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      1. Author :
        Hasenpusch, G.; Pfeifer, C.; Aneja, M. K.; Wagner, K.; Reinhardt, D.; Gilon, M.; Ohana, P.; Hochberg, A.; Rudolph, C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        6
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29, Administration, Inhalation; Aerosols; Animals; Cell Line, Tumor; Cell Proliferation/drug effects; Cell Transformation, Neoplastic; Humans; Lung Neoplasms/drug therapy/genetics/*pathology/*secondary; Mice; Oncogenes/genetics; Plasmids/*administration & dosage/chemistry/*pharmacology; Polyethyleneimine/chemistry
      12. Abstract :
        Despite numerous efforts, drug based treatments for patients suffering from lung cancer remains poor. As a promising alternative, we investigated the therapeutic potential of BC-819 for the treatment of lung cancer in mouse tumor models. BC-819 is a novel plasmid DNA which encodes for the A-fragment of Diphtheria toxin and has previously been shown to successfully inhibit tumor growth in human clinical study of bladder carcinoma. In a first set of experiments, we examined in vitro efficacy of BC-819 in human lung cancer cell-lines NCI-H460, NCI-H358 and A549, which revealed >90% reduction of cell growth. In vivo efficacy was examined in an orthotopic mouse xenograft lung cancer model and in a lung metastasis model using luminescent A549-C8-luc adenocarcinoma cells. These cells resulted in peri- and intra-bronchiolar tumors upon intrabronchial application and parenchymal tumors upon intravenous injection, respectively. Mice suffering from these lung tumors were treated with BC-819, complexed to branched polyethylenimine (PEI) and aerosolized to the mice once per week for a period of 10 weeks. Using this regimen, growth of intrabronchially induced lung tumors was significantly inhibited (p = 0.01), whereas no effect could be observed in mice suffering from lung metastasis. In summary, we suggest that aerosolized PEI/BC-819 is capable of reducing growth only in tumors arising from the luminal part of the airways and are therefore directly accessible for inhaled BC-819.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21687669
      14. Call Number :
        PKI @ kd.modi @ 9
      15. Serial :
        10450
      1. Author :
        Defresne, F.; Bouzin, C.; Grandjean, M.; Dieu, M.; Raes, M.; Hatzopoulos, A. K.; Kupatt, C.; Feron, O.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc,
      12. Abstract :
        Tumor progression is associated with the release of signaling substances from the primary tumor into the bloodstream. Tumor-derived cytokines are known to promote the mobilization and the recruitment of cells from the bone marrow, including endothelial progenitor cells (EPC). Here, we examined whether such paracrine influence could also influence the capacity of EPC to interfere with circulating metastatic cells. We therefore consecutively injected EPC pre-stimulated by tumor conditioned medium (CM-EPC) and luciferase-expressing B16 melanoma cells to mice. A net decrease in metastases spreading (vs non-stimulated EPC) led us to carry out a 2D-DIGE proteomic study to identify possible mediators of EPC-driven protection. Among 33 proteins exhibiting significant changes in expression, SPARC presented the highest induction after EPC exposure to CM. We then showed that contrary to control EPC, SPARC-silenced EPC were not able to reduce the extent of metastases when injected with B16 melanoma cells. Using adhesion tests and the hanging drop assay, we further documented that cell-cell interactions between CM-EPC and melanoma cells were promoted in a SPARC-dependent manner. This interaction led to the engulfment of melanoma cells by CM-EPC, a process prevented by SPARC silencing and mimicked by recombinant SPARC. Finally, we showed that contrary to melanoma cells, the pro-metastatic human breast cancer cell line MDA-MB231-D3H2 reduced SPARC expression in human EPC and stimulated metastases spreading. Our findings unravel the influence of tumor cells on EPC phenotypes through a SPARC-driven accentuation of macrophagic capacity associated with limitations to metastatic spread.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21616936
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10354
      1. Author :
        Defresne, F.; Bouzin, C.; Grandjean, M.; Dieu, M.; Raes, M.; Hatzopoulos, A. K.; Kupatt, C.; Feron, O.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-D3H2Ln, IVIS, Bioluminescence
      12. Abstract :
