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      1. Author :
        Casarez, Eli V; Dunlap-Brown, Marya E; Conaway, Mark R; Amorino, George P
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Cancer research
      6. Products :
      7. Volume :
        67
      8. Issue :
        17
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Carcinoma; Estradiol; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; PC-3M-luc; Phosphorylation; Prostatic Neoplasms; Radiation-Sensitizing Agents; Subcutaneous Tissue; Transplantation, Heterotopic; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
      12. Abstract :
        2-Methoxyestradiol (2ME2) is an endogenous estradiol metabolite that inhibits microtubule polymerization, tumor growth, and angiogenesis. Because prostate cancer is often treated with radiotherapy, and 2ME2 has shown efficacy as a single agent against human prostate carcinoma, we evaluated 2ME2 as a potential radiosensitizer in prostate cancer models. A dose-dependent decrease in mitogen-activated protein kinase phosphorylation was observed in human PC3 prostate cancer cells treated with 2ME2 for 18 h. This decrease correlated with in vitro radiosensitization measured by clonogenic assays, and these effects were blocked by the expression of constitutively active MEK. Male nude mice with subcutaneous PC3 xenografts in the hind leg were treated with 2ME2 (75 mg/kg) p.o. for 5 days, and 2 Gy radiation fractions were delivered each day at 4 h after drug treatment. A statistically significant super-additive effect between radiation and 2ME2 was observed in this subcutaneous model, using analysis of within-animal slopes. A PC-3M orthotopic model was also used, with bioluminescence imaging as an end point. PC-3M cells stably expressing the luciferase gene were surgically implanted into the prostates of male nude mice. Mice were given oral doses of 2ME2 (75 mg/kg), with radiation fractions (3 Gy) delivered 4 h later. Mice were then imaged weekly for 4 to 5 weeks with a Xenogen system. A significant super-additive effect was also observed in the orthotopic model. These data show that 2ME2 is an effective radiosensitizing agent against human prostate cancer xenografts, and that the mechanism may involve a decrease in mitogen-activated protein kinase phosphorylation by 2ME2.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17804747
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8972
      1. Author :
        Carlisle, R.; Seymour, L. W.; Coussios, C. C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Pharm 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 :
        PURPOSE: To improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium. METHODS: PSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel streptavidin-protein G linker molecule. Loading of PSGL1 liposomes with luciferin allowed their binding to e-selectin and activated HUVEC to be quantified in vitro and their stability, pharmacokinetics and tumor accumulation to be tested in vivo using murine models. RESULTS: PSGL1 liposomes showed 5-fold (p < 0.05) greater selectin binding than identically formulated control liposomes modified with ligand that did not contain the selectin binding domain. When added to HUVEC, PSGL1 liposomes showed >7-fold (p < 0.001) greater attachment than control liposomes. In in vivo studies PSGL1 liposomes showed similar stability and circulation to control liposomes but demonstrated a >3-fold enhancement in the level of delivery to tumors (p < 0.05). CONCLUSIONS: The technologies and strategies described here may contribute to clinical improvements in the selectivity and efficacy of liposomal drug delivery agents.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22992830
      14. Call Number :
        PKI @ kd.modi @ 19
      15. Serial :
        10529
      1. Author :
        Cao, L.; Kobayakawa, S.; Yoshiki, A.; Abe, K.
