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      1. Author :
        Hsieh, C. H.; Chang, H. T.; Shen, W. C.; Shyu, W. C.; Liu, R. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Imaging Biol
      6. Products :
      7. Volume :
        14
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MMPSense, IVIS, Animals; Cell Hypoxia; Cell Line, Tumor; Cell Movement; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases/metabolism; Gene Knockdown Techniques; Glioblastoma/*enzymology/*pathology; Humans; JNK Mitogen-Activated Protein Kinases/metabolism; Matrix Metalloproteinase 9/metabolism; Mice; Mice, SCID; Molecular Imaging/*methods; NADPH Oxidase/*metabolism; NF-kappa B/metabolism; Neoplasm Invasiveness; Reactive Oxygen Species/metabolism; Tumor Microenvironment; Xenograft Model Antitumor Assays
      12. Abstract :
        PURPOSE: We determined the impact of the cycling hypoxia tumor microenvironment on tumor cell invasion and infiltration in U87 human glioblastoma cells and investigated the underlying mechanisms using molecular bio-techniques and imaging. PROCEDURES: The invasive phenotype of U87 cells and xenografts exposed to experimentally imposed cycling hypoxic stress in vitro and in vivo was determined by the matrigel invasion assay in vitro and dual optical reporter gene imaging in vivo. RNAi-knockdown technology was utilized to study the role of the NADPH oxidase subunit 4 (Nox4) on cycling hypoxia-mediated tumor invasion. RESULTS: Cycling hypoxic stress significantly promoted tumor invasion in vitro and in vivo. However, Nox4 knockdown inhibited this effect. Nox4-generated reactive oxygen species (ROS) are required for cycling hypoxia-induced invasive potential in U87 cells through the activation of NF-kappaB- and ERK-mediated stimulation of MMP-9. CONCLUSIONS: Cycling hypoxia-induced ROS via Nox4 should be considered for therapeutic targeting of tumor cell invasion and infiltration in glioblastoma.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21870211
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10461
      1. Author :
        Ibarra, J. M.; Jimenez, F.; Martinez, H. G.; Clark, K.; Ahuja, S. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Int J Inflam
      6. Products :
      7. Volume :
        2011
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MMPSense, IVIS
      12. Abstract :
        The Standard measures of experimental arthritis fail to detect, visualize, and quantify early inflammation and disease activity. Here, we describe the use of an injectable MMP-activated fluorescence agent for in vivo quantification of acute inflammation produced by collagen-antibody-induced arthritis (CAIA) in CC chemokine receptor-2 (Ccr2(-/-)) null mice. Although Ccr2(-/-) DBA1/J mice were highly susceptible to and rapidly developed CAIA, the standard clinical assessment of fore or hind paw thicknesses was unable to detect significant acute inflammatory changes (days 3-10). Remarkably, noninvasive, in situ, MMP-activatable fluorescent imaging of Ccr2(-/-) DBA1/J mice with CAIA displayed acute joint pathology in advance of clinically measurable acute inflammation (days 5, 7, and 10). These results were confirmed by the histology of ankle joints, which showed significant inflammation, bone loss, and synovial hyperplasia, compared to control mice at postimmunization day 5. The MMP-mediated fluorescence technique holds tremendous implications for quantifiable examination of arthritis disease activity of acute joint inflammation.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21755029
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10462
      1. Author :
        Wallis de Vries, B. M.; van Dam, G. M.; Tio, R. A.; Hillebrands, J. L.; Slart, R. H.; Zeebregts, C. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        J Vasc Surg
      6. Products :
      7. Volume :
        48
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MMPSense, IVIS, Atherosclerosis/complications/*diagnosis; Carotid Stenosis/*diagnosis/etiology; Diagnostic Imaging/*methods; Humans; Reproducibility of Results
      12. Abstract :
        BACKGROUND: There is increasing evidence that plaque vulnerability, rather than the degree of stenosis, is important in predicting the occurrence of subsequent cerebral ischemic events in patients with carotid artery stenosis. The many imaging modalities currently available have different properties with regard to the visualization of the extent of vulnerability in carotid plaque formation. METHODS: Original published studies were identified using the MEDLINE database (January 1966 to March 2008). Manual cross-referencing was also performed. RESULTS: There is no single imaging modality that can produce definitive information about the state of vulnerability of an atherosclerotic plaque. Each has its own specific drawbacks, which may be the use of ionizing radiation