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      1. Author :
        Beck, Benjamin H; Kim, Hyung-Gyoon; Kim, Hyunki; Samuel, Sharon; Liu, Zhiyong; Shrestha, Robin; Haines, Hilary; Zinn, Kurt; Lopez, Richard D
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Breast cancer research and treatment
      6. Products :
      7. Volume :
        122
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2; Adenocarcinoma; Animals; Bioware; Breast Neoplasms; Cell Line, Tumor; Chemotaxis, Leukocyte; Cytotoxicity, Immunologic; Female; Humans; Immunotherapy, Adoptive; Indium Radioisotopes; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Knockout; Neoplasm Transplantation; Radiopharmaceuticals; Receptors, Antigen, T-Cell, gamma-delta; Spleen; Tissue Distribution; T-Lymphocyte Subsets; Tomography, Emission-Computed, Single-Photon; Transplantation, Heterologous; Transplantation, Isogeneic
      12. Abstract :
        In contrast to antigen-specific alphabeta-T cells (adaptive immune system), gammadelta-T cells can recognize and lyse malignantly transformed cells almost immediately upon encounter in a manner that does not require the recognition of tumor-specific antigens (innate immune system). Given the well-documented capacity of gammadelta-T cells to innately kill a variety of malignant cells, efforts are now actively underway to exploit the antitumor properties of gammadelta-T cells for clinical purposes. Here, we present for the first time preclinical in vivo mouse models of gammadelta-T cell-based immunotherapy directed against breast cancer. These studies were explicitly designed to approximate clinical situations in which adoptively transferred gammadelta-T cells would be employed therapeutically against breast cancer. Using radioisotope-labeled gammadelta-T cells, we first show that adoptively transferred gammadelta-T cells localize to breast tumors in a mouse model (4T1 mammary adenocarcinoma) of human breast cancer. Moreover, by using an antibody directed against the gammadelta-T cell receptor (TCR), we determined that localization of adoptively transferred gammadelta-T cells to tumor is a TCR-dependant process. Additionally, biodistribution studies revealed that adoptively transferred gammadelta-T cells traffic differently in tumor-bearing mice compared to healthy mice with fewer gammadelta-T cells localizing into the spleens of tumor-bearing mice. Finally, in both syngeneic (4T1) and xenogeneic (2Lmp) models of breast cancer, we demonstrate that adoptively transferred gammadelta-T cells are both effective against breast cancer and are otherwise well-tolerated by treated animals. These findings provide a strong preclinical rationale for using ex vivo expanded adoptively transferred gammadelta-T cells as a form of cell-based immunotherapy for the treatment of breast cancer. Additionally, these studies establish that clinically applicable methods for radiolabeling gammadelta-T cells allows for the tracking of adoptively transferred gammadelta-T cells in tumor-bearing hosts.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19763820
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8939
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Angiogenesis
      6. Products :
      7. Volume :
        13
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        angiogenesis imaging; in vivo imaging; Angiogenesis; Bioluminescence; Fluorescence; Molecular imaging; Optical imaging
      12. Abstract :
        In recent years, molecular imaging gained significant importance in biomedical research. Optical imaging developed into a modality which enables the visualization and quantification of all kinds of cellular processes and cancerous cell growth in small animals. Novel gene reporter mice and cell lines and the development of targeted and cleavable fluorescent “smart” probes form a powerful imaging toolbox. The development of systems collecting tomographic bioluminescence and fluorescence data enabled even more spatial accuracy and more quantitative measurements. Here we describe various bioluminescent and fluorescent gene reporter models and probes that can be used to specifically image and quantify neovascularization or the angiogenic process itself.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911541/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4488
      1. Author :
        Snoeks, T. J.; Lowik, C. W.; Kaijzel, E. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Angiogenesis
      6. Products :
      7. Volume :
        13
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense,, Animals; Diagnostic Imaging/*methods; Fluorescent Dyes/metabolism; Genes, Reporter; Neovascularization, Pathologic/*diagnosis; *Optical Phenomena
      12. Abstract :
        In recent years, molecular imaging gained significant importance in biomedical research. Optical imaging developed into a modality which enables the visualization and quantification of all kinds of cellular processes and cancerous cell growth in small animals. Novel gene reporter mice and cell lines and the development of targeted and cleavable fluorescent “smart” probes form a powerful imaging toolbox. The development of systems collecting tomographic bioluminescence and fluorescence data enabled even more spatial accuracy and more quantitative measurements. Here we describe various bioluminescent and fluorescent gene reporter models and probes that can be used to specifically image and quantify neovascularization or the angiogenic process itself.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20449766
