Entity

Time filter

Source Type


Lin W.-D.,Central Hospital of Taizhou | Zhuo X.-N.,Taishun Hospital of Traditional Chinese Medicine | Yang Z.-H.,Central Hospital of Taizhou
Chinese Journal of Cancer Prevention and Treatment | Year: 2012

To investigate the expression of Snai2 protein and E-cadherin protein and their relationship with lymph metastasis status in gastric cancer tissues. The expression of Snai2 protein and E-cadherin protein was detected by using immunohistochemical S-P method in 54 cases of gastric cancer and para-cancerous mucosa. The positive rate of E-cadherin immunostaining in gastric cancer was lower than that in adjacent tissues (33.33% vs 100.00%, P < 0.05), and the positive rate of Snai2 immunostaining in gastric cancer was higher than that in adjacent tissues (61.11% vs 20.37%, P < 0.05). The expression of Snai2 protein and the decreased expression of E-cadherin protein were both significantly related with the depth of tumor invasion and lymph node metastasis, P < 0.05. There was a significant negative correlation between expression of E-cadherin and expression of Snai2 in gastric cancer (r=-0.564, P < 0.01). Those that characterized by both positive expression of Snai2 and negative expression of E-cadherin among the cases with lymph node metastasis was significantly higher than that among the cases without lymph node metastasis (78.57% vs 26.92%, P < 0.01), both explessions were positively correlated (P < 0.01). The expression of Snai2 and the decreased expression of E-cadherin may play a important role in carcinogenesis and progression in gastric carcinoma. Snai2 may promote invasion and metastasis through inducing Epithelial-to-Mesenchymal Transition by inhibiting E-cadherin gene expression in gastric cancer. The combined detection of Snai2 and E-cadherin is valuable for evaluating lymph metastasis status in gastric cancer. Source


Chen J.,Kansas State University | McDowell C.,Kansas State University | Chen J.,Central Hospital of Taizhou
Journal of Molecular Biology | Year: 2013

The negative regulatory domain (NRD) of the p53 tumor suppressor is intrinsically disordered. It contains several posttranslational modification (PTM) sites that are important for regulation of p53 activity. Calcium-dependent binding of dimeric S100B(ββ) to p53-NRD blocks access to these PTM sites and disrupts the p53 tetramer to inhibit p53 activation. Previous nuclear magnetic resonance (NMR) structural studies have suggested that p53-NRD folds into a stable helix upon binding to S100B(ββ). Intriguingly, despite the well-converged and stably folded nature of the NMR structure ensemble, experimentally resolved intermolecular nuclear Overhauser enhancements (NOEs) are extremely weak; most have 5- to 6-Å upper bounds, and mainly involve the C-terminal segment of p53-NRD. Such a systematic lack of strong intermolecular NOEs could suggest that the p53/S100B(ββ) interface is more dynamic than currently believed. Indeed, extensive atomistic simulations in explicit solvent (with 1.0 μs total effective sampling) revealed large heterogeneity in the S100B(ββ)-bound conformation of p53-NRD. Helix unwinding at the C-terminus allows key hydrophobic residues (Leu383 and Phe385) to make more extensive intermolecular contacts, whereas the highly helical N-terminus displays substantial flexibility in packing with S100B(ββ). Importantly, the predicted heterogeneous ensemble as a whole is highly consistent with experimental intermolecular NOEs, although many conformational sub-states coexist and individual sub-states satisfy only subsets of the NOE restraints. Furthermore, the simulated ensemble provides similar shielding of key PTM sites to support p53 inhibition. This study not only provides new insights into the structural basis of the p53/S100B(ββ) recognition but also highlights the importance of recognizing dynamic complexes in structural studies of intrinsically disordered protein interactions. © 2013 Elsevier Ltd. All rights reserved. Source

Discover hidden collaborations