or nephrotoxic contrast agents, an invasive character, low patient tolerability, or simply the paucity of information obtained on plaque vulnerability. Functional molecular imaging techniques such as positron emission tomography (PET), single photon emission-computed tomography (SPECT) and near infra-red spectroscopy (NIRS) do seem able accurately to visualize and even quantify features of plaque vulnerability and its pathophysiologic processes. Promising new techniques like near infra-red fluorescence imaging are being developed and may be beneficial in this field. CONCLUSION: There is a promising role for functional molecular imaging modalities like PET, SPECT, or NIRS related to improvement of selection criteria for carotid intervention, especially when combined with CT or MRI to add further anatomical details to molecular information. Further information will be needed to define whether and where this functional molecular imaging will fit into a clinical strategy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18804942
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10464
      1. Author :
        Chen, Y.; Jacamo, R.; Shi, Y. X.; Wang, R. Y.; Battula, V. L.; Konoplev, S.; Strunk, D.; Hofmann, N. A.; Reinisch, A.; Konopleva, M.; Andreeff, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Blood
      6. Products :
      7. Volume :
        119
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, IVIS, Animals; Bone Marrow Cells/*cytology/metabolism/physiology; Bone Marrow Transplantation/*methods/physiology; Cells, Cultured; Cellular Microenvironment/genetics/*physiology; Hematopoiesis, Extramedullary/genetics/*physiology; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism; Interleukin Receptor Common gamma Subunit/genetics; Mice; Mice, Inbred NOD; Mice, SCID; Mice, Transgenic; Models, Animal; Osteogenesis/genetics/physiology; Species Specificity; *Transplantation, Heterotopic
      12. Abstract :
        The interactions between hematopoietic cells and the bone marrow (BM) microenvironment play a critical role in normal and malignant hematopoiesis and drug resistance. These interactions within the BM niche are unique and could be important for developing new therapies. Here, we describe the development of extramedullary bone and bone marrow using human mesenchymal stromal cells and endothelial colony-forming cells implanted subcutaneously into immunodeficient mice. We demonstrate the engraftment of human normal and leukemic cells engraft into the human extramedullary bone marrow. When normal hematopoietic cells are engrafted into the model, only discrete areas of the BM are hypoxic, whereas leukemia engraftment results in widespread severe hypoxia, just as recently reported by us in human leukemias. Importantly, the hematopoietic cell engraftment could be altered by genetical manipulation of the bone marrow microenvironment: Extramedullary bone marrow in which hypoxia-inducible factor 1alpha was knocked down in mesenchymal stromal cells by lentiviral transfer of short hairpin RNA showed significant reduction (50% +/- 6%; P = .0006) in human leukemic cell engraftment. These results highlight the potential of a novel in vivo model of human BM microenvironment that can be genetically modified. The model could be useful for the study of leukemia biology and for the development of novel therapeutic modalities aimed at modifying the hematopoietic microenvironment.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22490334
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10465
      1. Author :
        Kozloff, K. M.; Quinti, L.; Patntirapong, S.; Hauschka, P. V.; Tung, C. H.; Weissleder, R.; Mahmood, U.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Bone
      6. Products :
      7. Volume :
        44
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, IVIS Animals; Animals, Newborn; Bone Development; Bone Resorption/enzymology; Calcification, Physiologic; Cathepsin K; Cathepsins/genetics/*metabolism; Cell Survival; Cells, Cultured; Cryoultramicrotomy; Female; Femur/pathology; Fluorescence; Humans; Mice; Mice, Inbred BALB C; *Molecular Probe Techniques; Molecular Probes/metabolism; Osteoclasts/cytology/*enzymology; Ovariectomy; RNA, Messenger/genetics/metabolism; Up-Regulation
      12. Abstract :
        Osteoclasts degrade bone matrix by demineralization followed by degradation of type I collagen through secretion of the cysteine protease, cathepsin K. Current imaging modalities are insufficient for sensitive observation of osteoclast activity, and in vivo live imaging of osteoclast resorption of bone has yet to be demonstrated. Here, we describe a near-infrared fluorescence reporter probe whose activation by cathepsin K is shown in live osteoclast cells and in mouse models of development and osteoclast upregulation. Cathepsin K probe activity was monitored in live osteoclast cultures and correlates with cathepsin K gene expression. In ovariectomized mice, cathepsin K probe upregulation precedes detection of bone loss by micro-computed tomography. These results are the first to demonstrate non-invasive visualization of bone degrading enzymes in models of accelerated bone loss, and may provide a means for early diagnosis of upregulated resorption and rapid feedback on efficacy of treatment protocols prior to significant loss of bone in the patient.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19007918
