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      1. Author :
        Kim, J. B.; Urban, K.; Cochran, E.; Lee, S.; Ang, A.; Rice, B.; Bata, A.; Campbell, K.; Coffee, R.; Gorodinsky, A.; Lu, Z.; Zhou, H.; Kishimoto, T. K.; Lassota, P.
      2. Title :
        Non-invasive detection of a small number of bioluminescent cancer cells in vivo
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PLoS One
      6. Products :

        Bioware cell lines

      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen, VIS, 4T1-luc2, Animals; Cell Line, Tumor; Diagnostic Imaging/*methods; Female; Genetic Vectors/genetics; Lentivirus/genetics; Luciferases/genetics/*metabolism; Luminescent Measurements/instrumentation/*methods; Lung Neoplasms/diagnosis/metabolism/secondary; Mammary Neoplasms, Experimental/diagnosis/genetics/*metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms/genetics/metabolism/pathology; Sensitivity and Specificity; Time Factors; Transfection; Tumor Burden
      12. Abstract :
        Early detection of tumors can significantly improve the outcome of tumor treatment. One of the most frequently asked questions in cancer imaging is how many cells can be detected non-invasively in a live animal. Although many factors limit such detection, increasing the light emission from cells is one of the most effective ways of overcoming these limitations. Here, we describe development and utilization of a lentiviral vector containing enhanced firefly luciferase (luc2) gene. The resulting single cell clones of the mouse mammary gland tumor (4T1-luc2) showed stable light emission in the range of 10,000 photons/sec/cell. In some cases individual 4T1-luc2 cells inserted under the skin of a nu/nu mouse could be detected non-invasively using a cooled CCD camera in some cases. In addition, we showed that only few cells are needed to develop tumors in these mice and tumor progression can be monitored right after the cells are implanted. Significantly higher luciferase activity in these cells allowed us to detect micrometastases in both, syngeneic Balb/c and nu/nu mice.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20186331
      14. Call Number :
        139615
      15. Serial :
        7111
      1. Author :
        Kim, Jae-Beom; Urban, Konnie; Cochran, Edward; Lee, Steve; Ang, Angel; Rice, Bradley; Bata, Adam; Campbell, Kenneth; Coffee, Richard; Gorodinsky, Alex; Lu, Zhan; Zhou, He; Kishimoto, Takashi Kei; Lassota, Peter
      2. Title :
        Non-invasive detection of a small number of bioluminescent cancer cells in vivo
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PloS one
      6. Products :

        Bioware cell lines

      7. Volume :
        5
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2; Animals; Bicuculline; Bioware; Cell Line, Tumor; Diagnostic Imaging; Female; Genetic Vectors; Lentivirus; Luciferases; Luminescent Measurements; Lung Neoplasms; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms; Sensitivity and Specificity; Time Factors; Transfection; Tumor Burden
      12. Abstract :
        Early detection of tumors can significantly improve the outcome of tumor treatment. One of the most frequently asked questions in cancer imaging is how many cells can be detected non-invasively in a live animal. Although many factors limit such detection, increasing the light emission from cells is one of the most effective ways of overcoming these limitations. Here, we describe development and utilization of a lentiviral vector containing enhanced firefly luciferase (luc2) gene. The resulting single cell clones of the mouse mammary gland tumor (4T1-luc2) showed stable light emission in the range of 10,000 photons/sec/cell. In some cases individual 4T1-luc2 cells inserted under the skin of a nu/nu mouse could be detected non-invasively using a cooled CCD camera in some cases. In addition, we showed that only few cells are needed to develop tumors in these mice and tumor progression can be monitored right after the cells are implanted. Significantly higher luciferase activity in these cells allowed us to detect micrometastases in both, syngeneic Balb/c and nu/nu mice.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20186331
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8938
      1. Author :
        N/A
      2. Title :
        New symmetrically esterified m-bromobenzyl non-aminobisphosphonates inhibited breast cancer growth and metastases
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        PloS one
      6. Products :

