Sonographic findings in a case of congenital pyloric diaphragm.
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Adult↗
Biomedical subjects
J C Sheu
Publications and source records attributed to J C Sheu.
Hypermethylation in human cancers of the RIZ1 tumor suppressor gene, a member of a histone/protein methyltransferase superfamily.
The retinoblastoma protein-interacting zinc finger gene RIZ1 is a tumor suppressor gene and a member of a nuclear histone/protein methyltransferase superfamily. RIZ1 inactivation is commonly found in many types of human cancers and occurs through loss of mRNA expression, frameshift mutation, chromosomal deletion, and missense mutation. RIZ1 is also a tumor susceptibility gene in mice. We now show that loss of RIZ1 mRNA in human cancers is associated with DNA methylation of its promoter CpG island. Methylation of the RIZ1 promoter strongly correlated with lost or decreased RIZ1 mRNA expression in breast, liver, colon, and lung cancer cell lines as well as in liver cancer tissues. Treatment with the methylation inhibitor 5-aza-2'-deoxycytidine activated RIZ1 mRNA expression in cancer cells. Furthermore, methylation was found in 11 of 25 (44%) breast cancer specimens and 20 of 32 (62%) liver cancer specimens. Our results suggest that DNA methylation is a common mechanism in inactivating the RIZ1 tumor suppressor gene in human liver and breast cancers.
Animals↗
Deletion mapping of chromosome 16q24 in hepatocellular carcinoma in Taiwan and mutational analysis of the 17-beta-HSD gene localized to the region.
Human chromosome band 16q24 commonly undergoes loss of heterozygosity (LOH) in human hepatocellular carcinoma (HCC). To further localize the region of deletion on 16q24 and to evaluate the genetic role of 17-beta-HSD, which is near 16q24, in HCC, we examined the pattern of loss of heterozygosity in 88 HCC patients. DNAs from 88 pairs of HCCs and corresponding non-tumor parts were prepared. Loss of heterozygosity on chromosomes 16q24 was investigated by 11 sets of microsatellite markers. Mutation analysis of type II 17-beta-HSD was performed by automatic sequencing. LOH on 16q24 for at least 1 locus was found in 43 of the 88 tumor DNAs (49%). Three non-overlapping regions of frequent LOH were defined in these 43 tumors with partial deletions. The first region was between D16S516 loci and D16S507, encompassed by a 1-cM region, defined by the D16S504. The second region was defined by the 17HSDB2 locus between D16S505 and D16S422, encompassed approximately by a 1-cM region. The third region was between D16S520 and D16S413, defined by D16S3048, encompassed approximately by a 4-cM region. Homozygous deletions of any exons in 17HSDB2 gene were identified in 7 of 27 cases (26%). Automated sequencing analysis of 17HSDB2 failed to demonstrate mutations in any of these specimens. Our data suggest that the 17HSDB2 locus is a frequent target of deletion in HCC but the inactivation of 17HSDB2 may not involve sequence mutations. Furthermore, the presence of the other 2 frequent LOH regions suggest that the putative tumor suppressor genes at these locations might be involved in the development of HCC.
17-Hydroxysteroid Dehydrogenases↗
Expressions of cancer-testis antigens in human hepatocellular carcinomas.
Though regular sonographic examination can early detect small hepatocellular carcinoma, the therapeutic results remains unsatisfactory. Antigen-specific immunotherapy is an alternative approach for controlling tumors. The prerequisite for antigen-specific cancer immunotherapy is the identification of appropriate tumor antigens. Recently, a new category of tumor-specific shared antigens, called cancer-testis antigens, has been identified. The cancer-testis antigens have been found in a variety of cancers. However, the expression of cancer-testis antigens in human hepatocellular carcinomas is unknown. The aim of this current study is to investigate the expression of cancer-testis antigens in human hepatocellular carcinomas. Reverse-transcription polymerase chain reaction (RT-PCR) was used to investigate the expression of the SSX-1,-2,-4,-5, SCP-1, NY-ESO-1 genes in tumorous and corresponding non-tumorous liver tissues. In the 30 hepatocellular carcinomas studied, SSX-1,-2,-4,-5, SCP-1, and NY-ESO-1 mRNA expressions were detected in 24 (80%), 14 (46.7%), 22 (73.3%), 10 (33.3%), 2 (6.7%), and 11 (36.7%), respectively. Expressions of these genes were detected in few non-tumor liver tissues. The cancer-testis antigens are expressed in a high percentage of hepatocellular carcinomas. These cancer-testis antigen gene products are potential targets for antigen-specific immunotherapy of hepatocellular carcinoma.
