Regulation of XAF1 expression in human colon cancer cell by interferon beta: activation by the transcription regulator STAT1.

XIAP-associated factor 1 (XAF1) is a novel tumor suppressor and interferon stimulated gene (ISG). Interferon beta (IFNbeta) exerts anti-proliferative effect and induces apoptosis through the Jak-Stat signaling cascade by the type I Interferon receptor (IFN-R), which initiates gene transcription of those biological effectors of IFNbeta. The aim of this study is to determine the effect of IFNbeta on XAF1 expression and the putative mechanisms mediated by the critical role of signal transducers and activators of transcription 1 (Stat1). Gene expression was detected by RT-PCR and Western blot analysis. The promoter activity of XAF1 was examined by luciferase reporter assay. The activity of interferon stimulated response element (ISRE) was assessed by electrophoretic mobility shift assay (EMSA) and quantitative chromatin immunoprecipitation assay (Q-ChIP). Results showed that IFNbeta stimulated XAF1 promoter activity in colon cancer cell line DLD1 in a time- and dose-dependent manner. A high affinity ISRE binding element (ISRE-XAF1) was located in -55 to -66 nt upstream of the first ATG site of XAF1 gene. Deletion of ISRE-XAF1 completely abrogated basal and IFNbeta-induced promoter activity. IFNbeta-induced XAF1 expression was mediated by Stat1 through the interaction with ISRE-XAF1. Knocking down of the Stat1 expression and blocking its phosphorylation decreased IFNbeta-induced XAF1 expression. Results suggested that induction of an immediate early response gene-XAF1 by IFNbeta was mediated by the transcription regulator Stat1 through the ISRE site within the promoter region of XAF1 gene in colon cancer.

Attitudes and knowledge of colorectal cancer and screening in Hong Kong: a population-based study.

BACKGROUND: Colorectal cancer (CRC) ranks third of all cancer mortalities in Hong Kong. CRC screening can reduce mortality. However, participation in the CRC screening program depends on the knowledge and attitude of the population. The aim of this study is to investigate the knowledge and attitude towards CRC screening in the Hong Kong population. METHODS: One thousand and thirty-three patients were interviewed by telephone survey. Knowledge and attitudes were assessed by using questionnaires. RESULTS: Only 8.9% of the respondents were able to mention that CRC was the second commonest cancer cause of death; 4.5% believed they would have a higher chance of developing CRC as compared to other cancers, and 7.4% could mention one of the screening methods. Approximately half (50.3%) were unable to identify any available screening venue. Approximately one-third (29.5%) indicated that they would definitely join a free CRC screening program, but the percentage dropped to 7.9% when a paid screening program was offered. Some (30.4%) of the respondents had the wrong impression that they did not require CRC screening because they were asymptomatic. Multivariate analysis showed that the independent predictor for participating in free screening was the concern level of getting CRC, while that for a paid screening program was a positive family history of CRC and the concern level. The concern level was dependent on a positive family history and knowledge of CRC. CONCLUSION: The general population in Hong Kong had deficient knowledge of CRC and screening. Education on the impact of CRC and beneficial effects of CRC screening should be offered before launching a CRC screening program.

Differing coping mechanisms, stress level and anorectal physiology in patients with functional constipation.

AIM: To investigate coping mechanisms, constipation symptoms and anorectal physiology in 80 constipated subjects and 18 controls. METHODS: Constipation was diagnosed by Rome II criteria. Coping ability and anxiety/depression were assessed by validated questionnaires. Transit time and balloon distension test were performed. RESULTS: 34.5% patients were classified as slow transit type of constipation. The total colonic transit time (56 h vs 10 h, P<0.0001) and rectal sensation including urge sensation (79 mL vs 63 mL, P = 0.019) and maximum tolerable volume (110 mL vs 95 mL, P = 0.03) differed in patients and controls. Constipated subjects had significantly higher anxiety and depression scores and lower SF-36 scores in all categories. They also demonstrated higher scores of 'monitoring' coping strategy (14+/-6 vs 9+/-3, P = 0.001), which correlated with the rectal distension sensation (P = 0.005), urge sensation (P=0.002), and maximum tolerable volume (P = 0.035). The less use of blunting strategy predicted slow transit constipation in both univariate (P = 0.01) and multivariate analysis (P = 0.03). CONCLUSION: Defective or ineffective use of coping strategies may be an important etiology in functional constipation and subsequently reflected in abnormal anorectal physiology.