Biomedical subjects

I O Ng

Publications and source records attributed to I O Ng.

At least 19 recordsLinked to original sources

PubMed2005

Impact of precore and core promoter mutations on hepatic histology in patients with chronic hepatitis B.

BACKGROUND: The details of liver histology of patients with precore and core promoter mutations are still not clear. AIM: To determine the role of precore and core promoter mutations in liver histology in Chinese patients with chronic hepatitis B. PATIENTS AND METHODS: Intrahepatic hepatitis B virus DNA (by COBAS Amplicor hepatitis B virus Monitor test) and precore and core promoter mutations (by a line probe assay) were measured in 54 chronic hepatitis B patients. Expression of hepatitis B core antigen, hepatitis B e antigen and hepatitis B surface antigen was determined by immunohistological staining. Histological activity index was scored according to Knodell's criteria. RESULTS: Compared with patients without core promoter mutations, patients with core promoter mutations had more severe intrahepatic inflammation and fibrosis, and more cytoplasmic expression of hepatitis B core antigen (P = 0.028). No such differences were found in patients with and without precore mutations. Logistic regression showed that core promoter mutations were independently associated with cytoplasmic expression of hepatitis B core antigen (P = 0.026). Intrahepatic hepatitis B virus DNA levels correlated with serum hepatitis B virus DNA levels (r = 0.71, P < 0.001) and the percentage of hepatitis B core antigen-positive hepatocytes (r = 0.37, P = 0.047), but had no correlation with serum alanine aminotransferase levels nor the degree of inflammation and fibrosis. CONCLUSIONS: Patients with core promoter mutations had more severe inflammation and fibrosis, and more frequent cytoplasmic expression of hepatitis B core antigen. This suggested that core promoter mutations might cause more serious liver disease.

Adult↗

PubMed2004

Unicystic ameloblastoma--use of Carnoy's solution after enucleation.

A retrospective analysis of 29 patients with a histologically confirmed diagnosis of unicystic ameloblastoma is reported with special emphasis on a treatment regime employing enucleation and application of Carnoy's solution. Despite the finding that 93% of lesions exhibited mural invasion, a recurrence rate of 10% after treatment is reported, suggesting a possible benefit of Carnoy's solution against recurrence.

Acetic Acid↗

PubMed2003

Clinicopathologic significance of genetic alterations in hepatocellular carcinoma.

Hepatocarcinogenesis may involve multiple mutations with distinctive pathogenetic and clinicopathologic significance. To test this hypothesis, 68 cases of hepatocellular carcinoma (HCC) were studied prospectively for genetic-clinicopathologic correlation. Ten pathologic characteristics were evaluated. TP53 (alias p53) gene mutation was studied by a polymerase chain reaction (PCR)-single-strand conformation polymorphism-sequencing; CDKN2B (alias p15) and CDKN2A (alias p16) gene methylation by methylation-specific PCR; and genetic imbalances by comparative genomic hybridization (CGH). TP53 gene mutations occurred in 25% of cases, more than half being codon 249 G to T transversion. Methylation of CDKN2A was frequent (61.7%); of CDKN2B, rare (5.9%). The CGH analysis showed a median of nine aberrations per case, with amplifications more frequent than deletions. Isochromosomes might be involved in about 25% of cases. Amplifications of 1q and 8q were most frequent. Clinicopathologic correlations showed that CDKN2A methylation was significantly associated with tumors arising in cirrhotic livers; amplifications of 17q was significant in multiple parameters of tumor invasiveness (size, venous invasion, poor cellular differentiation, microsatellite formation); other amplifications (1q, 6p, 10p, and 20p) were also significant in tumor invasion; and deletions (at 1p, 11q, 4q, and 14q) were significant in tumor growth. Consistent patterns of genetic alterations were defined in HCC, which might represent distinctive pathways in hepatocarcinogenesis.

Adolescent↗

PubMed2001

Exogenous expression of p21(WAF1/CIP1) exerts cell growth inhibition and enhances sensitivity to cisplatin in hepatoma cells.

