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      1. Author :
        Yang, Li; Johansson, Jan; Ridsdale, Ross; Willander, Hanna; Fitzen, Michael; Akinbi, Henry T; Weaver, Timothy E
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Journal of immunology (Baltimore, Md.: 1950)
      6. Products :
      7. Volume :
        184
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Hydrogen-Ion Concentration; Immunity, Innate; Klebsiella pneumoniae; Macrophages, Alveolar; Mice; Mice, Transgenic; Protein Precursors; Protein Structure, Tertiary; Proteolipids; Saposins; Staphylococcus aureus; Tissue Distribution; Xen5
      12. Abstract :
        Surfactant protein B (SP-B) proprotein contains three saposin-like protein (SAPLIP) domains: a SAPLIP domain corresponding to the mature SP-B peptide is essential for lung function and postnatal survival; the function of SAPLIP domains in the N-terminal (SP-BN) and C-terminal regions of the proprotein is not known. In the current study, SP-BN was detected in the supernatant of mouse bronchoalveolar lavage fluid (BALF) and in nonciliated bronchiolar cells, alveolar type II epithelial cells, and alveolar macrophages. rSP-BN indirectly promoted the uptake of bacteria by macrophage cell lines and directly killed bacteria at acidic pH, consistent with a lysosomal, antimicrobial function. Native SP-BN isolated from BALF also killed bacteria but only at acidic pH; the bactericidal activity of BALF at acidic pH was completely blocked by SP-BN Ab. Transgenic mice overexpressing SP-BN and mature SP-B peptide had significantly decreased bacterial burden and increased survival following intranasal inoculation with bacteria. These findings support the hypothesis that SP-BN contributes to innate host defense of the lung by supplementing the nonoxidant antimicrobial defenses of alveolar macrophages.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20007532
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9995
      1. Author :
        Sjollema, Jelmer; Sharma, Prashant K; Dijkstra, Rene J B; van Dam, Gooitzen M; van der Mei, Henny C; Engelsman, Anton F; Busscher, Henk J
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        31
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Infective Agents; Bacteria; Bacterial Infections; Biocompatible Materials; Biofilms; Bioware; Coated Materials, Biocompatible; Fluorescent Dyes; Humans; Image Enhancement; Light; Luminescent Measurements; Luminescent Proteins; Microscopy, Fluorescence; Prosthesis-Related Infections; Sensitivity and Specificity; Xen29
      12. Abstract :
        This review presents the current state of Bioluminescence and Fluorescent Imaging technologies (BLI and FLI) as applied to Biomaterial-Associated Infections (BAI). BLI offers the opportunity to observe the in vivo course of BAI in small animals without the need to sacrifice animals at different time points after the onset of infection. BLI is highly dependent on the bacterial cell metabolism which makes BLI a strong reporter of viable bacterial presence. Fluorescent sources are generally more stable than bioluminescent ones and specifically targeted, which renders the combination of BLI and FLI a promising tool for imaging BAI. The sensitivity and spatial resolution of both imaging tools are, however, dependent on the imaging system used and the tissue characteristics, which makes the interpretation of images, in terms of the location and shape of the illuminating source, difficult. Tomographic reconstruction of the luminescent source is possible in the most modern instruments, enabling exact localization of a colonized implant material, spreading of infecting organisms in surrounding tissue and immunological tissue reactions. BLI studies on BAI have successfully distinguished between different biomaterials with respect to the development and clearance of BAI in vivo, simultaneously reducing animal use and experimental variation. It is anticipated that bio-optical imaging will become an indispensable technology for the in vivo evaluation of antimicrobial coatings.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19969345
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9038
      1. Author :
        Sjollema, J.; Sharma, P. K.; Dijkstra, R. J.; van Dam, G. M.; van der Mei, H. C.; Engelsman, A. F.; Busscher, H. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        31
