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Biomedical subjects

J C Sheu

Publications and source records attributed to J C Sheu.

At least 37 records · Page 2Linked to original sources
PubMed1998

Clinicopathological significance of altered loci of replication error and microsatellite instability-associated mutations in gastric cancer.

Replication errors (RERs) judged by microsatellite instability and its associated mutations have been recognized as an important mechanism in tumorigenesis of gastric cancers (GCs). To gain a deeper insight into its significance, we examined the frequency of RERs using nine microsatellite markers and screened mutations in the polydeoxyadenine tract of the transforming growth factor beta type II receptor gene (TGF-betaRII) and polydeoxyguanine tracts of insulin-like growth factor II receptor and BAX genes. Twenty-four (30%) of 80 patients with GC had RERs, of which 3, 8, and 13 had one, two, and three or more loci, respectively. In 13 tumors with RERs in three or more loci, frameshift mutations of TGF-betaRII, insulin-like growth factor II receptor, and BAX were identified in 12, 3, and 2, respectively. Compared with GC with none, one or two RER-positive loci as a group, GC with RERs in three or more loci showed a significantly higher frequency of antral location (12 of 13 versus 35 of 67; P = 0.01), intestinal subtype (11 of 13 versus 30 of 67; P = 0.01), and previous Helicobacter pylori infection (12 of 13 versus 41 of 67; P = 0.05) and a lower incidence of lymph node metastasis (5 of 13 versus 49 of 67; P = 0.02) and tended to be in an advanced stage (12 of 13 versus 54 of 67; P = 0.28). These data indicate that GC with multiple RERs manifest distinct clinicopathological characteristics, and that a high frequency of frameshift mutations involving the TGF-betaRII gene may be causatively linked with tumorigenesis and progression.

Adult↗
PubMed1998

Hepatocyte growth factor stimulates the growth and activates mitogen-activated protein kinase in human hepatoma cells.

Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes and various epithelial cells. Unexpectedly, it has been reported to inhibit the growth of hepatoma cells in vitro. To clarify this phenomenon, we examined the effects of recombinant baculovirus-expressed HGF on the growth of 6 human hepatoma cell lines. The growth of Hep3B and HepG2 cells was markedly stimulated to 1.8- and 1.7-fold, respectively, PLC/PRF/5 to 1.4-fold, and SK-Hep-1 to 1.2-fold in a dose-dependent manner under HGF concentrations below 20 ng/ml. Neither HuH-7 nor HCC36 were affected. None of these cells were inhibited. All these cells expressed c-Met, the membrane receptor for HGF, and their c-Met would be activated to be phosphorylated upon addition of HGF. They also contained the ERK2 subgroup of mitogen-activated protein kinases (MAPKs). When HGF was added, their ERK2 would also be phosphorylated. The extent of ERK2 phosphorylation was partially correlated to their growth response to HGF. In conclusion, HGF could stimulate the growth of certain human hepatoma cells, probably through activation of c-Met and MAPKs.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Icteric type hepatocellular carcinoma: revisited 20 years later.

Icteric type hepatocellular carcinoma is rare, and a poor prognosis has been demonstrated in the past. We performed this study to re-evaluate prognosis since the availability of modern diagnostic modalities. Of 3921 patients with hepatocellular carcinoma in our hospital, 9 patients who presented with tumor fragments in common bile duct and had a patent portal vein were submitted for analysis. Cholangiocarcinoma was suspected in 7 patients before the study was completed, and icteric type hepatocellular carcinoma was diagnosed in all 9 patients after serial studies that included serum alpha-fetoprotein levels, computed tomography, angiography, and histology. The prognosis was better in the 4 resectable patients (survival time 16, 31, 33, and 63 months, respectively), and was extremely poor for the 5 patients who received palliative treatment only (mean survival time, 4.5 months). Because of the apparently discrepant outcomes, this specific type of hepatocellular carcinoma should be kept in mind in areas where hepatocellular carcinomas are prevalent, and the suspected cases should be thoroughly investigated, because prognosis may be improved when resection is done at an earlier stage.

Aged↗
PubMed1998

Results of surgery for vesicoureteral reflux in children: 6 years' experience in an Asian country.

