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      1. Author :
        Steve H. Thorne; Yoram Barak; Wenchuan Liang; Michael H. Bachmann; Jianghong Rao; Christopher H. Contag; A. Matin
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Molecular Cancer Therapeutics
      6. Products :
      7. Volume :
        8
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Cancer; in vivo imaging; drug discovery; chemotherapy
      12. Abstract :
        We report the discovery of a new prodrug, 6-chloro-9-nitro-5-oxo-5H-benzo(a)phenoxazine (CNOB). This prodrug is efficiently activated by ChrR6, the highly active prodrug activating bacterial enzyme we have previously developed. The CNOB/ChrR6 therapy was effective in killing several cancer cell lines in vitro. It also efficiently treated tumors in mice with up to 40% complete remission. 9-Amino-6-chloro-5H-benzo(a)phenoxazine-5-one (MCHB) was the only product of CNOB reduction by ChrR6. MCHB binds DNA; at nonlethal concentration, it causes cell accumulation in the S phase, and at lethal dose, it induces cell surface Annexin V and caspase-3 and caspase-9 activities. Further, MCHB colocalizes with mitochondria and disrupts their electrochemical potential. Thus, killing by CNOB involves MCHB, which likely induces apoptosis through the mitochondrial pathway. An attractive feature of the CNOB/ChrR6 regimen is that its toxic product, MCHB, is fluorescent. This feature proved helpful in in vitro studies because simple fluorescence measurements provided information on the kinetics of CNOB activation within the cells, MCHB killing mechanism, its generally efficient bystander effect in cells and cell spheroids, and its biodistribution. The emission wavelength of MCHB also permitted its visualization in live animals, allowing noninvasive qualitative imaging of MCHB in mice and the tumor microenvironment. This feature may simplify exploration of barriers to the penetration of MCHB in tumors and their amelioration.
      13. URL :
        http://mct.aacrjournals.org/content/8/2/333.abstract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4500
      1. Author :
        Kim DE, Kim JY, Schellingerhout D, Shon SM, Jeong SW, Kim EJ and Kim WK
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Molecular Imaging
      6. Products :
      7. Volume :
        8
      8. Issue :
        5
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        ProSense; in vivo imaging
      12. Abstract :
        Inflammation in atherosclerotic plaques causes plaque vulnerability and rupture, leading to thromboembolic complications. Cathepsin B (CatB) proteases secreted by macrophages play a major role in plaque inflammation. We used a CatB-activatable near-infrared fluorescence (NIRF) imaging agent to demonstrate the inflammatory component in mice atheromata and the atherosclerosis- modulating effects of atorvastatin or glucosamine treatments. Apolipoprotein E knockout mice (n = 35) were fed normal chow, a Western diet, a Western diet + atorvastatin, a Western diet + glucosamine, or a Western diet + atorvastatin + glucosamine for 14 weeks. Twenty-four hours after the intravenous injection of a CatB-activatable probe, ex vivo NIRF imaging of the aortas and brains was performed, followed by histology. The CatB-related signal, observed in the aortas but not in the cerebral arteries, correlated very well with protease activity and the presence of macrophages on histology. Animals on Western diets could be distinguished from animals on a normal diet. The antiatherosclerotic effects of atorvastatin and glucosamine could be demonstrated, with reduced CatB-related signal compared with untreated animals. Plaque populations were heterogeneous within individuals, with some plaques showing a high and others a lower CatB-related signal. These differences in signal intensity could not be predicted by visual inspection of the plaques but did correlate with histologic evidence of inflammation in every case. This suggests that vulnerable inflamed plaques can be identified by optical molecular imaging.
