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Biomedical subjects

Fon-Jou Hsieh

Publications and source records attributed to Fon-Jou Hsieh.

At least 19 recordsLinked to original sources
PubMed2006

Placenta growth factor not vascular endothelial growth factor A or C can predict the early recurrence after radical resection of hepatocellular carcinoma.

The purpose of this study was to evaluate the relationship between the expression of PlGF in tumor tissue and clinical outcomes in HCC patients. Tumor PlGF and vascular endothelial growth factor (VEGF)-A and VEGF-C mRNA were analyzed. Results demonstrated that patients with PlGF expression levels higher than median tended to have early recurrence compared to patients with PlGF expression lower than median (P=.031). In patients with AJCC stage II-III disease, this difference was even more significant (P=.002). In contrast, VEGF-A and VEGF-C could not predict early recurrence-free survival. Since PlGF expression correlated with early recurrence of HCC, PlGF may be an important prognostic indicator in HCC.

Base Sequence↗
PubMed2006

Expression of inducible nitric oxide synthase and cyclooxygenase-2 in angiogenesis and clinical outcome of human gastric cancer.

BACKGROUND AND OBJECTIVES: It has been recognized that inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) produce important endogenous factors of human tumors such as nitric oxide (NO) and prostaglandins, which is involved in the process of carcinogenesis and tumor progression. This study aimed to evaluate the association of clinicopathologic factors, microvessel density, and patient survival with the expression of iNOS and COX-2 in patients with gastric adenocarcinoma. MATERIALS AND METHODS: Seventy-nine specimens, resected from patients with gastric adenocarcinoma, were investigated by immunohistochemical stain against iNOS and COX-2. Microvessels were stained using anti-CD34 antibody and counted as microvessel density. RESULTS: Positive iNOS and COX-2 expressions were significantly correlated with microvessel density by multivariate analysis, respectively (P = 0.0127 vs. P = 0.0214). There was significant difference among the four groups (both iNOS and COX-2 positive, iNOS positive only, COX-2 positive only, and both negative) in serosal invasion (P = 0.038), lymph node metastasis (P = 0.038), Helicobacter pylori infection (P = 0.025), vascular invasion (P = 0.035), and microvessel density (P = 0.019). In patients with gastric cancer that co-expressed iNOS and COX-2, prognosis was significantly poorer than in those that expressed either iNOS or COX-2, or did not express both of them (P = 0.01738). The Cox proportional hazard regression analysis indicated that iNOS expression, vascular invasion, serosal invasion, and microvessel density are independent prognostic factors for patients with gastric cancer. CONCLUSIONS: iNOS and COX-2 expression of gastric cancer are related to tumor angiogenesis, tumor progression, and patient survival in human gastric cancer.

Adenocarcinoma↗
PubMed2006

Angiotensin-converting enzyme gene polymorphism in children with idiopathic nephrotic syndrome.

AIMS: To investigate the genetic polymorphism of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) in children with idiopathic nephrotic syndrome (INS), as well as its relationship with patient's clinical response to steroid therapy. METHODS: Fifty-nine patients with INS were recruited and divided into 2 groups according to their clinical response to steroids: steroid-sensitive (SS) with 19 patients and non-SS with 40 patients, which was further divided into steroid-dependent (SD) and steroid-resistant (SR) groups with 35 and 5 patients, respectively. Seventy-nine children without previous renal diseases and negative proteinuria were enrolled as a control group. The genotypes for ACE I/D polymorphism, including DD, ID, and II, were analyzed. RESULTS: The distribution of ACE DD, ID, and II genotypes in INS patients were 52.5, 10.2 and 37.3%, respectively; the corresponding numbers for the control group were 2.5, 25.3 and 72.2%, respectively. Patients with INS had a significantly higher percentage of DD genotype (p <0.001) than the control group. This higher incidence of the DD genotype was observed in both the SS and non-SS groups. A higher percentage of the DD genotype in the non-SS group and in the SD group as compared to the SS group (both p < 0.05) was also noted. CONCLUSION: Our data shows that INS is associated with a higher incidence of the DD genotype, especially in non-SS patients. This finding suggests that the DD genotype may be a risk factor for INS and play a role in the clinical response to steroids.