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen14, Xen 14, E. coli Xen14, IVIS, Animals; Anti-Infective Agents/*pharmacology/therapeutic use; Bacteria/*drug effects/pathogenicity; Bacterial Infections/drug therapy/*etiology; Biocompatible Materials/*adverse effects/chemistry; Biofilms; Coated Materials, Biocompatible/chemistry; Fluorescent Dyes/chemistry/metabolism; Humans; Image Enhancement/methods; Light; Luminescent Measurements/instrumentation/*methods; Luminescent Proteins/metabolism; Microscopy, Fluorescence/instrumentation/*methods; Prosthesis-Related Infections/drug therapy/microbiology; Sensitivity and Specificity
      12. Abstract :
        This review presents the current state of Bioluminescence and Fluorescent Imaging technologies (BLI and FLI) as applied to Biomaterial-Associated Infections (BAI). BLI offers the opportunity to observe the in vivo course of BAI in small animals without the need to sacrifice animals at different time points after the onset of infection. BLI is highly dependent on the bacterial cell metabolism which makes BLI a strong reporter of viable bacterial presence. Fluorescent sources are generally more stable than bioluminescent ones and specifically targeted, which renders the combination of BLI and FLI a promising tool for imaging BAI. The sensitivity and spatial resolution of both imaging tools are, however, dependent on the imaging system used and the tissue characteristics, which makes the interpretation of images, in terms of the location and shape of the illuminating source, difficult. Tomographic reconstruction of the luminescent source is possible in the most modern instruments, enabling exact localization of a colonized implant material, spreading of infecting organisms in surrounding tissue and immunological tissue reactions. BLI studies on BAI have successfully distinguished between different biomaterials with respect to the development and clearance of BAI in vivo, simultaneously reducing animal use and experimental variation. It is anticipated that bio-optical imaging will become an indispensable technology for the in vivo evaluation of antimicrobial coatings.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19969345
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10397
      1. Author :
        Palma, Joann P; Wang, Yi-Chun; Rodriguez, Luis E; Montgomery, Debra; Ellis, Paul A; Bukofzer, Gail; Niquette, Amanda; Liu, Xuesong; Shi, Yan; Lasko, Loren; Zhu, Gui-Dong; Penning, Thomas D; Giranda, Vincent L; Rosenberg, Saul H; Frost, David J; Donawho, Cherrie K
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Clinical cancer research: an official journal of the American Association for Cancer Research
      6. Products :
      7. Volume :
        15
      8. Issue :
        23
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Bioware; Dacarbazine; DNA Damage; DNA Modification Methylases; DNA Repair; DNA Repair Enzymes; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; MDA-MB-231-D3H2LN cells; Mice; Mice, SCID; Neoplasm Metastasis; Neoplasm Transplantation; Tumor Suppressor Proteins
      12. Abstract :
        PURPOSE ABT-888, currently in phase 2 trials, is a potent oral poly(ADP-ribose) polymerase inhibitor that enhances the activity of multiple DNA-damaging agents, including temozolomide (TMZ). We investigated ABT-888+TMZ combination therapy in multiple xenograft models representing various human tumors having different responses to TMZ. EXPERIMENTAL DESIGN ABT-888+TMZ efficacy in xenograft tumors implanted in subcutaneous, orthotopic, and metastatic sites was assessed by tumor burden, expression of poly(ADP-ribose) polymer, and O(6)-methylguanine methyltransferase (MGMT). RESULTS Varying levels of ABT-888+TMZ sensitivity were evident across a broad histologic spectrum of models (55-100% tumor growth inhibition) in B-cell lymphoma, small cell lung carcinoma, non-small cell lung carcinoma, pancreatic, ovarian, breast, and prostate xenografts, including numerous regressions. Combination efficacy in otherwise TMZ nonresponsive tumors suggests that TMZ resistance may be overcome by poly(ADP-ribose) polymerase inhibition. Profound ABT-888+TMZ efficacy was seen in experimental metastases models that acquired resistance to TMZ. Moreover, TMZ resistance was overcome in crossover treatments, indicating that combination therapy may overcome acquired TMZ resistance. Neither tumor MGMT, mismatch repair, nor poly(ADP-ribose) polymer correlated with the degree of sensitivity to ABT-888+TMZ. CONCLUSIONS Robust ABT-888+TMZ efficacy is observed across a spectrum of tumor types, including orthotopic and metastatic implantation. As many TMZ nonresponsive tumors proved sensitive to ABT-888+TMZ, this novel combination may broaden the clinical use of TMZ beyond melanoma and glioma. Although TMZ resistance may be influenced by MGMT, neither MGMT nor other mechanisms of TMZ resistance (mismatch repair) precluded sensitivity to ABT-888+TMZ. Underlying mechanisms of TMZ resistance in these models are not completely understood but likely involve mechanisms independent of MGMT.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19934293
