ABSTRACT: Guggulsterone is a dietary plant sterone possessing therapeutic potential against cancers. However, the antitumor effect of this natural compound on pancreatic cancer has not been determined yet. This study was designed to investigate the therapeutic efficacy of guggulsterone in pancreatic cancer.
In this study, we examined the effect of guggulsterone on cell proliferation and apoptosis in pancreatic cancer cell lines, and then, we investigated the mechanisms responsible for the effect of guggulsterone. Finally, we investigated whether the combination of guggulsterone and gemcitabine had an additional therapeutic effect compared to gemcitabine single regimen in pancreatic cancer cell lines (in vitro) and in a xenograft model using nude mice (in vivo).
In vitro, the combination treatment resulted in more growth inhibition and apoptosis through the down-regulation of nuclear factor κB activity with suppression of Akt and BcL-2 and through the activation of c-Jun NH(2)-terminal kinase and Bax in pancreatic cancer cell lines. In vivo, the combination therapy augmented tumor growth inhibition through the same mechanisms in tumor tissue.
The combination of guggulsterone to gemcitabine enhanced antitumor efficacy through apoptosis induction by suppressing Akt and nuclear factor κB activity and by modulating apoptosis-related protein expression in pancreatic cancer.
Pancreas 04/2012; 41(7):1048-57. · 2.39 Impact Factor
ABSTRACT: Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCAC) are often confused with other intrahepatic cystic diseases.
The aims of this study were to investigate predictive factors of biliary cystic tumor (BCT) and clinical characteristic of BCAC.
We retrospectively reviewed preoperative diagnoses, overall characteristics and postoperative outcome of 20 BCTs and 19 cystadenoma-mimicking simple cysts that were pathologically confirmed.
Comparing with atypical simple cysts, symptoms, left-lobe cyst, thick wall, septation, mural nodule, bile duct dilatation and an increase of serum alkaline phosphatase were associated with BCTs. However, on multivariate analysis, mural nodule, left-lobe cyst, and an increase of serum alkaline phosphatase were significantly frequent in BCTs with odds ratios of 75.5, 13.8, and 33.0, respectively. Among the 20 BCTs, seven BCACs were diagnosed. The characteristics of BCACs were mural nodule (P<0.01), intrahepatic cyst debris (P<0.01), and bile duct dilation (P=0.04). Cystic fluid analysis provided no significant differences between BCT and simple cyst. After fine needle aspiration cytology of BCTs, all except one BCAC with atypical cell showed nonspecific findings. After complete surgical excision (97.4% of patients), only one patient with BCAC had recurrence during 29 months of follow-up period.
In hepatic cysts with mural nodule, left-lobe cyst or increment of serum alkaline phosphatase seem to be indicative of BCTs in the diagnosis of suspicious hepatic cyst. Intracystic debris, bile duct dilation, and mural nodule may be suggestive clinical features of malignancy in BCTs.
European journal of gastroenterology & hepatology 03/2010; 22(8):989-96. · 1.66 Impact Factor
ABSTRACT: The conformability of uncovered self-expandable metal stents (SEMSs) plays an important role in maintaining stent patency. However, whether increased conformability can prolong the duration of SEMS patency remains to be proved.
The aim of this study was to examine the efficacy and complication rates of the Niti-D biliary uncovered metal stent (NDS), which is more conformable than the uncovered Wallstent.
Nonrandomized, retrospective study.
Tertiary-care academic medical center.
From March 2005 to July 2007, 101 patients received an NDS (41 cases) or a Wallstent (60 cases) for malignant biliary obstruction.
Stent occlusion occurred in 11 patients (26.8%) with the NDS and 17 patients (28.3%) with the Wallstent. The median duration of stent patency tended to be longer for the NDS group (153 days) than for the Wallstent group (124 days); however, the difference was not statistically significant (P = .204). The median duration of overall survival of patients was 160 days for the NDS and 148 days for the Wallstent. The subgroup analysis showed that 27 patients had hilar obstruction (NDS 13, Wallstent 14). The median duration of stent patency was 249 days for the NDS group and 76 days for the Wallstent group; this difference was statistically significant (P = .006). The complications included pancreatitis in 3 NDS cases and 5 Wallstent cases.
The absence of prospective randomized recruitment.
The results of this study showed no significant differences between the NDS and the Wallstent for the palliative endoscopic management of malignant biliary obstruction. There were no significant differences in patency, complication rates, and patient survival between the more conformable NDS and the conventional Wallstent. However, the NDS, which has good conformability, may be preferred for hilar obstruction.
Gastrointestinal endoscopy 08/2009; 70(1):45-51. · 6.71 Impact Factor
ABSTRACT: Endoscopic intervention is considered to be the primary treatment for biliary stricture after adult living donor liver transplantation (LDLT) with duct-to-duct biliary reconstruction. The aim of this study was to investigate the risk factors of biliary stricture and the clinical outcomes and predictors of failure after endoscopic retrograde cholangiography with balloon dilation (ERC-D). We enrolled 239 adult patients who underwent LDLT between 2000 and 2006. Sixty-eight patients (28.4%) developed biliary stricture. Twenty-nine patients with anastomotic biliary stricture were treated with ERC-D and stenting. We retrospectively analyzed the risk factors of biliary stricture and the clinical outcomes of ERC-D. The median follow-up period was 31 months. The risk factors of biliary stricture on multiple logistic regression analysis were a graft with multiple bile ducts, a previous history of bile leakage, and hepatic artery stenosis. The overall success rate of ERC-D was 64.5%. On simple logistic regression, the failure of primary ERC-D was associated with late biliary stricture over 24 weeks and more than 8 weeks between a 2-fold increase of serum alkaline phosphatase from the stable level and ERC-D, even though these were not statistically significant on multiple logistic regression. The relapse rate of stricture after successful ERC-D was 30%. The duration of stenting in the recurrence group was shorter than that in the nonrecurrence group (11.8 +/- 5.03 versus 29.0 +/- 11.6 weeks, P = 0.004). ERC-D is effective for the management of anastomotic biliary stricture. However, the failure rate of primary ERC-D may be high in patients with late onset and delayed diagnosis of biliary stricture. The recurrence seems to occur frequently in patients with a short duration of stenting.
Liver Transplantation 05/2009; 15(4):369-80. · 3.39 Impact Factor
ABSTRACT: Since pancreatic endocrine tumors (PET) are rare and heterogeneous diseases, their survival and prognosis are not well known. Due to recent advances in CT/MRI technology, incidentalomas of the pancreas are detected with increasing frequency. This study presents results of clinical manifestations of PET and predictive factors associated with survival.
From year 1990 through 2006, medical records of 98 patients (56 men, 42 women) who were diagnosed as PET pathologically at Seoul National University Hospital were reviewed retrospectively.
Ages ranged from 17 to 76 years (mean 51.6+/-1.3 years) with a mean follow-up of 3.6+/-0.4 years (range 0-10.1 years). Overall 5-year survival rate was 68.1%, and 5-year survival rate of the patients who had distant metastases at initial diagnosis was 43.9%. Functioning tumors [hazard ratio (HR) 0.229, 95% confidence interval (CI) 0.056-0.943, p=0.041] and lymph node or liver metastases (HR 5.537, 95% CI 2.106-14.555, p<0.001) were the significant prognostic factors associated with survival rate. However, tumor size and pathology showed no significant association with survival.
Because small and pathologically benign nature do not predict good prognosis in PET, aggressive treatment such as curative resection would be considered initially even in the case of incidental PET.
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 09/2008; 52(3):171-8.