Serum Anti-Gal-3 Autoantibody is a Predictive Marker of the Efficacy of Platinum-Based Chemotherapy against Pulmonary Adenocarcinoma

Background: Identification of predictive markers for the efficacy of platinum-based chemotherapy is necessary to improve the quality of the life of cancer patients. Materials and Methods: We detected proteins recognized by autoantibodies in pretreated sera from patients with lung adenocarcinoma (AC) evaluated as showing progressive disease (PD) or a partial response (PR) after cisplatin-based chemotherapy by proteomic analysis. Then, the levels of the candidate autoantibodies in the pretreated serum were validated by dot-blot analysis for 22 AC patients who received platinum-based chemotherapy, and the expression of identified proteins was immunohistochemically analyzed in 40 AC biopsy specimens. Results: An autoantibody against galectin-3 (Gal-3) was detected in pretreated sera from an AC patient with PD. Serum IgG levels of anti-Gal-3 autoantibody were significantly higher in patients evaluated with PD than in those with PR and stable disease (SD) (p = 0.0084). Furthermore, pretreated biopsy specimens taken from patients evaluated as showing PD following platinumbased chemotherapy showed a tendency to have a higher positive rate of Gal-3 than those with PR and SD (p = 0.0601). Conclusions: These results suggest that serum IgG levels of anti-Gal-3 autoantibody may be useful to predict the efficacy of platinum-based chemotherapy for patients with lung AC.     

Gene silencing of β-catenin by RNAi inhibits proliferation of human esophageal cancer cells by inducing G0/G1 cell cycle arrest

Objectives: The aim of the present study was to explore mechanisms underlying the effects of down-regulatingß-catenin expression on esophageal carcinoma (EC) cells. Methods: Cell cycle distribution and apoptosis weredetermined using flow cytometry and annexin V apoptosis assay, respectively. Transmission electron microscopy(TEM) was used to examine changes in ultrastructure, while expression of cyclin D1 protein and mRNA wasdetected by western blot and real-time PCR. Proliferating cell nuclear antigen (PCNA) and extracellularsignal-regulated kinase (ERK) 1⁄2 were evaluated by Western blot analysis. PCNA labeling index (LI) wasdetermined by immunocytochemistry. Results: Compared with pGen-3-con transfected and Eca-109 cells,the percentage of G0/G1-phase pGen-3-CTNNB1 transfected cells was obviously increased (P<0.05), with nosignificant difference among the three groups with regard to apoptosis (P>0.05). pGen-3-CTNNB1 transfectedcells exhibited obvious decrease in cyclin D1 mRNA and protein expression (P<0.05) and the ultrastructure ofEca-109 cells underwent a significant change after being transfected with pGen-3-CTNNB1, suggesting thatdown-regulating β-catenin expression can promote the differentiation and maturation. The expression of PCNAand the ERKI/2 phosphorylation state were also down-regulated in pGen-3-CTNNB1 transfected cells (P<0.05).At the same time, the PCNA labeling index was decreased accordingly (P<0.05). Conclusion: Inhibition of ECEca-109 cellproliferation by down-regulating ß-catenin expression could improve cell ultrastructure by mediatingblockade in G0/G1 through inhibiting cyclin D1, PCNA and the MAPK pathway (p-ERK1/2).