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Po-Huang Lee

Publications and source records attributed to Po-Huang Lee.

At least 55 records · Page 3Linked to original sources
PubMed2005

Feasibility of salvage liver transplantation for patients with recurrent hepatocellular carcinoma.

BACKGROUND: Recurrence is the most frequent cause of treatment failure after hepatocellular carcinoma (HCC) resection. Salvage liver transplantation is an alternative treatment for recurrent HCC. The transplantability for patients with recurrent HCC has not been well studied. STUDY DESIGN: This study sought to determine how many patients with recurrent HCC are still candidates for liver transplantation, and to ascertain the possible time from HCC recurrence to the loss of transplantability. In an university hospital setting, 154 of the 252 patients receiving primary HCC resection, from January 1992 through December 1996, had recurrence and were analyzed. The mean follow-up time was 6 years. Among the 154 patients, 74 patients (group 1) were not eligible for liver transplantation according to the Milan criteria, while 80 patients were eligible (group 2). Demographic characteristics of both groups were compared and the curve of transplantability was calculated. RESULTS: When compared with group 1 patients, group 2 patients displayed more cirrhosis (p = 0.007), lower pTNM stage (p = 0.004), were older (p = 0.004), presented with smaller tumors (p < 0.001), and displayed a longer disease-free interval (p < 0.001). In group 1, only 47% (35/74) patients were eligible for liver transplantation at the time of index hepatectomy, in contrast to 84% (67/80) in the group 2 patients, p < 0.001. The median time from HCC recurrence to the time they were no longer transplantable was 38 months. The total time from the index HCC resection to the time of loss of transplantability was 83 months. CONCLUSION: In a cohort of patients after resection for their primary HCC, 33% patients had no recurrence and were not in need for liver transplantation in a mean follow-up of 72 months. About 52% of the patients with recurrent HCC still meet the criteria for liver transplantation. For patients with some certain characteristics, resection of the primary HCC may postpone the time of liver transplantation and prolong the time in which a suitable donor searched, while primary liver transplantation may be considered for those patients with factors of low transplantability after recurrence.

Age Factors↗
PubMed2005

Expanding the donor pool: use of renal transplants from non-heart-beating donors supported with extracorporeal membrane oxygenation.

In response to organ shortage, we used the renal grafts from non-heart-beating donors (NHBDs). Extracorporeal membrane oxygenation (ECMO) was used to maintain NHBDs before organ procurement. We compared the results of renal transplantation from different donors, including heart-beating donors (HBDs), living-related donors (LDs), and NHBDs supported with ECMO. From February 1998 to June 2003, we recruited 219 patients receiving renal transplantation at National Taiwan University Hospital. Among them, 31 received kidneys from NHBDs supported with ECMO, 120 from HBDs, and 68 from LDs. Multiple organ transplant recipients were not included in this study. We compared the graft survival, serum creatinine levels, and estimated glomerular filtration rates of the three groups. The rate of delayed graft function was higher in NHBD recipients (41.9%) than in HBD recipients (27.0%) and LD recipients (10.9%) (p = 0.003). In the NHBD group, the recipients of grafts with delayed function had significantly longer ECMO runs (63.1 +/- 3.0 min) than those without delayed function (53.7 +/- 2.5 min) (p = 0.024). Estimated glomerular filtration rate (p = 0.472) and mean serum creatinine level (p = 0.286) were not significantly different between the three groups using a longitudinal approach. The 5-yr graft survival rates for NHBD (88.4%, 95% CI: 0.680-0.962), HBD (83.2%, 95% CI: 0.728-0.899), and LD transplant recipients (89.3%, 95% CI: 0.619-0.974) were not significantly different (p = 0.239). The 5-yr patient survival rates for NHBD, HBD, and LD transplant recipients were 100, 93.0 (95% CI: 0.859-0.966) and 100% respectively. The long-term allograft survival and function of kidneys from NHBDs supported by ECMO, HBD, and LD did not differ significantly. Long ECMO running time tended to delay graft function.

