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      1. Author :
        Izukuri, K.; Suzuki, K.; Yajima, N.; Ozawa, S.; Ito, S.; Kubota, E.; Hata, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Transgenic Res
      6. Products :
      7. Volume :
        19
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        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
      12. Abstract :
        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.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20333465
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10348
      1. Author :
        J-C Tseng; T Granot; V DiGiacomo; B Levin; D Meruelo
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cancer Gene Therapy
      6. Products :
      7. Volume :
        17
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Sindbis virus; viral vector; vascular leakiness; molecular imaging; chemotherapy; cancer
      12. Abstract :
        Genetic instability of cancer cells generates resistance after initial responses to chemotherapeutic agents. Several oncolytic viruses have been designed to exploit specific signatures of cancer cells, such as important surface markers or pivotal signaling pathways for selective replication. It is less likely for cancer cells to develop resistance given that mutations in these cancer signatures would negatively impact tumor growth and survival. However, as oncolytic viral vectors are large particles, they suffer from inefficient extravasation from tumor blood vessels. Their ability to reach cancer cells is an important consideration in achieving specific oncolytic targeting and potential vector replication. Our previous studies indicated that the Sindbis viral vectors target tumor cells by the laminin receptor. Here, we present evidence that modulating tumor vascular leakiness, using VEGF and/or metronomic chemotherapy regimens, significantly enhances tumor vascular permeability and directly enhances oncolytic Sindbis vector targeting in tumor models. Because host-derived vascular endothelium cells are genetically stable and less likely to develop resistance to chemotherapeutics, a combined metronomic chemotherapeutics and oncolytic vector regimen should provide a new approach for cancer therapy. This mechanism could explain the synergistic treatment outcomes observed in clinical trials of combined therapies.
      13. URL :
        http://www.nature.com/cgt/journal/v17/n4/full/cgt200970a.html
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4485
      1. Author :
        Jadert, C.; Petersson, J.; Massena, S.; Ahl, D.; Grapensparr, L.; Holm, L.; Lundberg, J. O.; Phillipson, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Free Radic Biol Med
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29
      12. Abstract :
        Nitric oxide (NO) generated by vascular NO synthases can exert anti-inflammatory effects, partly through its ability to decrease leukocyte recruitment. Inorganic nitrate and nitrite, from endogenous or dietary sources, have emerged as alternative substrates for NO formation in mammals. Bioactivation of nitrate is believed to require initial reduction to nitrite by oral commensal bacteria. Here we investigated the effects of inorganic nitrate and nitrite on leukocyte recruitment in microvascular inflammation and in NSAID-induced small-intestinal injury. We show that leukocyte emigration in response to the proinflammatory chemokine MIP-2 is reduced by 70% after 7days of dietary nitrate supplementation as well as by acute intravenous nitrite administration. Nitrite also reduced leukocyte adhesion to a similar extent and this effect was inhibited by the soluble guanylyl cyclase inhibitor ODQ, whereas the effect on emigrated leukocytes was not altered by this treatment. Further studies in TNF-alpha-stimulated endothelial cells revealed that nitrite dose-dependently reduced the expression of ICAM-1. In rats and mice subjected to a challenge with diclofenac, dietary nitrate prevented the increase in myeloperoxidase and P-selectin levels in small-intestinal tissue. Antiseptic mouthwash, which eliminates oral nitrate reduction, markedly blunted the protective effect of dietary nitrate on P-selectin levels. Despite attenuation of the acute immune response, the overall ability to clear an infection with Staphylococcus aureus was not suppressed by dietary nitrate as revealed by noninvasive IVIS imaging. We conclude that dietary nitrate markedly reduces leukocyte recruitment to inflammation in a process involving attenuation of P-selectin and ICAM-1 upregulation. Bioactivation of dietary nitrate requires intermediate formation of nitrite by oral nitrate-reducing bacteria and then probably further reduction to NO and other bioactive nitrogen oxides in the tissues.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22178413
      14. Call Number :
        PKI @ kd.modi @ 18
      15. Serial :
        10452
      1. Author :
        Jan Grimm; David G. Kirsch; Stephen D. Windsor; Carla F. Bender Kim; Philip M. Santiago; Vasilis Ntziachristos; Tyler Jacks; Ralph Weissleder
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        PNAS
      6. Products :
      7. Volume :
        102
      8. Issue :
        40
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        gene expression profiling; lung cancer; immunohistochemistry; Western blotting; in vivo imaging; moleuclar imaging; fluorescence molecular tomography
      12. Abstract :