From January 1990 to December 1995, a total of 181 patients underwent reimplantation of 318 ureters for primary vesicoureteral reflux (VUR); 87.8% received bilateral reimplantation. Surgical indications included breakthrough infection (35%), high-grade (> or = IV) reflux (33%), or both (29%). The operative success rate was 99.4% at 3 months postoperatively and 100% ultimately. The complications included: contralateral sequential reflux in 3.9%, postoperative bladder diverticula in 1.1%, postoperative urinary infection in 1.1%, residual reflux in 0.3%, postoperative vesicoureteral stenosis in 0.3%, and slippage of the drainage tube in 0.3% of cases. Two patients had renal failure due to VUR that was proven by renal biopsy (one 4-year-old and one 8-year-old). The incidence of associated anomalies was higher than in the normal population. The average number of hospital admission days was 7.9 (3-63). After 1992, no ureteral stent was left in postoperatively. All patients received prophylactic antibiotics for 3 months postoperatively until the VUR disappeared. The surgical results were satisfactory in this series.

Adolescent↗
PubMed1998

Prenatal and neonatal intussusception.

Intussusception found in the 1st month of life is rare and usually discussed as one entity, neonatal intussusception, but in fact, includes the intussusceptions occurring both prenatally and neonatally, of which the clinical presentations and results are different. Four full-term babies with prenatal intussusception presenting as intestinal atresia (IA) and three premature babies with neonatal intussusception mimicking necrotizing enterocolitis (NEC) are presented. Prenatal intussusception, as one of the causes of IA produces prominent signs of intestinal obstruction immediately after birth. Preoperative evaluation usually fails to yield a definitive diagnosis, but surgery is usually performed in time and is successful. In neonatal intussusception, full-term infants usually have a pathological lead point and the colon is almost always involved. A barium enema is thus useful in diagnosis. Premature babies, on the other hand, rarely have a colonic component, and the clinical features are insidious and similar to NEC. This results in diagnostic confusion that may lead to a dangerous delay in appropriate surgical correction. A high level of suspicion about this condition in cases diagnosed presumptively with NEC is important. Serial abdominal sonograms may be helpful in the early diagnosis of neonatal intussusception.

Fatal Outcome↗
PubMed1998

Is surgery necessary for primary non-refluxing megaureter?

From January 1990 to December 1995, a total of 22 patients with primary non-refluxing megaureter were treated in our hospital. The age distribution was 7 days to 8 years. The follow-up period was from 1 to 6 years. Nineteen of these 22 children underwent surgical intervention: 3 were operated upon at the time of diagnosis; the other 16 were initially treated conservatively, but underwent subsequent surgery due to impairment of renal function (13) or breakthrough infections (3). The failure rate for conservative management was about 84% (16/19): only 3 patients treated conservatively showed spontaneous resolution. The surgical success rate was 89.5% (17/19). The pathological change in the ureterovesical junction (UVJ) was adynamic in 13 cases and fibrotic in 6 (including 1 ectopic ureter). The postoperative complications were vesicoureteric reflux in 3 cases, with spontaneous resolution 6 months later, and UVJ stenosis in 1, which was resolved by reoperation. It is concluded that surgery is not necessary in every case, but still plays an important role in most cases. Early surgery can achieve good results and reduce renal damage.

Child↗
PubMed1998

Infrequent mutations and no methylation of CDKN2A (P16/MTS1) and CDKN2B (p15/MTS2) in hepatocellular carcinoma in Taiwan.

CDKN2A (p16INK4A/MTS1) and CDKN2B (p15INK4B/MTS2) have recently been shown to be potent inhibitors of the cyclin D/cyclin-dependent kinase-4 complex. Both genes are candidates for the putative tumour suppressor genes located at chromosome 9p21 and are frequently inactivated in many human cancers through homozygous deletion. More recently, another reported pathway of inactivation involves loss of transcription associated with de novo methylation of the 5' CpG island of p16/MTS1 and p15/MTS2 in human cancers. We examined a total of 34 tumours from 30 hepatocellular carcinoma (HCC) patients for deletion, mutation and DNA methylation of these two genes by polymerase chain reaction (PCR) amplification, sequence analysis and Southern blot. Homozygous deletions of P16/MTS1 exon 1 were only identified in 1 of 30 cases (3%). Homozygous deletions of p15 exon 1 or exon 2 were found in 7 of 30 cases (13%). Automated sequencing analysis of p16 exon 1 and 2 and p15 exon 1 and 2 failed to demonstrate mutations in either p16 or p15 in any of these specimens. No aberrant 5' CpG island hypermethylation of p16 or p15 was found in any of the primary tumours by Southern blot. These data suggest that the p16/MTS1 gene has a limited role in HCC. However, deletions of the p15/MTS2 gene are found in 13% HCC and might be involved in a subset of HCC.

Adult↗
PubMed1998

Telomerase activity and telomere length in human hepatocellular carcinoma.

