1. Resources
  2. Citations Library

Headers act as filters

  • Records
      1. Author :
        Goldberg, M. S.; Xing, D.; Ren, Y.; Orsulic, S.; Bhatia, S. N.; Sharp, P. A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Proc Natl Acad Sci U S A
      6. Products :
      7. Volume :
        108
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        VivoTag, IVIS, Vivotag, Animals; BRCA1 Protein/*genetics; Drug Carriers; Drug Delivery Systems; Female; Humans; Mice; Nanoparticles/*chemistry; Nanotechnology/methods; Neoplasm Transplantation; Ovarian Neoplasms/*genetics/*therapy; Poly(ADP-ribose) Polymerases/*genetics; RNA Interference; RNA, Small Interfering/*metabolism; Treatment Outcome
      12. Abstract :
        Inhibition of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) with small molecules has been shown to be an effective treatment for ovarian cancer with BRCA mutations. Here, we report the in vivo administration of siRNA to Parp1 in mouse models of ovarian cancer. A unique member of the lipid-like materials known as lipidoids is shown to deliver siRNA to disseminated murine ovarian carcinoma allograft tumors following intraperitoneal (i.p.) injection. siParp1 inhibits cell growth, primarily by induction of apoptosis, in Brca1-deficient cells both in vitro and in vivo. Additionally, the treatment extends the survival of mice bearing tumors derived from Brca1-deficient ovarian cancer cells but not from Brca1 wild-type cells, confirming the proposed mechanism of synthetic lethality. Because there are 17 members of the Parp family, the inherent complementarity of RNA affords a high level of specificity for therapeutically addressing Parp1 in the context of impaired homologous recombination.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21187397
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10566
      1. Author :
        Kwong, G. A.; von Maltzahn, G.; Murugappan, G.; Abudayyeh, O.; Mo, S.; Papayannopoulos, I. A.; Sverdlov, D. Y.; Liu, S. B.; Warren, A. D.; Popov, Y.; Schuppan, D.; Bhatia, S. N.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Biotechnol
      6. Products :
      7. Volume :
        31
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        VivoTag, IVIS, Vivotag
      12. Abstract :
        Biomarkers are becoming increasingly important in the clinical management of complex diseases, yet our ability to discover new biomarkers remains limited by our dependence on endogenous molecules. Here we describe the development of exogenously administered 'synthetic biomarkers' composed of mass-encoded peptides conjugated to nanoparticles that leverage intrinsic features of human disease and physiology for noninvasive urinary monitoring. These protease-sensitive agents perform three functions in vivo: they target sites of disease, sample dysregulated protease activities and emit mass-encoded reporters into host urine for multiplexed detection by mass spectrometry. Using mouse models of liver fibrosis and cancer, we show that these agents can noninvasively monitor liver fibrosis and resolution without the need for invasive core biopsies and substantially improve early detection of cancer compared with current clinically used blood biomarkers. This approach of engineering synthetic biomarkers for multiplexed urinary monitoring should be broadly amenable to additional pathophysiological processes and point-of-care diagnostics.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23242163
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10567
      1. Author :
        Tafreshi, N. K.; Bui, M. M.; Bishop, K.; Lloyd, M. C.; Enkemann, S. A.; Lopez, A. S.; Abrahams, D.; Carter, B. W.; Vagner, J.; Grobmyer, S. R.; Gillies, R. J.; Morse, D. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Clin Cancer Res
      6. Products :
      7. Volume :
        18
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        VivoTag, IVIS, Vivotag, Animals; Antibodies, Monoclonal/*diagnostic use/immunology/pharmacokinetics; Antigens, Neoplasm/*metabolism; Blotting, Western; Breast/immunology/metabolism/pathology; Breast Neoplasms/*diagnosis/immunology/metabolism; Carbonic Anhydrases/*metabolism; Carcinoma, Ductal, Breast/*diagnosis/immunology/metabolism; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/immunology/metabolism; *Diagnostic Imaging; Female; Fluorescent Antibody Technique; Gene Expression Profiling; Humans; Luciferases/metabolism; Luminescent Measurements; Lymphatic Metastasis; Mice; Mice, Nude; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; RNA, Messenger/genetics; Real-Time Polymerase Chain Reaction; Tissue Array Analysis; Tissue Distribution; Tumor Cells, Cultured; Tumor Markers, Biological/genetics/metabolism
