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      1. Author :
        Peter, Christoph; Kielstein, Jan T; Clarke-Katzenberg, Regina; Adams, M Christopher; Pitsiouni, Maria; Kambham, Neeraja; Karimi, Mobin A; Kengatharan, Ken M; Cooke, John P
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        The Journal of urology
      6. Products :
      7. Volume :
        177
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; carcinoma, renal cell; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Firefly Luciferin; HT-29-luc-D6 cells; Humans; Kidney Neoplasms; Luminescence; Luminescent Agents; Male; Mice; Mice, SCID; Models, Biological; Tumor Burden
      12. Abstract :
        PURPOSE Bioluminescent imaging permits sensitive in vivo detection and quantification of cells engineered to emit light. We developed a bioluminescent human renal cancer cell line for in vitro and in vivo studies. MATERIAL AND METHODS The 2 human renal cell carcinoma cell lines SN12-C and SN12-L1 were stably transfected to constitutively express luciferase using a retroviral shuttle. The bioluminescent signal was correlated with tumor cell numbers in vitro. Parental and transfected cells were compared by growth kinetics and histology. Tumor burden after heterotopic injection in immune deficient mice was monitored up to 39 days. The kinetics of the bioluminescent signal was evaluated for 1 to 60 minutes following luciferin injection. RESULTS Bioengineered renal cancer cell lines stably expressed luciferase. The growth kinetics of the cells in vitro and the histology of tumors resulting from implantation of these cells were unaffected by retroviral transfection with the luciferase gene. As few as 1,000 cells could be reliably detected. The intensity of the bioluminescent signal correlated with the number of tumor cells in vitro. Photon emission in vivo and ex vivo correlated significantly with tumor weight at sacrifice. After intraperitoneal injection of luciferin there was a time dependent change in the intensity of the bioluminescent signal with maximum photon emission at 20 minutes (optimal 17 to 25). CONCLUSIONS Luciferase transfected human renal cancer lines allow reliable, rapid, noninvasive and longitudinal monitoring of tumor growth in vivo. The ability to assess tumor development in vivo with time is economical and effective compared to end point data experiments.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17509355
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9009
      1. Author :
        Razavi, Reza; Harrison, Lawrence E
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Annals of surgical oncology
      6. Products :
      7. Volume :
        17
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Carcinoma; Cell Proliferation; Colonic Neoplasms; DNA Damage; Drug Therapy, Combination; Female; HT-29-luc-D6 cells; Humans; Hydrogen peroxide; Hyperthermia, Induced; Injections, Intraperitoneal; Mice; Mice, Nude; Oxidants; Oxidative Stress; Survival Rate; tert-Butylhydroperoxide; Treatment Outcome; Tumor Cells, Cultured
      12. Abstract :
        BACKGROUND The purpose of this study was to extend our in vitro observations that induced oxidative stress under hyperthermic conditions decreases tumor cell growth into a preclinical murine model of hyperthermic perfusion. METHODS A nude mouse model of colon cancer carcinomatosis with HT-29-Luc-D6 colon cancer cells was established, and tumor growth was measured by serial bioluminescent imaging. RESULTS By means of a survival model of hyperthermic perfusion, we demonstrated that perfusion with normothermic saline decreased tumor growth compared with no perfusion controls, and tumor growth was further decreased with hyperthermic perfusion alone. The induction of oxidative stress with hydrogen peroxide in the perfusate at concentrations as high as 600 microM was well tolerated in this model of hyperthermic perfusion. Importantly, induced oxidative stress using hydrogen peroxide under hyperthermic conditions significantly decreased in vivo tumor cell growth compared with all other controls. CONCLUSIONS On the basis of our observations, thermal sensitization through modulation of cellular oxidative stress may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19711132
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9008
      1. Author :
        Scatena, Caroline D; Hepner, Mischa A; Oei, Yoko A; Dusich, Joan M; Yu, Shang-Fan; Purchio, Tony; Contag, Pamela R; Jenkins, Darlene E
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2004
      5. Publication :
        The Prostate
      6. Products :
      7. Volume :
        59
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Disease Models, Animal; Humans; LnCaP-luc cells; Luciferases; Luminescent Measurements; Male; Mice; Mice, SCID; Neoplasm Metastasis; Phenotype; Plasmids; Prostatic Neoplasms; Transfection; Transplantation, Heterologous; Tumor Cells, Cultured
      12. Abstract :
        BACKGROUND Animal experiments examining hormone-sensitive metastatic prostate cancer using the human LNCaP cell line have been limited to endpoint analyses. To permit longitudinal studies, we generated a luciferase-expressing cell line and used bioluminescent imaging (BLI) to non-invasively monitor the in vivo growth of primary LNCaP tumors and metastasis. METHODS LNCaP.FGC cells were transfected to constitutively express firefly luciferase. LNCaP-luc-M6 cells were tested for bioluminescent signal intensity and hormone responsiveness in vitro. The cells were implanted in subcutaneous and orthotopic sites in SCID-bg mice and imaged over time. RESULTS The LNCaP-luc-M6 cells formed subcutaneous and orthotopic tumors in SCID-bg mice, and nearly all tumor-bearing animals developed pulmonary metastases. Early detection and temporal growth of primary tumors and metastatic lesions was successfully monitored by BLI. CONCLUSIONS The LNCaP-luc-M6 cell line is a bioluminescent, hormone-sensitive prostate cancer cell line applicable for BLI studies to non-invasively monitor subcutaneous and orthotopic prostate tumor growth and metastasis in vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/15042605
