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      1. Author :
        Quintela-Fandino, Miguel; Arpaia, Enrico; Brenner, Dirk; Goh, Theo; Yeung, Faith Au; Blaser, Heiko; Alexandrova, Roumiana; Lind, Evan F; Tusche, Mike W; Wakeham, Andrew; Ohashi, Pamela S; Mak, Tak W
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Proceedings of the National Academy of Sciences of the United States of America
      6. Products :
      7. Volume :
        107
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Actins; Animals; B16-F10-luc-G5; Bioware; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cofilin 1; Cytoskeleton; Female; Humans; Immunoblotting; Immunoprecipitation; Male; Mammary Neoplasms, Experimental; MDA-MB-231-D3H2LN cells; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Invasiveness; Neoplasm Metastasis; Phosphorylation; Protein Binding; Protein Kinases; Protein Phosphatase 2; Protein-Serine-Threonine Kinases; RNA Interference; Transplantation, Heterologous
      12. Abstract :
        Metastasis leads to the death of most cancer patients, and basal breast cancer is the most aggressive breast tumor type. Metastasis involves a complex cell migration process dependent on cytoskeletal remodeling such that targeting such remodeling in tumor cells could be clinically beneficial. Here we show that Hormonally Up-regulated Neu-associated Kinase (HUNK) is dramatically down-regulated in tumor samples and cell lines derived from basal breast cancers. Reconstitution of HUNK expression in basal breast cancer cell lines blocked actin polymerization and reduced cell motility, resulting in decreased metastases in two in vivo murine cancer models. Mechanistically, HUNK overexpression sustained the constitutive phosphorylation and inactivation of cofilin-1 (CFL-1), thereby blocking the incorporation of new actin monomers into actin filaments. HUNK reconstitution in basal breast cancer cell lines prevented protein phosphatase 2-A (PP2A), a phosphatase putatively acting on CFL-1, from binding to CFL-1. Our investigation of HUNK suggests that the interaction between PP2A and CFL-1 may be a target for antimetastasis therapy, particularly for basal breast cancers.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20133759
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8951
      1. Author :
        Matthias Nahrendorf, Peter Waterman, Greg Thurber, Kevin Groves, Milind Rajopadhye, Peter Panizzi, Brett Marinelli, Elena Aikawa, Mikael J Pittet, Filip K Swirski and Ralph Weissleder
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Arteriosclerosis, Thrombosis, and Vascular Biology
      6. Products :
      7. Volume :
        29
      8. Issue :
        10
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        FMT-CT; molecular imaging; atherosclerosis; protease activity; inflammation; in vivo imaging; fluorescence molecular tomography; ProSense
      12. Abstract :
        Objective: Proteases are emerging biomarkers of inflammatory diseases. In atherosclerosis, these enzymes are often secreted by inflammatory macrophages, digest the extracellular matrix of the fibrous cap and destabilize atheromata. Protease function can be monitored with protease activatable imaging probes and quantitated in vivo by fluorescence molecular tomography (FMT). To address two major constraints currently associated with imaging of murine atherosclerosis (lack of highly sensitive probes and absence of anatomical information), we compared protease sensors (PS) of variable size and pharmacokinetics and co-registered FMT datasets with computed tomography (FMT-CT).

        Methods and results: Co-registration of FMT and CT was achieved with a multimodal imaging cartridge containing fiducial markers detectable by both modalities. A high-resolution CT angiography protocol accurately localized fluorescence to the aortic root of atherosclerotic apoE-/- mice. To identify suitable sensors, we first modeled signal kinetics in-silico and then compared three probes with identical oligo-L-lysine cleavage sequences: PS-5, 5nm in diameter containing 2 fluorochromes , PS-25, a 25nm version with an elongated lysine chain and PS-40, a polymeric nanoparticle. Serial FMT-CT showed fastest kinetics for PS-5 but, surprisingly, highest fluorescence in lesions of the aortic root for PS-40. PS-40 robustly reported therapeutic effects of atorvastatin, corroborated by ex vivo imaging and qPCR for the model protease cathepsin B.