Adult↗
PubMed2005

Clonality analysis of multiple hepatocellular carcinomas by loss of heterozygosity pattern determined by chromosomes 16q and 13q.

BACKGROUND AND AIM: Loss of heterozygosity (LOH) on chromosomes 16q and 13q, associated with tumor development, is frequently found in hepatocellular carcinoma (HCC). In light of this, an attempt was made to use the LOH pattern determined by microsatellite markers on 16q and 13q to discriminate clonality. METHODS: In an effort to locate the LOH region more precisely and select the appropriate markers, LOH studies on 88 HCC using a panel of 35 microsatellite markers on 16q were carried out. Nine independent regions of frequent LOH were defined. In combination with a previous study of deletion mapping of 13q by the same authors, 12 markers on 16q and 13q were selected and polymerase chain reaction amplification, from microdissection-extracted DNA, was used to allelotype microsatellite polymorphism as an indication of clonality. RESULTS: Two patterns of LOH were observed. In pattern A, in 8 of 16 (50%) patients, the LOH pattern of the first tumor was preserved in the second sample, with some tumors also showing additional LOH. In these patients, the original and second tumors are presumed to arise from the same original clone with or without progressive accumulation of LOH. In pattern B (8 of 16, 50%), LOH seen in the first tumor was not preserved in the second or recurrent tumors, as evidenced by retention of heterozygosity compared with the first tumor. CONCLUSION: The data suggest that the second tumor might have arisen from another independent clone. Moreover, this approach also provides a more sensitive and specific strategy to determine whether multiple or recurrent tumors are derived from the same or a different clone.

Alleles↗
PubMed2005

Effects of calcineurin inhibitors on sirolimus pharmacokinetics during staggered administration in renal transplant recipients.

STUDY OBJECTIVE: To compare the effects of different calcineurin inhibitors on sirolimus pharmacokinetics during long-term, staggered administration in kidney transplant recipients. Design. Randomized, open-label, parallel-group trial. SETTING: A medical center and one of its teaching hospitals in Taiwan. PATIENTS: Twenty-two de novo kidney transplant recipients. INTERVENTION: Patients received cyclosporine microemulsion or tacrolimus capsules twice/day in combination with once-daily sirolimus solution and corticosteroids. Sirolimus was administered 6 hours after the morning dose of cyclosporine or tacrolimus. After receiving a 6-mg loading dose of sirolimus, participants received sirolimus 2 mg/day for at least 7 days. Neither the cyclosporine nor the tacrolimus dosage was adjusted for at least 3 days before and during blood sampling for pharmacokinetic profiling. MEASUREMENTS AND MAIN RESULTS: One patient dropped out because of trimethoprim-sulfamethoxazole-related hepatotoxicity. We observed no differences between the two patient groups in terms of their demographic data, renal and liver function, or dosage of sirolimus during the study. During multiple-dose administration, the area under the whole-blood concentration-time curve and the peak and trough concentrations of sirolimus in the cyclosporine group were, respectively, 1.46 (95% confidence interval [CI] 1.21-1.71), 1.42 (95% CI 1.08-1.76), and 1.42 (95% CI 1.09-1.76) times higher than those of the tacrolimus group, even though sirolimus was administered 6 hours after the other agents. CONCLUSION: Sirolimus pharmacokinetics may change significantly when calcineurin inhibitors are switched, even with staggered administration, which may not completely prevent a drug interaction between cyclosporine and sirolimus solution.

Adult↗
PubMed2005

Effects of conversion from sirolimus oral solution to tablets in stable Taiwanese renal transplant recipients.