      12. Abstract :
        PURPOSE: To develop targeted molecular imaging probes for the noninvasive detection of breast cancer lymph node metastasis. EXPERIMENTAL DESIGN: Six cell surface or secreted markers were identified by expression profiling and from the literature as being highly expressed in breast cancer lymph node metastases. Two of these markers were cell surface carbonic anhydrase isozymes (CAIX and/or CAXII) and were validated for protein expression by immunohistochemistry of patient tissue samples on a breast cancer tissue microarray containing 47 normal breast tissue samples, 42 ductal carcinoma in situ, 43 invasive ductal carcinomas without metastasis, 46 invasive ductal carcinomas with metastasis, and 49 lymph node macrometastases of breast carcinoma. Targeted probes were developed by conjugation of CAIX- and CAXII-specific monoclonal antibodies to a near-infrared fluorescent dye. RESULTS: Together, these two markers were expressed in 100% of the lymph node metastases surveyed. Selectivity of the imaging probes were confirmed by intravenous injection into nude mice-bearing mammary fat pad tumors of marker-expressing cells and nonexpressing cells or by preinjection of unlabeled antibody. Imaging of lymph node metastases showed that peritumorally injected probes detected nodes harboring metastatic tumor cells. As few as 1,000 cells were detected, as determined by implanting, under ultrasound guidance, a range in number of CAIX- and CAXII-expressing cells into the axillary lymph nodes. CONCLUSION: These imaging probes have potential for noninvasive staging of breast cancer in the clinic and elimination of unneeded surgery, which is costly and associated with morbidities.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22016510
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10568
      1. Author :
        Vujanovic, L.; Ballard, W.; Thorne, S. H.; Vujanovic, N. L.; Butterfield, L. H.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Oncoimmunology
      6. Products :
      7. Volume :
        1
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        VivoTag, IVIS, Vivotag
      12. Abstract :
        Recombinant adenovirus-engineered dendritic cells (Ad.DC) are potent vaccines for induction of anti-viral and anti-cancer T cell immunity. The effectiveness of Ad.DC vaccines may depend on the newly described ability of Ad.DC to crosstalk with natural killer (NK) cells via cell-to-cell contact, and to mediate activation, polarization and bridging of innate and adaptive immunity. For this interaction to occur in vivo, Ad.DC must be able to attract NK cells from surrounding tissues or peripheral blood. We developed a novel live mouse imaging system-based NK-cell migration test, and demonstrated for the first time that human Ad.DC induced directional migration of human NK cells across subcutaneous tissues, indicating that Ad.DC-NK cell contact and interaction could occur in vivo. We examined the mechanism of Ad.DC-induced migration of NK cells in vitro and in vivo. Ad.DC produced multiple chemokines previously reported to recruit NK cells, including immunoregulatory CXCL10/IP-10 and proinflammatory CXCL8/IL-8. In vitro chemotaxis experiments utilizing neutralizing antibodies and recombinant human chemokines showed that CXCL10/IP-10 and CXCL8/IL-8 were critical for Ad.DC-mediated recruitment of CD56(hi)CD16(-) and CD56(lo)CD16(+) NK cells, respectively. The importance of CXCL8/IL-8 was further demonstrated in vivo. Pretreatment of mice with the neutralizing anti-CXCL8/IL-8 antibody led to significant inhibition of Ad.DC-induced migration of NK cells in vivo. These data show that Ad.DC can recruit spatially distant NK cells toward a vaccine site via specific chemokines. Therefore, an Ad.DC vaccine can likely induce interaction with endogenous NK cells via transmembrane mediators, and consequently mediate Th1 polarization and amplification of immune functions in vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22754763
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10570
      1. Author :
        Lee, H. L.; Chen, C. C.; Baasov, T.; Ron, Y.; Dougherty, J. P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Mol Ther
      6. Products :
      7. Volume :
        19
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        RediJect Coelenterazine h, XenoLight
      12. Abstract :
