Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

SummaryeNOS expression is elevated in human glioblastomas and correlated with increased tumor growth and aggressive character. We investigated the potential role of nitric oxide (NO) activity in the perivascular niche (PVN) using a genetic engineered mouse model of PDGF-induced gliomas. eNOS expression is highly elevated in tumor vascular endothelium adjacent to perivascular glioma cells expressing Nestin, Notch, and the NO receptor, sGC. In addition, the NO/cGMP/PKG pathway drives Notch signaling in PDGF-induced gliomas in vitro, and induces the side population phenotype in primary glioma cell cultures. NO also increases neurosphere forming capacity of PDGF-driven glioma primary cultures, and enhances their tumorigenic capacity in vivo. Loss of NO activity in these tumors suppresses Notch signaling in vivo and prolongs survival of mice. This mechanism is conserved in human PDGFR amplified gliomas. The NO/cGMP/PKG pathway's promotion of stem cell-like character in the tumor PVN may identify therapeutic targets for this subset of gliomas

EEV CCD39 wavefront sensor cameras for AO and interferometry

SciMeasure, in collaboration with Emory University and the Jet Propulsion Laboratory (JPL), has developed an extremely versatile CCD controller for use in adaptive optics, optical interferometry, and other applications requiring high-speed readout rates and/or low read noise. The overall architecture of this controller system will be discussed and its performance using both EEV CCD39 and MIT/LL CCID-19 detectors will be presented. Initially developed for adaptive optics applications, this controller is used in the Palomar Adaptive Optics program (PALAO), the AO system developed by JPL for the 200' Hale telescope at Palomar Mountain. An overview of the PALAO system is discussed and diffraction-limited science results will be shown. Recently modified under NASA SBIR Phase II funding for use in the Space Interferometry Mission testbeds, this controller is currently in use on the Micro- Arcsecond Metrology testbed at JPL. Details of a new vacuum- compatible remote CCD enclosure and specialized readout sequence programming will also be presented

EEV CCD39 wavefront sensor cameras for AO and interferometry

SciMeasure, in collaboration with Emory University and the Jet Propulsion Laboratory (JPL), has developed an extremely versatile CCD controller for use in adaptive optics, optical interferometry, and other applications requiring high-speed readout rates and/or low read noise. The overall architecture of this controller system will be discussed and its performance using both EEV CCD39 and MIT/LL CCID-19 detectors will be presented. Initially developed for adaptive optics applications, this controller is used in the Palomar Adaptive Optics program (PALAO), the AO system developed by JPL for the 200' Hale telescope at Palomar Mountain. An overview of the PALAO system is discussed and diffraction-limited science results will be shown. Recently modified under NASA SBIR Phase II funding for use in the Space Interferometry Mission testbeds, this controller is currently in use on the Micro- Arcsecond Metrology testbed at JPL. Details of a new vacuum- compatible remote CCD enclosure and specialized readout sequence programming will also be presented

Cancer stem cells in tumor heterogeneity.

Cancer cells within a given tumor were long regarded as a largely homogeneous group of cells originating from a common progenitor cell. However, it is increasingly appreciated that there is a considerable heterogeneity within tumors also on the tumor cell level. This heterogeneity extends to virtually all measurable properties of cancer cells, ranging from differentiation state, proliferation rate, migratory and invasive capacity to size, and therapeutic response. Such heterogeneity likely represents a major therapeutic hurdle, but the mechanisms underlying its emergence remain poorly understood and a controversial topic. The cancer stem cell model of tumor progression has gained increasing support during the past several years. In this review, I will discuss some major implications of the cancer stem cell hypothesis on the origins of tumor heterogeneity, focusing both on heterogeneity within the tumor cells proper and on potential transdifferentiation of cancer stem cells into stromal and endothelial lineages, as well as on heterogeneity of the therapeutic response. Evidence for and against a direct and causal role of cancer stem cells in the emergence of tumor heterogeneity will be weighed and alternative explanations for apparently contradictory observations discussed. Finally, I will discuss the potential origins of cancer stem cells and the various implications of origin to the contribution to tumor heterogeneity, and outline some future directions