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      1. Author :
        Xiao, K.; Li, Y.; Lee, J. S.; Gonik, A. M.; Dong, T.; Fung, G.; Sanchez, E.; Xing, L.; Cheng, H. R.; Luo, J.; Lam, K. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        72
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        SKOV3-luc-D3, SKOV3-luc, IVIS, Ovarian Cancer, Animals; Antineoplastic Agents, Phytogenic/*administration & dosage; Cell Line, Tumor; Drug Carriers/*chemical synthesis/chemistry/therapeutic use; Drug Delivery Systems/*methods; Female; Flow Cytometry; Humans; Integrin alpha Chains/metabolism; Mice; Mice, Nude; Micelles; Microscopy, Confocal; Nanoparticles/chemistry/therapeutic use; Ovarian Neoplasms/*drug therapy; Paclitaxel/*administration & dosage; Peptides/chemical synthesis/therapeutic use; Polyethylene Glycols/chemistry
      12. Abstract :
        Micellar nanoparticles based on linear polyethylene glycol (PEG) block dendritic cholic acids (CA) copolymers (telodendrimers), for the targeted delivery of chemotherapeutic drugs in the treatment of cancers, are reported. The micellar nanoparticles have been decorated with a high-affinity “OA02” peptide against alpha-3 integrin receptor to improve the tumor-targeting specificity which is overexpressed on the surface of ovarian cancer cells. “Click chemistry” was used to conjugate alkyne-containing OA02 peptide to the azide group at the distal terminus of the PEG chain in a representative PEG(5k)-CA(8) telodendrimer (micelle-forming unit). The conjugation of OA02 peptide had negligible influence on the physicochemical properties of PEG(5k)-CA(8) nanoparticles and as hypothesized, OA02 peptide dramatically enhanced the uptake efficiency of PEG(5k)-CA(8) nanoparticles (NP) in SKOV-3 and ES-2 ovarian cancer cells via receptor-mediated endocytosis, but not in alpha-3 integrin-negative K562 leukemia cells. When loaded with paclitaxel, OA02-NPs had significantly higher in vitro cytotoxicity against both SKOV-3 and ES-2 ovarian cancer cells as compared with nontargeted nanoparticles. Furthermore, the in vivo biodistribution study showed OA02 peptide greatly facilitated tumor localization and the intracellular uptake of PEG(5k)-CA(8) nanoparticles into ovarian cancer cells as validated in SKOV3-luc tumor-bearing mice. Finally, paclitaxel (PTX)-loaded OA02-NPs exhibited superior antitumor efficacy and lower systemic toxicity profile in nude mice bearing SKOV-3 tumor xenografts, when compared with equivalent doses of nontargeted PTX-NPs as well as clinical paclitaxel formulation (Taxol). Therefore, OA02-targeted telodendrimers loaded with paclitaxel have great potential as a new therapeutic approach for patients with ovarian cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22396491
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10543
      1. Author :
        Reppert, S.; Boross, I.; Koslowski, M.; Tureci, O.; Koch, S.; Lehr, H. A.; Finotto, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Nat Commun
      6. Products :
      7. Volume :
        2
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        LL/2-luc-M38, LL/2-luc, Lewis Lung Carcinoma, IVIS, Adenocarcinoma/drug therapy/genetics/*immunology/metabolism/pathology; Administration, Intranasal; Adult; Aged; Animals; Antibodies, Neutralizing/administration & dosage/*therapeutic use; Antigens, CD/immunology; Female; Forkhead Transcription Factors/genetics/*immunology/metabolism; Gene Expression Regulation, Neoplastic/drug effects/*immunology; Humans; Immunologic Surveillance; Interferon-gamma/biosynthesis/immunology; Interleukin-17/immunology/metabolism; Interleukin-23/immunology/metabolism; Lung/drug effects/*immunology/metabolism/pathology; Lung Neoplasms/drug therapy/genetics/*immunology/metabolism/pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; T-Box Domain Proteins/deficiency/*genetics/immunology; T-Lymphocytes, Regulatory/immunology
      12. Abstract :
        Lung cancer is the leading cause of cancer deaths worldwide. The cytokine interleukin-17A supports tumour vascularization and growth, however, its role in lung cancer is unknown. Here we show, in the lungs of patients with lung adenocarcinoma, an increase in interleukin-17A that is inversely correlated with the expression of T-bet and correlated with the T regulatory cell transcription factor Foxp3. Local targeting of interleukin-17A in experimental lung adenocarcinoma results in a reduction in tumour load, local expansion of interferon-gamma-producing CD4(+) T cells and a reduction in lung CD4(+)CD25(+)Foxp3(+) regulatory T cells. T-bet((-/-)) mice have a significantly higher tumour load compared with wild-type mice. This is associated with the local upregulation of interleukin-23 and induction of interleukin-17A/interleukin-17R-expressing T cells infiltrating the tumour. Local anti-interleukin-17A antibody treatment partially improves the survival of T-bet((-/-)) mice. These results suggest that local anti-interleukin-17A antibody therapy could be considered for the treatment of lung tumours.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22186896
