The aberrant activation of Wnt pathway caused by ß-catenin mutation and its prognostic significance in NK/T-cell lymphoma.

The aberrant activation of the Wnt/ß-catenin signal has an important role in the progression of cancers. Herein, we investigated ß-catenin mutation and the activation of the Wnt pathway in association with the clinical-pathological characteristics, chemo-resistance and prognosis of NK/T-cell lymphoma (NKTCL). Real-time quantitative PCR, immunocytochemistry and immunohistochemistry SP methods detected the levels of ß-catenin, c-myc and cyclin D1 in human NKTCL cell lines (SNK-6 and YTS) and NKTCL tissues. Mutation analysis was detected in exon 3 of ß-catenin gene; and we analyzed cell viability after histone deacetylase inhibitor (HDACi) treatment. As a result, 19 (38%) of NK/T-cell lymphoma displayed nuclear ß-catenin and 16 (32%) contained mutations in exon 3; while no mutations were detected in lymphomas negative for ß-catenin nuclear staining (p<0.05). Most mutations affecting ß-catenin were adjacent to regulatory phosphorylation sites. ß-catenin, c-myc and cyclin D1 were significantly elevated in SNK-6 and YTS cell lines compared to normal NK/T cells (p<0.05). Furthermore, the high expression of ß-catenin, c-myc and cyclin D1 significantly correlated with the III/IV Ann Arbor stage. Additionally, the expression of ß-catenin in the SNK-6 cell line decreased significantly after treatment with HDACi, and Kaplan-Meier survival analysis revealed that the elevated expression of ß-catenin correlated with poor prognosis in NKTCL patients (23.66±2.77 months vs 31.65±1.78 months, p=0.023). In conclusion: mutations in exon 3 of ß-catenin and the activated Wnt pathway are common in NK/T-cell lymphoma that has nuclear ß-catenin, and it is closely correlated with the Ann Arbor stage and prognosis in NKTCL patients.

A new method for the quantitation of aflatoxin M1 in urine by high performance liquid chromatography and its application to the etiologic study of hepatoma.

A high performance liquid chromatographic (HPLC) method for the analysis of aflatoxin M1 (AFM1) in urine is described. Urine samples were treated with saturated lead acetate and AFM1 was extracted with chloroform. After washing with water to remove impurities the compound was derivatized with trifluoroacetic acid and the AFM1 derivative was analyzed quantitatively by HPLC. The sample pretreatment is simple and more selective. A good line correlation between AFM1 peak height and its concentration was obtained when AFM1 content was in the range of 50-400 pg. The ratio of recovery was 87.42%. Sensitivity is 0.01 ppb. The method is applicable to trace analysis. Results in urine of residents who live in the high/low liver cancer incidence area in Fushui county were the same as that of previous epidemiological investigation.