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      1. Author :
        Rocks, N.; Bekaert, S.; Coia, I.; Paulissen, G.; Gueders, M.; Evrard, B.; Van Heugen, J. C.; Chiap, P.; Foidart, J. M.; Noel, A.; Cataldo, D.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Br J Cancer
      6. Products :
      7. Volume :
        107
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        LL/2-luc-M38, LL/2-luc, Lewis Lung Carcinoma, IVIS
      12. Abstract :
        BACKGROUND: Overall clinical outcome for advanced lung cancer remains very disappointing despite recent advances in treatment. Curcumin has been reported as potentially active against cancer. METHODS: Owing to poor curcumin solubility, we have used cyclodextrins (CD) as an excipient allowing a considerable increase of aqueous solubility and bioavailability of curcumin. The effects of solubilised curcumin have been evaluated in cell cultures as well as in an in vivo orthotopic lung tumour mouse model. RESULTS: Cell proliferation was reduced while apoptosis rates were increased when lung epithelial tumour cells were cultured in the presence of curcumin-CD complexes. For in vivo experiments, cells were grafted into lungs of C57Bl/6 mice treated by an oral administration of a non-soluble form of curcumin, CDs alone or curcumin-CD complexes, combined or not with gemcitabine. The size of orthotopically implanted lung tumours was reduced upon curcumin complex administration as compared with treatments with placebo or non-solubilised curcumin. Moreover, curcumin potentiated the gemcitabine-mediated antitumour effects. CONCLUSION: Our data demonstrate that curcumin, when given orally in a CD-solubilised form, reduces lung tumour size in vivo. In vitro experiments show impaired tumour cell proliferation and increased cell apoptosis. Moreover, our data underline a potential additive effect of curcumin with gemcitabine thus providing an efficient therapeutic option for antilung cancer therapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22929882
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10545
      1. Author :
        Wensman, H.; Kamgari, N.; Johansson, A.; Grujic, M.; Calounova, G.; Lundequist, A.; Ronnberg, E.; Pejler, G.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Immunol
      6. Products :
      7. Volume :
        50
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        LL/2-luc-M38, LL/2-luc, Lewis Lung Carcinoma, IVIS, Animals; Antigens, CD137/genetics/*immunology; Carcinoma, Lewis Lung/genetics/*immunology/metabolism; Gene Expression Profiling; Gene Expression Regulation, Neoplastic/genetics/*immunology; Humans; Immunohistochemistry; Mast Cells/*immunology/metabolism; Oligonucleotide Array Sequence Analysis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation
      12. Abstract :
        Mast cells (MCs) can have either detrimental or beneficial effects on malignant processes but the underlying mechanisms are poorly understood. Here we addressed this issue by examining the interaction between Lewis Lung Carcinoma (LLC) cells and MCs. In vivo, LLC tumors caused a profound accumulation of MCs, suggesting that LLC tumors have the capacity to attract MCs. Indeed, transwell migration assays showed that LLC-conditioned medium had chemotactic activity towards MCs, which was blocked by an antibody towards stem cell factor. In order to gain insight into the molecular mechanisms operative in tumor-MC interactions, the effect of LLC on the MC gene expression pattern was examined. As judged by gene array analysis, conditioned medium from LLC cells caused significant upregulation of numerous cell surface receptors and a pro-angiogenic Runx2/VEGF/Dusp5 axis in MCs, the latter in line with a role for MCs in promoting tumor angiogenesis. Among the genes showing the highest extent of upregulation was Tnfrsf9, encoding the anti-tumorigenic protein 4-1BB, suggesting that also anti-tumorigenic factors are induced. Quantitative RT-PCR analysis showed that 4-1BB was upregulated in a transient manner, and it was also shown that tumor cells induce 4-1BB in human MCs. Immunohistochemical analysis showed that LLC-conditioned medium induced 4-1BB also at the protein level. Together, this study provides novel insight into the molecular events associated with MC-tumor interactions and suggests that tumor cells induce both pro- and anti-tumorigenic responses in MCs.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22343053