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10544
      1. Author :
        Lee, S. K.; Han, M. S.; Asokan, S.; Tung, C. H.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Small
      6. Products :
      7. Volume :
        7
      8. Issue :
        N/A
      9. Page Numbers :
        364-70
      10. Research Area :
        N/A
      11. Keywords :
        LnCaP-luc2, Prostate Cancer, IVIS, *Gene Silencing; *Gold; Metal Nanoparticles/*chemistry/ultrastructure; Microscopy, Electron, Transmission; Polylysine/chemistry; RNA, Small Interfering/*genetics
      12. Abstract :
        Small interfering RNA (siRNA) has been widely proposed to treat various diseases by silencing genes, but its delivery remains a challenge. A well controlled assembly approach is applied to prepare a protease-assisted nanodelivery system. Protease-degradable poly-L-lysine (PLL) and siRNA are fabricated onto gold nanoparticles (AuNPs), by alternating the charged polyelectrolytes. In this study, up to 4 layers of PLL and 3 layers of siRNA (sR3P) are coated. Due to the slow degradation of PLL, the incorporated siRNA is released gradually and shows extended gene-silencing effects. Importantly, the inhibition effect in cells is found to correlate with the number of siRNA layers.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21294265
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10547
      1. Author :
        Ragas, X.; Sanchez-Garcia, D.; Ruiz-Gonzalez, R.; Dai, T.; Agut, M.; Hamblin, M. R.; Nonell, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        J Med Chem
      6. Products :
      7. Volume :
        53
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen31, Xen 31, MRSA, S. aureus, IVIS, Bioluminescence, Animals; Bacterial Infections/*drug therapy; Burns/drug therapy/microbiology; Candida/drug effects; Cations; Gram-Negative Bacteria/drug effects; Gram-Positive Bacteria/drug effects; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; *Photochemotherapy; Photosensitizing Agents/*chemical synthesis/chemistry/pharmacology; Porphyrins/*chemical synthesis/chemistry/pharmacology; Solubility; Staphylococcal Infections/drug therapy/microbiology; Structure-Activity Relationship
      12. Abstract :
        Structures of typical photosensitizers used in antimicrobial photodynamic therapy are based on porphyrins, phthalocyanines, and phenothiazinium salts, with cationic charges at physiological pH values. However, derivatives of the porphycene macrocycle (a structural isomer of porphyrin) have barely been investigated as antimicrobial agents. Therefore, we report the synthesis of the first tricationic water-soluble porphycene and its basic photochemical properties. We successfully tested it for in vitro photoinactivation of different Gram-positive and Gram-negative bacteria, as well as a fungal species (Candida) in a drug-dose and light-dose dependent manner. We also used the cationic porphycene in vivo to treat an infection model comprising mouse third degree burns infected with a bioluminescent methicillin-resistant Staphylococcus aureus strain. There was a 2.6-log(10) reduction (p < 0.001) of the bacterial bioluminescence for the PDT-treated group after irradiation with 180 J.cm(-2) of red light.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20936792
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10555
      1. Author :
        Nguyen, V. H.; Kim, H. S.; Ha, J. M.; Hong, Y.; Choy, H. E.; Min, J. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        70
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen26, Xen 26, Salmonella typhumurium, Animals; Blotting, Western; Cell Line, Tumor; Diagnostic Imaging/methods; Gene Therapy/*methods; Genetic Engineering/*methods; Genetic Vectors/*therapeutic use; Humans; Male; Mice; Mice, Inbred BALB C; Neoplasms/*therapy; Perforin/*genetics/therapeutic use; Promoter Regions, Genetic; Salmonella typhimurium/*genetics; bcl-Associated Death Protein/genetics
      12. Abstract :
