Functional Hierarchy and Cooperation of EMT Master Transcription Factors in Breast Cancer Metastasis.

Several master transcription factors (TF) can activate the epithelial-to-mesenchymal transition (EMT). However, their individual and combinatorial contributions to EMT in breast cancer are not defined. We show that overexpression of EMT-TFs individually in epithelial cells upregulated endogenous SNAI2, ZEB1/2, TCF4, and TWIST1/2 as a result of positive feedback mediated in part by suppression of their negative regulator miRNAs miR200s/203/205.

Do Out-of-Hospital Cardiac Arrest Patients Have Increased Chances of Survival When Transported to a Cardiac Resuscitation Center?

Background Patients suffering from an out-of-hospital cardiac arrest are often transported to the closest hospital. Although it has been suggested that these patients be transported to cardiac resuscitation centers, few jurisdictions have acted on this recommendation. To better evaluate the evidence on this subject, a systematic review and meta-analysis of the currently available literature evaluating the association between the destination hospital's capability (cardiac resuscitation center or not) and resuscitation outcomes for adult patients suffering from an out-of-hospital cardiac arrest was performed.

Case Report of Methylone, Oxymorphone and Ethanol in a Fatality Case with Tissue Distribution.

It is reasonable to expect the presence of multiple drugs to present a complicated picture of toxicity. We report a fatal case involving a young man who purchased illicit drugs and knowingly consumed them. After consuming these drugs and going to sleep in his friend's car, he was found unresponsive the next morning with no signs of physical violence.

AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis.

AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1.

KAP1 promotes proliferation and metastatic progression of breast cancer cells.

KAP1 (TRIM28) is a transcriptional regulator in embryonic development that controls stem cell self-renewal, chromatin organization, and the DNA damage response, acting as an essential corepressor for KRAB family zinc finger proteins (KRAB-ZNF). To gain insight into the function of this large gene family, we developed an antibody that recognizes the conserved zinc fingers linker region (ZnFL) in multiple KRAB-ZNF. Here, we report that the expression of many KRAB-ZNF along with active SUMOlyated KAP1 is elevated widely in human breast cancers.

The microRNA-200 family targets multiple non-small cell lung cancer prognostic markers in H1299 cells and BEAS-2B cells.

Lung cancer remains the leading cause of cancer-related mortality for both men and women. Tumor recurrence and metastasis is the major cause of lung cancer treatment failure and death. The microRNA‑200 (miR-200) family is a powerful regulator of the epithelial-mesenchymal transition (EMT) process, which is essential in tumor metastasis.

Suppression of the epithelial-mesenchymal transition by Grainyhead-like-2.

Grainyhead genes are involved in wound healing and developmental neural tube closure. In light of the high degree of similarity between the epithelial-mesenchymal transitions (EMT) occurring in wound-healing processes and the cancer stem cell-like compartment of tumors, including TGF-β dependence, we investigated the role of the Grainyhead gene, Grainyhead-like-2 (GRHL2) in oncogenic EMT. GRHL2 was downregulated specifically in the claudin-low subclass breast tumors and in basal-B subclass breast cancer cell lines.

A KLF4-miRNA-206 autoregulatory feedback loop can promote or inhibit protein translation depending upon cell context.

Krüppel-like factor 4 (KLF4), a transcription factor that regulates cell fate in a context-dependent fashion, is normally induced upon growth arrest or differentiation. In many cancer cells there is dysregulation, with increased expression in proliferating cells. To identify sequence elements that mediate KLF4 suppression in normal epithelial cells, we utilized a luciferase reporter and RK3E cells, which undergo a proliferation-differentiation switch to form an epithelial sheet.

Low concentrations of methamphetamine detectable in urine in the presence of high concentrations of amphetamine.

Twenty-two urine specimens reported by military drug-testing laboratories for the presence of high concentrations of amphetamine only were subject to further analysis for the presence of methamphetamine. The 22 urine specimens had concentrations of amphetamine in the range of 28,028 to 241,142 ng/mL. The specimens were also assayed for the respective isomeric ratio of d (S) and l (R) amphetamine and methamphetamine.