Publications (20)86.83 Total impact
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Article: Endoscopic submucosal dissection for early colorectal neoplasms: clinical experience in a tertiary medical center in taiwan.
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ABSTRACT: Objectives. Endoscopic submucosal dissection (ESD) is a promising technique to treat early colorectal neoplasms by facilitating en bloc resection without size limitations. Although ESD for early gastrointestinal epithelial neoplasms has been popular in Japan, clinical experience with colorectal ESD has been rarely reported in Taiwan. Methods. From March 2006 to December 2011, 92 consecutive patients with early colorectal neoplasms resected by ESD at Tri-Service General Hospital were included. ESD was performed for colorectal epithelial neoplasms with a noninvasive pit pattern which had the following criteria: (1) lesions difficult to remove en bloc with a snare, such as laterally spreading tumors-nongranular type (LST-NG) ≧20 mm and laterally spreading tumors-granular type (LST-G) ≧30 mm; (2) lesions with fibrosis or which had recurred after endoscopic mucosal resection with a nonlifting sign. Results. The mean age of the patients was 66.3 ± 12.9 years, and the male-female ratio was 1.8 : 1. The mean tumor size was 37.2 ± 17.9 mm. The en bloc resection rate was 90.2% and the R0 resection rate was 89.1%. Perforations during ESD occurred in 11 patients (12.0%) and all of them were effectively treated by endoscopic closure with hemoclips. No delayed perforation or postoperative bleeding was recorded. There were no procedure-related morbidities or mortalities. Conclusion. ESD is an effective method for en bloc resection of large early colorectal neoplasms and those with a nonlifting sign. An endoscopic technique to close perforations is essential for colorectal ESD.Gastroenterology Research and Practice 01/2013; 2013:891565. · 0.98 Impact Factor -
Article: Hepatitis C Virus Core Protein Down-Regulates p21(Waf1/Cip1) and Inhibits Curcumin-Induced Apoptosis through MicroRNA-345 Targeting in Human Hepatoma Cells.
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ABSTRACT: Hepatitis C virus (HCV) has been reported to regulate cellular microRNAs. The HCV core protein is considered to be a potential oncoprotein in HCV-related hepatocellular carcinoma, but HCV core-modulated cellular microRNAs are unknown. The HCV core protein regulates p21(Waf1/Cip1) expression. However, the mechanism of HCV core-associated p21(Waf1/Cip1) regulation remains to be further clarified. Therefore, we attempted to determine whether HCV core-modulated cellular microRNAs play an important role in regulating p21(Waf1/Cip1) expression in human hepatoma cells. Cellular microRNA profiling was investigated in core-overexpressing hepatoma cells using TaqMan low density array. Array data were further confirmed by TaqMan real-time qPCR for single microRNA in core-overexpressing and full-length HCV replicon-expressing cells. The target gene of microRNA was examined by reporter assay. The gene expression was determined by real-time qPCR and Western blotting. Apoptosis was examined by annexin V-FITC apoptosis assay. Cell cycle analysis was performed by propidium iodide staining. Cell proliferation was analyzed by MTT assay. HCV core protein up- or down-regulated some cellular microRNAs in Huh7 cells. HCV core-induced microRNA-345 suppressed p21(Waf1/Cip1) gene expression through targeting its 3' untranslated region in human hepatoma cells. Moreover, the core protein inhibited curcumin-induced apoptosis through p21(Waf1/Cip1)-targeting microRNA-345 in Huh7 cells. HCV core protein enhances the expression of microRNA-345 which then down-regulates p21(Waf1/Cip1) expression. It is the first time that HCV core protein has ever been shown to suppress p21(Waf1/Cip1) gene expression through miR-345 targeting.PLoS ONE 01/2013; 8(4):e61089. · 4.09 Impact Factor -
Article: Carbon dioxide insufflation does not reduce pain scores during colonoscope insertion in unsedated patients: a randomized, controlled trial.
