The transcriptional coactivator TAZ regulates mesenchymal differentiation in malignant glioma.

Recent molecular classification of glioblastoma (GBM) has shown that patients with a mesenchymal (MES) gene expression signature exhibit poor overall survival and treatment resistance. Using regulatory network analysis of available expression microarray data sets of GBM, including The Cancer Genome Atlas (TCGA), we identified the transcriptional coactivator with PDZ-binding motif (TAZ), to be highly associated with the MES network. TAZ expression was lower in proneural (PN) GBMs and lower-grade gliomas, which correlated with CpG island hypermethylation of the TAZ promoter compared with MES GBMs. Silencing of TAZ in MES glioma stem cells (GSCs) decreased expression of MES markers, invasion, self-renewal, and tumor formation. Conversely, overexpression of TAZ in PN GSCs as well as murine neural stem cells (NSCs) induced MES marker expression and aberrant osteoblastic and chondrocytic differentiation in a TEAD-dependent fashion. Using chromatin immunoprecipitation (ChIP), we show that TAZ is directly recruited to a majority of MES gene promoters in a complex with TEAD2. The coexpression of TAZ, but not a mutated form of TAZ that lacks TEAD binding, with platelet-derived growth factor-B (PDGF-B) resulted in high-grade tumors with MES features in a murine model of glioma. Our studies uncover a direct role for TAZ and TEAD in driving the MES differentiation of malignant glioma.

A review of the FDA-approved molecular testing platforms for human papillomavirus.

The advent of US Food and Drug Administration (FDA)-approved molecular testing for human papillomavirus (HPV) has resulted in a dramatic shift from cytological testing alone to a combination of cytology and molecular testing for primary HPV screening. HPV testing has quickly become an essential component of daily practice in most laboratories and clinical practices. Although the principle of HPV testing is now familiar, it is important to understand the mechanisms behind these platforms in order to properly interpret the results and understand the limits of each method. HPV tests are more automated and reproducible than cytology, but are by no means perfect. None of these platforms will identify every HSIL/CIN2+ or cancer. This fact must be kept in mind when correlating the results of HPV testing with cytology or biopsy findings. The goal of this paper is to review the FDA- approved molecular testing platforms for HPV, including methodology, limitations, and specifications. The concordance between the platforms will also be discussed. Package inserts of the 5 FDA- approved molecular testing platforms for HPV, as well as a literature review of the platforms, were reviewed and assimilated into the article. Due to the multiple modalities available for detection of hrHPV, the concordance between these assays becomes important. Prior publications have compared HC2, Cervista, cobas, and Aptima, with most studies comparing to HC2 because it is considered the reference standard. With the newly approved BD platform, concordance studies were reviewed as well.

Western diet, but not high fat diet, causes derangements of fatty acid metabolism and contractile dysfunction in the heart of Wistar rats.

Obesity and diabetes are associated with increased fatty acid availability in excess of muscle fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in the development of skeletal-muscle insulin resistance. We tested the hypothesis that 'Western' and high fat diets differentially cause maladaptation of cardiac- and skeletal-muscle fatty acid oxidation, resulting in cardiac contractile dysfunction. Wistar rats were fed on low fat, 'Western' or high fat (10, 45 or 60% calories from fat respectively) diet for acute (1 day to 1 week), short (4-8 weeks), intermediate (16-24 weeks) or long (32-48 weeks) term. Oleate oxidation in heart muscle ex vivo increased with high fat diet at all time points investigated. In contrast, cardiac oleate oxidation increased with Western diet in the acute, short and intermediate term, but not in the long term. Consistent with fatty acid oxidation maladaptation, cardiac power decreased with long-term Western diet only. In contrast, soleus muscle oleate oxidation (ex vivo) increased only in the acute and short term with either Western or high fat feeding. Fatty acid-responsive genes, including PDHK4 (pyruvate dehydrogenase kinase 4) and CTE1 (cytosolic thioesterase 1), increased in heart and soleus muscle to a greater extent with feeding a high fat diet compared with a Western diet. In conclusion, we implicate inadequate induction of a cassette of fatty acid-responsive genes, and impaired activation of fatty acid oxidation, in the development of cardiac dysfunction with Western diet.

Normal karyotype in a case of acute myeloid leukemia with monocytic differentiation and hemophagocytosis by leukemic blasts.

We report the case of a 39-year-old woman with acute myeloid leukemia (AML) with monocytic differentiation showing hemophagocytosis by leukemic blasts. This phenomenon is known to be associated with certain chromosomal changes, including t(8;16), der(8), inv(8), and t(16;21); however, in this case, the patient had a normal female karyotype. To our knowledge, this is the first published case of normal karyotype AML with hemophagocytosis by leukemic blasts.

Multiple Human Papilloma Virus Infections and Their Impact on the Development of High-Risk Cervical Lesions.

OBJECTIVE: Individuals are often infected with multiple genotypes of human papillomavirus (HPV) simultaneously, but the role these infections play in the development of cervical disease is not well established. This study aimed to determine the association of multiple HPV infections with high-risk cervical lesions (hrCLs). STUDY DESIGN: HPV genotyping was performed on 798 SurePath specimens collected between December 1, 2009, and April 30, 2011. The cases were classified as hrCL (n = 90) or non-hrCL (n = 708) based on cytology diagnoses. The association between hrCL and HPV infection patterns was analyzed. RESULTS: Multiple HPV infections were frequently encountered (38.2%) in the cohort. Increased frequency of hrCLs was associated with a single high-risk HPV (hrHPV) infection. An additive or synergistic effect was not observed for hrCL in multiple HPV infections. The hrCL rates appeared to decrease in various patterns of multiple HPV infections, but the reduction was not statistically significant. CONCLUSIONS: Multiple HPV infections are common with no additive or synergistic effect on the development of hrCL. Conversely, reduced hrCL rates were observed in various patterns of multiple HPV infections compared to their single-genotype infection counterparts, suggestive of possible intergenotypic competition or more effective immune response triggered by multiple infections. Further studies in larger cohorts are needed.