Alleles↗
PubMed2006

The influence of biologic factors on the surgical decision in advanced neuroblastoma.

BACKGROUND: Molecular markers greatly affect the outcome of neuroblastoma. This study evaluated the influence of Trk-A and myelocytomatosis viral-related oncogene, neuroblastoma-derived (MYCN) on the role of surgery in advanced neuroblastoma. METHODS: Ten stage 3 and 35 stage 4 neuroblastoma patients were included. Tumor resection was classified into gross total resection (GTR) and incomplete resection. Patients were classified into three biological risk groups according to Trk-A expression and myelocytomatosis viral-related oncogene, neuroblastoma-derived (MYCN) status in tumor tissues studied by immunohistochemistry and fluorescence in situ hybridization, respectively: low risk (positive Trk-A and normal MYCN), intermediate risk (negative Trk-A and normal MYCN), and high risk (positive or negative Trk-A and MYCN amplification). The effect of tumor resection on prognosis was studied and stratified according to the risk grouping. RESULTS: GTR was achieved in 21 patients (46.7%) with a higher complication rate (33% vs. 8% in the incomplete resection group, P = .036). GTR was easier to achieve in low-risk tumors than in intermediate- or high-risk tumors (12 of 13, 4 of 17, and 5 of 15, respectively; P < .001). GTR predicted a favorable prognosis for intermediate-risk patients (P = .037; log-rank test), but not for low- or high-risk patients because of the overall favorable and poor prognosis, respectively. CONCLUSIONS: GTR carries a potentially higher possibility of complication. Although GTR can be achieved easily in low-risk neuroblastoma patients with a favorable prognosis, surgeons should do their best to achieve GTR for intermediate-risk patients to improve outcome. Nevertheless, sacrificing vital organs to achieve GTR for high-risk patients is not justified.

Biomarkers, Tumor↗
PubMed2006

Identification of forty-five novel and twenty-three known NF1 mutations in Chinese patients with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1), characterized by skin neurofibromas and an excess of café-au-lait spots, is due to mutations in the neurofibromin (NF1) gene. Identifying the genetic defect in individuals with the disease represents a significant challenge because the gene is extremely large with a high incidence of sporadic mutations across the entire gene ranging from single nucleotide substitutes to large deletions. In the present study, we have used a combination of techniques (heteroduplex analysis, sequencing, loss of heterozygosity and quantification of gene dosage) to define the genetic defect in 68 individuals from a cohort of 107 NF1 Taiwanese patients of Chinese origin. Fifty-eight were initially identified using heteroduplex analytical techniques and confirmed by sequence analysis. A further five were identified by direct sequence analysis alone. The reminders were shown to carry large deletions in the NF1 gene by demonstrating loss of heterozygosity that was confirmed by gene dosage measurements using quantitative-PCR techniques. Mis-sense, non-sense, frame-shift or splice-site mutations were identified across the entire gene of which the majority (45/68) were novel in nature. The detection rate with the various analytical techniques and the types of mutation detected are consistent with published data involving both individuals and large cohort studies from other ethnic backgrounds.

Adolescent↗
PubMed2006

Tuboovarian abscesses in postmenopausal women.

OBJECTIVE: To compare the clinical features of tuboovarian abscess (TOA) in pre- and postmenopausal women. MATERIALS AND METHODS: Between January 1992 and December 2000, all patients with surgically documented TOA at National Taiwan University Hospital were enrolled into this retrospective study. Salient information with respect to the history, current illnesses, risk factors, physical findings, laboratory data, surgeries and postoperative complications was obtained from medical records. RESULTS: Of 74 patients with TOA, nine were postmenopausal women. Compared with the premenopausal group, postmenopausal patients were significantly more likely to have contributing medical disorders (p < 0.001) and concomitant pelvic malignant tumors (p = 0.037). CONCLUSION: Thorough investigation for concomitant pelvic malignant tumors and meticulous medical care should be provided for postmenopausal women with TOA.

