The short-term prediction of preterm birth: a systematic review and diagnostic metaanalysis.

OBJECTIVE: To assess the diagnostic accuracy of fetal fibronectin (fFN), fetal breathing movements (FBM), and cervical length (CL) for the short-term prediction of preterm birth in symptomatic patients. STUDY DESIGN: Diagnostic metaanalysis using bivariate methods. RESULTS: Pooled sensitivities for fFN, FBM, and CL for delivery within 48 hours of testing were 0.62 (95% confidence interval [CI], 0.43-0.78), 0.75 (95% CI, 0.57-0.87) and 0.77 (95% CI, 0.54-0.90), respectively. Pooled specificities for fFN, FBM, and CL for delivery within 48 hours were 0.81 (95% CI, 0.74-0.86), 0.93 (95% CI, 0.75-0.98) and 0.88 (95% CI, 0.84-0.91). Pooled sensitivities for fFN, FBM, and CL for delivery within 7 days were 0.75 (95% CI, 0.69-0.80), 0.67 (95% CI, 0.43-0.84), and 0.74 (95% CI, 0.58-0.85). Pooled specificities for fFN, FBM, and CL for delivery within 7 days were 0.79 (95% CI, 0.76-0.83), 0.98 (95% CI, 0.83-1.00) and 0.89 (95% CI, 0.85-0.92). Based on a pretest probability of 10% for delivery within 48 hours, posttest probabilities (positive and negative) were 27% and 5% for fFN, 54% and 3% for fFN, and 42% and 3% for CL. For a pretest probability of 20% for delivery within 7 days, posttest probabilities (positive and negative) were 48% and 7% for fFN, 89% and 8% for FBM, and 63% and 7% for CL. CONCLUSION: In symptomatic patients, for fFN, absence of FBM, and CL have diagnostic use as predictors of delivery within 48 hours and within 7 days of testing. Absence of FBM appears to be the best test for predicting preterm birth.

Histone deacetylase inhibitor belinostat represses survivin expression through reactivation of transforming growth factor beta (TGFbeta) receptor II leading to cancer cell death.

Survivin is a cancer-associated gene that functions to promote cell survival, cell division, and angiogenesis and is a marker of poor prognosis. Histone deacetylase inhibitors induce apoptosis and re-expression of epigenetically silenced tumor suppressor genes in cancer cells. In association with increased expression of the tumor suppressor gene transforming growth factor ß receptor II (TGFßRII) induced by the histone deacetylase inhibitor belinostat, we observed repressed survivin expression. We investigated the molecular mechanisms involved in survivin down-regulation by belinostat downstream of reactivation of TGFß signaling. We identified two mechanisms. At early time points, survivin protein half-life was decreased with its proteasomal degradation. We observed that belinostat activated protein kinase A at early time points in a TGFß signaling-dependent mechanism. After longer times (48 h), survivin mRNA was also decreased by belinostat. We made the novel observation that belinostat mediated cell death through the TGFß/protein kinase A signaling pathway. Induction of TGFßRII with concomitant survivin repression may represent a significant mechanism in the anticancer effects of this drug. Therefore, patient populations exhibiting high survivin expression with epigenetically silenced TGFßRII might potentially benefit from the use of this histone deacetylase inhibitor.

Mouse mammary gland is refractory to the effects of ethanol after natural lactation.

Ethanol is a dietary factor that dose-dependently increases breast cancer risk in women. We previously have shown that ethanol increases mammary epithelial density through increased branching after dietary exposure during puberty in CD2/F1 mice. To extend these studies to parous mice in a breast cancer model, we used a transgenic mouse model of human parity-associated breast cancer, the FVB-MMTV-Her2/Neu mouse, which overexpresses wildtype EGFR2, resulting in constitutive activation of growth signaling in the mammary epithelium. Here we describe the short-term effects of ethanol feeding on progression through involution. Mice were fed diets supplemented with 0%, 0.5%, 1%, or 2% ethanol for 4, 9, or 14 d starting on day 21 of lactation (that is, at the start of natural postlactational involution). Unlike peripubertal mice exposed to ethanol, postlactational dams showed no changes in body weight; liver, spleen, and kidney weights; and pathology. Ethanol exposure had no effect on mammary gland lobular density and adipocyte size throughout involution. Likewise, the infiltration of inflammatory cells and serum oxidized lipid species were unchanged by diet, suggesting that ethanol feeding had no effect on local inflammation (leukocyte infiltration) or systemic inflammation (oxidized lipids). In conclusion, ethanol exposure of parous dams had no effect on mammary gland structure or the regression of the lactating mammary gland to a resting state. The period of involution that follows natural lactation appears to be refractory to developmental effects of ethanol on mammary epithelium.