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      1. Author :
        Lambrechts, Saskia A G; Demidova, Tatiana N; Aalders, Maurice C G; Hasan, Tayyaba; Hamblin, Michael R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        Photochemical & photobiological sciences: Official journal of the European Photochemistry Association and the European Society for Photobiology
      6. Products :
      7. Volume :
        4
      8. Issue :
        7
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Burns; Mice; Photochemotherapy; Staphylococcal Infections; Staphylococcus aureus; Xen8.1
      12. Abstract :
        The rise of multiply antibiotic resistant bacteria has led to searches for novel antimicrobial therapies to treat infections. Photodynamic therapy (PDT) is a potential candidate; it uses the combination of a photosensitizer with visible light to produce reactive oxygen species that lead to cell death. We used PDT mediated by meso-mono-phenyl-tri(N-methyl-4-pyridyl)-porphyrin (PTMPP) to treat burn wounds in mice with established Staphylococcus aureus infections The third degree burn wounds were infected with bioluminescent S. aureus. PDT was applied after one day of bacterial growth by adding a 25% DMSO/500 microM PTMPP solution to the wound followed by illumination with red light and periodic imaging of the mice using a sensitive camera to detect the bioluminescence. More than 98% of the bacteria were eradicated after a light dose of 210 J cm(-2) in the presence of PTMPP. However, bacterial re-growth was observed. Light alone or PDT both delayed the wound healing. These data suggest that PDT has the potential to rapidly reduce the bacterial load in infected burns. The treatment needs to be optimized to reduce wound damage and prevent recurrence.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/15986057
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9993
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        Nature
      6. Products :
      7. Volume :
        433
      8. Issue :
        7025
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Aging; Animals; Antigens, CD36; Cell Line; Dimerization; Ethylnitrosourea; Gene Deletion; Glycerides; Homozygote; Humans; Immunologic Deficiency Syndromes; Lipopeptides; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutagenesis; Mutation; Oligopeptides; Peptidoglycan; Phenotype; Receptors, Cell Surface; Signal Transduction; Staphylococcal Infections; Staphylococcus aureus; Toll-Like Receptor 2; Toll-Like Receptors; Tumor Necrosis Factor-alpha; Zymosan
      12. Abstract :
        Toll-like receptor 2 (TLR2) is required for the recognition of numerous molecular components of bacteria, fungi and protozoa. The breadth of the ligand repertoire seems unusual, even if one considers that TLR2 may form heteromers with TLRs 1 and 6 (ref. 12), and it is likely that additional proteins serve as adapters for TLR2 activation. Here we show that an N-ethyl-N-nitrosourea-induced nonsense mutation of Cd36 (oblivious) causes a recessive immunodeficiency phenotype in which macrophages are insensitive to the R-enantiomer of MALP-2 (a diacylated bacterial lipopeptide) and to lipoteichoic acid. Homozygous mice are hypersusceptible to Staphylococcus aureus infection. Cd36(obl) macrophages readily detect S-MALP-2, PAM(2)CSK(4), PAM(3)CSK(4) and zymosan, revealing that some--but not all--TLR2 ligands are dependent on CD36. Already known as a receptor for endogenous molecules, CD36 is also a selective and nonredundant sensor of microbial diacylglycerides that signal via the TLR2/6 heterodimer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/15690042
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9991
      1. Author :
        David G Kirsch; Daniela M Dinulescu; John B Miller; Jan Grimm; Philip M Santiago1; Nathan P Young; G Petur Nielsen; Bradley J Quade; Christopher J Chaber; Christian P Schultz; Osamu Takeuchi; Roderick T Bronson; Denise Crowley; Stanley J Korsmeyer; Sam S Yoon; Francis J Hornicek; Ralph Weissleder; Tyler Jacks
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Nature Medicine
      6. Products :
      7. Volume :
        13
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        sarcoma; imaging; apoptosis; metatasis; FMT
      12. Abstract :
        Soft tissue sarcomas are mesenchymal tumors that are fatal in approximately one-third of patients. To explore mechanisms of sarcoma pathogenesis, we have generated a mouse model of soft tissue sarcoma. Intramuscular delivery of an adenovirus expressing Cre recombinase in mice with conditional mutations in Kras and Trp53 was sufficient to initiate high-grade sarcomas with myofibroblastic differentiation. Like human sarcomas, these tumors show a predilection for lung rather than lymph node metastasis. Using this model, we showed that a prototype handheld imaging device can identify residual tumor during intraoperative molecular imaging. Deletion of the Ink4a-Arf locus (Cdkn2a), but not Bak1 and Bax, could substitute for mutation of Trp53 in this model. Deletion of Bak1 and Bax, however, was able to substitute for mutation of Trp53 in the development of sinonasal adenocarcinoma. Therefore, the intrinsic pathway of apoptosis seems sufficient to mediate p53 tumor suppression in an epithelial cancer, but not in this model of soft tissue sarcoma.
      13. URL :
        http://www.nature.com/nm/journal/v13/n8/abs/nm1602.html
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4506
      1. Author :
        Kozloff KM, Volakis LI, Marini JC and Caird MS
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Journal of Bone and Mineral Research
      6. Products :
      7. Volume :
        25
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        Physiology
      11. Keywords :
        FMT; bone; OsteoSense; FRFP; in vivo imaging
      12. Abstract :
        Bisphosphonate use has expanded beyond traditional applications to include treatment of a variety of low-bone-mass conditions. Complications associated with long-term bisphosphonate treatment have been noted, generating a critical need for information describing the local bisphosphonate-cell interactions responsible for these observations. This study demonstrates that a fluorescent bisphosphonate analogue, far-red fluorescent pamidronate (FRFP), is an accurate biomarker of bisphosphonate deposition and retention in vivo and can be used to monitor site-specific local drug concentration. In vitro, FRFP is competitively inhibited from the surface of homogenized rat cortical bone by traditional bisphosphonates. In vivo, FRFP delivery to the skeleton is rapid, with fluorescence linearly correlated with bone surface area. Limb fluorescence increases linearly with injected dose of FRFP; injected FRFP does not interfere with binding of standard bisphosphonates at the doses used in this study. Long-term FRFP retention studies demonstrated that FRFP fluorescence decreases in conditions of normal bone turnover, whereas fluorescence was retained in conditions of reduced bone turnover, demonstrating preservation of local FRFP concentration. In the mandible, FRFP localized to the alveolar bone and bone surrounding the periodontal ligament and molar roots, consistent with findings of osteonecrosis of the jaw. These findings support a role for FRFP as an effective in vivo marker for bisphosphonate site-specific deposition, turnover, and long-term retention in the skeleton.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20200982
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4527
      1. Author :
        Stangenberg L, Ellson C, Cortez-Retamozo V, Ortiz-Lopez A, Yuan H, Blois J, Smith RA, Yaffe MB, Weissleder R, Benoist C, Mathis D, Josephson L and Mahmood U
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Arthritis and Rheumatism
      6. Products :
      7. Volume :
        60
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        Physiology
      11. Keywords :
        ProSense; AngioSense; arthritis; in vivo imaging
      12. Abstract :
        OBJECTIVE: To test a novel self-activating viridin (SAV) prodrug that slowly releases wortmannin, a potent phosphoinositide 3-kinase inhibitor, in a model of antibody-mediated inflammatory arthritis.