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ABSTRACT: CO(2) is rapidly absorbed from the colon and eliminated via the lung. Insufflation of CO(2) instead of air during colonoscopy can reduce distention-induced pain. This study aimed to evaluate the effects of CO(2) insufflation on pain during intubation and extubation and to identify predictors of pain and discomfort during colonoscope insertion. Prospective, randomized, controlled trial. Single tertiary medical center in Taiwan. A total of 193 patients enrolled from September 2010 through June 2011. Colonoscope insertion with either air or CO(2) insufflation. CO(2) was used for extubation in both groups. The main outcome measurement was pain, recorded on a 10-point visual analog scale (VAS) for left-sided colonoscope insertion and right-sided colonoscope insertion and at 1, 3, 6, and 24 hours post-procedure. Colonoscope cecal intubation time and extubation time, completeness of intubation, and loop formation were also assessed. CO(2) insufflation during colonoscope intubation was used in 98 patients and air in 97 patients. The mean pain scores during intubation were low (2-3) for patients undergoing air insufflation and were not reduced further in patients receiving CO(2). A mean pain score of 0 was reported by both groups for all postprocedure time points. Multivariate analysis identified sex, loop formation of the sigmoid colon, time to reach the transverse colon, and requested sedation as factors that significantly affect VAS pain scores. This study was limited in scope to a single medical center with experienced endoscopists. We detected no significant benefit to the use of CO(2) insufflation compared with air insufflation during intubation for colonoscopy performed by experienced colonoscopists. The absence of postprocedure pain in both groups supports previous observations that CO(2) insufflation during extubation is effective in reducing postprocedure pain. Female sex and loop formation were identified as key factors influencing pain scores on colonoscope insertion. (Clinical trial registration number: TSGHIRB-099-05-081.).Gastrointestinal endoscopy 01/2013; 77(1):79-89. · 6.71 Impact Factor -
Article: Frequent concomitant epigenetic silencing of SOX1 and SFRPs in human hepatocellular carcinoma.
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ABSTRACT: BACKGROUND AND AIM: Except for genetic mutations, epigenetic changes are also involved in the development of human cancers. Recently, we have identified SOX1, SRY (sex determining region Y)-box 1, is hypermethylated in cervical cancer and ovarian cancer. Therefore, we investigated whether promoter hypermethylation of SOX1 is common in hepatocellular carcinoma (HCC). METHODS: We used methylation-specific PCR (MS-PCR) and bisulfite sequencing to analyze the methyaltion level of the SOX1 promoter in 7 HCC cell lines, 54 clinical HCCs, 42 cirrhotic livers, 21 livers with chronic hepatitis, and 15 control livers. Then, we employed quantitative MS-PCR (QMS-PCR) to validate in an independent set of samples (60 paired HCCs and 30 control livers). Finally, we used luciferase reporter and colony formation assay to check the effect of SOX1 in HCC. RESULTS: Promoter methylation of SOX1 was significantly frequent in HCC cell lines and clinical HCCs, cirrhotic livers, but not in control livers (P< 0.0001). There is a significant correlation between down-regulation of SOX1 expression and promoter methylation. QMS-PCR results confirmed that promoter hypermethylation of SOX1 is significantly more frequent in HCCs than control livers (P < 0.0001). The frequency of SOX1 methylation in patients with SFRPs (secreted frizzled-related proteins) methylation is significantly higher than patients without SFRPs methylation (P<0.0001). Furthermore, ectopic expression of SOX-1 could suppress TCF-dependent transcriptional activity and colony formation number in HCCs. CONCLUSIONS: Concomitant epigenetic silencing of SOX1 and SFRPs through promoter hypermethylation is frequent in HCCs and this might contribute to abnormal activation of canonical Wnt signal pathway.Journal of Gastroenterology and Hepatology 12/2012; · 2.87 Impact Factor -
Article: NF-κB down-regulates human UDP-glucuronosyltransferase 1A1: a novel mechanism involved in inflammation-associated hyperbilirubinemia.