Telomerase activity is activated and telomere length altered in various types of cancers, including hepatocellular carcinoma (HCC). A total of 39 HCC tissues and the corresponding non-tumour livers were analysed and correlated with clinical parameters. Telomere length was determined by terminal restriction fragment assay, and telomerase activity was assayed by telomeric repeat amplification protocol. Telomerase activity was positive in 24 of the 39 tumour tissues (1.15-285.13 total product generated (TPG) units) and in six of the 39 non-tumour liver tissues (1.05-1.73 TPG units). In the 28 cases analysed for telomere length, telomere length was shortened in 11 cases, lengthened in six cases, and unaltered in 11 cases compared with non-tumour tissues. Neither telomere length nor telomerase activity was correlated to any clinical parameters.

Adult↗
PubMed1998

Differential tyrosine phosphorylation/activation of oncogenic proline-directed protein kinase F(A)/GSK-3alpha in well and poorly differentiated human prostate carcinoma cells.

Computer analysis of protein phosphorylation site sequences revealed that transcriptional factors and viral oncoproteins are prime targets for regulation of proline-directed protein phosphorylation, suggesting an association of the proline-directed protein kinase (PDPK) family with neoplastic transformation and tumorigenesis. In this report, an immunoprecipitate activity assay of proline-directed protein kinase F(A)/glycogen synthase kinase-3alpha (PDPK F(A)/GSK-3alpha) has been optimized to demonstrate significantly increased (p < 0.01) activity in poorly differentiated human prostate carcinoma PC-3 cells (55.5+/-3.8 units/mg) when compared to well-differentiated LNCaP cells (28.1+/-2.3 units/mg). Immunoblotting analysis revealed that increased activity of this PDPK in PC-3 cells is due not to overexpression of the protein, but to enhanced tyrosine phosphorylation of the kinase. When treated with genistein (a protein tyrosine kinase PTK inhibitor), the enhanced tyrosine phosphorylation/activation of the kinase in PC-3 cells can be blocked. Conversely, when treated with vanadate (a protein tyrosine phosphatase PTP inhibitor), the phosphotyrosine content of PDPK F(A)/GSK-3alpha in LNCaP cells can be promoted to the level of PC-3 cells. In sharp contrast, the PTK inhibitor has little effect on the tyrosine phosphorylation level of the kinase in LNCaP cells, whereas the PTP inhibitor has little effect on the tyrosine phosphorylation level of the kinase in PC-3 cells. Taken together, the results provide initial evidence that the tyrosine phosphorylation/activation levels of this oncogenic PDPK can be differentially regulated in well- and poorly differentiated prostate carcinoma cells.

Amino Acid Sequence↗
PubMed1998

Overexpression of p53 in different subtypes of intestinal metaplasia and gastric cancer.

p53 immunostaining was evaluated in cancerous epithelia and adjacent intestinal metaplasia of 135 gastric cancer specimens. The differential p53 overexpression in different subtypes of intestinal metaplasia and gastric cancer suggests that type III intestinal metaplasia is the commonest lesion in dysplasia-carcinoma transition, particularly in the intestinal type of gastric cancer.

Humans↗
PubMed1998

Prevalence and infectivity of hepatitis G virus and its strain variant, the GB agent, in volunteer blood donors in Taiwan.

BACKGROUND: The prevalence of hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C) is high in non-virus-inactivated plasma products, but, persistent infection in recipients is relatively low. STUDY DESIGN AND METHODS: Stored samples from transfusion donors and recipients in a prospective study of posttransfusion hepatitis were tested for HGV RNA and antibody to the E2 protein (anti-E2). RESULTS: Thirty-two (2.1%) of the 1500 qualified donors were positive for HGV RNA. Twenty-four persons had received a transfusion of blood from one of these 32 viremic donors. Of these 24 recipients, 3 were positive for HGV RNA before transfusion. Of the remaining 21 recipients, 8 became viremic after transfusion, while the other 13 were not infected. Four of the eight infected recipients were persistently positive for HGV RNA, while four became negative in 1 to 3 years. Three of the four patients with HGV clearance seroconverted to anti-E2 positivity. Comparison of the viral titer, viral sequences at E2, storage period of blood donations, and clinical data in the infected and noninfected recipients revealed no significant differences. However, the noninfected recipients seemed to have a higher prevalence of anti-E2 before transfusion. CONCLUSION: The prevalence of HGV viremia in volunteer blood donors in Taiwan is 2.1 percent, and blood from 0.6 percent of them actually causes HGV infection in the recipients. In half of infected recipients, clearance of HGV occurs. Anti-E2 appears in most recipients whose viremia is cleared.

