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      1. Author :
        Noberini, R.; Rubio de la Torre, E.; Pasquale, E. B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cell Adh Migr
      6. Products :
      7. Volume :
        6
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        PC-3M-luc-C6, PC-3M-luc, IVIS, Bioware, Prostate cancer, Bioluminescence, Animals; Chromatography, Liquid; Enzyme-Linked Immunosorbent Assay; Ephrins/genetics/*metabolism; Humans; Mass Spectrometry/*methods; Mice; Receptor, EphA1/genetics/*metabolism
      12. Abstract :
        The Eph receptor tyrosine kinase family includes many members, which are often expressed together in various combinations and can promiscuously interact with multiple ephrin ligands, generating intricate networks of intracellular signals that control physiological and pathological processes. Knowing the entire repertoire of Eph receptors and ephrins expressed in a biological sample is important when studying their biological roles. Moreover, given the correlation between Eph receptor/ephrin expression and cancer pathogenesis, their expression patterns could serve important diagnostic and prognostic purposes. However, profiling Eph receptor and ephrin expression has been challenging. Here we describe a novel and straightforward approach to catalog the Eph receptors present in cultured cells and tissues. By measuring the binding of ephrin Fc fusion proteins to Eph receptors in ELISA and pull-down assays, we determined that a mixture of four ephrins is suitable for isolating both EphA and EphB receptors in a single pull-down. We then used mass spectrometry to identify the Eph receptors present in the pull-downs and estimate their relative levels. This approach was validated in cultured human cancer cell lines, human tumor xenograft tissue grown in mice, and mouse brain tissue. The new mass spectrometry approach we have developed represents a useful tool for the identification of the spectrum of Eph receptors present in a biological sample and could also be extended to profiling ephrin expression.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22568954
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10538
      1. Author :
        David E Sosnovik, Matthias Nahrendorf and Ralph Weissleder
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Nature Reviews Cardiology
      6. Products :
      7. Volume :
        5
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        in vivo imaging; fluorescence imaging, molecular imaging, MRI, myocardium, SPECT; MMPSense
      12. Abstract :
        Molecular imaging agents can be targeted to a specific receptor or protein on the cardiomyocyte surface, or to enzymes released into the interstitial space, such as cathepsins, matrix metalloproteinases and myeloperoxidase. Molecular imaging of the myocardium, however, requires the imaging agent to be small, sensitive (nanomolar levels or better), and able to gain access to the interstitial space. Several novel agents that fulfill these criteria have been used for targeted molecular imaging applications in the myocardium. Magnetic resonance, fluorescence, and single-photon emission CT have been used to image the molecular signals generated by these agents. The use of targeted imaging agents in the myocardium has the potential to provide valuable insights into the pathophysiology of myocardial injury and to facilitate the development of novel therapeutic strategies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597275/?tool=pubmed
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4650
      1. Author :
        Kim, J. B.; Urban, K.; Cochran, E.; Lee, S.; Ang, A.; Rice, B.; Bata, A.; Campbell, K.; Coffee, R.; Gorodinsky, A.; Lu, Z.; Zhou, H.; Kishimoto, T. K.; Lassota, P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen, VIS, 4T1-luc2, Animals; Cell Line, Tumor; Diagnostic Imaging/*methods; Female; Genetic Vectors/genetics; Lentivirus/genetics; Luciferases/genetics/*metabolism; Luminescent Measurements/instrumentation/*methods; Lung Neoplasms/diagnosis/metabolism/secondary; Mammary Neoplasms, Experimental/diagnosis/genetics/*metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms/genetics/metabolism/pathology; Sensitivity and Specificity; Time Factors; Transfection; Tumor Burden
      12. Abstract :