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ABSTRACT: Jaundice or hyperbilirubinemia is a common complication of sepsis. UDP-glucuronosyltransferase 1A1 (UGT1A1) is a critical gene for bilirubin metabolism and irinotecan detoxification. However, the molecular pathogenesis of hyperbilirubinemia during inflammation needs to be further clarified. Human hepatic UGT1A1 expression was analyzed by RT-PCR, qRT-PCR and Western blotting in response to lipopolysaccharide (LPS) stimulation. Transcription regulatory elements in the upstream promoter region of human UGT1A1 gene were determined by EMSA and ChIP assay. The important role of transcription regulatory element was examined by luciferase assay, and was determined by qRT-PCR using transcription factor activation inhibitor. LPS down-regulated the UGT1A1 mRNA expression in human hepatoma cell lines. A newly identified NF-κB-binding site located on the upstream promoter region (-725/-716) of human UGT1A1 gene. LPS-induced NF-κB activation and specific binding to NF-κB-binding site can suppress human UGT1A1 promoter activity and human UGT1A1 expression. We demonstrated that LPS mediates the suppression of human UGT1A1 expression through specific binding of NF-κB to a newly identified NF-κB-binding site in the upstream promoter of human UGT1A1 gene. This study may explain, in part, the molecular pathogenesis of inflammation-associated hyperbilirubinemia.Biochemical Journal 11/2012; · 4.90 Impact Factor -
Article: SOX1 functions as a tumor suppressor through antagonizing the WNT/β-catenin signaling pathway in hepatocellular carcinoma.
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ABSTRACT: Oncogenic activation of the Wnt/β-catenin signaling pathway is common in hepatocellular carcinoma (HCC). Our recent studies have demonstrated that SRY (sex determining region Y)-box 1 (SOX1) and Secreted Frizzled-Related Proteins (SFRPs) are concomitantly promoter hypermethylated and this might lead to abnormal activation of the Wnt signaling pathway in HCC. SOX1 encodes a transcription factor involved in the regulation of embryonic development and cell fate determination. However, the expression and functional role of SOX1 in HCC remains unclear. In this study, we confirmed that SOX1 was frequently downregulated through promoter hypermethylation in HCC cells and tissues by quantitative methylation-specific PCR (QMS-PCR). Overexpression of SOX1 by a constitutive or inducible approach could suppress cell proliferation, colony formation, and invasion ability in HCC cell lines, as well as tumor growth in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Conversely, knockdown of SOX1 by withdrawal of doxycycline (DOX)could partially restore cell proliferation and colony formation in HCC cells. We used a T-cell factor (TCF)-responsive luciferase reporter assay and Western blot to prove that SOX1 could regulate TCF-responsive transcriptional activity and inhibit the expression of Wnt downstream genes. Furthermore, we employed glutathione S-transferase (GST) pull-down, co-immunoprecipitation and confocal microscopy to demonstrate that SOX1 could interact with β-catenin but not with the β-catenin/TCF complex. Moreover, restoration of the expression of SOX1 induces significant cellular senescence in Hep3B cells. Conclusions: Our data showed that a developmental gene, SOX1, may function as a tumor suppressor through interfering with Wnt/β-catenin signaling in the development of HCC. (HEPATOLOGY 2012.).Hepatology 07/2012; · 11.66 Impact Factor -
Article: Modified Mallampati classification as a clinical predictor of peroral esophagogastroduodenoscopy tolerance.
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ABSTRACT: Unsedated esophagogastroduodenoscopy (EGD) is simpler and safer than sedated EGD; however, approximately 40% of patients cannot tolerate it. Early identification of patients likely to poorly tolerate unsedated EGD is valuable for improving compliance. The modified Mallampati classification (MMC) has been used to evaluate difficult tracheal intubation and laryngoscope insertion. We tried to assess the efficacy of MMC to predict the tolerance of EGD in unsedated patients. Two hundred patients who underwent an unsedated diagnostic EGD were recruited. They were stratified according to the view of the oropharynx as either MMC class I + II (good view) or class III + IV (poor view). EGD tolerance was assessed in three ways: gag reflex by endoscopist assessment, patient satisfaction by interview, and the degree of change in vital signs. MMC was significantly correlated to gag reflex (P < 0.001), patient satisfaction (P = 0.028), and a change of vital signs (P = 0.024). Patients in the poor view group had a 3.87-fold increased risk of gag reflex (P < 0.001), a 1.78-fold increased risk of unsatisfaction (P = 0.067), and a 1.96-fold increased risk of a change in vital signs (P = 0.025) compared to those in the good view group. MMC appears to be a clinically useful predictor of EGD tolerance. Patients with poor view of oropharynx by MMC criteria may be candidates for sedated or transnasal EGD.BMC Gastroenterology 02/2011; 11:12. · 2.42 Impact Factor -
Article: Endoscopic submucosal dissection with the pulley method for early-stage gastric cancer (with video).
