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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 :
        Lee, H. L.; Chen, C. C.; Baasov, T.; Ron, Y.; Dougherty, J. P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Mol Ther
      6. Products :
      7. Volume :
        19
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        RediJect Coelenterazine h, XenoLight
      12. Abstract :
        Cells have developed a mechanism to discriminate between premature termination codons (PTCs) and normal stop codons during translation, sparking vigorous research to develop drugs promoting readthrough at PTCs to treat genetic disorders caused by PTCs. It was posed that this concept could also be applied to regulated gene therapy protocols by incorporating a PTC into a therapeutic gene, so active protein would only be made after administration of a readthrough agent. The strengths of the system are highlighted here by results demonstrating: (i) background expression levels were reduced to 0.01% to 0.0005% of wild type in unselected mass populations of cells depending upon the specific stop codon utilized and its position within the gene; (ii) expression levels responded well to multiple “On” and “Off” regulation cycles in vivo in human xenograft systems; (iii) the level of induction approached three logs using aminoglycoside activators including NB54, a newly synthesized aminoglycoside with significantly reduced toxicity; and (iv) expression levels could be appreciably altered when employing different promoters in a variety of cell types. These results strongly support the contention that this system should have important clinical applications when tight control of gene expression is required.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21587212
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10422
      1. Author :
        Zhang, Z.; Hu, Z.; Gupta, J.; Krimmel, J. D.; Gerseny, H. M.; Berg, A. F.; Robbins, J. S.; Du, H.; Prabhakar, B.; Seth, P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cancer Gene Ther
      6. Products :
      7. Volume :
        19
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2, IVIS, Bioluminescence, Adenoviridae/genetics/*metabolism/physiology; Administration, Intravenous; Animals; Bone Neoplasms/secondary/*therapy; Cell Line, Tumor; Female; Humans; Immunocompetence; Luminescent Measurements/methods; Mammary Neoplasms, Experimental/pathology/*therapy; Mice; Mice, Inbred BALB C; Oncolytic Virotherapy/methods; Oncolytic Viruses/genetics/metabolism/physiology; Phosphorylation; Promoter Regions, Genetic; Protein-Serine-Threonine Kinases/genetics/*metabolism; Receptors, Transforming Growth Factor beta/genetics/*metabolism; Signal Transduction; Smad2 Protein/genetics/metabolism; Telomerase/genetics; Transforming Growth Factor beta1/genetics/metabolism; Transplantation, Isogeneic/methods; Tumor Stem Cell Assay/methods; Virus Replication
      12. Abstract :
        We have examined the effect of adenoviruses expressing soluble transforming growth factor receptorII-Fc (sTGFbetaRIIFc) in a 4T1 mouse mammary tumor bone metastasis model using syngeneic BALB/c mice. Infection of 4T1 cells with a non-replicating adenovirus, Ad(E1-).sTbetaRFc, or with two oncolytic adenoviruses, Ad.sTbetaRFc and TAd.sTbetaRFc, expressing sTGFbetaRIIFc (the human TERT promoter drives viral replication in TAd.sTbetaRFc) produced sTGFbetaRIIFc protein. Oncolytic adenoviruses produced viral replication and induced cytotoxicity in 4T1 cells. 4T1 cells were resistant to the cytotoxic effects of TGFbeta-1 (up to 10 ng ml(-1)). However, TGFbeta-1 induced the phosphorylation of SMAD2 and SMAD3, which were inhibited by co-incubation with sTGFbetaRIIFc protein. TGFbeta-1 also induced interleukin-11, a well-known osteolytic factor. Intracardiac injection of 4T1-luc2 cells produced bone metastases by day 4. Intravenous injection of Ad.sTbetaRFc (on days 5 and 7) followed by bioluminescence imaging (BLI) of mice on days 7, 11 and 14 in tumor-bearing mice indicated inhibition of bone metastasis progression (P<0.05). X-ray radiography of mice on day 14 showed a significant reduction of the lesion size by Ad.sTbetaRFc (P<0.01) and TAd.sTbetaRFc (P<0.05). Replication-deficient virus Ad(E1-).sTbetaRFc expressing sTGFbetaRIIFc showed some inhibition of bone metastasis, whereas Ad(E1-).Null was not effective in inhibiting bone metastases. Thus, systemic administration of Ad.sTbetaRFc and TAd.sTbetaRFc can inhibit bone metastasis in the 4T1 mouse mammary tumor model, and can be developed as potential anti-tumor agents for breast cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22744210
      14. Call Number :
        PKI @ kd.modi @ 7