        Tumor-targeting bacteria have been studied in terms of their ability to visualize the infection pathway (through imaging probes) or to carry therapeutic molecules to tumors. To integrate these monitoring and therapeutic functions, we engineered attenuated Salmonella typhimurium defective in guanosine 5'-diphosphate-3'-diphosphate synthesis to carry cytotoxic proteins (cytolysin A) and express reporter genes. We successfully visualized the therapeutic process with these engineered bacteria in mice and found that they often mediated complete tumor (CT-26) eradication on cytotoxic gene induction. Furthermore, treatment with the engineered bacteria markedly suppressed metastatic tumor growth.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20028866
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10560
      1. Author :
        Lu, Z.; Dai, T.; Huang, L.; Kurup, D. B.; Tegos, G. P.; Jahnke, A.; Wharton, T.; Hamblin, M. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Nanomedicine (Lond)
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen44, Xen 44, Proteus mirabilis, bioluminescence imaging, Animals; Fullerenes/*chemistry; Male; Mice; Mice, Inbred BALB C; Photochemotherapy/*methods; Photosensitizing Agents/*chemistry; Pseudomonas Infections/*drug therapy; Pseudomonas aeruginosa/drug effects; Wound Infection/*drug therapy
      12. Abstract :
        AIMS: Fullerenes are under intensive study for potential biomedical applications. We have previously reported that a C60 fullerene functionalized with three dimethylpyrrolidinium groups (BF6) is a highly active broad-spectrum antimicrobial photosensitizer in vitro when combined with white-light illumination. We asked whether this high degree of in vitro activity would translate into an in vivo therapeutic effect in two potentially lethal mouse models of infected wounds. MATERIALS & METHODS: We used stable bioluminescent bacteria and a low light imaging system to follow the progress of the infection noninvasively in real time. An excisional wound on the mouse back was contaminated with one of two bioluminescent Gram-negative species, Proteus mirabilis (2.5 x 10(7) cells) and Pseudomonas aeruginosa (5 x 10(6) cells). A solution of BF6 was placed into the wound followed by delivery of up to 180 J/cm(2) of broadband white light (400-700 nm). RESULTS: In both cases there was a light-dose-dependent reduction of bioluminescence from the wound not observed in control groups (light alone or BF6 alone). Fullerene-mediated photodynamic therapy of mice infected with P. mirabilis led to 82% survival compared with 8% survival without treatment (p < 0.001). Photodynamic therapy of mice infected with highly virulent P. aeruginosa did not lead to survival, but when photodynamic therapy was combined with a suboptimal dose of the antibiotic tobramycin (6 mg/kg for 1 day) there was a synergistic therapeutic effect with a survival of 60% compared with a survival of 20% with tobramycin alone (p < 0.01). CONCLUSION: These data suggest that cationic fullerenes have clinical potential as an antimicrobial photosensitizer for superficial infections where red light is not needed to penetrate tissue.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21143031
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10563
      1. Author :
        Lorentzen, D.; Durairaj, L.; Pezzulo, A. A.; Nakano, Y.; Launspach, J.; Stoltz, D. A.; Zamba, G.; McCray, P. B., Jr.; Zabner, J.; Welsh, M. J.; Nauseef, W. M.; Banfi, B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Free Radic Biol Med
      6. Products :
      7. Volume :
        50
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen8.1, Xen 8.1, S. aureus, IVIS, bioluminescence imaging
      12. Abstract :
        A recently discovered enzyme system produces antibacterial hypothiocyanite (OSCN(-)) in the airway lumen by oxidizing the secreted precursor thiocyanate (SCN(-)). Airway epithelial cultures have been shown to secrete SCN(-) in a CFTR-dependent manner. Thus, reduced SCN(-) availability in the airway might contribute to the pathogenesis of cystic fibrosis (CF), a disease caused by mutations in the CFTR gene and characterized by an airway host defense defect. We tested this hypothesis by analyzing the SCN(-) concentration in the nasal airway surface liquid (ASL) of CF patients and non-CF subjects and in the tracheobronchial ASL of CFTR-DeltaF508 homozygous pigs and control littermates. In the nasal ASL, the SCN(-) concentration was ~30-fold higher than in serum independent of the CFTR mutation status of the human subject. In the tracheobronchial ASL of CF pigs, the SCN(-) concentration was somewhat reduced. Among human subjects, SCN(-) concentrations in the ASL varied from person to person independent of CFTR expression, and CF patients with high SCN(-) levels had better lung function than those with low SCN(-) levels. Thus, although CFTR can contribute to SCN(-) transport, it is not indispensable for the high SCN(-) concentration in ASL. The correlation between lung function and SCN(-) concentration in CF patients may reflect a beneficial role for SCN(-).
