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Biomedical subjects

Sheung Tat Fan

Publications and source records attributed to Sheung Tat Fan.

At least 37 records · Page 2Linked to original sources
PubMed2006

The gene expression of adrenomedullin, calcitonin-receptor-like receptor and receptor activity modifying proteins (RAMPs) in CCl4-induced rat liver cirrhosis.

This study was undertaken to determine AM expression in carbon tetrachloride (CCl4)-induced liver cirrhosis developed with peritoneal ascites. Sprague-Dawley rats received subcutaneous injections of CCl4 twice weekly in olive oil (1:1, 0.3 ml per kg body weight) for 6 or 12 weeks until ascites developed, or saline in olive oil as control. At 6 weeks, fibrosis developed and at 12 weeks cirrhosis developed with ascites formation. At both 6 and 12 weeks, increases in plasma renin and AM were evident, as was the gene expression of AM. At 12 weeks after CCl4 injection, the gene expression of calcitonin-like-receptor (CRLR) and receptor activity modifying proteins (RAMP1, RAMP2 and RAMP3) were all elevated when compared to the control. The results suggest that liver cirrhosis increases mRNA expressions of AM, CRLR and RAMP1, RAMP2 and RAMP3 and that the increase in AM gene expression precedes the development of cirrhosis. The increase in AM synthesis as reflected by an increase in AM gene expression, together with a lack of increase in AM peptide at both 6 and 12 weeks may suggest an elevation of AM release. Given the potent vasodilatory action of AM, the increase in the synthesis and release of AM in the cirrhotic liver may also contribute to peripheral vasodilatation in liver cirrhosis.

Adrenomedullin↗
PubMed2006

Estimating liver weight of adults by body weight and gender.

AIM: To estimate the standard liver weight for assessing adequacies of graft size in live donor liver transplantation and remnant liver in major hepatectomy for cancer. METHODS: In this study, anthropometric data of body weight and body height were tested for a correlation with liver weight in 159 live liver donors who underwent donor right hepatectomy including the middle hepatic vein. Liver weights were calculated from the right lobe graft weight obtained at the back table, divided by the proportion of the right lobe on the computed tomography. RESULTS: The subjects, all Chinese, had a mean age of 35.8+/-10.5 years, and a female to male ratio of 118:41. The mean volume of the right lobe was 710.14+/-131.46 mL and occupied 64.55%+/-4.47% of the whole liver on computed tomography. Right lobe weighed 598.90+/-117.39 g and the estimated liver weight was 927.54+/-168.78 g. When body weight and body height were subjected to multiple stepwise linear regression analysis, body height was found to be insignificant. Females of the same body weight had a slightly lower liver weight. A formula based on body weight and gender was derived: Estimated standard liver weight (g) = 218 + BW (kg) x 12.3 + gender x 51 (R2 = 0.48) (female = 0, male = 1). Based on the anthropometric data of these 159 subjects, liver weights were calculated using previously published formulae derived from studies on Caucasian, Japanese, Korean, and Chinese. All formulae overestimated liver weights compared to this formula. The Japanese formula overestimated the estimated standard liver weight (ESLW) for adults less than 60 kg. CONCLUSION: A formula applicable to Chinese males and females is available. A formula for individual races appears necessary.

Adult↗
PubMed2006

Gold(III) compound is a novel chemocytotoxic agent for hepatocellular carcinoma.

Recently, a series of gold(III) meso-tetraarylporphyrins that are stable against demetallation in physiological conditions have been synthesized. In the present study, the antitumor effects of one of these compounds, gold(III) meso-tetraarylporphyrin 1a (gold-1a) was investigated in an orthotopic rat hepatocellular carcinoma (HCC) model as well as using a HCC cell line. The rat HCC model was induced by injection of rat hepatoma cells, McA-RH7777, into the left lobe of the liver. Seven days after tumor cell inoculation, gold-1a was injected directly into the tumor nodule at different doses, followed by the same doses via intraperitoneal injection twice a week. Gold-1a administration significantly prolonged the survival of HCC-bearing rats. Importantly, gold-1a induced necrosis as well as apoptosis in the tumor tissues, but not in the normal liver tissues. Furthermore, gold-1a treatment neither caused significant drop in body weight of the rats nor affected plasma aspartate aminotransferase level. In the in vitro studies, we observed that gold-1a treatment inhibited the proliferation of McA-RH7777 cells. Gold-1a upregulated genes that increase apoptosis, stabilize p53, decrease proliferation and downregulated genes playing roles in angiogenesis, invasion, and metabolism, as demonstrated by microarray. In particular, the compound upregulated 2 members of the growth arrest and DNA damage (Gadd) inducible gene family, Gadd34 and Gadd153. Suppression of Gadd34 and Gadd153 in McA-RH7777 cells by small hairpin RNA reduced the gold-1a-induced apoptosis and growth inhibition, indicating that gold-1a mediated its effects via upregulation of Gadd34 and Gadd153. Results from our study demonstrated that gold-1a might be a novel promising chemocytotoxic agent for treating HCC.

