Prophylactic fluconazole reduces the incidence of colonization and invasive candida infection in neonates weighing less than 1500 g at birth. The benefit of treating candida colonization is unclear. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).

No abstract

is considered an oncomicroRNA given its abilities to suppress the actions of several tumor suppressor genes and to promote tumor cell growth, invasion and metastasis. Recently, transforming growth factor-beta (TGF-b) is found to up-regulate the expression of miR-21, and elevated miR-21 expression is seen frequently in breast cancer. To evaluate the effect of miR-21 on disease progression and its association with TGF-b, we analyzed miR-21 expression in breast cancer. Fresh tumor samples were collected during surgery from 344 patients diagnosed with primary breast cancer. The expression of miR-21 in tumor samples was measured with a TaqMan Ò microRNA assay using U6 as reference. Levels of miR-21 expression by disease stage, tumor grade, histology, hormone receptor status and lymph node involvement were compared. Cox proportional hazards regression analysis was performed to assess the association of miR-21 expression with disease-free and overall survival. The study results showed that the expression of miR-21 was detected in all tumor samples with substantial variation. High miR-21 expression was associated with features of aggressive disease, including high tumor grade, negative hormone receptor status, and ductal carcinoma. High miR-21 was also positively correlated with TGF-b1. No associations were found between patient survival and miR-21 expression among all patients, but high miR-21 was associated with poor disease-free survival in early stage patients (HR = 2.08, 95% CI: 1.08-4.00) despite no value for prognosis. The study supports the notion that miR-21 is an onco-microRNA for breast cancer. Elevated miR-21 expression may facilitate tumor progression, and TGF-b may up-regulate its expression.

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To investigate the mechanisms through which p130Cas adaptor protein is linked to tumorigenesis, we generated mouse mammary tumor virus (MMTV)-p130Cas mice overexpressing p130Cas in the mammary gland. MMTVp130Cas transgenic mice are characterized by extensive mammary epithelial hyperplasia during development and pregnancy and by delayed involution at the end of lactation. These phenotypes are associated with activation of Src kinase, extracellular signalregulated kinase 1/2, mitogen-activated protein kinase, and Akt pathways, leading to an increased rate of proliferation and a decreased apoptosis. A double-transgenic line derived from crossing MMTV-p130Cas with MMTV-HER2-Neu mice expressing the activated form of the HER2-Neu oncogene develops multifocal mammary tumors with a significantly shorter latency than the HER2-Neu parental strain alone. Mammary epithelial cells isolated from tumors of double-transgenic mice display increased tyrosine phosphorylation, c-Src, and Akt activation compared with cells derived from HER2-Neu tumors. In addition, p130Cas down-regulation by RNA interference increases apoptosis in HER2-Neu-expressing cells, indicating that p130Cas regulates cell survival. Consistently with the double-transgenic mice model, p130Cas is overexpressed in a significant subset of human breast cancers and high levels of p130Cas in association with HER2 expression correlate with elevated proliferation. These findings provide evidences for a role of p130Cas as a positive regulator of both proliferation and survival in normal and transformed mammary epithelial cells. Its overexpression contributes to HER2-Neu-induced breast tumorigenesis, thus identifying this protein as a putative target for clinical therapy. (Cancer Res 2006; 66(9): 4672-80)