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      1. Author :
        Rahul Anil Sheth; Rabi Upadhyay; Lars Stangenberg; Rucha Sheth; Ralph Weissleder; Umar Mahmood
      2. Title :
        Improved detection of ovarian cancer metastases by intraoperative quantitative fluorescence protease imaging in a pre-clinical model
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Gynecologic Oncology
      6. Products :

        ProSense

      7. Volume :
        112
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Ovarian cancer; Molecular imaging; Intraoperative imaging; Fluorescence imaging
      12. Abstract :
        OBJECTIVES: Cytoreductive surgery is a cornerstone of therapy in metastatic ovarian cancer. While conventional white light (WL) inspection detects many obvious tumor foci, careful histologic comparison has shown considerable miss rates for smaller foci. The goal of this study was to compare tumor detection using WL versus near infrared (NIR) imaging with a protease activatable probe, as well as to evaluate the ability to quantify NIR fluorescence using a novel quantitative optical imaging system.

        METHODS: A murine model for peritoneal carcinomatosis was generated and metastatic foci were imaged using WL and NIR imaging following the i.v. administration of the protease activatable probe ProSense750. The presence of tumor was confirmed by histology. Additionally, the ability to account for variations in fluorescence signal intensity due to changes in distance between the catheter and target lesion during laparoscopic procedures was evaluated.

        RESULTS: NIR imaging with a ProSense750 significantly improved upon the target-to-background ratios (TBRs) of tumor foci in comparison to WL imaging (minimum improvement was approximately 3.5 fold). Based on 52 histologically validated samples, the sensitivity for WL imaging was 69%, while the sensitivity for NIR imaging was 100%. The effects of intraoperative distance changes upon fluorescence intensity were corrected in realtime, resulting in a decrease from 89% to 5% in signal variance during fluorescence laparoscopy.

        CONCLUSIONS: With its molecular specificity, low background autofluorescence, high TBRs, and quantitative signal, optical imaging with NIR protease activatable probes greatly improves upon the intraoperative detection of ovarian cancer metastases.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19135233?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4497
      1. Author :
        Mathew, B.; Lennon, F.E.; Siegler, J.; Mirzapoiazova, T.; Mambetsariev, N.; Sammani, S.; Gerhold, L.M.; Lariviere, P.J.; Chen, C.-T.; Garcia, J.G.N.; Salgia, R.; Moss, J.; Singleton, P.A.
      2. Title :
        The novel role of the mu opioid receptor in lung cancer progression: a laboratory investigation
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Anesthesia and Analgesia
      6. Products :