      14. Call Number :
        PKI @ kd.modi @ 10
      15. Serial :
        10379
      1. Author :
        Hu, Z.; Gerseny, H.; Zhang, Z.; Chen, Y. J.; Berg, A.; Stock, S.; Seth, P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Mol Ther
      6. Products :
      7. Volume :
        19
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-luc2, IVIS, Breast Cancer, Bioware
      12. Abstract :
        In recent years, oncolytic adenoviruses have shown some promise as a novel class of antitumor agents. However, their utility in targeting bone metastases is relatively less studied. We have examined whether the systemic therapy of oncolytic adenoviruses expressing the soluble form of transforming growth factor-beta (TGFbeta) receptor II fused with human immunoglobulin G1 can be developed for the treatment of established breast cancer bone metastases. MDA-MB-231-luc2 human breast cancer cells were injected in the left heart ventricle of nude mice to establish bone metastasis. Mice with hind limb tumors were administered (on days 8 and 11) oncolytic adenoviruses-Ad.sTbetaRFc or mhTERTAd.sTbetaRFc. Skeletal tumor growth was monitored weekly by bioluminescence imaging (BLI) and radiography. At the termination time on day 28, hind limb bones were analyzed for tumor burden, synchrotron micro-computed tomography, and osteoclast activation. Intravenous delivery of Ad.sTbetaRFc and mhTERTAd.sTbetaRFc induced significant inhibition of tumor growth, reduction of tumor burden, osteoclast activation, and increased animals' survival. Oncolytic adenoviruses were safer than dl309, a wild-type virus. A slight elevation of liver enzyme activity was observed after Ad.sTbetaRFc administration; this subsided with time. Based on these studies, we believe that Ad.sTbetaRFc and mhTERTAd.sTbetaRFc can be developed as a safe and effective approach for the treatment of established bone metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21712815
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10493
      1. Author :
        Xing, H. R.; Zhang, Q.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Methods Mol Biol
      6. Products :
      7. Volume :
        872
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; Antineoplastic Agents/therapeutic use; Diagnostic Imaging/*methods; Female; Mammary Neoplasms, Animal/metabolism/pathology; Mice; Mice, Nude; Neoplasm Transplantation; Neovascularization, Pathologic/drug therapy/*pathology
      12. Abstract :
        In vivo angiogenesis assays provide more physiologically relevant information about tumor vascularization than in vitro studies because they take the complex interactions among cancer cells, endothelial cells, mural cells, and tumor stroma into consideration. Traditional microscopic assessment of vascular density conducted by immunostaining of tissue sections or by lectin angiogram visualization of tumor vessels is invasive and requires the sacrifice of tumor-bearing animals. Therefore, it prohibits longitudinal time-course observation in a single animal and requires a large number of animals at each time point to derive statistically-meaningful observations. Additionally, heterogenous behavior among different tumors will inevitably introduce individual biological variance that may obscure reliable interpretation of the results. While various artificial in vivo angiogenesis assays, such as the Matrigel implant assay, chick chorioallatoic membrane assay, and dorsal skin fold chamber assay have been developed and employed to more directly observe the progression of physiological angiogenesis, they can not appropriately assess tumor angiogenic progression or tumor vascular regression in response to therapeutic intervention. Here, we describe a noninvasive method and a detailed protocol that we have developed and optimized using the Olympus OV-100 in vivo imaging system for real-time high-resolution visualization and assessment of tumor angiogenesis and vascular response to anticancer therapies in live animals. We show that using this approach, tumor vessels can be monitored longitudinally through the whole vasculogenesis and angiogenesis process in the same mouse. Further, morphologic changes of the same vessel prior to and after drug treatments can be captured with microscopic high resolution. Moreover, the multichannel co-imaging capability of the OV-100 allows us to analyze and compare tumor vessel permeability before and after antiangiogenesis therapy by employing a near-infrared blood pool reagent, or by visualizing improved cytotoxic drug delivery upon tumor vessel normalization by using a fluorophore tagged drug. This noninvasive method can be readily applied to orthotopically transplanted breast cancer models as well as to subcutaneously-transplanted tumor models.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22700407