        Bioware cell lines

      7. Volume :
        4
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Antineoplastic Agents; Bioware; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Diphosphonates; Esterification; Female; Humans; Hydrophobic and Hydrophilic Interactions; MDA-MB-231-D3H2LN cells; Neoplasm Metastasis; Structure-Activity Relationship
      12. Abstract :
        BACKGROUND Although there was growing evidence in the potential use of Bisphosphonates (BPs) in cancer therapy, their strong osseous affinities that contrast their poor soft tissue uptake limited their use. Here, we developed a new strategy to overcome BPs hydrophilicity by masking the phosphonic acid through organic protecting groups and introducing hydrophobic functions in the side chain. METHODOLOGY/PRINCIPAL FINDINGS We synthesized non-nitrogen BPs (non N-BPs) containing bromobenzyl group (BP7033Br) in their side chain that were symmetrically esterified with hydrophobic 4-methoxphenyl (BP7033BrALK) and assessed their effects on breast cancer estrogen-responsive cells (T47D, MCF-7) as well as on non responsive ones (SKBR3, MDA-MB-231 and its highly metastatic derived D3H2LN subclone). BP7033Br ALK was more efficient in inhibiting tumor cell proliferation, migration and survival when compared to BP7033Br. Although both compounds inhibited tumor growth without side effects, only BP7033Br ALK abrogated tumor angiogenesis and D3H2LN cells-induced metastases formation. CONCLUSION/SIGNIFICANCE Taken together these data suggest the potential therapeutic use of this new class of esterified Bisphosphonates (BPs) in the treatment of tumor progression and metastasis without toxic adverse effects.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19262688
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8958
      1. Author :
        N/A
      2. Title :
        Imaging of disease dynamics during meningococcal sepsis
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        PloS one
      6. Products :

        Bioware bacteria

      7. Volume :
        2
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Adhesins, Bacterial; Animals; Antigens, CD46; Bacteremia; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Translocation; Bioware; Blood-Brain Barrier; Central Nervous System; Disease Progression; Female; Luminescent Measurements; Luminescent Proteins; Male; Meningitis, Meningococcal; Meningococcal Infections; Mice; Mice, Transgenic; Nasal Cavity; pXen-13; Recombinant Fusion Proteins; Respiratory System; Sepsis; Thyroid Gland
      12. Abstract :
        Neisseria meningitidis is a human pathogen that causes septicemia and meningitis with high mortality. The disease progression is rapid and much remains unknown about the disease process. The understanding of disease development is crucial for development of novel therapeutic strategies and vaccines against meningococcal disease. The use of bioluminescent imaging combined with a mouse disease model allowed us to investigate the progression of meningococcal sepsis over time. Injection of bacteria in blood demonstrated waves of bacterial clearance and growth, which selected for Opa-expressing bacteria, indicating the importance of this bacterial protein. Further, N. meningitidis accumulated in the thyroid gland, while thyroid hormone T4 levels decreased. Bacteria reached the mucosal surfaces of the upper respiratory tract, which required expression of the meningococcal PilC1 adhesin. Surprisingly, PilC1 was dispensable for meningococcal growth in blood and for crossing of the blood-brain barrier, indicating that the major role of PilC1 is to interact with mucosal surfaces. This in vivo study reveals disease dynamics and organ targeting during meningococcal disease and presents a potent tool for further investigations of meningococcal pathogenesis and vaccines in vivo. This might lead to development of new strategies to improve the outcome of meningococcal disease in human patients.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17311106
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9032
      1. Author :
        Apidianakis, Y.; Mindrinos, M. N.; Xiao, W.; Tegos, G. P.; Papisov, M. I.; Hamblin, M. R.; Davis, R. W.; Tompkins, R. G.; Rahme, L. G.
      2. Title :
        Involvement of Skeletal Muscle Gene Regulatory Network in Susceptibility to Wound Infection Following Trauma
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        PLoS One
      6. Products :

