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      1. Author :
        Cortez-Retamozo, V.; Etzrodt, M.; Newton, A.; Rauch, P. J.; Chudnovskiy, A.; Berger, C.; Ryan, R. J.; Iwamoto, Y.; Marinelli, B.; Gorbatov, R.; Forghani, R.; Novobrantseva, T. I.; Koteliansky, V.; Figueiredo, J. L.; Chen, J. W.; Anderson, D. G.; Nahrendorf, M.; Swirski, F. K.; Weissleder, R.; Pittet, M. J.
      2. Title :
        Origins of tumor-associated macrophages and neutrophils
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Proc Natl Acad Sci U S A
      6. Products :

        AngioSense

      7. Volume :
        109
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; Humans; Macrophages/*immunology; Mice; Neoplasms/immunology/*pathology; Neutrophils/*immunology; Spleen/immunology/pathology
      12. Abstract :
        Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) can control cancer growth and exist in almost all solid neoplasms. The cells are known to descend from immature monocytic and granulocytic cells, respectively, which are produced in the bone marrow. However, the spleen is also a recently identified reservoir of monocytes, which can play a significant role in the inflammatory response that follows acute injury. Here, we evaluated the role of the splenic reservoir in a genetic mouse model of lung adenocarcinoma driven by activation of oncogenic Kras and inactivation of p53. We found that high numbers of TAM and TAN precursors physically relocated from the spleen to the tumor stroma, and that recruitment of tumor-promoting spleen-derived TAMs required signaling of the chemokine receptor CCR2. Also, removal of the spleen, either before or after tumor initiation, reduced TAM and TAN responses significantly and delayed tumor growth. The mechanism by which the spleen was able to maintain its reservoir capacity throughout tumor progression involved, in part, local accumulation in the splenic red pulp of typically rare extramedullary hematopoietic stem and progenitor cells, notably granulocyte and macrophage progenitors, which produced CD11b(+) Ly-6C(hi) monocytic and CD11b(+) Ly-6G(hi) granulocytic cells locally. Splenic granulocyte and macrophage progenitors and their descendants were likewise identified in clinical specimens. The present study sheds light on the origins of TAMs and TANs, and positions the spleen as an important extramedullary site, which can continuously supply growing tumors with these cells.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22308361
      14. Call Number :
        PKI @ kd.modi @ 14
      15. Serial :
        10432
      1. Author :
        Earley, S.; Vinegoni, C.; Dunham, J.; Gorbatov, R.; Feruglio, P. F.; Weissleder, R.
      2. Title :
        In vivo imaging of drug-induced mitochondrial outer membrane permeabilization at single-cell resolution
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cancer Res
      6. Products :

        AngioSenseAnnexin Vivo

      7. Volume :
        72
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Annexin Vivo, Annexin-Vivo, Aniline Compounds/*pharmacology; Animals; Antineoplastic Agents/*pharmacology; *Apoptosis; Breast Neoplasms/drug therapy/*physiopathology; Cell Line, Tumor; Female; Green Fluorescent Proteins; Humans; Image Processing, Computer-Assisted; Mice; Mice, Nude; Mitochondrial Membranes/drug effects/*physiology; Mitochondrial Proteins/metabolism; Molecular Imaging/*methods; Pancreatic Neoplasms/drug therapy/*physiopathology; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors; Recombinant Fusion Proteins/metabolism; Single-Cell Analysis; Sulfonamides/*pharmacology; Tumor Microenvironment
      12. Abstract :
        Observing drug responses in the tumor microenvironment in vivo can be technically challenging. As a result, cellular responses to molecularly targeted cancer drugs are often studied in cell culture, which does not accurately represent the behavior of cancer cells growing in vivo. Using high-resolution microscopy and fluorescently labeled genetic reporters for apoptosis, we developed an approach to visualize drug-induced cell death at single-cell resolution in vivo. Stable expression of the mitochondrial intermembrane protein IMS-RP was established in human breast and pancreatic cancer cells. Image analysis was then used to quantify release of IMS-RP into the cytoplasm upon apoptosis and irreversible mitochondrial permeabilization. Both breast and pancreatic cancer cells showed higher basal apoptotic rates in vivo than in culture. To study drug-induced apoptosis, we exposed tumor cells to navitoclax (ABT-263), an inhibitor of Bcl-2, Bcl-xL, and Bcl-w, both in vitro and in vivo. Although the tumors responded to Bcl-2 inhibition in vivo, inducing apoptosis in around 20% of cancer cells, the observed response was much higher in cell culture. Together, our findings show an imaging technique that can be used to directly visualize cell death within the tumor microenvironment in response to drug treatment.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22505651
      14. Call Number :
        PKI @ kd.modi @ 11
      15. Serial :
        10433
      1. Author :
        Fu, A.; Wilson, R. J.; Smith, B. R.; Mullenix, J.; Earhart, C.; Akin, D.; Guccione, S.; Wang, S. X.; Gambhir, S. S.
      2. Title :
        Fluorescent magnetic nanoparticles for magnetically enhanced cancer imaging and targeting in living subjects
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        ACS Nano
      6. Products :