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10443
      1. Author :
        Rice, B W; Cable, M D; Nelson, M B
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2001
      5. Publication :
        Journal of biomedical optics
      6. Products :
      7. Volume :
        6
      8. Issue :
        4
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Diagnostic Imaging; Fluorescent Dyes; Green Fluorescent Proteins; Luciferases; Luminescent Measurements; Luminescent Proteins; Mice; Mice, Inbred BALB C; Neoplasms; PC-3M-luc; Pneumonia
      12. Abstract :
        In vivo imaging of cells tagged with light-emitting probes, such as firefly luciferase or fluorescent proteins, is a powerful technology that enables a wide range of biological studies in small research animals. Reporters with emission in the red to infrared (>600 nm) are preferred due to the low absorption in tissue at these wavelengths. Modeling of photon diffusion through tissue indicates that bioluminescent cell counts as low as a few hundred can be detected subcutaneously, while approximately 10(6) cells are required to detect signals at approximately 2 cm depth in tissue. Signal-to-noise estimates show that cooled back-thinned integrating charge coupled devices (CCDs) are preferred to image-intensified CCDs for this application, mainly due to their high quantum efficiency (approximately 85%) at wavelengths >600 nm where tissue absorption is low. Instrumentation for in vivo imaging developed at Xenogen is described and several examples of images of mice with bioluminescent cells are presented.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/11728202
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8984
      1. Author :
        Oashi, K.; Furukawa, H.; Nishihara, H.; Ozaki, M.; Oyama, A.; Funayama, E.; Hayashi, T.; Kuge, Y.; Yamamoto, Y.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Invest Dermatol
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        B16-F10-luc2, Melanoma, B16F10-luc2, IVIS
      12. Abstract :
        In-transit metastasis (ITM) is a unique manifestation of intralymphatic tumor dissemination, characterized by the presence of melanoma cells between the primary lesion and the draining regional lymph node basin that is clinically associated with poor prognosis. In this study, we aimed to establish an experimental animal model of melanoma ITM, as research progress in this field has been hampered by a lack of suitable experimental models. We reproduced melanoma ITM in a mouse hind limb by transplanting melanoma cells into the footpad of a mouse with lymphedema (LE). The tumor cells at the ITM site were highly proliferative, and mice with ITMs were more likely than control mice to develop distant lymph node and lung metastases. Peritumoral lymphatic vessels and tumor-associated blood vessels were increased in the primary tumor site of the LE mice. Our established ITM melanoma mouse model enabled us to clarify the molecular determinants and pathophysiology of ITM. This ITM model is also comparable to the unfavorable clinical behavior of melanoma ITM in humans and, moreover, underlined the importance of lymphangiogenic factors in the tumor dissemination through the lymphatic system.Journal of Investigative Dermatology advance online publication, 6 September 2012; doi:10.1038/jid.2012.274.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22951727
      14. Call Number :
        PKI @ kd.modi @ 10
      15. Serial :
        10501
      1. Author :
        Ketonis, C.; Barr, S.; Adams, C. S.; Shapiro, I. M.; Parvizi, J.; Hickok, N. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Antimicrob Agents Chemother
      6. Products :
      7. Volume :
        55
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen36, Xen 36, Staphylococcus aureus Xen36, IVIS, Anti-Bacterial Agents/chemistry/*pharmacology; Bacterial Adhesion/drug effects; Biofilms/drug effects/growth & development; *Bone Transplantation; Bone and Bones/*chemistry/*microbiology; Cell Adhesion/drug effects; Cell Line; Colony Count, Microbial; Humans; Microscopy, Confocal; Osteoblasts/cytology; Staphylococcus aureus/drug effects/*growth & development/physiology; Vancomycin/chemistry/*pharmacology
      12. Abstract :
        Infection is an important medical problem associated with the use of bone allografts. To retard bacterial colonization, we have recently reported on the modification of bone allografts with the antibiotic vancomycin (VAN). In this report, we examine the ability of this antibiotic-modified allograft to resist bacterial colonization and biofilm formation. When antibiotic was coupled to the allograft, a uniform distribution of the antibiotic was apparent. Following challenges with Staphylococcus aureus for 6 h, the covalently bonded VAN decreased colonization as a function of inoculum, ranging from 0.8 to 2.0 log(10) CFU. Furthermore, the VAN-modified surface resisted biofilm formation, even in topographical niches that provide a protected environment for bacterial adhesion. Attachment of the antibiotic to the allograft surface was robust, and the bonded VAN was stable whether incubated in aqueous media or in air, maintaining levels of 75 to 100% of initial levels over 60 days. While the VAN-modified allograft inhibited the Gram-positive S. aureus colonization, in keeping with VAN's spectrum of activity, the VAN-modified allograft was readily colonized by the Gram-negative Escherichia coli. Finally, initial toxicity measures indicated that the VAN-modified allograft did not influence osteoblast colonization or viability. Since the covalently tethered antibiotic is stable, is active, retains its specificity, and does not exhibit toxicity, it is concluded that this modified allograft holds great promise for decreasing bone graft-associated infections.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21098245