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ABSTRACT: Using EMR techniques, physicians frequently remove tumors >15 mm by piecemeal resection, which is associated with an increased rate of disease recurrence and difficulty in histologically evaluating the specimen. Endoscopic submucosal dissection (ESD) of early-stage gastric cancer improves the rate of successful en bloc resection, but it is associated with more complications, such as bleeding and perforation, than conventional EMR. To describe a simple technique that uses the pulley method to facilitate ESD procedures in the excision of large early-stage gastric cancers. Case series. Tertiary medical center in Taiwan. Eleven patients with early-stage gastric cancers or adenomas >20 mm underwent ESD. The pulley method with standard clips and dental floss was used to provide traction to improve visualization of the dissection plane during ESD. Proportion with complete en bloc resection. En bloc resection of the lesion was achieved in 11 patients. No perforation or emergent surgery was noted. One endoscopist performed all procedures, and only 11 patients were studied in an uncontrolled manner. The pulley method seems to facilitate en bloc ESD of early-stage gastric cancers >20 mm.Gastrointestinal endoscopy 10/2010; 73(1):163-7. · 6.71 Impact Factor -
Article: Rapid development of severe thrombocytopenia in a female with chronic hepatitis C after single-dose pegylated interferon therapy.
Digestive and Liver Disease 08/2009; 42(3):233-4. · 3.05 Impact Factor -
Article: Characterization of LMX-1A as a metastasis suppressor in cervical cancer.
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ABSTRACT: DNA methylation is important in cancer development and is a promising biomarker for cancer detection. An epigenomic approach used in our previous work showed that LMX-1A is methylation-silenced in cervical cancer. LMX-1A, a LIM-homeobox gene, is known to participate in developmental events; however, there are at present no data on the role of LMX-1A in cancers. In this study, we characterized the function of this transcription factor by examining cell lines, animal models and human cervical neoplastic tissues, and found that over-expression of LMX-1A does not affect cell proliferation or the cell cycle of cervical cancer cell lines but significantly inhibits colony formation and invasion in vitro. Analysis of changes in epithelial-mesenchymal transition (EMT) markers, such as CDH1, CDH2, VIMENTIN, SNAIL, SLUG and TWIST, revealed involvement of the EMT in LMX-1A-mediated cancer invasion; this result was validated in a stable transfectant over-expressing LMX-1A with RNA interference. Xenograft studies using immunocompromised mice confirmed the suppressor effects of LMX-1A on tumour formation and distant metastasis in cervical cancer cell lines. LMX-1A immunohistochemical staining of tissue arrays containing the full spectrum of cervical neoplasms, including normal cervix, low-grade cervical intra-epithelial neoplasia (CIN), high-grade CIN, locally invasive and distant metastatic cancers, demonstrated the critical role of LMX-1A in invasion and metastasis. Furthermore, we found by analysing TGFbeta-BMP signalling that BMP4 and BMP6 are down-regulated by LMX-1A. The results of this study suggest that LMX-1A suppresses cancer invasion and metastasis in cervical cancer through an incomplete EMT.The Journal of Pathology 06/2009; 219(2):222-31. · 6.32 Impact Factor -
Article: The basal body gene, RPGRIP1L, is a candidate tumour suppressor gene in human hepatocellular carcinoma.