        METHODS: The SAV prodrug was administered to K/BxN mice or to C57BL/6 (B6) mice that had been injected with K/BxN serum. Ankle thickness was measured, and histologic changes were scored after a 10-day disease course (serum-transfer arthritis). Protease activity was measured by a near-infrared imaging approach using a cleavable cathepsin-selective probe. Further near-infrared imaging techniques were used to analyze early changes in vascular permeability after serum injection, as well as neutrophil-endothelial cell interactions. Neutrophil functions were assessed using an oxidative burst assay as well as a degranulation assay.

        RESULTS: SAV prevented ankle swelling in mice with serum-transfer arthritis in a dose-dependent manner. It also markedly reduced the extent of other features of arthritis, such as protease activity and histology scores for inflammation and joint erosion. Moreover, SAV was an effective therapeutic agent. The underlying mechanisms for the antiinflammatory activity were manifold. Endothelial permeability after serum injection was reduced, as was firm neutrophil attachment to endothelial cells. Endothelial cell activation by tumor necrosis factor alpha was impeded by SAV, as measured by the expression of vascular cell adhesion molecule. Crucial neutrophil functions, such as generation of reactive oxygen species and degranulation of protease-laden vesicles, were decreased by SAV administration.

        CONCLUSION: A novel SAV prodrug proved strongly antiinflammatory in a murine model of antibody-induced inflammatory arthritis. Its activity could be attributed, at least in part, to the inhibition of neutrophil and endothelial cell functions.
      13. URL :
        http://onlinelibrary.wiley.com/doi/10.1002/art.24704/abstract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4528
      1. Author :
        Kenneth M Kozloff, Ralph Weissleder and Umar Mahmood
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Journal of Bone and Mineral Research
      6. Products :
      7. Volume :
        22
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        Physiology
      11. Keywords :
        FMT; OsteoSense; ProSense bone mineralization; bone turnover markers; molecular imaging; bisphosphonates; in vivo imaging
      12. Abstract :
        Abstract: FRFP binds to mineral at osteoblastic, osteoclastic, and quiescent surfaces, with accumulation likely modulated by vascular delivery. In vivo visualization and quantification of binding can be accomplished noninvasively in animal models through optical tomographic imaging.