        Using gene expression profiling, we identified cathepsin cysteine proteases as highly up-regulated genes in a mouse model of human lung adenocarcinoma. Overexpression of cathepsin proteases in these lung tumors was confirmed by immunohistochemistry and Western blotting. Therefore, an optical probe activated by cathepsin proteases was selected to detect murine lung tumors in vivo as small as 1 mm in diameter and spatially separated. We generated 3D maps of the fluorescence signal and fused them with anatomical computed tomography images to show a close correlation between fluorescence signal and tumor burden. By serially imaging the same mouse, optical imaging was used to follow tumor progression. This study demonstrates the capability for molecular imaging of a primary lung tumor by using endogenous proteases expressed by a tumor. It also highlights the feasibility of using gene expression profiling to identify molecular targets for imaging lung cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1242291/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4524
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        International Journal of Cardiovascular Imaging
      6. Products :
      7. Volume :
        26
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        Cardiovascular disease; Atherosclerosis; Vulnerable plaque; Spectroscopy; Intravascular; in vivo imaging; MMPSense
      12. Abstract :
        Many apparent healthy persons die from cardiovascular disease, despite major advances in prevention and treatment of cardiovascular disease. Traditional cardiovascular risk factors are able to predict cardiovascular events in the long run, but fail to assess current disease activity or nearby cardiovascular events. There is a clear relation between the occurrence of cardiovascular events and the presence of so-called vulnerable plaques. These vulnerable plaques are characterized by active inflammation, a thin cap and a large lipid pool. Spectroscopy is an optical imaging technique which depicts the interaction between light and tissues, and thereby shows the biochemical composition of tissues. In recent years, impressive advances have been made in spectroscopy technology and intravascular spectroscopy is able to assess the composition of plaques of interest and thereby to identify and actually quantify plaque vulnerability. This review summarizes the current evidence for spectroscopy as a measure of plaque vulnerability and discusses the potential role of intravascular spectroscopic imaging techniques.
      13. URL :
        http://www.springerlink.com/content/kx38073782g98666/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4552
      1. Author :
        Jason R. McCarthy, Purvish Patel, Ion Botnaru, Pouneh Haghayeghi, Ralph Weissleder and Farouc A. Jaffer
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Bioconjugate Chemistry
      6. Products :
      7. Volume :
        20
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        In vivo imaging; thrombi; VivoTag
      12. Abstract :
        Thrombosis underlies numerous life-threatening cardiovascular syndromes. Development of thrombosis-specific molecular imaging agents to detect and monitor thrombogenesis and fibrinolysis in vivo could improve the diagnosis, risk stratification, and treatment of thrombosis syndromes. To this end, we have synthesized efficient multimodal nanoagents targeted to two different constituents of thrombi, namely, fibrin and activated factor XIII. These agents are targeted via the conjugation of peptide-targeting ligands to the surface of fluorescently labeled magnetic nanoparticles. As demonstrated by in vitro and in vivo studies, both nanoagents possess high affinities for thrombi, and enable mutimodal fluorescence and magnetic resonance imaging.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19456115
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4647
      1. Author :
        Jeffrey D Peterson; Timothy P LaBranche; Kristine O Vasquez; Sylvie Kossodo; Michele Melton; Randall Rader; John T Listello; Mark A Abrams; Thomas P Misko
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Arthritis Research & Therapy
      6. Products :
      7. Volume :
        12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        optical tomography; in vivo imaging; inflammation; Fluorescence molecular tomographic; FMT
      12. Abstract :
        Introduction: Standard measurements used to assess murine models of rheumatoid arthritis, notably paw thickness and clinical score, do not align well with certain aspects of disease severity as assessed by histopathology. We tested the hypothesis that non-invasive optical tomographic imaging of molecular biomarkers of inflammation and bone turnover would provide a superior quantitative readout and would discriminate between a disease-modifying anti-rheumatic drug (DMARD) and a non-DMARD treatment.

        Methods: Using two protease-activated near-infrared fluorescence imaging agents to detect inflammation-associated cathepsin and matrix metalloprotease activity, and a third agent to detect bone turnover, we quantified fluorescence in paws of mice with collagen antibody-induced arthritis. Fluorescence molecular tomographic (FMT) imaging results, which provided deep tissue detection and quantitative readouts in absolute picomoles of agent fluorescence per paw, were compared with paw swelling, clinical scores, a panel of plasma biomarkers, and histopathology to discriminate between steroid (prednisolone), DMARD (p38 mitogen-activated protein kinase (MAPK) inhibitor) and non-DMARD (celecoxib, cyclooxygenase-2 (COX-2) inhibitor) treatments.

