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      1. Author :
        Pesnel, S.; Pillon, A.; Creancier, L.; Lerondel, S.; Le Pape, A.; Recher, C.; Demur, C.; Guilbaud, N.; Kruczynski, A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        7
      8. Issue :
        N/A
      9. Page Numbers :
        e30690
      10. Research Area :
        N/A
      11. Keywords :
        HCT-116-luc2, HCT116-luc2, IVIS, Animals; Antibodies, Monoclonal/administration & dosage/*immunology; Antigens, CD45/metabolism; Cell Line, Tumor; Cell Transformation, Neoplastic/pathology; Disease Models, Animal; Flow Cytometry; Fluorescent Dyes/*metabolism; Humans; Imaging, Three-Dimensional/*methods; Injections, Intravenous; Leukemia/*diagnosis/*pathology; Leukemia, Myeloid, Acute/pathology; Longevity; Luminescent Measurements; Mice; Mice, SCID; Reproducibility of Results; Spectroscopy, Near-Infrared/*methods
      12. Abstract :
        BACKGROUND: The assessment of anticancer agents to treat leukemia needs to have animal models closer to the human pathology such as implantation in immunodeficient mice of leukemic cells from patient samples. A sensitive and early detection of tumor cells in these orthotopic models is a prerequisite for monitoring engraftment of leukemic cells and their dissemination in mice. Therefore, we developed a fluorescent antibody based strategy to detect leukemic foci in mice bearing patient-derived leukemic cells using fluorescence reflectance imaging (FRI) to determine when to start treatments with novel antitumor agents. METHODS: Two mAbs against the CD44 human myeloid marker or the CD45 human leukocyte marker were labeled with Alexa Fluor 750 and administered to leukemia-bearing mice after having verified the immunoreactivity in vitro. Bioluminescent leukemic cells (HL60-Luc) were used to compare the colocalization of the fluorescent mAb with these cells. The impact of the labeled antibodies on disease progression was further determined. Finally, the fluorescent hCD45 mAb was tested in mice engrafted with human leukemic cells. RESULTS: The probe labeling did not modify the immunoreactivity of the mAbs. There was a satisfactory correlation between bioluminescence imaging (BLI) and FRI and low doses of mAb were sufficient to detect leukemic foci. However, anti-hCD44 mAb had a strong impact on the tumor proliferation contrary to anti-hCD45 mAb. The use of anti-hCD45 mAb allowed the detection of leukemic patient cells engrafted onto NOD/SCID mice. CONCLUSIONS: A mAb labeled with a near infrared fluorochrome is useful to detect leukemic foci in disseminated models provided that its potential impact on tumor proliferation has been thoroughly documented.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22303450
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10503
      1. Author :
        Welti, J. C.; Powles, T.; Foo, S.; Gourlaouen, M.; Preece, N.; Foster, J.; Frentzas, S.; Bird, D.; Sharpe, K.; van Weverwijk, A.; Robertson, D.; Soffe, J.; Erler, J. T.; Pili, R.; Springer, C. J.; Mather, S. J.; Reynolds, A. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Angiogenesis
      6. Products :
      7. Volume :
        15
      8. Issue :
        N/A
      9. Page Numbers :
        623-41
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2, 4T1, Bioware, IVIS
      12. Abstract :
        Sunitinib is a potent and clinically approved tyrosine kinase inhibitor that can suppress tumour growth by inhibiting angiogenesis. However, conflicting data exist regarding the effects of this drug on the growth of metastases in preclinical models. Here we use 4T1 and RENCA tumour cells, which both form lung metastases in Balb/c mice, to re-address the effects of sunitinib on the progression of metastatic disease in mice. We show that treatment of mice with sunitinib prior to intravenous injection of tumour cells can promote the seeding and growth of 4T1 lung metastases, but not RENCA lung metastases, showing that this effect is cell line dependent. However, increased metastasis occurred only upon administration of a very high sunitinib dose, but not when lower, clinically relevant doses were used. Mechanistically, high dose sunitinib led to a pericyte depletion effect in the lung vasculature that correlated with increased seeding of metastasis. By administering sunitinib to mice after intravenous injection of tumour cells, we demonstrate that while sunitinib does not inhibit the growth of 4T1 lung tumour nodules, it does block the growth of RENCA lung tumour nodules. This contrasting response was correlated with increased myeloid cell recruitment and persistent vascularisation in 4T1 tumours, whereas RENCA tumours recruited less myeloid cells and were more profoundly devascularised upon sunitinib treatment. Finally, we show that progression of 4T1 tumours in sunitinib treated mice results in increased hypoxia and increased glucose metabolism in these tumours and that this is associated with a poor outcome. Taken together, these data suggest that the effects of sunitinib on tumour progression are dose-dependent and tumour model-dependent. These findings have relevance for understanding how anti-angiogenic agents may influence disease progression when used in the adjuvant or metastatic setting in cancer patients.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22843200
