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      1. Author :
        Emmett, M. S.; Lanati, S.; Dunn, D. B.; Stone, O. A.; Bates, D. O.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Microcirculation
      6. Products :
      7. Volume :
        18
      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 :
        OBJECTIVE: To determine whether chemotactic-metastasis, the preferential growth of melanomas towards areas of high lymphatic density, is CCL21/CCR7 dependent in vivo. Lymphatic endothelial cells (LECs) produce the chemokine CCL21. Metastatic melanoma cells express CCR7, its receptor, and exhibit chemotactic-metastasis, whereby metastatic cells recognise and grow towards areas of higher lymphatic density. METHODS: We used two in vivo models of directional growth towards depots of LECs of melanoma cells over-expressing CCR7. Injected LEC were tracked by intravital fluorescence microscopy, and melanoma growth by bioluminescence. RESULTS: Over-expression of the chemokine receptor CCR7 enables non-metastatic tumor cells to recognise and grow towards LECs (3.9 fold compared with control), but not blood endothelial cells (0.9 fold), in vitro and in vivo in the absence of increased lymphatic clearance. Chemotactic metastasis was inhibited by a CCL21 neutralising antibody (4-17% of control). Furthermore, CCR7 expression in mouse B16 melanomas resulted in in-transit metastasis (50-100% of mice) that was less often seen with control tumors (0-50%) in vivo. CONCLUSION: These results suggest that recognition of LEC by tumors expressing receptors for lymphatic specific ligands contributes towards the identification and invasion of lymphatics by melanoma cells and provides further evidence for a chemotactic metastasis model of tumor spread.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21166932
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10355
      1. Author :
        Ragas, X.; Sanchez-Garcia, D.; Ruiz-Gonzalez, R.; Dai, T.; Agut, M.; Hamblin, M. R.; Nonell, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        J Med Chem
      6. Products :
      7. Volume :
        53
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen31, Xen 31, MRSA, S. aureus, IVIS, Bioluminescence, Animals; Bacterial Infections/*drug therapy; Burns/drug therapy/microbiology; Candida/drug effects; Cations; Gram-Negative Bacteria/drug effects; Gram-Positive Bacteria/drug effects; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; *Photochemotherapy; Photosensitizing Agents/*chemical synthesis/chemistry/pharmacology; Porphyrins/*chemical synthesis/chemistry/pharmacology; Solubility; Staphylococcal Infections/drug therapy/microbiology; Structure-Activity Relationship
      12. Abstract :
        Structures of typical photosensitizers used in antimicrobial photodynamic therapy are based on porphyrins, phthalocyanines, and phenothiazinium salts, with cationic charges at physiological pH values. However, derivatives of the porphycene macrocycle (a structural isomer of porphyrin) have barely been investigated as antimicrobial agents. Therefore, we report the synthesis of the first tricationic water-soluble porphycene and its basic photochemical properties. We successfully tested it for in vitro photoinactivation of different Gram-positive and Gram-negative bacteria, as well as a fungal species (Candida) in a drug-dose and light-dose dependent manner. We also used the cationic porphycene in vivo to treat an infection model comprising mouse third degree burns infected with a bioluminescent methicillin-resistant Staphylococcus aureus strain. There was a 2.6-log(10) reduction (p < 0.001) of the bacterial bioluminescence for the PDT-treated group after irradiation with 180 J.cm(-2) of red light.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20936792
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10555
      1. Author :
        Ragas, X.; Sanchez-Garcia, D.; Ruiz-Gonzalez, R.; Dai, T.; Agut, M.; Hamblin, M. R.; Nonell, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        J Med Chem
      6. Products :
      7. Volume :
        53
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen31, Xen 31, MRSA, S. aureus, IVIS, Bioluminescence, Animals; Bacterial Infections/*drug therapy; Burns/drug therapy/microbiology; Candida/drug effects; Cations; Gram-Negative Bacteria/drug effects; Gram-Positive Bacteria/drug effects; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; *Photochemotherapy; Photosensitizing Agents/*chemical synthesis/chemistry/pharmacology; Porphyrins/*chemical synthesis/chemistry/pharmacology; Solubility; Staphylococcal Infections/drug therapy/microbiology; Structure-Activity Relationship
      12. Abstract :