        IVIS Imaging SystemsBioware bacteria

      7. Volume :
        2
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen, Xen5
      12. Abstract :
        Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows severe trauma. We show that P. aeruginosa compromises skeletal muscle gene (SMG) expression at the injury site to promote infection. We demonstrate that activation of SMG structural components is under the control of cJun-N-terminal Kinase (JNK) Kinase, Hemipterous (Hep), and activation of this pathway promotes local resistance to P. aeruginosa in flies and mice. Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue. Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18159239
      14. Call Number :
        135889
      15. Serial :
        6705
      1. Author :
        Zhou, H.; Roy, S.; Cochran, E.; Zouaoui, R.; Chu, C. L.; Duffner, J.; Zhao, G.; Smith, S.; Galcheva-Gargova, Z.; Karlgren, J.; Dussault, N.; Kwan, R. Y.; Moy, E.; Barnes, M.; Long, A.; Honan, C.; Qi, Y. W.; Shriver, Z.; Ganguly, T.; Schultes, B.; Venkataraman, G.; Kishimoto, T. K.
      2. Title :
        M402, a novel heparan sulfate mimetic, targets multiple pathways implicated in tumor progression and metastasis
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        PLoS One
      6. Products :

        Bioware cell lines

      7. Volume :
        6
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, 4T1-luc2
      12. Abstract :
        Heparan sulfate proteoglycans (HSPGs) play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment and activation, as well as promoting tumor progression, metastasis, and survival. M402 is a rationally engineered, non-cytotoxic heparan sulfate (HS) mimetic, designed to inhibit multiple factors implicated in tumor-host cell interactions, including VEGF, FGF2, SDF-1alpha, P-selectin, and heparanase. A single s.c. dose of M402 effectively inhibited seeding of B16F10 murine melanoma cells to the lung in an experimental metastasis model. Fluorescent-labeled M402 demonstrated selective accumulation in the primary tumor. Immunohistological analyses of the primary tumor revealed a decrease in microvessel density in M402 treated animals, suggesting anti-angiogenesis to be one of the mechanisms involved in-vivo. M402 treatment also normalized circulating levels of myeloid derived suppressor cells in tumor bearing mice. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis and prolonged survival in an orthotopic 4T1 murine mammary carcinoma model. These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21698156
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10362
      1. Author :
        Pello, O. M.; Chevre, R.; Laoui, D.; De Juan, A.; Lolo, F.; Andres-Manzano, M. J.; Serrano, M.; Van Ginderachter, J. A.; Andres, V.
      2. Title :
        In Vivo Inhibition of c-MYC in Myeloid Cells Impairs Tumor-Associated Macrophage Maturation and Pro-Tumoral Activities
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        PLoS One
      6. Products :

        IntegriSense

      7. Volume :
        7
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense
      12. Abstract :
        Although tumor-associated macrophages (TAMs) are involved in tumor growth and metastasis, the mechanisms controlling their pro-tumoral activities remain largely unknown. The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macrophages infiltrating human tumors. In this study, we exploited the predominant expression of LysM in myeloid cells to generate c-Myc(fl/fl) LysM(cre/+) mice, which lack c-Myc in macrophages, to investigate the role of macrophage c-MYC expression in cancer. Under steady-state conditions, immune system parameters in c-Myc(fl/fl) LysM(cre/+) mice appeared normal, including the abundance of different subsets of bone marrow hematopoietic stem cells, precursors and circulating cells, macrophage density, and immune organ structure. In a model of melanoma, however, TAMs lacking c-Myc displayed a delay in maturation and showed an attenuation of pro-tumoral functions (e.g., reduced expression of VEGF, MMP9, and HIF1alpha) that was associated with impaired tissue remodeling and angiogenesis and limited tumor growth in c-Myc(fl/fl) LysM(cre/+) mice. Macrophage c-Myc deletion also diminished fibrosarcoma growth. These data identify c-Myc as a positive regulator of the pro-tumoral program of TAMs and suggest c-Myc inactivation as an attractive target for anti-cancer therapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23028984
      14. Call Number :
        PKI @ kd.modi @ 33
      15. Serial :
        10376
      1. Author :
        Tsurumi, C.; Esser, N.; Firat, E.; Gaedicke, S.; Follo, M.; Behe, M.; Elsasser-Beile, U.; Grosu, A. L.; Graeser, R.; Niedermann, G.
      2. Title :
        Non-invasive in vivo imaging of tumor-associated CD133/prominin
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PLoS One
      6. Products :