BACKGROUND AND PURPOSE: Sirolimus (SRL) has a considerable inter- and intra- individual variability in clearance. Steady-state trough concentration (C(0)) is a reliable index of SRL exposure. This study assessed the effect of conversion of SRL oral solution to tablet form on C(0) in stable renal transplant recipients. METHODS: Twenty two stable renal transplant recipients who had received calcineurin inhibitor (CNI)/SRL solution/ steroid for more than 3 months before conversion from SRL solution to tablets were included. C(0) values of SRL were compared for the periods of use of each dosage form. The relation between liver function and SRL levels was also assessed. RESULTS: With a dose of 0.03 mg/kg/day, SRL solution and tablets achieved a similar dose-adjusted C(0) (mean +/- SEM, 2.9 +/- 0.3 ng/mL/mg) upon conversion. Similar results were found when multiple SRL C(0) values from different dosage form periods were compared. Four patients with persistent liver enzyme elevation had significantly higher dose-adjusted SRL C(0) values with both the solution (mean +/- SEM, 4.5 +/- 0.7 vs 2.3 +/- 0.1 ng/mL/mg; p < 0.01) and the tablet formulation (4.0 +/- 0.5 vs 2.6 +/- 0.2 ng/mL/mg; p < 0.05). CONCLUSIONS: Conversion from SRL solution to SRL tablets did not significantly affect the dose-adjusted SRL C(0). The dose-adjusted C(0) of SRL in patients with persistent liver enzyme elevation was significantly higher than in those with normal liver function.

Administration, Oral↗
PubMed2005

Prognostic significance of six-month estimated glomerular filtration rate in cadaveric renal transplantation.

BACKGROUND AND PURPOSE: We hypothesized a linear relative-risk model for graft survival of cadaveric renal transplantation, with a 6-month estimated glomerular filtration rate (GFR) employed as the linear parameter quantifying functioning renal mass and the detrimental effects of early chronic allograft nephropathy. METHODS: A retrospective study was conducted in a 15-year series of cadaveric renal transplantations (n = 227) with cyclosporin-based immunosuppression in a single transplant center. The Cockcroft-Gault formula was used for estimation of GFR, with a correction factor of 0.85 used for women. Stepwise Cox's regression analyses were applied to examine the prognostic significance of the 6-month estimated GFR. RESULTS: The Kaplan-Meier 5- and 10-year graft survival rates for this study were 80.67% and 59.43%, respectively. From univariate analysis, recipient gender, acute rejection and 6-month estimated GFR were significantly associated with graft survival (p < 0.05). Acute rejection became less significant (p = 0.0033) than 6-month estimated GFR (p = 0.0001) when 6-month estimated GFR was introduced in the stepwise regression procedures. CONCLUSION: We demonstrated that 6-month estimated GFR is a significant prognostic indicator in cadaveric renal transplantation and is an essential parameter in the regression modeling of long-term graft survival.

Adolescent↗
PubMed2005

Viral infections and prolonged fever after liver transplantation in young children with inborn errors of metabolism.

BACKGROUND AND PURPOSE: Liver transplantation could be a useful treatment for selected inborn errors of metabolism. This study evaluated the outcome and viral infections after liver transplantation in young children and infants with these diseases. METHODS: The outcome of liver transplantation and clinical characteristics of the following 4 patients were assessed: 1 infant with ornithine transcarbamylase deficiency (OTCD) who received liver transplant aged 3 years and 4 months; 1 infant with carbamyl phosphate synthetase I deficiency (CPSID) who received liver transplant at 14 months of age; and 2 infants with methylmalonic acidemia (MMA) who received liver transplant at 8 months and 11 months of age, respectively. All donors, except the 8-month-old infant with MMA, showed serologic evidence of previous cytomegalovirus (CMV) infection before transplantation. All 4 of these donors showed serologic evidence of previous infection of Epstein-Barr virus (EBV). None of the recipients had previous CMV infection. Both the infant with OTCD and the 8-month-old infant with MMA had previous EBV infection, while the other 2 patients did not. Preoperative hemodialysis was performed in both infants with MMA. Postoperative follow-up included metabolic stability, disability degree, and viral infections. RESULTS: None of the patients developed severe metabolic decompensation after transplantation and all increased protein intake postoperatively. Symptomatic viral infections, however, were present in all patients postoperatively, including CMV infection in the infant with OTCD and the 11-month-old infant with MMA, reactivation of EBV infection in the infant with OTCD and the 8-month-old infant with MMA, and primary EBV infection in the infant with CPSID. CONCLUSIONS: Liver transplantation was an effective treatment for all 4 of these patients with inborn errors of metabolism. The risk of symptomatic viral infections for these patients was high. This was likely associated with conditions including immunosuppression, young age, endemic nature of CMV and EBV infections, and lack of CMV prophylaxis.