        Tumor progression is associated with the release of signaling substances from the primary tumor into the bloodstream. Tumor-derived cytokines are known to promote the mobilization and the recruitment of cells from the bone marrow, including endothelial progenitor cells (EPC). Here, we examined whether such paracrine influence could also influence the capacity of EPC to interfere with circulating metastatic cells. We therefore consecutively injected EPC pre-stimulated by tumor conditioned medium (CM-EPC) and luciferase-expressing B16 melanoma cells to mice. A net decrease in metastases spreading (vs non-stimulated EPC) led us to carry out a 2D-DIGE proteomic study to identify possible mediators of EPC-driven protection. Among 33 proteins exhibiting significant changes in expression, SPARC presented the highest induction after EPC exposure to CM. We then showed that contrary to control EPC, SPARC-silenced EPC were not able to reduce the extent of metastases when injected with B16 melanoma cells. Using adhesion tests and the hanging drop assay, we further documented that cell-cell interactions between CM-EPC and melanoma cells were promoted in a SPARC-dependent manner. This interaction led to the engulfment of melanoma cells by CM-EPC, a process prevented by SPARC silencing and mimicked by recombinant SPARC. Finally, we showed that contrary to melanoma cells, the pro-metastatic human breast cancer cell line MDA-MB231-D3H2 reduced SPARC expression in human EPC and stimulated metastases spreading. Our findings unravel the influence of tumor cells on EPC phenotypes through a SPARC-driven accentuation of macrophagic capacity associated with limitations to metastatic spread.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21616936
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10415
      1. Author :
        Bendaoud, M.; Vinogradov, E.; Balashova, N. V.; Kadouri, D. E.; Kachlany, S. C.; Kaplan, J. B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Bacteriol
      6. Products :
      7. Volume :
        193
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen29, Xen 29, Staphylococcus aureus Xen29, IVISBacterial Physiological Phenomena/drug effects; Bacterial Proteins/genetics/metabolism; Biofilms/*drug effects; *Down-Regulation/drug effects; Fungi/drug effects/physiology; Kingella kingae/chemistry/genetics/*metabolism; Molecular Sequence Data; Polysaccharides, Bacterial/biosynthesis/chemistry/*pharmacology
      12. Abstract :
        Cell-free extracts prepared from Kingella kingae colony biofilms were found to inhibit biofilm formation by Aggregatibacter actinomycetemcomitans, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Candida albicans, and K. kingae. The extracts evidently inhibited biofilm formation by modifying the physicochemical properties of the cell surface, the biofilm matrix, and the substrate. Chemical and biochemical analyses indicated that the biofilm inhibition activity in the K. kingae extract was due to polysaccharide. Structural analyses showed that the extract contained two major polysaccharides. One was a linear polysaccharide with the structure -->6)-alpha-d-GlcNAcp-(1-->5)-beta-d-OclAp-(2-->, which was identical to a capsular polysaccharide produced by Actinobacillus pleuropneumoniae serotype 5. The second was a novel linear polysaccharide, designated PAM galactan, with the structure -->3)-beta-d-Galf-(1-->6)-beta-d-Galf-(1-->. Purified PAM galactan exhibited broad-spectrum biofilm inhibition activity. A cluster of three K. kingae genes encoding UDP-galactopyranose mutase (ugm) and two putative galactofuranosyl transferases was sufficient for the synthesis of PAM galactan in Escherichia coli. PAM galactan is one of a growing number of bacterial polysaccharides that exhibit antibiofilm activity. The biological roles and potential technological applications of these molecules remain unknown.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21602333
      14. Call Number :
        PKI @ kd.modi @ 17
      15. Serial :
        10446
      1. Author :
        Penna, F. J.; Freilich, D. A.; Alvarenga, C.; Nguyen, H. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Urology
      6. Products :
      7. Volume :
        78
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Fluorescence; Fluorescent Dyes/*diagnostic use; Guinea Pigs; Lymph Node Excision/*methods; Male; Models, Animal; *Molecular Imaging; Retroperitoneal Space
      12. Abstract :
        OBJECTIVES: To propose that fluorescent molecular imaging has utility in specifically identifying the lymph nodes, thereby enabling more definitive lymph node visualization and dissection. Retroperitoneal lymph node dissection (RPLND) is an invasive procedure with significant morbidity. A minimally invasive approach would be of great clinical benefit but has been limited by the extensive perivascular dissection required to remove all lymphatic tissue. Directed lymph node visualization would allow a limited dissection, making a laparoscopic approach more feasible. METHODS: Ten male Hartley guinea pigs underwent nonsurvival RPLND, 5 with the protease activatable in vivo fluorescent molecular imaging agent, ProSense and 5 without image guidance (control). ProSense was administered 24 hours before surgery and detected 24 hours later using a photodynamic detector. In group 1, RPLND was first performed without molecular imaging followed by image-guided lymph node dissection for residual nodes. In group 2, the near infrared