Shih-Chang Chuang

Decreased microRNA-221 is associated with high levels of TNF-α in human adipose tissue-derived mesenchymal stem cells from obese woman.

Aim: The present study aimed to investigate the regulation and involvement of miR-221 in the differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs). The relationships between miR-221 and pro-inflammatory markers and adipokines were also explored. Methods: Eight adipose tissues were obtained from four obese (mean body mass index (BMI) =31.7 kg/m2) and four lean (mean BMI= 21.5 kg/m2) women. hASCs were induced to differentiate, and the related gene expression were measured in the hASC-differentiated adipocytes using real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR). Results: During adipogenesis, miR-221 was significantly down-regulated; furthermore, miR-221 levels were lower in hASC-differentiated adipocytes from obese subjects than in the corresponding adipocytes from lean subjects. Higher TNF-α mRNA levels were associated with lower levels of miR-221. In addition, the miR-221 levels in the adipocytes were inversely correlated with BMI. Conclusion: Our results support the link between miR-221 and obesity development as well as obesity related inflammatory status.

Multiple genetic polymorphisms in the prediction of clinical outcome of metastatic colorectal cancer patients treated with first-line FOLFOX-4 chemotherapy.

Objectives The objective of the study is to investigate whether multiple chemotherapeutic agent-related genetic polymorphisms are associated with the clinical outcomes of Taiwanese metastatic colorectal cancers (mCRC) patients treated with the first-line FOLFOX-4 chemotherapy. Methods Consecutive mCRC patients were prospectively enrolled into this study. Peripheral blood samples were used for genotyping of polymorphisms in MTHFR, DPD, GSTP1, MDR1, TYMS, ERCC1, XRCC1, and ERCC2 genes by polymerase chain reaction–restriction fragment length polymorphism technique and DNA sequencing. The primary end point of the study was to investigate the association of each genetic polymorphism with progression-free survival and overall survival (OS). Results Favorable genotypes from polymorphisms in ERCC1 codon 118C/C [hazard ratio (HR)=0.061, 95% confidence interval (CI): 0.014–0.274, P<0.001] and XRCC1 codon 399G/G (HR=0.306, 95% CI: 0.103–0.905, P=0.032) that are associated with progression-free survival were identified. Furthermore, ERCC1 codon 118C/C (HR=0.065, 95% CI: 0.011–0.377, P=0.002) and XRCC1 codon 399G/G (HR=0.152, 95% CI: 0.041–0.568, P=0.005) were significantly associated with favorable OS. Combining ERCC1 and XRCC1 genetic polymorphisms, patients with both favorable genotypes of ERCC1 codon 118C/C and XRCC1 codon 399G/G were associated with the better OS than those with one or without any favorable genotypes (P<0.001). Conclusion The genetic polymorphisms of ERCC1 and XRCC1 may be useful in predicting clinical outcome in Taiwanese mCRC patients treated with FOLFOX-4. However, further prospective studies will be needed for the potential clinical implication.

Immunohistochemical Study of DPC4 and p53 Proteins in Gallbladder and Bile Duct Cancers

Gallbladder and bile duct carcinomas belong to the family of biliary tract tumors, but they demonstrate different clinical behavior. We evaluated a series of biliary tract carcinomas to determine whether they also had genotypic differences by analysis of the tumor suppressor genes DPC4 and p53. Twenty-one gallbladder cancers, 20 intrahepatic bile duct carcinomas, and 10 extrahepatic bile duct carcinomas were retrieved from the surgical pathology files of Kaohsiung Medical University Hospital. Sections were immunostained with monoclonal antibodies to the DPC4 and P53 proteins. Statistical differences between gallbladder cancer and bile duct carcinomas were determined using ?2 analysis or the Fisher’s exact test, when appropriate. Two of the 21 gallbladder cancers (9.5%), 7 of the 20 intrahepatic bile duct carcinomas (35%), and five of the 10 extrahepatic bile duct carcinomas (50%) were negatively labeled for DPC4. The differences were significant between gallbladder carcinoma and both intrahepatic bile duct carcinomas (p = 0.023) and extrahepatic bile duct carcinomas (p = 0.012). A higher frequency of P53 overexpression was found in gallbladder cancers (61.9%) than in intrahepatic bile duct carcinomas (26.3%) (p = 0.024). This study suggests that the DPC4 gene may play a limited role in gallbladder carcinoma; however, p53 gene mutation is more frequently found in gallbladder cancers. In contrast, DPC4 deletion may be more common in bile duct carcinomas, especially in those arising from the extrahepatic bile duct. These findings support the concept that gallbladder and bile duct carcinomas are different tumors with differing etiologies and tumorigenesis.

The effect of preoperative transarterial chemoembolization of resectable hepatocellular carcinoma on clinical and economic outcomes

Hepatocellular carcinoma (HCC) is one of the most malignant cancers in the world. The effect of preoperative transarterial chemoembolization (TACE) for resectable HCC is still controversial and cost‐associated treatments are unknown.

Mucin genes in gallstone disease

Gallstone disease is a complex disorder that can be caused by environmental influences, common genetic factors and their interactions. Three major pathogenic abnormalities are considered to involve in gallstone formation: cholesterol supersaturation in bile, precipitation and nucleation of excess cholesterol, and gallbladder hypomotility, while, mucin takes part in the cholesterol nucleation process. Up to date, more than 20 mucin genes have been reported, 9 of them are identified at the mRNA and/or protein level in native gallbladder and its associated diseases. In the gallbladder, mucin is essential for best protection against detergent effect of high concentration of bile acids. Over the past decade, the properties, expressions and functions of the gallbladder mucins are delineated in animal and human studies. Alteration expressions of mucins are thought to response during the pathogenesis of gallstone formation. Moreover, recent genetic association study demonstrated mucin gene polymorphisms may also influence susceptibility to gallstone disease. This review is not to provide a complete coverage of all the aspects of mucin glycoproteins, but focus on the role and expression of mucins involve in the regulation of cholelithogenesis.