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10466
      1. Author :
        Wen, D.; Qing, L.; Harrison, G.; Golub, E.; Akintoye, S. O.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Oral Dis
      6. Products :
      7. Volume :
        17
      8. Issue :
        N/A
      9. Page Numbers :
        427-32
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Maestro, Animals; Bone Density Conservation Agents/administration & dosage/*pharmacokinetics; Bone and Bones/*metabolism; Calcium/metabolism; Chelating Agents; Decalcification Technique; Diphosphonates/administration & dosage/*pharmacokinetics; Durapatite/metabolism; Edetic Acid; Female; Femur/metabolism; Fibula/metabolism; Fluorescent Dyes/diagnostic use; Fluorometry; Humerus/metabolism; Injections, Intravenous; Mandible/metabolism; Models, Animal; Radius/metabolism; Rats; Rats, Nude; Spectrophotometry, Atomic; Tibia/metabolism; Tissue Distribution; Ulna/metabolism
      12. Abstract :
        OBJECTIVES: Bisphosphonates commonly used to treat osteoporosis, Paget's disease, multiple myeloma, hypercalcemia of malignancy and osteolytic lesions of cancer metastasis have been associated with bisphosphonate-associated jaw osteonecrosis (BJON). The underlying pathogenesis of BJON is unclear, but disproportionate bisphosphonate concentration in the jaw has been proposed as one potential etiological factor. This study tested the hypothesis that skeletal biodistribution of intravenous bisphosphonate is anatomic site-dependent in a rat model system. MATERIALS AND METHODS: Fluorescently labeled pamidronate was injected intravenously in athymic rats of equal weights followed by in vivo whole body fluorimetry, ex vivo optical imaging of oral, axial, and appendicular bones and ethylenediaminetetraacetic acid bone decalcification to assess hydroxyapatite-bound bisphosphonate. RESULTS: Bisphosphonate uptake and bisphosphonate released per unit calcium were similar in oral and appendicular bones but lower than those in axial bones. Hydroxyapatite-bound bisphosphonate liberated by sequential acid decalcification was the highest in oral, relative to axial and appendicular bones (P < 0.05). CONCLUSIONS: This study demonstrates regional differences in uptake and release of bisphosphonate from oral, axial, and appendicular bones of immune deficient rats.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21122034
      14. Call Number :
        PKI @ kd.modi @ 11
      15. Serial :
        10467
      1. Author :
        Ale, A.; Ermolayev, V.; Herzog, E.; Cohrs, C.; de Angelis, M. H.; Ntziachristos, V.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Methods
      6. Products :
      7. Volume :
        9
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Bone Remodeling; Disease Models, Animal; Equipment Design; Female; Fluorescence; Head and Neck Neoplasms/pathology/radiography; Image Processing, Computer-Assisted/*methods; Lung Neoplasms/pathology/radiography; Mammary Neoplasms, Experimental/pathology/radiography; Mice; Osteogenesis Imperfecta/pathology/radiography; Tomography, Optical/*methods; Tomography, X-Ray Computed/*methods
      12. Abstract :
        The development of hybrid optical tomography methods to improve imaging performance has been suggested over a decade ago and has been experimentally demonstrated in animals and humans. Here we examined in vivo performance of a camera-based hybrid fluorescence molecular tomography (FMT) system for 360 degrees imaging combined with X-ray computed tomography (XCT). Offering an accurately co-registered, information-rich hybrid data set, FMT-XCT has new imaging possibilities compared to stand-alone FMT and XCT. We applied FMT-XCT to a subcutaneous 4T1 tumor mouse model, an Aga2 osteogenesis imperfecta model and a Kras lung cancer mouse model, using XCT information during FMT inversion. We validated in vivo imaging results against post-mortem planar fluorescence images of cryoslices and histology data. Besides offering concurrent anatomical and functional information, FMT-XCT resulted in the most accurate FMT performance to date. These findings indicate that addition of FMT optics into the XCT gantry may be a potent upgrade for small-animal XCT systems.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22561987
      14. Call Number :
        PKI @ kd.modi @ 12
      15. Serial :
