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      1. Author :
        Edinger, M; Cao, Y-a; Hornig, Y S; Jenkins, D E; Verneris, M R; Bachmann, M H; Negrin, R S; Contag, C H
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2002
      5. Publication :
        European journal of cancer (Oxford, England: 1990)
      6. Products :
      7. Volume :
        38
      8. Issue :
        16
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Diagnostic Imaging; Forecasting; Luminescent Measurements; Mice; Models, Animal; Neoplasms; PC-3M-luc; Sensitivity and Specificity
      12. Abstract :
        Malignant disease is the final manifestation of complex molecular and cellular events leading to uncontrolled cellular proliferation and eventually tissue destruction and metastases. While the in vitro examination of cultured tumour cells permits the molecular dissection of early pathways in tumorigenesis on cellular and subcellular levels, only interrogation of these processes within the complexity of organ systems of the living animal can reveal the full range of pathophysiological changes that occur in neoplastic disease. Such analyses require technologies that facilitate the study of biological processes in vivo, and several approaches have been developed over the last few years. These strategies, in the nascent field of in vivo molecular and cellular imaging, combine molecular biology with imaging modalities as a means to real-time acquisition of functional information about disease processes in living systems. In this review, we will summarise recent developments in in vivo bioluminescence imaging (BLI) and discuss the potential of this imaging strategy for the future of cancer research.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/12387838
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8983
      1. Author :
        Thomas Christen, Matthias Nahrendorf, Moritz Wildgruber, Filip K. Swirski, Elena Aikawa, Peter Waterman, Koichi Shimizu, Ralph Weissleder and Peter Libby
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Circulation
      6. Products :
      7. Volume :
        119
      8. Issue :
        14
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        In vivo imaging; inflammation; leukocytes; rejection; transplantation; fluorescence molecular tomography; FMT; Prosense
      12. Abstract :
        Background: Clinical detection of transplant rejection by repeated endomyocardial biopsy requires catheterization and entails risks. Recently developed molecular and cellular imaging techniques that visualize macrophage host responses could provide a noninvasive alternative. Yet, which macrophage functions may provide useful markers for detecting parenchymal rejection remains uncertain.

        Methods and Results: We transplanted isografts from B6 mice and allografts from Balb/c mice heterotopically into B6 recipients. In this allograft across major histocompatability barriers, the transplanted heart undergoes predictable progressive rejection, leading to graft failure after 1 week. During rejection, crucial macrophage functions, including phagocytosis and release of proteases, render these abundant innate immune cells attractive imaging targets. Two or 6 days after transplantation, we injected either a fluorescent protease sensor or a magnetofluorescent phagocytosis marker. Histological and flow cytometric analyses established that macrophages function as the major cellular signal source. In vivo, we obtained a 3-dimensional functional map of macrophages showing higher phagocytic uptake of magnetofluorescent nanoparticles during rejection using magnetic resonance imaging and higher protease activity in allografts than in isografts using tomographic fluorescence. We further assessed the sensitivity of imaging to detect the degree of rejection. In vivo imaging of macrophage response correlated closely with gradually increasing allograft rejection and attenuated rejection in recipients with a genetically impaired immune response resulting from a deficiency in recombinase-1 (RAG-1-/-).

        Conclusions: Molecular imaging reporters of either phagocytosis or protease activity can detect cardiac allograft rejection noninvasively, promise to enhance the search for novel tolerance-inducing strategies, and have translational potential.
