A polymorphic minisatellite region of BORIS regulates gene expression and its rare variants correlate with lung cancer susceptibility

Aberrant expression of BORIS/CTCFL (Brother of the Regulator of Imprinted Sites/CTCF-like protein) is reported in different malignancies. In this study, we characterized the entire promoter region of BORIS/CTCFL, including the CpG islands, to assess the relationship between BORIS expression and lung cancer. To simplify the construction of luciferase reporter cassettes with various-sized portions of the upstream region, genomic copies of BORIS were isolated using TAR cloning technology. We analyzed three promoter blocks: the GATA/CCAAT box, the CpG islands and the minisatellite region BORIS-MS2. Polymorphic minisatellite sequences were isolated from genomic DNA prepared from the blood of controls and cases. Of the three promoter blocks, the GATA/CCAAT box was determined to be a critical element of the core promoter, while the CpG islands and the BORIS-MS2 minisatellite region were found to act as regulators. Interestingly, the polymorphic minisatellite region BORIS-MS2 was identified as a negative regulator that repressed the expression levels of luciferase reporter cassettes less effectively in cancer cells compared with normal cells. We also examined the association between the size of BORIS-MS2 and lung cancer in a case–control study with 590 controls and 206 lung cancer cases. Rare alleles of BORIS-MS2 were associated with a statistically significantly increased risk of lung cancer (odds ratio, 2.04; 95% confidence interval, 1.02–4.08; and P=0.039). To conclude, our data provide information on the organization of the BORIS promoter region and gene regulation in normal and cancer cells. In addition, we propose that specific alleles of the BORIS-MS2 region could be used to identify the risk for lung cancer.

Gecko Proteins Exert Anti-Tumor Effect against Cervical Cancer Cells Via PI3-Kinase/Akt Pathway

Anti-tumor activity of the proteins from Gecko (GP) on cervical cancer cells, and its signaling mechanisms were assessed by viable cell counting, propidium iodide (PI) staining, and Western blot analysis. GP induced the cell death of HeLa cells in a dose-dependent manner while it did not affect the viability of normal cells. Western blot analysis showed that GP decreased the activation of Akt, and co-administration of GP and Akt inhibitors synergistically exerted anti-tumor activities on HeLa cells, suggesting the involvement of PI3-kinase/Akt pathway in GP-induced cell death of the cancer cells. Indeed, the cytotoxic effect of GP against HeLa cells was inhibited by overexpression of constituvely active form of Akt in HeLa cells. The candidates of the functional proteins in GP were analyzed by Mass-spectrum. Taken together, our results suggest that GP elicits anti-tumor activity against HeLa cells by inhibition of PI3-kinase/Akt pathway.

Two-year Prospective Study of Seizure Recurrence in Newly Diagnosed Partial Epilepsy: Can MRI Predict the Recurrence of Seizure?

BACKGROUND: It has been known that several factors are associated with seizure recurrence. We performed this study to determine whether an MRI can independently predict seizure recurrence in newly diagnosed partial epilepsy. METHODS: We found 91 newly diagnosed partial epilepsy patients with whom we prospectively followed up for at least 2 years. Variables for statistical analysis were cumulative recurrence rates according to MRI findings as well as age of onset, etiology and epilepsy syndrome. We divided MRI findings into paired groups of normal and abnormal groups, age of onset into or =28 years groups, etiology into symptomatic and cryptogenic groups and epilepsy syndrome into temporal lobe epilepsy and extratemporal lobe epilepsy groups respectively. RESULTS: The seizure recurrence rate was 24% at 1 year and 36% at 2 years follow-up. Among prognostic variables, the epilepsy syndrome, etiology and MRI findings could significantly predict the seizure recurrence at 2 years but age of onset could not predict recurrence at 2 years follow-up. Univariate analysis showed the odds ratio of the seizure recurrence as follows: temporal lobe epilepsy was 1.91 (95%CI 0.89~4.12), symptomatic etiology was 2.27 (95%CI 1.13~4.57), abnormal MRI finding was 2.80 (1.40~5.60). Multivariate analyses showed that only abnormal MRI findings could independently predict the seizure recurrence. CONCLUSIONS: We conclude that abnormal MRI finding can independently predict seizure recurrence at 2 years follow-up.

Concomitance of Childhood Absence Epilepsy and Benign Rolandic Spikes / 대한간질학회지

Childhood absence epilepsy (CAE) and benign epilepsy of childhood with centro-temporal spikes (BECT) are common forms of idiopathic epilepsy of childhood onset and share many features such as the marked age dependence of onset. The occurrence of generalized 3 Hz spike and waves in BECT or rolandic spikes in CAE has rarely been reported. We report 2 cases of concomitance of CAE and benign rolandic spikes. All of the two patients were female and had clinically absence seizure only. On EEG the two patients simultaneously showed centro-temporal spikes as well as ictal onset of absence seizure consisting of generalized 3 Hz spike and waves. All of the two patients have become seizure-free with valporic acid. It is rare but not impossible that (Rolandic spikes can concur with CAE rather than as a continuum between CAE and BECT), because all of the two patients have not shown BECT so far.