Abdominal Pain↗
PubMed2006

A gene expression profile for vascular invasion can predict the recurrence after resection of hepatocellular carcinoma: a microarray approach.

BACKGROUND: Recurrence after hepatocellular carcinoma (HCC) resection is the major obstacle to improved survival. The presence of vascular invasion (VI) in pathology specimens is a well-known unfavorable prognostic factor for HCC recurrence. Though some VI-related genes have been reported, their association with recurrence-free survival is not known. We hypothesized that a gene expression profile for VI can predict the recurrence of HCC after liver resection. METHODS: Eighteen patients receiving complete HCC resection were included as a "training group". Genome-wide gene expression profile was obtained for each tumor using a microarray technique. Datasets were subjected to clustering analysis supervised by the presence or absence of VI to obtain 14 discriminative genes. We then applied those genes to execute pattern recognition using the k-Nearest Neighbor (KNN) classification method, and the best model for this VI gene signature to predict recurrence-free survival in the training group was obtained. The resulting model was then tested in an independent "test group" of 35 patients. RESULTS: A 14-gene profile was extracted which could accurately separate ten patients with VI and eight patients without VI in the "training group". In the "test group", significant difference in disease-free survival was found between patients predicted to have and not to have recurrence (P = .02823). In patients with stage_I disease, this model can also predict outcomes (P = .000205). CONCLUSIONS: Using the 14-gene expression profile extracted from microarrays based on the presence of VI can effectively predict recurrence after HCC resection. This approach might facilitate "personalized medicine" for HCC patients after surgical resection.

Aged↗
PubMed2005

Gene expression profile predicts patient survival of gastric cancer after surgical resection.

PURPOSE: This study was conducted to characterize gene expression profile of survival in patients with surgically curable gastric cancer by using an in-house membrane microarray and developing a survival prediction model. MATERIALS AND METHODS: Data of cDNA microarrays were obtained from 18 pairs of cancerous and noncancerous gastric tissues. Nine patients who survived > 30 months were identified as good survival, and the other nine, who survived < 12 months, were identified as poor survival. Supervised analysis was performed to identify a gene expression profile by good and poor survival. Semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to confirm the microarray data in 10 patients with sufficient RNA. Using these 10 patients and another 10 patients selected randomly from 40 newly enrolled patients as the training group, the RT-PCR status of the confirmed genes was used for predicting good versus poor survival. Finally, the prediction model was tested in the remaining 30 newly enrolled gastric cancer patients. RESULTS: A survival prediction model consisting of three genes (CD36, SLAM, PIM-1) was developed. This model could correctly predict poor or good survival in 23 (76.7%) of 30 newly enrolled patients, and yielded a specificity of 80% and a sensitivity of 73.3%. The survival rate of the patients predicted to have good survival was significantly higher than that of those predicted to have poor survival in the test group as a whole (N = 30; P = .00531) and in stage III patients (n = 16; P = .04467). CONCLUSION: The semiquantitative RT-PCR gene expression profiling of three genes extracted from microarray study can accurately predict surgery-related outcome in gastric cancer patients.

Gastrectomy↗
PubMed2005

Opposite roles of human pancreatitis-associated protein and REG1A expression in hepatocellular carcinoma: association of pancreatitis-associated protein expression with low-stage hepatocellular carcinoma, beta-catenin mutation, and favorable prognosis.