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ABSTRACT: Loss of heterozygosity (LOH) on chromosome 16q is one of the most frequent genetic alterations in hepatocellular carcinoma (HCC). Our previous data showed that the smallest common deleted region was between D16S415 and D16S419, encompassed approximately by a 0.75cM region on 16q12.2, suggesting that the putative tumour suppressor genes (TSGs) at this locus might be involved in the development of HCC. Of the four genes (CHD9, RBL2, AKTIP and RPGRIP1L) located in this region, only RPGRIP1L was downregulated in HCCs. Downregulation of RPGRIP1L was found in 91% (10/11) HCC cell lines and in 35% (14/40) HCCs, respectively. To investigate the role of RPGRIP1L in HCCs, we used the overexpression of RPGRIP1L in four HCC cell lines (HepG2, Huh6, Huh7 and Hep3B). Overexpression of RPGRIP1L suppressed colony formation of tumour cells. Conversely, expression of RPGRIP1LM (dominant negative form) in HCC cells enhanced colony formation. Furthermore, knockdown RPGRIP1L by RNA interference in SK-HepI cells promoted colony formation. Taken together, these data strongly suggest that RPGRIP1L might be the putative TSG in HCC. Moreover, we showed that Mad2, Survivin and Securin were elevated in RPGRIP1LM-HepG2 transfectants and RPGRIP1L-shRNA-SK-HepI transfectants. After knockdown of MAD2 in RPGRIP1L-shRNA-SK-HepI transfectants partly reverse cellular colony formation capability. These data suggest that RPGRIP1L suppresses anchorage-independent growth partly through the mitotic checkpoint protein Mad2.European journal of cancer (Oxford, England: 1990) 05/2009; 45(11):2041-9. · 4.12 Impact Factor -
Article: SFRP1 and SFRP2 suppress the transformation and invasion abilities of cervical cancer cells through Wnt signal pathway.
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ABSTRACT: Aberrant activation of the Wnt/beta-catenin signaling pathway is common in human cancers, including cervical cancer. The secreted frizzled-related proteins (SFRPs) function as Wnt antagonists and play important implications in carcinogenesis. Recently, we have shown that SFRP1 and SFRP2 are frequently downregulated through promoter hypermethylation. However, the function of SFRP1 and SFRP2 in cervical cancer remains unclear. To improve our understanding of the role of SFRP1 and SFRP2 in cervical cancer cells, we use overexpression or shRNA approach in cervical cancer cell lines. Restoration of the expression of SFRP1 and SFRP2 attenuated Wnt signaling in CaSki cells, decreased abnormal accumulation of free beta-catenin in the nucleus, and suppressed cancer cell growth. In addition, different statuses of beta-catenin accumulation in the cytoplasm of CaSki or HeLa3rd cells were observed, suggesting that different Wnt pathways are executed. Furthermore, we demonstrated that SFRP1 and SFRP2 enhance the expression of the epithelial marker E-cadherin, through inhibition of the expression of SLUG, TWIST and SNAIL, three transcription factors involved in the epithelial mesenchymal transition (EMT) program. Finally, in a xenograft animal model, we showed that SFRP1 suppresses tumorigenicity of cancer cells in vivo. Taken together, these data strongly suggest that epigenetic silencing of SFRP genes leads to oncogenic activation of the Wnt pathway and contributes to cervical cancer progression through the EMT program.Gynecologic Oncology 01/2009; 112(3):646-53. · 3.89 Impact Factor -
Article: Promoter methylation of SFRPs gene family in cervical cancer.