        Structures of typical photosensitizers used in antimicrobial photodynamic therapy are based on porphyrins, phthalocyanines, and phenothiazinium salts, with cationic charges at physiological pH values. However, derivatives of the porphycene macrocycle (a structural isomer of porphyrin) have barely been investigated as antimicrobial agents. Therefore, we report the synthesis of the first tricationic water-soluble porphycene and its basic photochemical properties. We successfully tested it for in vitro photoinactivation of different Gram-positive and Gram-negative bacteria, as well as a fungal species (Candida) in a drug-dose and light-dose dependent manner. We also used the cationic porphycene in vivo to treat an infection model comprising mouse third degree burns infected with a bioluminescent methicillin-resistant Staphylococcus aureus strain. There was a 2.6-log(10) reduction (p < 0.001) of the bacterial bioluminescence for the PDT-treated group after irradiation with 180 J.cm(-2) of red light.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20936792
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10556
      1. Author :
        Baoum, A.; Ovcharenko, D.; Berkland, C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Int J Pharm
      6. Products :
      7. Volume :
        427
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        A549-luc-C8, A549-luc, IVIS, Bioware, Calcium/chemistry; Cell Line; Cell-Penetrating Peptides/administration & dosage/*chemistry; Drug Carriers/administration & dosage/adverse effects/*chemistry; *Gene Silencing; Genetic Therapy/*methods; Humans; Luciferases; Nanoparticles/administration & dosage/chemistry; RNA, Small Interfering/*administration & dosage/chemistry; Tissue Distribution
      12. Abstract :
        The development of short-interfering RNA (siRNA) offers new strategies for manipulating specific genes responsible for pathological disorders. Myriad cationic polymer and lipid formulations have been explored, but an effective, non-toxic carrier remains a major barrier to clinical translation. Among the emerging candidates for siRNA carriers are cell penetrating peptides (CPPs), which can traverse the plasma membrane and facilitate the intracellular delivery of siRNA. Previously, a highly efficient and non-cytotoxic means of gene delivery was designed by complexing plasmid DNA with CPPs, then condensing with calcium. Here, the CPP TAT and a longer, 'double' TAT (dTAT) were investigated as potential carriers for siRNA. Various N/P ratios and calcium concentrations were used to optimize siRNA complexes in vitro. Upon addition of calcium, 'loose' siRNA/CPP complexes were condensed into small nanoparticles. Knockdown of luciferase expression in the human epithelial lung cell line A549-luc-C8 was high (up to 93%) with no evidence of cytotoxicity. Selected formulations of the dTAT complexes were dosed intravenously up to 1000 mg/kg with minimal toxicity. Biodistribution studies revealed high levels of gene knockdown in the lung and muscle tissue suggesting these simple vectors may offer a translatable approach to siRNA delivery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21856394
      14. Call Number :
        PKI @ kd.modi @ 9
      15. Serial :
        10519
      1. Author :
        Ogunniyi, A. D.; Paton, J. C.; Kirby, A. C.; McCullers, J. A.; Cook, J.; Hyodo, M.; Hayakawa, Y.; Karaolis, D. K.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Vaccine
      6. Products :
      7. Volume :
        26
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen, Xen10
      12. Abstract :
        Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or pneumococcal surface protein A (PspA) before pneumococcal challenge, were investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of Streptococcus pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in a significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and a significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18640167
      14. Call Number :
        141772
      15. Serial :
        5663
      1. Author :
        Bendaoud, M.; Vinogradov, E.; Balashova, N. V.; Kadouri, D. E.; Kachlany, S. C.; Kaplan, J. B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Bacteriol
      6. Products :
      7. Volume :
        193
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen29, Xen 29, Staphylococcus aureus Xen29, IVISBacterial Physiological Phenomena/drug effects; Bacterial Proteins/genetics/metabolism; Biofilms/*drug effects; *Down-Regulation/drug effects; Fungi/drug effects/physiology; Kingella kingae/chemistry/genetics/*metabolism; Molecular Sequence Data; Polysaccharides, Bacterial/biosynthesis/chemistry/*pharmacology
      12. Abstract :
