Opposing roles of ICAT and Wnt/ß-catenin signaling in NSC67657-induced monocytic differentiation.

NSC67657 is a new steroid drug that induces monocytic differentiation of acute myeloid leukemia cells. Here, we demonstrate that NSC67657 has opposing effects on expression of downstream targets of inhibitor of ß-catenin and TCF (ICAT) and Wnt signaling in HL60 cells. ICAT binds to ß-catenin, and this interaction is further increased in NSC67657-differentiated cells. ICAT overexpression decreases expression of Wnt downstream targets and increases sensitivity of HL60 cells to NSC67657, while ICAT silencing increases Wnt signaling and delays the NSC67657-induced cell differentiation. In addition, pharmacological inhibition of Wnt/ß-catenin signaling increases the NSC67657-induced cell differentiation, while activation of Wnt/ß-catenin signaling inhibits the differentiation, indicating Wnt/ß-catenin signaling inhibits NSC67657-induced monocytic differentiation of HL60 cells. Our data demonstrate the opposing roles of ICAT and Wnt signaling in the NSC67657-induced monocytic differentiation, and suggest that ICAT and Wnt signaling may serve as therapeutic targets for leukemia chemotherapy.

Analytical performances and heart failure research of the BNP and NT-proBNP assays on the Cobas E601 and ADVIA Centaur.

BACKGROUND: The analytical performances of the NT-proBNP and BNP assays on the Cobas E601 and ADVIA Centaur were thoroughly evaluated. In addition, the values of BNP and NT-proBNP, which are heart failure markers, were compared in the diagnosis of HF patients with or without acute cerebral infarction since they could also be elevated in ischemic stroke. METHODS: Clinical and Laboratory Standards Institute (CLSI) documents were employed in the analytical evaluation of NT-proBNP and BNP assays on the Cobas E601 and ADVIA Centaur. Then 100 heart failure patients and 103 cerebral infarction complicated with heart failure patients, who had been diagnosed by clinical doctors blinded to NT-proBNP and BNP concentrations, were chosen to compare their values in the diagnosis of heart failure with or without acute cerebral infarction. RESULTS: The NT-proBNP and BNP methods are precise and accurate (total CV < 2.9%, deviation < 3.6%), have wide dynamic measuring ranges (8 pg/mL to 35 126 pg/mL and 2.0 pg/mL to 5094 pg/mL, respectively) with maximum dilutability of 1:2, and are free of common interferences. The most suitable sample types for NT-proBNP and BNP are serum and EDTA plasma, respectively, and both methods correlate well in simple-HF patients. Unlike BNP, the level of NT-proBNP is much higher in HF patients with acute cerebral infarction (p < 0.001). The Cobas E601 and ADVIA Centaur systems have good analytical performances. CONCLUSIONS: In HF patients with acute cerebral infarction, the NT-proBNP and BNP levels did not correlate and thus had implications for clinical diagnosis.

Two Epstein-Barr virus-related serologic antibody tests in nasopharyngeal carcinoma screening: results from the initial phase of a cluster randomized controlled trial in Southern China.

A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.

Epidemiological trends of nasopharyngeal carcinoma in China.

Research papers and data concerning NPC epidemiology in China available worldwide were reviewed. It was found that although the results of three national all death-causes sampling surveys in China showed mortality rates in most sampling areas and all as overall to be declining continuously and remarkably, figures for 1987-2000 in some selected areas of China released by the World Health Organization were relatively stable, and the NPC incidence and mortality rates reported by Zhongshan and Sihui cities of Guangdong Province in China had shown ascending or stable trends, respectively. Differences with regard to change in NPC incidence and mortality rates over time may be caused by variation in the data quality from divergent sources, but the exact reasons clearly warrant further analysis.