Carbamoyl-Phosphate Synthase I Deficiency Disease↗
PubMed2004

The significance of placenta growth factor in angiogenesis and clinical outcome of human gastric cancer.

Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family of proangiogenic factors and its overexpression has been linked to pathological angiogenesis. We studied the relationship between the expression of PlGF and VEGF in human gastric cancer tissues and microvessel density (MVD), as well as clinical outcome in 79 patients with gastric cancer by using an enzyme immunoassay for PlGF and VEGF expression levels in gastric cancers and surrounding non-cancerous mucosa. PlGF protein levels were significantly higher in tumor than in the corresponding non-tumorous mucosa (median value 48.5 vs 9.8 pg/mg, P < 0.001). In contrast, VEGF protein levels were not (66.7 vs 80.7 pg/mg, P = 0.522). VEGF expression level was not significantly correlated with MVD, patient survival, and clinicopathological factors except Lauren classification in this study. PlGF may be an important angiogenic factor in human gastric cancer, and PlGF expression level was significantly correlated with serosal invasion, positive lymph node metastases, tumor stages, and patient survival.

Biomarkers, Tumor↗
PubMed2004

RBMY, a male germ cell-specific RNA-binding protein, activated in human liver cancers and transforms rodent fibroblasts.

The RNA-binding motif (RRM) gene on Y chromosome (RBMY), encoding a male germ cell-specific RNA-binding protein associated with spermatogenesis, was found inserted by hepatitis B virus (HBV) DNA in one childhood hepatocellular carcinoma (HCC). This study is aimed to explore the oncogenic potential of the RBMY protein. The RBMY transcripts, expressed exclusively in the testis of normal people, were detected by reverse transcription-polymerase chain reaction in 36% of HCCs from 90 males and in 67% of hepatoblastoma from six boys. The nontumor liver counter parts, cirrhotic liver tissues from children with biliary atresia, and other types of cancers, such as bile duct, colon, stomach, lung, prostate, and kidney, were all negative for RBMY expression. One to four types of RBMY transcripts, including wild type and variants with N-terminal RRM deletion, C-terminal SRGY (serine-arginine-glycine-tyrosine) boxes deletion, or deletion of both domains, were found in the testis and liver cancer tissues. The wild-type RBMY protein was expressed in the nucleus and demonstrated its tumorigenicity by transformation of mouse fibroblast NIH3T3 cells and in vivo tumor formation. The RBMY variant protein with deletion of C-terminal exons 9-12 was trapped in the cytoplasm and showed decreased tumorigenicity. Our results suggest that RBMY is a new candidate oncogene specific for male liver cancer.

3T3 Cells↗
PubMed2004

Expression of eukaryotic initiation factor 4E in gastric adenocarcinoma and its association with clinical outcome.