        Cells have developed a mechanism to discriminate between premature termination codons (PTCs) and normal stop codons during translation, sparking vigorous research to develop drugs promoting readthrough at PTCs to treat genetic disorders caused by PTCs. It was posed that this concept could also be applied to regulated gene therapy protocols by incorporating a PTC into a therapeutic gene, so active protein would only be made after administration of a readthrough agent. The strengths of the system are highlighted here by results demonstrating: (i) background expression levels were reduced to 0.01% to 0.0005% of wild type in unselected mass populations of cells depending upon the specific stop codon utilized and its position within the gene; (ii) expression levels responded well to multiple “On” and “Off” regulation cycles in vivo in human xenograft systems; (iii) the level of induction approached three logs using aminoglycoside activators including NB54, a newly synthesized aminoglycoside with significantly reduced toxicity; and (iv) expression levels could be appreciably altered when employing different promoters in a variety of cell types. These results strongly support the contention that this system should have important clinical applications when tight control of gene expression is required.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21587212
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10422
      1. Author :
        Cernak, I.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Front Neurol
      6. Products :
      7. Volume :
        1
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, RediJect Inflammation Probe, chemiluminescence, XenoLight
      12. Abstract :
        Due to complex injurious environment where multiple blast effects interact with the body parallel, blast-induced neurotrauma is a unique clinical entity induced by systemic, local, and cerebral responses. Activation of autonomous nervous system; sudden pressure increase in vital organs such as lungs and liver; and activation of neuroendocrine-immune system are among the most important mechanisms that contribute significantly to molecular changes and cascading injury mechanisms in the brain. It has been hypothesized that vagally mediated cerebral effects play a vital role in the early response to blast: this assumption has been supported by experiments where bilateral vagotomy mitigated bradycardia, hypotension, and apnea, and also prevented excessive metabolic alterations in the brain of animals exposed to blast. Clinical experience suggests specific blast-body-nervous system interactions such as (1) direct interaction with the head either through direct passage of the blast wave through the skull or by causing acceleration and/or rotation of the head; and (2) via hydraulic interaction, when the blast overpressure compresses the abdomen and chest, and transfers its kinetic energy to the body's fluid phase, initiating oscillating waves that traverse the body and reach the brain. Accumulating evidence suggests that inflammation plays important role in the pathogenesis of long-term neurological deficits due to blast. These include memory decline, motor function and balance impairments, and behavioral alterations, among others. Experiments using rigid body- or head protection in animals subjected to blast showed that head protection failed to prevent inflammation in the brain or reduce neurological deficits, whereas body protection was successful in alleviating the blast-induced functional and morphological impairments in the brain.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21206523
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10420
      1. Author :
        Cheung, R.; Shen, F.; Phillips, J. H.; McGeachy, M. J.; Cua, D. J.; Heyworth, P. G.; Pierce, R. H.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Clin Invest
      6. Products :
      7. Volume :
        121
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, RediJect Inflammation Probe, chemiluminescence, XenoLight, Adaptor Proteins, Signal Transducing/metabolism; Animals; Cell Differentiation; Concanavalin A/toxicity; Dengue Hemorrhagic Fever/etiology; Disease Models, Animal; Disease Progression; Female; Humans; Immunity, Innate; Intracellular Signaling Peptides and Proteins/metabolism; Lectins, C-Type/deficiency/genetics/*immunology; Liver/metabolism/pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Immunological; Myeloid Cells/*immunology/pathology; Nitric Oxide/biosynthesis; Nitric Oxide Synthase Type II/metabolism; Nitric Oxide Synthase Type III/metabolism; Phosphatidylinositol 3-Kinases/metabolism; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins c-akt/metabolism; Receptors, Cell Surface/deficiency/genetics/*immunology; Receptors, Immunologic/metabolism; Shock/*etiology/*immunology/metabolism/pathology; Signal Transduction; Systemic Inflammatory Response; Syndrome/etiology/immunology/metabolism/pathology; Tumor Necrosis Factor-alpha/biosynthesis
