Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression.

The oncogenic role of WNT is well characterized. Wntless (WLS) (also known as GPR177, or Evi), a key modulator of WNT protein secretion, was recently found to be highly overexpressed in malignant astrocytomas. We hypothesized that this molecule may be aberrantly expressed in other cancers known to possess aberrant WNT signaling such as ovarian, gastric, and breast cancers. Immunohistochemical analysis using a TMA platform revealed WLS overexpression in a subset of ovarian, gastric, and breast tumors; this overexpression was associated with poorer clinical outcomes in gastric cancer (P=0.025). In addition, a strong correlation was observed between WLS expression and human epidermal growth factor receptor 2 (HER2) overexpression. Indeed, 100% of HER2-positive intestinal gastric carcinomas, 100% of HER2-positive serous ovarian carcinomas, and 64% of HER2-positive breast carcinomas coexpressed WLS protein. Although HER2 protein expression or gene amplification is an established predictive biomarker for trastuzumab response in breast and gastric cancers, a significant proportion of HER2-positive tumors display resistance to trastuzumab, which may be in part explainable by a possible mechanistic link between WLS and HER2.

Wnt pathway inhibitors are upregulated in XLH dental pulp cells in response to odontogenic differentiation / 国际口腔科学杂志·英文版

X-linked hypophosphatemia (XLH) represents the most common form of familial hypophosphatemia. Although significant advances have been made in the treatment of bone pathology, patients undergoing therapy continue to experience significantly decreased oral health-related quality of life. The following study addresses this persistent oral disease by further investigating the effect of DMP1 expression on the differentiation of XLH dental pulp cells. Dental pulp cells were isolated from the third molars of XLH and healthy controls and stable transduction of full-length human DMP1 were achieved. RNA sequencing was performed to evaluate the genetic changes following the induction of odontogenic differentiation. RNAseq data shows the upregulation of inhibitors of the canonical Wnt pathway in XLH cells, while constitutive expression of full-length DMP1 in XLH cells reversed this effect during odontogenic differentiation. These results imply that inhibition of the canonical Wnt pathway may contribute to the pathophysiology of XLH and suggest a new therapeutic strategy for the management of oral disease.

Chiral Separation by Capillary Electrochromatography with PhysicallyAdsorbed Stationary Phase and Dynamically Modified Stationary Phase / 分析化学

A novel mode of chiral separation in electrochromatography (CEC) with dynamically modified stationary phase (DMS-CEC) was presented. The capillary column was packed with strong anionic exchange stationary phase, the sulfated β-cyclodextrin (S-CD), which was added in the mobile phase, dynamically adsorbed to the packing surface and a new layer of chiral stationary phase was formed. The separation of enantiomer was based on their different interaction with the new stationary phase. The enantionmers of tryptophan, atropine and verapamil were successfully separated in this system with resolution of 2.06, 10.1 and 1.96, and the column effeciency for the enantiomers were varied from 85000 plates/m to 412000 plates/m. The relative standard deviation (RSD) of void time and the tryptophan enantiomers′ migration time for 17 consecutive runs were 0.5%, 0.6% and 0.7%, respectively. Enantiomer separation by capillary electrochromatography with adsorbed bovine serum albumin (BSA) and sulfated cyclodextrin (S-CD) as chiral stationary phases were also studied. The resolution for tryptophan enantiomers in the two systems were 3.86 and 2.97, respectively. It was found that the superiority of DMS-CEC over the adsorbed S-CD column CEC was that better repeatability could be obtained in DMS-CEC.