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      1. Author :
        Galina Gabriely, Thomas Wurdinger, Santosh Kesari, Christine C. Esau, Julja Burchard, Peter S. Linsley and Anna M. Krichevsky
      2. Title :
        MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Molecular and Cellular Biology
      6. Products :

        MMPSense

      7. Volume :
        28
      8. Issue :
        17
      9. Page Numbers :
        N/A
      10. Research Area :
        Neuroscience
      11. Keywords :
        in vivo imaging; MMPSense; microRNA 21; glioma
      12. Abstract :
        Substantial data indicate that microRNA 21 (miR-21) is significantly elevated in glioblastoma (GBM) and in many other tumors of various origins. This microRNA has been implicated in various aspects of carcinogenesis, including cellular proliferation, apoptosis, and migration. We demonstrate that miR-21 regulates multiple genes associated with glioma cell apoptosis, migration, and invasiveness, including the RECK and TIMP3 genes, which are suppressors of malignancy and inhibitors of matrix metalloproteinases (MMPs). Specific inhibition of miR-21 with antisense oligonucleotides leads to elevated levels of RECK and TIMP3 and therefore reduces MMP activities in vitro and in a human model of gliomas in nude mice. Moreover, downregulation of miR-21 in glioma cells leads to decreases of their migratory and invasion abilities. Our data suggest that miR-21 contributes to glioma malignancy by downregulation of MMP inhibitors, which leads to activation of MMPs, thus promoting invasiveness of cancer cells. Our results also indicate that inhibition of a single oncomir, like miR-21, with specific antisense molecules can provide a novel therapeutic approach for “physiological” modulation of multiple proteins whose expression is deregulated in cancer.
      13. URL :
        http://mcb.asm.org/cgi/content/abstract/28/17/5369
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4546
      1. Author :
        John Baeten; Jodi Haller; Helen Shih; Vasilis Ntziachristos
      2. Title :
        In Vivo Investigation of Breast Cancer Progression by Use of an Internal Control
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Neoplasia
      6. Products :

        ProSenseMMPSenseAngioSense

      7. Volume :
        11
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        in vivo imaging; optical imaging; breast cancer; molecular imaging
      12. Abstract :
        Optical imaging of breast cancer has been considered for detecting functional and molecular characteristics of diseases in clinical and preclinical settings. Applied to laboratory research, photonic investigations offer a highly versatile tool for preclinical imaging and drug discovery. A particular advantage of the optical method is the availability of multiple spectral bands for performing imaging. Herein, we capitalize on this feature to demonstrate how it is possible to use different wavelengths to offer internal controls and significantly improve the observation accuracy in molecular imaging applications. In particular, we show the independent in vivo detection of cysteine proteases along with tumor permeability and interstitial volume measurements using a dual-wavelength approach. To generate results with a view toward clinically geared studies, a transgenic Her2/neu mouse model that spontaneously developed mammary tumors was used. In vivo findings were validated against conventional ex vivo tests such as histology and Western blot analyses. By correcting for biodistribution parameters, the dual-wavelength method increases the accuracy of molecular observations by separating true molecular target from probe biodistribution. As such, the method is highly appropriate for molecular imaging studies where often probe delivery and target presence are not independently assessed. On the basis of these findings, we propose the dual-wavelength/normalization approach as an essential method for drug discovery and preclinical imaging studies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647724/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4494
      1. Author :
        Houari Korideck; Jeffrey D. Peterson
      2. Title :
        Noninvasive quantitative tomography of the therapeutic response to dexamethasone in ovalbumin-induced murine asthma
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Journal of Pharmacology and Experimental Therapeutics
      6. Products :