        Cell-free extracts prepared from Kingella kingae colony biofilms were found to inhibit biofilm formation by Aggregatibacter actinomycetemcomitans, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Candida albicans, and K. kingae. The extracts evidently inhibited biofilm formation by modifying the physicochemical properties of the cell surface, the biofilm matrix, and the substrate. Chemical and biochemical analyses indicated that the biofilm inhibition activity in the K. kingae extract was due to polysaccharide. Structural analyses showed that the extract contained two major polysaccharides. One was a linear polysaccharide with the structure -->6)-alpha-d-GlcNAcp-(1-->5)-beta-d-OclAp-(2-->, which was identical to a capsular polysaccharide produced by Actinobacillus pleuropneumoniae serotype 5. The second was a novel linear polysaccharide, designated PAM galactan, with the structure -->3)-beta-d-Galf-(1-->6)-beta-d-Galf-(1-->. Purified PAM galactan exhibited broad-spectrum biofilm inhibition activity. A cluster of three K. kingae genes encoding UDP-galactopyranose mutase (ugm) and two putative galactofuranosyl transferases was sufficient for the synthesis of PAM galactan in Escherichia coli. PAM galactan is one of a growing number of bacterial polysaccharides that exhibit antibiofilm activity. The biological roles and potential technological applications of these molecules remain unknown.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21602333
      14. Call Number :
        PKI @ kd.modi @ 17
      15. Serial :
        10446
      1. Author :
        Liu, W.; McDaniel, J.; Li, X.; Asai, D.; Quiroz, F. G.; Schaal, J.; Park, J. S.; Zalutsky, M.; Chilkoti, A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        72
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        PC-3M-luc2, PC3M-luc2, IVIS, Prostate Cancer, Bioware
      12. Abstract :
        Brachytherapy is a common clinical technique involving implantation of sealed radioactive “seeds” within a tumor to selectively irradiate the tumor mass while minimizing systemic toxicity. To mitigate the disadvantages associated with complex surgical implantation and subsequent device removal procedures, we have developed an alternative approach using a genetically encoded peptide polymer solution composed of a thermally responsive elastin-like polypeptide (ELP) radiolabeled with (131)I that self-assembles into radionuclide seeds upon intratumoral injection. The formation of these nontoxic and biodegradable polymer seeds led to prolonged intratumoral retention (~85% ID/tumor 7 days postinjection) of the radionuclide, elicited a tumor growth delay in 100% of the tumors in two human xenografts (FaDu and PC-3), and cured more than 67% of tumor-bearing animals after a single administration of labeled ELP. These results suggest that in situ self-assembly of biodegradable and injectable radionuclide-containing polypeptide seeds could be a promising therapeutic alternative to conventional brachytherapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23155121
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10487
      1. Author :
        Hunter, John J.; Neben, Tamlyn Yee; Purchio, Tony; Jenkins, Darlene
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        AACR Meeting Abstracts
      6. Products :
      7. Volume :
        2005
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; SKOV3-luc-D3 cells
      12. Abstract :
        Peritoneal dissemination is a common feature of human ovarian carcinoma. While this can be mimicked in preclinical models by intraperitoneal injection of human ovarian tumor cells into immunocompromised mice, the resulting tumor burden is difficult to monitor and quantify. Intraperitoneal tumor growth is typically evaluated indirectly by measured changes in mouse abdominal girth and body weight or, directly, by macroscopic and histological examination at the endpoint of the study. In order to establish a model system that allows continuous and accurate assessment of ovarian cancer growth and spread over time we transfected SKOV-3 cells with the firefly luciferase gene. The resulting cell line, SKOV3-luc-D3, expresses stable levels of luciferase in vitro and emits a strong luminescent signal when exposed to luciferin. Xenograft tumors established with this cell line can be tracked and quantified non-invasively by bioluminescent imaging using a highly sensitive, cooled CCD camera (IVIS(R) Imaging System, Xenogen Corp). In addition to providing a direct measure of primary tumor burden and growth, the SKOV3-luc-D3 cell line also allows for real-time evaluation of tumor response to various therapeutic agents, as well as enhanced detection of distal metastases.