BACKGROUND AND OBJECTIVES: Overexpression of eIF4E can result in oncogenic transformation and uncontrolled growth of mammalian cells, presumably by facilitating the expression of growth-control gene products, which are normally translationally repressed. Overexpression of eIF4E was present in human breast carcinoma and human head and neck squamous cell carcinoma, and may be of prognostic value in breast carcinomas. In order to elucidate the clinical significance of eIF4E expression, this study was conducted to quantify expression of eIF4E in human gastric cancer tissue and correlate them with clinicopathological factors and patient survival. METHODS: Specimens from sixty-nine patients with gastric adenocarcinoma were analyzed and eIF4E overexpression was quantified by Western blot analysis. Quantification of eIF4E levels in cancer was expressed relative to controls from non-tumorous mucosa of the same patients. Confirmation of eIF4E overexpression at the cellular level was performed using immunohistochemical staining. The association of clinicopathologic factors and survival with eIF4E expression was analyzed. RESULTS: In non-tumorous parts of specimens, overexpression of eIF4E was always present in gastric glands but not in gastric pits lining mucosa, and it was also expressed in the areas of intestinal metaplasia and dysplasia. In the 69 specimens, the mean eIF4E expression was 5.77 +/- 8.55-fold (mean +/- standard deviation), ranged from from 0.1-fold to 38-fold. The degree of eIF4E expression appeared to be independent of invasion depth of tumor, lymph node metastasis, Lauren classification, Borrmann types, and Helicobacter pylori infection. Marked overexpression of eIF4E (more than seven-fold) was correlated with tumor vascular invasion (P = 0.046, Fisher exact-test). The survival rate of the patients with underexpression or mild overexpression of eIF4E (less than sevenfold) was significantly higher than that with marked eIF4E overexpression (more than sevenfold) (P = 0.01734, log rank test). CONCLUSIONS: Marked eIF4E overexpression in gastric cancer was found to be associated with vascular invasion. The prognosis for gastric cancer patients with marked overexpression of eIF4E was worse than those with underexpression. It may serve as an additional prognostic and therapeutic factor in gastric cancer, and deserves further investigation.

Adenocarcinoma↗
PubMed2004

The role of B7 ligands (CD80 and CD86) in CD152-mediated allograft tolerance: a crosscheck hypothesis.

BACKGROUND: The regulatory mechanism by which the B7 ligands (CD80 and CD86) direct the CD28/CD152 costimulatory pathways is unclear. This study investigated the role of CD80 and CD86 in a CD152-mediated allograft tolerance model. METHODS: A low-responding cardiac transplant model (BALB/c-->B10.A) with possible long-term acceptance was used. Immunocytochemical and flow cytometric analyses of the graft-infiltrating cells were conducted to characterize this transplant model. The influence of anti-CD80 and anti-CD86 treatments on the proliferation and interleukin (IL)-2 productions of the tolerated splenocytes (SC) was analyzed. The role of CD80 and CD86 in the induction and maintenance of the graft acceptance in this transplant model were also tested. RESULTS: B10.A mice could accept the BALA/c cardiac allografts (11/22), and an anti-CD152 antibody blocked the graft acceptance (10/10). Immunocytochemical and flow cytometric analyses showed that CD152+ cells were predominant among the CD4+ cells infiltrating the 100-day grafts of the B10.A recipients (B10.A-100). Either anti-CD80 or anti-CD86 treatment significantly enhanced polyclonal proliferation and IL-2 production of the B10.A-100 SC. Blockade of either CD80 or CD86 prohibited the tolerance transmitted by adoptive transfer, and anti-CD80 or anti-CD86 plus skin grafting undermined the established allograft tolerance. CONCLUSIONS: Both CD80 and CD86 were essential for the induction and maintenance of the CD152-mediated allograft tolerance.

Adoptive Transfer↗
PubMed2004

Hepatitis B genotypes correlate with tumor recurrence after curative resection of hepatocellular carcinoma.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC), compared with genotype B. This study aims to investigate whether HBV genotypes influence the clinicopathologic features and long-term prognosis of patients after curative resection of HCC. METHODS: Stored serum samples from 62 patients with HBV-related HCC were tested for HBV genotype using a molecular method. RESULTS: Sixty of 62 patients (96.8%) undergoing curative resection of HCC were infected with genotype B or C. Concomitant cirrhosis was encountered more frequently in patients with genotype C. During a mean follow-up period of 26.3 +/- 9.8 months, patients with genotype B had a lower overall tumor recurrence rate than those with genotype C (22% vs. 46%; P = 0.04). Stepwise multiple Cox proportional hazards regression analysis showed that multiplicity of tumor (hazard ratio, 6.84; 95% confidence interval [CI], 1.45-32.2; P = 0.02) was associated with tumor recurrence, whereas genotype C and age were associated with borderline significance (P = 0.06). Stratified analysis showed that genotype C was still associated with tumor recurrence in cirrhotic patients with borderline significance by univariate analysis (hazard ratio, 3.8; 95% CI, 0.84-17.6; P = 0.07). However, cumulative 2-year survival rates were similar between patients with genotype B and C (92% vs. 85%; P = 0.23). CONCLUSIONS: Our data suggest that patients with HCC with genotype C have a greater tumor recurrence rate after curative resection of HCC compared with those with genotype B. Prolonged follow-up is needed to clarify the impact of HBV genotype on postoperative outcome.