        Introduction: The development of near-infrared optical markers as reporters of bone metabolism will be useful for early diagnosis of disease. Bisphosphonates bind differentially to osteoblastic and osteoclastic surfaces depending on choice of side-chain and dose, and fluorescently tagged bisphosphonates provide a convenient way to visualize these sites. This study examines the ability of a fluorescently labeled pamidronate imaging probe to bind to regions of bone formation and resorption in vivo.

        Materials and Methods: In vitro binding of a far-red fluorescent pamidronate (FRFP) to mineral was assessed using intact and demineralized dentine slices. In vivo, FRFP binding was studied in three models: developing neonatal mouse, bone healing after injury, and metastasis-induced osteolysis and fracture. 3D fluorescence molecular tomographic (FMT) imaging was used to visualize signal deep within the body.

        Results: FRFP binding to bone depends on the quantity of mineral present and can be liberated from the bone during decalcification. In vivo, FRFP binds to surfaces of actively forming bone, as assessed by alkaline phosphatase staining, surfaces undergoing active resorption, as noted by scalloped bone border and presence of osteoclasts, and to quiescent surfaces not involved in formation or resorption. Binding is likely modulated by vascular delivery of the imaging agent to the exposed mineral surface and total quantity of surface exposed.FMT imaging is capable of visualizing regions of bone formation because of a large volume of labeled surface, but like radiolabeled bone scans, cannot discriminate pure osteolysis caused by metastasis.

        Conclusions: FRFP may function as a local biomarker of bisphosphonate deposition to assess interplay between drug and cellular environment or may be combined with other imaging agents or fluorescent cells for the noninvasive assessment of local bone metabolism in vivo.
      13. URL :
        http://onlinelibrary.wiley.com/doi/10.1359/jbmr.070504/references?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nat%20Med&rft.atitle=Shedding%20light%20onto%20live%20molecular%20targets&rft.volume=9&rf
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4530
      1. Author :
        Jenkins, Darlene E; Oei, Yoko; Hornig, Yvette S; Yu, Shang-Fan; Dusich, Joan; Purchio, Tony; Contag, Pamela R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2003
      5. Publication :
        Clinical & experimental metastasis
      6. Products :
      7. Volume :
        20
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        A549-luc-C8; Animals; Bioware; Cell Line, Tumor; Colonic Neoplasms; Fluorouracil; HT-29-luc-D6 cells; Humans; Image Interpretation, Computer-Assisted; Longitudinal Studies; Luciferases; Luminescent Measurements; Lung Neoplasms; Lymphatic Metastasis; Male; Mice; Mice, SCID; Mitomycin; Models, Biological; Neoplasm Transplantation; PC-3M-luc; Prostatic Neoplasms
      12. Abstract :
        Bioluminescent imaging (BLI) permits sensitive in vivo detection and quantification of cells specifically engineered to emit visible light. Three stable human tumor cell lines engineered to express luciferase were assessed for their tumorigenicity in subcutaneous, intravenous and spontaneous metastasis models. Bioluminescent PC-3M-luc-C6 human prostate cancer cells were implanted subcutaneously into SCID-beige mice and were monitored for tumor growth and response to 5-FU and mitomycin C treatments. Progressive tumor development and inhibition/regression following drug treatment were observed and quantified in vivo using BLI. Imaging data correlated to standard external caliper measurements of tumor volume, but bioluminescent data permitted earlier detection of tumor growth. In a lung colonization model, bioluminescent A549-luc-C8 human lung cancer cells were injected intravenously and lung metastases were monitored in vivo by whole animal imaging. Anesthetized mice were imaged weekly allowing a temporal assessment of in vivo lung tumor growth. This longitudinal study design permitted an accurate, real-time evaluation of tumor burden in the same animals over time. End-point bioluminescence measured in vivo correlated to total lung weight at necropsy. For a spontaneous metastatic tumor model, bioluminescent HT-29-luc-D6 human colon cancer cells implanted subcutaneously produced metastases to lung and lymph nodes in SCID-beige mice. Both primary tumors and micrometastases were detected by BLI in vivo. Ex vivo imaging of excised lung lobes and lymph nodes confirmed the in vivo signals and indicated a slightly higher frequency of metastasis in some mice. Levels of bioluminescence from in vivo and ex vivo images corresponded to the frequency and size of metastatic lesions in lungs and lymph nodes as subsequently confirmed by histology. In summary, BLI provided rapid, non-invasive monitoring of tumor growth and regression in animals. Its application to traditional oncology animal models offers quantitative and sensitive analysis of tumor growth and metastasis. The ability to temporally assess tumor development and responses to drug therapies in vivo also improves upon current standard animal models that are based on single end point data.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/14713107
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8980
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