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- Author
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Emmett, M. S.; Lanati, S.; Dunn, D. B.; Stone, O. A.; Bates, D. O. - Title
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- Type
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Journal Article - Year
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2011 - Publication
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Microcirculation - Products
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- Volume
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18 - Issue
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N/A - Page Numbers
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N/A - Research Area : N/A
- Keywords
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IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, - Abstract
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OBJECTIVE: To determine whether chemotactic-metastasis, the preferential growth of melanomas towards areas of high lymphatic density, is CCL21/CCR7 dependent in vivo. Lymphatic endothelial cells (LECs) produce the chemokine CCL21. Metastatic melanoma cells express CCR7, its receptor, and exhibit chemotactic-metastasis, whereby metastatic cells recognise and grow towards areas of higher lymphatic density. METHODS: We used two in vivo models of directional growth towards depots of LECs of melanoma cells over-expressing CCR7. Injected LEC were tracked by intravital fluorescence microscopy, and melanoma growth by bioluminescence. RESULTS: Over-expression of the chemokine receptor CCR7 enables non-metastatic tumor cells to recognise and grow towards LECs (3.9 fold compared with control), but not blood endothelial cells (0.9 fold), in vitro and in vivo in the absence of increased lymphatic clearance. Chemotactic metastasis was inhibited by a CCL21 neutralising antibody (4-17% of control). Furthermore, CCR7 expression in mouse B16 melanomas resulted in in-transit metastasis (50-100% of mice) that was less often seen with control tumors (0-50%) in vivo. CONCLUSION: These results suggest that recognition of LEC by tumors expressing receptors for lymphatic specific ligands contributes towards the identification and invasion of lymphatics by melanoma cells and provides further evidence for a chemotactic metastasis model of tumor spread. - URL
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http://www.ncbi.nlm.nih.gov/pubmed/21166932 - Call Number
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PKI @ kd.modi @ 2 - Serial
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10355
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- Author
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Fu, J. Y.; Zhang, W.; Blatchford, D. R.; Tetley, L.; McConnell, G.; Dufes, C. - Title
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- Type
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Journal Article - Year
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2011 - Publication
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J Control Release - Products
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- Volume
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N/A - Issue
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N/A - Page Numbers
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N/A - Research Area : N/A
- Keywords
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IVIS, B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, - Abstract
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The therapeutic potential of tocotrienol, a vitamin E extract with anti-cancer properties, is hampered by its failure to specifically reach tumors after intravenous administration. In this work, we demonstrated that novel transferrin-bearing, tocopheryl-based multilamellar vesicles entrapping tocotrienol significantly improved tocotrienol uptake by cancer cells overexpressing transferrin receptors. This led to a dramatically improved therapeutic efficacy in vitro, ranging from 17-fold to 72-fold improvement depending on the cell lines, compared to the free drug. In vivo, the intravenous administration of this novel tocotrienol formulation led to complete tumor eradication for 40% of B16-F10 murine melanoma tumors and 20% of A431 human epidermoid carcinoma tumors. Animal survival was improved by more than 20days compared to controls, for the two tumor models tested. These therapeutic effects, together with the lack of toxicity, potentially make transferrin-bearing vesicles entrapping tocotrienol a highly promising therapeutic system as part as an anti-cancer therapeutic strategy. - URL
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http://www.ncbi.nlm.nih.gov/pubmed/21539872 - Call Number
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PKI @ kd.modi @ 6 - Serial
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10356
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- Author
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Izukuri, K.; Suzuki, K.; Yajima, N.; Ozawa, S.; Ito, S.; Kubota, E.; Hata, R. - Title
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- Type
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Journal Article - Year
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2010 - Publication
