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      1. Author :
        Snoeks, T. J.; Khmelinskii, A.; Lelieveldt, B. P.; Kaijzel, E. L.; Lowik, C. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Bone
      6. Products :
      7. Volume :
        48
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Bone Neoplasms/radionuclide imaging/*secondary; Diagnostic Imaging/*methods; Forecasting; Optics and Photonics/*trends; Positron-Emission Tomography/methods; Tomography, Emission-Computed, Single-Photon/methods; X-Ray Microtomography/methods; X-Rays
      12. Abstract :
        Optical Imaging has evolved into one of the standard molecular imaging modalities used in pre-clinical cancer research. Bone research however, strongly depends on other imaging modalities such as SPECT, PET, x-ray and muCT. Each imaging modality has its own specific strengths and weaknesses concerning spatial resolution, sensitivity and the possibility to quantify the signal. An increasing number of bone specific optical imaging models and probes have been developed over the past years. This review gives an overview of optical imaging modalities, models and probes that can be used to study skeletal complications of cancer in small laboratory animals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20688203
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10476
      1. Author :
        Mieog, J. S.; Hutteman, M.; van der Vorst, J. R.; Kuppen, P. J.; Que, I.; Dijkstra, J.; Kaijzel, E. L.; Prins, F.; Lowik, C. W.; Smit, V. T.; van de Velde, C. J.; Vahrmeijer, A. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Breast Cancer Res Treat
      6. Products :
      7. Volume :
        128
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        ProSense, IVIS, Animals; Breast Neoplasms/pathology/*surgery; Cell Line, Tumor; Disease Models, Animal; Female; *Microscopy, Fluorescence; Rats; *Surgery, Computer-Assisted; Transplantation, Isogeneic; Xenograft Model Antitumor Assays
      12. Abstract :
        Tumor involvement of resection margins is found in a large proportion of patients who undergo breast-conserving surgery. Near-infrared (NIR) fluorescence imaging is an experimental technique to visualize cancer cells during surgery. To determine the accuracy of real-time NIR fluorescence imaging in obtaining tumor-free resection margins, a protease-activatable NIR fluorescence probe and an intraoperative camera system were used in the EMR86 orthotopic syngeneic breast cancer rat model. Influence of concentration, timing and number of tumor cells were tested in the MCR86 rat breast cancer cell line. These variables were significantly associated with NIR fluorescence probe activation. Dosing and tumor size were also significantly associated with fluorescence intensity in the EMR86 rat model, whereas time of imaging was not. Real-time NIR fluorescence guidance of tumor resection resulted in a complete resection of 17 out of 17 tumors with minimal excision of normal healthy tissue (mean minimum and a mean maximum tumor-free margin of 0.2 +/- 0.2 mm and 1.3 +/- 0.6 mm, respectively). Moreover, the technique enabled identification of remnant tumor tissue in the surgical cavity. Histological analysis revealed that the NIR fluorescence signal was highest at the invasive tumor border and in the stromal compartment of the tumor. In conclusion, NIR fluorescence detection of breast tumor margins was successful in a rat model. This study suggests that clinical introduction of intraoperative NIR fluorescence imaging has the potential to increase the number of complete tumor resections in breast cancer patients undergoing breast-conserving surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20821347
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10429
      1. Author :
        Proulx, S. T.; Luciani, P.; Derzsi, S.; Rinderknecht, M.; Mumprecht, V.; Leroux, J. C.; Detmar, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        70
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals, B16-F10-luc2, B16F10-luc2; Coloring Agents/administration & dosage/*diagnostic use; Indocyanine Green/administration & dosage/*diagnostic use; Injections, Intradermal; Liposomes/administration & dosage; Lymphatic Metastasis; Lymphatic Vessels/metabolism/*pathology; Melanoma, Experimental/blood supply/metabolism/*pathology; Mice; Mice, Inbred C57BL; Vascular Endothelial Growth Factor C/biosynthesis
      12. Abstract :
        Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system, but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift toward longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase-expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near-IR imaging of intradermally injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C-expressing tumors without metastases, whereas a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method will likely facilitate quantitative studies of lymphatic function in preclinical investigations and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20823159
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10350
      1. Author :
        Bernthal, N. M.; Stavrakis, A. I.; Billi, F.; Cho, J. S.; Kremen, T. J.; Simon, S. I.; Cheung, A. L.; Finerman, G. A.; Lieberman, J. R.; Adams, J. S.; Miller, L. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29, Animals; Anti-Bacterial Agents/*therapeutic use; Arthroplasty/*adverse effects; Disease Models, Animal; Humans; Joint Diseases/drug therapy/*microbiology/surgery; Joints/microbiology/surgery; Male; Mice; Mice, Inbred C57BL; Minocycline/therapeutic use; Postoperative Complications/drug therapy/microbiology/*prevention &; control; Prostheses and Implants; Rifampin/therapeutic use; Staphylococcal Infections/drug therapy/microbiology/*prevention &; control/surgery; Staphylococcus aureus/drug effects/genetics/*physiology
      12. Abstract :
        BACKGROUND: Post-arthroplasty infections represent a devastating complication of total joint replacement surgery, resulting in multiple reoperations, prolonged antibiotic use, extended disability and worse clinical outcomes. As the number of arthroplasties in the U.S. will exceed 3.8 million surgeries per year by 2030, the number of post-arthroplasty infections is projected to increase to over 266,000 infections annually. The treatment of these infections will exhaust healthcare resources and dramatically increase medical costs. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate novel preventative therapeutic strategies against post-arthroplasty infections, a mouse model was developed in which a bioluminescent Staphylococcus aureus strain was inoculated into a knee joint containing an orthopaedic implant and advanced in vivo imaging was used to measure the bacterial burden in real-time. Mice inoculated with 5x10(3) and 5x10(4) CFUs developed increased bacterial counts with marked swelling of the affected leg, consistent with an acute joint infection. In contrast, mice inoculated with 5x10(2) CFUs developed a low-grade infection, resembling a more chronic infection. Ex vivo bacterial counts highly correlated with in vivo bioluminescence signals and EGFP-neutrophil fluorescence of LysEGFP mice was used to measure the infection-induced inflammation. Furthermore, biofilm formation on the implants was visualized at 7 and 14 postoperative days by variable-pressure scanning electron microscopy (VP-SEM). Using this model, a minocycline/rifampin-impregnated bioresorbable polymer implant coating was effective in reducing the infection, decreasing inflammation and preventing biofilm formation. CONCLUSIONS/SIGNIFICANCE: Taken together, this mouse model may represent an alternative pre-clinical screening tool to evaluate novel in vivo therapeutic strategies before studies in larger animals and in human subjects. Furthermore, the antibiotic-polymer implant coating evaluated in this study was clinically effective, suggesting the potential for this strategy as a therapeutic intervention to combat post-arthroplasty infections.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20830204
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10447
      1. Author :
        Adachi, T.; Kawakami, E.; Ishimaru, N.; Ochiya, T.; Hayashi, Y.; Ohuchi, H.; Tanihara, M.; Tanaka, E.; Noji, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Dev Growth Differ
      6. Products :
      7. Volume :
        52
      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, Animals; Base Sequence; Cell Line, Tumor; Collagen/*chemistry; DNA Primers; *Gene Silencing; Mice; RNA, Small Interfering/*administration & dosage/*chemistry; Reverse Transcriptase Polymerase Chain Reaction
      12. Abstract :
