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      1. Author :
        Sottnik, Joseph L; U'Ren, Lance W; Thamm, Douglas H; Withrow, Stephen J; Dow, Steven W
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cancer immunology, immunotherapy: CII
      6. Products :
      7. Volume :
        59
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Chronic Disease; Disease Models, Animal; Immunity, Innate; Killer Cells, Natural; Macrophages; Mice; Mice, Inbred C3H; Mice, Inbred Strains; Monocytes; Neoplasms; Neovascularization, Pathologic; Osteomyelitis; Osteosarcoma; Staphylococcal Infections; Xen36
      12. Abstract :
        Clinical studies over the past several years have reported that metastasis-free survival times in humans and dogs with osteosarcoma are significantly increased in patients that develop chronic bacterial osteomyelitis at their surgical site. However, the immunological mechanism by which osteomyelitis may suppress tumor growth has not been investigated. Therefore, we used a mouse model of osteomyelitis to assess the effects of bone infection on innate immunity and tumor growth. A chronic Staphylococcal osteomyelitis model was established in C3H mice and the effects of infection on tumor growth of syngeneic DLM8 osteosarcoma were assessed. The effects of infection on tumor angiogenesis and innate immunity, including NK cell and monocyte responses, were assessed. We found that osteomyelitis significantly inhibited the growth of tumors in mice, and that the effect was independent of the infecting bacterial type, tumor type, or mouse strain. Depletion of NK cells or monocytes reversed the antitumor activity elicited by infection. Moreover, infected mice had a significant increase in circulating monocytes and numbers of tumor associated macrophages. Infection suppressed tumor angiogenesis but did not affect the numbers of circulating endothelial cells. Therefore, we concluded that chronic localized bacterial infection could elicit significant systemic antitumor activity dependent on NK cells and macrophages.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19701748
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9980
      1. Author :
        Mathew, B.; Jacobson, J. R.; Berdyshev, E.; Huang, Y.; Sun, X.; Zhao, Y.; Gerhold, L. M.; Siegler, J.; Evenoski, C.; Wang, T.; Zhou, T.; Zaidi, R.; Moreno-Vinasco, L.; Bittman, R.; Chen, C. T.; LaRiviere, P. J.; Sammani, S.; Lussier, Y. A.; Dudek, S. M.; Natarajan, V.; Weichselbaum, R. R.; Garcia, J. G.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Faseb J
      6. Products :
      7. Volume :
        25
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Bronchoalveolar Lavage Fluid/chemistry; Ceramides/metabolism; Female; Gene Deletion; Gene Expression Regulation/physiology; Lung/*radiation effects; Lysophospholipids/*chemistry/*pharmacology; Mice; Mice, Inbred C57BL; Mice, Knockout; *Radiation Injuries, Experimental; Receptors, Lysosphingolipid/genetics/metabolism; Sphingolipids/*metabolism; Sphingosine/*analogs & derivatives/chemistry/pharmacology
      12. Abstract :
        Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components serve as modulators and novel therapeutic targets of RILI. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to sphingosine 1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage fluid, and lung tissue. Mice with a targeted deletion of SphK1 (SphK1(-/-)) or with reduced expression of S1P receptors (S1PR1(+/-), S1PR2(-/-), and S1PR3(-/-)) exhibited marked RILI susceptibility. Finally, studies of 3 potent vascular barrier-protective S1P analogs, FTY720, (S)-FTY720-phosphonate (fTyS), and SEW-2871, identified significant RILI attenuation and radiation-induced gene dysregulation by the phosphonate analog, fTyS (0.1 and 1 mg/kg i.p., 2x/wk) and to a lesser degree by SEW-2871 (1 mg/kg i.p., 2x/wk), compared with those in controls. These results support the targeting of S1P signaling as a novel therapeutic strategy in RILI.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21712494
      14. Call Number :
        PKI @ kd.modi @ 18
      15. Serial :
        10371
      1. Author :
        Panizzi, P.; Nahrendorf, M.; Figueiredo, J. L.; Panizzi, J.; Marinelli, B.; Iwamoto, Y.; Keliher, E.; Maddur, A. A.; Waterman, P.; Kroh, H. K.; Leuschner, F.; Aikawa, E.; Swirski, F. K.; Pittet, M. J.; Hackeng, T. M.; Fuentes-Prior, P.; Schneewind, O.; Bock, P. E.; Weissleder, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Nat Med
      6. Products :
      7. Volume :
        17
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29, Animals; Coagulase/metabolism; Endocarditis, Bacterial/*diagnosis; Mice; Microscopy, Fluorescence; Positron-Emission Tomography; Protein Engineering; Prothrombin/*diagnostic use/*metabolism; Quorum Sensing/physiology; Staphylococcus aureus/*metabolism/pathogenicity