      15. Serial :
        10479
      1. Author :
        Hu, Z.; Gerseny, H.; Zhang, Z.; Chen, Y. J.; Berg, A.; Stock, S.; Seth, P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Mol Ther
      6. Products :
      7. Volume :
        19
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-luc2, IVIS, Breast Cancer, Bioware
      12. Abstract :
        In recent years, oncolytic adenoviruses have shown some promise as a novel class of antitumor agents. However, their utility in targeting bone metastases is relatively less studied. We have examined whether the systemic therapy of oncolytic adenoviruses expressing the soluble form of transforming growth factor-beta (TGFbeta) receptor II fused with human immunoglobulin G1 can be developed for the treatment of established breast cancer bone metastases. MDA-MB-231-luc2 human breast cancer cells were injected in the left heart ventricle of nude mice to establish bone metastasis. Mice with hind limb tumors were administered (on days 8 and 11) oncolytic adenoviruses-Ad.sTbetaRFc or mhTERTAd.sTbetaRFc. Skeletal tumor growth was monitored weekly by bioluminescence imaging (BLI) and radiography. At the termination time on day 28, hind limb bones were analyzed for tumor burden, synchrotron micro-computed tomography, and osteoclast activation. Intravenous delivery of Ad.sTbetaRFc and mhTERTAd.sTbetaRFc induced significant inhibition of tumor growth, reduction of tumor burden, osteoclast activation, and increased animals' survival. Oncolytic adenoviruses were safer than dl309, a wild-type virus. A slight elevation of liver enzyme activity was observed after Ad.sTbetaRFc administration; this subsided with time. Based on these studies, we believe that Ad.sTbetaRFc and mhTERTAd.sTbetaRFc can be developed as a safe and effective approach for the treatment of established bone metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21712815
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10493
      1. Author :
        Wang, S.; Noberini, R.; Stebbins, J. L.; Das, S.; Zhang, Z.; Wu, B.; Mitra, S.; Billet, S.; Fernandez, A.; Bhowmick, N. A.; Kitada, S.; Pasquale, E. B.; Fisher, P. B.; Pellecchia, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Clin Cancer Res
      6. Products :
      7. Volume :
        19
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        PC-3M-luc-C6, PC-3M-luc, IVIS, Bioware, Prostate cancer, Bioluminescence
      12. Abstract :
        PURPOSE: YSA is an EphA2-targeting peptide that effectively delivers anticancer agents to prostate cancer tumors. Here, we report on how we increased the drug-like properties of this delivery system. EXPERIMENTAL DESIGN: By introducing non-natural amino acids, we have designed two new EphA2 targeting peptides: YNH, where norleucine and homoserine replace the two methionine residues of YSA, and dYNH, where a D-tyrosine replaces the L-tyrosine at the first position of the YNH peptide. We describe the details of the synthesis of YNH and dYNH paclitaxel conjugates (YNH-PTX and dYNH-PTX) and their characterization in cells and in vivo. RESULTS: dYNH-PTX showed improved stability in mouse serum and significantly reduced tumor size in a prostate cancer xenograft model and also reduced tumor vasculature in a syngeneic orthotopic allograft mouse model of renal cancer compared with vehicle or paclitaxel treatments. CONCLUSION: This study reveals that targeting EphA2 with dYNH drug conjugates could represent an effective way to deliver anticancer agents to a variety of tumor types. Clin Cancer Res; 19(1); 128-37. (c)2012 AACR.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23155185
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10541
      1. Author :
        Neal K. Devaraj; Edmund J. Keliher; Greg M. Thurber; Matthias Nahrendorf; Ralph Weissleder
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Bioconjugate Chemistry
      6. Products :
      7. Volume :
        20
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        in vivo imaging; fluorescence molecular tomography
      12. Abstract :
        We report the synthesis and in vivo characterization of an 18F modified trimodal nanoparticle (18F-CLIO). This particle consists of cross-linked dextran held together in core-shell formation by a superparamagnetic iron oxide core and functionalized with the radionuclide 18F in high yield via “click” chemistry. The particle can be detected with positron emission tomography, fluorescence molecular tomography, and magnetic resonance imaging. The presence of 18F dramatically lowers the detection threshold of the nanoparticles, while the facile conjugation chemistry provides a simple platform for rapid and efficient nanoparticle labeling.