The effects of exogenous expression of p21(WAF1/CIP1) in hepatoma cells were examined. Two stably p21(WAF1/CIP1)-transfected clones and one clone transfected with expression vector only were used for study. Introduction of p21(WAF1/CIP1) resulted in significant cell growth inhibition, and the magnitude of the cell growth inhibition in these transfected cells was proportional to the level of p21(WAF1/CIP1) protein expressed. Exogenous p21(WAF1/CIP1) expression also significantly enhanced chemosensitivity to cisplatin. In addition, apoptosis occurred earlier in cells transfected with p21(WAF1/CIP1) after cisplatin treatment. These findings raise the potential that forced upregulation of p21(WAF1/CIP1) in hepatocellular carcinoma (HCC) may reduce the doses of cisplatin to achieve similar responses and suggest the possible use of p21(WAF1/CIP1) in HCC treatment.

Antineoplastic Agents↗

PubMed2001

Gene delivery using a receptor-mediated gene transfer system targeted to hepatocellular carcinoma cells.

For gene therapy to be effective in cancers, it is necessary to deliver therapeutic genes into cells with high specificity and efficiency. In this study, we examined the in vitro and in vivo gene delivery efficiency of a new, growth receptor-mediated gene transfer system in hepatocellular carcinoma (HCC). The effects of transfection of wild-type p53 using this system were also studied. The system consisted of a ligand oligopeptide for epidermal growth factor receptor (EGFR) recognition, a polypeptide for DNA binding, and an endosome-releasing oligopeptide for endosomolysis. Two human HCC cell lines and a normal liver cell line were used, and pCMV-beta-galactosidase (beta-gal) was used as a reporter gene. Both HCC cell lines had strong expression of EGFR and the in vitro transfer efficiency peaked at day 5 at about 50%. This finding was in contrast to the normal liver cell line, which had weak EGFR expression and less than 1% transfer efficiency throughout. For in vivo gene transfer in tumors produced by inoculating HCC cells in nude mice and with the vector-beta-gal gene complex injected peritumorally, beta-gal expression was detected within the tumors at 12 hr, peaked at day 5 involving about 50% of the tumor cells and persisted at 2 weeks. Using this vector system, transfection of wild-type p53 into Huh-7 cells that had mutated p53 resulted in significant growth inhibition of cancer cells accompanied by a decreased G2/M phase and increased p53 protein. In conclusion, this receptor-mediated gene transfer system appears to work specifically in HCC cells with high efficiency, and may be promising in delivering apoptotic and other genes into HCC cells.

Antineoplastic Agents↗

PubMed2001

beta-Catenin mutation and overexpression in hepatocellular carcinoma: clinicopathologic and prognostic significance.

BACKGROUND: beta-Catenin has been recognized as a critical member of the Wnt signaling pathway, and inappropriate activation of this pathway has been implicated in carcinogenesis. METHODS: To determine the clinical significance of beta-catenin in hepatocellular carcinoma (HCC), we performed mutational analysis at exon 3 of the gene, investigated the subcellular protein expression, and analyzed their clinicopathologic and prognostic significance in 60 patients with resected primary HCC. RESULTS: By direct DNA sequencing, somatic mutations of the beta-catenin gene were detected in 7 (12%) HCCs. All the mutations were found at the region (exon 3) responsible for phosphorylation and ubiquitination, therefore likely to result in stabilization of free cytoplasmic beta-catenin. Nuclear accumulation of the beta-catenin protein, similar to the response to the Wnt signal, was found in 10 (17%) HCCs and was closely associated with gene mutation (P < 0.001). In the remaining cases, nonnuclear type overexpression, that is, overexpression in the cytoplasm and/or cytoplasmic membrane, was observed in 31 (62%) HCCs, thus suggesting that the mechanisms leading to beta-catenin overexpression may be heterogeneous. HCCs with a nonnuclear type of beta-catenin overexpression were more frequently larger than 5 cm in diameter (P = 0.022) and had poorer cellular differentiation (P = 0.037), and the patients had significantly shorter disease-free survival lengths (P = 0.041). Review of the data from previous studies in HCC showed that beta-catenin mutations were more frequent in HCV-associated HCC than in HBV-associated ones. CONCLUSIONS: beta-catenin mutation and deregulation may play an important role in hepatocarcinogenesis. Nonnuclear type beta-catenin overexpression appeared to have pathologic and prognostic significance.

