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VILIP-1, a member of the neuronal Ca++ sensor protein family, acts as a tumor suppressor gene in an experimental animal model by inhibiting cell proliferation, adhesion and invasiveness of squamous cell carcinoma cells. Western Blot analysis of human tumor cells showed that VILIP-1 expression was undetectable in several types of human tumor cells, including 11 out of 12 non-small cell lung carcinoma (NSCLC) cell lines. The down-regulation of VILIP-1 was due to loss of VILIP-1 mRNA transcripts. Rearrangements, large gene deletions or mutations were not found. Hypermethylation of the VILIP-1 promoter played an important role in gene silencing. In most VILIP-1-silent cells the VILIP-1 promoter was methylated. In vitro methylation of the VILIP-1 promoter reduced its activity in a promoter-reporter assay. Transcriptional activity of endogenous VILIP-1 promoter was recovered by treatment with 5′-aza-2′-deoxycytidine (5′-Aza-dC). Trichostatin A (TSA), a histone deacetylase inhibitor, potently induced VILIP-1 expression, indicating that histone deacetylation is an additional mechanism of VILIP-1 silencing. TSA increased histone H3 and H4 acetylation in the region of the VILIP-1 promoter. Furthermore, statistical analysis of expression and promoter methylation (n = 150 primary NSCLC samples) showed a significant relationship between promoter methylation and protein expression downregulation as well as between survival and decreased or absent VILIP-1 expression in lung cancer tissues (p<0.0001). VILIP-1 expression is silenced by promoter hypermethylation and histone deacetylation in aggressive NSCLC cell lines and primary tumors and its clinical evaluation could have a role as a predictor of short-term survival in lung cancer patients.

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Purpose Examination of the hip provides information regarding risk for pre-arthritic hip disorders, knee injuries, and low back pain. The purpose of this study was to report a hip screening examination of asymptomatic female soccer athletes and to test the hypothesis that these findings vary by competition experience. Methods Asymptomatic females from a youth soccer club, a college, and a professional team were evaluated. Passive hip range of motion, hip abduction strength, and hip provocative tests were assessed. Data were compared for the grade/middle school, high school, college, and professional athletes. Results One hundred and seventy-two athletes with a mean age of 16.7 ± 5 years (range 10–30) participated. Professional athletes had less flexion (HF) for both hips (p < 0.0001) and less internal rotation (IR) for the preferred kicking leg (p < 0.05) compared to all other groups. Grade/middle school athletes had more external rotation in both hips as compared to all other groups (p < 0.0001). For the preferred kicking leg, collegiate athletes had less hip abduction strength as compared to other groups (p < 0.01). Positive provocative hip tests were found in 22 % of all players and 36 % of the professionals. In professionals, a positive provocative test was associated with ipsilateral decreased HF (p = 0.04). Conclusion Asymptomatic elite female soccer athletes with the most competition experience had less bilateral hip flexion and preferred kicking leg IR than less-experienced athletes. Positive provocative hip tests were found in 22 % of athletes. Future studies are needed to show whether these findings link to risk for intra-articular hip or lumbar spine and knee disorders. Level of evidence III.

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