Adult↗
Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma.
The RIZ (PRDM2) locus commonly undergoes loss of heterozygosity (LOH) and maps within the minimal deleted region on 1p36 in hepatocellular carcinoma (HCC). Although peptide-altering mutations of RIZ are rare in HCC, the RIZ1 product is commonly lost in HCC and has tumour suppressive activities. Here, we analysed RIZ gene mutations and LOH in HCC, breast cancer, familial melanoma, colon cancer, and stomach cancer. We found 7 polymorphisms but no mutations. By analysing the Pro704-deletion polymorphism, we detected LOH of RIZ in 31 of 79 (39%) informative HCC cases, 11 of 47 (23%) colon cancer cases, 8 of 43 (19%) breast cancer cases, 8 of 66 (12%) stomach cancer cases. Importantly, loss of the Pro704(+)allele was found in 74% of the 31 LOH positive HCC cases (P< 0.01), indicating a preferential loss and hence a stronger tumour suppressor role for this allele compared to the P704(-)allele. In addition, the Pro704(+)allele was found to be more common in Asians (0.61) than Caucasians (0.42) (P = 0.0000), suggesting an interesting link between gene polymorphisms and potential differences in tumour incidence between racial groups.
Alleles↗
Correlation of histologic subtypes and replication error phenotype with comparative genomic hybridization in gastric cancer.
To characterize phenotypic and genotypic changes in gastric cancer (GC), DNA copy number aberrations (CNAs) were assessed in 53 tumors using comparative genomic hybridization (CGH) and correlated with clinicopathologic characteristics and status of TP53 and replication error (RER). The number of CNAs per tumor was 6.8 (gain 5.3, loss 1.5), and the number of changes was significantly higher in tumors with advanced stage, TP53 mutation, and without RER than in those with early stage (7.7 vs. 3.0), no TP53 mutations (12.4 vs. 4.8) or RER phenotype (8.2 vs. 2.6). Frequent abnormalities included gains on chromosomal arms 8q (43%), 6q (26%), 11q (26%), 13q (24%), 7p (23%), 17q (23%), and 20q (23%), and losses on chromosomal arms 16q (26%), 19p (23%), 5q (19%), 3p (15%), 4q(15%), and 1p (15%). Advanced GC demonstrated a higher prevalence of gains of 8q (51% vs. 10%, P < 0.05) and loss of 16q (33% vs. 0%, P < 0.05) than early GC. Gains on 8q (64% vs. 20%, P < 0.05), 17q (39% vs. 4%, P < 0.05) and losses on 3p (25% vs. 4%, P = 0.05) and 5q (32% vs. 4%, P < 0.05) were higher in intestinal GC than in diffuse GC. On the other hand, gains on 13q were more common in the diffuse type (40% vs. 11%, P < 0.05). As compared with noncardia cancer, cardia cancer showed more gains on 7p (58% vs. 12%, P < 0.05) and 20q (58% vs. 12%, P < 0.05) and more losses on 4q (50% vs. 5%, P < 0.05). The finding of histology-related aberrations and the combination of CGH and molecular data thus provide additional evidence suggesting genetic heterogeneity of GC.
Chromosome Aberrations↗
Hepatic lymphangioma--a case report.
A patient presented with a huge, pedunculated abdominal cystic lymphangioma arising from the quadrate lobe of the liver near the round ligament. Microscopically, dilated hepatic ducts with scant liver tissue could be recognized in the main cyst. A review of the literature reveals no previous report of a lymphangioma arising in this manner or from this area.
Diagnosis, Differential↗
Incidence and clinical presentation of posttransfusion TT virus infection in prospectively followed transfusion recipients: emphasis on its relevance to hepatitis.
BACKGROUND: A novel transfusion-transmissible human DNA virus, TT virus (TTV), has been discovered recently. An attempt was made to determine the incidence and clinical outcome of TTV infection in recipients of blood transfusion. STUDY DESIGN AND METHODS: Serial serum samples collected as part of a prospective study of posttransfusion hepatitis were examined for TTV DNA by a nested PCR assay. RESULTS: Among 150 adults undergoing cardiac surgery, posttransfusion specimens from 59 individuals were positive for TTV DNA. Pretransfusion sera were found to be positive in 13 of these individuals. Therefore, 46 (33.6%) of the 137 previously uninfected patients developed new TTV viremia after transfusion. Among the 46 patients, 3 were coinfected with HCV, 5 were coinfected with HGV, and 38 were infected with TTV alone. No apparent symptoms or signs were noted in the 38 patients infected by TTV alone or the 5 infected with HGV plus TTV. The average peak serum ALT activity was 31 IU per L, with persistently normal levels in 34 of the 38 patients with TTV infection alone. In 8 other patients who subsequently developed well-documented non-A-G hepatitis, 3 were positive for TTV (3/8 vs. 46/137, p = 0.8). In 12 patients followed for more than 1 year, TTV viremia persisted in every case. CONCLUSION: In this population, TTV is transmitted by transfusion to approximately 30 percent of patients who undergo cardiac surgery. Most of the infections appear to become persistent. Despite the high prevalence rate, TTV does not appear to cause hepatitis on its own.
