RESUMEN
BACKGROUND/AIMS: Combination therapy utilizing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in conjunction with other anticancer agents, is a promising strategy to overcome TRAIL resistance in malignant cells. Recently, parthenolide (PT) has proved to be a promising anticancer agent, and several studies have explored its use in combination therapy. Here, we investigated the molecular mechanisms by which PT sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis. METHODS: HT-29 cells (TRAIL-resistant) were treated with PT and/or TRAIL for 24 hours. The inhibitory effect on proliferation was detected using the 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Annexin V staining, cell cycle analysis, and Hoechst 33258 staining were used to assess apoptotic cell death. Activation of an apoptotic pathway was confirmed by Western blot. RESULTS: Treatment with TRAIL alone inhibited the proliferation of HCT 116 cells in a dose-dependent manner, whereas proliferation was not affected in HT-29 cells. Combination PT and TRAIL treatment significantly inhibited cell growth and induced apoptosis of HT-29 cells. We observed that the synergistic effect was associated with misregulation of B-cell lymphoma 2 (Bcl-2) family members, release of cytochrome C to the cytosol, activation of caspases, and increased levels of p53. CONCLUSION: Combination therapy using PT and TRAIL might offer an effetive strategy to overcome TRAIL resistance in certain CRC cells.
RESUMEN
BACKGROUND/AIMS: The frequency of symptomatic acute HAV infections in adulthood are increasing in Korea. This study analyzes the clinical severity in patients with acute HAV infection and investigates risk factors associated with three severe complications: prolonged cholestasis, acute kidney injury, and acute liver failure. METHODS: We performed a retrospective analysis of 726 patients diagnosed from January 2006 to December 2010 at three tertiary hospitals in Jeonbuk Province, Republic of Korea with acute HAV infection. RESULTS: In the group of 726 patients, the mean age was 30.3 years, 426 (58.6%) were male, and 34 (4.7%) were HBsAg positive. Severe complications from acute HAV infection occurred as follows: prolonged cholestasis in 33 (4.6%), acute kidney injury in 17 (2.3%), and acute liver failure in 16 (2.2%). Through multivariate analysis, age ≥40 years (OR 2.63, p=0.024) and peak PT (INR) ≥1.5 (OR 5.81, p=0.035) were found to be significant risk factors for prolonged cholestasis. Age ≥40 years (OR 5.24, p=0.002) and female gender (OR 3.11, p=0.036) were significant risk factors for acute kidney injury. Age ≥40 years (OR 6.91, p=0.002), HBsAg positivity (OR 5.02, p=0.049), and peak total bilirubin (OR 1.11, p=0.001) were significant risk factors for acute liver failure. CONCLUSIONS: Age ≥40 years, female gender, HBsAg positivity, peak PT (INR) ≥1.5, and peak total bilirubin were significant risk factors for severe complications in acute HAV infections.