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Transgenic Res - Products
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- Volume
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19 - Issue
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N/A - Page Numbers
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N/A - Research Area : N/A
- Keywords
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Animals, B16-F10-luc2, B16F10-luc2; Base Sequence; Carcinoma, Lewis Lung/blood supply/genetics/immunology/therapy; Cell Line, Tumor; Chemokines, CXC/*genetics/*immunology; DNA Primers/genetics; Female; Gene Expression; Humans; Kidney/immunology; Male; Melanoma, Experimental/blood supply/genetics/immunology/therapy; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neoplasm Transplantation; Neoplasms, Experimental/blood supply/genetics/*immunology/*therapy; RNA, Messenger/genetics; Recombinant Proteins/genetics/immunology; Transplantation, Heterologous - Abstract
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We reported previously that the forced expression of the chemokine BRAK, also called CXCL14 in head and neck squamous cell carcinoma (HNSCC) cells decreased the rate of tumor formation and size of tumor xenografts compared with mock-vector treated cells in athymic nude mice or in severe combined immunodeficiency mice. This suppression occurred even though the growth rates of these cells were the same under in vitro culture conditions, suggesting that a high expression level of the gene in tumor cells is important for the suppression of tumor establishment in vivo. The aim of this study was to determine whether CXCL14/BRAK transgenic mice show resistance to tumor cell xenografts or not. CXCL14/BRAK cDNA was introduced into male C57BL/6 J pronuclei, and 10 founder transgenic mice (Tg) were obtained. Two lines of mice expressed over 10 times higher CXCL14/BRAK protein levels (14 and 11 ng/ml plasma, respectively) than normal blood level (0.9 ng/ml plasma), without apparent abnormality. The sizes of Lewis lung carcinoma and B16 melanoma cell xenografts in Tg mice were significantly smaller than those in control wild-type mice, indicating that CXCL14/BRAK, first found as a suppressor of tumor progression of HNSCC, also suppresses the progression of a carcinoma of other tissue origin. Immunohistochemical studies showed that invasion of blood vessels into tumors was suppressed in tumor xenografts of CXCL14/BRAK Tg mice. These results indicate that CXCL14/BRAK suppressed tumor cell xenografts by functioning paracrine or endocrine fashion and that CXCL14/BRAK is a very promising molecular target for tumor suppression without side effects. - URL
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http://www.ncbi.nlm.nih.gov/pubmed/20333465 - Call Number
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PKI @ kd.modi @ 5 - Serial
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10348
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- Author
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Mumprecht, V.; Honer, M.; Vigl, B.; Proulx, S. T.; Trachsel, E.; Kaspar, M.; Banziger-Tobler, N. E.; Schibli, R.; Neri, D.; Detmar, M. - Title
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- Type
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Journal Article - Year
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2010 - Publication
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Cancer Res - Products
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- Volume
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70 - Issue
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N/A - Page Numbers
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N/A - Research Area : N/A
- Keywords
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Animals, B16-F10-luc2, B16F10-luc2; Antibodies, Monoclonal/diagnostic use/immunology; *Diagnostic Imaging; Female; Fluorodeoxyglucose F18/diagnostic use; Glycoproteins/*immunology; Humans; Inflammation/*complications/immunology/pathology; Iodine Radioisotopes/diagnostic use/pharmacokinetics; Luminescent Measurements; Lymph Nodes/immunology/pathology/*radionuclide imaging; *Lymphangiogenesis; Lymphatic Metastasis; Melanoma, Experimental/*complications/immunology/pathology; Mice; Mice, Inbred C57BL; Mice, Transgenic; *Positron-Emission Tomography; Prognosis; Radiopharmaceuticals/diagnostic use; Skin/metabolism; Tissue Distribution; Vascular Endothelial Growth Factor C/metabolism; Vascular Endothelial Growth Factor Receptor-3/immunology - Abstract
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Metastasis to regional lymph nodes (LN) is a prognostic indicator for cancer progression. There is a great demand for sensitive and noninvasive methods to detect metastasis to LNs. Whereas conventional in vivo imaging approaches have focused on the detection of cancer cells, lymphangiogenesis within tumor-draining LNs might be the earliest sign of metastasis. In mouse models of LN lymphangiogenesis, we found that systemically injected antibodies to lymphatic epitopes accumulated in the lymphatic vasculature in tissues and LNs. Using a (124)I-labeled antibody against the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), we imaged, for the first time, inflammation- and tumor-draining LNs with expanded lymphatic networks in vivo by positron emission tomography (PET). Anti-LYVE-1 immuno-PET enabled visualization of lymphatic vessel expansion in LNs bearing metastases that were not detected by [(18)F]fluorodeoxyglucose-PET, which is clinically applied to detect cancer metastases. Immuno-PET with lymphatic-specific antibodies may open up new avenues for the early detection of metastasis, and the images obtained might be used as biomarkers for the progression of diseases associated with lymphangiogenesis. - URL