      14. Call Number :
        PKI @ kd.modi @ 10
      15. Serial :
        10504
      1. Author :
        Domanska, U. M.; Timmer-Bosscha, H.; Nagengast, W. B.; Oude Munnink, T. H.; Kruizinga, R. C.; Ananias, H. J.; Kliphuis, N. M.; Huls, G.; De Vries, E. G.; de Jong, I. J.; Walenkamp, A. M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Neoplasia
      6. Products :
      7. Volume :
        14
      8. Issue :
        N/A
      9. Page Numbers :
        709-18
      10. Research Area :
        N/A
      11. Keywords :
        PC-3-luc2, Prostate Cancer, Bioware, IVIS
      12. Abstract :
        Several in vitro and in vivo models have revealed the key role of CXCR4/CXCL12 axis in tumor-stroma interactions. Stromal cells present in the tumor microenvironment express high levels of CXCL12 protein, directly stimulating proliferation and migration of CXCR4-expressing cancer cells. This specific prosurvival influence of stromal cells on tumor cells is thought to protect them from cytotoxic chemotherapy and is postulated as a possible explanation for the minimal residual disease in hematological and solid cancers. Therefore, CXCR4/CXCL12 signaling is an attractive therapeutic target in cancer, as proven in preclinical leukemia mouse models, where CXCR4 inhibition sensitized cancer cells to conventional chemotherapy. This study investigates whether inhibition of CXCR4 with the specific inhibitor AMD3100 sensitizes human prostate cancer cells to docetaxel. We showed that both mouse and human stromal cell lines have a protective effect on PC3-luc cells by promoting their survival after chemotherapy. Furthermore, we demonstrated that AMD3100 sensitizes PC3-luc cells to docetaxel. In a subcutaneous xenograft mouse model of human prostate carcinoma, we showed that a combination of docetaxel and AMD3100 exerts increased antitumor effect compared with docetaxel alone. We concluded that CXCR4 inhibition chemosensitizes prostate cancer cells, both in vitro and in vivo. To explore the relevance of these findings, we analyzed CXCR4 expression levels in human prostate cancer samples. We found that cancer cells present in bone metastatic lesions express higher CXCR4 levels relative to the cells present in primary tumors and lymph node metastatic lesions. These findings underscore the potential of CXCR4 inhibitors as chemosensitizing agents.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22952424
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10507
      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 :
        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 :
        Yamaoka, Ippei; Kikuchi, Takeshi; Endo, Naoyuki; Ebisu, Goro
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2014
      5. Publication :
        BMC gastroenterology
      6. Products :
      7. Volume :
        14
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        BALB/c CrSlc mice; enteral nutrition; Ex vivo; Gastrosense 750; Hine® E-gel; in vivo; IVIS® Spectrum; Nev11121; pectin
      12. Abstract :
        BACKGROUND: Semi-solidification by gelation or increased viscosity could slow the influx of liquid enteral nutrition (EN) into the small intestine. A liquid EN formula containing pectin that gels under acidic conditions such as those found in the stomach has been developed. A new near-infrared fluorescent imaging reagent was used to non-invasively acquire real time images of gastric emptying in a murine model in vivo. We postulated that the EN formula delays gastric emptying and tested this hypothesis using imaging in vivo.
        METHODS: Male BALB/c mice were given an oral bolus injection of a liquid EN containing the fluorescence reagent GastroSense750 with or without pectin. The EN in the stomach was visualized in vivo at various intervals using a non-invasive live imaging system and fluorescent signals were monitored from the stomach, which was removed at 60 min after EN ingestion.
        RESULTS: The fluorescence intensity of signals in stomachs in vivo and in resected stomachs was lower and attenuated over time in mice given EN without, than with pectin.