        AngioSense

      7. Volume :
        6
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; Cell Line, Tumor; Fluorescent Dyes/*chemistry/*diagnostic use; Glioblastoma/*pathology; Humans; Magnetic Fields; Magnetite Nanoparticles/*diagnostic use; Materials Testing; Mice; Mice, SCID; Microscopy, Fluorescence/*methods; Nanocapsules/*chemistry/ultrastructure; Particle Size
      12. Abstract :
        Early detection and targeted therapy are two major challenges in the battle against cancer. Novel imaging contrast agents and targeting approaches are greatly needed to improve the sensitivity and specificity of cancer theranostic agents. Here, we implemented a novel approach using a magnetic micromesh and biocompatible fluorescent magnetic nanoparticles (FMN) to magnetically enhance cancer targeting in living subjects. This approach enables magnetic targeting of systemically administered individual FMN, containing a single 8 nm superparamagnetic iron oxide core. Using a human glioblastoma mouse model, we show that nanoparticles can be magnetically retained in both the tumor neovasculature and surrounding tumor tissues. Magnetic accumulation of nanoparticles within the neovasculature was observable by fluorescence intravital microscopy in real time. Finally, we demonstrate that such magnetically enhanced cancer targeting augments the biological functions of molecules linked to the nanoparticle surface.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22857784
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10434
      1. Author :
        Kozlowski, C.; Weimer, R. M.
      2. Title :
        An automated method to quantify microglia morphology and application to monitor activation state longitudinally in vivo
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        PLoS One
      6. Products :

        AngioSense

      7. Volume :
        7
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; Antigens, CD/metabolism; Antigens, Differentiation, Myelomonocytic/metabolism; Calcium-Binding Proteins/metabolism; Central Nervous System/metabolism; Green Fluorescent Proteins/genetics/*metabolism; Immunohistochemistry/*methods; Lipopolysaccharides/pharmacology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microfilament Proteins/metabolism; Microglia/cytology/drug effects/*metabolism; Microscopy, Confocal/*methods; Receptors, Cytokine/genetics/metabolism; Receptors, HIV/genetics/metabolism; Reproducibility of Results
      12. Abstract :
        Microglia are specialized immune cells of the brain. Upon insult, microglia initiate a cascade of cellular responses including a characteristic change in cell morphology. To study the dynamics of microglia immune response in situ, we developed an automated image analysis method that enables the quantitative assessment of microglia activation state within tissue based solely on cell morphology. Per cell morphometric analysis of fluorescently labeled microglia is achieved through local iterative threshold segmentation, which reduces errors caused by signal-to-noise variation across large volumes. We demonstrate, utilizing systemic application of lipopolysaccharide as a model of immune challenge, that several morphological parameters, including cell perimeter length, cell roundness and soma size, quantitatively distinguish resting versus activated populations of microglia within tissue comparable to traditional immunohistochemistry methods. Furthermore, we provide proof-of-concept data that monitoring soma size enables the longitudinal assessment of microglia activation in the mouse neocortex imaged via 2-photon in vivo microscopy. The ability to quantify microglia activation automatically by shape alone allows unbiased and rapid analysis of both fixed and in vivo central nervous system tissue.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22457705
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10435
      1. Author :
        Lee, S.; Vinegoni, C.; Feruglio, P. F.; Fexon, L.; Gorbatov, R.; Pivoravov, M.; Sbarbati, A.; Nahrendorf, M.; Weissleder, R.
      2. Title :
        Real-time in vivo imaging of the beating mouse heart at microscopic resolution
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Commun
      6. Products :