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8954
      1. Author :
        Qamri, Zahida; Preet, Anju; Nasser, Mohd W; Bass, Caroline E; Leone, Gustavo; Barsky, Sanford H; Ganju, Ramesh K
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Molecular cancer therapeutics
      6. Products :
      7. Volume :
        8
      8. Issue :
        11
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Apoptosis; Benzoxazines; Bioware; Breast Neoplasms; Cannabinoids; Cell Cycle; Cell Growth Processes; Cell Line, Tumor; Cell Movement; Cyclooxygenase 2; Dinoprostone; Female; Humans; Immunohistochemistry; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; MDA-MB-231-D3H2LN cells; Mice; Mice, Inbred C3H; Mice, SCID; Mice, Transgenic; Microscopy, Confocal; Morpholines; Naphthalenes; Neoplasm Metastasis; Neovascularization, Pathologic; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; RNA, Small Interfering; Signal Transduction; Transfection; Xenograft Model Antitumor Assays
      12. Abstract :
        Cannabinoids have been reported to possess antitumorogenic activity. Not much is known, however, about the effects and mechanism of action of synthetic nonpsychotic cannabinoids on breast cancer growth and metastasis. We have shown that the cannabinoid receptors CB1 and CB2 are overexpressed in primary human breast tumors compared with normal breast tissue. We have also observed that the breast cancer cell lines MDA-MB231, MDA-MB231-luc, and MDA-MB468 express CB1 and CB2 receptors. Furthermore, we have shown that the CB2 synthetic agonist JWH-133 and the CB1 and CB2 agonist WIN-55,212-2 inhibit cell proliferation and migration under in vitro conditions. These results were confirmed in vivo in various mouse model systems. Mice treated with JWH-133 or WIN-55,212-2 showed a 40% to 50% reduction in tumor growth and a 65% to 80% reduction in lung metastasis. These effects were reversed by CB1 and CB2 antagonists AM 251 and SR144528, respectively, suggesting involvement of CB1 and CB2 receptors. In addition, the CB2 agonist JWH-133 was shown to delay and reduce mammary gland tumors in the polyoma middle T oncoprotein (PyMT) transgenic mouse model system. Upon further elucidation, we observed that JWH-133 and WIN-55,212-2 mediate the breast tumor-suppressive effects via a coordinated regulation of cyclooxygenase-2/prostaglandin E2 signaling pathways and induction of apoptosis. These results indicate that CB1 and CB2 receptors could be used to develop novel therapeutic strategies against breast cancer growth and metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19887554
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8953
      1. Author :
        Engelsman, Anton F; van Dam, Gooitzen M; van der Mei, Henny C; Busscher, Henk J; Ploeg, Rutger J
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Annals of surgery
      6. Products :
      7. Volume :
        251
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Abdominal Wall; Animals; Bioware; Female; Luminescent Measurements; Mice; Mice, Inbred BALB C; Polypropylenes; Polytetrafluoroethylene; pXen-5; Staphylococcal Infections; Staphylococcus aureus; Surgical Mesh; Xen29
      12. Abstract :
        OBJECTIVE To study the influence of morphology of surgical meshes on the course of bacterial infection under the influence of the host immune system in an in vivo chronic bacterial infection model. BACKGROUND The use of prosthetic meshes has increased dramatically the last decades in abdominal wall reconstructive surgery. Whereas infection is becoming a more frequent complication, attention is increasingly drawn to the influence of the surgeon's mesh choice on the course of this complication. METHODS Samples of 6 often applied surgical meshes were contaminated with a bioluminescent strain of Staphylococcus aureus and implanted subcutaneously in an immunocompetent BALB/c mouse. The intensity and the spreading of bioluminescence (ie, p/s/cm/sr) were analyzed non-invasively in vivo during a 10-day follow-up period. RESULTS Over the course of infection, multifilament polypropylene and hydrophobic materials showed a significantly higher persistence of bacteria as well as spreading of infection compared to all other meshes. In contrast, infection resolved in almost all animals with a low-weight polyester mesh. CONCLUSION The results of this study are in accordance with circumstantial evidence from limited clinical reports on infection involving surgical meshes and suggest that multifilament and hydrophobic meshes significantly increase bacterial persistence or spreading in the infected area in contrast to monofilament polypropylene and lightweight meshes. Therefore, the surgeon should consider this outcome when choosing a mesh graft for limiting infection in abdominal wall repair.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19864938