      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 :
        AngioSense, Abdomen; Animals; Imaging, Three-Dimensional; Liver/cytology; Mice; Mice, Transgenic; Microscopy/*instrumentation/*methods; Molecular Imaging/*instrumentation/*methods; Pancreas/cytology/ultrastructure; Time-Lapse Imaging
      12. Abstract :
        Intravital imaging of brain and bone marrow cells in the skull with subcellular resolution has revolutionized neurobiology, immunology and hematology. However, the application of this powerful technology in studies of abdominal organs has long been impeded by organ motion caused by breathing and heartbeat. Here we describe for the first time a simple device designated 'microstage' that effectively reduces organ motions without causing tissue lesions. Combining this microstage device with an upright intravital laser scanning microscope equipped with a unique stick-type objective lens, the system enables subcellular-level imaging of abdominal organs in live mice. We demonstrate that this technique allows for the quantitative analysis of subcellular structures and gene expressions in cells, the tracking of intracellular processes in real-time as well as three-dimensional image construction in the pancreas and liver of the live mouse. As the aforementioned analyses based on subcellular imaging could be extended to other intraperitoneal organs, the technique should offer great potential for investigation of physiological and disease-specific events of abdominal organs. The microstage approach adds an exciting new technique to the in vivo imaging toolbox.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22479464
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10431
      1. Author :
        Cabral, Horacio; Nishiyama, Nobuhiro; Kataoka, Kazunori
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Journal of controlled release: official journal of the Controlled Release Society
      6. Products :
      7. Volume :
        121
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antineoplastic Agents; Bioware; Cell Line, Tumor; Drug Carriers; Drug Delivery Systems; Female; Hela Cells; HeLa-luc; Humans; Mice; Mice, SCID; Micelles; Neoplasms; Organoplatinum Compounds; Platinum; Polymers; Xenograft Model Antitumor Assays
      12. Abstract :
        Polymeric micelles are promising nanocarriers, which might enhance the efficacy of antitumor drugs. Herein, polymeric micelles incorporating dichloro(1,2-diamino-cyclohexane)platinum(II) (DACHPt), the oxaliplatin parent complex, were prepared through the polymer-metal complex formation of DACHPt with poly(ethylene glycol)-b-poly(glutamic acid) [PEG-b-P(Glu)] block copolymer having different lengths of the poly(glutamic acid) block [p(Glu): 20, 40, and 70 U]. The resulting micelles were studied with the aim of optimizing the system's biological performance. DACHPt-loaded micelles (DACHPt/m) were approximately 40 nm in diameter and had a narrow size distribution. In vivo biodistribution and antitumor activity experiments (CDF1 mice bearing the murine colon adenocarcinoma C-26 inoculated subcutaneously) showed 20-fold greater accumulation of DACHPt/m at the tumor site than free oxaliplatin to achieve substantially higher antitumor efficacy. Moreover, the micelles prepared from PEG-b-P(Glu) with 20 U of P(Glu) exhibited the lowest non-specific accumulation in the liver and spleen to critically reduce non-specific accumulation, resulting in higher specificity to solid tumors. The antitumor effect of DACHPt/m was also evaluated on multiple metastases generated from intraperitoneally injected bioluminescent HeLa (HeLa-Luc) cells. The in vivo bioluminescent data indicated that DACHPt/m decreased the signal 10-to 50-fold compared to the control indicating a very strong antitumor activity. These results suggest that DACHPt/m could be an outstanding drug delivery system for oxaliplatin in the treatment of solid tumors.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17628162
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9007
      1. Author :
        Burkatovskaya, Marina; Tegos, George P; Swietlik, Emilia; Demidova, Tatiana N; P Castano, Ana; Hamblin, Michael R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        27
      8. Issue :
        22
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Acetates; Alginates; Animals; Anti-Infective Agents; Bandages; Bioware; Chitosan; Glucuronic Acid; Hexuronic Acids; Male; Mice; Mice, Inbred BALB C; Occlusive Dressings; Proteus mirabilis; Pseudomonas aeruginosa; Silver Sulfadiazine; Staphylococcus aureus; Wound Healing; Wound Infection; Xen8.1, Xen5, Xen44
      12. Abstract :
        HemCon bandage is an engineered chitosan acetate preparation used as a hemostatic control dressing, and its chemical structure suggests that it should also be antimicrobial. We tested its ability to rapidly kill bacteria in vitro and in mouse models of infected wounds. We used the Gram-negative species Pseudomonas aeruginosa and Proteus mirabilis and the Gram-positive Staphylococcus aureus that had all been stably transduced with the entire bacterial lux operon to allow in vivo bioluminescence imaging. An excisional wound in Balb/c mice was inoculated with 50-250 million cells followed after 30 min by application of HemCon bandage, alginate sponge bandage, silver sulfadiazine cream or no treatment. HemCon was more adhesive to the wound and conformed well to the injury compared to alginate. Animal survival was followed over 15 days with observations of bioluminescence emission and animal activity daily. Chitosan acetate treated mice infected with P. aeruginosa and P. mirabilis all survived while those receiving no treatment, alginate and silver sulfadiazine demonstrated 25-100% mortality. Chitosan acetate was much more effective than other treatments in rapidly reducing bioluminescence in the wound consistent with its rapid bactericidal activity in vitro as well as its light-scattering properties. S. aureus formed only non-lethal localized infections after temporary immunosuppression of the mice but HemCon was again more effective in reducing bioluminescence. The data suggest that chitosan acetate rapidly kills bacteria in the wound before systemic invasion can take place, and is superior to alginate bandage and silver sulfadiazine that may both encourage bacterial growth in the short term.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16616364
