Proteome analysis and tissue array for profiling protein markers associated with type B thymoma subclassification / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The prognostic relevance of World Health Organization (WHO) subtypes within type B thymomas is still controversial. Understanding of the molecular characteristics of the different histologic types of thymomas will provide meaningful information for diagnosis and therapeutic management in type B thymoma.</p><p><b>METHODS</b>Proteins extracted from twelve type B thymoma tissue specimens (six type B1 and six type B2) were analyzed by two-dimensional electrophoresis (2-DE) coupled with MALDI-TOF-MS. Differentially expressed proteins were then assayed in sixty-nine type B thymoma tissues (including B1, B2 and B3) by tissue array analysis with immunohistochemistry staining. The relationship of their expression with clinicopathological parameters, such as tumor stage or WHO classification, was estimated by Spearman's Rank Correlation Test.</p><p><b>RESULTS</b>Sixteen differentially expressed proteins between type B1 and B2 thymoma tissues were identified. The differential levels of ezrin and glutathione S-transferase pi (GSTP1) were validated using immunohistochemistry staining. A statistically significant difference was observed in the positive rate of ezrin expression between type B1 thymoma and type B3 thymoma (Z = -2.963, P < 0.01). Ezrin showed a tendency to be expressed in higher classification tumors from type B1 to B3. A statistical analysis demonstrated that type B2 and B3 tumors had significantly higher positive expression of GSTP1 than the B1 group (type B2 vs. B1: Z = -2.582, P = 0.01; type B3 vs. B1: Z = -4.012, P ≤ 0.001). The results also showed a strong correlation between GSTP1 and WHO type staging of B1 to B3 tumors (Spearman's correlation coefficient: 0.633, P ≤ 0.001). Statistical analysis showed that there was close correlation between GSTP1 and ezrin expression with the clinical stage (Spearman's correlation coefficients, ezrin: 0.481, P < 0.05; GSTP1: 0.484, P < 0.01).</p><p><b>CONCLUSIONS</b>Differentially expressed proteins between type B1 and B2 thymoma tissues were analyzed by comparative proteomic analysis. The techniques of proteomic analysis and tissue array provide a potential tool for screening of key molecules in type B thymoma histological sub-classifications. The statistical analysis of ezrin and GSTP1 expression by immunohistochemistry, especially GSTP1, may be a useful approach for type B thymoma classification.</p>

Establishing a paclitaxel-resistant BNX mouse model of human lung cancer / 第二军医大学学报

Objective To establish a paclitaxel-resistant BNX mouse model of human lung carcinoma, so as to provide evidences for studying chemoresistant mechanism and for screening of the reversal drugs in vivo. Methods The resistant model was produced by repeating a crossover subcutaneous injection of human lung cancer A549-Taxol cells and transplantation of tumor fragment into immune deficiency mice, so as to increase the tumor forming rate of A549-Taxol cells and shorten the tumor forming time. The expressions of GST-k, P-gpl70 and MMP-7 were examined by immunohistochemical staining. The chemosensitivities of tumor cells to Taxol were tested and IC50 was measured by MTT. Results Tumor niduses were observed subcutaneously in SCID mice 4 months after injection of A549-Taxol cells, and then the tumor fragment or the tumor cells suspension were injected to SCID mice again. After 3 times of crossover injection, the tumor cells grew faster and tumor niduses were formed 2 months after injection. The same procedure was done in BNX mice. Finally, we achieved a successful rate of 80% in tumor implantation in BNX mice; the tumor niduses could be formed in 3 weeks. P-gpl70, GST-* and MMP-7 expression was higher in the experiment group than that in the A549 control group. IC50 value of paclitaxel for A549-Taxol cells was 520 folds that of A549 cells. Conclusion We have successfully established paclitaxel-resistant lung carcinoma model in mice, which provides a new platform for further study on chemoresistant reversal strategy and individualized clinical treatment.