        CONCLUSIONS: Adding a gelling agent such as pectin delayed the transit of liquid EN from the stomach. Fluorescence imaging can visualize the delayed gastric emptying of EN containing pectin.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/25263497
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        11641
      1. Author :
        Wen, D.; Qing, L.; Harrison, G.; Golub, E.; Akintoye, S. O.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Oral Dis
      6. Products :
      7. Volume :
        17
      8. Issue :
        N/A
      9. Page Numbers :
        427-32
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Maestro, Animals; Bone Density Conservation Agents/administration & dosage/*pharmacokinetics; Bone and Bones/*metabolism; Calcium/metabolism; Chelating Agents; Decalcification Technique; Diphosphonates/administration & dosage/*pharmacokinetics; Durapatite/metabolism; Edetic Acid; Female; Femur/metabolism; Fibula/metabolism; Fluorescent Dyes/diagnostic use; Fluorometry; Humerus/metabolism; Injections, Intravenous; Mandible/metabolism; Models, Animal; Radius/metabolism; Rats; Rats, Nude; Spectrophotometry, Atomic; Tibia/metabolism; Tissue Distribution; Ulna/metabolism
      12. Abstract :
        OBJECTIVES: Bisphosphonates commonly used to treat osteoporosis, Paget's disease, multiple myeloma, hypercalcemia of malignancy and osteolytic lesions of cancer metastasis have been associated with bisphosphonate-associated jaw osteonecrosis (BJON). The underlying pathogenesis of BJON is unclear, but disproportionate bisphosphonate concentration in the jaw has been proposed as one potential etiological factor. This study tested the hypothesis that skeletal biodistribution of intravenous bisphosphonate is anatomic site-dependent in a rat model system. MATERIALS AND METHODS: Fluorescently labeled pamidronate was injected intravenously in athymic rats of equal weights followed by in vivo whole body fluorimetry, ex vivo optical imaging of oral, axial, and appendicular bones and ethylenediaminetetraacetic acid bone decalcification to assess hydroxyapatite-bound bisphosphonate. RESULTS: Bisphosphonate uptake and bisphosphonate released per unit calcium were similar in oral and appendicular bones but lower than those in axial bones. Hydroxyapatite-bound bisphosphonate liberated by sequential acid decalcification was the highest in oral, relative to axial and appendicular bones (P < 0.05). CONCLUSIONS: This study demonstrates regional differences in uptake and release of bisphosphonate from oral, axial, and appendicular bones of immune deficient rats.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21122034
      14. Call Number :
        PKI @ kd.modi @ 11
      15. Serial :
        10467
      1. Author :
        Xing, H. R.; Zhang, Q.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Methods Mol Biol
      6. Products :
      7. Volume :
        872
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; Antineoplastic Agents/therapeutic use; Diagnostic Imaging/*methods; Female; Mammary Neoplasms, Animal/metabolism/pathology; Mice; Mice, Nude; Neoplasm Transplantation; Neovascularization, Pathologic/drug therapy/*pathology
      12. Abstract :
        In vivo angiogenesis assays provide more physiologically relevant information about tumor vascularization than in vitro studies because they take the complex interactions among cancer cells, endothelial cells, mural cells, and tumor stroma into consideration. Traditional microscopic assessment of vascular density conducted by immunostaining of tissue sections or by lectin angiogram visualization of tumor vessels is invasive and requires the sacrifice of tumor-bearing animals. Therefore, it prohibits longitudinal time-course observation in a single animal and requires a large number of animals at each time point to derive statistically-meaningful observations. Additionally, heterogenous behavior among different tumors will inevitably introduce individual biological variance that may obscure reliable interpretation of the results. While various artificial in vivo angiogenesis assays, such as the Matrigel implant assay, chick chorioallatoic membrane assay, and dorsal skin fold chamber assay have been developed and employed to more directly observe the progression of physiological angiogenesis, they can not appropriately assess tumor angiogenic progression or tumor vascular regression in response to therapeutic intervention. Here, we describe a noninvasive method and a detailed protocol that we have developed and optimized using the Olympus OV-100 in vivo imaging system for real-time high-resolution visualization and assessment of tumor angiogenesis and vascular response to anticancer therapies in live animals. We show that using this approach, tumor vessels can be monitored longitudinally through the whole vasculogenesis and angiogenesis process in the same mouse. Further, morphologic changes of the same vessel prior to and after drug treatments can be captured with microscopic high resolution. Moreover, the multichannel co-imaging capability of the OV-100 allows us to analyze and compare tumor vessel permeability before and after antiangiogenesis therapy by employing a near-infrared blood pool reagent, or by visualizing improved cytotoxic drug delivery upon tumor vessel normalization by using a fluorophore tagged drug. This noninvasive method can be readily applied to orthotopically transplanted breast cancer models as well as to subcutaneously-transplanted tumor models.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22700407
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10443
      1. Author :
        Swirski, F. K.; Nahrendorf, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Immunol Cell Biol
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense
      12. Abstract :
        Macrophages are central regulators of disease progression in both atherosclerosis and myocardial infarction (MI). In atherosclerosis, macrophages are the dominant leukocyte population that influences lesional development. In MI, which is caused by atherosclerosis, macrophages accumulate readily and have important roles in inflammation and healing. Molecular imaging has grown considerably as a field and can reveal biological process at the molecular, cellular and tissue levels. Here, we explore how various imaging modalities, from intravital microscopy in mice to organ-level imaging in patients, are contributing to our understanding of macrophages and their progenitors in cardiovascular disease.Immunology and Cell Biology advance online publication, 4 December 2012; doi:10.1038/icb.2012.72.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23207281
      14. Call Number :
        PKI @ kd.modi @ 12
      15. Serial :
        10441
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