        Silencing gene expression by small interfering RNAs (siRNAs) has become a powerful tool for the genetic analysis of many animals. However, the rapid degradation of siRNA and the limited duration of its action in vivo have called for an efficient delivery technology. Here, we describe that siRNA complexed with a synthetic collagen poly(Pro-Hyp-Gly) (SYCOL) is resistant to nucleases and is efficiently transferred into cells in vitro and in vivo, thereby allowing long-term gene silencing in vivo. We found that the SYCOL-mediated local application of siRNA targeting myostatin, coding a negative regulator of skeletal muscle growth, in mouse skeletal muscles, caused a marked increase in the muscle mass within a few weeks after application. Furthermore, in vivo administration of an anti-luciferase siRNA/SYCOL complex partially reduced luciferase expression in xenografted tumors in vivo. These results indicate a SYCOL-based non-viral delivery method could be a reliable simple approach to knockdown gene expression by RNAi in vivo as well as in vitro.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20874713
      14. Call Number :
        PKI @ kd.modi @ 11
      15. Serial :
        10352
      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 :
        Lorenz, U.; Schafer, T.; Ohlsen, K.; Tiurbe, G. C.; Buhler, C.; Germer, C. T.; Kellersmann, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Vasc Endovasc Surg
      6. Products :
      7. Volume :
        41
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29, Acetates; Animals; *Biofilms; Bioprosthesis; Blood Vessel Prosthesis/*microbiology; Cattle; Colony Count, Microbial; Luminescent Measurements/*methods; Mice; Microbial Viability; Pericardium; *Photons; Polyesters; Polytetrafluoroethylene; Prospective Studies; Prosthesis-Related Infections/*diagnosis; Random Allocation; Silver Compounds; Staphylococcus aureus/isolation & purification/*physiology
      12. Abstract :
        OBJECTIVES: Biophotonic imaging was compared to standard enumeration method both for counting Staphylococcus aureus in biofilm and bacterial susceptibility tests of different graft materials. DESIGN: Prospective, randomized, controlled animal study. MATERIAL AND METHODS: Five types of vascular grafts were placed subcutaneously in 35 mice and challenged with bioluminescent S. aureus. The mice were divided into equal groups as follows: group A (polyester), group B (polytetrafluoroethylene), group C and D (two types of silver acetate-coated polyester) and group E (bovine pericardium). Controls were given only the bacteria. The bioluminescence signal of S. aureus, able to predict number of viable bacteria in biofilm without any manipulation, was measured at different time points. Five days postinfection, regular cultures of adherent bacteria on grafts were obtained. Comparative analyses between bioluminescence activity and culture enumeration were performed. RESULTS: The number of viable bacteria on silver-coated prostheses was the slightest, indicating superior bacterial resistance. The density of bacteria on polytetrafluoroethylene and polyester was comparable, with a non-significant advantage for polytetrafluoroethylene. Moreover, bioluminescence detected the number of viable S. aureus in biofilm more exactly compared to enumeration of bacteria. CONCLUSION: Bioluminescence imaging can be considered a useful tool to characterize susceptibility of any graft material to bacterial biofilm prior to implantation.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20943422
      14. Call Number :
        PKI @ kd.modi @ 12
      15. Serial :
        10453
      1. Author :
        Leszczynska, K.; Namiot, A.; Cruz, K.; Byfield, F. J.; Won, E.; Mendez, G.; Sokolowski, W.; Savage, P. B.; Bucki, R.; Janmey, P. A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Appl Microbiol
      6. Products :
      7. Volume :
        110
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen 5, Pseudomonas aeruginosa Xen 5, Anti-Bacterial Agents/administration & dosage/*pharmacology/therapeutic; use; Antimicrobial Cationic Peptides/chemistry; Biofilms/drug effects; Cholic Acid/chemistry; Cystic Fibrosis/microbiology; Hemolysis/drug effects; Humans; *Poloxamer; Pseudomonas Infections/drug therapy; Pseudomonas aeruginosa/drug effects/growth & development; Skin Diseases, Bacterial/drug therapy; Staphylococcus aureus/drug effects; Steroids/administration & dosage/*pharmacology/therapeutic use; *Surface-Active Agents
      12. Abstract :
