Background/AimsCombination 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.MethodsHT-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.ResultsTreatment 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.ConclusionCombination therapy using PT and TRAIL might offer an effetive strategy to overcome TRAIL resistance in certain CRC cells.
Afferent loop syndrome following pylorus preserving pancreaticoduodenectomy (PPPD) is a rare complication and it's usually caused by malignant obstruction, radiation enteritis, or markedly angulated afferent loop. Early determination of the etiology is quite important because the choice of treatment modality depends on the causal factor. We here in report a rare case of recurrent cholangitis caused by stenosis of afferent loop following PPPD misdiagnosed as the stenosis of hepaticojejunostomy site.
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