      13. URL :
        http://www.aacrmeetingabstracts.org/cgi/content/abstract/2005/1/256-b
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9014
      1. Author :
        Kadurugamuwa, J. L.; Francis, K. P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Methods in Molecular Biology
      6. Products :
      7. Volume :
        431
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware, Xen29, Animals, Bacteria/chemistry/ genetics, Bacterial Infections/diagnosis/ microbiology, Biofilms/ growth & development, Diagnostic Imaging/methods, Luminescent Measurements/ methods IVIS, Xenogen, Xen5, Xen44
      12. Abstract :
        Whole body biophotonic imaging (BPI) is a technique that has contributed significantly to the way researchers study bacterial pathogens and develop pre-clinical treatments to combat their ensuing infections in vivo. Not only does this approach allow disease profiles and drug efficacy studies to be conducted non-destructively in live animals over the entire course of the disease, but in many cases, it enables investigators to observe disease profiles that could otherwise easily be missed using conventional methodologies. The principles of this technique are that bacterial pathogens engineered to express bioluminescence (visible light) can be readily monitored from outside of the living animal using specialized low-light imaging equipment, enabling their movement, expansion and treatment to be seen completely non-invasively. Moreover, because the same group of animals can be imaged at each time-point throughout the study, the overall number of animals used is dramatically reduced, saving lives, time, and money. Also, as each animal acts as its own control over time, the issues associated with animal-to-animal variation are circumvented, thus improving the quality of the biostatistical data generated. The ability to monitor infections in vivo in a longitudinal fashion is especially appealing to assess chronic infections such as those involving implanted devices. Typically, bacteria grow as biofilms on these foreign bodies and are reputably difficult to monitor with conventional methods. Because of the non-destructive and non-invasive nature of BPI, the procedure can be performed repeatedly in the same animal, allowing the biofilm to be studied in situ without detachment or disturbance. This ability not only allows unique patterns of disease relapse to be seen following termination of antibiotic therapy but also in vivo resistance development during prolonged treatment, both of which are common occurrences with device-related infections. This chapter describes the bioluminescent engineering of both Gram-positive and Gram-negative bacteria and overviews their use in device-associated infections in several anatomical sites in a variety of animal models.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18287760
      14. Call Number :
        139321
      15. Serial :
        5568
      1. Author :
        Jenkins, Darlene E; Oei, Yoko; Hornig, Yvette S; Yu, Shang-Fan; Dusich, Joan; Purchio, Tony; Contag, Pamela R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2003
      5. Publication :
        Clinical & experimental metastasis
      6. Products :
      7. Volume :
        20
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        A549-luc-C8; Animals; Bioware; Cell Line, Tumor; Colonic Neoplasms; Fluorouracil; HT-29-luc-D6 cells; Humans; Image Interpretation, Computer-Assisted; Longitudinal Studies; Luciferases; Luminescent Measurements; Lung Neoplasms; Lymphatic Metastasis; Male; Mice; Mice, SCID; Mitomycin; Models, Biological; Neoplasm Transplantation; PC-3M-luc; Prostatic Neoplasms
      12. Abstract :
        Bioluminescent imaging (BLI) permits sensitive in vivo detection and quantification of cells specifically engineered to emit visible light. Three stable human tumor cell lines engineered to express luciferase were assessed for their tumorigenicity in subcutaneous, intravenous and spontaneous metastasis models. Bioluminescent PC-3M-luc-C6 human prostate cancer cells were implanted subcutaneously into SCID-beige mice and were monitored for tumor growth and response to 5-FU and mitomycin C treatments. Progressive tumor development and inhibition/regression following drug treatment were observed and quantified in vivo using BLI. Imaging data correlated to standard external caliper measurements of tumor volume, but bioluminescent data permitted earlier detection of tumor growth. In a lung colonization model, bioluminescent A549-luc-C8 human lung cancer cells were injected intravenously and lung metastases were monitored in vivo by whole animal imaging. Anesthetized mice were imaged weekly allowing a temporal assessment of in vivo lung tumor growth. This longitudinal study design permitted an accurate, real-time evaluation of tumor burden in the same animals over time. End-point bioluminescence measured in vivo correlated to total lung weight at necropsy. For a spontaneous metastatic tumor model, bioluminescent HT-29-luc-D6 human colon cancer cells implanted subcutaneously produced metastases to lung and lymph nodes in SCID-beige mice. Both primary tumors and micrometastases were detected by BLI in vivo. Ex vivo imaging of excised lung lobes and lymph nodes confirmed the in vivo signals and indicated a slightly higher frequency of metastasis in some mice. Levels of bioluminescence from in vivo and ex vivo images corresponded to the frequency and size of metastatic lesions in lungs and lymph nodes as subsequently confirmed by histology. In summary, BLI provided rapid, non-invasive monitoring of tumor growth and regression in animals. Its application to traditional oncology animal models offers quantitative and sensitive analysis of tumor growth and metastasis. The ability to temporally assess tumor development and responses to drug therapies in vivo also improves upon current standard animal models that are based on single end point data.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/14713107
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8980
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