PURPOSE: Pancreatitis-associated protein (PAP) and regenerating protein 1 alpha (Reg1A) are up-regulated during the pancreas regeneration. This study is to investigate the clinicopathologic denotation of their expression in hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: PAP and REG1A mRNA levels were measured in 265 surgically removed unifocal primary HCCs using reverse transcription-PCR. RESULTS: PAP and REG1A mRNAs were detected in 97 (36.6%) and 55 (20.8%) HCCs, respectively, including 46 with coexpression but in none of the 219 nontumorous livers. HCCs with PAP expression correlated with low-stage tumors without evidence of vascular invasion (P = 0.013) but the REG1A expression did not. By a combination analysis, HCCs with PAP expression alone showed the lowest frequency of p53 mutation (P < 0.036), the highest rates of grade 1 and low-stage tumors (P < 0.007 and P < 0.001, respectively), less frequent early tumor recurrence (P = 0.051), and hence a better 5-year survival (P = 0.044) than groups expressing PAP and REG1A, REG1A alone, and neither PAP or REG1A. Besides, PAP expressing HCCs had significantly frequent beta-catenin mutation, regardless of REG1A expression, P < 0.00001. In the subset of HCCs that has no mutations of p53 and beta-catenin but showed PAP expression, coexpression of REG1A and PAP was associated with more frequent vascular invasion than PAP expression alone (P < 0.005). CONCLUSIONS: These data suggest that PAP expression designate a subset of low-grade, low-stage HCC with frequent beta-catenin mutation and hence more favorable prognosis, whereas further genetic or epigenetic alterations, such as p53 mutation and REG1A expression, lead to more advanced HCCs.

Adolescent↗
PubMed2005

GRP78 expression correlates with histologic differentiation and favorable prognosis in neuroblastic tumors.

Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum protein, is essential for the differentiation of neuroblastoma cells and is selectively induced when the cells are undergoing apoptosis. These findings suggest that GRP78 may affect the tumor behavior of neuroblastoma. Our study evaluates the association of clinicopathologic factors and patient survival with the expression of GRP78 in patients with neuroblastoma. GRP78 expression in 68 neuroblastic tumors was investigated semiquantitatively by immunohistochemistry. GRP78 mRNA and protein levels in 7 tumor tissues were also quantified by real-time PCR and Western blot respectively and correlated well with the immunohistochemical results. Forty (58.8%) of the 68 neuroblastic tumors showed positive GRP78 expression. The percentage of positive GRP78 immunostaining increased as the tumor histology became differentiated (p = 0.001). Furthermore, positive GRP78 expression strongly correlated with early clinical stages (P = 0.002) but inversely correlated with MYCN amplification (p = 0.001). Kaplan-Meier analysis showed that patients with positive GRP78 expression did have better survival than those with negative expression (5-year survival rate, 72.9% and 23.4% respectively, p < 0.001). Multivariate analysis further showed that GRP78 expression was an independent prognostic factor. Moreover, GRP78 expression predicted better survival in patients with either undifferentiated or differentiated histologies. GRP78 expression still had significant prognostic value when the analysis was restricted to tumors of advanced stages or without MYCN amplification. Thus, GRP78 can serve as a novel independent favorable prognostic factor for patients with neuroblastoma.

Base Sequence↗
PubMed2005

The evolving national birth prevalence of Down syndrome in Taiwan. A study on the impact of second-trimester maternal serum screening.