Adult↗
PubMed2004

Alveolar hydatid disease causing total occlusion of the inferior vena cava.

Alveolar hydatid disease is a malignancy-like parasitic disease. It is invasive, metastatic, and almost always lethal if left untreated. A case of alveolar hyatid disease presenting with total of the inferior vena cava is reported. This 28-year-old man was referred for elevation of obstructive jaundice. He was a lama and had recently arrived in Taiwan after touring temples in Nepal, India, and Singapore. Computed tomography showed calcified mass which occupied the right hepatic lobe with extension to the left hepatic lobe. The inferior vena cava was occluded and stricture of biliary tree and portal vein at the hilum was also noted. The patient was treated successfully with palliative resection combined with postoperative albendazole. With increasing travel and immigration, clinicians will be more likely to encounter this rare disease, and thus should be able to recognize its symptoms.

Adult↗
PubMed2004

Hand-assisted versus total laparoscopic live donor nephrectomy.

BACKGROUND AND PURPOSE: The optimal minimally invasive procedure to procure live donor kidneys for renal transplantation has not been established. This study compared the donor outcome of hand-assisted laparoscopic live donor nephrectomy (H-LLDN) with total laparoscopic live donor nephrectomy (T-LLDN). METHODS: The outcomes of 12 donors undergoing H-LLDN were compared to that of a subsequent series of 12 donors undergoing T-LLDN. Body mass index, operation time, warm ischemia time, hospital stay, surgical complications, and short-term graft function were compared between the 2 groups. RESULTS: LLDN was successfully performed in all 24 donors. Both approaches resulted in excellent early graft function. The mean operation time in T-LLDN (215 minutes) was slightly shorter than that in H-LLDN (258 minutes), suggesting that the skills developed as surgeons learned the H-LLDN procedure had transferred to their performance of T-LLDN. The mean warm ischemia time of the T-LLDN group (4.5 minutes) was longer than that of the H-LLDN group (3.8 minutes), although this difference was not significant. One minor tear of the lumbar vein occurred in the H-LLDN group and the resultant bleeding necessitated blood transfusion. One mechanical failure occurred when the renal vein was divided by endoscopic gastrointestinal anastomosis in the T-LLDN group. The length of hospital stay, resumption of diet, and the use of narcotic analgesics were not different between the 2 groups. CONCLUSIONS: Both H-LLDN and T-LLDN are safe and effective approaches for the procurement of live donor kidneys. The benefits of the H-LLDN technique include direct manual control of the operative field and increased safety margin. The development of a hospital LLDN program by starting with a hand-assisted approach may reduce the potential bleeding complications and facilitate the safe transition to the cosmetically preferable total laparoscopic approach.

Adult↗
PubMed2003

The role of gelatinase in hepatic metastasis of colorectal cancer.

PURPOSE: To determine the role of gelatinase in the hepatic metastatic process of colorectal cancer, we correlated gelatinolytic activity in colorectal tumor tissue both to the presence of intravasated colorectal epithelial cells and to the formation of liver metastasis. EXPERIMENTAL DESIGN: The gelatinolytic activity was analyzed in tumor tissue samples from 68 colorectal cancer patients by using gelatin substrate zymography. The presence of intravasated colorectal epithelial cells was defined as detection of guanylyl cyclase C mRNA in blood sampled from drainage vein of a tumor-bearing colorectal segment. RESULTS: Forty of 68 patients were noted to have guanylyl cyclase C mRNA expression in their drainage venous blood. Fifteen patients were noted to have liver metastasis at the time of surgery, and another 15 patients developed liver metastasis during median follow-up period of 53 months. Either individual or total gelatinolytic activity in colorectal tumor tissue failed to predict the presence of intravasated colorectal epithelial cells in the drainage venous blood or formation of liver metastasis. Presence of both intravasated colorectal epithelial cells and high total gelatinolytic activity in colorectal tumor tissue, however, is a strong predictor of liver metastasis (P = 0.004). CONCLUSION: Our data suggested that gelatinolytic activity in colorectal tumor tissues may facilitate the hepatic metastatic process in the steps after intravasation but not during or before intravasation.