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21334431
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10564
      1. Author :
        Lin, S. A.; Patel, M.; Suresch, D.; Connolly, B.; Bao, B.; Groves, K.; Rajopadhye, M.; Peterson, J. D.; Klimas, M.; Sur, C.; Bednar, B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Int J Mol Imaging
      6. Products :
      7. Volume :
        2012
      8. Issue :
        N/A
      9. Page Numbers :
        189254
      10. Research Area :
        N/A
      11. Keywords :
        FMT, Prosense, CatB, Cathepsin B, fluorescence imaing, tomography, microCT
      12. Abstract :
        Inflammation as a core pathological event of atherosclerotic lesions is associated with the secretion of cathepsin proteases and the expression of alpha(v)beta(3) integrin. We employed fluorescence molecular tomographic (FMT) noninvasive imaging of these molecular activities using cathepsin sensing (ProSense, CatB FAST) and alpha(v)beta(3) integrin (IntegriSense) near-infrared fluorescence (NIRF) agents. A statistically significant increase in the ProSense and IntegriSense signal was observed within the chest region of apoE(-/-) mice (P < 0.05) versus C57BL/6 mice starting 25 and 22 weeks on high cholesterol diet, respectively. In a treatment study using ezetimibe (7 mg/kg), there was a statistically significant reduction in the ProSense and CatB FAST chest signal of treated (P < 0.05) versus untreated apoE(-/-) mice at 31 and 21 weeks on high cholesterol diet, respectively. The signal of ProSense and CatB FAST correlated with macrophage counts and was found associated with inflammatory cells by fluorescence microscopy and flow cytometry of cells dissociated from aortas. This report demonstrates that cathepsin and alpha(v)beta(3) integrin NIRF agents can be used as molecular imaging biomarkers for longitudinal detection of atherosclerosis, and cathepsin agents can monitor anti-inflammatory effects of ezetimibe with applications in preclinical testing of therapeutics and potentially for early diagnosis of atherosclerosis in patients.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23119157
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10571
      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
      1. Author :
        Snoeks, T. J.; Lowik, C. W.; Kaijzel, E. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Angiogenesis
      6. Products :
      7. Volume :
        13
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense,, Animals; Diagnostic Imaging/*methods; Fluorescent Dyes/metabolism; Genes, Reporter; Neovascularization, Pathologic/*diagnosis; *Optical Phenomena
      12. Abstract :
        In recent years, molecular imaging gained significant importance in biomedical research. Optical imaging developed into a modality which enables the visualization and quantification of all kinds of cellular processes and cancerous cell growth in small animals. Novel gene reporter mice and cell lines and the development of targeted and cleavable fluorescent “smart” probes form a powerful imaging toolbox. The development of systems collecting tomographic bioluminescence and fluorescence data enabled even more spatial accuracy and more quantitative measurements. Here we describe various bioluminescent and fluorescent gene reporter models and probes that can be used to specifically image and quantify neovascularization or the angiogenic process itself.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20449766
      14. Call Number :
        PKI @ kd.modi @ 10
      15. Serial :
        10379
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