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      1. Author :
        Daugimont, L.; Vandermeulen, G.; Defresne, F.; Bouzin, C.; Mir, L. M.; Bouquet, C.; Feron, O.; Preat, V.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Pharm Biopharm
      6. Products :
      7. Volume :
        78
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, IVIS
      12. Abstract :
        BACKGROUND: Despite the discovery of novel inhibitors of tumor angiogenesis, protein-based antiangiogenic cancer therapy suffers some limitations that antiangiogenic gene therapy could overcome. We investigated whether intra-tumoral electrotransfer of three angiogenic plasmids could inhibit tumor growth and metastasis. METHODS: Plasmids encoding recombinant disintegrin domain of ADAM-15 (RDD), thrombospondin 1 (TSP-1), and the soluble isoform of the VEGF receptor 1 (sFlt-1) were injected into B16F10 melanoma-bearing C57BL/6 mice followed by electroporation. Tumor volume was measured daily using a digital caliper. Metastasis was monitored by in vivo bioluminescence after surgical removal of the primary luciferase-encoding B16F10 tumor 5 days after intra-tumoral electrotransfer. Markers of vascularization and cell proliferation were quantified by immunohistochemistry. RESULTS: Intra-tumoral electrotransfer of the antiangiogenic plasmids induced a significant inhibition of tumor growth, doubling of mean survival time and long-term survivors ( approximately 40% vs 0% in control). When the tumor was removed by surgery after intra-tumoral plasmid electrotransfer, a significant decrease in tumor metastasis was observed leading to long-term tumor-free survival especially after treatment with pRDD plasmid (84% vs 0% in control). Unlike pTSP-1 and psFlt-1, pRDD significantly decreased cell proliferation in B16F10 primary tumors which express alphavbeta3 and alpha5beta1 integrins. No effect of antiangiogenic plasmid electrotransfer on normal skin blood flow was detected. CONCLUSION: The intra-tumoral electrotransfer of the three antiangiogenic plasmids is a promising method for the treatment of melanoma. The plasmid encoding RDD seems to be particularly effective due to its direct antitumoral activity combined with angiogenesis suppression, and its marked inhibition of metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21316447
      14. Call Number :
        PKI @ kd.modi @ 12
      15. Serial :
        10353
      1. Author :
        Lee, S. K.; Han, M. S.; Asokan, S.; Tung, C. H.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Small
      6. Products :
      7. Volume :
        7
      8. Issue :
        N/A
      9. Page Numbers :
        364-70
      10. Research Area :
        N/A
      11. Keywords :
        LnCaP-luc2, Prostate Cancer, IVIS, *Gene Silencing; *Gold; Metal Nanoparticles/*chemistry/ultrastructure; Microscopy, Electron, Transmission; Polylysine/chemistry; RNA, Small Interfering/*genetics
      12. Abstract :
        Small interfering RNA (siRNA) has been widely proposed to treat various diseases by silencing genes, but its delivery remains a challenge. A well controlled assembly approach is applied to prepare a protease-assisted nanodelivery system. Protease-degradable poly-L-lysine (PLL) and siRNA are fabricated onto gold nanoparticles (AuNPs), by alternating the charged polyelectrolytes. In this study, up to 4 layers of PLL and 3 layers of siRNA (sR3P) are coated. Due to the slow degradation of PLL, the incorporated siRNA is released gradually and shows extended gene-silencing effects. Importantly, the inhibition effect in cells is found to correlate with the number of siRNA layers.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21294265
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10547
      1. Author :
        Keereweer, S.; Sterenborg, H. J.; Kerrebijn, J. D.; Van Driel, P. B.; de Jong, R. J.; Lowik, C. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Head Neck
      6. Products :
      7. Volume :
        34
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense
      12. Abstract :
        A key aspect for the postoperative prognosis of patients with head and neck cancer is complete tumor resection. In current practice, the intraoperative assessment of the tumor-free margin is dependent on visual appearance and palpation of the tumor. Optical imaging has the potential of traversing the gap between radiology and surgery by providing real-time visualization of the tumor, thereby allowing for image-guided surgery. The use of the near-infrared light spectrum offers 2 essential advantages: increased tissue penetration of light and an increased signal-to-background ratio of contrast agents. In this review, the current practice and limitations of image-guided surgery by optical imaging using intrinsic fluorescence or contrast agents are described. Furthermore, we provide an overview of the various molecular contrast agents targeting specific hallmarks of cancer that have been used in other fields of oncologic surgery, and we describe perspectives on its future use in head and neck cancer surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21284051
      14. Call Number :
        PKI @ kd.modi @ 31
      15. Serial :
        10369
      1. Author :
        Takaba, J.; Mishima, Y.; Hatake, K.; Kasahara, T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Mediators of Inflammation
      6. Products :
      7. Volume :
        2010
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        bone marrow cells; Cancer; cell labeling; in vitro; in vivo imaging; Olympus IV-100; tail vein injection; VivoTag 750