      13. URL :
        http://www.bcdecker.com/pubMedLinkOut.aspx?pub=MIO&vol=8&iss=5&page=291
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4558
      1. Author :
        Qamri, Zahida; Preet, Anju; Nasser, Mohd W; Bass, Caroline E; Leone, Gustavo; Barsky, Sanford H; Ganju, Ramesh K
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Molecular cancer therapeutics
      6. Products :
      7. Volume :
        8
      8. Issue :
        11
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Apoptosis; Benzoxazines; Bioware; Breast Neoplasms; Cannabinoids; Cell Cycle; Cell Growth Processes; Cell Line, Tumor; Cell Movement; Cyclooxygenase 2; Dinoprostone; Female; Humans; Immunohistochemistry; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; MDA-MB-231-D3H2LN cells; Mice; Mice, Inbred C3H; Mice, SCID; Mice, Transgenic; Microscopy, Confocal; Morpholines; Naphthalenes; Neoplasm Metastasis; Neovascularization, Pathologic; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; RNA, Small Interfering; Signal Transduction; Transfection; Xenograft Model Antitumor Assays
      12. Abstract :
        Cannabinoids have been reported to possess antitumorogenic activity. Not much is known, however, about the effects and mechanism of action of synthetic nonpsychotic cannabinoids on breast cancer growth and metastasis. We have shown that the cannabinoid receptors CB1 and CB2 are overexpressed in primary human breast tumors compared with normal breast tissue. We have also observed that the breast cancer cell lines MDA-MB231, MDA-MB231-luc, and MDA-MB468 express CB1 and CB2 receptors. Furthermore, we have shown that the CB2 synthetic agonist JWH-133 and the CB1 and CB2 agonist WIN-55,212-2 inhibit cell proliferation and migration under in vitro conditions. These results were confirmed in vivo in various mouse model systems. Mice treated with JWH-133 or WIN-55,212-2 showed a 40% to 50% reduction in tumor growth and a 65% to 80% reduction in lung metastasis. These effects were reversed by CB1 and CB2 antagonists AM 251 and SR144528, respectively, suggesting involvement of CB1 and CB2 receptors. In addition, the CB2 agonist JWH-133 was shown to delay and reduce mammary gland tumors in the polyoma middle T oncoprotein (PyMT) transgenic mouse model system. Upon further elucidation, we observed that JWH-133 and WIN-55,212-2 mediate the breast tumor-suppressive effects via a coordinated regulation of cyclooxygenase-2/prostaglandin E2 signaling pathways and induction of apoptosis. These results indicate that CB1 and CB2 receptors could be used to develop novel therapeutic strategies against breast cancer growth and metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19887554
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8953
      1. Author :
        van der Horst, G.; van der Pluijm, G.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Future Oncol
      6. Products :
      7. Volume :
        8
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Bone Neoplasms/*diagnosis/*secondary; Diagnostic Imaging/*methods; Disease Models, Animal; Disease Progression; Humans; Molecular Imaging/methods; Neoplasm Metastasis/diagnosis
      12. Abstract :
        Bone metastasis is a complex process that ultimately leads to devastating metastatic bone disease. It is therefore of key interest to unravel the mechanisms underlying the multistep process of skeletal metastasis and cancer-induced bone disease, and to develop better treatment and management of patients with this devastating disease. Fortunately, novel technologies are rapidly emerging that allow real-time imaging of molecules, pathogenic processes, drug delivery and drug response in preclinical in vivo models. The outcome of these experimental studies will facilitate clinical cancer research by improving the detection of cancer cell invasion, metastasis and therapy response.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22515445
      14. Call Number :
        PKI @ kd.modi @ 30
      15. Serial :
        10384
      1. Author :
        Nowatzki, P. J.; Koepsel, R. R.; Stoodley, P.; Min, K.; Harper, A.; Murata, H.; Donfack, J.; Hortelano, E. R.; Ehrlich, G. D.; Russell, A. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Acta Biomater
      6. Products :
      7. Volume :
        8
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen14, Xen 14, E. coli Xen14, IVIS
      12. Abstract :
        Biofilm-associated infections are a major complication of implanted and indwelling medical devices like urological and venous catheters. They commonly persist even in the presence of an oral or intravenous antibiotic regimen, often resulting in chronic illness. We have developed a new approach to inhibiting biofilm growth on synthetic materials through controlled release of salicylic acid from a polymeric coating. Herein we report the synthesis and testing of a ultraviolet-cured polyurethane acrylate polymer composed, in part, of salicyl acrylate, which hydrolyzes upon exposure to aqueous conditions, releasing salicylic acid while leaving the polymer backbone intact. The salicylic acid release rate was tuned by adjusting the polymer composition. Anti-biofilm performance of the coatings was assessed under several biofilm forming conditions using a novel combination of the MBEC Assay biofilm multi-peg growth system and bioluminescence monitoring for live cell quantification. Films of the salicylic acid-releasing polymers were found to inhibit biofilm formation, as shown by bioluminescent and GFP reporter strains of Pseudomonas aeruginosa and Escherichia coli. Urinary catheters coated on their inner lumens with the salicylic acid-releasing polymer significantly reduced biofilm formation by E. coli for up to 5 days under conditions that simulated physiological urine flow.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22342353