        Conclusions: FMT-CT is a robust and observer-independent tool for non-invasive assessment of inflammatory murine atherosclerosis. Reporter-containing nanomaterials may have unique advantages over small molecule agents for in vivo imaging.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746251/?tool=pubmed
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4568
      1. Author :
        Matthias Nahrendorf; Edmund Keliher; Brett Marinelli; Peter Waterman; Paolo Fumene Feruglio; Lioubov Fexon; Misha Pivovarov; Filip K. Swirski; Mikael J. Pittet; Claudio Vinegoni; Ralph Weissleder
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PNAS
      6. Products :
      7. Volume :
        107
      8. Issue :
        17
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        fluorescence molecular tomography; FMT; Fluorescence Imaging Agents; ProSense; fluorescence-mediated tomography; molecular imaging; multimodal image fusion; computed tomography; cancer
      12. Abstract :
        Fusion imaging of radionuclide-based molecular (PET) and structural data [x-ray computed tomography (CT)] has been firmly established. Here we show that optical measurements [fluorescence-mediated tomography (FMT)] show exquisite congruence to radionuclide measurements and that information can be seamlessly integrated and visualized. Using biocompatible nanoparticles as a generic platform (containing a 18F isotope and a far red fluorochrome), we show good correlations between FMT and PET in probe concentration (r2 > 0.99) and spatial signal distribution (r2 > 0.85). Using a mouse model of cancer and different imaging probes to measure tumoral proteases, macrophage content and integrin expression simultaneously, we demonstrate the distinct tumoral locations of probes in multiple channels in vivo. The findings also suggest that FMT can serve as a surrogate modality for the screening and development of radionuclide-based imaging agents.
      13. URL :
        http://www.pnas.org/content/107/17/7910.abstract?sid=084c1ba8-0b02-4833-acdd-b57bea226faf
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4468
      1. Author :
        Nahrendorf, M.; Keliher, E.; Marinelli, B.; Waterman, P.; Feruglio, P. F.; Fexon, L.; Pivovarov, M.; Swirski, F. K.; Pittet, M. J.; Vinegoni, C.; Weissleder, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Proc Natl Acad Sci U S A
      6. Products :
      7. Volume :
        107
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Flow Cytometry; Fluorescent Dyes/*diagnostic use; Image Processing, Computer-Assisted/methods; Mice; Mice, Inbred C57BL; Nanoparticles/*diagnostic use; Neoplasms/*diagnosis; Positron-Emission Tomography/*methods; Tomography, X-Ray Computed/*methods
      12. Abstract :
        Fusion imaging of radionuclide-based molecular (PET) and structural data [x-ray computed tomography (CT)] has been firmly established. Here we show that optical measurements [fluorescence-mediated tomography (FMT)] show exquisite congruence to radionuclide measurements and that information can be seamlessly integrated and visualized. Using biocompatible nanoparticles as a generic platform (containing a (18)F isotope and a far red fluorochrome), we show good correlations between FMT and PET in probe concentration (r(2) > 0.99) and spatial signal distribution (r(2) > 0.85). Using a mouse model of cancer and different imaging probes to measure tumoral proteases, macrophage content and integrin expression simultaneously, we demonstrate the distinct tumoral locations of probes in multiple channels in vivo. The findings also suggest that FMT can serve as a surrogate modality for the screening and development of radionuclide-based imaging agents.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20385821
      14. Call Number :
        PKI @ kd.modi @ 21
      15. Serial :
        10375
      1. Author :
        Filip K. Swirski, Matthias Nahrendorf, Martin Etzrodt, Moritz Wildgruber, Virna Cortez-Retamozo, Peter Panizzi, Jose-Luiz Figueiredo, Rainer H. Kohler, Aleksey Chudnovskiy, Peter Waterman, Elena Aikawa, Thorsten R. Mempel, Peter Libby, Ralph Weissleder and Mikael J. Pittet
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Science
      6. Products :
      7. Volume :
        325
      8. Issue :
        5940
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research; Immunology
      11. Keywords :
        splenic monocytes; in vivo imaging; ProSense; FMT; fluorescence molecular tomography
      12. Abstract :
        A current paradigm states that monocytes circulate freely and patrol blood vessels but differentiate irreversibly into dendritic cells (DCs) or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation.