        AngioSense

      7. Volume :
        3
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense
      12. Abstract :
        Real-time imaging of moving organs and tissues at microscopic resolutions represents a major challenge in studying the complex biology of live animals. Here we present a technique based on a novel stabilizer setup combined with a gating acquisition algorithm for the imaging of a beating murine heart at the single-cell level. The method allows serial in vivo fluorescence imaging of the beating heart in live mice in both confocal and nonlinear modes over the course of several hours. We demonstrate the utility of this technique for in vivo optical sectioning and dual-channel time-lapse fluorescence imaging of cardiac ischaemia. The generic method could be adapted to other moving organs and thus broadly facilitate in vivo microscopic investigations.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22968700
      14. Call Number :
        PKI @ kd.modi @ 7
      15. Serial :
        10436
      1. Author :
        Matsumoto, K.; Azami, T.; Otsu, A.; Takase, H.; Ishitobi, H.; Tanaka, J.; Miwa, Y.; Takahashi, S.; Ema, M.
      2. Title :
        Study of normal and pathological blood vessel morphogenesis in Flt1-tdsRed BAC Tg mice
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Genesis
      6. Products :

        AngioSense

      7. Volume :
        50
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; Blood Vessels/embryology/*physiology; Chromosomes, Artificial, Bacterial; Embryo, Mammalian; Endothelial Cells/cytology/metabolism; Endothelium, Vascular/cytology/embryology/metabolism; Female; Founder Effect; Gene Expression Regulation, Developmental; Genes, Reporter; Mice; *Mice, Transgenic; Microscopy, Fluorescence; Morphogenesis/physiology; *Neovascularization, Pathologic; *Neovascularization, Physiologic; Retina/embryology/*physiology; Vascular Endothelial Growth Factor A/genetics/metabolism; Vascular Endothelial Growth Factor Receptor-1/genetics/*metabolism; Vascular Endothelial Growth Factor Receptor-2/genetics/metabolism
      12. Abstract :
        Blood vessel development and network patterning are controlled by several signaling molecules, including VEGF, FGF, TGF-ss, and Ang-1,2. Among these, the role of VEGF-A signaling in vessel morphogenesis is best understood. The biological activity of VEGF-A depends on its reaction with specific receptors Flt1 and Flk1. Roles of VEGF-A signaling in endothelial cell proliferation, migration, survival, vascular permeability, and induction of tip cell filopodia have been reported. In this study, we have generated Flt1-tdsRed BAC transgenic (Tg) mice to monitor Flt1 gene expression during vascular development. We show that tdsRed fluorescence is observed within blood vessels of adult mice and embryos, indicative of retinal angiogenesis and tumor angiogenesis. Flt1 expression recapitulated by Flt1-tdsRed BAC Tg mice overlapped well with Flk1, while Flt1 was expressed more abundantly in endothelial cells of large blood vessels such as dorsal aorta and presumptive stalk cells in retina, providing a unique model to study blood vessel development.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22489010
      14. Call Number :
        PKI @ kd.modi @ 10
      15. Serial :
        10437
      1. Author :
        Rao, S. M.; Auger, J. L.; Gaillard, P.; Weissleder, R.; Wada, E.; Torres, R.; Kojima, M.; Benoist, C.; Mathis, D.; Binstadt, B. A.
      2. Title :
        The neuropeptide neuromedin U promotes autoantibody-mediated arthritis
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Arthritis Res Ther
      6. Products :

        AngioSense

      7. Volume :
        14
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; Arthritis/genetics/*immunology/metabolism; Autoantibodies/*immunology; Bone Marrow Cells/immunology/metabolism/pathology; Calcium/immunology/metabolism; Female; Male; Mast Cells/immunology/metabolism/pathology; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Knockout; Mice, Transgenic; Neuropeptides/deficiency/genetics/*immunology; Protein Isoforms/deficiency/genetics/immunology; Receptors, Neurotensin/deficiency/genetics/immunology; Receptors, Neurotransmitter/deficiency/genetics/*immunology; Spleen/immunology/metabolism/pathology
      12. Abstract :
        INTRODUCTION: Neuromedin U (NMU) is a neuropeptide with pro-inflammatory activity. The primary goal of this study was to determine if NMU promotes autoantibody-induced arthritis. Additional studies addressed the cellular source of NMU and sought to define the NMU receptor responsible for its pro-inflammatory effects. METHODS: Serum containing arthritogenic autoantibodies from K/BxN mice was used to induce arthritis in mice genetically lacking NMU. Parallel experiments examined whether NMU deficiency impacted the early mast-cell-dependent vascular leak response induced by these autoantibodies. Bone-marrow chimeric mice were generated to determine whether pro-inflammatory NMU is derived from hematopoietic cells or stromal cells. Mice lacking the known NMU receptors singly and in combination were used to determine susceptibility to serum-transferred arthritis and in vitro cellular responses to NMU. RESULTS: NMU-deficient mice developed less severe arthritis than control mice. Vascular leak was not affected by NMU deficiency. NMU expression by bone-marrow-derived cells mediated the pro-arthritogenic effect. Deficiency of all of the known NMU receptors, however, had no impact on arthritis severity and did not affect the ability of NMU to stimulate intracellular calcium flux. CONCLUSIONS: NMU-deficient mice are protected from developing autoantibody-induced inflammatory arthritis. NMU derived from hematopoietic cells, not neurons, promotes the development of autoantibody-induced inflammatory arthritis. This effect is mediated by a receptor other than the currently known NMU receptors.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22314006
      14. Call Number :
        PKI @ kd.modi @ 13
      15. Serial :
        10438
      1. Author :
        Smith, B. R.; Kempen, P.; Bouley, D.; Xu, A.; Liu, Z.; Melosh, N.; Dai, H.; Sinclair, R.; Gambhir, S. S.
      2. Title :
        Shape matters: intravital microscopy reveals surprising geometrical dependence for nanoparticles in tumor models of extravasation
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nano Lett
      6. Products :