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9987
      1. Author :
        Burkatovskaya, Marina; Castano, Ana P; Demidova-Rice, Tatiana N; Tegos, George P; Hamblin, Michael R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Wound repair and regeneration: official publication of the Wound Healing Society [and] the European Tissue Repair Society
      6. Products :
      7. Volume :
        16
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Infective Agents; Bandages; Biocompatible Materials; Bioware; Chitosan; Cyclophosphamide; Male; Mice; Mice, Inbred BALB C; Staphylococcal Skin Infections; Staphylococcus aureus; Wound Healing; Wound Infection; Xen8.1
      12. Abstract :
        HemCon bandage is an engineered chitosan acetate preparation designed as a hemostatic dressing, and is under investigation as a topical antimicrobial dressing. We studied its effects on healing of excisional wounds that were or were not infected with Staphylococcus aureus, in normal mice or mice previously pretreated with cyclophosphamide (CY). CY significantly suppressed wound healing in both the early and later stages, while S. aureus alone significantly stimulated wound healing in the early stages by preventing the initial wound expansion. CY plus S. aureus showed an advantage in early stages by preventing expansion, but a significant slowing of wound healing in later stages. In order to study the conflicting clamping and stimulating effects of chitosan acetate bandage on normal wounds, we removed the bandage from wounds at times after application ranging from 1 hour to 9 days. Three days application gave the earliest wound closure, and all application times gave a faster healing slope after removal compared with control wounds. Chitosan acetate bandage reduced the number of inflammatory cells in the wound at days 2 and 4, and had an overall beneficial effect on wound healing especially during the early period where its antimicrobial effect is most important.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18471261
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9986
      1. Author :
        Bucki, Robert; Leszczynska, Katarzyna; Byfield, Fitzroy J; Fein, David E; Won, Esther; Cruz, Katrina; Namiot, Andrzej; Kulakowska, Alina; Namiot, Zbigniew; Savage, Paul B; Diamond, Scott L; Janmey, Paul A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Antimicrobial agents and chemotherapy
      6. Products :
      7. Volume :
        54
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Bacterial Infections; Biofilms; Cathelicidins; Cattle; Cells, Cultured; Dexamethasone; Drug Design; Humans; Interleukins; Macrophages; Microbial Sensitivity Tests; Neutrophils; Phagocytosis; Pseudomonas aeruginosa; Receptors, Glucocorticoid; Spermine; Staphylococcus aureus; Xen5
      12. Abstract :
        The rising number of antibiotic-resistant bacterial strains represents an emerging health problem that has motivated efforts to develop new antibacterial agents. Endogenous cationic antibacterial peptides (CAPs) that are produced in tissues exposed to the external environment are one model for the design of novel antibacterial compounds. Here, we report evidence that disubstituted dexamethasone-spermine (D2S), a cationic corticosteroid derivative initially identified as a by-product of synthesis of dexamethasone-spermine (DS) for the purpose of improving cellular gene delivery, functions as an antibacterial peptide-mimicking molecule. This moiety exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa present in cystic fibrosis (CF) sputa, and Pseudomonas aeruginosa biofilm. Although compromised in the presence of plasma, D2S antibacterial activity resists the proteolytic activity of pepsin and is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage (BAL) fluid. D2S also enhances S. aureus susceptibility to antibiotics, such as amoxicillin (AMC), tetracycline (T), and amikacin (AN). Inhibition of interleukin-6 (IL-6) and IL-8 release from lipopolysaccharide (LPS)- or lipoteichoic acid (LTA)-treated neutrophils in the presence of D2S suggests that this molecule might also prevent systemic inflammation caused by bacterial wall products. D2S-mediated translocation of green fluorescent protein (GFP)-labeled glucocorticoid receptor (GR) in bovine aorta endothelial cells (BAECs) suggests that some of its anti-inflammatory activities involve engagement of glucocorticoid receptors. The combined antibacterial and anti-inflammatory activities of D2S suggest its potential as an alternative to natural CAPs in the prevention and treatment of some bacterial infections.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20308375
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9996
      1. Author :
        Bratlie, K. M.; Dang, T. T.; Lyle, S.; Nahrendorf, M.; Weissleder, R.; Langer, R.; Anderson, D. 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 :
