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      1. Author :
        Hamrahi, V.; Hamblin, M. R.; Jung, W.; Benjamin, J. B.; Paul, K. W.; Fischman, A. J.; Tompkins, R. G.; Carter, E. A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Interdiscip Perspect Infect Dis
      6. Products :
      7. Volume :
        2012
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen44, Xen 44, Proteus mirabilis, bioluminescence imaging
      12. Abstract :
        Sepsis remains the major cause of death in patients with major burn injuries. In the present investigation we evaluated the interaction between burn injuries of varying severity and preexisting distant infection. We used Gram-negative bacteria (Pseudomonas aeruginosa and Proteus mirabilis) that were genetically engineered to be bioluminescent, which allowed for noninvasive, sequential optical imaging of the extent and severity of the infection. The bioluminescent bacteria migrated from subcutaneous abscesses in the leg to distant burn wounds on the back depending on the severity of the burn injury, and this migration led to increased mortality of the mice. Treatment with ciprofloxacin, injected either in the leg with the bacterial infection or into the burn eschar, prevented this colonization of the wound and decreased mortality. The present data suggest that burn wounds can readily become colonized by infections distant from the wound itself.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22899912
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10562
      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 :
        Ibarra, J. M.; Jimenez, F.; Martinez, H. G.; Clark, K.; Ahuja, S. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Int J Inflam
      6. Products :
      7. Volume :
        2011
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MMPSense, IVIS
      12. Abstract :
        The Standard measures of experimental arthritis fail to detect, visualize, and quantify early inflammation and disease activity. Here, we describe the use of an injectable MMP-activated fluorescence agent for in vivo quantification of acute inflammation produced by collagen-antibody-induced arthritis (CAIA) in CC chemokine receptor-2 (Ccr2(-/-)) null mice. Although Ccr2(-/-) DBA1/J mice were highly susceptible to and rapidly developed CAIA, the standard clinical assessment of fore or hind paw thicknesses was unable to detect significant acute inflammatory changes (days 3-10). Remarkably, noninvasive, in situ, MMP-activatable fluorescent imaging of Ccr2(-/-) DBA1/J mice with CAIA displayed acute joint pathology in advance of clinically measurable acute inflammation (days 5, 7, and 10). These results were confirmed by the histology of ankle joints, which showed significant inflammation, bone loss, and synovial hyperplasia, compared to control mice at postimmunization day 5. The MMP-mediated fluorescence technique holds tremendous implications for quantifiable examination of arthritis disease activity of acute joint inflammation.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21755029
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10462
      1. Author :
        Takaba, J.; Mishima, Y.; Hatake, K.; Kasahara, T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Mediators of Inflammation
      6. Products :
      7. Volume :
        2010
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        bone marrow cells; Cancer; cell labeling; in vitro; in vivo imaging; Olympus IV-100; tail vein injection; VivoTag 750
      12. Abstract :
        Mucosal damage is a common side effect of many cancer treatments, especially radiotherapy and intensive chemotherapy, which often induce bone marrow (BM) suppression. We observed that acetic acid- (AA-) induced mucosal damage in the colon of mice was worsened by simultaneous treatment with irradiation or 5-FU. However, irradiation 14 days prior to the AA treatment augmented the recovery from mucosal damage, suggesting that the recovery from BM suppression had an advantageous effect on the mucosal repair. In addition, BM transplantation also augmented the recovery from AA-induced mucosal damage. We further confirmed that transplanted BM-derived cells, particularly F4/80+Gr1+ “inflammatory” monocytes (Subset 1), accumulated in the damaged mucosal area in the early healing phase, and both of Subset 1 and F4/80+Gr1- “resident” monocytes (Subset 2) accumulated in this area in later phases. Our results suggest that monocytes/macrophages contribute to the mucosal recovery and regeneration following mucosal damage by anticancer drug therapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21274263
      14. Call Number :
        PKI @ user @ 8445
      15. Serial :
        4808
      1. Author :