        10468
      1. Author :
        Derwall, M.; Malhotra, R.; Lai, C. S.; Beppu, Y.; Aikawa, E.; Seehra, J. S.; Zapol, W. M.; Bloch, K. D.; Yu, P. B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Arterioscler Thromb Vasc Biol
      6. Products :
      7. Volume :
        32
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Anti-Inflammatory Agents/pharmacology; Antioxidants/pharmacology; Atherosclerosis/etiology/genetics/metabolism/pathology/*prevention & control; Bone Morphogenetic Protein Receptors, Type I/metabolism; Bone Morphogenetic Proteins/*antagonists & inhibitors/metabolism; Cardiovascular Agents/*pharmacology; Cholesterol, LDL/blood; Diet, High-Fat; Disease Models, Animal; Endothelial Cells/drug effects/metabolism; Fatty Liver/etiology/metabolism/prevention & control; Female; Hep G2 Cells; Humans; Lipoproteins, LDL/metabolism; Liver/drug effects/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Pyrazoles/*pharmacology; Pyrimidines/*pharmacology; Reactive Oxygen Species/metabolism; Receptors, LDL/deficiency/genetics; Recombinant Fusion Proteins/metabolism; Signal Transduction/*drug effects; Time Factors; Vascular Calcification/etiology/genetics/metabolism/pathology/*prevention &; control
      12. Abstract :
        OBJECTIVE: The expression of bone morphogenetic proteins (BMPs) is enhanced in human atherosclerotic and calcific vascular lesions. Although genetic gain- and loss-of-function experiments in mice have supported a causal role of BMP signaling in atherosclerosis and vascular calcification, it remains uncertain whether BMP signaling might be targeted pharmacologically to ameliorate both of these processes. METHODS AND RESULTS: We tested the impact of pharmacological BMP inhibition on atherosclerosis and calcification in LDL receptor-deficient (LDLR-/-) mice. LDLR-/- mice fed a high-fat diet developed abundant vascular calcification within 20 weeks. Prolonged treatment of LDLR-/- mice with the small molecule BMP inhibitor LDN-193189 was well-tolerated and potently inhibited development of atheroma, as well as associated vascular inflammation, osteogenic activity, and calcification. Administration of recombinant BMP antagonist ALK3-Fc replicated the antiatherosclerotic and anti-inflammatory effects of LDN-193189. Treatment of human aortic endothelial cells with LDN-193189 or ALK3-Fc abrogated the production of reactive oxygen species induced by oxidized LDL, a known early event in atherogenesis. Unexpectedly, treatment of mice with LDN-193189 lowered LDL serum cholesterol by 35% and markedly decreased hepatosteatosis without inhibiting HMG-CoA reductase activity. Treatment with BMP2 increased, whereas LDN-193189 or ALK3-Fc inhibited apolipoprotein B100 secretion in HepG2 cells, suggesting that BMP signaling contributes to the regulation of cholesterol biosynthesis. CONCLUSION: These results definitively implicate BMP signaling in atherosclerosis and calcification, while uncovering a previously unidentified role for BMP signaling in LDL cholesterol metabolism. BMP inhibition may be helpful in the treatment of atherosclerosis and associated vascular calcification.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22223731
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10469
      1. Author :
        Hjortnaes, J.; New, S. E.; Aikawa, E.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Trends Cardiovasc Med
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense
      12. Abstract :
        Cardiovascular calcification is currently viewed as an active disease process similar to embryonic bone formation. Cardiovascular calcification mainly affects the aortic valve and arteries and is associated with increased mortality risk. Aortic valve and arterial calcification share similar risk factors, including age, gender, diabetes, chronic renal disease, and smoking. However, the exact cellular and molecular mechanism of cardiovascular calcification is unknown. Late-stage cardiovascular calcification can be visualized with conventional imaging modalities such as echocardiography and computed tomography. However, these modalities are limited in their ability to detect the development of early calcification and the progression of calcification until advanced tissue mineralization is apparent. Due to the subsequent late diagnosis of cardiovascular calcification, treatment is usually comprised of invasive interventions such as surgery. The need to understand the process of calcification is therefore warranted and requires new imaging modalities which are able to visualize early cardiovascular calcification. This review focuses on the use of new imaging techniques to visualize novel concepts of cardiovascular calcification.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23290463
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10470
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