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      1. Author :
        Ranganath, Sudhir H; Fu, Yilong; Arifin, Davis Y; Kee, Irene; Zheng, Lin; Lee, How-Sung; Chow, Pierce K-H; Wang, Chi-Hwa
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        31
      8. Issue :
        19
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antineoplastic Agents; Bioware; Brain Neoplasms; Cell Line, Tumor; Drug Implants; Glioblastoma; Male; Metabolic Clearance Rate; Mice; Mice, Inbred BALB C; Nanostructures; Paclitaxel; Treatment Outcome; U-87 MG-luc2
      12. Abstract :
        Pharmacokinetics and therapeutic efficacy of submicron/nanoscale, intracranial implants were evaluated for treating malignant glioblastoma in mice. 9.1% (w/w) paclitaxel-loaded polylactide-co-glycolide (PLGA) nanofiber discs (F3) were fabricated and characterized for morphology and size distribution. Along with F3, three other formulations, 9.1% (w/w) paclitaxel-loaded PLGA submicron-fiber discs (F2), 16.7% (w/w) paclitaxel-loaded PLGA microspheres entrapped in hydrogel matrices (H80 and M80) were intracranially implanted in BALB/c mice and the coronal brain sections were analyzed for bio-distribution of paclitaxel on 14, 28 and 42 days post-implantation. BALB/c nude mice with intracranial human glioblastoma (U87 MG-luc2) were used in the therapeutic efficacy study. Animals were randomized to intracranial implantation of F3 and H80 with paclitaxel dose of 10mg/kg, placebo F3, placebo H80, weekly intratumoral injection of Taxol (10mg/kg) or no treatment and the treatment response was analyzed by bioluminescence imaging and histological (H&E, Ki-67) examinations. Enhanced, therapeutic paclitaxel penetration (approximately 1 microm) in the mouse brain up to 5mm from the implant site even after 42 days post-implantation from F3 and H80 was confirmed and deduced to be diffusion/elimination controlled. F3 and H80 demonstrated significant (approximately 30 fold) tumor inhibition and significantly low tumor proliferation index after 41 days of treatment in comparison to sham and placebo controls. The submicron/nanoscale implants are able to demonstrate optimal paclitaxel pharmacokinetics in the brain/tumor with significant tumor inhibition in a glioblastoma xenograft model in mice and hence could be potentially useful to treat highly recurrent GBM.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20350766
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8942
      1. Author :
        Razavi, Reza; Harrison, Lawrence E
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Annals of surgical oncology
      6. Products :
      7. Volume :
        17
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Carcinoma; Cell Proliferation; Colonic Neoplasms; DNA Damage; Drug Therapy, Combination; Female; HT-29-luc-D6 cells; Humans; Hydrogen peroxide; Hyperthermia, Induced; Injections, Intraperitoneal; Mice; Mice, Nude; Oxidants; Oxidative Stress; Survival Rate; tert-Butylhydroperoxide; Treatment Outcome; Tumor Cells, Cultured
      12. Abstract :
        BACKGROUND The purpose of this study was to extend our in vitro observations that induced oxidative stress under hyperthermic conditions decreases tumor cell growth into a preclinical murine model of hyperthermic perfusion. METHODS A nude mouse model of colon cancer carcinomatosis with HT-29-Luc-D6 colon cancer cells was established, and tumor growth was measured by serial bioluminescent imaging. RESULTS By means of a survival model of hyperthermic perfusion, we demonstrated that perfusion with normothermic saline decreased tumor growth compared with no perfusion controls, and tumor growth was further decreased with hyperthermic perfusion alone. The induction of oxidative stress with hydrogen peroxide in the perfusate at concentrations as high as 600 microM was well tolerated in this model of hyperthermic perfusion. Importantly, induced oxidative stress using hydrogen peroxide under hyperthermic conditions significantly decreased in vivo tumor cell growth compared with all other controls. CONCLUSIONS On the basis of our observations, thermal sensitization through modulation of cellular oxidative stress may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19711132
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9008
      1. Author :
