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      1. Author :
        Ru, P.; Steele, R.; Newhall, P.; Phillips, N. J.; Toth, K.; Ray, R. B.
      2. Title :
        miRNA-29b suppresses prostate cancer metastasis by regulating epithelial-mesenchymal transition signaling
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Cancer Ther
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        11
      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
      12. Abstract :
        Prostate cancer remains the second leading cause of cancer deaths among American men. Early diagnosis increases survival rate in patients; however, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment are necessary for inhibiting prostate cancer disease progression. Here, we have shown that miRNA-29b (miR-29b) expression was lower in prostate cancer cells (PC3 and LNCaP) as compared with immortalized prostate epithelial cells. Between these two prostate cancer cell lines, metastatic prostate cancer PC3 cells displayed lower expression of miR-29b. We also observed a significant downregulation of miR-29b expression in human prostate cancer tissues as compared with patient-matched nontumor tissues. PC3 cells ectopically expressing miR-29b inhibited wound healing, invasiveness, and failed to colonize in the lungs and liver of severe combined immunodeficient mice after intravenous injection, while PC3 cells expressing a control miRNA displayed metastasis. Epithelial cell marker E-cadherin expression was enhanced miR-29b transfected in prostate cancer cells as compared with cells expressing control miRNA. On the other hand, N-cadherin, Twist, and Snail expression was downregulated in PC3 cells expressing miR-29b. Together these results suggested that miR-29b acts as an antimetastatic miRNA for prostate cancer cells at multiple steps in a metastatic cascade. Therefore, miR-29b could be a potentially new attractive target for therapeutic intervention in prostate cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22402125
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10539
      1. Author :
        Zuluaga, M. F.; Sekkat, N.; Gabriel, D.; van den Bergh, H.; Lange, N.
      2. Title :
        Selective Photodetection and Photodynamic Therapy of Prostate Cancer through Targeting of Proteolytic Activity
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Cancer Ther
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        N/A
      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
      12. Abstract :
        Frequent side effects of radical treatment modalities and the availability of novel diagnostics have raised the interest in focal therapies for localized prostate cancer. To improve the selectivity and therapeutic efficacy of such therapies, we developed a minimally invasive procedure, based on a novel polymeric photosensitizer prodrug sensitive to urokinase-like plasminogen activator (uPA). The compound is inactive in its prodrug form and accumulates passively at the tumor site by the enhanced permeability and retention effect. There, the prodrug is selectively converted to its photoactive form by uPA which is over-expressed by prostate cancer cells. Irradiation of the activated photosensitizer exerts a tumor-selective phototoxic effect. The prodrug alone (8 microM) showed no toxic effect on PC-3 cells, but upon irradiation the cell viability was reduced by 90%. In vivo, after systemic administration of the prodrug, PC-3 xenografts became selectively fluorescent. This is indicative of the prodrug accumulation in the tumor and selective local enzymatic activation. Qualitative analysis of the activated compound confirmed that the enzymatic cleavage occurred selectively in the tumor, with only trace amounts in the neighboring skin or muscle. Subsequent photodynamic therapy studies demonstrated complete tumor eradication of animals treated with light (150 J/cm2 at 665 nm) 16 hours after the injection of the prodrug (7.5 mg/kg). These promising results evidence the excellent selectivity of our prodrug with the potential to be used for both, imaging and therapy of localized prostate cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23270928
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10542
      1. Author :
        Xiao, K.; Li, Y.; Lee, J. S.; Gonik, A. M.; Dong, T.; Fung, G.; Sanchez, E.; Xing, L.; Cheng, H. R.; Luo, J.; Lam, K. S.
      2. Title :
        “OA02” peptide facilitates the precise targeting of paclitaxel-loaded micellar nanoparticles to ovarian cancer in vivo
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cancer Res
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        72
