Shortly after completing synchronous mitoses that generate a new 16-cell cyst, all the germ cells enter the first meiosis-specific process, pre-meiotic S phase. The strong reduction in meiotic, 16- cell cyst formation that we observed when ecdysone signaling is reduced, suggests that hormones control meiotic entry during Drosophila oogenesis. Meiosis in many lower organisms is induced by nutrient limitation and modulated by nutrient-sensitive pathways. Ecdysone signals may help determine when cysts have been starved sufficiently to enter meiosis, much as they assess nutrient sufficiency at other decision points. If steroid signaling in the ovarian soma acts to mediate the extraordinary metabolic demands of female gamete production, then the absence of a male requirement is not surprising. The metabolic demands of egg production are immense, unlike those of sperm production. Thus, decisions affecting oocyte progression may have evolved to employ conserved mechanisms also used during life stage transitions such as dauer formation in C. elegans or the larval/pupal transition. This fundamental difference between male and female gametogenesis may apply to a wide range of organisms and might explain why sex-specific steroid signaling is a common aspect of gametogenesis. Steroid hormone signaling plays a major role in mammalian sex determination and gametogenesis. Transcriptional changes controlled by the Y chromosome-linked SRY gene and hormonal differences dependent on the Sf1 nuclear receptor begin to orchestrate divergent germ cell developmental fates in the bipotential mouse gonad. At this stage, germ cells in both the both male and female gonad are engaged in cyst formation. Whether estrogen mediates cyst completion and meiotic entry in female mice in a manner similar to the role of ecdysone in Drosophila remains an interesting question. Squamous, pre-granulosa cells surround mouse germline cysts at the time of follicle formation, and treatment of pregnant animals with estrogen or progesterone enhances the production of multi-oocyte follicles. This raises the possibility that steroid signaling also plays a conserved role during mammalian follicle formation. Over the last decade, our understanding of tumor biology has expanded to include host CPI-613 stromal elements as important determinants in malignant transformation and progression. Therapies targeting stromal cells have, in part, resulted from the molecular characterization of tumor-stromal interactions. There is considerable evidence that stromal inflammation contributes to the proliferation and survival of malignant cells, facilitates genomic instability, stimulates angiogenesis and metastasis, and alters the response to anti-cancer therapies. When chronically produced in the tumor microenvironment, TNF-a is a major mediator of stromal inflammation. TNF-a is important in early events in tumorigenesis, controlling a cascade of cytokines, chemokines, adhesion molecules, and pro-angiogenic activities. The most well-characterized actions of malignant cellderived TNF-a are on vascular endothelial cells. Vascular endothelial cells actively participate in and regulate the inflammatory response in both normal and diseased tissues, and emerging data suggests that endothelial cells directly influence tumor behavior. Nevertheless, little is known regarding the role of endothelial inflammation in promoting tumor growth and its influence on the prognosis of human cancers. Gene expression profiling of clinical tumors has led to the discovery of numerous molecular signatures.