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9017
      1. Author :
        Okuda, Tomoyuki; Kawaguchi, Yasuhisa; Okamoto, Hirokazu
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Current topics in medicinal chemistry
      6. Products :
      7. Volume :
        9
      8. Issue :
        12
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; Gene Silencing; PC-3M-luc; Peptides; Proteins; RNA Interference; Transfection
      12. Abstract :
        RNA interference (RNAi) is an attractive phenomenon for practical use that specifically inhibits gene expression and is carried out by small double-stranded RNAs (dsRNAs) including small interfering RNA (siRNA) or short hairpin RNA (shRNA). In addition, RNAi is of great interest for clinical use to cure refractory diseases related to the expression of a specific gene. To achieve gene silencing in the body, a sufficient amount of dsRNA must be delivered and internalized into target cells. However, dsRNAs have a large molecular weight and net negative charge, which limits their membrane-permeating ability. Moreover, dsRNAs are rapidly degraded by endonucleses in the body. Therefore, for the efficient delivery of dsRNAs, many approaches based on drug delivery systems have been carried out. In this review, we focus on recent reports about the application of functional peptides and proteins designed for the efficient delivery of dsRNAs.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19860710
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8962
      1. Author :
        Thobe, M N; Gurusamy, D; Pathrose, P; Waltz, S E
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Oncogene
      6. Products :
      7. Volume :
        29
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antigens, CD31; Bioware; Blotting, Western; Cell Line; Cell Line, Tumor; Cell Movement; Chemokine CXCL1; Chemokine CXCL5; Chemokines; Endothelial Cells; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Interleukin-8; Male; Mice; Mice, Nude; Neoplasms, Experimental; Neovascularization, Pathologic; NF-kappa B; PC-3M-luc2; Prostatic Neoplasms; Receptor Protein-Tyrosine Kinases; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Transplantation, Heterologous
      12. Abstract :
        Overexpression of the Ron receptor tyrosine kinase has recently been shown in a wide variety of human cancers. However, no studies have examined Ron receptor expression or function during prostate tumorigenesis. In this study we report that Ron is highly expressed in human prostate adenocarcinoma and metastatic lymph nodes when compared with normal prostate or benign prostate hyperplasia. Furthermore, we show that Ron is overexpressed in PC-3 and DU145 prostate cancer cell lines, and that the levels of angiogenic chemokines produced by prostate cancer cells positively correlate with Ron expression. The knockdown of Ron in PC-3 or DU145 cells results in a significant decrease in angiogenic chemokine production and is associated with a decreased activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Moreover, exogenous overexpression of Ron in LNCaP cells is sufficient to induce a significant increase in angiogenic chemokines that can be abrogated by inhibition of NF-kappaB signaling. Given that the function of angiogenic chemokines is important in the development of new blood vessels, we also examined the ability of Ron to modulate endothelial cell migration. Our data show that knockdown of Ron in prostate cancer cells results in significantly less endothelial cell chemotaxis when compared with Ron-expressing cells in vitro as well as in reduced tumor growth and decreased microvessel density after orthotopic transplantation into the prostate in vivo. In total, our data suggest that the Ron receptor is important in modulating prostate tumor growth by modulating angiogenic chemokine production and subsequent endothelial cell recruitment.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19838218