        ProSenseMMPSense

      7. Volume :
        112
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Cancer; flank tumor; In vivo; MMPSense 750; ProSense 680; tomography; VisEn FMT
      12. Abstract :
        <AbstractText Label=“BACKGROUND” NlmCategory=“BACKGROUND”>The possibility that μ opioid agonists can influence cancer recurrence is a subject of recent interest. Epidemiologic studies suggested that there were differences in cancer recurrence in breast and prostate cancer contingent on anesthetic regimens. In this study, we identify a possible mechanism for these epidemiologic findings on the basis of μ opioid receptor (MOR) regulation of Lewis lung carcinoma (LLC) tumorigenicity in cell and animal models.</AbstractText> <AbstractText Label=“METHODS” NlmCategory=“METHODS”>We used human lung tissue and human non-small cell lung cancer (NSCLC) cell lines and evaluated MOR expression using immunoblot and immunohistochemical analysis. LLC cells were treated with the peripheral opioid antagonist methylnaltrexone (MNTX) or MOR shRNA and evaluated for proliferation, invasion, and soft agar colony formation in vitro and primary tumor growth and lung metastasis in C57BL/6 and MOR knockout mice using VisEn fluorescence mediated tomography imaging and immunohistochemical analysis.</AbstractText> <AbstractText Label=“RESULTS” NlmCategory=“RESULTS”>We provide several lines of evidence that the MOR may be a potential target for lung cancer, a disease with high mortality and few treatment options. We first observed that there is ~5- to 10-fold increase in MOR expression in lung samples from patients with NSCLC and in several human NSCLC cell lines. The MOR agonists morphine and [d-Ala(2), N-MePhe(4), Gly-ol]-enkephalin (DAMGO) increased in vitro LLC cell growth. Treatment with MNTX or silencing MOR expression inhibited LLC invasion and anchorage-independent growth by 50%-80%. Injection of MOR silenced LLC lead to a ~65% reduction in mouse lung metastasis. In addition, MOR knockout mice do not develop significant tumors when injected with LLC in comparison with wild-type controls. Finally, continuous infusion of the peripheral opioid antagonist MNTX attenuates primary LLC tumor growth and reduces lung metastasis.</AbstractText> <AbstractText Label=“CONCLUSIONS” NlmCategory=“CONCLUSIONS”>Taken together, our data suggest a possible direct effect of opiates on lung cancer progression, and provide a plausible explanation for the epidemiologic findings. Our observations further suggest a possible therapeutic role for opioid antagonists.</AbstractText>
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21156980
      14. Call Number :
        PKI @ user @ 8557
      15. Serial :
        4797
      1. Author :
        N/A
      2. Title :
        Macrophage mannose receptor on lymphatics controls cell trafficking
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Blood
      6. Products :

        Bioware cell lines

      7. Volume :
        112
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antigen Presentation; Antigens, Neoplasm; B16-F10-luc-G5 cells; Bioware; B-Lymphocytes; Cell Adhesion; Cell Line, Tumor; Cell Movement; dendritic cells; Female; Lectins, C-Type; Lymphatic Metastasis; Lymphatic System; Macrophages; Male; Mannose-Binding Lectins; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Cell Surface; T-Lymphocytes
      12. Abstract :
        Macrophage mannose receptor (MR) participates in pathogen recognition, clearance of endogenous serum glycoproteins, and antigen presentation. MR is also present on lymphatic vessels, where its function is unknown. Here we show that migration of lymphocytes from the skin into the draining lymph nodes through the afferent lymphatics is reduced in MR-deficient mice, while the structure of lymphatic vasculature remains normal in these animals. Moreover, in a tumor model the primary tumors grow significantly bigger in MR(-/-) mice than in the wild-type (WT) controls, whereas the regional lymph node metastases are markedly smaller. Adhesion of both normal lymphocytes and tumor cells to lymphatic vessels is significantly decreased in MR-deficient mice. The ability of macrophages to present tumor antigens is indistinguishable between the 2 genotypes. Thus, MR on lymphatic endothelial cells is involved in leukocyte trafficking and contributes to the metastatic behavior of cancer cells. Blocking of MR may provide a new approach to controlling inflammation and cancer metastasis by targeting the lymphatic vasculature.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18434610
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9000
      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 :
        Potential of ceragenin CSA-13 and its mixture with pluronic F-127 as treatment of topical bacterial infections
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Appl Microbiol
      6. Products :

        Bioware bacteriaIVIS Imaging Systems

      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 :
        Cortez-Retamozo, V.; Etzrodt, M.; Newton, A.; Rauch, P. J.; Chudnovskiy, A.; Berger, C.; Ryan, R. J.; Iwamoto, Y.; Marinelli, B.; Gorbatov, R.; Forghani, R.; Novobrantseva, T. I.; Koteliansky, V.; Figueiredo, J. L.; Chen, J. W.; Anderson, D. G.; Nahrendorf, M.; Swirski, F. K.; Weissleder, R.; Pittet, M. J.
      2. Title :
        Origins of tumor-associated macrophages and neutrophils
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Proc Natl Acad Sci U S A
      6. Products :