        AngioSense

      7. Volume :
        12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; *Disease Models, Animal; Ear Neoplasms/*blood supply/pathology; Humans; Mice; Microscopy, Fluorescence; Nanoparticles/*chemistry; *Nanotechnology; Nanotubes, Carbon/chemistry; Neoplasms, Experimental/*blood supply/pathology; Particle Size; Quantum Dots; Surface Properties
      12. Abstract :
        Delivery is one of the most critical obstacles confronting nanoparticle use in cancer diagnosis and therapy. For most oncological applications, nanoparticles must extravasate in order to reach tumor cells and perform their designated task. However, little understanding exists regarding the effect of nanoparticle shape on extravasation. Herein we use real-time intravital microscopic imaging to meticulously examine how two different nanoparticles behave across three different murine tumor models. The study quantitatively demonstrates that high-aspect ratio single-walled carbon nanotubes (SWNTs) display extravasational behavior surprisingly different from, and counterintuitive to, spherical nanoparticles although the nanoparticles have similar surface coatings, area, and charge. This work quantitatively indicates that nanoscale extravasational competence is highly dependent on nanoparticle geometry and is heterogeneous.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22650417
      14. Call Number :
        PKI @ kd.modi @ 9
      15. Serial :
        10439
      1. Author :
        Bendaoud, M.; Vinogradov, E.; Balashova, N. V.; Kadouri, D. E.; Kachlany, S. C.; Kaplan, J. B.
      2. Title :
        Broad-spectrum biofilm inhibition by Kingella kingae exopolysaccharide
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Bacteriol
      6. Products :

        Bioware bacteriaIVIS Imaging Systems

      7. Volume :
        193
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen29, Xen 29, Staphylococcus aureus Xen29, IVISBacterial Physiological Phenomena/drug effects; Bacterial Proteins/genetics/metabolism; Biofilms/*drug effects; *Down-Regulation/drug effects; Fungi/drug effects/physiology; Kingella kingae/chemistry/genetics/*metabolism; Molecular Sequence Data; Polysaccharides, Bacterial/biosynthesis/chemistry/*pharmacology
      12. Abstract :
        Cell-free extracts prepared from Kingella kingae colony biofilms were found to inhibit biofilm formation by Aggregatibacter actinomycetemcomitans, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Candida albicans, and K. kingae. The extracts evidently inhibited biofilm formation by modifying the physicochemical properties of the cell surface, the biofilm matrix, and the substrate. Chemical and biochemical analyses indicated that the biofilm inhibition activity in the K. kingae extract was due to polysaccharide. Structural analyses showed that the extract contained two major polysaccharides. One was a linear polysaccharide with the structure -->6)-alpha-d-GlcNAcp-(1-->5)-beta-d-OclAp-(2-->, which was identical to a capsular polysaccharide produced by Actinobacillus pleuropneumoniae serotype 5. The second was a novel linear polysaccharide, designated PAM galactan, with the structure -->3)-beta-d-Galf-(1-->6)-beta-d-Galf-(1-->. Purified PAM galactan exhibited broad-spectrum biofilm inhibition activity. A cluster of three K. kingae genes encoding UDP-galactopyranose mutase (ugm) and two putative galactofuranosyl transferases was sufficient for the synthesis of PAM galactan in Escherichia coli. PAM galactan is one of a growing number of bacterial polysaccharides that exhibit antibiofilm activity. The biological roles and potential technological applications of these molecules remain unknown.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21602333
      14. Call Number :
        PKI @ kd.modi @ 17
      15. Serial :
        10446
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