      12. Abstract :
        Coagulase-positive Staphylococcus aureus (S. aureus) is the major causal pathogen of acute endocarditis, a rapidly progressing, destructive infection of the heart valves. Bacterial colonization occurs at sites of endothelial damage, where, together with fibrin and platelets, the bacteria initiate the formation of abnormal growths known as vegetations. Here we report that an engineered analog of prothrombin could be used to detect S. aureus in endocarditic vegetations via noninvasive fluorescence or positron emission tomography (PET) imaging. These prothrombin derivatives bound staphylocoagulase and intercalated into growing bacterial vegetations. We also present evidence for bacterial quorum sensing in the regulation of staphylocoagulase expression by S. aureus. Staphylocoagulase expression was limited to the growing edge of mature vegetations, where it was exposed to the host and co-localized with the imaging probe. When endocarditis was induced with an S. aureus strain with genetic deletion of coagulases, survival of mice improved, highlighting the role of staphylocoagulase as a virulence factor.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21857652
      14. Call Number :
        PKI @ kd.modi @ 16
      15. Serial :
        10454
      1. Author :
        Neben, Tamlyn Yee; Clermont, Anne O.; Esposito, Lin; Oei, Yoko; Neben, Tamlyn Yee; Jenkins, Darlene E.; Clermont, Anne O.; Esposito, Lin; Oei, Yoko; Jenkins, Darlene E.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        AACR Meeting Abstracts
      6. Products :
      7. Volume :
        2005
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; Lovo-6-luc-1 cells
      12. Abstract :
        Colorectal cancer is the fourth most common cancer in the United States with an estimated 130,000 new cases diagnosed each year. Many cases are asymptomatic and not diagnosed until late stage of disease. Identification of primary tumors at an earlier stage is advantageous in treatment planning and aids in decreasing the morbidity/mortality rate from recurrence. The aim of our studies is to establish a xenograft system for monitoring tumor growth and metastasis in vivo which allows continual evaluation of drug and drug regimen efficacy at all stages of tumor progression. LoVo-6-luc-1, a luciferase expressing cell line derived from LoVo human colorectal adenocarcinoma cells, was injected by various routes (subcutaneous, intraperitoneal and intracecal) into female SCID-bg mice. Tumor growth and metastatic spread was monitored weekly by in vivo imaging using the Xenogen IVISTM imaging platform. Visible bioluminescence signals were detected immediately after injection and high tumor take was seen in all of the models. In the subcutaneous model, we found a high correlation between mean bioluminescence and mean tumor volume. In the intraperitoneal and ceacum injected models, the onset of tumor spread was rapid and ex vivo imaging confirmed metastasis to multiple organs such as liver, lung, kidney, adrenal gland, spleen and ovary.
      13. URL :
        http://www.aacrmeetingabstracts.org/cgi/content/abstract/2005/1/908-d
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9016
      1. Author :
        Rahul Anil Sheth; Umar Mahmood
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        American Journal of Physiology: Gastrointestinal and Liver Physiology
      6. Products :
      7. Volume :
        299
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Colorectal cancer; optical imaging; molecular imaging; cancer genetics
      12. Abstract :
        Colorectal cancer remains a major cause of morbidity and mortality in the United States. The advent of molecular therapies targeted against specific, stereotyped cellular mutations that occur in this disease has ushered in new hope for treatment options. However, key questions regarding the optimal dosing schedules, dosing duration, and patient selection remain unanswered. In this review, we describe how recent advances in molecular imaging, specifically optical molecular imaging with fluorescent probes, offer potential solutions to these questions and may play a key role in improving outcomes. We begin with an overview of optical molecular imaging, including a discussion on the various methods of design for fluorescent probes and the clinically relevant imaging systems that have been built to image them. We then focus on the relevance of optical molecular imaging to colorectal cancer. We review the most recent data on how this imaging modality has been applied to the measurement of treatment efficacy for currently available as well as some as-of-yet developmental molecularly targeted therapies in animal studies. We then conclude with a discussion on how this imaging approach has already begun to be translated clinically for human use.