        AngioSense

      7. Volume :
        109
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; Humans; Macrophages/*immunology; Mice; Neoplasms/immunology/*pathology; Neutrophils/*immunology; Spleen/immunology/pathology
      12. Abstract :
        Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) can control cancer growth and exist in almost all solid neoplasms. The cells are known to descend from immature monocytic and granulocytic cells, respectively, which are produced in the bone marrow. However, the spleen is also a recently identified reservoir of monocytes, which can play a significant role in the inflammatory response that follows acute injury. Here, we evaluated the role of the splenic reservoir in a genetic mouse model of lung adenocarcinoma driven by activation of oncogenic Kras and inactivation of p53. We found that high numbers of TAM and TAN precursors physically relocated from the spleen to the tumor stroma, and that recruitment of tumor-promoting spleen-derived TAMs required signaling of the chemokine receptor CCR2. Also, removal of the spleen, either before or after tumor initiation, reduced TAM and TAN responses significantly and delayed tumor growth. The mechanism by which the spleen was able to maintain its reservoir capacity throughout tumor progression involved, in part, local accumulation in the splenic red pulp of typically rare extramedullary hematopoietic stem and progenitor cells, notably granulocyte and macrophage progenitors, which produced CD11b(+) Ly-6C(hi) monocytic and CD11b(+) Ly-6G(hi) granulocytic cells locally. Splenic granulocyte and macrophage progenitors and their descendants were likewise identified in clinical specimens. The present study sheds light on the origins of TAMs and TANs, and positions the spleen as an important extramedullary site, which can continuously supply growing tumors with these cells.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22308361
      14. Call Number :
        PKI @ kd.modi @ 14
      15. Serial :
        10432
      1. Author :
        Cheng, H. H.; Kuo, C. C.; Yan, J. L.; Chen, H. L.; Lin, W. C.; Wang, K. H.; Tsai, K. K.; Guven, H.; Flaberg, E.; Szekely, L.; Klein, G.; Wu, K. K.
      2. Title :
        Control of cyclooxygenase-2 expression and tumorigenesis by endogenous 5-methoxytryptophan
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Proc Natl Acad Sci U S A
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        109
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        A549-luc-C8, A549-luc, IVIS, Bioware, Acetylserotonin O-Methyltransferase/metabolism; Animals; Biocatalysis/drug effects; Cell Line, Tumor; Cell Movement/drug effects; Cell Proliferation/drug effects; Cell Transformation, Neoplastic/drug effects/*pathology; Cyclooxygenase 2/*metabolism; Cyclooxygenase 2 Inhibitors/pharmacology; Fibroblasts/drug effects/metabolism; Humans; Metabolic Networks and Pathways/drug effects; Metabolomics; Mice; Neoplasm Metastasis; Solubility/drug effects; Subcellular Fractions/drug effects/metabolism; Tryptophan/*analogs & derivatives/biosynthesis/metabolism/pharmacology; Tryptophan Hydroxylase/metabolism; Xenograft Model Antitumor Assays
      12. Abstract :
        Cyclooxygenase-2 (COX-2) expression is induced by mitogenic and proinflammatory factors. Its overexpression plays a causal role in inflammation and tumorigenesis. COX-2 expression is tightly regulated, but the mechanisms are largely unclear. Here we show the control of COX-2 expression by an endogenous tryptophan metabolite, 5-methoxytryptophan (5-MTP). By using comparative metabolomic analysis and enzyme-immunoassay, our results reveal that normal fibroblasts produce and release 5-MTP into the extracellular milieu whereas A549 and other cancer cells were defective in 5-MTP production. 5-MTP was synthesized from L-tryptophan via tryptophan hydroxylase-1 and hydroxyindole O-methyltransferase. 5-MTP blocked cancer cell COX-2 overexpression and suppressed A549 migration and invasion. Furthermore, i.p. infusion of 5-MTP reduced tumor growth and cancer metastasis in a murine xenograft tumor model. We conclude that 5-MTP synthesis represents a mechanism for endogenous control of COX-2 overexpression and is a valuable lead for new anti-cancer and anti-inflammatory drug development.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22851770
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10521
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