      12. Abstract :
        Mucosal damage is a common side effect of many cancer treatments, especially radiotherapy and intensive chemotherapy, which often induce bone marrow (BM) suppression. We observed that acetic acid- (AA-) induced mucosal damage in the colon of mice was worsened by simultaneous treatment with irradiation or 5-FU. However, irradiation 14 days prior to the AA treatment augmented the recovery from mucosal damage, suggesting that the recovery from BM suppression had an advantageous effect on the mucosal repair. In addition, BM transplantation also augmented the recovery from AA-induced mucosal damage. We further confirmed that transplanted BM-derived cells, particularly F4/80+Gr1+ “inflammatory” monocytes (Subset 1), accumulated in the damaged mucosal area in the early healing phase, and both of Subset 1 and F4/80+Gr1- “resident” monocytes (Subset 2) accumulated in this area in later phases. Our results suggest that monocytes/macrophages contribute to the mucosal recovery and regeneration following mucosal damage by anticancer drug therapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21274263
      14. Call Number :
        PKI @ user @ 8445
      15. Serial :
        4808
      1. Author :
        Griffin, A. J.; Li, L. X.; Voedisch, S.; Pabst, O.; McSorley, S. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Infect Immun
      6. Products :
      7. Volume :
        79
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen26, Xen 26, Salmonella typhumurium, Animals; Anti-Bacterial Agents/therapeutic use; Cell Separation; Disease Models, Animal; Flow Cytometry; Fluoroquinolones/therapeutic use; Intestine, Small/microbiology; Lymph Nodes/*microbiology; Mesentery/immunology/microbiology; Mice; Mice, Inbred C57BL; Monocytes/immunology/*microbiology; Recurrence; Salmonella Infections, Animal/immunology/*microbiology/pathology; Salmonella typhi/immunology
      12. Abstract :
        Enteric pathogens can cause relapsing infections in a proportion of treated patients, but greater understanding of this phenomenon is hindered by the lack of appropriate animal models. We report here a robust animal model of relapsing primary typhoid that initiates after apparently successful antibiotic treatment of susceptible mice. Four days of enrofloxacin treatment were sufficient to reduce bacterial loads below detectable levels in all major organs, and mice appeared otherwise healthy. However, any interruption of further antibiotic therapy allowed renewed fecal shedding and renewed bacterial growth in systemic tissues to occur, and mice eventually succumbed to relapsing infection. In vivo imaging of luminescent Salmonella identified the mesenteric lymph nodes (MLNs) as a major reservoir of relapsing infection. A magnetic-bead enrichment strategy isolated MLN-resident CD11b(+) Gr-1(-) monocytes associated with low numbers of persistent Salmonella. However, the removal of MLNs increased the severity of typhoid relapse, demonstrating that this organ serves as a protective filter to restrain the dissemination of bacteria during antibiotic therapy. Together, these data describe a robust animal model of typhoid relapse and identify an important intestinal phagocyte subset involved in protection against the systemic spread of enteric infection.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21263018
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10559
      1. Author :
        Ryan, P. L.; Christiansen, D. L.; Hopper, R. M.; Walters, F. K.; Moulton, K.; Curbelo, J.; Greene, J. M.; Willard, S. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Anim Sci
      6. Products :
      7. Volume :
        89
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen14, Xen 14, E. coli Xen14, IVIS, Horse, bioluminescence
      12. Abstract :
        Uterine and placental infections are the leading cause of abortion, stillbirth, and preterm delivery in the mare. Whereas uterine and placental infections in women have been studied extensively, a comprehensive examination of the pathogenic processes leading to this unsatisfactory pregnancy outcome in the mare has yet to be completed. Most information in the literature relating to late-term pregnancy loss in mares is based on retrospective studies of clinical cases submitted for necropsy. Here we report the development and application of a novel approach, whereby transgenically modified bacteria transformed with lux genes of Xenorhabdus luminescens or Photorhabdus luminescens origin and biophotonic imaging are utilized to better understand pathogen-induced preterm birth in late-term pregnant mares. This technology uses highly sensitive bioluminescence imaging camera systems to localize and monitor pathogen progression during tissue invasion by measuring the bioluminescent signatures emitted by the lux-modified pathogens. This method has an important advantage in that it allows for the potential tracking of pathogens in vivo in real time and over time, which was hitherto impossible. Although the application of this technology in domestic animals is in its infancy, investigators were successful in identifying the fetal lungs, sinuses, nares, urinary, and gastrointestinal systems as primary tissues for pathogen invasion after experimental infection of pregnant mares with lux-modified Escherichia coli. It is important that pathogens were not detected in other vital organs, such as the liver, brain, and cardiac system. Such precision in localizing sites of pathogen invasion provides potential application for this novel approach in the development of more targeted therapeutic interventions for pathogen-related diseases in the equine and other domestic species.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21239661