      13. URL :
        http://pubs.acs.org/doi/abs/10.1021/bc8004649
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4498
      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 :
        Jenkins, Darlene E; Oei, Yoko; Hornig, Yvette S; Yu, Shang-Fan; Dusich, Joan; Purchio, Tony; Contag, Pamela R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2003
      5. Publication :
        Clinical & experimental metastasis
      6. Products :
      7. Volume :
        20
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        A549-luc-C8; Animals; Bioware; Cell Line, Tumor; Colonic Neoplasms; Fluorouracil; HT-29-luc-D6 cells; Humans; Image Interpretation, Computer-Assisted; Longitudinal Studies; Luciferases; Luminescent Measurements; Lung Neoplasms; Lymphatic Metastasis; Male; Mice; Mice, SCID; Mitomycin; Models, Biological; Neoplasm Transplantation; PC-3M-luc; Prostatic Neoplasms
      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 :
        http://www.ncbi.nlm.nih.gov/pubmed/14713107
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8980
      1. Author :
        Jenkins, Darlene E; Yu, Shang-Fan; Hornig, Yvette S; Purchio, Tony; Contag, Pamela R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2003
      5. Publication :
        Clinical & experimental metastasis
      6. Products :
      7. Volume :
        20
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antineoplastic Agents; Bioware; Cell Line, Tumor; Disease Models, Animal; Heart Neoplasms; Humans; Injections, Subcutaneous; Luminescent Measurements; Lung Neoplasms; Lymphatic Metastasis; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Recurrence, Local; PC-3M-luc; Prostatic Neoplasms
      12. Abstract :
        We used the bioluminescent human prostate carcinoma cell line PC-3M-luc-C6 to non-invasively monitor in vivo growth and response of tumors and metastasis before, during and after treatments. Our goal was to determine the utility of a luciferase-based prostate cancer animal model to specifically assess tumor and metastatic recurrence in vivo following chemotherapy. Bioluminescent PC-3M-luc-C6 cells, constitutively expressing luciferase, were implanted into the prostate or under the skin of mice for primary tumor assessment. Cells were also injected into the left ventricle of the heart as an experimental metastasis model. Weekly serial in vivo images were taken of anesthetized mice that were untreated or treated with 5-fluorouracil or mitomycin C. Ex vivo imaging and/or histology was used to confirm and localize metastatic lesions in various tissues initially detected by images in vivo. Our in vivo data detected and quantified early inhibition of subcutaneous and orthotopic prostate tumors in mice as well as significant tumor regrowth post-treatment. Local and distal metastasis was observed within seven days following intracardiac injection of PC-3M-luc-C6 cells. Differential drug responses and metastatic tumor relapse patterns were distinguished over time by in vivo imaging depending on the metastatic site. The longitudinal evaluation of bioluminescent tumor and metastatic development within the same cohorts of animals permitted sensitive and quantitative assessment of both primary and metastatic prostate tumor response and recurrence in vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/14713108
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8981
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