        Cheung, Alison M.; Brown, Allison S.; Shaked, Yuval; Franco, Marcela; Kerbel, Robert S.; Foster, F. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        AACR Meeting Abstracts
      6. Products :
      7. Volume :
        2006
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; PC-3M-luc; hVEGF-luc-PC3M
      12. Abstract :
        Background: Preclinical cancer studies increasingly utilize non-invasive imaging modalities. In the current study we have monitored tumor growth and vascular changes using two in vivo imaging tools: surface bioluminescence (BLI) and ultrasound biomicroscopy (UBM). BLI permits visualization of tumor location in the context of the whole body, including metastases localization. UBM imaging then permits high resolution 3D volumetric tumor measurements as well as blood flow estimates down to 200 microns/s. Measurements obtained from these complementary modalities were analyzed and compared to conventional, biochemical markers. Methods: Human prostate cancer cells expressing Firefly Luciferase constitutively (PC-3M-luc-C6) or under the control of hVEGF promoter (hVEGF-luc/PC3M) were implanted into male nude mice via an intradermal or subcutaneous injection. Tumor-bearing mice were subsequently imaged every week for nine weeks starting at week 2, by UBM to measure tumor burden using 3D volumetric analysis, or to estimate blood flow using speckle-variance flow processing. Surface bioluminescence was also acquired 10 minutes post i.p. injection of D-luciferin. In a longitudinal drug intervention study anti-hVEGF antibody (Bevacizumab, 200 ug) was injected i.p. into nude mice with subcutaneous xenografts of PC-3M-luc-C6 or hVEGF-luc/PC-3M twice per week for three weeks, starting at 14 days post-xenograft. UBM and surface BLI imaging were conducted every week. In order to study the correlation between VEGF expression in hVEGF-luc/PC3M xenografts (estimated by BLI) to tumor hypoxia level, mice were injected with pimonidazole hydrochloride (60 mg/kg i.v.) after three weeks of treatment and tumors were harvested for immunostaining analysis. Results: Surface BLI outputs (photons/s) from subcutaneous PC-3M-luc-C6 xenografts were highly correlated to tumor volumes measured using 3D UBM for small tumors (<100 mm3, r=0.92, n=8), yet poorly correlated to tumors of large size (>100 mm3, r=0.079, n=8). BLI signals in subcutaneous hVEGF-luc/PC3M xenografts showed an inverse trend to tumor blood flow. PC-3M-luc-C6 tumors treated with Bevacizumab showed growth inhibition by day 28 as demonstrated by 3D UBM (control vs treated = 67.27 vs 48.54 mm3). Moreover, control xenografts showed increased average BLI output over time, whereas treated tumors showed variation in BLI output. Necrosis, hypoxia and blood flow estimates were also investigated. Conclusions: Surface bioluminescence imaging demonstrated high correlations to accurate 3D UBM volumetric measurements of small tumor volumes, suggesting its usefulness in tracking early tumor growth quantitatively in drug intervention studies. A complementary imaging modality, like ultrasound biomicroscopy, is recommended to monitor tumor burden in advanced stages.
      13. URL :
        http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/646-a
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8977
      1. Author :
        Hunter, John J.; Neben, Tamlyn Yee; Purchio, Tony; Jenkins, Darlene
      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; SKOV3-luc-D3 cells
      12. Abstract :
        Peritoneal dissemination is a common feature of human ovarian carcinoma. While this can be mimicked in preclinical models by intraperitoneal injection of human ovarian tumor cells into immunocompromised mice, the resulting tumor burden is difficult to monitor and quantify. Intraperitoneal tumor growth is typically evaluated indirectly by measured changes in mouse abdominal girth and body weight or, directly, by macroscopic and histological examination at the endpoint of the study. In order to establish a model system that allows continuous and accurate assessment of ovarian cancer growth and spread over time we transfected SKOV-3 cells with the firefly luciferase gene. The resulting cell line, SKOV3-luc-D3, expresses stable levels of luciferase in vitro and emits a strong luminescent signal when exposed to luciferin. Xenograft tumors established with this cell line can be tracked and quantified non-invasively by bioluminescent imaging using a highly sensitive, cooled CCD camera (IVIS(R) Imaging System, Xenogen Corp). In addition to providing a direct measure of primary tumor burden and growth, the SKOV3-luc-D3 cell line also allows for real-time evaluation of tumor response to various therapeutic agents, as well as enhanced detection of distal metastases.