      13. URL :
        http://circ.ahajournals.org/cgi/content/abstract/circulationaha;119/14/1925
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4640
      1. Author :
        Giubellino, Alessio; Gao, Yang; Lee, Sunmin; Lee, Min-Jung; Vasselli, James R; Medepalli, Sampath; Trepel, Jane B; Burke, Terrence R, Jr; Bottaro, Donald P
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Cancer research
      6. Products :
      7. Volume :
        67
      8. Issue :
        13
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; GRB2 Adaptor Protein; Humans; Mice; Mice, SCID; Microscopy, Fluorescence; Neoplasm Metastasis; Neoplasm Transplantation; PC-3M-luc; Protein Binding; Protein Structure, Tertiary; Tetrazolium Salts; Thiazoles
      12. Abstract :
        Metastasis, the primary cause of death in most forms of cancer, is a multistep process whereby cells from the primary tumor spread systemically and colonize distant new sites. Blocking critical steps in this process could potentially inhibit tumor metastasis and dramatically improve cancer survival rates; however, our understanding of metastasis at the molecular level is still rudimentary. Growth factor receptor binding protein 2 (Grb2) is a widely expressed adapter protein with roles in epithelial cell growth and morphogenesis, as well as angiogenesis, making it a logical target for anticancer drug development. We have previously shown that a potent antagonist of Grb2 Src homology-2 domain-binding, C90, blocks growth factor-driven cell motility in vitro and angiogenesis in vivo. We now report that C90 inhibits metastasis in vivo in two aggressive tumor models, without affecting primary tumor growth rate. These results support the potential efficacy of this compound in reducing the metastatic spread of primary solid tumors and establish a critical role for Grb2 Src homology-2 domain-mediated interactions in this process.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17616655
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8969
      1. Author :
        Minakuchi, Yoshiko; Takeshita, Fumitaka; Kosaka, Nobuyoshi; Sasaki, Hideo; Yamamoto, Yusuke; Kouno, Makiko; Honma, Kimi; Nagahara, Shunji; Hanai, Koji; Sano, Akihiko; Kato, Takashi; Terada, Masaaki; Ochiya, Takahiro
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2004
      5. Publication :
        Nucleic acids research
      6. Products :
      7. Volume :
        32
      8. Issue :
        13
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; B16-F10-luc-G5 cells; Bioware; Cell Division; Cell Line, Tumor; Collagen; Humans; Injections; Male; Mice; Mice, Nude; RNA Interference; RNA Stability; RNA, Small Interfering; Testicular Neoplasms; Transduction, Genetic; Xenograft Model Antitumor Assays
      12. Abstract :
        Silencing gene expression by siRNAs is rapidly becoming a powerful tool for the genetic analysis of mammalian cells. However, the rapid degradation of siRNA and the limited duration of its action call for an efficient delivery technology. Accordingly, we describe here that Atelocollagen complexed with siRNA is resistant to nucleases and is efficiently transduced into cells, thereby allowing long-term gene silencing. Site-specific in vivo administration of an anti-luciferase siRNA/Atelocollagen complex reduced luciferase expression in a xenografted tumor. Furthermore, Atelocollagen-mediated transfer of siRNA in vivo showed efficient inhibition of tumor growth in an orthotopic xenograft model of a human non-seminomatous germ cell tumor. Thus, for clinical applications of siRNA, an Atelocollagen-based non-viral delivery method could be a reliable approach to achieve maximal function of siRNA in vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/15272050
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9003
      1. Author :
        Neal K. Devaraj; Ralph Weissleder; Scott A. Hilderbrand
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Bioconjugate Chemistry
      6. Products :
      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
      1. Author :
        Virna Cortez-Retamozo, Filip K. Swirski, Peter Waterman, Hushan Yuan, Jose Luiz Figueiredo, Andita P. Newton, Rabi Upadhyay, Claudio Vinegoni, Rainer Kohler, Joseph Blois, Adam Smith, Matthias Nahrendorf, Lee Josephson, Ralph Weissleder and Mikael J. Pittet
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Journal of Clinical Investigation
      6. Products :
      7. Volume :
        118
      8. Issue :
        12
      9. Page Numbers :
        N/A
      10. Research Area :
        Physiology
      11. Keywords :
        FMT; in vivo imaging; ProSense; MMPSense
      12. Abstract :
