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      1. Author :
        Zollo, M.; Di Dato, V.; Spano, D.; De Martino, D.; Liguori, L.; Marino, N.; Vastolo, V.; Navas, L.; Garrone, B.; Mangano, G.; Biondi, G.; Guglielmotti, A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Clin Exp Metastasis
      6. Products :
      7. Volume :
        29
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        PC-3M-luc2, PC3M-luc2, IVIS, Prostate Cancer, Bioware, Animals; Breast Neoplasms/*pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chemokine CCL2/*biosynthesis/chemistry/metabolism; Female; Humans; Indazoles/*pharmacology; Macrophages/metabolism; Male; Mice; Mice, Inbred BALB C; NF-kappa B/metabolism; Neoplasm Metastasis; Neoplasm Transplantation; Propionates/*pharmacology; Prostatic Neoplasms/*pathology; Signal Transduction
      12. Abstract :
        Prostate and breast cancer are major causes of death worldwide, mainly due to patient relapse upon disease recurrence through formation of metastases. Chemokines are small proteins with crucial roles in the immune system, and their regulation is finely tuned in early inflammatory responses. They are key molecules during inflammatory processes, and many studies are focusing on their regulatory functions in tumor growth and angiogenesis during metastatic cell seeding and spreading. Bindarit is an anti-inflammatory indazolic derivative that can inhibit the synthesis of MCP-1/CCL2, with a potential inhibitory function in tumor progression and metastasis formation. We show here that in vitro, bindarit can modulate cancer-cell proliferation and migration, mainly through negative regulation of TGF-beta and AKT signaling, and it can impair the NF-kappaB signaling pathway through enhancing the expression of the NF-kappaB inhibitor IkB-alpha. In vivo administration of bindarit results in impaired metastatic disease in prostate cancer xenograft mice (PC-3M-Luc2 cells injected intra-cardially) and impairment of local tumorigenesis in syngeneic Balb/c mice injected under the mammary gland with murine breast cancer cells (4T1-Luc cells). In addition, bindarit treatment significantly decreases the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in 4T1-Luc primary tumors. Overall, our data indicate that bindarit is a good candidate for new therapies against prostate and breast tumorigenesis, with an action through impairment of inflammatory cell responses during formation of the tumor-stroma niche microenvironment.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22484917
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10489
      1. Author :
        Kim, J. K.; Won, Y. W.; Lim, K. S.; Kim, Y. H.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Pharm Res
      6. Products :
      7. Volume :
        29
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, Animals; Antineoplastic Agents/*administration & dosage/pharmacokinetics/therapeutic use; Delayed-Action Preparations/*chemistry; Male; Methylcellulose/*chemistry; Mice; Mice, Inbred C57BL; *Micelles; Neoplasms/drug therapy; Poloxamer/*chemistry; Taxoids/*administration & dosage/pharmacokinetics/therapeutic use
      12. Abstract :
        PURPOSE: To develop low-molecular-weight methylcellulose (LMw MC)-based gel/Pluronic F127 micelle combination system for local and sustained delivery of docetaxel (DTX). METHODS: LMw MC and Pluronic F127 were used to formulate an injectable thermo-reversible gel/micelle combination system containing DTX. The DTX-loaded combination system was characterized and its therapeutic efficacy evaluated in a subcutaneous tumor model. RESULTS: Mixtures of LMw MC, AS, and Pluronic F127 formed gel at ~15-40 degrees C depending on AS concentration. The combination system released DTX for >30 days with a biphasic and sustained release pattern, and DTX stability was maintained during release. The combination system significantly enhanced anti-cancer effects of DTX and prolonged survival of the model mouse in comparison with free DTX. CONCLUSIONS: The LMw MC gel/Pluronic F127 micelle combination system constitutes a promising tool for reducing tumor size and eradicating remaining tumor cells before and after surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21904934
      14. Call Number :
        PKI @ kd.modi @ 16
      15. Serial :
        10531
      1. Author :
        Galina Gabriely, Thomas Wurdinger, Santosh Kesari, Christine C. Esau, Julja Burchard, Peter S. Linsley and Anna M. Krichevsky
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Molecular and Cellular Biology
      6. Products :
      7. Volume :
        28
      8. Issue :
        17
      9. Page Numbers :
        N/A
      10. Research Area :
        Neuroscience
      11. Keywords :