        Kuo, Chaincy; Coquoz, Olivier; Troy, Tamara L; Xu, Heng; Rice, Brad W
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Journal of biomedical optics
      6. Products :
      7. Volume :
        12
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Luminescent Proteins; Male; Mice; Microscopy, Fluorescence, Multiphoton; PC-3M-luc; Prostatic Neoplasms; Whole Body Imaging
      12. Abstract :
        A new method is described for obtaining a 3-D reconstruction of a bioluminescent light source distribution inside a living animal subject, from multispectral images of the surface light emission acquired on charge-coupled device (CCD) camera. The method uses the 3-D surface topography of the animal, which is obtained from a structured light illumination technique. The forward model of photon transport is based on the diffusion approximation in homogeneous tissue with a local planar boundary approximation for each mesh element, allowing rapid calculation of the forward Green's function kernel. Absorption and scattering properties of tissue are measured a priori as input to the algorithm. By using multispectral images, 3-D reconstructions of luminescent sources can be derived from images acquired from only a single view. As a demonstration, the reconstruction technique is applied to determine the location and brightness of a source embedded in a homogeneous phantom subject in the shape of a mouse. The technique is then evaluated with real mouse models in which calibrated sources are implanted at known locations within living tissue. Finally, reconstructions are demonstrated in a PC3M-luc (prostate tumor line) metastatic tumor model in nude mice.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17477722
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8968
      1. Author :
        Orihuela, Carlos J; Gao, Geli; Francis, Kevin P; Yu, Jun; Tuomanen, Elaine I
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2004
      5. Publication :
        The Journal of infectious diseases
      6. Products :
      7. Volume :
        190
      8. Issue :
        9
      9. Page Numbers :
        1661-1669
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bacteremia; Bacterial Proteins; Cerebrospinal Fluid; Disease Models, Animal; Female; Lung; Meningitis, Pneumococcal; Mice; Mice, Inbred BALB C; Mutation; N-Acetylmuramoyl-L-alanine Amidase; Nasopharynx; Neuraminidase; Pneumococcal Infections; Pneumonia, Pneumococcal; Pyruvate Oxidase; Streptococcus pneumoniae; Streptolysins; Virulence Factors; Xen7
      12. Abstract :
        We assessed the ability of Streptococcus pneumoniae mutants deficient in either choline binding protein A (CbpA), pneumolysin (Pln), pyruvate oxidase (SpxB), autolysin (LytA), pneumococcal surface protein A, or neuraminidase A (NanA) to replicate in distinct anatomical sites and translocate from one site to the next. Intranasal, intratracheal, and intravenous models of disease were assessed in 4-week-old BALB/cJ mice by quantitation of bacterial titers in the relevant organs. Mice were also observed by use of real-time bioluminescent imaging (BLI). BLI allowed visualization of the bacteria in sites not tested by sampling. All mutants were created in D39 Xen7, a fully virulent derivative of capsular type 2 strain D39 that contains an optimized luxABCDE cassette. NanA, SpxB, and, to a lesser extent, CbpA contributed to prolonged nasopharyngeal colonization, whereas CbpA and NanA contributed to the transition to the lower respiratory tract. Once lung infection was established, Pln, SpxB, and LytA contributed to bacterial replication in the lungs and translocation to the bloodstream. In the bloodstream, only Pln and LytA were required for high-titer replication, whereas CbpA was required for invasion of the cerebrospinal fluid. We conclude that transitions between body sites require virulence determinants distinct from those involved in organ-specific replication.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/15478073
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        10002
      1. Author :
        Inglefield, Jon R; Dumitru, Calin Dan; Alkan, Sefik S; Gibson, Sheila J; Lipson, Kenneth E; Tomai, Mark A; Larson, Chris J; Vasilakos, John P
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research
      6. Products :