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9015
      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
      1. Author :
        Xiao, Kai; Luo, Juntao; Fowler, Wiley L; Li, Yuanpei; Lee, Joyce S; Xing, Li; Cheng, R Holland; Wang, Li; Lam, Kit S
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        30
      8. Issue :
        30
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Albumins; Animals; Antineoplastic Agents; Biocompatible Materials; Bioware; Cell Line, Tumor; Drug Delivery Systems; Emulsifying Agents; Female; Humans; Male; Maximum Tolerated Dose; Mice; Mice, Nude; Nanoparticles; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; SKOV3-luc-D3 cells; Spectroscopy, Near-Infrared
      12. Abstract :
        Paclitaxel (PTX) is one of the most effective chemotherapeutic drugs for the treatment of a variety of cancers. However, it is associated with serious side effects caused by PTX itself and the Cremophor EL emulsifier. In the present study, we report the development of a well-defined amphiphilic linear-dendritic copolymer (named as telodendrimer) composed of polyethylene glycol (PEG), cholic acid (CA, a facial amphiphilic molecule) and lysine, which can form drug-loaded core/shell micelles when mixed with hydrophobic drug, such as PTX, under aqueous condition. We have used PEG(5k)-CA(8), a representive telodendrimer, to prepare paclitaxel-loaded nanoparticles (PTX-PEG(5k)-CA(8) NPs) with high loading capacity (7.3 mg PTX/mL) and a size of 20-60 nm. This novel nanoformulation of PTX was found to exhibit similar in vitro cytotoxic activity against ovarian cancer cells as the free drug (Taxol) or paclitaxel/human serum albumin nanoaggregate (Abraxane). The maximum tolerated doses (MTDs) of PTX-PEG(5k)-CA(8) NPs after single dose and five consecutive daily doses in mice were approximately 75 and 45 mg PTX/kg, respectively, which were 2.5-fold higher than those of Taxol. In both subcutaneous and orthotopic intraperitoneal murine models of ovarian cancer, PTX-PEG(5k)-CA(8) NPs achieved superior toxicity profiles and anti-tumor effects compared to Taxol and Abraxane at equivalent PTX doses, which were attributed to their preferential tumor accumulation, and deep penetration into tumor tissue, as confirmed by near infrared fluorescence (NIRF) imaging.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19660809
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9013
      1. Author :
        Engelsman, Anton F; Krom, Bastiaan P; Busscher, Henk J; van Dam, Gooitzen M; Ploeg, Rutger J; van der Mei, Henny C
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Acta biomaterialia
      6. Products :
      7. Volume :
        5
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Bioware; Connective Tissue; Diffusion; Drug Implants; Female; Mice; Mice, Inbred BALB C; Nitric Oxide; Polyvinyls; Prostheses and Implants; pXen-5; Staphylococcal Infections; Xen29
      12. Abstract :
        Infection of surgical meshes used in abdominal wall reconstructions often leads to removal of the implant and increases patient morbidity due to repetitive operations and hospital administrations. Treatment with antibiotics is ineffective due to the biofilm mode of growth of the infecting bacteria and bears the risk of inducing antibiotic resistance. Hence there is a need for alternative methods to prevent and treat mesh infection. Nitric oxide (NO)-releasing coatings have been demonstrated to possess bactericidal properties in vitro. It is the aim of this study to assess possible benefits of a low concentration NO-releasing carbon-based coating on monofilament polypropylene meshes with respect to infection control in vitro and in vivo. When applied on surgical meshes, NO-releasing coatings showed significant bactericidal effect on in vitro biofilms of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and CNS. However, using bioluminescent in vivo imaging, no beneficial effects of this NO-releasing coating on subcutaneously implanted surgical meshes in mice could be observed.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19251498
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9019
      1. Author :
        Engelsman, Anton F; van Dam, Gooitzen M; van der Mei, Henny C; Busscher, Henk J; Ploeg, Rutger J
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Annals of surgery
      6. Products :
      7. Volume :
        251
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Abdominal Wall; Animals; Bioware; Female; Luminescent Measurements; Mice; Mice, Inbred BALB C; Polypropylenes; Polytetrafluoroethylene; pXen-5; Staphylococcal Infections; Staphylococcus aureus; Surgical Mesh; Xen29
      12. Abstract :