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10408
      1. Author :
        Engelsman, Anton F; van der Mei, Henny C; Francis, Kevin P; Busscher, Henk J; Ploeg, Rutger J; van Dam, Gooitzen M
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Journal of biomedical materials research. Part B, Applied biomaterials
      6. Products :
      7. Volume :
        88
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Infective Agents; Bacterial Adhesion; Biofilms; Bioware; Chromosomes, Bacterial; Colony Count, Microbial; Disease Models, Animal; Female; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Prostheses and Implants; pXen-5; Soft Tissue Infections; Staphylococcal Infections; Staphylococcus aureus; Xen29
      12. Abstract :
        Infection is the main cause of biomaterials-related failure. A simple technique to test in-vivo new antimicrobial and/or nonadhesive implant coatings is unavailable. Current in vitro methods for studying bacterial adhesion and growth on biomaterial surfaces lack the influence of the host immune system. Most in vivo methods to study biomaterials-related infections routinely involve implant-removal, preventing comprehensive longitudinal monitoring. In vivo imaging circumvents these drawbacks and is based on the use of noninvasive optical imaging of bioluminescent bacteria. Staphylococcus aureus Xen29 is genetically modified to be stably bioluminescent, by the introduction of a modified full lux operon onto its chromosome. Surgical meshes with adhering S. aureus Xen29 were implanted in mice and bacterial growth and spread into the surrounding tissue was monitored longitudinally from bioluminescence with a highly sensitive CCD camera. Distinct spatiotemporal bioluminescence patterns, extending beyond the mesh area into surrounding tissues were observed. After 10 days, the number of living organisms isolated from explanted meshes was found to correlate with bioluminescence prior to sacrifice of the animals. Therefore, it is concluded that in vivo imaging using bioluminescent bacteria is ideally suited to study antimicrobial coatings taking into account the host immune system. In addition, longitudinal monitoring of infection in one animal will significantly reduce the number of experiments and animals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18618733
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9020
      1. Author :
        Engelsman, A. F.; Mei, H. C. van der; Francis, K. P.; Busscher, H. J.; Ploeg, R. J.; Dam, G. M. van
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        J Biomed Mater Res B Appl Biomater
      6. Products :
      7. Volume :
        88
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; IVIS, Xenogen; Xen29
      12. Abstract :
        Infection is the main cause of biomaterials-related failure. A simple technique to test in-vivo new antimicrobial and/or nonadhesive implant coatings is unavailable. Current in vitro methods for studying bacterial adhesion and growth on biomaterial surfaces lack the influence of the host immune system. Most in vivo methods to study biomaterials-related infections routinely involve implant-removal, preventing comprehensive longitudinal monitoring. In vivo imaging circumvents these drawbacks and is based on the use of noninvasive optical imaging of bioluminescent bacteria. Staphylococcus aureus Xen29 is genetically modified to be stably bioluminescent, by the introduction of a modified full lux operon onto its chromosome. Surgical meshes with adhering S. aureus Xen29 were implanted in mice and bacterial growth and spread into the surrounding tissue was monitored longitudinally from bioluminescence with a highly sensitive CCD camera. Distinct spatiotemporal bioluminescence patterns, extending beyond the mesh area into surrounding tissues were observed. After 10 days, the number of living organisms isolated from explanted meshes was found to correlate with bioluminescence prior to sacrifice of the animals. Therefore, it is concluded that in vivo imaging using bioluminescent bacteria is ideally suited to study antimicrobial coatings taking into account the host immune system. In addition, longitudinal monitoring of infection in one animal will significantly reduce the number of experiments and animals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18618733
      14. Call Number :
        137698
      15. Serial :
        7462
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