      13. URL :
        http://ajpgi.physiology.org/cgi/content/abstract/ajpgi.00195.2010v1
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4484
      1. Author :
        Ogunniyi, A. D.; Paton, J. C.; Kirby, A. C.; McCullers, J. A.; Cook, J.; Hyodo, M.; Hayakawa, Y.; Karaolis, D. K.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Vaccine
      6. Products :
      7. Volume :
        26
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen, Xen10
      12. Abstract :
        Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or pneumococcal surface protein A (PspA) before pneumococcal challenge, were investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of Streptococcus pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in a significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and a significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18640167
      14. Call Number :
        141772
      15. Serial :
        5663
      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 :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Proc Natl Acad Sci U S A
      6. Products :
      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
      1. Author :
        Smith, B. R.; Kempen, P.; Bouley, D.; Xu, A.; Liu, Z.; Melosh, N.; Dai, H.; Sinclair, R.; Gambhir, S. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nano Lett
      6. Products :
      7. Volume :
        12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; *Disease Models, Animal; Ear Neoplasms/*blood supply/pathology; Humans; Mice; Microscopy, Fluorescence; Nanoparticles/*chemistry; *Nanotechnology; Nanotubes, Carbon/chemistry; Neoplasms, Experimental/*blood supply/pathology; Particle Size; Quantum Dots; Surface Properties
      12. Abstract :
        Delivery is one of the most critical obstacles confronting nanoparticle use in cancer diagnosis and therapy. For most oncological applications, nanoparticles must extravasate in order to reach tumor cells and perform their designated task. However, little understanding exists regarding the effect of nanoparticle shape on extravasation. Herein we use real-time intravital microscopic imaging to meticulously examine how two different nanoparticles behave across three different murine tumor models. The study quantitatively demonstrates that high-aspect ratio single-walled carbon nanotubes (SWNTs) display extravasational behavior surprisingly different from, and counterintuitive to, spherical nanoparticles although the nanoparticles have similar surface coatings, area, and charge. This work quantitatively indicates that nanoscale extravasational competence is highly dependent on nanoparticle geometry and is heterogeneous.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22650417
      14. Call Number :
        PKI @ kd.modi @ 9
      15. Serial :
        10439
      1. Author :
        Agarwal, A.; Mackey, M. A.; El-Sayed, M. A.; Bellamkonda, R. V.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        ACS Nano
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        4919-26
      10. Research Area :
        N/A
      11. Keywords :
        Annexin Vivo, Annexin-Vivo, IVIS, Animals; Antineoplastic Agents/*administration & dosage; Apoptosis; Cell Line, Tumor; Doxorubicin/*administration & dosage; Drug Carriers; Drug Delivery Systems; Female; Glioblastoma/drug therapy; Gold/chemistry; Humans; Liposomes/*chemistry; Metal Nanoparticles/chemistry; Mice; Mice, Nude; Nanostructures/chemistry; Neoplasms/*drug therapy; Polyethylene Glycols/chemistry
      12. Abstract :
        Delivery of chemotherapeutic agents after encapsulation in nanocarriers such as liposomes diminishes side-effects, as PEGylated nanocarrier pharmacokinetics decrease dosing to healthy tissues and accumulate in tumors due to the enhanced permeability and retention effect. Once in the tumor, however, dosing of the chemotherapeutic to tumor cells is limited potentially by the rate of release from the carriers and the size-constrained, poor diffusivity of nanocarriers in tumor interstitium. Here, we report the design and fabrication of a thermosensitive liposomal nanocarrier that maintains its encapsulation stability with a high concentration of doxorubicin payload, thereby minimizing “leak” and attendant toxicity. When used synergistically with PEGylated gold nanorods and near-infrared stimulation, remote triggered release of doxorubicin from thermosensitive liposomes was achieved in a mouse tumor model of human glioblastoma (U87), resulting in a significant increase in efficacy when compared to nontriggered or nonthermosensitive PEGylated liposomes. This enhancement in efficacy is attributed to increase in tumor-site apoptosis, as was evident from noninvasive apoptosis imaging using Annexin-Vivo 750 probe. This strategy affords remotely triggered control of tumor dosing of nanocarrier-encapsulated doxorubicin without sacrificing the ability to differentially dose drugs to tumors via the enhanced permeation and retention effect.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21591812
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10430
      1. Author :
        Hasenpusch, G.; Pfeifer, C.; Aneja, M. K.; Wagner, K.; Reinhardt, D.; Gilon, M.; Ohana, P.; Hochberg, A.; Rudolph, C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        6
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29, Administration, Inhalation; Aerosols; Animals; Cell Line, Tumor; Cell Proliferation/drug effects; Cell Transformation, Neoplastic; Humans; Lung Neoplasms/drug therapy/genetics/*pathology/*secondary; Mice; Oncogenes/genetics; Plasmids/*administration & dosage/chemistry/*pharmacology; Polyethyleneimine/chemistry
      12. Abstract :
        Despite numerous efforts, drug based treatments for patients suffering from lung cancer remains poor. As a promising alternative, we investigated the therapeutic potential of BC-819 for the treatment of lung cancer in mouse tumor models. BC-819 is a novel plasmid DNA which encodes for the A-fragment of Diphtheria toxin and has previously been shown to successfully inhibit tumor growth in human clinical study of bladder carcinoma. In a first set of experiments, we examined in vitro efficacy of BC-819 in human lung cancer cell-lines NCI-H460, NCI-H358 and A549, which revealed >90% reduction of cell growth. In vivo efficacy was examined in an orthotopic mouse xenograft lung cancer model and in a lung metastasis model using luminescent A549-C8-luc adenocarcinoma cells. These cells resulted in peri- and intra-bronchiolar tumors upon intrabronchial application and parenchymal tumors upon intravenous injection, respectively. Mice suffering from these lung tumors were treated with BC-819, complexed to branched polyethylenimine (PEI) and aerosolized to the mice once per week for a period of 10 weeks. Using this regimen, growth of intrabronchially induced lung tumors was significantly inhibited (p = 0.01), whereas no effect could be observed in mice suffering from lung metastasis. In summary, we suggest that aerosolized PEI/BC-819 is capable of reducing growth only in tumors arising from the luminal part of the airways and are therefore directly accessible for inhaled BC-819.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21687669
      14. Call Number :
        PKI @ kd.modi @ 9
      15. Serial :
        10450
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