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      1. Author :
        Reppert, S.; Boross, I.; Koslowski, M.; Tureci, O.; Koch, S.; Lehr, H. A.; Finotto, S.
      2. Title :
        A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Nat Commun
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        2
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        LL/2-luc-M38, LL/2-luc, Lewis Lung Carcinoma, IVIS, Adenocarcinoma/drug therapy/genetics/*immunology/metabolism/pathology; Administration, Intranasal; Adult; Aged; Animals; Antibodies, Neutralizing/administration & dosage/*therapeutic use; Antigens, CD/immunology; Female; Forkhead Transcription Factors/genetics/*immunology/metabolism; Gene Expression Regulation, Neoplastic/drug effects/*immunology; Humans; Immunologic Surveillance; Interferon-gamma/biosynthesis/immunology; Interleukin-17/immunology/metabolism; Interleukin-23/immunology/metabolism; Lung/drug effects/*immunology/metabolism/pathology; Lung Neoplasms/drug therapy/genetics/*immunology/metabolism/pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; T-Box Domain Proteins/deficiency/*genetics/immunology; T-Lymphocytes, Regulatory/immunology
      12. Abstract :
        Lung cancer is the leading cause of cancer deaths worldwide. The cytokine interleukin-17A supports tumour vascularization and growth, however, its role in lung cancer is unknown. Here we show, in the lungs of patients with lung adenocarcinoma, an increase in interleukin-17A that is inversely correlated with the expression of T-bet and correlated with the T regulatory cell transcription factor Foxp3. Local targeting of interleukin-17A in experimental lung adenocarcinoma results in a reduction in tumour load, local expansion of interferon-gamma-producing CD4(+) T cells and a reduction in lung CD4(+)CD25(+)Foxp3(+) regulatory T cells. T-bet((-/-)) mice have a significantly higher tumour load compared with wild-type mice. This is associated with the local upregulation of interleukin-23 and induction of interleukin-17A/interleukin-17R-expressing T cells infiltrating the tumour. Local anti-interleukin-17A antibody treatment partially improves the survival of T-bet((-/-)) mice. These results suggest that local anti-interleukin-17A antibody therapy could be considered for the treatment of lung tumours.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22186896
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10544
      1. Author :
        N/A
      2. Title :
        Primary involvement of pharynx and peyer's patch in inhalational and intestinal anthrax
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        PLoS pathogens
      6. Products :

        Bioware bacteria

      7. Volume :
        3
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anthrax; Bacillus anthracis; Bioware; Disease Models, Animal; Gastrointestinal Diseases; Inhalation Exposure; Luciferases; Luminescence; Luminescent Measurements; Lymph Nodes; Mice; Mice, Inbred BALB C; Nasal Cavity; Organisms, Genetically Modified; Peyer's Patches; Pharynx; pXen-5; Skin; Spores, Bacterial
      12. Abstract :
        Bacillus anthracis causes three forms of anthrax: inhalational, gastrointestinal, and cutaneous. Anthrax is characterized by both toxemia, which is caused by secretion of immunomodulating toxins (lethal toxin and edema toxin), and septicemia, which is associated with bacterial encapsulation. Here we report that, contrary to the current view of B. anthracis pathogenesis, B. anthracis spores germinate and establish infections at the initial site of inoculation in both inhalational and cutaneous infections without needing to be transported to draining lymph nodes, and that inhaled spores establish initial infection in nasal-associated lymphoid tissues. Furthermore, we found that Peyer's patches in the mouse intestine are the primary site of bacterial growth after intragastric inoculation, thus establishing an animal model of gastrointestinal anthrax. All routes of infection progressed to the draining lymph nodes, spleen, lungs, and ultimately the blood. These discoveries were made possible through the development of a novel dynamic mouse model of B. anthracis infection using bioluminescent non-toxinogenic capsulated bacteria that can be visualized within the mouse in real-time, and demonstrate the value of in vivo imaging in the analysis of B. anthracis infection. Our data imply that previously unrecognized portals of bacterial entry demand more intensive investigation, and will significantly transform the current perception of inhalational, gastrointestinal, and cutaneous B. anthracis pathogenesis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17542645
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9022
      1. Author :
        Lee, S.; Vinegoni, C.; Feruglio, P. F.; Fexon, L.; Gorbatov, R.; Pivoravov, M.; Sbarbati, A.; Nahrendorf, M.; Weissleder, R.
      2. Title :
        Real-time in vivo imaging of the beating mouse heart at microscopic resolution
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Commun
      6. Products :