      7. Volume :
        28
      8. Issue :
        4
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Aminoquinolines; Animals; B16-F10-luc-G5 cells; Bioware; Cell Line, Tumor; Cell Proliferation; Cell Survival; Culture Media, Conditioned; dendritic cells; Humans; Interferon Type I; Leukocytes, Mononuclear; Lung; Melanoma; Mice; Neoplasms; Oligodeoxyribonucleotides; Quinolines; Subcellular Fractions; Sulfonamides; Toll-Like Receptor 7
      12. Abstract :
        Antitumor effects of the toll-like receptor 7 (TLR7) agonist, 852A, were evaluated. Supernatants from human peripheral blood mononuclear cells (PBMC) stimulated with 852A inhibited the proliferation of tumor cell lines Hs294T and 769-P but had no effect on others (786-O and Caki-1). Because addition of 852A directly to the Hs294T cells did not inhibit their proliferation, the mechanism(s) of inhibition of tumor cell proliferation was investigated. Low nanomolar concentrations of 852A stimulated the production of interferon-alpha (IFN-alpha), IFN-inducible protein-10 (IP-10), interleukin-1 receptor antagonist (IL-1Ra), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from human PBMCs. Cytokines stimulated by submicromolar concentrations of 852A were sufficient to inhibit Hs294T proliferation. At higher concentrations (3-30 microM), 852A induced the production of IL-12p70, IL-18, and IFN-gamma. PBMC cultures depleted of plasmacytoid dendritic cells (pDC) did not produce IFN-alpha, and their conditioned medium did not inhibit Hs294T proliferation. Anti-IFN-alpha/beta receptor (IFNAR) and anti-IFN-alpha antibodies partially abrogated Hs294T proliferation inhibition by 852A-stimulated PBMC supernatants, whereas separate neutralization of TRAIL, tumor necrosis factor-alpha (TNF-alpha, IFN-gamma, IFN-beta, or IFN-omega had no effect. In vivo, six doses of 852A administration significantly delayed the onset of lung colonies in a B16 melanoma model. Thus, the results demonstrate that the TLR7 agonist 852A inhibits in vitro proliferation of some tumor cells in a pDC-dependent and IFN-alpha-dependent manner and can delay tumor growth in vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18439103
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9001
      1. Author :
        Echchannaoui, H.; Frei, K.; Schnell, C.; Leib, S. L.; Zimmerli, W.; Landmann, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2002
      5. Publication :
        Journal of Infectious Diseases
      6. Products :
      7. Volume :
        186
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals, Ceftriaxone/therapeutic use, Cephalosporins/therapeutic use, Disease Models, Animal, Disease Susceptibility, Drosophila Proteins, Inflammation/genetics/immunology/microbiology/pathology, Listeria Infections/genetics/immunology, Listeria monocytogenes/genetics/immunology, Membrane Glycoproteins/ deficiency/genetics, Meningitis, Bacterial/ genetics/ immunology/microbiology/pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Pneumococcal Infections/genetics/immunology/microbiology/pathology, Receptors, Cell Surface/ deficiency/genetics, Streptococcus pneumoniae/ immunology, Time Factors, Toll-Like Receptor 2, Toll-Like Receptors IVIS, Xenogen, Xen10
      12. Abstract :
        Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacterial wall components. TLR2 function was investigated in a murine Streptococcus pneumoniae meningitis model in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. TLR2(-/-) mice showed earlier time of death than wt mice (P<.02). Plasma interleukin-6 levels and bacterial numbers in blood and peripheral organs were similar for both strains. With ceftriaxone therapy, none of the wt but 27% of the TLR2(-/-) mice died (P<.04). Beyond 3 hours after infection, TLR2(-/-) mice had higher bacterial loads in brain than did wt mice, as assessed with luciferase-tagged S. pneumoniae by means of a Xenogen-CCD (charge-coupled device) camera. After 24 h, tumor necrosis factor activity was higher in cerebrospinal fluid of TLR2(-/-) than wt mice (P<.05) and was related to increased blood-brain barrier permeability (Evans blue staining, P<.02). In conclusion, the lack of TLR2 was associated with earlier death from meningitis, which was not due to sepsis but to reduced brain bacterial clearing, followed by increased intrathecal inflammation.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/12198614