Adult↗
Dilatation of the biliary tree in children: sonographic diagnosis and its clinical significance.
We evaluated sonographically 162 children who met the criteria for biliary tract dilatation in the past 18 years. Of these, 131 patients were diagnosed as having anomalous dilatations of the biliary tree (including 112 with choledochal cysts and 19 with biliary duct dilatation and biliary atresia). Biliary tract dilatations in the other 31 patients were due to secondary causes or normal variants. All cases of intrahepatic biliary tree dilatation and those with both intra- and extrabiliary duct dilatations were anomalous. In 117 cases of extrahepatic biliary tract dilatation only, the mean diameter was widest in cases of choledochal cyst (21.4 +/- 12.1 mm, compared with cases of biliary tract dilatation with biliary atresia (10 +/- 2.4 mm), secondary biliary duct dilatation (8.5 +/- 1.5 mm), and normal variants (4.4 +/- 1.2 mm) (P < 0.001). Of the 43 infants with biliary tree dilatation, 24 (56%) had choledochal cysts and 19 (44%) had biliary tract dilatation associated with biliary atresia. Excluding cases associated with biliary atresia, the accuracy of diagnosing choledochal cysts in extrahepatic biliary tract dilatation was 71% and 97% using cutoffs of 7 mm and 10 mm as the minimum diameter, respectively.
Bile Ducts↗
Distinct clinicopathologic and genetic profiles in sporadic gastric cancer with different mutator phenotypes.
A subset of sporadic gastric cancers (GC) exhibits microsatellite instability (MSI). To define the precise role of MSI in GC, a total of 100 patients with sporadic GC were classified into three groups, i.e., high-frequency MSI (MSI-H), low-frequency MSI (MSI-L), and microsatellite stable (MSS), based on 10 microsatellite markers. Mutational analyses of TGFbetaRII, IGFIIR, BAX, MSH3, MSH6, E2F4, MSH2, MLH1, and TP53 genes, and methylation and protein expression of MLH1 and MSH2 were performed and correlated. Twenty-seven percent of GC showed MSI at least in one locus and could be further graded as MSI-H (14%) and MSI-L (13%). No clinicopathologic difference was noted between GC with MSI-L and MSS. Compared with GC with MSI-L or MSS, GC with MSI-H had a significantly higher frequency of antral location, intestinal subtype, H. pylori seropositivity, but a lower incidence of lymph node metastasis, and displayed a higher frequency of frameshift mutations of TGFbetaRII, IGFIIR, BAX, MSH3, and E2F4 genes but a lower incidence of TP53 mutations. Furthermore, hypermethylation of the MLH1 promoter was responsible for the loss of protein function in 13 of 14 MSI-H tumors. It was concluded that a specific phenotype and a distinct profile of genetic alterations exist in MSI-H GC. We speculate that epigenetic inactivation of MLH1 by methylation plays a crucial role in initiating such a pathway of carcinogenesis. In contrast, GCs with MSS and MSI-L exhibit clinicopathologic features that are distinct from MSI-H tumors and have a higher frequency of TP53 mutations, suggesting that they may evolve through an entirely different pathway.
Adaptor Proteins, Signal Transducing↗
Mapping of a minimal deleted region in human hepatocellular carcinoma to 1p36.13-p36.23 and mutational analysis of the RIZ (PRDM2) gene localized to the region.
