Chenodeoxycholic Acid Enhances the Effect of Sorafenib in Inhibiting HepG2 Cell Growth Through EGFR/Stat3 Pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly invasive disease with a high mortality rate. Our previous study found that Chenodeoxycholic acid (CDCA) as an endogenous metabolite can enhance the anti-tumor effect. Sorafenib has limited overall efficacy as a first-line agent in HCC, and combined with CDCA may improve its efficacy. METHODS: HepG2 cells and Balb/c nude mice were used respectively for in vitro and in vivo experiments. Flow cytometry, Western blotting, HE and immunohistochemical staining and immunofluorescence were used to study the effects of CDCA combined with sorafenib on HepG2 cell growth and apoptosis-related proteins. Magnetic bead coupling, protein profiling and magnetic bead immunoprecipitation were used to find the targets of CDCA action. The effect of CDCA on EGFR/Stat3 signaling pathway was further verified by knocking down Stat3 and EGFR. Finally, fluorescence confocal, and molecular docking were used to study the binding site of CDCA to EGFR. RESULTS: In this study, we found that CDCA enhanced the effect of sorafenib in inhibiting the proliferation, migration and invasion of HepG2 cells. Magnetic bead immunoprecipitation and protein profiling revealed that CDCA may enhance the effect of sorafenib by affecting the EGFR/Stat3 signaling pathway. Further results from in vitro and in vivo gene knockdown experiments, confocal experiments and molecular docking showed that CDCA enhances the efficacy of sorafenib by binding to the extracellular structural domain of EGFR. CONCLUSION: This study reveals the mechanism that CDCA enhances the inhibitory effect of sorafenib on HepG2 cell growth in vitro and in vivo, providing a potential new combination strategy for the treatment of HCC.

Proteomic profiling identifies signatures associated with progression of precancerous gastric lesions and risk of early gastric cancer.

BACKGROUND: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management. METHODS: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280-473 days), and an independent case-control study from Beijing (n = 99). FINDINGS: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78-0.99) vs. 0.56 (0.36-0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins. INTERPRETATION: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention. FUNDING: The funders are listed in the Acknowledgement.

Primary duodenal tuberculosis misdiagnosed as tumor by imaging examination: A case report.

BACKGROUND: Primary duodenal tuberculosis is very rare. Due to a lack of specificity for its presenting symptoms, it is easily misdiagnosed clinically. Review of the few case reports and literature on the topic will help to improve the overall understanding of this disease and aid in differential diagnosis to improve patient outcome. CASE SUMMARY: A 71-year-old man with a 30-plus year history of bronchiectasis and bronchitis presented to the Gastroenterology Department of our hospital complaining of intermittent upper abdominal pain. Initial imaging examination revealed a duodenal space-occupying lesion; subsequent upper abdominal contrast-enhanced computed tomography indicated duodenal malignant tumor. Physical and laboratory examinations showed no obvious abnormalities. In order to confirm further the diagnosis, electronic endoscopy was performed and tissue biopsies were taken. Duodenal histopathology showed granuloma and necrosis. In-depth tuberculosis-related examination did not rule out tuberculosis, so we initiated treatment with anti-tuberculosis drugs. At 6 mo after the anti-tuberculosis drug course, there were no signs of new development of primary lesions by upper abdominal computed tomography, and no complications had manifested. CONCLUSION: This case emphasizes the importance of differential diagnosis for gastrointestinal diseases. Duodenal tuberculosis requires a systematic examination and physician awareness.

Cases Report the Cronkhite-Canada Syndrome: Improving the Prognosis.

Cronkhite-Canada syndrome (CCS) is a rare nongenetic polyposis syndrome first reported by Cronkhite and Canada in 1955. Up to the present time, the literature consists of ∼400 cases of CCS with the majority being reported from Japan although 49 cases have been described in China.CCS is characterized by diffuse polyposis of the digestive tract in association with ectodermal changes, such as onychomadesis, alopecia, and cutaneous hyperpigmentation. The principal symptoms of CCS are diarrhea, weight loss, abdominal pain, and other gastrointestinal complications, such as protein-losing enteropathy and malnutrition.It has been traditional to consider that CCS is associated with a poor prognosis. This paper describes a relatively mild case and reviews the literature, which more recently, suggests that it may be a more benign condition that might actually be reversible with treatment.There is some evidence that infection or disturbed immunity may be involved in the pathophysiology and that targeting such abnormalities could have therapeutic potential.A strong case could be made for establishing an international case registry for this disease so that the pathophysiology, treatment, and prognosis could become much better understood.