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10546
      1. Author :
        Lee, S. K.; Han, M. S.; Asokan, S.; Tung, C. H.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Small
      6. Products :
      7. Volume :
        7
      8. Issue :
        N/A
      9. Page Numbers :
        364-70
      10. Research Area :
        N/A
      11. Keywords :
        LnCaP-luc2, Prostate Cancer, IVIS, *Gene Silencing; *Gold; Metal Nanoparticles/*chemistry/ultrastructure; Microscopy, Electron, Transmission; Polylysine/chemistry; RNA, Small Interfering/*genetics
      12. Abstract :
        Small interfering RNA (siRNA) has been widely proposed to treat various diseases by silencing genes, but its delivery remains a challenge. A well controlled assembly approach is applied to prepare a protease-assisted nanodelivery system. Protease-degradable poly-L-lysine (PLL) and siRNA are fabricated onto gold nanoparticles (AuNPs), by alternating the charged polyelectrolytes. In this study, up to 4 layers of PLL and 3 layers of siRNA (sR3P) are coated. Due to the slow degradation of PLL, the incorporated siRNA is released gradually and shows extended gene-silencing effects. Importantly, the inhibition effect in cells is found to correlate with the number of siRNA layers.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21294265
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10547
      1. Author :
        Gule, N. P.; de Kwaadsteniet, M.; Cloete, T. E.; Klumperman, B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Water Res
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen39, Xen26, Xen14, Xen36, Xen 5, Xen 39, Xen 26, Xen 14, Xen 36, Psuedomonas aeruginosa, S. aureus, Klebsiella, E. coli, Salmonella,
      12. Abstract :
        The 3(2H) furanone derivative 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) was investigated for its antimicrobial and cell-adhesion inhibition properties against Klebsiella pneumoniae Xen 39, Staphylococcus aureus Xen 36, Escherichia coli Xen 14, Pseudomonas aeruginosa Xen 5 and Salmonella typhimurium Xen 26. Nanofibers electrospun from solution blends of DMHF and poly(vinyl alcohol) (PVA) were tested for their ability to inhibit surface-attachment of bacteria. Antimicrobial and adhesion inhibition activity was determined via the plate counting technique. To quantify viable but non-culturable cells and to validate the plate counting results, bioluminescence and fluorescence studies were carried out. Nanofiber production was upscaled using the bubble electrospinning technique. To ascertain that no DMHF leached into filtered water, samples of water filtered through the nanofibrous mats were analyzed using gas chromatography coupled with mass spectrometry (GC-MS). Scanning electron microscopy (SEM) and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) were used to characterize the electrospun nanofibers.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23261340
      14. Call Number :
        PKI @ kd.modi @ 7
      15. Serial :
        10548
      1. Author :
        Gule, N. P.; de Kwaadsteniet, M.; Cloete, T. E.; Klumperman, B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Water Res
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen39, Xen26, Xen14, Xen36, Xen 5, Xen 39, Xen 26, Xen 14, Xen 36, Psuedomonas aeruginosa, S. aureus, Klebsiella, E. coli, Salmonella,
      12. Abstract :
        The 3(2H) furanone derivative 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF) was investigated for its antimicrobial and cell-adhesion inhibition properties against Klebsiella pneumoniae Xen 39, Staphylococcus aureus Xen 36, Escherichia coli Xen 14, Pseudomonas aeruginosa Xen 5 and Salmonella typhimurium Xen 26. Nanofibers electrospun from solution blends of DMHF and poly(vinyl alcohol) (PVA) were tested for their ability to inhibit surface-attachment of bacteria. Antimicrobial and adhesion inhibition activity was determined via the plate counting technique. To quantify viable but non-culturable cells and to validate the plate counting results, bioluminescence and fluorescence studies were carried out. Nanofiber production was upscaled using the bubble electrospinning technique. To ascertain that no DMHF leached into filtered water, samples of water filtered through the nanofibrous mats were analyzed using gas chromatography coupled with mass spectrometry (GC-MS). Scanning electron microscopy (SEM) and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) were used to characterize the electrospun nanofibers.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23261340