OBJECTIVES: The aim of the present study was to determine whether the liberal use of second-trimester maternal serum screening in Taiwan started in 1994 had a measurable impact on birth prevalence of infants with Down syndrome (DS) in the past decade. METHODS: We based our study on the databases of 'National Birth Defect Registration and Notification System', 'Amniocentesis in Pregnant Women', and 'Demographic Fact Book' in Taiwan. Collected data included total registered birth number, the registered number of stillbirths, the registered numbers of live births and of DS stillbirths affected with DS, amniocentesis rates each year in pregnant women aged 35 or more, and the age distribution of pregnant women in Taiwan. The live birth rate of and total birth rate of fetuses affected with DS, and the rates of live birth and stillbirth to total birth with DS, were analyzed year by year, in order to understand the change of birth rate of infants affected with DS between 1993 and 2001. Those with isolated cleft palate (ICP) were also analyzed as internal control variable. Confidence interval of live birth rate of infants with DS under Poisson distribution was calculated. Chi-square test for trend in binomial proportions was performed to see if there is an increasing (or decreasing) trend in the proportion of incidence of fetuses affected with DS. The difference was statistically significant if a p value was <0.05. RESULTS: A total of 1 331 616 deliveries were collected during the study period, including 840 cases of DS confirmed by karyotyping study. A marked decrease in the live birth rates of case with DS occurred in 1994-95, from 0.63 per 1000 births to 0.23 per 1000 births. There was a crossover from more live births with DS to more stillbirths with DS during 1994 to 1996 after the implementation of second-trimester maternal serum screening for DS in 1994. In 1993, 76.9% of births diagnosed with DS were born alive, compared to 32.5% in 2001 (p < 0.001). CONCLUSIONS: The policy of prenatal diagnosis program including amniocentesis for pregnant women aged 35 or more and the liberal application of maternal serum screening for DS in younger women was responsible for the marked decrease in the live births affected with DS in Taiwan from 1993 to 2001.

Age Distribution↗
PubMed2005

Vascular endothelial growth factor in preterm infants with respiratory distress syndrome.

Respiratory distress syndrome (RDS) secondary to surfactant deficiency is a common cause of morbidity and mortality in premature infants. Increasing evidence suggests that vascular endothelial growth factor (VEGF) may contribute to surfactant secretion and pulmonary maturation. However, differences in cord blood VEGF concentrations in infants with and without respiratory distress syndrome have not been reported. We hypothesized that premature infants with higher VEGF levels in cord blood had a lower risk of developing RDS. Cord blood samples were obtained from preterm infants born at 32 weeks of gestation or earlier. Infants were excluded if there was evidence of prenatal maternal infection or any infection within the first 3 days of life. Cord blood VEGF levels were measured using an enzyme-linked immunosorbent assay (ELISA). We found that neonates with clinically diagnosed RDS had a lower gestational age (GA), lower birth weight (BW), higher incidence of mechanical ventilation requirements, longer duration of mechanical ventilation, and lower Apgar scores at 1 and 5 min. Infants with RDS had significantly lower cord blood VEGF levels. GA, BW, premature rupture of membranes (PROM), and antenatal steroid treatment were not associated with changes in cord blood VEGF levels. The specificity of cord blood VEGF above 34 pg/ml for predicting the absence of RDS was 86%, the sensitivity was 53%, the positive predictive value was 84%, and the negative predictive value was 56%. Our data demonstrated that cord blood VEGF elevation was significantly correlated with an absence of RDS.

Apgar Score↗
PubMed2005

Association of the C677T methylenetetrahydrofolate reductase mutation with congenital heart diseases.

BACKGROUND: To investigate whether the cytosine-to-thymine mutation at base 677 of the gene for methylenetetrahydrofolate reductase (MTHFR) is associated with congenital heart diseases (CHD), using high throughput heteroduplex analysis based upon the powerful technique of denaturing high-performance liquid chromatography. METHODS: We investigated the MTHFR genotype of a cytosine-to-thymine mutation at base 677 for 213 patients of CHDs as confirmed by cardiac catheterization and also for 195 healthy controls. RESULTS: The overall genotype frequencies of the MTHFR C677T polymorphism were not significantly different between the CHD patients and the healthy control (P = 0.345). Furthermore, taking various subgroups of CHD patients into consideration, we noted a significantly increased proportion of homozygous TT genotypes for patients suffering from valvular pulmonary stenosis (PS) or pulmonary atresia with an intact ventricular septum (PA + IVS) (p = 0.0005). For patients revealing heterotaxy syndrome, a conotruncal anomaly including tetralogy of Fallot, an interruption of the aortic arch, persistent truncus arteriosus, and aortopulmonary window, no statistically significant difference existed. CONCLUSIONS: The discrepancy in the distribution of MTHFR genotypes amongst various subtypes of CHD reflects some heterogeneity in the developmental mechanism of CHD. The increased percentage of homozygous TT genotypes might contribute to the pathogenesis of valvular PS and PA + IVS.