detector was used initially for lymph node excision followed by traditionally unassisted extraction of the residual lymph nodes. The lymph nodes were extracted, counted, and sent for histopathologic analysis. RESULTS: With the assistance of molecular imaging, no additional lymph nodes were identified after complete dissection, and all tissue identified by ProSense was confirmed by histopathologic analysis to be lymph nodes. Without molecular imaging, all lymph nodes were not identified, and in 2 instances, the tissue was incorrectly thought to be lymphatic tissue. CONCLUSIONS: Molecular image-guided RPLND is a promising technique to improve in vivo, live visualization and dissection of lymph nodes and has the potential for application in improving the diagnosis and treatment of other urologic malignancies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21601249
      14. Call Number :
        PKI @ kd.modi @ 13
      15. Serial :
        10474
      1. Author :
        Agarwal, A.; Mackey, M. A.; El-Sayed, M. A.; Bellamkonda, R. V.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        ACS Nano
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        4919-26
      10. Research Area :
        N/A
      11. Keywords :
        Annexin Vivo, Annexin-Vivo, IVIS, Animals; Antineoplastic Agents/*administration & dosage; Apoptosis; Cell Line, Tumor; Doxorubicin/*administration & dosage; Drug Carriers; Drug Delivery Systems; Female; Glioblastoma/drug therapy; Gold/chemistry; Humans; Liposomes/*chemistry; Metal Nanoparticles/chemistry; Mice; Mice, Nude; Nanostructures/chemistry; Neoplasms/*drug therapy; Polyethylene Glycols/chemistry
      12. Abstract :
        Delivery of chemotherapeutic agents after encapsulation in nanocarriers such as liposomes diminishes side-effects, as PEGylated nanocarrier pharmacokinetics decrease dosing to healthy tissues and accumulate in tumors due to the enhanced permeability and retention effect. Once in the tumor, however, dosing of the chemotherapeutic to tumor cells is limited potentially by the rate of release from the carriers and the size-constrained, poor diffusivity of nanocarriers in tumor interstitium. Here, we report the design and fabrication of a thermosensitive liposomal nanocarrier that maintains its encapsulation stability with a high concentration of doxorubicin payload, thereby minimizing “leak” and attendant toxicity. When used synergistically with PEGylated gold nanorods and near-infrared stimulation, remote triggered release of doxorubicin from thermosensitive liposomes was achieved in a mouse tumor model of human glioblastoma (U87), resulting in a significant increase in efficacy when compared to nontriggered or nonthermosensitive PEGylated liposomes. This enhancement in efficacy is attributed to increase in tumor-site apoptosis, as was evident from noninvasive apoptosis imaging using Annexin-Vivo 750 probe. This strategy affords remotely triggered control of tumor dosing of nanocarrier-encapsulated doxorubicin without sacrificing the ability to differentially dose drugs to tumors via the enhanced permeation and retention effect.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21591812
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10430
      1. Author :
        Lee, H. L.; Chen, C. C.; Baasov, T.; Ron, Y.; Dougherty, J. P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Mol Ther
      6. Products :
      7. Volume :
        19
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        RediJect Coelenterazine h, XenoLight
      12. Abstract :
        Cells have developed a mechanism to discriminate between premature termination codons (PTCs) and normal stop codons during translation, sparking vigorous research to develop drugs promoting readthrough at PTCs to treat genetic disorders caused by PTCs. It was posed that this concept could also be applied to regulated gene therapy protocols by incorporating a PTC into a therapeutic gene, so active protein would only be made after administration of a readthrough agent. The strengths of the system are highlighted here by results demonstrating: (i) background expression levels were reduced to 0.01% to 0.0005% of wild type in unselected mass populations of cells depending upon the specific stop codon utilized and its position within the gene; (ii) expression levels responded well to multiple “On” and “Off” regulation cycles in vivo in human xenograft systems; (iii) the level of induction approached three logs using aminoglycoside activators including NB54, a newly synthesized aminoglycoside with significantly reduced toxicity; and (iv) expression levels could be appreciably altered when employing different promoters in a variety of cell types. These results strongly support the contention that this system should have important clinical applications when tight control of gene expression is required.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21587212
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10422
      1. Author :