Alanine Transaminase↗
PubMed2006

TNP-470 blockage of VEGF synthesis is dependent on MAPK/COX-2 signaling pathway in PDGF-BB-activated hepatic stellate cells.

Angiogenesis is a key pathogenic event in hepatic fibrogenesis, which is mediated by activated hepatic stellate cells (HSCs). TNP-470 is a known anti-angiogenic agent in cancer, and in this study, we investigated the regulatory mechanisms of TNP-470 blockage of vascular endothelial growth factor (VEGF) synthesis in activated HSCs. Primary HSCs were isolated from rat liver, cultured in vitro, and activated with platelet-derived growth factor-BB (PDGF-BB). After treatment with TNP-470, Nimesulide, PD98059, SB203580 or SP600125, activated HSCs were analyzed by immunoblotting, quantitative RT-PCR, and ELISA for mitogen-activated protein kinase (MAPK) family [ERKs, JNK, and p38], cyclooxygenase-2 (COX-2), and VEGF levels. Phosphorylation of p44/42 MAPK, which was followed by increased expressions of COX-2 and VEGF, was observed in PDGF-BB-activated HSCs; these events could be ameliorated by addition with TNP-470 in time- and dose-dependent manners. TNP-470 also inhibited the secretion of VEGF from activated HSCs into culture supernatant. Furthermore, TNP-470 blockage of VEGF production in activated HSCs could be nullified by exogenous inoculation with prostaglandin E(2). In summary, our findings suggest that TNP-470 exhibits the observed anti-angiogenic properties in activated HSCs by targeting the COX-2/phospho-p44/42 MAPK pathway to inhibit VEGF production.

Angiogenesis Inhibitors↗
PubMed2006

Therapeutic potential of cardiotrophin 1 in fulminant hepatic failure: dual roles in antiapoptosis and cell repair.

HYPOTHESIS: Administration of cardiotrophin 1 (CT-1) can treat experimental fulminant hepatic failure (FHF). DESIGN: Rat model with FHF induced by D-galactosamine (D-gal). SETTING: Fulminant hepatic failure is a rapidly progressive disease that lacks effective nonsurgical treatment. Cardiotrophin 1 is a member of the interleukin 6 family that can protect cells from damage in some animal disease models. ANIMALS: A rat model of FHF was induced by an intraperitoneal injection of D-gal (1.4 g/kg of body weight). Cardiotrophin 1 was administered at different time points after D-gal injection. RESULTS: Administration of CT-1 at 12 and 18 hours had a survival rate of 80% (12/15) and 70% (7/10), respectively, which was significantly higher than that of nontreatment (28% [5/18]). In addition, improvement of liver histologic findings, shortening of activated clotting time, and decrease in serum levels of total bilirubin and alanine aminotransferase were detected with CT-1 treatment. Administration of CT-1 decreased apoptotic cells and increased Ki-67 cells in the liver tissues. In vitro, CT-1 administration significantly decreased apoptotic cells and sequentially down-regulated the expression of proapoptotic molecules and up-regulated the expression of antiapoptotic molecules at different culture periods. D-galactosamine culture induced morphologic damage in a hepatocyte cell line, which was greatly improved by CT-1 administration. In addition, CT-1-treated cells demonstrated increased expression of glycoprotein 130 and up-regulation of cyclin D1 and heat shock protein 90. CONCLUSION: Cardiotrophin 1 may improve the outcome of D-gal-induced FHF through its effects on antiapoptosis and cell repair.