Adult↗
PubMed1998

Favorable outcome in a fetus with an early-onset extensive cystic hygroma colli and intralesional hemorrhage.

We present a rare occurrence of an early-onset extensive cystic hygroma colli with intralesional hemorrhage and a favorable outcome. A 23-year-old primigravida woman was referred for management of a left isolated extensive cystic hygroma colli at 22 weeks' gestation. Amniocentesis revealed a 46, XY karyotype. Ultrasound-guidance in utero paracentesis was performed weekly or fortnightly from 22 to 36 gestational weeks. The aspirated fluid was chocolate-colored and contained abundant lymphocytes, erythrocytes, and protein. Despite multiple aspirations, the fetal cystic hygroma colli increased in size from 5.2x4.2 cm at 22 weeks' gestation to 9x9.7 cm at 36 weeks' gestation. The woman underwent cesarean section at 36 week's gestation and a-2808 g neonate was born with a 10x6 cm left neck mass, which did not impair spontaneous normal respiration. At the age of 4 days, the neonate underwent simple excision of the cystic hygroma, which was confined to the anterior superficial neck. The neonate was discharged 4 days after operation in good condition. In the present case, in utero paracentesis did not prevent the progressive growth of an early-onset extensive cystic hygroma colli with intralesional hemorrhage. However, lack of extension of the lesion into the surrounding structures and successful postnatal surgery contributed to the favorable outcome of this patient.

Adult↗
PubMed1998

Clinical impact of screening first-degree relatives of patients with hepatocellular carcinoma.

Family history is a risk factor for hepatocellular carcinoma (HCC). However, the risk of first-degree relatives is not known. To investigate the risk of HCC among the first-degree relatives of probands and whether screening can lead to early diagnosis of HCCs in these relatives, we conducted a screening program. The probands' first-degree relatives who were >20 years old were included. Serum aminotransferase, hepatitis viral marker, alpha-fetoprotein, and abdominal sonography were done. HCCs were found in 20 (1.9%) of the 1,046 first-degree relatives, especially in the male siblings. Eighty-five percent of these 20 HCC patients were hepatitis B virus carriers. Forty percent of these 20 HCC patients had tumors <5 cm. Approximately 55% of these 20 HCCs were resectable. The 1-year survival rate in these 20 HCC patients with resectable HCCs was 72.7%. However, the overall 1-year survival rate was only 40%. We found HCC in 1.9% of the first-degree relatives of HCC patients. The male relatives, especially the older brothers, were the group at highest risk. The familial HCCs were closely related to the hepatitis B virus infection. To detect HCCs early, initial screening should be done as early as possible on the HCC family members.

Adult↗
PubMed1998

Overexpression of mutant p53 and c-erbB-2 proteins and mutations of the p15 and p16 genes in human gastric carcinoma: with respect to histological subtypes and stages.

Although the mechanism remains obscure, two histological subtypes of gastric carcinoma (GC), the diffuse and intestinal types, differ drastically in epidemiological, clinical, pathological and biological characteristics. We investigated whether the genetic alterations of several oncogenes and tumour suppressor genes could be correlated with the two histological subtypes. In 60 patients with GC, the overexpression of mutant p53 and c-erbB-2 oncoproteins was studied using immunohistochemical stains. Mutations of the p15 and p16 tumour suppressor genes were assessed by polymerase chain reaction, Southern blotting, and direct DNA sequencing. Overexpression of c-erbB-2 and p53 was found in 21 (35.0%) and 27 (45.0%) patients, respectively. Overexpression of the c-erbB-2 oncoprotein was more common in the intestinal type (15/32, 46.9%) and the advanced stage (19/45, 42.2%) than in the diffuse type (6/28, 21.4%) and the early stage (2/15, 13.3%) of GC (P<0.05). Similarly, p53 overexpression was more frequently found in the intestinal type (19/32, 59.4%) and the advanced stage (24/45, 53.3%) than in the diffuse type (8/28, 28.6%) and the early stage (3/15, 20.0%) of GC (P<0.05). Homozygous deletions of p16 in exon 1 were found in six (10.0%) patients. Five of them had the intestinal-type advanced GC. Neither point mutations of p16 nor alterations of p15 were detected. The frequency of alterations of p53, c-erbB-2, and p16 was not related to sex and Helicobacter pylori infection. No correlation of genetic changes between any two genes was observed. Our preliminary results indicate alterations in the p15 gene were not important in gastric tumorigenesis, while infrequent homozygous deletions in the p16 gene play a limited role in tumour progression of intestinal-type GC. Moreover, overexpression of c-erbB-2 and p53 is frequently encountered in the intestinal-type advanced GC. Alterations of p53, c-erbB-2 and p16 genes may function independently of each other in gastric carcinogenesis. The association between genetic alterations and histological subtypes supports the notion that a distinct pathogenesis may exist in different histological subtypes.