Human chromosome band 1p36 commonly undergoes loss of heterozygosity (LOH) in hepatocellular carcinoma (HCC) but the minimal deleted region remains to be mapped. This chromosomal region contains a candidate HCC suppressor gene, RIZ (PRDM2), that is a member of the PR (PRDI-BF1-RIZ homology)-domain-containing zinc finger gene family. One characteristic of this family is the unusual yin-yang involvement in human cancers. The PR-domain-containing RIZ1 product of the RIZ locus, in contrast to the PR-domain-minus product RIZ2, is commonly lost or underexpressed in HCC. Furthermore, RIZ1 can induce cell cycle arrest, apoptosis, or both and suppress HCC tumorigenicity in nude mice. To help identify the putative HCC locus on 1p36 and to evaluate a genetic role of RIZ in HCC, we studied 97 HCC cases and mapped a minimal deleted region in HCC to 1p36.13-p36. 23 between markers D1S434 and D1S436. Notably, RIZ mapped within this region and was found to undergo LOH in 37% (25/67) of HCC cases. Single-strand conformation polymorphism (SSCP) analysis, however, did not show mutations in the PR-domain region of RIZ1 in 49 cases of HCC examined. Our data suggest that the RIZ locus is a target of frequent deletion in HCC, but that the more common way of RIZ inactivation in HCC may not involve mutations that alter peptide sequences. Genes Chromosomes Cancer 28:269-275, 2000.
Alleles↗
Prenatal sonographic detection of adrenal hemorrhage confirmed by postnatal surgery.
We report a case of adrenal hemorrhage in a newborn first detected by sonography at a menstrual age of 21 weeks 4 days. An echogenic mass was noted above the right kidney. The mass became larger and hypoechoic on follow-up sonograms after birth. The mass was also seen on abdominal CT. Because it was difficult to differentiate the lesion from cystic neuroblastoma and because it shrank only modestly by 2 months after birth, we performed a surgical exploration when the patient was 2 months old, and adrenal hemorrhage was confirmed. This case suggests that adrenal hemorrhage can occur as early as the second trimester of pregnancy.
Adrenal Gland Diseases↗
Chromosomal abnormality in hepatocellular carcinoma by comparative genomic hybridisation in Taiwan.
The elucidation of the genetic changes of hepatocellular carcinoma (HCC) is very important for understanding the molecular mechanism of liver carcinogenesis. In order to identify the gains or losses in DNA sequence copy number in HCC, we used comparative genomic hybridisation to study 40 cases (44 tumours) of HCC. Tumour DNA and DNA from non-neoplastic liver tissue were labelled with different fluorochromes and then simultaneously hybridised to normal metaphase spread chromosomes. An image acquisition system was used to quantitate signal intensities contributed by tumour and reference DNA along the entire length of each chromosome. Regions of amplification and deletion were demonstrated as quantitative alterations. Losses were prevalent on chromosome regions 16q (43%), 17p (20%), 13q (20%), 4q (15%) and 8p (15%). Gains frequently occurred on 8q (30%), 1q (20%), 6p (20%) and 17q (18%). Hepatitis B virus carriers had a significantly higher frequency of losses on chromosome 16q. Furthermore, the minimal region of losses was narrowed down to 16q11-q22. This study confirms the presence of previously known chromosomal aberrations in HCC and highlights a new significant correlation between losses on chromosome 16q and hepatitis B virus carriers.
Adult↗
Loss of heterozygosity at chromosome 13q in hepatocellular carcinoma: identification of three independent regions.
Loss of heterozygosity (LOH) on chromosome 13q is one of the most common genetic alterations in hepatocellular carcinoma (HCC) and might be involved in liver cancer development through inactivation of tumour suppressor genes. In order to narrow down the region of 13q loss, we examined the pattern of loss of heterozygosity (LOH) in tumours from 88 HCC patients, using 18 microsatellite markers on 13q. Thirty-eight of the 88 tumours (43%) showed LOH for at least one marker. Of these, two tumours (5%) showed 13q whole arm allelic loss, while the remaining 36 tumours (95%) had partial allelic loss. The LOH pattern defined by the 36 tumours suggested the existence of at least three different smallest common deleted regions which might be involved in the carcinogenesis of HCC. The first, the most centromeric in the 13q12.3 is, close to the BRCA2 gene, defined by D13S171; the second, the most telomeric region in the 13q31-32 band, is defined by D13S154 and D13S157; the third, the intermediate region at 13q14.3, which is near the RB gene, is defined by loci D13S268. The rate of LOH at 13q31-32 was significantly higher in Hepatitis B-surface antigen (HBsAg)-positive patients than HBsAg-negative HCC patients, pointing to a candidate gene related to the development of HBsAg-positive HCCs.
BRCA2 Protein↗
Loss of heterozygosity and microsatellite instability in hepatocellular carcinoma in Taiwan.