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ABSTRACT: Oncogenic activation of the Wnt/beta-catenin signaling pathway is common in human cancers, including cervical cancer. The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and play an important role in carcinogenesis. Frequent promoter hypermethylation of SFRPs has been identified in human cancers; however, the precise role of SFRPs in cervical cancer is not clear. The methylation status of SFRPs gene family was analyzed in two cervical cancer cell lines and a full spectrum of cervical neoplasia, including 45 low-grade squamous intraepithelial lesions (LSIL), 49 high-grade squamous intraepithelial lesions (HSIL), 109 squamous cell carcinomas (SCC), and 45 normal controls. The SFRP1 promoter was hypermethylated in 33.9% of SCC, 8.2% of HSIL, 2.2% of LSIL, but not in normal tissues. The SFRP2 promoter was hypermethylated in 80.7% of SCC, 16.3% of HSIL, 15.6% LSIL and 4.4% normal tissues. The SFRP4 promoter was hypermethylated in 67.9% of SCC, 36.7% of HSIL, 4.4% of LSIL, but not in normal tissues. The SFRP5 promoter was hypermethylated in 10.1% of SCC, 4.1% of HSIL, 13.3% of LSIL and 4.4% normal tissues. The frequency of SFRP1, SFRP2 and SFRP4 promoter methylation in tumors was significantly higher than in normal, LSIL, and HSIL samples (P<0.0001). SFRP5 methylation was significantly different in patients with or without lymph-node metastases (0% vs 15.2%, respectively, P<0.05). Our data suggest that promoter hypermethylation of SFRP1, SFRP2 and SFRP4 is associated with cervical carcinogenesis, which could be used for molecular screening of cervical neoplasias in future.Gynecologic Oncology 12/2008; 112(2):301-6. · 3.89 Impact Factor -
Article: Dexamethasone reduced invasiveness of human malignant glioblastoma cells through a MAPK phosphatase-1 (MKP-1) dependent mechanism.
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ABSTRACT: Dexamethasone has been shown to inhibit tumor invasiveness. In the present study, the effects of dexamethasone on matrix metalloproteinases-2 (MMP-2) secretion, cell invasiveness, and intravasation in human U87MG glioma cells were examined. Dexamethasone decreased MMP-2 secretion and cell invasiveness in human glioma cells. Incubation of cells with dexamethasone increased mitogen activated protein kinase phosphatase-1 (MKP-1) expression. Ectopic expression of MKP-1 decreased cell invasiveness in vitro and intravasation in vivo. Because expression of inducible nitric oxide synthase (iNOS) has been implicated in the progression of malignant gliomas, we next investigated the possible roles of NO(-) in MMP-2 secretion and cell invasiveness in human U87MG glioma cells. Treatment of glioma cells with nitric oxide donor, sodium nitroprusside (SNP), increased MMP-2 secretion and the capacity of cell invasion in U87MG cells. Addition of dexamethasone or ectopic expression of wild-type MKP-1 suppressed the SNP-stimulated MMP-2 activation and glioma cell invasiveness in U87MG cells. Taken together, these results suggest that dexamethasone may suppress MMP-2 secretion and cell invasion through MKP-1 induction in human glioma cells.European Journal of Pharmacology 09/2008; 593(1-3):1-9. · 2.52 Impact Factor -
Article: A prospective trial of variable stiffness colonoscopes with different tip diameters in unsedated patients.
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ABSTRACT: Few data exist comparing the clinical versatility of variable stiffness (VS) colonoscopes with different tip diameters and stiffness ranges. We compared the intubation time and success rate, maneuvering ease, and patient comfort of three colonoscopes: pediatric VS (PVSC), nonmagnifying adult VS (AVSC), and magnifying VS (MVSC). Two hundred sixteen consecutive patients scheduled for routine colonoscopy were randomized to undergo colonoscopy with one of the three different colonoscopes (PVSC N = 72, AVSC N = 72, MVSC N = 72). Outcome measurements included time required for cecal intubation, success rate for cecal intubation, maneuvering ease, and patient comfort. The overall success rate for cecal intubation was 95.83%. Intubation time was significantly different among the groups (PVSC 12.88 +/- 7.11 min, AVSC 9.25 +/- 5.16 min, MVSC 9.62 +/- 5.55 min; P < 0.01). Intubation time with PVSC required about 3 min more when compared with AVSC or MVSC. Multivariate analyses revealed that colonoscopy with AVSC required 3 min less when compared with PVSC (P= 0.03). Age greater than 55 yr, waist circumference, prior hysterectomy, and pain experienced by patients were also factors affecting intubation time. In this study, a PVSC might not decrease patient discomfort or intubation time. The ideal colonoscope is the AVSC that has a modest diameter and stiffness range and thus is capable of achieving both a short intubation time and an acceptable comfort level. We also should bear in mind that MVSC has an additional function of magnifying observation.The American Journal of Gastroenterology 07/2008; 103(6):1365-71. · 7.28 Impact Factor -
Article: Spontaneous intracranial hemorrhage in cirrhotic patients.