Aged↗
PubMed1998

Characteristics of hepatocellular carcinoma presenting with variceal bleeding.

Patients with hepatocellular carcinoma may present with variceal bleeding as the initial symptoms. The aims of this study is to investigate the characteristics of such patients. A total of 1046 hepatocellular carcinoma cases were retrospectively retrieved from our computer records between 1980 and 1993. The medical records and image studies were reviewed. The status of each patient was assessed at the time of presentation. A total of 14 (about 1 %) patients with hepatocellular carcinoma presented with variceal bleeding. Five (36%) did not have past history of liver disease. The tumour size ranged from 2.5 to 11.3 cm. Compared with hepatocellular carcinoma patients not presenting with variceal bleeding, these patients had a higher percentage of portal vein thrombosis (57.1 vs 19.4%). In two patients, the hepatic tumours were missed in the initial abdominal sonography. The average survival time was 71 days. Seven patients died within 2 months mainly due to variceal bleeding (41.6%). Variceal bleeding might be a clue to the presence of hepatocellular carcinoma with portal vein thrombosis even in patients without a previous history of liver disease. The tumours in such patients might be the infiltrative type, and thus the portal vein should be carefully worked-up. Overall, these patients have an extremely poor prognosis. In the management of patients with variceal bleeding, the possibility of hepatocellular carcinoma with portal vein thrombosis should not be overlooked, especially in areas where this cancer is prevalent.

Carcinoma, Hepatocellular↗
PubMed1998

Acute inductive effects on oncogenic proline-directed protein kinase FA/GSK-3 alpha in NIH 3T3 cells by ethanol and cadmium.

Exposure of NIH 3T3 cells to 375 mM ethanol at 37 degrees C for 20 min could induce a rapid increase in the protein level and cellular activity of oncogenic proline-directed protein kinase FA/glycogen synthase kinase-3 alpha (PDPK FA/GSK-3 alpha), up to approximately 300% of the control level, in a time- and concentration-dependent manner. The maximal inductive effect on PDPK FA/GSK-3 alpha also occurred within 40 min when cells were treated with only 100 mM ethanol. Similarly, exposure of NIH 3T3 cells to 100 microM cadmium for 2 h could induce a rapid increase in the protein level and cellular activity of PDPK FA/GSK-3 alpha, up to approximately 250% of the control level, in a time- and concentration-dependent manner. The maximal inductive effect on this kinase reached within 3 h when cells were treated with only 50 microM cadmium. The results demonstrate that PDPK FA/GSK-3 alpha may not represent a constitutively active/mitogen-inactivated protein kinase as previously conceived. Taken together with the previous report that PDPK FA/GSK-3 alpha is a heat-inducible protein kinase, the results further demonstrate that PDPK FA/GSK-3 alpha may represent a typical cellular stresses-inducible protein kinase subject to early induction by heat, ethanol and cadmium.

3T3 Cells↗
PubMed1997

Loss of imprinting and overexpression of IGF2 gene in gastric adenocarcinoma.

Both insulin-like growth factor II (IGF2) and H19 gene are located on chromosome 11p15.5 in close vicinity to each other, and are imprinted on different parental alleles. Although the exact mechanism remains unclear, loss of imprinting (LOI) leading to the biallelic expression of IGF2 and H19 genes has recently been reported in a variety of tumors. To study the role of IGF2 and H19 genes in gastric carcinogenesis, the LOI and loss of heterozygosity (LOH) status of these two genes were determined in 70 patients with gastric cancer. Among them, 30 patients were heterozygous for IGF2, 28 patients were heterozygous for H19, and 42 patients were heterozygous for either IGF2 or H19 gene. Among the 30 patients who were heterozygous for IGF2, one exhibited LOH (1/30, 3.3%) and 10 exhibited LOI (10/29, 34.5%). None of the 28 patients heterozygous for H19 gene had either LOH or LOI. LOI of IGF2 was more frequently found in the diffuse type (8/15, 53.3%) than the intestinal type (2/14, 14.3%, P < 0.05) gastric cancer. Five out of the six tumors with LOI of IGF2 exhibited overexpression of mRNA, but no obvious alterations of expression of H19 were noted by Northern hybridization. These data suggest that LOI leading to overexpression of IGF2 plays an important role in carcinogenesis of diffuse type gastric cancer.

Adenocarcinoma↗