        Early detection of tumors can significantly improve the outcome of tumor treatment. One of the most frequently asked questions in cancer imaging is how many cells can be detected non-invasively in a live animal. Although many factors limit such detection, increasing the light emission from cells is one of the most effective ways of overcoming these limitations. Here, we describe development and utilization of a lentiviral vector containing enhanced firefly luciferase (luc2) gene. The resulting single cell clones of the mouse mammary gland tumor (4T1-luc2) showed stable light emission in the range of 10,000 photons/sec/cell. In some cases individual 4T1-luc2 cells inserted under the skin of a nu/nu mouse could be detected non-invasively using a cooled CCD camera in some cases. In addition, we showed that only few cells are needed to develop tumors in these mice and tumor progression can be monitored right after the cells are implanted. Significantly higher luciferase activity in these cells allowed us to detect micrometastases in both, syngeneic Balb/c and nu/nu mice.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20186331
      14. Call Number :
        139615
      15. Serial :
        7111
      1. Author :
        Kim, Jae-Beom; Urban, Konnie; Cochran, Edward; Lee, Steve; Ang, Angel; Rice, Bradley; Bata, Adam; Campbell, Kenneth; Coffee, Richard; Gorodinsky, Alex; Lu, Zhan; Zhou, He; Kishimoto, Takashi Kei; Lassota, Peter
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PloS one
      6. Products :
      7. Volume :
        5
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2; Animals; Bicuculline; Bioware; Cell Line, Tumor; Diagnostic Imaging; Female; Genetic Vectors; Lentivirus; Luciferases; Luminescent Measurements; Lung Neoplasms; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms; Sensitivity and Specificity; Time Factors; Transfection; Tumor Burden
      12. Abstract :
        Early detection of tumors can significantly improve the outcome of tumor treatment. One of the most frequently asked questions in cancer imaging is how many cells can be detected non-invasively in a live animal. Although many factors limit such detection, increasing the light emission from cells is one of the most effective ways of overcoming these limitations. Here, we describe development and utilization of a lentiviral vector containing enhanced firefly luciferase (luc2) gene. The resulting single cell clones of the mouse mammary gland tumor (4T1-luc2) showed stable light emission in the range of 10,000 photons/sec/cell. In some cases individual 4T1-luc2 cells inserted under the skin of a nu/nu mouse could be detected non-invasively using a cooled CCD camera in some cases. In addition, we showed that only few cells are needed to develop tumors in these mice and tumor progression can be monitored right after the cells are implanted. Significantly higher luciferase activity in these cells allowed us to detect micrometastases in both, syngeneic Balb/c and nu/nu mice.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20186331
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8938
      1. Author :
        Beckers, Annelies; Organe, Sophie; Timmermans, Leen; Vanderhoydonc, Frank; Deboel, Ludo; Derua, Rita; Waelkens, Etienne; Brusselmans, Koen; Verhoeven, Guido; Swinnen, Johannes V
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Molecular cancer therapeutics
      6. Products :
      7. Volume :
        5
      8. Issue :
        9
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Adenosine Triphosphate; Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Bioware; Breast Neoplasms; Carcinoma, Squamous Cell; Cell Line, Tumor; DNA, Neoplasm; Drug Synergism; Enzyme Activation; Humans; Lipids; Methotrexate; Multienzyme Complexes; Nucleotide Deaminases; PC-3M-luc; Phosphoribosylaminoimidazolecarboxamide Formyltransferase; Phosphoribosylglycinamide Formyltransferase; Protein-Serine-Threonine Kinases; Purines; Ribonucleosides; Ribonucleotides; RNA Interference
      12. Abstract :
        Because of its ability to mimic a low energy status of the cell, the cell-permeable nucleoside 5-aminoimidazole-4-carboxamide (AICA) riboside was proposed as an antineoplastic agent switching off major energy-consuming processes associated with the malignant phenotype (lipid production, DNA synthesis, cell proliferation, cell migration, etc.). Key to the antineoplastic action of AICA riboside is its conversion to ZMP, an AMP mimetic that at high concentrations activates the AMP-activated protein kinase (AMPK). Here, in an attempt to increase the efficacy of AICA riboside, we pretreated cancer cells with methotrexate, an antimetabolite blocking the metabolism of ZMP. Methotrexate enhanced the AICA riboside-induced accumulation of ZMP and led to a decrease in the levels of ATP, which functions as an intrasteric inhibitor of AMPK. Consequently, methotrexate markedly sensitized AMPK for activation by AICA riboside and potentiated the inhibitory effects of AICA riboside on tumor-associated processes. As cotreatment elicited antiproliferative effects already at concentrations of compounds that were only marginally effective when used alone, our findings on the cooperation between methotrexate and AICA riboside provide new opportunities both for the application of classic antimetabolic chemotherapeutics, such as methotrexate, and for the exploitation of the energy-sensing machinery as a target for cancer intervention.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16985054