        Prosense, IVIS, Animals; Biocompatible Materials/*diagnostic use; Diagnostic Imaging/*methods; *Fluorescence; Macrophage Activation; Materials Testing/*methods; Mice; Models, Animal; Peptide Hydrolases/metabolism; Phagocytes
      12. Abstract :
        BACKGROUND: Many materials are unsuitable for medical use because of poor biocompatibility. Recently, advances in the high throughput synthesis of biomaterials has significantly increased the number of potential biomaterials, however current biocompatibility analysis methods are slow and require histological analysis. METHODOLOGY/PRINCIPAL FINDINGS: Here we develop rapid, non-invasive methods for in vivo quantification of the inflammatory response to implanted biomaterials. Materials were placed subcutaneously in an array format and monitored for host responses as per ISO 10993-6: 2001. Host cell activity in response to these materials was imaged kinetically, in vivo using fluorescent whole animal imaging. Data captured using whole animal imaging displayed similar temporal trends in cellular recruitment of phagocytes to the biomaterials compared to histological analysis. CONCLUSIONS/SIGNIFICANCE: Histological analysis similarity validates this technique as a novel, rapid approach for screening biocompatibility of implanted materials. Through this technique there exists the possibility to rapidly screen large libraries of polymers in vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20386609
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10427
      1. Author :
        Brandl, K.; Plitas, G.; Schnabl, B.; DeMatteo, R. P.; Pamer, E. G.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        J Exp Med
      6. Products :
      7. Volume :
        204
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals, Bone Marrow Cells/metabolism/microbiology, Gene Expression Regulation, Intestines/metabolism, Kinetics, Lectins/chemistry, Listeria Infections/*metabolism/*prevention & control, Listeria monocytogenes/*metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myeloid Differentiation Factor 88/metabolism/*physiology, Proteins/*metabolism, Recombinant Proteins/metabolism, Toll-Like Receptors/metabolism IVIS, Xenogen, Xen32
      12. Abstract :
        Listeria monocytogenes is a food-borne bacterial pathogen that causes systemic infection by traversing the intestinal mucosa. Although MyD88-mediated signals are essential for defense against systemic L. monocytogenes infection, the role of Toll-like receptor and MyD88 signaling in intestinal immunity against this pathogen has not been defined. We show that clearance of L. monocytogenes from the lumen of the distal small intestine is impaired in MyD88(-/-) mice. The distal ileum of wild-type (wt) mice expresses high levels of RegIII gamma, which is a bactericidal lectin that is secreted into the bowel lumen, whereas RegIII gamma expression in MyD88(-/-) mice is nearly undetectable. In vivo depletion of RegIII gamma from the small intestine of wt mice diminishes killing of luminal L. monocytogenes, whereas reconstitution of MyD88-deficient mice with recombinant RegIII gamma enhances intestinal bacterial clearance. Experiments with bone marrow chimeric mice reveal that MyD88-mediated signals in nonhematopoietic cells induce RegIII gamma expression in the small intestine, thereby enhancing bacterial killing. Our findings support a model of MyD88-mediated epithelial conditioning that protects the intestinal mucosa against bacterial invasion by inducing RegIII gamma.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17635956
      14. Call Number :
        136402
      15. Serial :
        7029
      1. Author :
        Brand, A. M.; de Kwaadsteniet, M.; Dicks, L. M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Lett Appl Microbiol
      6. Products :
      7. Volume :
        51
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen36, Xen 36, Staphylococcus aureus Xen36, IVIS, Animals; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Nisin/*pharmacology; Peritoneal Cavity/*microbiology; Staphylococcal Infections/*prevention & control; Staphylococcus aureus/*drug effects/growth & development
      12. Abstract :
        AIMS: To determine the ability of nisin F to control systematic infection caused by Staphylococcus aureus, using C57BL/6 mice as a model. METHODS AND RESULTS: Twelve mice were intraperitoneally injected with 1 x 10(8) viable cells of Staph. aureus Xen 36 containing the modified Photorhabdus luminescence luxABCDE operon on plasmid pAUL-A Tn4001. After 4 h, six mice were intraperitoneally injected with 640 arbitrary units (AU) nisin F, and six were injected with sterile saline. Six mice, not infected with Staph. aureus, were treated with nisin F, and six not infected were left untreated. The viability of Staph. aureus Xen 36 was monitored over 48 h by recording photon emission levels. Nisin F suppressed Staph. aureus for 15 min in vivo. No abnormalities were recorded in blood analyses and internal organs of mice treated with nisin F. CONCLUSIONS: Nisin F suppressed the growth of Staph. aureus in the peritoneal cavity for at least 15 min. Re-emergence of Staph. aureus bioluminescence over the next 44 h suggests that nisin F was inactivated, most probably by proteolytic enzymes. SIGNIFICANCE AND IMPACT OF THE STUDY: A single dosage of nisin F administered in the peritoneal cavity controlled the growth of Staph. aureus for at least 15 min in vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21029139
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10410
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