Analysis of Variance↗
PubMed2006

Comparable survival in patients with unresectable hepatocellular carcinoma treated by radiofrequency ablation or transarterial chemoembolization.

HYPOTHESIS: The survival benefits of radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) are similar for patients with unresectable hepatocellular carcinoma amenable to either treatment. DESIGN: Retrospective comparative study. SETTING: Tertiary care institution. PATIENTS: From February 22, 2001, to March 10, 2004, 91 patients with unresectable hepatocellular carcinoma (tumor diameter <5 cm and <4 tumor nodules) treated by either TACE or RFA were analyzed from a prospective database. MAIN OUTCOME MEASURES: The treatment-related morbidity, mortality, overall survival, and time to disease progression. RESULTS: Forty patients received TACE and 51 patients received RFA during the study period. Demographic data were comparable in both groups of patients. The treatment-related morbidities of TACE and RFA were 10% and 28%, respectively (P = .04). There was no treatment-related mortality in either group. There was 1 patient (2%) with complete tumor remission in the TACE group, and the complete ablation rate in the RFA group was 96%. The time to disease progression was similar in both groups (P = .95). The overall survival rates at 1 and 2 years were 80% and 58%, respectively, in the TACE group and 82% and 72%, respectively, in the RFA group (P = .21). CONCLUSIONS: The overall survival and time for disease progression were similar in both groups of patients. In terms of the survival result, the efficacies of RFA and TACE were comparable for patients with unresectable hepatocellular carcinoma.

Adult↗
PubMed2006

Safety limit of large-volume hepatic radiofrequency ablation in a rat model.

BACKGROUND: Large-volume hepatic radiofrequency ablation (RFA) has been used to treat large liver tumors, but its safety limit is unknown. This study aimed to investigate the possible systemic responses of large-volume hepatic RFA and to estimate its safety limit in normal and cirrhotic rats. HYPOTHESIS: Large-volume hepatic RFA causes a significant systemic inflammatory reaction. DESIGN: Experimental study. SETTING: University teaching hospital. INTERVENTION: Using the Cool-tip RF System (Radionics, Burlington, Mass), RFA was performed for different percentages of the liver volume by weight in normal and cirrhotic Sprague-Dawley rats. MAIN OUTCOME MEASURES: Changes in concentrations of serum inflammatory markers (tumor necrosis factor alpha [TNF-alpha] and interleukin [IL] 6), functions of various end organs, and survival rates were assessed. RESULTS: In the normal liver groups, the concentrations of TNF-alpha and IL-6 were significantly elevated in the early postoperative period when 50% (mean +/- SD TNF-alpha concentration, 130.3 +/- 15.6 pg/mL; mean +/- SD IL-6 concentration, 163.2 +/- 12.2 pg/mL) and 60% (mean +/- SD TNF-alpha concentration, 145.7 +/- 13.0 pg/mL; mean +/- SD IL-6 concentration, 180.8 +/- 11.0 pg/mL) of the liver volume were ablated compared with the control group (mean +/- SD TNF-alpha concentration, 30.4 +/- 9.9 pg/mL, P<.001; mean +/- SD IL-6 concentration, 28.4 +/- 6.7 pg/mL, P<.001). The concentrations of TNF-alpha and IL-6 in other groups remained similar to those in the control group. Thrombocytopenia, prolonged clotting time, and interstitial pneumonitis occurred when 50% and 60% of the liver volume were ablated. The 4-week survival rates were 100%, 60%, and 0% when 40%, 50%, and 60%, respectively, of the liver volume were ablated. Similar systemic inflammatory responses and poor survival rates were observed among the cirrhotic liver groups when 30% and 40% of the liver volume were ablated. CONCLUSIONS: The normal rats can tolerate RFA of 40% of the liver volume with minimal morbidity and no mortality whereas the cirrhotic rats can only tolerate 20% of the ablated liver volume. Beyond that limit, RFA would cause significant systemic inflammatory responses and poor survival.

Animals↗
PubMed2006

Significance of circulating endothelial progenitor cells in hepatocellular carcinoma.