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8943
      1. Author :
        Curbelo, J; Moulton, K; Willard, S
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Theriogenology
      6. Products :
      7. Volume :
        73
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Cattle; Escherichia coli; Female; Genitalia, Female; Optical Phenomena; Photons; Xen14
      12. Abstract :
        The objectives of this study were to (1) characterize the photonic properties of Escherichia coli-Xen14 and (2) conduct photonic imaging of E. coli-Xen14 within bovine reproductive tract segments (RTS) ex vivo (Bos indicus). E. coli-Xen14 was grown for 24h in Luria Bertani medium (LB), with or without kanamycin (KAN). Every 24h, for an 8-d interval, inoculums were imaged and photonic emissions (PE) collected. Inoculums were subcultured and plated daily to determine the colony forming units (CFU) and ratio of photon emitters to nonemitters. In the second objective, abattoir-derived bovine reproductive tracts (n=9) were separated into posterior and anterior vagina, cervix, uterine body, and uterine horns. Two concentrations (3.2x10(8) and 3.2x10(6) CFU/200microL for relative [High] and [Low], respectively) of E. coli-Xen14 were placed in translucent tubes for detection of PE through RTS. The CFU did not differ (P=0.31) over time with or without KAN presence; they remained stable with 99.93% and 99.98% photon emitters, respectively. However, PE were lower (P<0.0001) in cultures containing KAN than in those containing no KAN (629.8+/-117.7 vs. 3012.0+/-423.5 relative lights units per second [RLU/sec], respectively). On average, the percentage of PE between RTS, for both concentrations, was higher (P<0.05) in the uterine body. In summary, E. coli-Xen14 remained stable with respect to the proportions of photon emitters with or without KAN (used to selectively culture E. coli-Xen14). However, KAN presence suppressed photonic activity. The ability to detect PE through various segments of the reproductive tract demonstrated the feasibility of monitoring the presence of E. coli-Xen14 in the bovine reproductive tract ex vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19819541
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        10004
      1. Author :
        Curbelo, J.; Moulton, K.; Willard, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Theriogenology
      6. Products :
      7. Volume :
        73
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen14, Xen 14, E. coli Xen14, IVIS, Animals; Cattle; Escherichia coli/*cytology/isolation & purification/physiology; Female; Genitalia, Female/*microbiology; Optical Phenomena; *Photons
      12. Abstract :
        The objectives of this study were to (1) characterize the photonic properties of Escherichia coli-Xen14 and (2) conduct photonic imaging of E. coli-Xen14 within bovine reproductive tract segments (RTS) ex vivo (Bos indicus). E. coli-Xen14 was grown for 24h in Luria Bertani medium (LB), with or without kanamycin (KAN). Every 24h, for an 8-d interval, inoculums were imaged and photonic emissions (PE) collected. Inoculums were subcultured and plated daily to determine the colony forming units (CFU) and ratio of photon emitters to nonemitters. In the second objective, abattoir-derived bovine reproductive tracts (n=9) were separated into posterior and anterior vagina, cervix, uterine body, and uterine horns. Two concentrations (3.2x10(8) and 3.2x10(6) CFU/200microL for relative [High] and [Low], respectively) of E. coli-Xen14 were placed in translucent tubes for detection of PE through RTS. The CFU did not differ (P=0.31) over time with or without KAN presence; they remained stable with 99.93% and 99.98% photon emitters, respectively. However, PE were lower (P<0.0001) in cultures containing KAN than in those containing no KAN (629.8+/-117.7 vs. 3012.0+/-423.5 relative lights units per second [RLU/sec], respectively). On average, the percentage of PE between RTS, for both concentrations, was higher (P<0.05) in the uterine body. In summary, E. coli-Xen14 remained stable with respect to the proportions of photon emitters with or without KAN (used to selectively culture E. coli-Xen14). However, KAN presence suppressed photonic activity. The ability to detect PE through various segments of the reproductive tract demonstrated the feasibility of monitoring the presence of E. coli-Xen14 in the bovine reproductive tract ex vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19819541
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10391