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ABSTRACT: The major characteristics of spontaneous intracranial hemorrhage (SICH) in cirrhotic patients have not been completely defined. Cirrhotic patients with SICH were thus analyzed in an effort to better understand the risk factors for SICH and predict patient outcomes. From 1997 to 2006, 4515 hospitalized cirrhotic patients were recruited, with a focus on 36 cirrhotic patients with SICH who had no history of cerebral vascular accidents, head injuries, or cerebral arteriovenous malformations. The patient characteristics, severity of cirrhosis, location of the hematoma, and prognosis were analyzed. Of the patients, 78% were males, 72% consumed alcohol, and 81% had a mild-to-moderate degree of cirrhosis. The overall incidence of SICH was related to the etiology of cirrhosis as follows: virus-related cirrhosis (0.3%), alcohol-related cirrhosis (1.9%), and combined virus- and alcohol-related cirrhosis (3%). The outcome of patients with SICH was associated with the size of the hematoma (P<0.005), the initial Glasgow Coma Scale score (P<0.05), the Child-Pugh classification (P=0.05), and the serum total bilirubin level (P<0.05). SICH occurs primarily in young males with mild-to-moderate alcoholic cirrhosis of the liver. The etiology of cirrhosis is related to the incidence of SICH, but not to the patient outcome. The severity of liver cirrhosis is associated with patient outcome, but not the incidence of SICH.Clinical Neurology and Neurosurgery 03/2008; 110(3):253-8. · 1.58 Impact Factor -
Article: SFRP1 suppressed hepatoma cells growth through Wnt canonical signaling pathway.
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ABSTRACT: Oncogenic activation of the Wnt/beta-catenin signaling pathway is common in hepatocellular carcinoma (HCC). The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications for carcinogenesis. Promoter hypermethylation of SFRP genes is common in human cancers. However, the role of SFRPs in HCC is not clear. Recently, we have shown that SFRP1 is frequently downregulated through promoter hypermethylation. To confirm and extend these findings, the methylation status of the other SFRP members, including SFRP2, SFRP4 and SFRP5, was examined by methylation-specific polymerase chain reaction (MS-PCR). Hypermethylation of SFRP genes, except for SFRP4, is frequent in HCCs and the levels found here were significantly higher than those seen in cirrhotic livers, chronic hepatitis livers and normal controls (p < 0.0001 for SFRP1 and SFRP2, p < 0.05 for SFRP5). To investigate the role of SFRP1 in HCCs, we used re-expression of SFRP1 in beta-catenin-dependent HCC cell lines: Huh6 and HepG2. Restoration of SFRP1 attenuated Wnt signaling in those Huh6 hepatoma cells with a beta-catenin gene point mutation, decreased abnormal accumulation of beta-catenin in the nucleus and suppressed cell growth. Conversely, restoration of SFRP1 in HepG2 hepatoma cells with truncated beta-catenin could not block the Wnt signaling pathway. Furthermore, knocking down SFRP1 by RNA interference in beta-catenin-deficient cell lines (SK-Hep1) stimulated Wnt signaling and promoted cell growth. Our data suggested that SFRP1 suppressed liver cancer cells growth through Wnt canonical signaling. Moreover, beta-catenin-independent noncanonical pathway might be involved in Wnt signaling activation through unknown molecules in HCC.International Journal of Cancer 10/2007; 121(5):1028-35. · 5.44 Impact Factor -
Article: Promoter methylation of the secreted frizzled-related protein 1 gene SFRP1 is frequent in hepatocellular carcinoma.