        Seo, G. M.; Rachakatla, R. S.; Balivada, S.; Pyle, M.; Shrestha, T. B.; Basel, M. T.; Myers, C.; Wang, H.; Tamura, M.; Bossmann, S. H.; Troyer, D. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Biol Rep
      6. Products :
      7. Volume :
        39
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals, B16-F10-luc2, B16F10-luc2
      12. Abstract :
        Gene-directed enzyme prodrug therapy (GDEPT) has been investigated as a means of cancer treatment without affecting normal tissues. This system is based on the delivery of a suicide gene, a gene encoding an enzyme which is able to convert its substrate from non-toxic prodrug to cytotoxin. In this experiment, we have developed a targeted suicide gene therapeutic system that is completely contained within tumor-tropic cells and have tested this system for melanoma therapy in a preclinical model. First, we established double stable RAW264.7 monocyte/macrophage-like cells (Mo/Ma) containing a Tet-On(R) Advanced system for intracellular carboxylesterase (InCE) expression. Second, we loaded a prodrug into the delivery cells, double stable Mo/Ma. Third, we activated the enzyme system to convert the prodrug, irinotecan, to the cytotoxin, SN-38. Our double stable Mo/Ma homed to the lung melanomas after 1 day and successfully delivered the prodrug-activating enzyme/prodrug package to the tumors. We observed that our system significantly reduced tumor weights and numbers as targeted tumor therapy after activation of the InCE. Therefore, we propose that this system may be a useful targeted melanoma therapy system for pulmonary metastatic tumors with minimal side effects, particularly if it is combined with other treatments.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21567204
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10351
      1. Author :
        Fu, J. Y.; Zhang, W.; Blatchford, D. R.; Tetley, L.; McConnell, G.; Dufes, C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Control Release
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc,
      12. Abstract :
        The therapeutic potential of tocotrienol, a vitamin E extract with anti-cancer properties, is hampered by its failure to specifically reach tumors after intravenous administration. In this work, we demonstrated that novel transferrin-bearing, tocopheryl-based multilamellar vesicles entrapping tocotrienol significantly improved tocotrienol uptake by cancer cells overexpressing transferrin receptors. This led to a dramatically improved therapeutic efficacy in vitro, ranging from 17-fold to 72-fold improvement depending on the cell lines, compared to the free drug. In vivo, the intravenous administration of this novel tocotrienol formulation led to complete tumor eradication for 40% of B16-F10 murine melanoma tumors and 20% of A431 human epidermoid carcinoma tumors. Animal survival was improved by more than 20days compared to controls, for the two tumor models tested. These therapeutic effects, together with the lack of toxicity, potentially make transferrin-bearing vesicles entrapping tocotrienol a highly promising therapeutic system as part as an anti-cancer therapeutic strategy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21539872
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10356
      1. Author :
        Ran, C.; Zhang, Z.; Hooker, J.; Moore, A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Imaging Biol
      6. Products :
      7. Volume :
        14
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-D3H1, MDA-MB-231-luc-D3H1, IVIS, Bioware, Breast Cancer. Animals; Cell Line, Tumor; Chromatography, Liquid; Diagnostic Imaging/*methods; *Elementary Particles; Firefly Luciferin/chemistry/metabolism; Fluorodeoxyglucose F18/diagnostic use; Humans; *Light; Luminescent Measurements; Mass Spectrometry; Mice; Mice, Nude; Solutions
      12. Abstract :
        PURPOSE: The poor tissue penetration of visible light has been a major barrier for optical imaging, photoactivatable conversions, and photodynamic therapy for in vivo targets with depths beyond 10 mm. In this report, as a proof-of-concept, we demonstrated that a positron emission tomography (PET) radiotracer, 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)FDG), could be used as an alternative light source for photoactivation. PROCEDURES: We utilized (18)FDG, which is a metabolic activity-based PET probe, as a source of light to photoactivate caged luciferin in a breast cancer animal model expressing luciferase. RESULTS: Bioluminescence produced from luciferin allowed for the real-time monitoring of Cherenkov radiation-promoted uncaging of the substrate. CONCLUSION: The proposed method may provide a very important option for in vivo photoactivation, in particular for activation of photosensitizers for photodynamic therapy and eventually for combining radioisotope therapy and photodynamic therapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21538154
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10517