Adult↗

PubMed2001

Clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma: a study of a prospective cohort.

PURPOSE: This study aims to clarify the clinicopathologic features of long-term survivors and disease-free survivors after resection of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The clinicopathologic features of 5-year survivors and disease-free survivors were elucidated in a cohort of 230 patients prospectively observed for > 5 years (64 to 192 months) after curative resection of HCC. RESULTS: The incidence of 5-year overall and disease-free survivors were 37% (85 of 230) and 20% (45 of 230), respectively. Clinicopathologic features associated with 5-year survivors included female sex (P =.024), preoperative serum albumin > or= 40 g/L (P =.033), AST < 50 u/L (P =.001), tumor < 5 cm (P =.001), solitary tumor (P =.035), encapsulated tumor (P =.021), no venous invasion (P =.001), no microsatellite nodule (P =.001), and early pathologic tumor-node-metastasis (pTNM) stage (I or II, P <.001). Features favoring 5-year disease-free survivors were preoperative serum AST < 50 u/L (P =.007), tumor < 5 cm (P =.005), encapsulated tumor (P =.007), no venous invasion (P <.001), no microsatellite nodule (P =.001), and early pTNM stage (I or II, P <.001). By multivariate analysis, pTNM stage was the only significant predictive factor for both overall and disease-free survival. CONCLUSION: This study shows that long-term disease-free survival > 5 years after resection of HCC can be achieved in patients with favorable tumor characteristics. Early pTNM stage was the most reliable predictor of both long-term overall and disease-free survivors.

Adolescent↗

PubMed2001

Liver transplantation in rats using small-for-size grafts: a study of hemodynamic and morphological changes.

BACKGROUND: Damage to a small-for-size liver graft after reperfusion is frequently observed but the mechanism of injury remains unclear. HYPOTHESIS: Injury to a small-for-size liver graft is related to the changes of portal pressure and blood flow. MAIN OUTCOME MEASURES: Survival rates, portal hemodynamics, microcirculatory changes, and morphological changes (by light microscopy and electron microscopy). SETTING: A rat model of nonarterialized orthotopic liver transplantation comparing 2 groups of rats transplanted with whole grafts (100% of recipient liver weight) and small-for-size grafts (30% of recipient liver weight). RESULTS: Median survival of the rats with small-for-size grafts was 30 hours (range, 27-37 hours). During the first 15 minutes after reperfusion, mean arterial pressure of the small-for-size graft group was significantly lower than that of the whole graft group (10-minute: 100 vs 132 mm Hg, P =.04; 15-minute: 96 vs 127 mm Hg, P =.04). Portal pressure (in centimeters of water) of the small-for-size graft group was significantly higher in the first 20 minutes after reperfusion than the level before the anhepatic phase (5-minute: 15.1 vs 9.3, P =.02; 10-minute: 16.1 vs 9.3, P =.03; 15-minute, 13.5 vs 9.3, P =.03; 20-minute: 13.4 vs 9.3, P =.03) and was significantly higher than that of the whole graft group in the first 10 minutes after reperfusion (5-minute: 15.1 vs 9.6, P =.02; 10-minute: 16.1 vs 10.3, P =.04). Hepatic microcirculatory blood flow (in milliliters per minute per 100 g) was also significantly higher in the small-for-size graft group during the first 40 minutes after reperfusion (5-minute: 16.3 vs 9.3, P =.02; 10-minute: 14.9 vs 6.6, P =.02; 15-minute: 14.8 vs 5.5, P =.02; 20-minute: 13.1 vs 7.0, P =.02; 30-minute: 13.2 vs 8.8, P =.04; 40-minute: 14.6 vs 7.1, P =.02). Light and electron microscopy showed normal morphological features of whole graft up to 24 hours after reperfusion. The small-for-size graft, however, showed sinusoidal congestion, tremendous swelling of mitochondria of hepatocytes, irregular large gap of sinusoidal lining cells, and collapse of the space of Disse. CONCLUSIONS: In a rat model, the portal hemodynamic changes in small-for-size grafts are transient. Progressive damage of the graft may result from microcirculatory failure due to irreversible endothelial injury after reperfusion.