        OBJECTIVE To study the influence of morphology of surgical meshes on the course of bacterial infection under the influence of the host immune system in an in vivo chronic bacterial infection model. BACKGROUND The use of prosthetic meshes has increased dramatically the last decades in abdominal wall reconstructive surgery. Whereas infection is becoming a more frequent complication, attention is increasingly drawn to the influence of the surgeon's mesh choice on the course of this complication. METHODS Samples of 6 often applied surgical meshes were contaminated with a bioluminescent strain of Staphylococcus aureus and implanted subcutaneously in an immunocompetent BALB/c mouse. The intensity and the spreading of bioluminescence (ie, p/s/cm/sr) were analyzed non-invasively in vivo during a 10-day follow-up period. RESULTS Over the course of infection, multifilament polypropylene and hydrophobic materials showed a significantly higher persistence of bacteria as well as spreading of infection compared to all other meshes. In contrast, infection resolved in almost all animals with a low-weight polyester mesh. CONCLUSION The results of this study are in accordance with circumstantial evidence from limited clinical reports on infection involving surgical meshes and suggest that multifilament and hydrophobic meshes significantly increase bacterial persistence or spreading in the infected area in contrast to monofilament polypropylene and lightweight meshes. Therefore, the surgeon should consider this outcome when choosing a mesh graft for limiting infection in abdominal wall repair.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19864938
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9017
      1. Author :
        Engelsman, Anton F; van der Mei, Henny C; Francis, Kevin P; Busscher, Henk J; Ploeg, Rutger J; van Dam, Gooitzen M
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Journal of biomedical materials research. Part B, Applied biomaterials
      6. Products :
      7. Volume :
        88
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Infective Agents; Bacterial Adhesion; Biofilms; Bioware; Chromosomes, Bacterial; Colony Count, Microbial; Disease Models, Animal; Female; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Prostheses and Implants; pXen-5; Soft Tissue Infections; Staphylococcal Infections; Staphylococcus aureus; Xen29
      12. Abstract :
        Infection is the main cause of biomaterials-related failure. A simple technique to test in-vivo new antimicrobial and/or nonadhesive implant coatings is unavailable. Current in vitro methods for studying bacterial adhesion and growth on biomaterial surfaces lack the influence of the host immune system. Most in vivo methods to study biomaterials-related infections routinely involve implant-removal, preventing comprehensive longitudinal monitoring. In vivo imaging circumvents these drawbacks and is based on the use of noninvasive optical imaging of bioluminescent bacteria. Staphylococcus aureus Xen29 is genetically modified to be stably bioluminescent, by the introduction of a modified full lux operon onto its chromosome. Surgical meshes with adhering S. aureus Xen29 were implanted in mice and bacterial growth and spread into the surrounding tissue was monitored longitudinally from bioluminescence with a highly sensitive CCD camera. Distinct spatiotemporal bioluminescence patterns, extending beyond the mesh area into surrounding tissues were observed. After 10 days, the number of living organisms isolated from explanted meshes was found to correlate with bioluminescence prior to sacrifice of the animals. Therefore, it is concluded that in vivo imaging using bioluminescent bacteria is ideally suited to study antimicrobial coatings taking into account the host immune system. In addition, longitudinal monitoring of infection in one animal will significantly reduce the number of experiments and animals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18618733
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9020
      1. Author :
        Francis, K P; Yu, J; Bellinger-Kawahara, C; Joh, D; Hawkinson, M J; Xiao, G; Purchio, T F; Caparon, M G; Lipsitch, M; Contag, P R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2001
      5. Publication :
        Infection and immunity
      6. Products :
      7. Volume :
        69
      8. Issue :
        5
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Amoxicillin; Animals; Bioware; DNA Transposable Elements; Female; Luminescent Measurements; Lung; Mice; Mice, Inbred BALB C; Nasopharynx; Operon; Promoter Regions, Genetic; pXen-5; Streptococcus pneumoniae; Transformation, Bacterial, Xen10, Xen7
      12. Abstract :
        Animal studies with Streptococcus pneumoniae have provided valuable models for drug development. In order to monitor long-term pneumococcal infections noninvasively in living mice, a novel gram-positive lux transposon cassette, Tn4001 luxABCDE Km(r), that allows random integration of lux genes onto the bacterial chromosome was constructed. The cassette was designed so that the luxABCDE and kanamycin resistance genes were linked to form a single promoterless operon. Bioluminescence and kanamycin resistance only occur in a bacterial cell if this operon has transposed downstream of a promoter on the bacterium's chromosome. S. pneumoniae D39 was transformed with plasmid pAUL-A Tn4001 luxABCDE Km(r), and a number of highly bioluminescent colonies were recovered. Genomic DNA from the brightest D39 strain was used to transform a number of clinical S. pneumoniae isolates, and several of these strains were tested in animal models, including a pneumococcal lung infection model. Strong bioluminescent signals were seen in the lungs of the animals containing these pneumococci, allowing the course and antibiotic treatment of the infections to be readily monitored in real time in the living animals. Recovery of the bacteria from the animals showed that the bioluminescent signal corresponded to the number of CFU and that the lux construct was highly stable even after several days in vivo. We believe that this lux transposon will greatly expand the ability to evaluate drug efficacy against gram-positive bacteria in living animals using bioluminescence.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/11292758
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9027