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ABSTRACT: The secreted frizzled-related protein 1 gene (SFRP1) encodes a Wnt/beta-catenin signaling antagonist and frequently is inactivated by promoter methylation in many tumors. However, the role of SFRP1 in hepatocellular carcinoma (HCC) is not clear. Therefore, the authors investigated whether methylation of the SFRP1 promoter is common in HCC and whether it may influence SFRP1 expression. Four HCC cell lines, 54 HCCs, 42 cirrhotic livers, 21 livers with chronic hepatitis, and 15 normal control tissues were analyzed for 1) SFRP1 promoter methylation by using methylation-specific polymerase chain reaction analysis and bisulfite sequencing, 2) SFRP1 messenger RNA expression by using quantitative reverse transcriptase-polymerase chain reaction analysis, and 3) loss of heterozygosity (LOH) by using microsatellite markers flanking the SFRP1 locus. HCC cells were treated with the demethylating agent 5-aza-2'-deoxycytidine to determine whether it could restore SFRP1 expression. SFRP1 promoter methylation was observed in 75%, 48.2%, 21.4%, 14.3% and 0% in HCC cell lines, primary HCCs, cirrhotic livers, livers with chronic hepatitis, and normal control tissues, respectively. Methylation of the SFRP1 promoter region in HCCs increased significantly compared with control tissues. All samples with SFRP1 methylation showed down-regulation of SFRP1 expression. Demethylation treatment with 5-aza-2'-deoxycytidine in HCC cells restored SFRP1 expression. Moreover, LOH of markers D8S505 and D8S1722 was found in 25% and 27.6% of the informative samples, respectively. The current results suggested that promoter hypermethylation of SFRP1 is a common event in HCC and plays an important role in the regulation of SFRP1 expression. In addition to methylation-mediated down-regulation of SFRP1, LOH also may play a role.Cancer 09/2006; 107(3):579-90. · 4.77 Impact Factor -
Article: Helicobacter pylori infection in relation to E-cadherin gene promoter polymorphism and hypermethylation in sporadic gastric carcinomas.
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ABSTRACT: To study Helicobacter pylori (H. pylori) infection in relation to E-cadherin (E-cad) promoter polymorphism and hypermethylation in GCs. Specimens were taken from representative cancerous lesions and adjacent non-cancerous epithelia of 67 resected GCs. H. pylori was detected by real-time PCR of the cagA gene from non-neoplastic epithelium. E-cad promoter polymorphism and hypermethylation were determined by restriction fragment length polymorphism analysis and methylation-specific PCR, respectively. Expression of E-cad protein was determined by immunohistochemistry. H. pylori was found in 57% of patients with GC. H. pylori infection was more frequently found in tumors with the -160C/C genotype than those with the -160C/A and -160A/A genotypes (74% vs 47%, P = 0.02). H. pylori infection was associated with E-cad methylation in non-neoplastic epithelium; however, no significant difference in H. pylori was observed between methylated and unmethylated cancerous lesions. Patients with the -160C/C genotype might require H. pylori infection to promote the inactivation of CDH1, suggesting that H. pylori infection might affect GC in an initial stage because polymorphism is germ line. Mechanism of hypermethylation of CDH1 promoter in GC is complex, and H. pylori infection might affect it in an initial stage.World Journal of Gastroenterology 10/2005; 11(33):5174-9. · 2.47 Impact Factor -
Article: The influence of pacifier sucking on mesenteric blood flow in infants.
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ABSTRACT: Thirty-six neonates were randomly assigned to 2 groups of 18 neonates each. In the pacifier group, infants were given a pacifier before milk feeding. Newborns in the control group were fed without preprandial use of a pacifier. Doppler measurement of peak systolic velocity, end-diastolic velocity, and Pourcelot resistance index in the superior mesenteric artery was performed in both groups. Peak systolic and end-diastolic velocities were significantly increased after pacifier sucking in the preprandial stage. The resistance index decreased significantly after milk feeding but not after pacifier sucking. The feeding volume was not affected by preprandial pacifier sucking.Clinical Pediatrics 42(6):543-6. · 1.15 Impact Factor
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2006–2013
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National Defense Medical Center
- • Tri-Service General Hospital
- • Graduate Institute of Medical Sciences
Taipei, Taipei, Taiwan
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2008–2010
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Tri-Service General Hospital
Taipei, Taipei, Taiwan
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