The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described.

microRNAs are thought to regulate tumor progression and invasion via direct interaction with target genes within cells. Here the microRNA17/20 cluster is shown to govern cellular migration and invasion of nearby cells via heterotypic secreted signals. micro-RNA17/20 abundance is reduced in highly invasive breast cancer cell lines and node-positive breast cancer specimens. Cell-conditioned medium from microRNA17/20-overexpressing noninvasive breast cancer cell MCF7 was sufficient to inhibit MDA-MB-231 cell migration and invasion through inhibiting secretion of a subset of cytokines, and suppressing plasminogen activation via inhibition of the secreted plasminogen activators (cytokeratin 8 and α-enolase). microRNA17/20 directly repressed IL-8 by targeting its 3′ UTR, and inhibited cytokeratin 8 via the cell cycle control protein cyclin D1. At variance with prior studies, these results demonstrated a unique mechanism of how the altered microRNA17/20 expression regulates cellular secretion and tumor microenvironment to control migration and invasion of neighboring cells in breast cancer. These findings not only reveal an antiinvasive function of miR-17/20 in breast cancer, but also identify a heterotypic secreted signal that mediates the microRNA regulation of tumor metastasis.M icroRNAs (miRNAs) are 21-to 22-nucleotide molecules that regulate cellular phenotype through altering the stability or translational efficiency of targeted mRNAs (1). Important associations between miRNA gene expression and human cancer have implicated miRNA in human tumorigenesis (2-4). miRNA encoding genes are frequently located at fragile sites, common breakpoints, or minimal regions of amplification (5). The human miR-17/20 cluster, located on chromosome 13q31, undergoes loss of heterozygosity in several different cancers, including breast cancer. In the human B cell line P493-6, miR-17/20 inhibits cell growth via suppression of E2F1 expression (6). In mice, transgenic mice overexpressing miR-17 alone showed overall tissue growth retardation, smaller organs, and greatly reduced hematopoietic cell lineages (7). Analysis of miRNAs regulated in cyclin D1 transgenic mammary tumors and reciprocally regulated in cyclin D1-knockout mice identified the miR-17/20 cluster as an important regulatory switch in mammary tumor growth. miR-17/20 inhibited breast cancer tumor growth through repression of cyclin D1 expression via the 3′ UTR binding site (8). Recent evidence implicates miRNA in breast cancer metastasis by inhibiting target genes. miR-335 inhibited human breast cancer cell metastasis via repression of SOX4, a regulator of progenitor cell development and migration (9). miR-10b promotes cell migration in vitro and initiates breast tumor invasion in vivo by targeting gene HOXD10 (10). miR-200 family prevented epithelial to mesenchymal transition of breast cancer cells by repressing ZEB1 and SIP1 (11). However, the role of the miR-17/20 cluster in regulation of breast cancer metastasis remains unknown.Tumor cell migration and invasion is in par...

The role of mammary epithelial cell (MEC) NF-kB in tumor progression in vivo is unknown, as murine NF-kB components and kinases either are required for murine survival or interfere with normal mammary gland development. As NF-kB inhibitors block both tumor-associated macrophages (TAM) and MEC NF-kB, the importance of MEC NF-kB to tumor progression in vivo remained to be determined. Herein, an MEC-targeted inducible transgenic inhibitor of NF-kB (IkBaSR) was developed in ErbB2 mammary oncomice. Inducible suppression of NF-kB in the adult mammary epithelium delayed the onset and number of new tumors. Within similar sized breast tumors, TAM and tumor neoangiogenesis was reduced. Coculture experiments demonstrated MEC NF-kB enhanced TAM recruitment. Genome-wide expression and proteomic analysis showed that IkBaSR inhibited tumor stem cell pathways. IkBaSR inhibited breast tumor stem cell markers in transgenic tumors, reduced stem cell expansion in vitro, and repressed expression of Nanog and Sox2 in vivo and in vitro. MEC NF-kB contributes to mammary tumorigenesis. As we show that NF-kB contributes to expansion of breast tumor stem cells and heterotypic signals that enhance TAM and vasculogenesis, these processes may contribute to NF-kB-dependent mammary tumorigenesis.