        Results: Paw thickness, clinical score, and plasma biomarkers failed to discriminate well between a p38 MAPK inhibitor and a COX-2 inhibitor. In contrast, FMT quantification using near-infrared agents to detect protease activity or bone resorption yielded a clear discrimination between the different classes of therapeutics. FMT results agreed well with inflammation scores, and both imaging and histopathology provided clearer discrimination between treatments as compared with paw swelling, clinical score, and serum biomarker readouts.

        Conclusions: Non-invasive optical tomographic imaging offers a unique approach to monitoring disease pathogenesis and correlates with histopathology assessment of joint inflammation and bone resorption. The specific use of optical tomography allowed accurate three-dimensional imaging, quantitation in picomoles rather than intensity or relative fluorescence, and, for the first time, showed that non-invasive imaging assessment can predict the pathologist's histology inflammation scoring and discriminate DMARD from non-DMARD activity.
      13. URL :
        http://arthritis-research.com/content/12/3/R105
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4513
      1. Author :
        Jenkins, D. E.; Oei, Y.; Hornig, Y. S.; Yu, S. F.; Dusich, J.; Purchio, T.; Contag, P. R.
      2. Title :
        Bioluminescent imaging (BLI) to improve and refine traditional murine models of tumor growth and metastasis
      3. Type :
        Journal Article
      4. Year :
        2003
      5. Publication :
        Clinical and Experimental Metastasis
      6. Products :
      7. Volume :
        20
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        A549-luc-C8 cells; Animals, Cell Line, Tumor, Colonic Neoplasms/pathology, Fluorouracil/therapeutic use, Humans, Image Interpretation, Computer-Assisted, Longitudinal Studies, Luciferases/diagnostic use, Luminescent Measurements, Lung Neoplasms/ secondary, Lymphatic Metastasis, Male, Mice, Mice, SCID, Mitomycin/therapeutic use, Models, Biological, Neoplasm Transplantation, Prostatic Neoplasms/drug therapy/ pathology IVIS, Xenogen
      12. Abstract :
        Bioluminescent imaging (BLI) permits sensitive in vivo detection and quantification of cells specifically engineered to emit visible light. Three stable human tumor cell lines engineered to express luciferase were assessed for their tumorigenicity in subcutaneous, intravenous and spontaneous metastasis models. Bioluminescent PC-3M-luc-C6 human prostate cancer cells were implanted subcutaneously into SCID-beige mice and were monitored for tumor growth and response to 5-FU and mitomycin C treatments. Progressive tumor development and inhibition/regression following drug treatment were observed and quantified in vivo using BLI. Imaging data correlated to standard external caliper measurements of tumor volume, but bioluminescent data permitted earlier detection of tumor growth. In a lung colonization model, bioluminescent A549-luc-C8 human lung cancer cells were injected intravenously and lung metastases were monitored in vivo by whole animal imaging. Anesthetized mice were imaged weekly allowing a temporal assessment of in vivo lung tumor growth. This longitudinal study design permitted an accurate, real-time evaluation of tumor burden in the same animals over time. End-point bioluminescence measured in vivo correlated to total lung weight at necropsy. For a spontaneous metastatic tumor model, bioluminescent HT-29-luc-D6 human colon cancer cells implanted subcutaneously produced metastases to lung and lymph nodes in SCID-beige mice. Both primary tumors and micrometastases were detected by BLI in vivo. Ex vivo imaging of excised lung lobes and lymph nodes confirmed the in vivo signals and indicated a slightly higher frequency of metastasis in some mice. Levels of bioluminescence from in vivo and ex vivo images corresponded to the frequency and size of metastatic lesions in lungs and lymph nodes as subsequently confirmed by histology. In summary, BLI provided rapid, non-invasive monitoring of tumor growth and regression in animals. Its application to traditional oncology animal models offers quantitative and sensitive analysis of tumor growth and metastasis. The ability to temporally assess tumor development and responses to drug therapies in vivo also improves upon current standard animal models that are based on single end point data.
      13. URL :
        N/A
      14. Call Number :
        139189
      15. Serial :
        5565
      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
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