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        SKOV3-luc-D3, SKOV3-luc, IVIS, Ovarian Cancer, Animals; Antineoplastic Agents, Phytogenic/*administration & dosage; Cell Line, Tumor; Drug Carriers/*chemical synthesis/chemistry/therapeutic use; Drug Delivery Systems/*methods; Female; Flow Cytometry; Humans; Integrin alpha Chains/metabolism; Mice; Mice, Nude; Micelles; Microscopy, Confocal; Nanoparticles/chemistry/therapeutic use; Ovarian Neoplasms/*drug therapy; Paclitaxel/*administration & dosage; Peptides/chemical synthesis/therapeutic use; Polyethylene Glycols/chemistry
      12. Abstract :
        Micellar nanoparticles based on linear polyethylene glycol (PEG) block dendritic cholic acids (CA) copolymers (telodendrimers), for the targeted delivery of chemotherapeutic drugs in the treatment of cancers, are reported. The micellar nanoparticles have been decorated with a high-affinity “OA02” peptide against alpha-3 integrin receptor to improve the tumor-targeting specificity which is overexpressed on the surface of ovarian cancer cells. “Click chemistry” was used to conjugate alkyne-containing OA02 peptide to the azide group at the distal terminus of the PEG chain in a representative PEG(5k)-CA(8) telodendrimer (micelle-forming unit). The conjugation of OA02 peptide had negligible influence on the physicochemical properties of PEG(5k)-CA(8) nanoparticles and as hypothesized, OA02 peptide dramatically enhanced the uptake efficiency of PEG(5k)-CA(8) nanoparticles (NP) in SKOV-3 and ES-2 ovarian cancer cells via receptor-mediated endocytosis, but not in alpha-3 integrin-negative K562 leukemia cells. When loaded with paclitaxel, OA02-NPs had significantly higher in vitro cytotoxicity against both SKOV-3 and ES-2 ovarian cancer cells as compared with nontargeted nanoparticles. Furthermore, the in vivo biodistribution study showed OA02 peptide greatly facilitated tumor localization and the intracellular uptake of PEG(5k)-CA(8) nanoparticles into ovarian cancer cells as validated in SKOV3-luc tumor-bearing mice. Finally, paclitaxel (PTX)-loaded OA02-NPs exhibited superior antitumor efficacy and lower systemic toxicity profile in nude mice bearing SKOV-3 tumor xenografts, when compared with equivalent doses of nontargeted PTX-NPs as well as clinical paclitaxel formulation (Taxol). Therefore, OA02-targeted telodendrimers loaded with paclitaxel have great potential as a new therapeutic approach for patients with ovarian cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22396491
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10543
      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 :
        Curcumin-cyclodextrin complexes potentiate gemcitabine effects in an orthotopic mouse model of lung cancer
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Br J Cancer
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      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 :
        Tumor-mast cell interactions: induction of pro-tumorigenic genes and anti-tumorigenic 4-1BB in MCs in response to Lewis Lung Carcinoma
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Immunol
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      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 :
        Gule, N. P.; de Kwaadsteniet, M.; Cloete, T. E.; Klumperman, B.
      2. Title :
        Furanone-containing poly(vinyl alcohol) nanofibers for cell-adhesion inhibition
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Water Res
      6. Products :

        Bioware bacteria

      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 :
        Furanone-containing poly(vinyl alcohol) nanofibers for cell-adhesion inhibition
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Water Res
      6. Products :

        Bioware bacteria

      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 :
        Immobilized furanone derivatives as inhibitors for adhesion of bacteria on modified poly(styrene-co-maleic anhydride)
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Biomacromolecules
      6. Products :

        Bioware bacteria

      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 :
        Antibacterial activity of the human host defence peptide LL-37 and selected synthetic cationic lipids against bacteria associated with oral and upper respiratory tract infections
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Antimicrob Chemother
      6. Products :

        Bioware bacteria

      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 :
        Full and broad-spectrum in vivo eradication of catheter-associated biofilms using gentamicin-EDTA antibiotic lock therapy
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Antimicrob Agents Chemother
      6. Products :

        Bioware bacteria

      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
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