        FMT Imaging SystemsProSense

      7. Volume :
        329
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research; Biology
      11. Keywords :
        in vivo imaging; therapeutics; asthma; pulmonary diseases; noninvasive; infrared imaging; fluorescence molecular tomography; FMT; Fluorescence Imaging Agents
      12. Abstract :
        Animal models of pulmonary inflammation are critical for understanding the pathophysiology of asthma and for developing new therapies. Current conventional assessments in mouse models of asthma and chronic obstructive pulmonary disease rely on invasive measures of pulmonary function and terminal characterization of cells infiltrating into the lung. The ability to noninvasively visualize and quantify the underlying biological processes in mouse pulmonary models in vivo would provide a significant advance in characterizing disease processes and the effects of therapeutics. We report the utility of near-infrared imaging agents, in combination with fluorescence molecular tomography (FMT) imaging, for the noninvasive quantitative imaging of mouse lung inflammation in an ovalbumin (OVA)-induced chronic asthma model. BALB/c mice were intraperitoneally sensitized with OVA-Alum (aluminum hydroxide) at days 0 and 14, followed by daily intranasal challenge with OVA in phosphate-buffered saline from days 21 to 24. Dexamethasone and control therapies were given intraperitoneally 4 h before each intranasal inhalation of OVA from days 21 to 24. Twenty-four hours before imaging, the mice were injected intravenously with 5 nmol of the cathepsin-activatable fluorescent agent, ProSense 680. Quantification by FMT revealed in vivo cysteine protease activity within the lung associated with the inflammatory eosinophilia, which decreased in response to dexamethasone treatment. Results were correlated with in vitro laboratory tests (bronchoalveolar lavage cell analysis and immunohistochemistry) and revealed good correlation between these measures and quantification of ProSense 680 activation. We have demonstrated the ability of FMT to noninvasively visualize and quantify inflammation in the lung and monitor therapeutic efficacy in vivo.
      13. URL :
        http://jpet.aspetjournals.org/content/329/3/882.full
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4473
      1. Author :
        Jason R. McCarthy, Purvish Patel, Ion Botnaru, Pouneh Haghayeghi, Ralph Weissleder and Farouc A. Jaffer
      2. Title :
        Multimodal nanoagents for the detection of intravascular thrombi
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Bioconjugate Chemistry
      6. Products :

        VivoTag

      7. Volume :
        20
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        In vivo imaging; thrombi; VivoTag
      12. Abstract :
        Thrombosis underlies numerous life-threatening cardiovascular syndromes. Development of thrombosis-specific molecular imaging agents to detect and monitor thrombogenesis and fibrinolysis in vivo could improve the diagnosis, risk stratification, and treatment of thrombosis syndromes. To this end, we have synthesized efficient multimodal nanoagents targeted to two different constituents of thrombi, namely, fibrin and activated factor XIII. These agents are targeted via the conjugation of peptide-targeting ligands to the surface of fluorescently labeled magnetic nanoparticles. As demonstrated by in vitro and in vivo studies, both nanoagents possess high affinities for thrombi, and enable mutimodal fluorescence and magnetic resonance imaging.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19456115
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4647
      1. Author :
        Neal K. Devaraj; Ralph Weissleder; Scott A. Hilderbrand
      2. Title :
        Tetrazine-Based Cycloadditions: Application to Pretargeted Live Cell Imaging
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Bioconjugate Chemistry
      6. Products :

        VivoTag

      7. Volume :
        19
      8. Issue :
        12
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        in vivo labelling; breast cancer; in vivo imaging
      12. Abstract :
        Bioorthogonal tetrazine cycloadditions have been applied to live cell labeling. Tetrazines react irreversibly with the strained dienophile norbornene forming dihydropyrazine products and dinitrogen. The reaction is high yielding, selective, and fast in aqueous media. Her2/neu receptors on live human breast cancer cells were targeted with a monoclonal antibody modified with a norbornene. Tetrazines conjugated to a near-infrared fluorochrome selectively and rapidly label the pretargeted antibody in the presence of serum. These findings indicate that this chemistry is suitable for in vitro labeling experiments, and suggests that it may prove a useful strategy for in vivo pretargeted imaging under numerous modalities.
      13. URL :
        http://pubs.acs.org/doi/abs/10.1021/bc8004446
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4499
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