Animals↗

PubMed2001

Correlation of serum basic fibroblast growth factor levels with clinicopathologic features and postoperative recurrence in hepatocellular carcinoma.

BACKGROUND: Basic fibroblast growth factor (bFGF) is an important positive regulator of tumor angiogenesis. This study evaluated the role of serum bFGF as a biological marker of tumor invasiveness and postresection recurrence in hepatocellular carcinoma (HCC). METHODS: Concentrations of bFGF in preoperative serum samples in 88 patients undergoing resection of HCC were measured by a quantitative enzyme-linked immunosorbent assay. A single pathologist performed histopathologic examination of all tumor specimens. All patients were prospectively monitored for tumor recurrence. RESULTS: The preoperative serum bFGF levels ranged from <0.22 to 71.2 pg/mL (median 10.8 pg/mL). There was significant correlation between high serum bFGF levels and large tumor >5 cm, presence of venous invasion or advanced pTNM stage. Patients with a serum bFGF level >10.8 pg/mL had worse disease-free survival than those with a level <10.8 pg/mL (median disease-free survival 11.2 versus 20 months, P = 0.044). Serum bFGF level >10.8 pg/mL (P = 0.035) and tumor size >5 cm (P = 0.004) were independent preoperative factors that predicted early recurrence after resection of HCC. CONCLUSIONS: This study supports a role of bFGF in tumor growth and invasion in HCC. A high preoperative serum bFGF level appears to be predictive of invasive tumor and early postoperative recurrence. The clinical implications of serum bFGF level in HCC warrant further investigation.

Biomarkers, Tumor↗

PubMed2001

Acute pancreatitis complicating acute exacerbation of chronic hepatitis B infection carries a poor prognosis.

The clinical outcome of acute pancreatitis complicating acute exacerbation of chronic hepatitis virus B (HBV) infection has never been studied. Ninety patients with acute pancreatitis were recruited. Five patients (5.6%) (Group 1) had acute pancreatitis superimposed on acute exacerbation of chronic HBV infection with no other causes of acute pancreatitis being identified. The clinical outcome of these five patients was compared to the 85 non-HBV infected patients (Group 2) with acute pancreatitis. A third group (Group 3) of patients (n=406) with acute exacerbation of chronic HBV infections without acute pancreatitis was also recruited for comparison. Group 1 had a significantly higher mortality rate (4 out of 5, 80%) compared to those of Group 2 (13 out of 85, 15.3%, P=0.0041) and Group 3 (9 out of 406, 2.2%, P < 0.0001). In Group 1 patients, the acute pancreatitis occurred during the initial rise of HBV DNA with relatively low or normal level of alanine aminotransferase (ALT) in two patients, during the rise of ALT with declining level of HBV DNA in one patient, and during the cholestatic phase of the acute exacerbation in one patient. The acute pancreatitis was clinically silent and only diagnosed by computerized tomography in the remaining patient. Direct viral damage and/or immunological attack to the pancreatic tissue were probably the underlying pathogenesis of the acute pancreatitis in these patients. In conclusion, acute pancreatitis complicating acute exacerbation of chronic HBV infection carried an extremely poor prognosis with high mortality.

Acute Disease↗

PubMed2001

Expression of p27(KIP1) and p21(WAF1/CIP1) in primary hepatocellular carcinoma: clinicopathologic correlation and survival analysis.