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8978
      1. Author :
        Engelsman, Anton F; Krom, Bastiaan P; Busscher, Henk J; van Dam, Gooitzen M; Ploeg, Rutger J; van der Mei, Henny C
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Acta biomaterialia
      6. Products :
      7. Volume :
        5
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Bioware; Connective Tissue; Diffusion; Drug Implants; Female; Mice; Mice, Inbred BALB C; Nitric Oxide; Polyvinyls; Prostheses and Implants; pXen-5; Staphylococcal Infections; Xen29
      12. Abstract :
        Infection of surgical meshes used in abdominal wall reconstructions often leads to removal of the implant and increases patient morbidity due to repetitive operations and hospital administrations. Treatment with antibiotics is ineffective due to the biofilm mode of growth of the infecting bacteria and bears the risk of inducing antibiotic resistance. Hence there is a need for alternative methods to prevent and treat mesh infection. Nitric oxide (NO)-releasing coatings have been demonstrated to possess bactericidal properties in vitro. It is the aim of this study to assess possible benefits of a low concentration NO-releasing carbon-based coating on monofilament polypropylene meshes with respect to infection control in vitro and in vivo. When applied on surgical meshes, NO-releasing coatings showed significant bactericidal effect on in vitro biofilms of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and CNS. However, using bioluminescent in vivo imaging, no beneficial effects of this NO-releasing coating on subcutaneously implanted surgical meshes in mice could be observed.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19251498
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9019
      1. Author :
        Bisland, Stuart K; Chien, Claudia; Wilson, Brian C; Burch, Shane
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Photochemical & photobiological sciences: Official journal of the European Photochemistry Association and the European Society for Photobiology
      6. Products :
      7. Volume :
        5
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Aminolevulinic Acid; Animals; Biofilms; Bioware; Cell Survival; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Implants, Experimental; Light; Luminescent Measurements; Methylene Blue; Osteomyelitis; Photochemotherapy; Photosensitizing Agents; Rats; Rats, Sprague-Dawley; Staphylococcus aureus; Xen29
      12. Abstract :
        Osteomyelitis can lead to severe morbidity and even death resulting from an acute or chronic inflammation of the bone and contiguous structures due to fungal or bacterial infection. Incidence approximates 1 in 1000 neonates and 1 in 5000 children in the United States annually and increases up to 0.36% and 16% in adults with diabetes or sickle cell anaemia, respectively. Current regimens of treatment include antibiotics and/or surgery. However, the increasing number of antibiotic resistant pathogens suggests that alternate strategies are required. We are investigating photodynamic therapy (PDT) as one such alternate treatment for osteomyelitis using a bioluminescent strain of biofilm-producing staphylococcus aureus (S. aureus) grown onto kirschner wires (K-wire). S. aureus-coated K-wires were exposed to methylene blue (MB) or 5-aminolevulinic acid (ALA)-mediated PDT either in vitro or following implant into the tibial medullary cavity of Sprague-Dawley rats. The progression of S. aureus biofilm was monitored non-invasively using bioluminescence and expressed as a percentage of the signal for each sample immediately prior to treatment. S. aureus infections were subject to PDT 10 days post inoculation. Treatment comprised administration of ALA (300 mg kg(-1)) intraperitoneally followed 4 h later by light (635 +/- 10 nm; 75 J cm(-2)) delivered transcutaneously via an optical fiber placed onto the tibia and resulted in significant delay in bacterial growth. In vitro, MB and ALA displayed similar cell kill with > or =4 log(10) cell kill. In vivo, ALA-mediated PDT inhibited biofilm implants in bone. These results confirm that MB or ALA-mediated PDT have potential to treat S. aureus cultures grown in vitro or in vivo using an animal model of osteomyelitis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16395425
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9054
      1. Author :
