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The aim of this study was to investigate the role of immunohistochemical (IHC) expression of p53 and other potential clinical parameters as prognostic markers for predicting neoplastic progression in Barrett oesophagus (BE) patients diagnosed as indefinite for dysplasia (IND). The study included patients with established BE of any extent who had a diagnosis of IND accompanied by concurrent p53 immunohistochemistry (IHC) stain at the index endoscopic procedure and at least one follow‐up examination between 2000 and 2021. Correlation between disease progression from IND to higher‐grade dysplasia [low‐grade dysplasia (LGD), high‐grade dysplasia (HGD) and oesophageal adenocarcinoma (EAC)] and clinicopathological parameters were analysed. A total of 149 patients (99 males; mean age 63.3 ± 10.0 years, range = 35–89) were included in the final analysis. Median follow‐up was 37.1 months [interquartile range (IQR) = 20.5–59.1 months]. Progression rates from IND to LGD and HGD were 12.1% (18 of 149) and 2.7% (four of 149), respectively. On multivariate analysis, the number of IND diagnoses was significantly associated with progression to both LGD and HGD (P = 0.016 and P < 0.001, respectively). Cox regression analysis showed that aberrant p53 expression was significantly associated with progression to LGD [hazard ratio (HR) = 4.87, 95% confidence interval (CI) = 1.91–12.45, P = 0.001] and HGD (HR = 21.81, 95% CI = 1.88–253.70, P = 0.014). Kaplan–Meier survival analysis also demonstrated that aberrant p53 expression was significantly associated with progression to LGD (P < 0.001) and HGD (P = 0.001). Our results suggest that frequency of IND diagnoses and status of p53 expression can help to stratify risk of neoplastic progression in BE patients with IND. [ABSTRACT FROM AUTHOR]

Abetalipoproteinemia (ABL) is a rare Mendelian disorder of lipid metabolism due to genetic deficiency in microsomal triglyceride transfer protein (MTP). It is associated with defects in MTP-mediated lipid transfer onto apolipoprotein B (APOB) and impaired secretion of APOB-containing lipoproteins. Recently, MTP was shown to regulate the CD1 family of lipid antigen-presenting molecules, but little is known about immune function in ABL patients. Here, we have shown that ABL is characterized by immune defects affecting presentation of self and microbial lipid antigens by group 1 (CD1a, CD1b, CD1c) and group 2 (CD1d) CD1 molecules. In dendritic cells isolated from ABL patients, MTP deficiency was associated with increased proteasomal degradation of group 1 CD1 molecules. Although CD1d escaped degradation, it was unable to load antigens and exhibited functional defects similar to those affecting the group 1 CD1 molecules. The reduction in CD1 function resulted in impaired activation of CD1-restricted T and invariant natural killer T (iNKT) cells and reduced numbers and phenotypic alterations of iNKT cells consistent with central and peripheral CD1 defects in vivo. These data highlight MTP as a unique regulator of human metabolic and immune pathways and reveal that ABL is not only a disorder of lipid metabolism but also an immune disease involving CD1., Introduction Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by mutations in the gene encoding microsomal triglyceride transfer protein (MTP) (1). MTP is an ER-resident protein that transfers triglycerides, [...]

Macrophages play a central role in the normal healing process after tissue injury and the host response to foreign objects such as biomaterials. The process leading to macrophage adhesion and activation on protein-adsorbed substrates is complex and unresolved. While the use of primary cells offers clinical relevancy, macrophage cell lines offer unique advantages such as availability and relatively homogeneous phenotype as models to probe the molecular mechanism of cell–surface interaction. Our goal was to better characterize the effect of the culture condition and surface-associated ligands on the extent of U937 adhesion. Tyrosine phosphorylation of intracellular proteins was surveyed as a basis to seek a greater understanding of the molecular mechanism involved in mediating U937 adhesion on various ligand-adsorbed surfaces. U937 viability and adhesion on tissue culture polystyrene (TCPS) increased with (i) increasing serum level, (ii) decreasing tyrosine phosphorylation inhibitor AG18 concentration, or (iii) increasing culture time. The adsorption of various adhesion proteins such as fibronectin and peptide ligands (i.e., RGD, PHSRN) on TCPS did not significantly increase the adherent density of U937 when compared with albumin and PBS ligand controls. However, ligand identity and the presence of phorbol myristate acetate dramatically affected the extent (i.e., increase or decrease) and the identity (i.e., molecular weight) of phosphotyrosine proteins in adherent U937 in a time-dependent manner. The extent and identity of phosphotyrosine proteins did not exhibit a clear AG18 dose dependency, rather the level of tyrosine phosphorylation for a distinct group of proteins was either increased or decreased for a given AG18 concentration. [Copyright &y& Elsevier]

Objective: To study the relationship between sensitivity to 5-FU and the status of a panel of microsatellite loci in three human colon cancer cell lines., Methods: Cell viability in several concentrations of 5-FU was assessed by the MTT test. Expression of hMSH2 and hMLH1 in LoVo, SW480 and SW1116 cells were analyzed by immunocytochemical staining.Ten mononucleotide and dinucleotide microsatellite loci were analyzed by the PCR-SSLP-silver staining method., Results: By MTT assay, it showed that LoVo cells were more sensitive than SW480 and SW1116 cells (0.8 micromol/L,2.2 micromol/L and 1.9 micromol/L, respectively, P < 0.05). By immunocytochemical staining, hMSH2 was expressed in SW480 and SW1116 cells but not in LoVo cells, while hMLH1 was positive in all three cell lines. The PCR-SSLP-silver staining of 10 microsatellite loci revealed that LoVo cells had a different pattern of electrophoretic bands compared with SW480 and SW1116 cells, manifesting both additions and band-shifts., Conclusion: Together with hMSH2 and hMLH1, the status of a panel of microsatellite loci may be used as convenient predictors for drug-optimization or prognosis-assessment in colorectal cancer patients before chemotherapy.