        IntegriSense

      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Antigens, CD/*biosynthesis/*metabolism; Flow Cytometry/methods; Glioma/metabolism; Glycoproteins/*biosynthesis/*metabolism; Humans; Hybridomas/metabolism; Mice; Mice, Transgenic; Models, Biological; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms/*metabolism; Neoplastic Stem Cells; Peptides/*metabolism; Recurrence
      12. Abstract :
        BACKGROUND: Cancer stem cells are thought to play a pivotal role in tumor maintenance, metastasis, tumor therapy resistance and relapse. Hence, the development of methods for non-invasive in vivo detection of cancer stem cells is of great importance. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe successful in vivo detection of CD133/prominin, a cancer stem cell surface marker for a variety of tumor entities. The CD133-specific monoclonal antibody AC133.1 was used for quantitative fluorescence-based optical imaging of mouse xenograft models based on isogenic pairs of CD133 positive and negative cell lines. A first set consisted of wild-type U251 glioblastoma cells, which do not express CD133, and lentivirally transduced CD133-overexpressing U251 cells. A second set made use of HCT116 colon carcinoma cells, which uniformly express CD133 at levels comparable to primary glioblastoma stem cells, and a CD133-negative HCT116 derivative. Not surprisingly, visualization and quantification of CD133 in overexpressing U251 xenografts was successful; more importantly, however, significant differences were also found in matched HCT116 xenograft pairs, despite the lower CD133 expression levels. The binding of i.v.-injected AC133.1 antibodies to CD133 positive, but not negative, tumor cells isolated from xenografts was confirmed by flow cytometry. CONCLUSIONS/SIGNIFICANCE: Taken together, our results show that non-invasive antibody-based in vivo imaging of tumor-associated CD133 is feasible and that CD133 antibody-based tumor targeting is efficient. This should facilitate developing clinically applicable cancer stem cell imaging methods and CD133 antibody-based therapeutics.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21187924
      14. Call Number :
        PKI @ kd.modi @ 15
      15. Serial :
        10382
      1. Author :
        Lamppa, J. W.; Ackerman, M. E.; Lai, J. I.; Scanlon, T. C.; Griswold, K. E.
      2. Title :
        Genetically engineered alginate lyase-PEG conjugates exhibit enhanced catalytic function and reduced immunoreactivity
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        PLoS One
      6. Products :

        Bioware bacteriaIVIS Imaging Systems

      7. Volume :
        6
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen5, Xen 5, Pseudomonas aeruginosa Xen 5
      12. Abstract :
        Alginate lyase enzymes represent prospective biotherapeutic agents for treating bacterial infections, particularly in the cystic fibrosis airway. To effectively deimmunize one therapeutic candidate while maintaining high level catalytic proficiency, a combined genetic engineering-PEGylation strategy was implemented. Rationally designed, site-specific PEGylation variants were constructed by orthogonal maleimide-thiol coupling chemistry. In contrast to random PEGylation of the enzyme by NHS-ester mediated chemistry, controlled mono-PEGylation of A1-III alginate lyase produced a conjugate that maintained wild type levels of activity towards a model substrate. Significantly, the PEGylated variant exhibited enhanced solution phase kinetics with bacterial alginate, the ultimate therapeutic target. The immunoreactivity of the PEGylated enzyme was compared to a wild type control using in vitro binding studies with both enzyme-specific antibodies, from immunized New Zealand white rabbits, and a single chain antibody library, derived from a human volunteer. In both cases, the PEGylated enzyme was found to be substantially less immunoreactive. Underscoring the enzyme's potential for practical utility, >90% of adherent, mucoid, Pseudomonas aeruginosa biofilms were removed from abiotic surfaces following a one hour treatment with the PEGylated variant, whereas the wild type enzyme removed only 75% of biofilms in parallel studies. In aggregate, these results demonstrate that site-specific mono-PEGylation of genetically engineered A1-III alginate lyase yielded an enzyme with enhanced performance relative to therapeutically relevant metrics.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21340021
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10388
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