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10549
      1. Author :
        Gule, N. P.; Bshena, O.; de Kwaadsteniet, M.; Cloete, T. E.; Klumperman, B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Biomacromolecules
      6. Products :
      7. Volume :
        13
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen 5, Pseudomonas aeruginosa
      12. Abstract :
        The ability of brominated furanones and other furanone compounds with 2(3H) and 2(5H) cores to inhibit bacterial adhesion of surfaces as well deactivate (destroy) them has been previously reported. The furanone derivatives 4-(2-(2-aminoethoxy)-2,5-dimethyl-3(2H)-furanone and 5-(2-(2-aminoethoxy)-ethoxy)methyl)-2(5H)-furanone were synthesized in our laboratory. These furanone derivatives were then covalently immobilized onto poly(styrene-co-maleic anhydride) (SMA) and electrospun to fabricate nonwoven nanofibrous mats with antimicrobial and cell-adhesion inhibition properties. The electrospun nanofibrous mats were tested for their ability to inhibit cell attachment by strains of bacteria commonly found in water ( Klebsiella pneumoniae Xen 39, Staphylococcus aureus Xen 36, Escherichia coli Xen 14, Pseudomonas aeruginosa Xen 5, and Salmonella tymphimurium Xen 26). Proton nuclear magnetic resonance spectroscopy ((1)H NMR), electrospray mass spectroscopy (ES-MS), and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) were used to confirm the structures of the synthesized furanones as well as their successful immobilization on SMA. To ascertain that the immobilized furanone compounds do not leach into filtered water, samples of water, filtered through the nanofibrous mats were analyzed using gas chromatography coupled with mass spectroscopy (GC-MS). The morphology of the electrospun nanofibers was characterized using scanning electron microscopy (SEM).
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22947312
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10550
      1. Author :
        Leszczynska, K.; Namiot, D.; Byfield, F. J.; Cruz, K.; Zendzian-Piotrowska, M.; Fein, D. E.; Savage, P. B.; Diamond, S.; McCulloch, C. A.; Janmey, P. A.; Bucki, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Antimicrob Chemother
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen 5, Pseudomonas aeruginosa
      12. Abstract :
        OBJECTIVES: We aim to develop antibacterial peptide mimics resistant to protease degradation, with broad-spectrum activity at sites of infection. METHODS: The bactericidal activities of LL-37, ceragenins CSA-13, CSA-90 and CSA-92 and the spermine-conjugated dexamethasone derivative D2S were evaluated using MIC and MBC measurements. Gingival fibroblast counting, interleukin-8 (IL-8) and lactate dehydrogenase (LDH) release from keratinocytes (HaCat) were used to determine effects on cell growth, pro-inflammatory response and toxicity. RESULTS: All tested cationic lipids showed stronger bactericidal activity than LL-37. Incubation of Staphylococcus aureus with half the MIC of LL-37 led to the appearance of bacteria resistant to its bactericidal effects, but identical incubations with CSA-13 or D2S did not produce resistant bacteria. Cathelicidin LL-37 significantly increased the total number of gingival fibroblasts, but ceragenins and D2S did not alter gingival fibroblast growth. Cationic lipids showed no toxicity to HaCat cells at concentrations resulting in bacterial killing. CONCLUSIONS: These data suggest that cationic lipids such as ceragenins warrant further testing as potential novel antibacterial agents.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23134677
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10551
      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 :
        Dai, T.; Tegos, G. P.; Zhiyentayev, T.; Mylonakis, E.; Hamblin, M. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Lasers Surg Med
      6. Products :
      7. Volume :
        42