        AngioSense

      7. Volume :
        3
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense
      12. Abstract :
        Real-time imaging of moving organs and tissues at microscopic resolutions represents a major challenge in studying the complex biology of live animals. Here we present a technique based on a novel stabilizer setup combined with a gating acquisition algorithm for the imaging of a beating murine heart at the single-cell level. The method allows serial in vivo fluorescence imaging of the beating heart in live mice in both confocal and nonlinear modes over the course of several hours. We demonstrate the utility of this technique for in vivo optical sectioning and dual-channel time-lapse fluorescence imaging of cardiac ischaemia. The generic method could be adapted to other moving organs and thus broadly facilitate in vivo microscopic investigations.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22968700
      14. Call Number :
        PKI @ kd.modi @ 7
      15. Serial :
        10436
      1. Author :
        Guo, K.; Tang, J. P.; Jie, L.; Al-Aidaroos, A. Q.; Hong, C. W.; Tan, C. P.; Park, J. E.; Varghese, L.; Feng, Z.; Zhou, J.; Chng, W. J.; Zeng, Q.
      2. Title :
        Engineering the first chimeric antibody in targeting intracellular PRL-3 oncoprotein for cancer therapy in mice
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Oncotarget
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        3
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        HCT-116-luc2, IVIS, Bioware, HCT116-luc2, Animals; Antibodies, Monoclonal/*immunology; Antibody-Dependent Cell Cytotoxicity/immunology; Carcinoma, Non-Small-Cell Lung/drug therapy; Carcinoma, Squamous Cell/drug therapy; Cell Line, Tumor; Colorectal Neoplasms/drug therapy; Humans; Immediate-Early Proteins/*immunology; Killer Cells, Natural/*immunology; Lymphocyte Activation/immunology; Melanoma/drug therapy; Mice; Mice, Nude; Mice, SCID; Molecular Targeted Therapy/*methods; Protein Tyrosine Phosphatases/*immunology; Recombinant Fusion Proteins/immunology/pharmacology/therapeutic use
      12. Abstract :
        Antibodies are considered as 'magic bullets' because of their high specificity. It is believed that antibodies are too large to routinely enter the cytosol, thus antibody therapeutic approach has been limited to extracellular or secreted proteins expressed by cancer cells. However, many oncogenic proteins are localized within the cell. To explore the possibility of antibody therapies against intracellular targets, we generated a chimeric antibody targeting the intracellular PRL-3 oncoprotein to assess its antitumor activities in mice. Remarkably, we observed that the PRL-3 chimeric antibody could efficiently and specifically reduce the formation of PRL-3 expressing metastatic tumors. We further found that natural killer (NK) cells were important in mediating the therapeutic effect, which was only observed in a nude mouse model (T-cell deficient), but not in a Severe Combined Immunodeficiency' (scid ) mouse model (B- and T-cell deficient), indicating the anticancer effect also depends on host B-cell activity. Our study involving 377 nude and scid mice suggest that antibodies targeting intracellular proteins can be developed to treat cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22374986
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10497
      1. Author :
        Zongjin Li, Kitchener D. Wilson, Bryan Smith, Daniel L. Kraft, Fangjun Jia, Mei Huang, Xiaoyan Xie, Robert C. Robbins, Sanjiv S. Gambhir, Irving L. Weissman and Joseph C. Wu
      2. Title :
        Functional and Transcriptional Characterization of Human Embryonic Stem Cell-Derived Endothelial Cells for Treatment of Myocardial Infarction
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        PLoS One
      6. Products :

        AngioSense

      7. Volume :
        4
      8. Issue :
        12
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        in vivo imaging; human embryonic stem cells; hESCs; endothelial cells; ECs; AngioSense
      12. Abstract :
        Background: Differentiation of human embryonic stem cells into endothelial cells (hESC-ECs) has the potential to provide an unlimited source of cells for novel transplantation therapies of ischemic diseases by supporting angiogenesis and vasculogenesis. However, the endothelial differentiation efficiency of the conventional embryoid body (EB) method is low while the 2-dimensional method of co-culturing with mouse embryonic fibroblasts (MEFs) require animal product, both of which can limit the future clinical application of hESC-ECs. Moreover, to fully understand the beneficial effects of stem cell therapy, investigators must be able to track the functional biology and physiology of transplanted cells in living subjects over time.

        Methodology: In this study, we developed an extracellular matrix (ECM) culture system for increasing endothelial differentiation and free from contaminating animal cells. We investigated the transcriptional changes that occur during endothelial differentiation of hESCs using whole genome microarray, and compared to human umbilical vein endothelial cells (HUVECs). We also showed functional vascular formation by hESC-ECs in a mouse dorsal window model. Moreover, our study is the first so far to transplant hESC-ECs in a myocardial infarction model and monitor cell fate using molecular imaging methods.

        Conclusion: Taken together, we report a more efficient method for derivation of hESC-ECs that express appropriate patterns of endothelial genes, form functional vessels in vivo, and improve cardiac function. These studies suggest that hESC-ECs may provide a novel therapy for ischemic heart disease in the future.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2795856/?tool=pubmed
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4557
      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
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