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http://www.ncbi.nlm.nih.gov/pubmed/20978206 - Call Number
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PKI @ kd.modi @ 2 - Serial
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10349
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- Author
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Proulx, S. T.; Luciani, P.; Derzsi, S.; Rinderknecht, M.; Mumprecht, V.; Leroux, J. C.; Detmar, M. - Title
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- Type
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Journal Article - Year
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2010 - Publication
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Cancer Res - Products
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- Volume
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70 - Issue
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N/A - Page Numbers
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N/A - Research Area : N/A
- Keywords
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Animals, B16-F10-luc2, B16F10-luc2; Coloring Agents/administration & dosage/*diagnostic use; Indocyanine Green/administration & dosage/*diagnostic use; Injections, Intradermal; Liposomes/administration & dosage; Lymphatic Metastasis; Lymphatic Vessels/metabolism/*pathology; Melanoma, Experimental/blood supply/metabolism/*pathology; Mice; Mice, Inbred C57BL; Vascular Endothelial Growth Factor C/biosynthesis - Abstract
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Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system, but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift toward longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase-expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near-IR imaging of intradermally injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C-expressing tumors without metastases, whereas a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method will likely facilitate quantitative studies of lymphatic function in preclinical investigations and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer. - URL
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http://www.ncbi.nlm.nih.gov/pubmed/20823159 - Call Number
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PKI @ kd.modi @ 1 - Serial
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10350
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- Author
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Seo, G. M.; Rachakatla, R. S.; Balivada, S.; Pyle, M.; Shrestha, T. B.; Basel, M. T.; Myers, C.; Wang, H.; Tamura, M.; Bossmann, S. H.; Troyer, D. L. - Title
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- Type
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Journal Article - Year
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2012 - Publication
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Mol Biol Rep - Products
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- Volume
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39 - Issue
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N/A - Page Numbers
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N/A - Research Area : N/A
- Keywords
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Animals, B16-F10-luc2, B16F10-luc2 - Abstract
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Gene-directed enzyme prodrug therapy (GDEPT) has been investigated as a means of cancer treatment without affecting normal tissues. This system is based on the delivery of a suicide gene, a gene encoding an enzyme which is able to convert its substrate from non-toxic prodrug to cytotoxin. In this experiment, we have developed a targeted suicide gene therapeutic system that is completely contained within tumor-tropic cells and have tested this system for melanoma therapy in a preclinical model. First, we established double stable RAW264.7 monocyte/macrophage-like cells (Mo/Ma) containing a Tet-On(R) Advanced system for intracellular carboxylesterase (InCE) expression. Second, we loaded a prodrug into the delivery cells, double stable Mo/Ma. Third, we activated the enzyme system to convert the prodrug, irinotecan, to the cytotoxin, SN-38. Our double stable Mo/Ma homed to the lung melanomas after 1 day and successfully delivered the prodrug-activating enzyme/prodrug package to the tumors. We observed that our system significantly reduced tumor weights and numbers as targeted tumor therapy after activation of the InCE. Therefore, we propose that this system may be a useful targeted melanoma therapy system for pulmonary metastatic tumors with minimal side effects, particularly if it is combined with other treatments. - URL