To investigate the possible roles of p27(KIP1) and p21(WAF1/CIP1), inhibitors of cyclin-dependent kinases, in hepatocellular carcinoma (HCC), we examined p27(KIP1) and p21(WAF1/CIP1) expression in primary HCC with immunohistochemistry and Northern blot hybridization and correlated the results with clinicopathologic features and survival. With immunohistochemistry, positive staining for p27(KIP1) and p21(WAF1/CIP1) protein was found in 54.3% and 63.8% of HCCs, respectively. Both p27(KIP1) and p21(WAF1/CIP1) scores of the tumors were significantly higher than those of the corresponding nontumorous livers (P <.0001 and.009, respectively). Higher levels of p27(KIP1) were associated with a lower incidence of direct liver invasion (P =.021) and, less significantly, with a low incidence of multiple tumor nodules (P =.056). Patients whose tumors had higher p27(KIP1) protein scores had longer disease-free survival (P =.011). For p21(WAF1/CIP1), in contrast to the overexpression of the p21(WAF1/CIP1) protein in HCC, the relative amounts of p21(WAF1/CIP1) messenger RNA (mRNA) in the tumors were found to be reduced compared with those of the nontumorous livers (P =.039). In conclusion, p27(KIP1) and p21(WAF1/CIP1) proteins were frequently overexpressed in HCC. Longer disease-free survival rates were seen in patients whose tumors had higher p27(KIP1) expression. The accumulation of p21(WAF1/CIP) protein in the presence of a reduced mRNA level suggests probable posttranslational protein stabilization, and the reduced transcription of p21(WAF1/CIP) may represent a form of dysfunction of cyclin-dependent kinase inhibitor involved in hepatocarcinogenesis.

Adult↗

PubMed2001

Serum vascular endothelial growth factor predicts venous invasion in hepatocellular carcinoma: a prospective study.

OBJECTIVE: To evaluate the correlation between serum vascular endothelial growth factor (VEGF) level and the clinicopathologic features in patients with hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: VEGF is an important angiogenic factor regulating tumor angiogenesis. A high serum VEGF level has been shown to be associated with tumor progression and metastasis in several human cancers, but its significance in HCC is unclear. The correlation between serum VEGF level and tumor pathologic features in patients with HCC has not been studied before. METHODS: Preoperative serum samples and tumor specimens were prospectively collected in 100 patients undergoing resection of HCC. Serum VEGF level was measured by enzyme-linked immunosorbent assay, and tumor VEGF expression was assessed by immunohistochemical study. Histopathologic examination was performed by a pathologist without prior knowledge of the serum VEGF level or tumor VEGF expression. RESULTS: Preoperative serum VEGF levels ranged from 15 to 1,789 pg/mL (median 269). When serum VEGF levels were compared between groups categorized by different clinicopathologic variables, significant correlation was found between a high serum VEGF level and absence of tumor capsule, presence of intrahepatic metastasis, presence of microscopic venous invasion, and advanced stage. There was a positive correlation between the serum VEGF level and tumor expression of VEGF as well as platelet count. When the 75th percentile serum VEGF level (500 pg/mL) was used as a cutoff level, the frequency of venous invasion in patients with a high serum VEGF level was significantly greater compared with patients with a low serum VEGF level. By multivariate analysis, a serum VEGF level of more than 500 pg/mL and tumor size more than 5 cm were independent preoperative factors predictive of microscopic venous invasion. During a median follow-up of 11.6 months, 48% of patients with a serum VEGF level of more than 500 pg/mL and 27% of those with a serum VEGF level of 500 pg/mL or less developed postoperative recurrence. CONCLUSIONS: These results show that a high preoperative serum VEGF level is a predictor of microscopic venous invasion in HCC, suggesting that the serum VEGF level may be useful as a biologic marker of tumor invasiveness and a prognostic factor in HCC.

Adult↗

PubMed2001

Liver transplantation in Asian patients with chronic hepatitis B using lamivudine prophylaxis.

