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 plateletderived 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.

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.

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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.

THE JOURNAL OF UROLOGY® this cell line do not develop metastasis. These studies were designed to develop an orthotopic model for human papillary bladder cancer and to study the possible mechanisms involved in progression from papillary to metastatic disease.METHODS: The human bladder cancer cell line RT4 was implanted into the muscular wall of the bladder of athymic nude mice. Tumors from each passage were harvested and cell lines established as follows: RT4vl, RT4v2, RT4v3, RT4v4, RT4v5, and RT4v6. Mice injected with RT4v6 developed lymph node metastasis and the cell line derived from the metastases was designated RT4LN. Tumors derived each passage were analyzed using immunohistochemical (IHC) staining for IL-8 (interleukin-8), VEGF (vascular endothelial growth factor), bFGF (basic fibroblastic growth factor), MMP-9 (matrix metalloproteinase-9), and Ecadherin. IHC staining intensity was measured and compared using optical densities.RESULTS: The in vivo-selected higher-passage (RT4v6) and metastatic (RT4LN) cell lines exhibited increased expression of IL-8, VEGF, MMP-9, E-cadherin, and bFGF ( p< 0.05) compared to the original cell line. In addition, the MMP-9:E-cadherin ratio, a measure of invasiveness, was significantly increased as well (p