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10394
      1. Author :
        van der Horst, G.; van der Pluijm, G.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Future Oncol
      6. Products :
      7. Volume :
        8
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Bone Neoplasms/*diagnosis/*secondary; Diagnostic Imaging/*methods; Disease Models, Animal; Disease Progression; Humans; Molecular Imaging/methods; Neoplasm Metastasis/diagnosis
      12. Abstract :
        Bone metastasis is a complex process that ultimately leads to devastating metastatic bone disease. It is therefore of key interest to unravel the mechanisms underlying the multistep process of skeletal metastasis and cancer-induced bone disease, and to develop better treatment and management of patients with this devastating disease. Fortunately, novel technologies are rapidly emerging that allow real-time imaging of molecules, pathogenic processes, drug delivery and drug response in preclinical in vivo models. The outcome of these experimental studies will facilitate clinical cancer research by improving the detection of cancer cell invasion, metastasis and therapy response.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22515445
      14. Call Number :
        PKI @ kd.modi @ 16
      15. Serial :
        10478
      1. Author :
        Okuda, Tomoyuki; Kawaguchi, Yasuhisa; Okamoto, Hirokazu
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Current topics in medicinal chemistry
      6. Products :
      7. Volume :
        9
      8. Issue :
        12
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; Gene Silencing; PC-3M-luc; Peptides; Proteins; RNA Interference; Transfection
      12. Abstract :
        RNA interference (RNAi) is an attractive phenomenon for practical use that specifically inhibits gene expression and is carried out by small double-stranded RNAs (dsRNAs) including small interfering RNA (siRNA) or short hairpin RNA (shRNA). In addition, RNAi is of great interest for clinical use to cure refractory diseases related to the expression of a specific gene. To achieve gene silencing in the body, a sufficient amount of dsRNA must be delivered and internalized into target cells. However, dsRNAs have a large molecular weight and net negative charge, which limits their membrane-permeating ability. Moreover, dsRNAs are rapidly degraded by endonucleses in the body. Therefore, for the efficient delivery of dsRNAs, many approaches based on drug delivery systems have been carried out. In this review, we focus on recent reports about the application of functional peptides and proteins designed for the efficient delivery of dsRNAs.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19860710
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8962
      1. Author :
        Mitchell, Dianne; Pobre, Eileen G; Mulivor, Aaron W; Grinberg, Asya V; Castonguay, Roselyne; Monnell, Travis E; Solban, Nicolas; Ucran, Jeffrey A; Pearsall, R Scott; Underwood, Kathryn W; Seehra, Jasbir; Kumar, Ravindra
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Molecular cancer therapeutics
      6. Products :
      7. Volume :
        9
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Activin Receptors, Type II; Animals; Bioware; Bone Morphogenetic Proteins; CHO Cells; Cricetinae; Cricetulus; Endothelial Cells; Endothelium, Vascular; Growth Differentiation Factor 2; Humans; MCF-7-luc-F5 cells; Mice; Neoplasms; Neovascularization, Pathologic; Surface Plasmon Resonance; Telangiectasia, Hereditary Hemorrhagic
      12. Abstract :
        Activin receptor-like kinase-1 (ALK1) is a type I, endothelial cell-specific member of the transforming growth factor-beta superfamily of receptors known to play an essential role in modulating angiogenesis and vessel maintenance. In the present study, we sought to examine the angiogenic and tumorigenic effects mediated upon the inhibition of ALK1 signaling using a soluble chimeric protein (ALK1-Fc). Of 29 transforming growth factor-beta-related ligands screened by surface plasmon resonance, only bone morphogenetic protein (BMP9) and BMP10 displayed high-affinity binding to ALK1-Fc. In cell-based assays, ALK1-Fc inhibited BMP9-mediated Id-1 expression in human umbilical vein endothelial cells and inhibited cord formation by these cells on a Matrigel substrate. In a chick chorioallantoic membrane assay, ALK1-Fc reduced vascular endothelial growth factor-, fibroblast growth factor-, and BMP10-mediated vessel formation. The growth of B16 melanoma explants was also inhibited significantly by ALK1-Fc in this assay. Finally, ALK1-Fc treatment reduced tumor burden in mice receiving orthotopic grafts of MCF7 mammary adenocarcinoma cells. These data show the efficacy of chimeric ALK1-Fc proteins in mitigating vessel formation and support the view that ALK1-Fc is a powerful antiangiogenic agent capable of blocking vascularization.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20124460
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9010
