factors. This article reviews prognostic and other clinical implications of circulating angiogenic factors in cancer patients. METHODS A MEDLINE search of literature was performed using the names of various angiogenic factors as the key words. Studies pertaining to circulating angiogenic factors in cancer patients were reviewed. Pertinent literature regarding tumor expression of common angiogenic factors and their prognostic relevance in human cancers were also examined. RESULTS A substantial number of studies have demonstrated a strong association between elevated tumor expression of vascular endothelial growth factor (VEGF) and advanced disease or poor prognosis in various cancers. This supports the pivotal role of VEGF in regulating tumor angiogenesis. More recently, there is mounting evidence that the level of circulating VEGF in patients with different types of cancer may be predictive of tumor status and prognosis. Preliminary data also suggest that circulating VEGF may be useful in predicting and monitoring tumor response to anticancer therapies and in follow-up surveillance for tumor relapse. There are reports supporting the prognostic value of other circulating angiogenic factors such as basic fibroblast growth factor, platelet-derived endothelial cell growth factor, transforming growth factor-beta, and angiogenin, but their clinical significance is less conclusive because of limited data. CONCLUSION Circulating VEGF seems to be a reliable surrogate marker of angiogenic activity and tumor progression in cancer patients. Evaluation of circulating angiogenic factors is a promising novel approach of prognostication in cancer patients that has the advantages of being convenient and noninvasive, and it may provide new prognostic information that is not afforded by conventional clinicopathologic prognostic indicators.