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      1. Author :
        Chauhan, A.; Lebeaux, D.; Ghigo, J. M.; Beloin, C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Antimicrob Agents Chemother
      6. Products :
      7. Volume :
        56
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen31, Xen 31, MRSA, S. aureus, IVIS, Bioluminescence
      12. Abstract :
        Biofilms that develop on indwelling devices are a major concern in clinical settings. While removal of colonized devices remains the most frequent strategy for avoiding device-related complications, antibiotic lock therapy constitutes an adjunct therapy for catheter-related infection. However, currently used antibiotic lock solutions are not fully effective against biofilms, thus warranting a search for new antibiotic locks. Metal-binding chelators have emerged as potential adjuvants due to their dual anticoagulant/antibiofilm activities, but studies investigating their efficiency were mainly in vitro or else focused on their effects in prevention of infection. To assess the ability of such chelators to eradicate mature biofilms, we used an in vivo model of a totally implantable venous access port inserted in rats and colonized by either Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, or Pseudomonas aeruginosa. We demonstrate that use of tetrasodium EDTA (30 mg/ml) as a supplement to the gentamicin (5 mg/ml) antibiotic lock solution associated with systemic antibiotics completely eradicated Gram-positive and Gram-negative bacterial biofilms developed in totally implantable venous access ports. Gentamicin-EDTA lock was able to eliminate biofilms with a single instillation, thus reducing length of treatment. Moreover, we show that this combination was effective for immunosuppressed rats. Lastly, we demonstrate that a gentamicin-EDTA lock is able to eradicate the biofilm formed by a gentamicin-resistant strain of methicillin-resistant S. aureus. This in vivo study demonstrates the potential of EDTA as an efficient antibiotic adjuvant to eradicate catheter-associated biofilms of major bacterial pathogens and thus provides a promising new lock solution.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23027191
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10552
      1. Author :
        Xie, B. W.; Mol, I. M.; Keereweer, S.; van Beek, E. R.; Que, I.; Snoeks, T. J.; Chan, A.; Kaijzel, E. L.; Lowik, C. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        7
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2, ProSense, MMPSense, CRi, Maestro, IVIS Animals; Benzenesulfonates/diagnostic use; Diagnostic Imaging/instrumentation/*methods; Disease Models, Animal; Disease Progression; Fluorescent Dyes/*diagnostic use; Indoles/diagnostic use; Luminescent Measurements/instrumentation/*methods; Mammary Neoplasms, Experimental/*diagnosis/pathology; Mice
      12. Abstract :
        Bioluminescence imaging (BLI) has shown its appeal as a sensitive technique for in vivo whole body optical imaging. However, the development of injectable tumor-specific near-infrared fluorescent (NIRF) probes makes fluorescence imaging (FLI) a promising alternative to BLI in situations where BLI cannot be used or is unwanted (e.g., spontaneous transgenic tumor models, or syngeneic mice to study immune effects).In this study, we addressed the questions whether it is possible to detect tumor progression using FLI with appropriate sensitivity and how FLI correlates with BLI measurements. In addition, we explored the possibility to simultaneously detect multiple tumor characteristics by dual-wavelength FLI (~700 and ~800 nm) in combination with spectral unmixing. Using a luciferase-expressing 4T1-luc2 mouse breast cancer model and combinations of activatable and targeting NIRF probes, we showed that the activatable NIRF probes (ProSense680 and MMPSense680) and the targeting NIRF probes (IRDye 800CW 2-DG and IRDye 800CW EGF) were either activated by or bound to 4T1-luc2 cells. In vivo, we implanted 4T1-luc2 cells orthotopically in nude mice and were able to follow tumor progression longitudinally both by BLI and dual-wavelength FLI. We were able to reveal different probe signals within the tumor, which co-localized with immuno-staining. Moreover, we observed a linear correlation between the internal BLI signals and the FLI signals obtained from the NIRF probes. Finally, we could detect pulmonary metastases both by BLI and FLI and confirmed their presence histologically.Taken together, these data suggest that dual-wavelength FLI is a feasible approach to simultaneously detect different features of one tumor and to follow tumor progression with appropriate specificity and sensitivity. This study may open up new perspectives for the detection of tumors and metastases in various experimental models and could also have clinical applications, such as image-guided surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22348134
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10426
      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
      1. Author :
        Jenkins, D. E.; Oei, Y.; Hornig, Y. S.; Yu, S. F.; Dusich, J.; Purchio, T.; Contag, P. R.