        Tsurumi, C.; Esser, N.; Firat, E.; Gaedicke, S.; Follo, M.; Behe, M.; Elsasser-Beile, U.; Grosu, A. L.; Graeser, R.; Niedermann, G.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Antigens, CD/*biosynthesis/*metabolism; Flow Cytometry/methods; Glioma/metabolism; Glycoproteins/*biosynthesis/*metabolism; Humans; Hybridomas/metabolism; Mice; Mice, Transgenic; Models, Biological; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms/*metabolism; Neoplastic Stem Cells; Peptides/*metabolism; Recurrence
      12. Abstract :
        BACKGROUND: Cancer stem cells are thought to play a pivotal role in tumor maintenance, metastasis, tumor therapy resistance and relapse. Hence, the development of methods for non-invasive in vivo detection of cancer stem cells is of great importance. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe successful in vivo detection of CD133/prominin, a cancer stem cell surface marker for a variety of tumor entities. The CD133-specific monoclonal antibody AC133.1 was used for quantitative fluorescence-based optical imaging of mouse xenograft models based on isogenic pairs of CD133 positive and negative cell lines. A first set consisted of wild-type U251 glioblastoma cells, which do not express CD133, and lentivirally transduced CD133-overexpressing U251 cells. A second set made use of HCT116 colon carcinoma cells, which uniformly express CD133 at levels comparable to primary glioblastoma stem cells, and a CD133-negative HCT116 derivative. Not surprisingly, visualization and quantification of CD133 in overexpressing U251 xenografts was successful; more importantly, however, significant differences were also found in matched HCT116 xenograft pairs, despite the lower CD133 expression levels. The binding of i.v.-injected AC133.1 antibodies to CD133 positive, but not negative, tumor cells isolated from xenografts was confirmed by flow cytometry. CONCLUSIONS/SIGNIFICANCE: Taken together, our results show that non-invasive antibody-based in vivo imaging of tumor-associated CD133 is feasible and that CD133 antibody-based tumor targeting is efficient. This should facilitate developing clinically applicable cancer stem cell imaging methods and CD133 antibody-based therapeutics.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21187924
      14. Call Number :
        PKI @ kd.modi @ 15
      15. Serial :
        10382
      1. Author :
        Lu, Z.; Dai, T.; Huang, L.; Kurup, D. B.; Tegos, G. P.; Jahnke, A.; Wharton, T.; Hamblin, M. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Nanomedicine (Lond)
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen 5, Pseudomonas aeruginosa Xen 5, Animals; Fullerenes/*chemistry; Male; Mice; Mice, Inbred BALB C; Photochemotherapy/*methods; Photosensitizing Agents/*chemistry; Pseudomonas Infections/*drug therapy; Pseudomonas aeruginosa/drug effects; Wound Infection/*drug therapy
      12. Abstract :
        AIMS: Fullerenes are under intensive study for potential biomedical applications. We have previously reported that a C60 fullerene functionalized with three dimethylpyrrolidinium groups (BF6) is a highly active broad-spectrum antimicrobial photosensitizer in vitro when combined with white-light illumination. We asked whether this high degree of in vitro activity would translate into an in vivo therapeutic effect in two potentially lethal mouse models of infected wounds. MATERIALS & METHODS: We used stable bioluminescent bacteria and a low light imaging system to follow the progress of the infection noninvasively in real time. An excisional wound on the mouse back was contaminated with one of two bioluminescent Gram-negative species, Proteus mirabilis (2.5 x 10(7) cells) and Pseudomonas aeruginosa (5 x 10(6) cells). A solution of BF6 was placed into the wound followed by delivery of up to 180 J/cm(2) of broadband white light (400-700 nm). RESULTS: In both cases there was a light-dose-dependent reduction of bioluminescence from the wound not observed in control groups (light alone or BF6 alone). Fullerene-mediated photodynamic therapy of mice infected with P. mirabilis led to 82% survival compared with 8% survival without treatment (p < 0.001). Photodynamic therapy of mice infected with highly virulent P. aeruginosa did not lead to survival, but when photodynamic therapy was combined with a suboptimal dose of the antibiotic tobramycin (6 mg/kg for 1 day) there was a synergistic therapeutic effect with a survival of 60% compared with a survival of 20% with tobramycin alone (p < 0.01). CONCLUSION: These data suggest that cationic fullerenes have clinical potential as an antimicrobial photosensitizer for superficial infections where red light is not needed to penetrate tissue.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21143031
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10390
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