      12. Abstract :
        Systemic inflammatory response syndrome (SIRS) is a potentially lethal condition, as it can progress to shock, multi-organ failure, and death. It can be triggered by infection, tissue damage, or hemorrhage. The role of tissue injury in the progression from SIRS to shock is incompletely understood. Here, we show that treatment of mice with concanavalin A (ConA) to induce liver injury triggered a G-CSF-dependent hepatic infiltration of CD11b+Gr-1+Ly6G+Ly6C+ immature myeloid cells that expressed the orphan receptor myeloid DAP12-associated lectin-1 (MDL-1; also known as CLEC5A). Activation of MDL-1 using dengue virus or an agonist MDL-1-specific antibody in the ConA-treated mice resulted in shock. The MDL-1+ cells were pathogenic, and in vivo depletion of MDL-1+ cells provided protection. Triggering MDL-1 on these cells induced production of NO and TNF-alpha, which were found to be elevated in the serum of treated mice and required for MDL-1-induced shock. Surprisingly, MDL-1-induced NO and TNF-alpha production required eNOS but not iNOS. Activation of DAP12, DAP10, Syk, PI3K, and Akt was critical for MDL-1-induced shock. In addition, Akt physically interacted with and activated eNOS. Therefore, triggering of MDL-1 on immature myeloid cells and production of NO and TNF-alpha may play a critical role in the pathogenesis of shock. Targeting the MDL-1/Syk/PI3K/Akt/eNOS pathway represents a potential new therapeutic strategy to prevent the progression of SIRS to shock.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22005300
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10421
      1. Author :
        Zhang, J.; Preda, D. V.; Vasquez, K. O.; Morin, J.; Delaney, J.; Bao, B.; Percival, M. D.; Xu, D.; McKay, D.; Klimas, M.; Bednar, B.; Sur, C.; Gao, D. Z.; Madden, K.; Yared, W.; Rajopadhye, M.; Peterson, J. D.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Am J Physiol Renal Physiol
      6. Products :
      7. Volume :
        303
      8. Issue :
        N/A
      9. Page Numbers :
        F593-603
      10. Research Area :
        N/A
      11. Keywords :
        ReninSense 680 FAST, FMT, Animal Feed/analysis; Animals; Cathepsin D; Cathepsin G; Female; Fluorescent Dyes/*pharmacology; Humans; Mice; Mice, Inbred C57BL; Peptides/*pharmacology; Peptidyl-Dipeptidase A/metabolism; Rats; Renin/*blood/*metabolism; Renin-Angiotensin System/physiology; Sensitivity and Specificity; Sodium, Dietary
      12. Abstract :
        The renin-angiotensin system (RAS) is well studied for its regulation of blood pressure and fluid homeostasis, as well as for increased activity associated with a variety of diseases and conditions, including cardiovascular disease, diabetes, and kidney disease. The enzyme renin cleaves angiotensinogen to form angiotensin I (ANG I), which is further cleaved by angiotensin-converting enzyme to produce ANG II. Although ANG II is the main effector molecule of the RAS, renin is the rate-limiting enzyme, thus playing a pivotal role in regulating RAS activity in hypertension and organ injury processes. Our objective was to develop a near-infrared fluorescent (NIRF) renin-imaging agent for noninvasive in vivo detection of renin activity as a measure of tissue RAS and in vitro plasma renin activity. We synthesized a renin-activatable agent, ReninSense 680 FAST (ReninSense), using a NIRF-quenched substrate derived from angiotensinogen that is cleaved specifically by purified mouse and rat renin enzymes to generate a fluorescent signal. This agent was assessed in vitro, in vivo, and ex vivo to detect and quantify increases in plasma and kidney renin activity in sodium-sensitive inbred C57BL/6 mice maintained on a low dietary sodium and diuretic regimen. Noninvasive in vivo fluorescence molecular tomographic imaging of the ReninSense signal in the kidney detected increased renin activity in the kidneys of hyperreninemic C57BL/6 mice. The agent also effectively detected renin activity in ex vivo kidneys, kidney tissue sections, and plasma samples. This approach could provide a new tool for assessing disorders linked to altered tissue and plasma renin activity and to monitor the efficacy of therapeutic treatments.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22674025
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10572