        in vivo imaging; MMPSense; microRNA 21; glioma
      12. Abstract :
        Substantial data indicate that microRNA 21 (miR-21) is significantly elevated in glioblastoma (GBM) and in many other tumors of various origins. This microRNA has been implicated in various aspects of carcinogenesis, including cellular proliferation, apoptosis, and migration. We demonstrate that miR-21 regulates multiple genes associated with glioma cell apoptosis, migration, and invasiveness, including the RECK and TIMP3 genes, which are suppressors of malignancy and inhibitors of matrix metalloproteinases (MMPs). Specific inhibition of miR-21 with antisense oligonucleotides leads to elevated levels of RECK and TIMP3 and therefore reduces MMP activities in vitro and in a human model of gliomas in nude mice. Moreover, downregulation of miR-21 in glioma cells leads to decreases of their migratory and invasion abilities. Our data suggest that miR-21 contributes to glioma malignancy by downregulation of MMP inhibitors, which leads to activation of MMPs, thus promoting invasiveness of cancer cells. Our results also indicate that inhibition of a single oncomir, like miR-21, with specific antisense molecules can provide a novel therapeutic approach for “physiological” modulation of multiple proteins whose expression is deregulated in cancer.
      13. URL :
        http://mcb.asm.org/cgi/content/abstract/28/17/5369
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4546
      1. Author :
        Inglefield, Jon R; Dumitru, Calin Dan; Alkan, Sefik S; Gibson, Sheila J; Lipson, Kenneth E; Tomai, Mark A; Larson, Chris J; Vasilakos, John P
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research
      6. Products :
      7. Volume :
        28
      8. Issue :
        4
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Aminoquinolines; Animals; B16-F10-luc-G5 cells; Bioware; Cell Line, Tumor; Cell Proliferation; Cell Survival; Culture Media, Conditioned; dendritic cells; Humans; Interferon Type I; Leukocytes, Mononuclear; Lung; Melanoma; Mice; Neoplasms; Oligodeoxyribonucleotides; Quinolines; Subcellular Fractions; Sulfonamides; Toll-Like Receptor 7
      12. Abstract :
        Antitumor effects of the toll-like receptor 7 (TLR7) agonist, 852A, were evaluated. Supernatants from human peripheral blood mononuclear cells (PBMC) stimulated with 852A inhibited the proliferation of tumor cell lines Hs294T and 769-P but had no effect on others (786-O and Caki-1). Because addition of 852A directly to the Hs294T cells did not inhibit their proliferation, the mechanism(s) of inhibition of tumor cell proliferation was investigated. Low nanomolar concentrations of 852A stimulated the production of interferon-alpha (IFN-alpha), IFN-inducible protein-10 (IP-10), interleukin-1 receptor antagonist (IL-1Ra), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from human PBMCs. Cytokines stimulated by submicromolar concentrations of 852A were sufficient to inhibit Hs294T proliferation. At higher concentrations (3-30 microM), 852A induced the production of IL-12p70, IL-18, and IFN-gamma. PBMC cultures depleted of plasmacytoid dendritic cells (pDC) did not produce IFN-alpha, and their conditioned medium did not inhibit Hs294T proliferation. Anti-IFN-alpha/beta receptor (IFNAR) and anti-IFN-alpha antibodies partially abrogated Hs294T proliferation inhibition by 852A-stimulated PBMC supernatants, whereas separate neutralization of TRAIL, tumor necrosis factor-alpha (TNF-alpha, IFN-gamma, IFN-beta, or IFN-omega had no effect. In vivo, six doses of 852A administration significantly delayed the onset of lung colonies in a B16 melanoma model. Thus, the results demonstrate that the TLR7 agonist 852A inhibits in vitro proliferation of some tumor cells in a pDC-dependent and IFN-alpha-dependent manner and can delay tumor growth in vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18439103
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9001
      1. Author :
        Meincke, M.; Tiwari, S.; Hattermann, K.; Kalthoff, H.; Mentlein, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Clin Exp Metastasis
      6. Products :
      7. Volume :
        28
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Breast Neoplasms/metabolism/*pathology; Cattle; Chemokine CXCL12/metabolism; Female; Fluorescent Dyes/diagnostic use; Glioma/metabolism/*pathology; Humans; Image Processing, Computer-Assisted; Mice; Mice, Nude; Receptors, CXCR/*metabolism; Receptors, CXCR4/*metabolism; Serum Albumin, Bovine/metabolism; Spectroscopy, Near-Infrared; Tumor Cells, Cultured
      12. Abstract :