OBJECTIVE: To report the results of liver transplantation in 31 Asian patients with chronic hepatitis B using lamivudine prophylaxis in an open-label study. SUMMARY BACKGROUND DATA: Chronic hepatitis B is a prevalent cause of end-stage liver disease in Asia, but the results of liver transplantation in these patients are poor. METHODS: Thirty-one Asian patients with chronic hepatitis B underwent liver transplantation using lamivudine prophylaxis (100 mg daily). Twenty-three (74%) patients had detectable serum hepatitis B envelope antigen (n = 18) or hepatitis B virus DNA (n = 11) before treatment, and seven had associated hepatocellular carcinoma. Lamivudine was continued indefinitely after transplantation, and hepatitis B immune globulin was not used. RESULTS: The actuarial patient and graft survival rates were 84% and 81%, respectively. Five patients died of causes unrelated to hepatitis B, and 26 patients were alive at a median follow-up of 16 months (range 6-47) after transplantation. One (3.8%) patient developed recurrent hepatitis B resulting from viral breakthrough at week 53 and survived after retransplantation using adefovir and hepatitis B immune globulin treatment. The remaining 25 surviving patients had no biochemical or histologic evidence of recurrent hepatitis, and serum hepatitis B virus DNA remained negative by polymerase chain reaction. In six patients, hepatitis B surface antigen (HBsAg) persisted or reappeared in serum. Among 19 patients who became negative for HBsAg from 5 to 431 days after transplantation, 13 developed anti-HBsAb that lasted a median of 6 months (range 1-21). None of the seven patients with hepatocellular carcinoma developed recurrent tumor. CONCLUSIONS: Asian patients with chronic hepatitis B may achieve a good outcome after liver transplantation using lamivudine prophylaxis.

Adolescent↗

PubMed2001

Improving survival results after resection of hepatocellular carcinoma: a prospective study of 377 patients over 10 years.

OBJECTIVE: To investigate whether the survival results after resection of hepatocellular carcinoma (HCC) have improved within the past decade by an analysis of a prospective cohort of patients over a 10-year period. SUMMARY BACKGROUND DATA: The surgical death rate after resection of HCC has greatly improved in recent years, but the long-term prognosis remains unsatisfactory. It remains unknown whether the survival results after resection of HCC have improved within the past decade. METHODS: The clinicopathologic and follow-up data of 377 patients who underwent curative resection of HCC between January 1989 and January 1999 were prospectively collected. These patients were categorized according to two time periods: before 1994 (group 1, n = 136) and after 1994 (group 2, n = 241). The two groups were compared for clinicopathologic data and survival results. The prognostic factors for disease-free survival were further analyzed to identify the factors that might have led to improved survival outcomes. RESULTS: The overall and disease-free survival results were significantly better in group 2 compared with group 1. Patients in group 2 had significantly higher proportions of subclinical presentation, small tumors, and tumors of early pTNM stage. There were also significantly lower frequencies of histologic margin involvement, less intraoperative blood loss, and a lower transfusion rate in group 2. By multivariate analysis, early pTNM stage, subclinical HCC, and no perioperative transfusion were independent favorable prognostic factors for disease-free survival. CONCLUSIONS: Significant improvement of overall and disease-free survival results after resection of HCC has been achieved within the past decade as a result of advances in the diagnosis and surgical management of HCC. Earlier diagnosis of HCC by better imaging modalities, increased detection of subclinical HCC by screening of high-risk patients, and a reduced perioperative transfusion rate were identified as the major contributory factors for the improved outcomes.

Adult↗

PubMed2001

Low molecular weight heparin-induced liver toxicity.

The authors report two cases of hepatotoxicity induced by low molecular weight heparin. A 26-year-old woman and a 33-year-old man were treated with low molecular weight heparin for pulmonary embolism and cerebral infarction, respectively. They both developed derangement in liver function tests a few days after commencement of the low molecular weight heparin. The derangement in liver function tests was associated with a decreased serum complement 3 activity. Their liver functions recovered over a period of 2 to 3 months after low molecular weight heparin was stopped. Liver biopsy in the woman demonstrated balloon degeneration with scattered foci of hepatocytic necrosis, suggesting a complement-mediated hepatocellular damage.