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10395
      1. Author :
        Napp, J.; Mathejczyk, J.E.; Alves, F.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Pediatric Radiology
      6. Products :
      7. Volume :
        41
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense 680; Cancer; glioblastoma xenograft; mice; tumor vascularization
      12. Abstract :
        To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21221568
      14. Call Number :
        PKI @ user @ 8559
      15. Serial :
        4796
      1. Author :
        Hutteman, M.; Mieog, J. S.; van der Vorst, J. R.; Dijkstra, J.; Kuppen, P. J.; van der Laan, A. M.; Tanke, H. J.; Kaijzel, E. L.; Que, I.; van de Velde, C. J.; Lowik, C. W.; Vahrmeijer, A. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Surg Oncol
      6. Products :
      7. Volume :
        37
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Colorectal Neoplasms/*metabolism/*secondary; Disease Models, Animal; Image Processing, Computer-Assisted; Integrin alphaVbeta3/*metabolism; Intraoperative Period; Liver Neoplasms/*pathology; Male; Neoplasm Transplantation; Rats; Spectroscopy, Near-Infrared/*methods; Tumor Cells, Cultured
      12. Abstract :
        AIM: Near-infrared (NIR) fluorescence optical imaging is a promising technique to assess the extent of colorectal metastases during curative-intended surgery. However, NIR fluorescence imaging of liver metastases is highly challenging due to hepatic uptake and clearance of many fluorescent dyes. In the current study, the biodistribution and the ability to demarcate liver and peritoneal metastases were assessed during surgery in a syngeneic rat model of colorectal cancer using an integrin alpha(v)beta(3)-directed NIR fluorescence probe. METHODS: Liver tumors and peritoneal metastases were induced in 7 male WAG/Rij rats by subcapsular inoculation of 0.5 x 10(6) CC531 colorectal cancer rat cells into three distinct liver lobes. Intraoperative and ex vivo fluorescence measurements were performed 24 (N = 3 rats, 7 tumors) and 48 h (N = 4 rats, 9 tumors) after intravenous administration of the integrin alpha(v)beta(3)-directed NIR fluorescence probe. RESULTS: Colorectal metastases had a minimal two-fold higher NIR fluorescence signal than healthy liver tissue and other abdominal organs (p < 0.001). The tumor-to-background ratio was independent of time of imaging (24 h vs. 48 h post-injection; p = 0.31), which facilitates flexible operation planning in future clinical applications. Total fluorescence intensity was significantly correlated with the size of metastases (R(2) = 0.92 for the 24 h group, R(2) = 0.96 for the 48 h group). CONCLUSION: These results demonstrate that colorectal intra-abdominal metastases can be clearly demarcated during surgery using an integrin alpha(v)beta(3) targeting NIR fluorescence probe. Translating these findings to the clinic will have an excellent potential to substantially improve the quality of cancer surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21215590
      14. Call Number :
        PKI @ kd.modi @ 23
      15. Serial :
        10366
      1. Author :
        Cernak, I.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Front Neurol
      6. Products :
      7. Volume :
        1
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, RediJect Inflammation Probe, chemiluminescence, XenoLight
      12. Abstract :
        Due to complex injurious environment where multiple blast effects interact with the body parallel, blast-induced neurotrauma is a unique clinical entity induced by systemic, local, and cerebral responses. Activation of autonomous nervous system; sudden pressure increase in vital organs such as lungs and liver; and activation of neuroendocrine-immune system are among the most important mechanisms that contribute significantly to molecular changes and cascading injury mechanisms in the brain. It has been hypothesized that vagally mediated cerebral effects play a vital role in the early response to blast: this assumption has been supported by experiments where bilateral vagotomy mitigated bradycardia, hypotension, and apnea, and also prevented excessive metabolic alterations in the brain of animals exposed to blast. Clinical experience suggests specific blast-body-nervous system interactions such as (1) direct interaction with the head either through direct passage of the blast wave through the skull or by causing acceleration and/or rotation of the head; and (2) via hydraulic interaction, when the blast overpressure compresses the abdomen and chest, and transfers its kinetic energy to the body's fluid phase, initiating oscillating waves that traverse the body and reach the brain. Accumulating evidence suggests that inflammation plays important role in the pathogenesis of long-term neurological deficits due to blast. These include memory decline, motor function and balance impairments, and behavioral alterations, among others. Experiments using rigid body- or head protection in animals subjected to blast showed that head protection failed to prevent inflammation in the brain or reduce neurological deficits, whereas body protection was successful in alleviating the blast-induced functional and morphological impairments in the brain.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21206523
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10420