        The chemokine CXCL12/SDF-1 and its receptors CXCR4 and CXCR7 play a major role in tumor invasion, proliferation and metastasis. Since both receptors are overexpressed on distinct tumor cells and on the tumor vasculature, we evaluated their potential as targets for detection of cancers by molecular imaging. We synthesized conjugates of CXCL12 and the near-infrared (NIR) fluorescent dye IRDye((R))800CW, tested their selectivity, sensitivity and biological activity in vitro and their feasibility to visualize tumors in vivo. Purified CXCL12-conjugates detected in vitro as low as 500 A764 human glioma cells or MCF-7 breast cancer cells that express CXCR7 alone or together with CXCR4. Binding was time- and concentration-dependent, and the label could be competitively displaced by the native peptide. Control conjugates with bovine serum albumin or lactalbumin failed to label the cells. In mice, the conjugate distributed rapidly. After 1-92 h, subcutaneous tumors of human MCF-7 and A764 cells in immunodeficient mice were detected with high sensitivity. Background was observed in particular in liver within the first 24 h, but also skull and hind limbs yielded some background. Overall, fluorescent CXCL12-conjugates are sensitive and selective probes to detect solid and metastatic tumors by targeting tumor cells and tumor vasculature.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21735100
      14. Call Number :
        PKI @ kd.modi @ 13
      15. Serial :
        10372
      1. Author :
        Hickson, Jonathan
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Urologic oncology
      6. Products :
      7. Volume :
        27
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Biological Markers; Bioware; Diagnostic Imaging; Image Processing, Computer-Assisted; Luminescent Measurements; Luminescent Proteins; Molecular Probes; Optical Devices; Optical Phenomena; PC-3M-luc; Reproducibility of Results
      12. Abstract :
        There has recently been an explosion in the availability of new technologies to noninvasively detect biological processes in preclinical models. One such modality, optical imaging, comprises using bioluminescent and fluorescent reporters and probes to repetitively interrogate molecular events and monitor disease progression in animal models. This review includes an overview of optical imaging technologies (e.g., hardware, reporters, probes) available for small animal imaging and their application in monitoring disease progression, therapeutic efficacy, and molecular processes such as proliferation, apoptosis, and angiogenesis. Also discussed are some of the challenges associated with in vivo optical imaging and the necessary controls and biological correlates one must include in experimental design and interpretation for successful preclinical studies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19414115
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8964
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Journal of orthopaedic research: official publication of the Orthopaedic Research Society
      6. Products :
      7. Volume :
        27
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Bioware; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Female; Fractures, Bone; Mice; Mice, Inbred C57BL; Osteomyelitis; Xen29
      12. Abstract :
        Osteomyelitis (OM) from multidrug-resistant (MDR) Acinetobacter has emerged in >30% of combat-related injuries in Iraq and Afghanistan. While most of these strains are sensitive to colistin, the drug is not available in bone void fillers for local high-dose delivery. To address this, we developed a mouse model with MDR strains isolated from wounded military personnel. In contrast to S. aureus OM, which is osteolytic and characterized by biofilm in necrotic bone, A. baumannii OM results in blastic lesions that do not contain apparent biofilm. We also found that mice mount a specific IgG response against three proteins (40, 47, and 56 kDa) regardless of the strain used, suggesting that these may be immuno-dominant antigens. PCR for the A. baumannii-specific parC gene confirmed a 100% infection rate with 75% of the MDR strains, and in vitro testing confirmed that all strains were sensitive to colistin. We also developed a real-time quantitative PCR (RTQ-PCR) assay that could detect as few as 10 copies of parC in a sample. To demonstrate the efficacy of colistin prophylaxis in this model, mice were treated with either parenteral colistin (0.2 mg colistinmethate i.m. for 7 days), local colistin (PMMA bead impregnated with 1.0 mg colistin sulfate), or an unloaded PMMA bead control. While the parenteral colistin failed to demonstrate any significant effects versus the placebo, the colistin PMMA bead significantly reduced the infection rate such that only 29.2% of the mice had detectable levels of parC at 19 days (p < 0.05 vs. i.m. colistin and placebo).