Adult↗
PubMed2003

Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation and its relationship to aflatoxin B1-DNA adducts and p53 mutation in hepatocellular carcinoma.

O(6)-methylguanine-DNA methyltransferase (MGMT) is a repair protein that specifically removes promutagenic alkyl groups from the O(6) position of guanine in DNA. MGMT is transcriptionally silenced by promoter hypermethylation in several human cancers. Methylation-specific PCR (MSP) was used to analyze the MGMT promoter methylation status of 83 hepatocellular carcinomas (HCC) and 2 HCC cell lines (HepG2 and Hep3B). Hypermethylation was detected in 32 of 83 (39%) HCC tissues, but it was not found in either HCC cell line. We also analyzed MGMT expression by immunohistochemical analysis of HCC tissue samples. The presence of aberrant hypermethylation was associated with loss of MGMT protein. The relationship between methylation status and risk factors and tumor markers including environmental exposure to aflatoxin B(1) (AFB(1)), measured as DNA adducts, and status of tumor suppressor gene p53 was also investigated. A statistically significant association was found between MGMT promoter hypermethylation and high level of AFB(1)-DNA adducts in tumor tissues (OR = 5.05, 95% CI = 1.29-19.73). A significant association was also found between methylation and p53 mutation status (OR = 2.97, 95% CI = 1.09-8.11). These results suggest that epigenetic inactivation of MGMT plays an important role in the development of HCC and exposure to environmental carcinogens may be related to altered methylation of genes involved in cancer development. The role of chemical carcinogens in hypermethylation needs further investigation.

Aflatoxin B1↗
PubMed2003

Antibiotics induce apoptosis of human peritoneal mesothelial cells.

The peritoneal mesothelial cell is a critical component of the peritoneal membrane. The intraperitoneal use of several antibiotics to treat bacterial peritonitis is current clinical practice. Our previous study showed that cephalothin (CPL) and cefotaxime (CFT) have cytotoxic effects on human peritoneal mesothelial cells (HPMC), however, the exact mechanism of cytotoxicity has not been elucidated. In the present study, flow cytometry, TdT-mediated dUTP nick-end labelling (TUNEL) staining and electron microscopy were used to detect the apoptosis of HPMCs. Immunofluorescent staining was used to evaluate the cytochrome c distribution pattern. Western blotting was used to assess apoptotic signalling proteins. We found that CPL (0.5 mg/mL) and CFT (1 mg/mL) induced apoptosis of HPMCs, whereas cefazolin (0.5 mg/mL) and ceftriaxone (0.5 mg/mL) failed to induce apoptosis of HPMCs. While the DNA content of CFT- or CPL-treated cells was reduced, as determined by flow cytometry, cefazolin and ceftriaxone had no such effect. The CFT- or CPL-treated cells displayed the features of apoptosis both under the electron microscope and by using TUNEL staining. However, cefazolin and ceftriaxone produced the same result as the medium controls. Furthermore, CFT and CPL increased the expression of Bax and p53, and caused the translocation of cytochrome c from the mitochondria to the cytoplasm. The HPMC treated by CFT but not by CPL induced the cleavage of procaspase-3 to form active caspase-3. In conclusion, cefotaxime and cephalothin induce apoptosis of HPMCs in vitro. Signal transduction may be through the mitochondrial pathway.

Anti-Bacterial Agents↗