Adult↗

PubMed2001

Microvessel density, vascular endothelial growth factor and its receptors Flt-1 and Flk-1/KDR in hepatocellular carcinoma.

Assessment of angiogenesis may yield important information for an effective antiangiogenic treatment for hepatocellular carcinoma (HCC) because HCC is characteristically hypervascular We examined the relationship of microvessel density (MVD), vascular endothelial growth factor (VEGF), and VEGF receptors Flt-1 and Flk-1/KDR in 50 patients with HCC and in 3 hepatoma cell lines. VEGF messenger RNA (mRNA) was overexpressed in 26 tumors (52%), and the 3 VEGF isoforms (121, 165, and 189) were present in high frequencies. Flt-1 mRNA was overexpressed in 34 tumors (68%), with levels significantly increased in HCCs compared with the nontumorous livers. Tumor Flt-1 mRNA significantly correlated with tumor VEGF mRNA levels. Within the group of tumors 8.5 cm or less in diameter, tumors with intrahepatic metastasis in the form of tumor microsatellite formation had significantly higher VEGF mRNA levels. MVD assessed by immunohistochemical analysis with CD34 antibody was inversely related to tumor size. Angiogenesis as assessed by MVD and tumor VEGF expression seems to have a more important role in tumor growth and intrahepatic metastasis in smaller HCCs. The differential up-regulation of Flt-1 suggests that it may have an important role in angiogenesis in HCC.

Adult↗

PubMed2001

[Allele-specific chromosome 9p deletion in oral cancer].

OBJECTIVE: The aim of this study was to investigate the relationship between loss of heterozygosity (LOH) on chromosome 9p and the pathogenesis of oral squamous cell carcinoma (OSCC). METHODS: A total of 24 human OSCC specimens were analyzed for LOH on chromosome 9p using 8 microsatellite markers by means of polymerase chain reaction. RESULTS: In 24 cases of OSCC, LOH on chromosome 9p was identified in 10 of 24 cases (41.67%) with at least one marker. The main LOH were found on 9p21 at locus D9S171 (21.05%) and D9S304 (10.00%). There were also a deletion on 9p22-23 at locus D9S168 (22.22%) and D9S162 (15.38%). However, there was no statistically significant correlation between LOH at these loci with such clinical parameters as pathological types, tumor size and lymph-node metastasis. Microsatellite instability (MSI) is rare for any of the 8 markers in 24 OSCC. No MSI could observed using the common criteria for defining MSI-its detection in two or more markers. CONCLUSION: We found that high frequency of LOH occurred at 9p21-23 band. Their results indicate that more than one tumor suppressor genes at chromosome 9p21-23 region related to a subset of OSCC, while MSI might not be a crucial event.

Carcinoma, Squamous Cell↗

PubMed2000

DLC-1 is deleted in primary hepatocellular carcinoma and exerts inhibitory effects on the proliferation of hepatoma cell lines with deleted DLC-1.

We investigated the expression and deletion of DLC-1 (frequently deleted in liver cancer gene), first reported in 1998 and having a high homology with rat p122RhoGAP in hepatocellular carcinoma (HCC). Six (20%) of 30 human HCC samples and 2 (40%) of 5 HCC cell lines were found to have no detectable DLC-1 expression by reverse transcription-PCR. Homozygous DLC-1 deletion was detected by Southern blotting in two of six HCC samples and in both HCC cell lines with no DLC-1 expression. Transfection of DLC-1 into 5 HCC cell lines (two with DLC-1 deletion and three with intact DLC-1) showed significant growth inhibition in these two HCC cell lines with deleted DLC-1 with both 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays but not in three other HCC cell lines with intact DLC-1. Our findings suggest that DLC-1 may play an important role in hepatocarcinogenesis.

Blotting, Southern↗