      13. URL :
        http://www.sciencemag.org/content/325/5940/612.abstract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4567
      1. Author :
        Penna, F. J.; Chow, J. S.; Minnillo, B. J.; Passerotti, C. C.; Barnewolt, C. E.; Treves, S. T.; Fahey, F. H.; Dunning, P. S.; Freilich, D. A.; Retik, A. B.; Nguyen, H. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Urol
      6. Products :
      7. Volume :
        185
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Diagnostic Imaging; Disease Models, Animal; Fluorescence; *Kidney Pelvis; Mice; Ureteral Obstruction/*diagnosis
      12. Abstract :
        PURPOSE: Radiological imaging is the mainstay of diagnosing ureteropelvic junction obstruction. Current established radiological modalities can potentially differentiate the varying degrees of obstruction but they are limited in functionality, applicability and/or comprehensiveness. Of particular concern is that some tests require radiation, which has long-term consequences, especially in children. MATERIALS AND METHODS: We investigated the novel use of Genhance 680 dynamic fluorescence imaging to assess ureteropelvic junction obstruction in 20 mice that underwent partial or complete unilateral ureteral obstruction. Ultrasound, mercaptoacetyltriglycine renography, magnetic resonance imaging and fluorescence imaging were performed. RESULTS: Our model of partial and complete obstruction could be distinguished by ultrasound, mercaptoacetyltriglycine renography and magnetic resonance imaging, and was confirmed by histological analysis. Using fluorescence imaging distinct vascular and urinary parameters were identified in the partial and complete obstruction groups compared to controls. CONCLUSIONS: Fluorescence imaging is a feasible alternative radiological imaging modality to diagnose ureteropelvic junction obstruction. It provides continuous, detailed imaging without the risk of radiation exposure.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21511294
      14. Call Number :
        PKI @ kd.modi @ 14
      15. Serial :
        10473
      1. Author :
        Valdivia, Y. Alvarado M.; Wong, K.; Cheng He, T.; Xue, Z.; Wong, S. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Vasc Interv Radiol
      6. Products :
      7. Volume :
        22
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Cell Line, Tumor; Fiber Optic Technology/*methods; Fluorescent Dyes/*administration & dosage/*diagnostic use; Humans; Injections, Intralesional; Lung Neoplasms/*pathology; Microscopy, Fluorescence/*methods; Molecular Imaging/*methods; Rabbits; Surgery, Computer-Assisted/*methods; Tomography, X-Ray Computed/methods
      12. Abstract :
        PURPOSE: To show the feasibility of computed tomography (CT) image-guided fiberoptic confocal fluorescence molecular imaging in a rabbit lung tumor model. MATERIALS AND METHODS: Eight lung tumor models were created by injection of a VX2 cell suspension. The fluorescent imaging agent IntegriSense 680 was given to the animals 3.5-4 hours before the procedure. CT images were obtained and transferred to the minimally invasive multimodality image-guided (MIMIG) system as a guidance map. A real-time electromagnetically tracked needle was inserted under the visual guidance of the MIMIG system. A second CT image was obtained to confirm the location of the needle tip. Next, fiberoptic fluorescence imaging was acquired along the needle track. Finally, tumor samples were obtained for histopathologic confirmation. RESULTS: All cases were performed during breath-hold. Tumor size was 12.5 mm +/- 1.6; the distance from the chest wall was 2.1 mm +/- 0.5. The needle tip reached the tumor in all cases with an accuracy of 3.3 mm +/- 1.6. Only one skin entry point was necessary, and no needle adjustments were required. No pneumothorax was observed. At least two-fold alpha(v)beta(3) integrin image contrast was detected in the tumor compared with normal lung tissue. Tumor samples were confirmed to have viable VX2 cells and contrast uptake. CONCLUSIONS: The MIMIG system enables effective in situ fluorescence molecular imaging in a needle biopsy lung procedure. In situ alpha(v)beta(3) integrin molecular imaging allows molecular characterization of lung tumors at multiple regions and can be used to guide biopsy procedures.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22019854
      14. Call Number :
        PKI @ kd.modi @ 14
      15. Serial :
        10383
      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 :
        Mieog, J. S.; Hutteman, M.; van der Vorst, J. R.; Kuppen, P. J.; Que, I.; Dijkstra, J.; Kaijzel, E. L.; Prins, F.; Lowik, C. W.; Smit, V. T.; van de Velde, C. J.; Vahrmeijer, A. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Breast Cancer Res Treat
      6. Products :
      7. Volume :
        128
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        ProSense, IVIS, Animals; Breast Neoplasms/pathology/*surgery; Cell Line, Tumor; Disease Models, Animal; Female; *Microscopy, Fluorescence; Rats; *Surgery, Computer-Assisted; Transplantation, Isogeneic; Xenograft Model Antitumor Assays
      12. Abstract :
        Tumor involvement of resection margins is found in a large proportion of patients who undergo breast-conserving surgery. Near-infrared (NIR) fluorescence imaging is an experimental technique to visualize cancer cells during surgery. To determine the accuracy of real-time NIR fluorescence imaging in obtaining tumor-free resection margins, a protease-activatable NIR fluorescence probe and an intraoperative camera system were used in the EMR86 orthotopic syngeneic breast cancer rat model. Influence of concentration, timing and number of tumor cells were tested in the MCR86 rat breast cancer cell line. These variables were significantly associated with NIR fluorescence probe activation. Dosing and tumor size were also significantly associated with fluorescence intensity in the EMR86 rat model, whereas time of imaging was not. Real-time NIR fluorescence guidance of tumor resection resulted in a complete resection of 17 out of 17 tumors with minimal excision of normal healthy tissue (mean minimum and a mean maximum tumor-free margin of 0.2 +/- 0.2 mm and 1.3 +/- 0.6 mm, respectively). Moreover, the technique enabled identification of remnant tumor tissue in the surgical cavity. Histological analysis revealed that the NIR fluorescence signal was highest at the invasive tumor border and in the stromal compartment of the tumor. In conclusion, NIR fluorescence detection of breast tumor margins was successful in a rat model. This study suggests that clinical introduction of intraoperative NIR fluorescence imaging has the potential to increase the number of complete tumor resections in breast cancer patients undergoing breast-conserving surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20821347
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10429
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