This study evaluated the significance of circulating bone marrow-derived endothelial progenitor cells (EPCs) in patients with hepatocellular carcinoma (HCC), a solid tumor with rich neovasculature. Eighty patients with HCC were recruited for the study, and 16 patients with liver cirrhosis and 14 healthy subjects were also included for comparison. Blood samples were taken before treatment. Total mononuclear cells were isolated from peripheral blood, preplated to eliminate mature circulating endothelial cells, and colony-forming units (CFUs) formed by circulating EPCs were counted. To validate the CFU scores, FACS quantification of EPCs using CD133, VEGFR2, and CD34 as markers was performed in 30 cases. Our study showed significantly higher mean CFU scores in patients with HCC compared to patients with cirrhosis and healthy controls (P = .001 and .009, respectively). Furthermore, the CFU scores of patients with HCC positively correlated with levels of serum alpha-fetoprotein (r = .303, P = .017), plasma VEGF (r = .242, P = .035), and plasma interleukin-8 (IL-8) (r = .258, P = .025). Patients with unresectable HCC had higher CFU scores than patients with resectable tumors (P = .027). Furthermore, for those who underwent curative surgery, higher preoperative CFU scores were observed in patients with recurrence within 1 year compared with those who were disease-free after 1 year (P = .013). In conclusion, higher circulating levels of EPCs are seen in patients with advanced unresectable HCC as compared to patients with resectable HCC or those with liver cirrhosis. Our evidence supports the potential use of circulating level of EPCs as a prognostic marker in patients with HCC.

Adult↗
PubMed2006

ATR dependent activation of Chk2.

ATM and ATR are essential regulators of DNA damage checkpoints in mammalian cells through their respective effectors, Chk2 and Chk1. Cross regulation of the ATM-Chk2 and ATR-Chk1 pathways is very limited, although ATM and ATR show overlapping function in a partnership and time-dependent manner. In this study, we report that Chk2 is a substrate of ATR in response to ionizing and ultraviolet radiation. ATR activation induced by ionizing radiation (IR) is weak in ATM+/+ cells. However, when ATM is inhibited by caffeine, ATR activation is markedly enhanced. Total Chk2 and Chk2 Thr68 are also hyperphosphorylated in the presence of caffeine. Both ATM+/+ and ATM-/- cells display normal ATR activation in response to UV radiation-induced DNA damage, which is caffeine sensitive. In two lines of ATM-deficient, as well as in an ATM siRNA silencing cell line, ATR is activated when the cells are exposed to IR and is able to phosphorylate Chk2 in vitro. These observations suggest that ATR is one of the kinases that is likely involved in phosphorylation of Chk2 in response to IR when ATM is deficient.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2006

Long-term biological consequences of donor right hepatectomy including the middle hepatic vein in adult-to-adult live donor liver transplantation.

The right lobe liver graft has become the workhorse of adult-to-adult live donor liver transplantation. Donor right hepatectomy is feasible only because of the immense regenerative ability of the liver. The long-term biological consequences of this very major donor procedure on the donor however are unknown. Twenty-nine donors of this procedure in our centre, all of whom included the middle hepatic vein, were studied. On long-term follow-up at a median of 47.4 months, there was a discernible but statistically insignificant decrease in size of the regenerated left lobe compared to the original whole liver volume. There was paradoxically a trend of incompleteness of regeneration in relation to the original liver volume for those with a larger remnant left lobe. The volume ratio of the regenerated left lobe to the original left lobe before hepatectomy was inversely proportional to the left lobe proportion preoperatively. This strong but inverse linear correlation reflected the good regenerative ability of the remnant left lobe. None of the donors developed thrombocytopenia. Although demonstrable decrease in white cell count, increase in serum alanine aminotransferase, aspartate aminotransferase, and creatinine did occur, the changes remained within normal limits and were of yet uncertain clinical significance. In conclusion, donor right hepatectomy including the middle hepatic vein is biologically acceptable to the live donor.

Adolescent↗
PubMed2006

Attenuation of acute phase shear stress by somatostatin improves small-for-size liver graft survival.