Elucidation of the basic genetic changes of human hepatocellular carcinoma is important for the understanding and treatment of this cancer. We used microsatellite polymorphism markers to study 30 cases of hepatocellular carcinoma (34 tumours) on all human chromosomes. DNA from 34 pairs of hepatocellular carcinomas and corresponding non-tumour parts was prepared. Loss of heterozygosity (LOH) and microsatellite instability on 23 chromosomes were investigated by 231 sets of microsatellite markers. More than 20% LOH was shown for loci on 16q (47.1%), 13q (32.4%), 17p (32.4%), 5q (26.5%), 11p (23.5%) and 9p (20.6%). The commonly affected regions were mapped to 16q12.1, 16q12.2, 16q24, 13q12.1-32, 17p13, 5q32, 5q34, 5q3, 11p15, 11q23-24 and 9p21. Hepatitis B virus carriers had a significantly higher frequency of LOH on chromosomes 5q, 11p and 16q. Furthermore, larger tumour size tended to have higher frequency of LOH at D16S409 locus (16q12.1). Microsatellte instability was only found in 12 of 231 markers and the frequency is very low. These data suggest that the chromosomes 16q, 13q, 17p, 5q, 11p and 9p might participate in hepatocarcinogenesis. However, microsatellite instability might play little role in the development of this cancer in Taiwan.
Adult↗
Bacterial infections associated with hepatic arteriography and transarterial embolization for hepatocellular carcinoma: a prospective study.
Sepsis and liver abscess are serious complications following transarterial embolization (TAE) for hepatocellular carcinoma (HCC). However, the exact incidence and the necessity of antibiotic prophylaxis remain undetermined. Between November 1996 and November 1997, we prospectively studied bacterial infections in 231 HCC patients who underwent 287 angiographic procedures without antibiotic prophylaxis, including 176 TAEs and 111 hepatic arteriographies (HAs). Four of the 111 HAs were complicated by transient asymptomatic bacteremia. Of the 176 TAEs, 2 were associated with asymptomatic bacteremia, and 7 (4%) were associated with symptomatic bacterial infection, including 3 cases of sepsis, 2 of liver abscess, and 2 of infected biloma. For patients with HCC, TAE was associated with a higher risk of developing symptomatic bacterial infections than was HA (4% vs. 0, respectively; P = .03). Previous gastrectomy was the only possible risk factor for liver abscess. Finally, early diagnosis and treatment of these infectious complications usually result in successful outcome.
Aged↗
High frequency of expression of MAGE genes in human hepatocellular carcinoma.
AIMS/BACKGROUND: Activation of human MAGE genes leads to the expression of a set of tumor rejection antigens, which are recognized by cytotoxic T lymphocytes. The antigens may become the targets of immunotherapy. The expression of MAGE genes was originally found in, but is not restricted, to melanomas. The aim of this study was to investigate the expression of MAGE genes in human hepatocellular carcinomas. METHODS: The expression of MAGE-1, -2, -3, -4 genes in tumorous and corresponding non-tumorous liver tissue was studied using a reverse-transcription polymerase chain reaction. RESULTS: In the 50 hepatocellular carcinomas studied, MAGE-1, -2, -3, -4 mRNA expression was detected in 23 (46%), 17 (34%), 21 (42%) and 8 (16%), respectively. Seventy-four percent of the hepatocellular carcinomas expressed at least one of the MAGE genes. MAGE mRNAs were not detected in the corresponding non-tumor liver tissues. MAGE gene expression was not significantly correlated with clinicopathological factors. CONCLUSIONS: The MAGE genes are expressed in a high percentage of hepatocellular carcinomas; the MAGE gene products are potential targets for tumor-specific immunotherapy.
Adult↗
Tissue hepatocyte growth factor and proliferating cell nuclear antigen in hepatocellular carcinoma.
To better understand the roles of hepatocyte growth factor (HGF) and proliferating cell nuclear antigen (PCNA) in hepatocellular carcinoma (HCC), 37 surgically resected HCCs and corresponding nontumorous liver tissue specimens were collected and the expression of these two factors was quantified by Western blot analysis. Both HGF and PCNA expression levels were significantly higher in tumor tissue than in nontumorous liver tissue. However, their expression levels in HCC tissue and nontumorous tissue did not show any significant correlation with the recurrence of HCC. In addition, HGF and PCNA did not correlate with Edmondson's grade, invasiveness of tumor, presence of tumor capsule, or tumor size. No correlation was found between the expression levels of HGF and PCNA in HCC tissue. We conclude that, although both HGF and PCNA are present at higher levels in HCC tissue than in nontumorous liver tissue, they play little role in the clinicopathologic manifestations of this tumor. HGF appears to contribute little, if at all, to the proliferative activity of HCC cells.
Adult↗