      13. URL :
        http://www.aacrmeetingabstracts.org/cgi/content/abstract/2005/1/256-b
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9014
      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 :
        Jenkins, Darlene E.; Hornig, Yvette S.; Oei, Yoko A.; Yu, Shang-Fan; Dusich, Joan M.; Jenkins, Darlene E.; Purchio, Tony; Hornig, Yvette S.; Oei, Yoko A.; Yu, Shang-Fan; Dusich, Joan M.; Purchio, Tony
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2004
      5. Publication :
        AACR Meeting Abstracts
      6. Products :
      7. Volume :
        2004
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; MCF-7-luc-F5 cells
      12. Abstract :
        A clonal human tumor cell line expressing firefly luciferase, MCF-7-luc-F5, was developed from parental MCF-7 breast carcinoma cells and characterized for bioluminescence in vitro and in vivo. As few as twenty cells were detectable in vitro and average bioluminescence measured approximately 680 photons/sec/cell. Tumorigenesis of MCF-7-luc-F5 cells was assessed with and without estrogen supplement in vivo following injection of cells into the mammary fat pad of nude-beige mice. Continuous tumor growth was observed by weekly bioluminescent imaging in mice receiving a slow release (60 day) estrogen pellet implant (0.36 mg/pellet), while no tumor growth occurred in mice without estrogen supplement. Caliper measurements of tumor volume indicated similar results. A kinetic analysis of luciferase activity in vivo demonstrated that peak signals were evident approximately 12-15 minutes after injection of luciferin substrate and were maintained at a relatively stable level for at least another 20-25 minutes. Spontaneous metastasis from the primary mammary fat pad tumor to thoracic and axillary regions was observed in vivo in 50% of the animals. Subsequent ex vivo images and histology identified metastatic sites in lung, rib, or lymph nodes depending on the mouse. Standard drug treatment on primary and secondary tumor growth was also monitored by bioluminescent imaging.
      13. URL :
        http://www.aacrmeetingabstracts.org/cgi/content/abstract/2004/1/1179-c
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9011
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Annals of the New York Academy of Sciences
      6. Products :
      7. Volume :
        1192
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Biofilms; Bioware; Bone Density Conservation Agents; Chronic Disease; Cytokines; Drug Evaluation, Preclinical; Humans; Immunity; Incidence; Jaw Diseases; Mice; Neovascularization, Physiologic; Osteoclasts; Osteomyelitis; Osteonecrosis; Staphylococcal Infections; Xen29
      12. Abstract :
        The effects of antiresorptive agents (e.g., alendronate [Aln], osteoprotegerin [OPG]) on bone infection are unknown. Thus, their effects on implant-associated osteomyelitis (OM) were investigated in mice using PBS (placebo), gentamycin, and etanercept (TNFR:Fc) controls. None of the drugs affected humoral immunity, angiogenesis, or chronic infection. However, the significant (P < 0.05 vs. PBS) inhibition of cortical osteolysis and decreased draining lymph node size in Aln- and OPG-treated mice was associated with a significant (P < 0.05) increase in the incidence of high-grade infections during the establishment of OM. In contrast, the high-grade infections in TNFR:Fc-treated mice were associated with immunosuppression, as evidenced by the absence of granulomas and presence of Gram(+) biofilm in the bone marrow. Collectively, these findings indicate that although antiresorptive agents do not exacerbate chronic OM, they can increase the bacterial load during early infection by decreasing lymphatic drainage and preventing the removal of necrotic bone that harbors the bacteria.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20392222
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9034