Apelin gene polymorphism influences apelin expression and obesity phenotypes in Chinese women

BACKGROUND Apelin, which is a newly identified adipokine, is related to obesity and insulin resistance. A positive correlation between plasma apelin concentrations and obesity traits was reported. OBJECTIVE We tested associations between apelin gene (APLN) polymorphisms, BMI, and waist circumference (WC) and compared APLN expression levels in cells of different genotypes. DESIGN Four tagging single nucleotide polymorphisms (SNPs) and one promoter SNP were genotyped in 1627 Chinese subjects. Because APLN was located on the chromosome X, statistical analyses were conducted in a sex-specific manner. Adipocytes of different genotypes were derived from the omental fat tissue of 10 women. We treated the primary adipocytes with high glucose plus insulin because of a close relation between insulin resistance and obesity. RESULTS SNP rs3115757 was significantly associated with BMI and WC in women. Compared with the CG or GG genotype, the CC genotype had an OR of 2.07 (95% CI: 1.23, 3.49) for having a high WC (P = 0.006) and an OR of 2.29 (95% CI: 1.25, 4.19) for having a BMI (in kg/m(2)) ≥27 (P = 0.007). None of the SNPs was associated with BMI or WC in men. In adipocytes that carried the CC genotype of rs3115757, APLN messenger RNA levels and protein concentrations were higher in cells treated with high glucose plus insulin than in those with normal glucose. There was no difference between the 2 conditions in adipocytes of the CG or GG genotype. CONCLUSION Both association and functional studies suggested that APLN polymorphisms were associated with risks of obesity phenotypes.

Genetics of Gallstone Disease

Gallstone disease (GSD) is one of the most common biliary tract disorders worldwide. The prevalence, however, varies from 5.9-21.9% in Western society to 3.1-10.7% in Asia. Most gallstones (75%) are silent. Approximately half of symptomatic gallstone carriers experience a second episode of biliary pain within 1 year. These individuals are at increased risk of developing acute cholecystitis, acute cholangitis, and biliary pancreatitis. As can be expected, these complications burden health care systems because of their invasive nature and surgical cost. Factors that contribute to gallstone formation include supersaturation of cholesterol in bile, gallbladder hypomotility, destabilization of bile by kinetic protein factors, and abnormal mucins. Epidemiologic studies have implicated multiple environmental factors and some common genetic elements in gallstone formation. Genetic factors that influence gallstone formation have been elaborated from linkage studies of twins, families, and ethnicities. Accumulating evidence suggests that genetic factors play a role in GSD.

Hypertriglyceridemia-associated Acute Pancreatitis with Chylous Ascites in Pregnancy

Both cholesterol and triglyceride levels in serum increase progressively during pregnancy. Hypertriglyceridemia is a well-recognized cause of acute pancreatitis, while pancreatitis-associated chylous ascites has rarely been reported. We report a 28-year-old female with coexistence of hypertriglyceridemia, acute pancreatitis, and chylous ascites during pregnancy. After emergency cesarean section, she was treated with nil per os, intravenous hydration, antibiotics, and analgesics as required. Due to the development of positive peritonitis 5 days later, an exploratory laparotomy was performed. Surgical interventions included pancreatic necrosectomy, right hemicolectomy and ileostomy, cholecystostomy, gastrostomy, and feeding jejunostomy. Postoperative treatment included antibiotics, total parenteral nutrition, and then low-fat diet with medium-chain triglyceride supplementation. She was discharged on the 43rd day after surgery and was free of symptoms during 6 months of follow-up. Ileocolostomy was performed 6 months after discharge. Fasting lipid profile should be regularly monitored during pregnancy due to the association of hypertriglyceridemia with development of acute pancreatitis in the mother.

Preoperative transarterial chemoembolization and resection for hepatocellular carcinoma: A nationwide Taiwan database analysis of long‐term outcome predictors

To explore long‐term predictors of outcome after TACE and resection in a population of patients with hepatocellular carcinoma (HCC).

Multiple mucin genes polymorphisms are associated with gallstone disease in Chinese men

BACKGROUND Gallstone is a complex disease caused by multiple environmental and genetic factors. One of these is mucin glycoproteins. This case-control study aimed to investigate the association between single nucleotide polymorphisms (SNPs) at the MUC1-4 genes and gallstone. METHODS The study included 475 cases and 941 controls. Eight tagging SNPs were selected: one at MUC1, two at MUC2, and five at MUC4. There was no available tagging SNP at MUC3. Genetic effects were initially evaluated by multivariate logistic regression. The combined effects from multiple genes were further evaluated, as well as the sex-specific effect. Permutation was used to correct for multiple testing. RESULTS The genotypes were all in Hardy-Weinberg equilibrium. SNP rs7396030 at MUC2 yielded a p value of 0.03. Further sex-specific analysis showed significance solely with male subjects (p=0.005). Similarly, SNP rs4072037 at MUC1 was only significant (p=0.035) in males. The permutation empirical p values were 0.005 for rs7396030 and 0.02 for rs4072037. For males, the combined genetic effect yielded an OR of 4.68 (p=0.0008). CONCLUSIONS The SNPs at MUC1 and MUC2 are significantly associated with gallstone in men but not in women. These genes can work jointly to further increase susceptibility to gallstone in a Chinese population.