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http://www.ncbi.nlm.nih.gov/pubmed/21567204 - Call Number
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PKI @ kd.modi @ 6 - Serial
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10351
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- Author
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Libreros S, Garcia-Areas R, Shibata Y, Carrio R, Torroella-Kouri M, Iragavarapu-Charyulu V. - Title
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Induction of proinflammatory mediators by CHI3L1 is reduced by chitin treatment: Decreased tumor metastasis in a breast cancer model - Type
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Journal Article - Year
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2011 - Publication
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International Journal of Cancer - Products
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- Volume
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N/A - Issue
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N/A - Page Numbers
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N/A - Research Area : N/A
- Keywords
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IVIS, 4T1-luc2 - Abstract
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N/A - URL
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N/A - Call Number
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PKI @ kd.modi @ 6 - Serial
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10360
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- Author
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Zhou, H.; Roy, S.; Cochran, E.; Zouaoui, R.; Chu, C. L.; Duffner, J.; Zhao, G.; Smith, S.; Galcheva-Gargova, Z.; Karlgren, J.; Dussault, N.; Kwan, R. Y.; Moy, E.; Barnes, M.; Long, A.; Honan, C.; Qi, Y. W.; Shriver, Z.; Ganguly, T.; Schultes, B.; Venkataraman, G.; Kishimoto, T. K. - Title
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- Type
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Journal Article - Year
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2011 - Publication
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PLoS One - Products
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- Volume
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6 - Issue
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N/A - Page Numbers
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N/A - Research Area : N/A
- Keywords
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IVIS, 4T1-luc2 - Abstract
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Heparan sulfate proteoglycans (HSPGs) play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment and activation, as well as promoting tumor progression, metastasis, and survival. M402 is a rationally engineered, non-cytotoxic heparan sulfate (HS) mimetic, designed to inhibit multiple factors implicated in tumor-host cell interactions, including VEGF, FGF2, SDF-1alpha, P-selectin, and heparanase. A single s.c. dose of M402 effectively inhibited seeding of B16F10 murine melanoma cells to the lung in an experimental metastasis model. Fluorescent-labeled M402 demonstrated selective accumulation in the primary tumor. Immunohistological analyses of the primary tumor revealed a decrease in microvessel density in M402 treated animals, suggesting anti-angiogenesis to be one of the mechanisms involved in-vivo. M402 treatment also normalized circulating levels of myeloid derived suppressor cells in tumor bearing mice. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis and prolonged survival in an orthotopic 4T1 murine mammary carcinoma model. These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis. - URL
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http://www.ncbi.nlm.nih.gov/pubmed/21698156 - Call Number
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PKI @ kd.modi @ 1 - Serial
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10362
- Author
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- Author
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Ale, A.; Ermolayev, V.; Herzog, E.; Cohrs, C.; de Angelis, M. H.; Ntziachristos, V. - Title
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- Type
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Journal Article - Year
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2012 - Publication
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Nat Methods - Products
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- Volume
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9 - Issue
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N/A - Page Numbers
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N/A - Research Area : N/A
- Keywords
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Animals; Bone Remodeling; Disease Models, Animal; Equipment Design; Female; Fluorescence; Head and Neck Neoplasms/pathology/radiography; Image Processing, Computer-Assisted/*methods; Lung Neoplasms/pathology/radiography; Mammary Neoplasms, Experimental/pathology/radiography; Mice; Osteogenesis Imperfecta/pathology/radiography; Tomography, Optical/*methods; Tomography, X-Ray Computed/*methods - Abstract