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19173261
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9043
      1. Author :
        Burkatovskaya, Marina; Tegos, George P; Swietlik, Emilia; Demidova, Tatiana N; P Castano, Ana; Hamblin, Michael R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        27
      8. Issue :
        22
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Acetates; Alginates; Animals; Anti-Infective Agents; Bandages; Bioware; Chitosan; Glucuronic Acid; Hexuronic Acids; Male; Mice; Mice, Inbred BALB C; Occlusive Dressings; Proteus mirabilis; Pseudomonas aeruginosa; Silver Sulfadiazine; Staphylococcus aureus; Wound Healing; Wound Infection; Xen8.1, Xen5, Xen44
      12. Abstract :
        HemCon bandage is an engineered chitosan acetate preparation used as a hemostatic control dressing, and its chemical structure suggests that it should also be antimicrobial. We tested its ability to rapidly kill bacteria in vitro and in mouse models of infected wounds. We used the Gram-negative species Pseudomonas aeruginosa and Proteus mirabilis and the Gram-positive Staphylococcus aureus that had all been stably transduced with the entire bacterial lux operon to allow in vivo bioluminescence imaging. An excisional wound in Balb/c mice was inoculated with 50-250 million cells followed after 30 min by application of HemCon bandage, alginate sponge bandage, silver sulfadiazine cream or no treatment. HemCon was more adhesive to the wound and conformed well to the injury compared to alginate. Animal survival was followed over 15 days with observations of bioluminescence emission and animal activity daily. Chitosan acetate treated mice infected with P. aeruginosa and P. mirabilis all survived while those receiving no treatment, alginate and silver sulfadiazine demonstrated 25-100% mortality. Chitosan acetate was much more effective than other treatments in rapidly reducing bioluminescence in the wound consistent with its rapid bactericidal activity in vitro as well as its light-scattering properties. S. aureus formed only non-lethal localized infections after temporary immunosuppression of the mice but HemCon was again more effective in reducing bioluminescence. The data suggest that chitosan acetate rapidly kills bacteria in the wound before systemic invasion can take place, and is superior to alginate bandage and silver sulfadiazine that may both encourage bacterial growth in the short term.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16616364
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9987
      1. Author :
        Sabbagh, Y.; Graciolli, F. G.; O'Brien, S.; Tang, W.; dos Reis, L. M.; Ryan, S.; Phillips, L.; Boulanger, J.; Song, W.; Bracken, C.; Liu, S.; Ledbetter, S.; Dechow, P.; Canziani, M. E.; Carvalho, A. B.; Jorgetti, V.; Moyses, R. M.; Schiavi, S. C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Bone Miner Res
      6. Products :
      7. Volume :
        27
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Biopsy; Bone Remodeling; Bone and Bones/metabolism/pathology; Calcification, Physiologic; Cardiovascular Abnormalities/blood/complications/pathology/physiopathology; *Disease Progression; Female; Gene Expression Profiling; Gene Expression Regulation; Glycoproteins/metabolism; Humans; Kidney Failure, Chronic/blood/complications/pathology/physiopathology; Male; Mice; Mice, Inbred C57BL; Middle Aged; Mutation/genetics; Osteoclasts/metabolism/pathology; Osteocytes/*metabolism/*pathology; Protein-Serine-Threonine Kinases/genetics; Renal Osteodystrophy/blood/*metabolism/*pathology/physiopathology; Vascular Calcification; *Wnt Signaling Pathway/genetics
      12. Abstract :
        Chronic kidney disease-mineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft-tissue calcification. Emerging evidence suggests that features of CKD-MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild-type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD-MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild-type mice. To capture the early molecular and cellular events in the progression of CKD-MBD we examined cell-specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor-Ser33/37-beta-catenin was observed both in mouse and human bones. Overall repression of Wnt/beta-catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF-kappaB ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late-stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD-MBD and suggest that repression of the Wnt/beta-catenin pathway is involved in the pathogenesis of renal osteodystrophy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22492547
      14. Call Number :
        PKI @ kd.modi @ 10
      15. Serial :
        10475
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