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen31, Xen 31, MRSA, S. aureus, IVIS, Bioluminescence, Administration, Cutaneous; Animals; Disease Models, Animal; Female; *Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; Photobleaching; *Photochemotherapy; Polyethyleneimine/administration & dosage; Porphyrins/*administration & dosage; Radiation-Sensitizing Agents/*administration & dosage; Staphylococcal Skin Infections/etiology/pathology/*therapy; Wound Infection/microbiology/pathology/*therapy
      12. Abstract :
        BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) skin infections are now known to be a common and important problem in the Unites States. The objective of this study was to investigate the efficacy of photodynamic therapy (PDT) for the treatment of MRSA infection in skin abrasion wounds using a mouse model. STUDY DESIGN/MATERIALS AND METHODS: A mouse model of skin abrasion wound infected with MRSA was developed. Bioluminescent strain of MRSA, a derivative of ATCC 33591, was used to allow the real-time monitoring of the extent of infection in mouse wounds. PDT was performed with the combination of a polyethylenimine (PEI)-ce6 photosensitizer (PS) and non-coherent red light. In vivo fluorescence imaging was carried out to evaluate the effect of photobleaching of PS during PDT. RESULTS: In vivo fluorescence imaging of conjugate PEI-ce6 applied in mice indicated the photobleaching effect of the PS during PDT. PDT induced on average 2.7 log(10) of inactivation of MRSA as judged by loss of bioluminescence in mouse skin abrasion wounds and accelerated the wound healing on average by 8.6 days in comparison to the untreated infected wounds. Photobleaching of PS in the wound was overcome by adding the PS solution in aliquots. CONCLUSION: PDT may represent an alternative approach for the treatment of MRSA skin infections.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20077489
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10553
      1. Author :
        Krespi, Y. P.; Kizhner, V.; Nistico, L.; Hall-Stoodley, L.; Stoodley, P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Am J Otolaryngol
      6. Products :
      7. Volume :
        32
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen31, Xen 31, MRSA, S. aureus, IVIS, Bioluminescence, Biofilms/drug effects/*radiation effects; Ciprofloxacin/*pharmacology; Culture Media; High-Energy Shock Waves; Humans; *Laser Therapy, Low-Level; Methicillin-Resistant Staphylococcus aureus/*growth &; development/physiology/*radiation effects; Microbial Sensitivity Tests; Reference Values; Sensitivity and Specificity; Spectroscopy, Near-Infrared; Staphylococcal Infections/drug therapy
      12. Abstract :
        OBJECTIVE: The aim of the study was to study the efficacy of 2 different lasers in vitro, in disrupting biofilm and killing planktonic pathogenic bacteria. MATERIALS AND METHODS: Biofilms of a stable bioluminescent of Staphylococcus aureus Xen 31 were grown in a 96-well microtiter plate for 3 days. The study included 7 arms: (a) control; (b) ciprofloxacin (3 mg/L, the established minimum inhibitory concentration [MIC]) alone; (c) shock wave (SW) laser alone; (d) near-infrared (NIR) laser alone; (e) SW laser and ciprofloxacin; (f) SW and NIR lasers; (g) SW, NIR lasers, and ciprofloxacin. The results were evaluated with an in vivo imaging system (IVIS) biophotonic system (for live bacteria) and optical density (OD) for total bacteria. RESULTS: Without antibiotics, there was a 43% reduction in OD (P < .05) caused by the combination of SW and NIR suggesting that biofilm had been disrupted. There was an 88% reduction (P < .05) in live biofilm. Ciprofloxacin alone resulted in a decrease of 28% of total live cells (biofilm remaining attached) and 58% of biofilm cells (both P > .05). Ciprofloxacin in combination with SW and SW + NIR lasers caused a decrease of more than 60% in total live biomass and more than 80% of biofilm cells, which was significantly greater than ciprofloxacin alone (P < .05). CONCLUSIONS: We have demonstrated an effective nonpharmacologic treatment method for methicillin-resistant Staphylococcus aureus (MRSA) biofilm disruption and killing using 2 different lasers. The preferred treatment sequence is a SW laser disruption of biofilm followed by NIR laser illumination. Treatment optimization of biofilm is possible with the addition of ciprofloxacin in concentrations consistent with planktonic MIC.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20434806
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10554