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The development of hybrid optical tomography methods to improve imaging performance has been suggested over a decade ago and has been experimentally demonstrated in animals and humans. Here we examined in vivo performance of a camera-based hybrid fluorescence molecular tomography (FMT) system for 360 degrees imaging combined with X-ray computed tomography (XCT). Offering an accurately co-registered, information-rich hybrid data set, FMT-XCT has new imaging possibilities compared to stand-alone FMT and XCT. We applied FMT-XCT to a subcutaneous 4T1 tumor mouse model, an Aga2 osteogenesis imperfecta model and a Kras lung cancer mouse model, using XCT information during FMT inversion. We validated in vivo imaging results against post-mortem planar fluorescence images of cryoslices and histology data. Besides offering concurrent anatomical and functional information, FMT-XCT resulted in the most accurate FMT performance to date. These findings indicate that addition of FMT optics into the XCT gantry may be a potent upgrade for small-animal XCT systems. - URL
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http://www.ncbi.nlm.nih.gov/pubmed/22561987 - Call Number
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PKI @ kd.modi @ 29 - Serial
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10363
- Author
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- Author
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He, T.; Xue, Z.; Lu, K.; Valdivia y Alvarado, M.; Wong, K. K.; Xie, W.; Wong, S. T. - Title
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- Type
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Journal Article - Year
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2012 - Publication
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Comput Med Imaging Graph - Products
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- Volume
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36 - Issue
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N/A - Page Numbers
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N/A - Research Area : N/A
- Keywords
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N/A - Abstract
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BACKGROUND: Lung cancer is the leading cause of cancer-related death in the United States, with more than half of the cancers are located peripherally. Computed tomography (CT) has been utilized in the last decade to detect early peripheral lung cancer. However, due to the high false diagnosis rate of CT, further biopsy is often necessary to confirm cancerous cases. This renders intervention for peripheral lung nodules (especially for small peripheral lung cancer) difficult and time-consuming, and it is highly desirable to develop new, on-the-spot earlier lung cancer diagnosis and treatment strategies. PURPOSE: The objective of this study is to develop a minimally invasive multimodality image-guided (MIMIG) intervention system to detect lesions, confirm small peripheral lung cancer, and potentially guide on-the-spot treatment at an early stage. Accurate image guidance and real-time optical imaging of nodules are thus the key techniques to be explored in this work. METHODS: The MIMIG system uses CT images and electromagnetic (EM) tracking to help interventional radiologists target the lesion efficiently. After targeting the lesion, a fiber-optic probe coupled with optical molecular imaging contrast agents is used to confirm the existence of cancerous tissues on-site at microscopic resolution. Using the software developed, pulmonary vessels, airways, and nodules can be segmented and visualized for surgical planning; the segmented results are then transformed onto the intra-procedural CT for interventional guidance using EM tracking. Endomicroscopy through a fiber-optic probe is then performed to visualize tumor tissues. Experiments using IntegriSense 680 fluorescent contrast agent labeling alphavbeta3 integrin were carried out for rabbit lung cancer models. Confirmed cancers could then be treated on-the-spot using radio-frequency ablation (RFA). RESULTS: The prototype system is evaluated using the rabbit VX2 lung cancer model to evaluate the targeting accuracy, guidance efficiency, and performance of molecular imaging. Using this system, we achieved an average targeting accuracy of 3.04 mm, and the IntegriSense signals within the VX2 tumors were found to be at least two-fold higher than those of normal tissues. The results demonstrate great potential for applying the system in human trials in the future if an optical molecular imaging agent is approved by the Food and Drug Administration (FDA). CONCLUSIONS: The MIMIG system was developed for on-the-spot interventional diagnosis of peripheral lung tumors by combining image-guidance and molecular imaging. The system can be potentially applied to human trials on diagnosing and treating earlier stage lung cancer. For current clinical applications, where a biopsy is unavoidable, the MIMIG system without contrast agents could be used for biopsy guidance to improve the accuracy and efficiency. - URL
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http://www.ncbi.nlm.nih.gov/pubmed/22483054 - Call Number
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PKI @ kd.modi @ 9 - Serial
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10364
- Author