      1. Author :
        Shimomura, Toshiyasu; Hasako, Shinichi; Nakatsuru, Yoko; Mita, Takashi; Ichikawa, Koji; Kodera, Tsutomu; Sakai, Takumi; Nambu, Tadahiro; Miyamoto, Mayu; Takahashi, Ikuko; Miki, Satomi; Kawanishi, Nobuhiko; Ohkubo, Mitsuru; Kotani, Hidehito; Iwasawa, Yoshikazu
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Molecular cancer therapeutics
      6. Products :
      7. Volume :
        9
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bioware; Cell Death; Cell Line, Tumor; Cell Proliferation; Cyclohexanecarboxylic Acids; HeLa-luc; Humans; Inhibitory Concentration 50; Mice; Mitosis; Protein kinase inhibitors; Protein-Serine-Threonine Kinases; Rats; Taxoids; Thiazoles; Xenograft Model Antitumor Assays
      12. Abstract :
        Aurora-A kinase is a one of the key regulators during mitosis progression. Aurora-A kinase is a potential target for anticancer therapies because overexpression of Aurora-A, which is frequently observed in some human cancers, results in aberrant mitosis leading to chromosomal instability and possibly tumorigenesis. MK-5108 is a novel small molecule with potent inhibitory activity against Aurora-A kinase. Although most of the Aurora-kinase inhibitors target both Aurora-A and Aurora-B, MK-5108 specifically inhibited Aurora-A kinase in a panel of protein kinase assays. Inhibition of Aurora-A by MK-5108 in cultured cells induced cell cycle arrest at the G(2)-M phase in flow cytometry analysis. The effect was confirmed by the accumulation of cells with expression of phosphorylated Histone H3 and inhibition of Aurora-A autophosphorylation by immunostaining assays. MK-5108 also induced phosphorylated Histone H3 in skin and xenograft tumor tissues in a nude rat xenograft model. MK-5108 inhibited growth of human tumor cell lines in culture and in different xenograft models. Furthermore, the combination of MK-5108 and docetaxel showed enhanced antitumor activities compared with control and docetaxel alone-treated animals without exacerbating the adverse effects of docetaxel. MK-5108 is currently tested in clinical trials and offers a new therapeutic approach to combat human cancers as a single agent or in combination with existing taxane therapies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20053775
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9006
      1. Author :
        Tai, Chien-Hsuan; Hsiung, Suz-Kai; Chen, Chih-Yuan; Tsai, Mei-Lin; Lee, Gwo-Bin
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Biomedical microdevices
      6. Products :
      7. Volume :
        9
      8. Issue :
        4
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        A549-luc-C8 cells; Bioware; Cell Line, Tumor; Cell Nucleus; Cell Separation; Electrophoresis; Humans; Microfluidic Analytical Techniques
      12. Abstract :
        This study reports a new biochip capable of cell separation and nucleus collection utilizing dielectrophoresis (DEP) forces in a microfluidic system comprising of micropumps and microvalves, operating in an automatic format. DEP forces operated at a low voltage (15 Vp-p) and at a specific frequency (16 MHz) can be used to separate cells in a continuous flow, which can be subsequently collected. In order to transport the cell samples continuously, a serpentine-shape (S-shape) pneumatic micropump device was constructed onto the chip device to drive the samples flow through the microchannel, which was activated by the pressurized air injection. The mixed cell samples were first injected into an inlet reservoir and driven through the DEP electrodes to separate specific samples. Finally, separated cell samples were collected individually in two outlet reservoirs controlled by microvalves. With the same operation principle, the nucleus of the specific cells can be collected after the cell lysis procedure. The pumping rate of the micropump was measured to be 39.8 microl/min at a pressure of 25 psi and a driving frequency of 28 Hz. For the cell separation process, the initial flow rate was 3 microl/min provided by the micropump. A throughput of 240 cells/min can be obtained by using the developed device. The DEP electrode array, microchannels, micropumps and microvalves are integrated on a microfluidic chip using micro-electro-mechanical-systems (MEMS) technology to perform several crucial procedures including cell transportation, separation and collection. The dimensions of the integrated chip device were measured to be 6x7 cm. By integrating an S-shape pump and pneumatic microvalves, different cells are automatically transported in the microchannel, separated by the DEP forces, and finally sorted to specific chambers. Experimental data show that viable and non-viable cells (human lung cancer cell, A549-luc-C8) can be successfully separated and collected using the developed microfluidic platform. The separation accuracy, depending on the DEP operating mode used, of the viable and non-viable cells are measured to be 84 and 81%, respectively. In addition, after cell lysis, the nucleus can be also collected using a similar scheme. The developed automatic microfluidic platform is useful for extracting nuclear proteins from living cells. The extracted nuclear proteins are ready for nuclear binding assays or the study of nuclear proteins.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17508288
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9005
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