        Eosinophils are multifunctional leukocytes that degrade and remodel tissue extracellular matrix through production of proteolytic enzymes, release of proinflammatory factors to initiate and propagate inflammatory responses, and direct activation of mucus secretion and smooth muscle cell constriction. Thus, eosinophils are central effector cells during allergic airway inflammation and an important clinical therapeutic target. Here we describe the use of an injectable MMP-targeted optical sensor that specifically and quantitatively resolves eosinophil activity in the lungs of mice with experimental allergic airway inflammation. Through the use of real-time molecular imaging methods, we report the visualization of eosinophil responses in vivo and at different scales. Eosinophil responses were seen at single-cell resolution in conducting airways using near-infrared fluorescence fiberoptic bronchoscopy, in lung parenchyma using intravital microscopy, and in the whole body using fluorescence-mediated molecular tomography. Using these real-time imaging methods, we confirmed the immunosuppressive effects of the glucocorticoid drug dexamethasone in the mouse model of allergic airway inflammation and identified a viridin-derived prodrug that potently inhibited the accumulation and enzyme activity of eosinophils in the lungs. The combination of sensitive enzyme-targeted sensors with noninvasive molecular imaging approaches permitted evaluation of airway inflammation severity and was used as a model to rapidly screen for new drug effects. Both fluorescence-mediated tomography and fiberoptic bronchoscopy techniques have the potential to be translated into the clinic.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2579705/?tool=pubmed
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4536
      1. Author :
        Zongjin Li, Kitchener D. Wilson, Bryan Smith, Daniel L. Kraft, Fangjun Jia, Mei Huang, Xiaoyan Xie, Robert C. Robbins, Sanjiv S. Gambhir, Irving L. Weissman and Joseph C. Wu
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        4
      8. Issue :
        12
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        in vivo imaging; human embryonic stem cells; hESCs; endothelial cells; ECs; AngioSense
      12. Abstract :
        Background: Differentiation of human embryonic stem cells into endothelial cells (hESC-ECs) has the potential to provide an unlimited source of cells for novel transplantation therapies of ischemic diseases by supporting angiogenesis and vasculogenesis. However, the endothelial differentiation efficiency of the conventional embryoid body (EB) method is low while the 2-dimensional method of co-culturing with mouse embryonic fibroblasts (MEFs) require animal product, both of which can limit the future clinical application of hESC-ECs. Moreover, to fully understand the beneficial effects of stem cell therapy, investigators must be able to track the functional biology and physiology of transplanted cells in living subjects over time.

        Methodology: In this study, we developed an extracellular matrix (ECM) culture system for increasing endothelial differentiation and free from contaminating animal cells. We investigated the transcriptional changes that occur during endothelial differentiation of hESCs using whole genome microarray, and compared to human umbilical vein endothelial cells (HUVECs). We also showed functional vascular formation by hESC-ECs in a mouse dorsal window model. Moreover, our study is the first so far to transplant hESC-ECs in a myocardial infarction model and monitor cell fate using molecular imaging methods.

        Conclusion: Taken together, we report a more efficient method for derivation of hESC-ECs that express appropriate patterns of endothelial genes, form functional vessels in vivo, and improve cardiac function. These studies suggest that hESC-ECs may provide a novel therapy for ischemic heart disease in the future.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795856/?tool=pubmed
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4557
      1. Author :
        Okuda, Tomoyuki; Kawaguchi, Yasuhisa; Okamoto, Hirokazu
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Current topics in medicinal chemistry
      6. Products :
      7. Volume :
        9
      8. Issue :
        12
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; Gene Silencing; PC-3M-luc; Peptides; Proteins; RNA Interference; Transfection
      12. Abstract :
        RNA interference (RNAi) is an attractive phenomenon for practical use that specifically inhibits gene expression and is carried out by small double-stranded RNAs (dsRNAs) including small interfering RNA (siRNA) or short hairpin RNA (shRNA). In addition, RNAi is of great interest for clinical use to cure refractory diseases related to the expression of a specific gene. To achieve gene silencing in the body, a sufficient amount of dsRNA must be delivered and internalized into target cells. However, dsRNAs have a large molecular weight and net negative charge, which limits their membrane-permeating ability. Moreover, dsRNAs are rapidly degraded by endonucleses in the body. Therefore, for the efficient delivery of dsRNAs, many approaches based on drug delivery systems have been carried out. In this review, we focus on recent reports about the application of functional peptides and proteins designed for the efficient delivery of dsRNAs.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19860710
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8962
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