The major concern of living donor liver transplantation is small-for-size graft injury at the early phase after transplantation. Novel therapeutic strategies should be developed. To investigate the protective effect of somatostatin related to hemodynamic stress on small-for-size liver graft injury, we applied a treatment regimen of low-dose somatostatin in a rat orthotopic liver transplantation model using small-for-size grafts (median, 38.7%; range, 35-42%). Somatostatin was given at 5 minutes before total hepatectomy and immediately after reperfusion in the recipient (20 microg/kg). Graft survival, portal hemodynamics, intragraft gene expression and hepatic ultrastructural changes were compared between the rats with or without somatostatin treatment. Seven-day graft survival rates in the somatostatin treatment group were significantly improved compared to the control group (66.7% vs. 16.7%, P = 0.036). In the treatment group, portal pressure and hepatic surface blood flow were significantly decreased within the first 30 minutes after reperfusion, whereas in the control group, transient portal hypertension and excessive hepatic blood flow were observed. Intragraft expression (both messenger RNA and protein) of endothelin-1 was significantly downregulated accompanied with upregulation of heme oxygenase-1 and A20. Better preservation of liver function was found in the treatment group. Hepatic ultrastructure, especially the integrity of sinusoids, was well protected in the treatment group. In conclusion, low-dose somatostatin rescues small-for-size grafts from acute phase injury in liver transplantation by attenuation of acute-phase shear stress that resulted from transient portal hypertension.

Animals↗
PubMed2006

Donor quality of life before and after adult-to-adult right liver live donor liver transplantation.

Donor right hepatectomy for adult-to-adult live donor liver transplantation (ALDLT) is a major surgical operation for the benefit of the recipient. Justification of procedure mandates knowledge of the possible physical and psychological negative effects on the donor. We prospectively and longitudinally quantified donor quality of life using generic and condition-specific questionnaires up to 1 year. The generic questionnaires were the Karnofsky Performance Status scale and the Chinese (Hong Kong) version of the Medical Outcomes Study 36-Item Short-Form Survey, which measures 8 health concepts: 4 physical components and 4 mental components. Within 1 year, 30 consecutive donors were included. These 11 male and 19 female donors (36.7% and 63.3%, respectively) had a median age of 35 years (range, 21-56 years). There was no donor mortality or major complications. Donor quality-of-life worsening was most significant in the first 3 postoperative months, particularly among the physical components. The physical and mental components returned to the previous levels in 6 to 12 months' time, though the Karnofsky performance scores were slightly lower at 1 year (P = 0.011). Twenty-six (86.7%) donors declared that they would donate again if there were such a need and it were technically possible. It was noticed that older donors were more likely to express unwillingness to donate again. In conclusion, the temporary worsening of donor quality of life substantiates ALDLT as an acceptable treatment modality.

Adult↗
PubMed2006

Adult-to-adult live-donor liver transplantation: the current status.

Adult-to-adult live-donor liver transplantation (ALDLT) has emerged successfully to partially relieve the refractory shortage of deceased donor grafts caused by the increasing demands of patients with endstage liver diseases. Following the first successful live-donor liver transplantation (LDLT) for a child with biliary atresia in 1989, further extension of the technique, using left-lobe liver grafts for LDLT for large adolescents and adults, has resulted in satisfactory graft and patient survival outcomes. However, small-for-size syndrome may occur in some patients with large body size, and in those with acute-on-chronic liver failure or severe portal hypertension. To overcome the problem of graft-to-body-size mismatch, ALDLT, using a right-lobe liver graft was developed. Although routine inclusion of the middle hepatic vein (MHV) in the right-lobe liver graft is still controversial, the importance of providing good venous drainage for the right anterior sector to ensure better early graft function has gained wide recognition. Preservation of the MHV in the donor is intuitively considered important in reducing the donor risk. However, there are scarce data supporting the contention that postoperative complication is related to the absence of the MHV in the left-liver remnant. Duct-to-duct biliary reconstruction has potential advantages over hepaticojejunostomy, and has become the preferred technique in ALDLT. However, biliary complications, especially biliary strictures on long-term follow-up, occur in about 30% of the recipients. The potential beneficial effect of internal or external biliary drainage in reducing the biliary complication rate after duct-to-duct biliary reconstruction in ALDLT also remains controversial. Dual-liver grafts and right-posterior sector grafts have been used in ALDLT, and are reported to result in satisfactory survival outcomes at selected transplant centers. There is no strong evidence supporting the postulate that patients with hepatitis C infection have an inferior survival outcome after ALDLT when compared with recipients of a deceased-donor liver transplant. ALDLT has contributed to satisfactory survival outcomes in patients with hepatocellular carcinoma (HCC). It allows early surgery for the patients and eliminates the uncertainty of prolonged waiting for a deceased-donor liver graft, and the risks of dropout related to disease progression. The exact selection criteria of patients with HCC for ALDLT have yet to be defined.