Asian People↗
PubMed2005

Effect of thalidomide in hepatocellular carcinoma: assessment with power doppler US and analysis of circulating angiogenic factors.

PURPOSE: To prospectively evaluate the feasibility of using power Doppler ultrasonography (US) and measurement of circulating angiogenic factors to assess the antiangiogenic effect of thalidomide in hepatocellular carcinoma. MATERIALS AND METHODS: The Ethics Committee of the National Taiwan University Hospital approved the study, and all patients gave prior written informed consent. Evaluation of response to thalidomide treatment was based on findings at computed tomography (CT) and change in serum alpha-fetoprotein level. Tumor vascularity index was evaluated with power Doppler US in patients with advanced hepatocellular carcinoma treated with 200-300 mg/d thalidomide. Serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and placental growth factor were measured with enzyme-linked immunoassay. The chi(2) test or Fisher exact test was used for categorical variables, and the nonparametric Mann-Whitney test was used for numeric variables. A P value of less than .05 was considered to indicate a statistically significant difference. RESULTS: Of 47 patients enrolled in the study who had disease that was bidimensionally assessable on CT scans, 44 were assessable for tumor response. Of the 44 evaluated, five were classified as showing objective response (responders): One each showed a complete and a partial response according to World Health Organization criteria, and three had a decrease in alpha-fetoprotein level by more than 50% and stable disease for 10.4, 5.3, or 3.5 months. The pretreatment vascularity index was significantly higher in responders (median, 7.42; range, 2.99-13.90) than in nonresponders (median, 2.15; range, 0-25.36) (P = .03). Four of five responders had a significant decrease in vascularity index with thalidomide. Serum levels of angiogenic factors did not differ significantly between responders and nonresponders. CONCLUSION: Higher vascularity index may be associated with a better chance of response to thalidomide in patients with advanced hepatocellular carcinoma. Serum levels of circulating angiogenic factors do not appear to be clinically useful as an indicator of response.

Adult↗
PubMed2005

Clinicopathologic correlation of up-regulated genes identified using cDNA microarray and real-time reverse transcription-PCR in human colorectal cancer.

PURPOSE: We hypothesize that changes in the transcription of up-regulated genes are biologically meaningful and may be linked to variations in tumor behavior and clinical features. This study aimed to find individual up-regulated genes responsible for clinicopathologic variations in human colorectal cancer. EXPERIMENTAL DESIGN: Genes up-regulated concurrently in four microarray experiments were taken as candidate genes; 20 candidate genes were verified using real-time reverse transcription-PCR in these four experiments, along with 27 new samples. The presence or absence of up-regulation of these genes was correlated with 10 clinicopathologic variables from 31 patients. The mRNA transcript levels of these 20 candidate genes in the 31 paired samples were also correlated with each other to disclose any expression relationship. RESULTS: Forty percent (8/20) of the candidate genes were verified by real-time reverse transcription-PCR to have a tumor/normal expression ratio > 2. Up-regulation of THY1 and PHLAD1 was associated with the presence of anemia in colon cancer patients (P = 0.036 and 0.009, respectively). Up-regulation of HNRPA1 was more significant in cancer growing in the right-sided colon than the left side (P = 0.027). Up-regulated GPX2 was related to a higher degree of tumor differentiation (P = 0.019). c-MYC was significantly over-expressed in specimens from male compared with female colon cancer patients (P = 0.012). GRO1 was significantly up-regulated in patients younger than 65 years old (P = 0.010) and was found to be frequently over-expressed when cancers were less invasive. In addition, we found that normalized transcript levels of HNRPA1 were tightly associated with that of c-MYC (r = 0.948). CONCLUSIONS: Validation of microarray data using another independent laboratory approach is mandatory and statistical correlation between gene expression status and the patient's clinical features may reveal individual genes relevant to tumor behavior and clinicopathologic variations in human colorectal cancer.

Adult↗
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↗