        AIMS: Ceragenin CSA-13 is a synthetic mimic of cationic antibacterial peptides, with facial amphiphilic morphology reproduced using a cholic acid scaffold. Previous data have shown that this molecule displays broad-spectrum antibacterial activity, which decreases in the presence of blood plasma. However, at higher concentrations, CSA-13 can cause lysis of erythrocytes. This study was designed to assess in vitro antibacterial and haemolytic activity of CSA-13 in the presence of pluronic F-127. METHODS AND RESULTS: CSA-13 bactericidal activity against clinical strains of bacteria associated with topical infections and in an experimental setting relevant to their pathophysiological environment, such as various epithelial tissue fluids and the airway sputum of patients suffering from cystic fibrosis (CF), was evaluated using minimum inhibitory and minimum bactericidal concentration (MIC/MBC) measurements and bacterial killing assays. We found that in the presence of pluronic F-127, CSA-13 antibacterial activity was only slightly decreased, but CSA-13 haemolytic activity was significantly inhibited. CSA-13 exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, including methicillin-resistant strains, Pseudomonas aeruginosa present in CF sputa, and biofilms formed by different Gram (+) and Gram (-) bacteria. CSA-13 bactericidal action is partially compromised in the presence of plasma, but is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage fluid. The synergistic action of CSA-13, determined by the use of a standard checkerboard assay, reveals an increase in CSA-13 antibacterial activity in the presence of host defence molecules such as the cathelicidin LL-37 peptide, lysozyme, lactoferrin and secretory phospholipase A (sPLA). CONCLUSION: These results suggest that CSA-13 may be useful to prevent and treat topical infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Combined application of CSA-13 with pluronic F-127 may be beneficial by reducing CSA-13 toxicity.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20961363
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10389
      1. Author :
        Mumprecht, V.; Honer, M.; Vigl, B.; Proulx, S. T.; Trachsel, E.; Kaspar, M.; Banziger-Tobler, N. E.; Schibli, R.; Neri, D.; Detmar, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        70
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals, B16-F10-luc2, B16F10-luc2; Antibodies, Monoclonal/diagnostic use/immunology; *Diagnostic Imaging; Female; Fluorodeoxyglucose F18/diagnostic use; Glycoproteins/*immunology; Humans; Inflammation/*complications/immunology/pathology; Iodine Radioisotopes/diagnostic use/pharmacokinetics; Luminescent Measurements; Lymph Nodes/immunology/pathology/*radionuclide imaging; *Lymphangiogenesis; Lymphatic Metastasis; Melanoma, Experimental/*complications/immunology/pathology; Mice; Mice, Inbred C57BL; Mice, Transgenic; *Positron-Emission Tomography; Prognosis; Radiopharmaceuticals/diagnostic use; Skin/metabolism; Tissue Distribution; Vascular Endothelial Growth Factor C/metabolism; Vascular Endothelial Growth Factor Receptor-3/immunology
      12. Abstract :
        Metastasis to regional lymph nodes (LN) is a prognostic indicator for cancer progression. There is a great demand for sensitive and noninvasive methods to detect metastasis to LNs. Whereas conventional in vivo imaging approaches have focused on the detection of cancer cells, lymphangiogenesis within tumor-draining LNs might be the earliest sign of metastasis. In mouse models of LN lymphangiogenesis, we found that systemically injected antibodies to lymphatic epitopes accumulated in the lymphatic vasculature in tissues and LNs. Using a (124)I-labeled antibody against the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), we imaged, for the first time, inflammation- and tumor-draining LNs with expanded lymphatic networks in vivo by positron emission tomography (PET). Anti-LYVE-1 immuno-PET enabled visualization of lymphatic vessel expansion in LNs bearing metastases that were not detected by [(18)F]fluorodeoxyglucose-PET, which is clinically applied to detect cancer metastases. Immuno-PET with lymphatic-specific antibodies may open up new avenues for the early detection of metastasis, and the images obtained might be used as biomarkers for the progression of diseases associated with lymphangiogenesis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20978206
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10349
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