A subtype of aggressive human muscle-invasive bladder cancer expresses basal epithelial markers and is sensitive to EGFR inhibition in preclinical models.

The occurrence of cell death by apoptosis was examined in blastocyst and pre-blastocyst stage bovine embryos. Zygotes were obtained by in vitro maturation and in vitro fertilization of oocytes from abattoir derived ovaries. Two-cell to hatched blastocyst stage embryos were stained with propidium iodide to label all nuclei and by terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP nick end-labelling (TUNEL) to label apoptotic nuclei, and were analysed by epifluorescent and confocal microscopy. Apoptosis was first observed at the 9–16-cell stage of development, decreasing at the morula stage before increasing at the blastocyst stage. Apoptotic dead cell index in day 7 blastocysts was negatively correlated with the total number of cells; the percentage of dead cells ranged from approximately 1 to 10% and occurred predominantly within the inner cell mass. In addition, apoptotic dead cell index was significantly higher (P < 0.05) in blastocysts cultured (from the two-cell stage) in the presence of 10% fetal bovine serum compared with those developed in serum-free medium. Embryos selected for early cleavage at < 29 h after fertilization and cultured together until the blastocyst stage showed a significantly lower rate of apoptosis (P < 0.01) compared with slower cleaving embryos.

The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to encourage communication of the very best cancer research from laboratories and clinics in all countries. The breadth of its coverage, its editorial independence and it consistent high standards, have made BJC one of the world's premier general cancer journals. Its increasing popularity is reflected by a steadily rising impact factor.

Extracting relevant information from large-scale data offers unprecedented opportunities in cancerology. We applied independent component analysis (ICA) to bladder cancer transcriptome data sets and interpreted the components using gene enrichment analysis and tumor-associated molecular, clinicopathological, and processing information. We identified components associated with biological processes of tumor cells or the tumor microenvironment, and other components revealed technical biases. Applying ICA to nine cancer types identified cancer-shared and bladder-cancer-specific components. We characterized the luminal and basal-like subtypes of muscle-invasive bladder cancers according to the components identified. The study of the urothelial differentiation component, specific to the luminal subtypes, showed that a molecular urothelial differentiation program was maintained even in those luminal tumors that had lost morphological differentiation. Study of the genomic alterations associated with this component coupled with functional studies revealed a protumorigenic role for PPARG in luminal tumors. Our results support the inclusion of ICA in the exploitation of multiscale data sets.