      14. Call Number :
        137638
      15. Serial :
        7950
      1. Author :
        Schwan, William R; Lehmann, Lynn; McCormick, James
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Infection and immunity
      6. Products :
      7. Volume :
        74
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Amino Acid Transport Systems, Neutral; Animals; Bacterial Proteins; Bioware; Blotting, Northern; Disease Models, Animal; Gene Expression Regulation, Bacterial; Humans; Lac Operon; Mice; Osmolar Concentration; Proline; pXen-5; Recombinant Fusion Proteins; Staphylococcal Infections; Staphylococcus aureus; Symporters; Transcriptional Activation
      12. Abstract :
        Staphylococcus aureus can grow virtually anywhere in the human body but needs to import proline through low- and high-affinity proline transporters to survive. This study examined the regulation of the S. aureus putP gene, which encodes a high-affinity proline permease. putP::lacZ and putP::lux transcriptional fusions were constructed and integrated into the genomes of several S. aureus strains. Enzyme activity was measured after growth in media with various osmolyte concentrations. As osmolarity rose, putP expression increased, with a plateau at 2 M for NaCl in strain LL3-1. Proline concentrations as low as 17.4 muM activated expression of the putP gene. The putP::lux fusion was also integrated into the genomes of S. aureus strains that were either SigB inactive (LL3-1, 8325-4, and SH1003) or SigB active (Newman and SH1000). SigB inactive strains showed increased putP gene expression as NaCl concentrations rose, whereas SigB active strains displayed a dramatic decrease in putP expression, suggesting that the alternative sigma factor B plays a negative role in putP regulation. Mice inoculated with S. aureus strains containing the putP::lux fusion exhibited up to a 715-fold increase in putP expression, although levels in the various murine organs differed. Moreover, urine from human patients infected with S. aureus showed elevated putP levels by use of a PCR procedure, whereas blood and some abscess material had no significant increase. Thus, putP is transcriptionally activated by a low-proline and high osmotic environment both in growth media and in murine or human clinical specimens.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16368996
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9023
      1. Author :
        Vintonenko, N.; Jais, J. P.; Kassis, N.; Abdelkarim, M.; Perret, G. Y.; Lecouvey, M.; Crepin, M.; Di Benedetto, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Pharmacol
      6. Products :
      7. Volume :
        82
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-luc-D3H2Ln, D3H2Ln, IVIS, Breast cancer, Bioware
      12. Abstract :
        Statins and bisphosphonates are two distinct classes of isoprenoid pathway inhibitors targeting downstream enzyme to HMG-CoA reductase (upstream enzyme) and farnesyl-pyrophosphate synthase, respectively. Here, we studied fluvastatin (Fluva) and zoledronate (Zol), representative molecules of each class, respectively. In vivo metastatic potentials of both molecules were assessed. For the first time, we observed a significant reduction in progression of established metastases with Fluva treatment. Treatment with both Zol at 100 mug/kg and Fluva at 15 mg/kg inhibited 80% of the metastasis bioluminescence signal and increased survival of mice. The Zol and Fluva transcriptomic profiles of treated MDA-MB-231 cells revealed analogous patterns of affected genes, but each of them reached with different kinetics. The observable changes in gene expression started after 24 h for Fluva IC(50 72 h) and only after 48 h for Zol IC(50 72 h). To obtain early changes in gene expression of Zol-treated cells, a 3 times higher dose of Zol IC(50 72 h) had to be applied. Combining Fluva and Zol in vivo showed no synergy, but a benefit of several days in survival of mice. This study demonstrated that Zol or Fluva is of potential clinical use for the treatment of established metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22723339
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10509
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