Adult↗
PubMed2006

Operative outcomes of adult-to-adult right lobe live donor liver transplantation: a comparative study with cadaveric whole-graft liver transplantation in a single center.

OBJECTIVE: To evaluate and compare the operative and survival outcomes of patients who underwent right lobe live donor liver transplantation (RLDLT) and cadaveric whole-graft liver transplant (CWLT) recipients in a single institution. SUMMARY BACKGROUND DATA: Current data suggest that RLDLT has an inferior graft survival outcome when compared with CWLT. PATIENTS AND METHODS: A prospective study was performed on 180 consecutive adult patients who underwent primary liver transplantation from January 2000 to February 2004. The operative and survival outcomes of RLDLT (n = 124) were compared with those of CWLT (n = 56). RESULTS: Fifty-five (44%) and 16 (29%) patients were on high-urgency list in the RLDLT group and the CWLT group, respectively (P = 0.045). The preoperative Model for End-Stage Liver Disease scores were comparable in both groups. The waiting time for liver transplantation was significantly shorter in the RLDLT group. The graft weight to estimated standard liver weight ratio was significantly lower in the RLDLT group. The postoperative hospital stay and hospital mortality were comparable in the RLDLT group (1.6%) and the CWLT group (5.4%). Thirty-one (25%) patients in the RLDLT group and 3 (5%) patients in the CWLT group developed biliary stricture on follow-up (P = 0.002). At a median follow-up of 27 months, the actuarial graft and patient survival rates were 88% and 90%, respectively, in the RLDLT group, and both were 84% in the CWLT group. CONCLUSION: RLDLT results in favorable operative outcomes comparable with those of CWLT. However, there is a significantly higher incidence of biliary stricture associated with RLDLT.

Adolescent↗
PubMed2006

Anterior approach versus conventional approach right hepatic resection for large hepatocellular carcinoma: a prospective randomized controlled study.

OBJECTIVE: To evaluate whether major right hepatectomy using the anterior approach technique for large hepatocellular carcinoma (HCC) results in better operative and long-term survival outcomes when compared with the conventional approach technique. SUMMARY BACKGROUND DATA: The anterior approach technique has been advocated recently for large right liver tumors. However, its beneficial effects on the operative and survival outcomes of the patients have not been evaluated prospectively. METHODS: A prospective randomized controlled study was performed on 120 patients who had large (> or =5 cm) right liver HCC and underwent curative major right hepatic resection during a 57-month period. The patients were randomized to undergo resection of the tumor using the anterior approach technique (AA group, n = 60) or the conventional approach technique (CA group, n = 60). The anterior approach technique involved initial vascular inflow control, completion of parenchymal transection, and complete venous outflow control before the right liver was mobilized. Operative and long-term survival outcomes of the two groups were analyzed. Quantitative assessments of markers of circulating tumor cells at various stages of surgery of the two techniques were also assessed by plasma albumin-mRNA. RESULTS: The overall operative blood loss, morbidity, and duration of hospital stay were comparable in both groups. Major operative blood loss of > or =2 L occurred less frequently in the AA group (8.3% vs. 28.3%, P = 0.005). As a result, blood transfusion requirement and number of patients requiring blood transfusion were significantly lower in the AA group. Hospital mortality occurred in 1 patient in the AA group and 6 patients in the CA group (P = 0.114). Median disease-free survival was 15.5 months in the AA group and 13.9 months in the CA group (P = 0.882). Overall survival was significantly better in the AA group (median >68.1 months) than in the CA group (median = 22.6 months, P = 0.006). The survival benefit appeared more obvious in patients with stage II disease and patients with lymphovascular permeation of the tumor. The anterior approach was also found to associate with significantly lower plasma albumin-mRNA levels at various stages of surgery compared with the CA technique. On multivariate analysis, tumor staging, anterior approach hepatic resection, and resection margin involved by the tumor were independent factors affecting overall survival. CONCLUSION: The anterior approach results in better operative and survival outcomes compared with the conventional approach. It is the preferred technique for major right hepatic resection for large HCC.

Blood Loss, Surgical↗