      2. Title :
        Bioluminescent imaging (BLI) to improve and refine traditional murine models of tumor growth and metastasis
      3. Type :
        Journal Article
      4. Year :
        2003
      5. Publication :
        Clinical and Experimental Metastasis
      6. Products :
      7. Volume :
        20
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        A549-luc-C8 cells; Animals, Cell Line, Tumor, Colonic Neoplasms/pathology, Fluorouracil/therapeutic use, Humans, Image Interpretation, Computer-Assisted, Longitudinal Studies, Luciferases/diagnostic use, Luminescent Measurements, Lung Neoplasms/ secondary, Lymphatic Metastasis, Male, Mice, Mice, SCID, Mitomycin/therapeutic use, Models, Biological, Neoplasm Transplantation, Prostatic Neoplasms/drug therapy/ pathology IVIS, Xenogen
      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 :
        N/A
      14. Call Number :
        139189
      15. Serial :
        5565
      1. Author :
        Kwong, G. A.; von Maltzahn, G.; Murugappan, G.; Abudayyeh, O.; Mo, S.; Papayannopoulos, I. A.; Sverdlov, D. Y.; Liu, S. B.; Warren, A. D.; Popov, Y.; Schuppan, D.; Bhatia, S. N.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Biotechnol
      6. Products :
      7. Volume :
        31
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        VivoTag, IVIS, Vivotag
      12. Abstract :
        Biomarkers are becoming increasingly important in the clinical management of complex diseases, yet our ability to discover new biomarkers remains limited by our dependence on endogenous molecules. Here we describe the development of exogenously administered 'synthetic biomarkers' composed of mass-encoded peptides conjugated to nanoparticles that leverage intrinsic features of human disease and physiology for noninvasive urinary monitoring. These protease-sensitive agents perform three functions in vivo: they target sites of disease, sample dysregulated protease activities and emit mass-encoded reporters into host urine for multiplexed detection by mass spectrometry. Using mouse models of liver fibrosis and cancer, we show that these agents can noninvasively monitor liver fibrosis and resolution without the need for invasive core biopsies and substantially improve early detection of cancer compared with current clinically used blood biomarkers. This approach of engineering synthetic biomarkers for multiplexed urinary monitoring should be broadly amenable to additional pathophysiological processes and point-of-care diagnostics.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23242163
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10567
      1. Author :
        Vasilis Ntziachristos
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        The Proceedings of the American Thoracic Society
      6. Products :
      7. Volume :
        6
      8. Issue :
        5
      9. Page Numbers :
        N/A
      10. Research Area :
        Physiology
      11. Keywords :
        ProSense; FMT; fluorescence; tomography; proteases; lung; inflammation; in vivo imaging
      12. Abstract :
        Biomedical imaging has become an important tool in the study of “-omics” fields by allowing the noninvasive visualization of functional and molecular events using in vivo staining and reporter gene approaches. This capacity can go beyond the understanding of the genetic basis and phenotype of such respiratory conditions as acute bronchitis, adult respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and asthma and investigate the development of disease and of therapeutic events longitudinally and in unperturbed environments. Herein, we show how the application of novel quantitative optical imaging methods, using transillumination and fluorescence molecular tomography (FMT), can allow visualization of pulmonary inflammation in small animals in vivo. The results confirm prior observations using a protease-sensitive probe. We discuss how this approach enables in vivo insights at the system level as to the dynamic role of proteases in respiratory pathophysiology and their potential as therapeutic targets. Overall, the proposed imaging method can be used with a significantly wider range of possible targets and applications in lung imaging.
      13. URL :
        http://pats.atsjournals.org/cgi/content/full/6/5/416
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4534
      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 :
        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 :
        Matsumoto, K.; Azami, T.; Otsu, A.; Takase, H.; Ishitobi, H.; Tanaka, J.; Miwa, Y.; Takahashi, S.; Ema, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Genesis
      6. Products :
      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 :
        van der Horst, G.; van der Pluijm, G.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Future Oncol
      6. Products :
      7. Volume :
        8
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Bone Neoplasms/*diagnosis/*secondary; Diagnostic Imaging/*methods; Disease Models, Animal; Disease Progression; Humans; Molecular Imaging/methods; Neoplasm Metastasis/diagnosis
      12. Abstract :
        Bone metastasis is a complex process that ultimately leads to devastating metastatic bone disease. It is therefore of key interest to unravel the mechanisms underlying the multistep process of skeletal metastasis and cancer-induced bone disease, and to develop better treatment and management of patients with this devastating disease. Fortunately, novel technologies are rapidly emerging that allow real-time imaging of molecules, pathogenic processes, drug delivery and drug response in preclinical in vivo models. The outcome of these experimental studies will facilitate clinical cancer research by improving the detection of cancer cell invasion, metastasis and therapy response.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22515445
      14. Call Number :
        PKI @ kd.modi @ 30
      15. Serial :
        10384
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