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      1. Author :
        Hokaiwado, Naomi; Takeshita, Fumitaka; Naiki-Ito, Aya; Asamoto, Makoto; Ochiya, Takahiro; Shirai, Tomoyuki
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Carcinogenesis
      6. Products :
      7. Volume :
        29
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Androgens; Animals; Animals, Genetically Modified; Apoptosis; Bioware; Blotting, Western; Cell Line, Tumor; Cell Proliferation; Glutathione S-Transferase pi; Humans; In Situ Nick-End Labeling; Male; Neoplasm Transplantation; Oligonucleotide Array Sequence Analysis; PC-3M-luc; Prostatic Neoplasms; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Small Interfering
      12. Abstract :
        Prostate cancers generally acquire an androgen-independent growth capacity with progression, resulting in resistance to antiandrogen therapy. Therefore, identification of the genes regulated through this process may be important for understanding the mechanisms of prostate carcinogenesis. We here utilized androgen-dependent/independent transplantable tumors, newly established with the 'transgenic rat adenocarcinoma in prostate' (TRAP) model, to analyze their gene expression using microarrays. Among the overexpressed genes in androgen-independent prostate cancers compared with the androgen-dependent tumors, glutathione S-transferase pi (GST-pi) was included. In line with this, human prostate cancer cell lines PC3 and DU145 (androgen independent) had higher expression of GST-pi compared with LNCaP (androgen dependent) as determined by semiquantitative reverse transcription-polymerase chain reaction analysis. To investigate the roles of GST-pi expression in androgen-independent human prostate cancers, GST-pi was knocked down by a small interfering RNA (siRNA), resulting in significant decrease of the proliferation rate in the androgen-independent PC3 cell line. In vivo, administration of GST-pi siRNA-atelocollagen complex decreased GST-pi protein expression, resulting in enhanced numbers of TdT mediated dUTP-biotin nick-end labering (TUNEL)-positive apoptotic cells. These findings suggest that GST-pi might play important roles in proliferation of androgen-independent human prostate cancer cells.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18413363
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8967
      1. Author :
        Lyons, Scott K; Lim, Ed; Clermont, Anne O; Dusich, Joan; Zhu, Lingyun; Campbell, Kenneth D; Coffee, Richard J; Grass, David S; Hunter, John; Purchio, Tony; Jenkins, Darlene
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Cancer research
      6. Products :
      7. Volume :
        66
      8. Issue :
        9
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Androgens; Animals; Bioware; Cell Transformation, Neoplastic; Disease Models, Animal; Genes, Reporter; Humans; Image Processing, Computer-Assisted; In Situ Hybridization; Luciferases, Firefly; Luminescent Measurements; Male; Mice; Mice, Transgenic; PC-3M-luc; Promoter Regions, Genetic; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms
      12. Abstract :
        Several transgenic mouse models of prostate cancer have been developed recently that are able to recapitulate many key biological features of the human condition. It would, therefore, be desirable to employ these models to test the efficacy of new therapeutics before clinical trial; however, the variable onset and non-visible nature of prostate tumor development limit their use for such applications. We now report the generation of a transgenic reporter mouse that should obviate these limitations by enabling noninvasive in vivo bioluminescence imaging of normal and spontaneously transformed prostate tissue in the mouse. We used an 11-kb fragment of the human prostate-specific antigen (PSA) promoter to achieve specific and robust expression of firefly luciferase in the prostate glands of transgenic mice. Ex vivo bioluminescence imaging and in situ hybridization analysis confirmed that luciferase expression was restricted to the epithelium in all four lobes of the prostate. We also show that PSA-Luc mice exhibit decreased but readily detectable levels of in vivo bioluminescence over extended time periods following androgen ablation. These results suggest that this reporter should enable in vivo imaging of both androgen-dependent and androgen-independent prostate tumor models. As proof-of-principle, we show that we could noninvasively image SV40 T antigen-induced prostate tumorigenesis in mice with PSA-Luc. Furthermore, we show that our noninvasive imaging strategy can be successfully used to image tumor response to androgen ablation in transgenic mice and, as a result, that we can rapidly identify individual animals capable of sustaining tumor growth in the absence of androgen.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16651422
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8975
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Angiogenesis
      6. Products :
      7. Volume :
        13
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        angiogenesis imaging; in vivo imaging; Angiogenesis; Bioluminescence; Fluorescence; Molecular imaging; Optical imaging
      12. Abstract :
        In recent years, molecular imaging gained significant importance in biomedical research. Optical imaging developed into a modality which enables the visualization and quantification of all kinds of cellular processes and cancerous cell growth in small animals. Novel gene reporter mice and cell lines and the development of targeted and cleavable fluorescent “smart” probes form a powerful imaging toolbox. The development of systems collecting tomographic bioluminescence and fluorescence data enabled even more spatial accuracy and more quantitative measurements. Here we describe various bioluminescent and fluorescent gene reporter models and probes that can be used to specifically image and quantify neovascularization or the angiogenic process itself.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911541/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4488
      1. Author :
        Aki Hanyu; Kiyotsugu Kojima; Kiyohiko Hatake; Kimie Nomura; Hironori Murayama; Yuichi Ishikawa; Satoshi Miyata; Masaru Ushijima; Masaaki Matsuura; Etsuro Ogata; Keiji Miyazawa;Takeshi Imamura
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Cancer Science
      6. Products :
      7. Volume :
        100
      8. Issue :
        11
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Angiogenesis; metastasis; in vivo imaging; fluorescence imaging
      12. Abstract :
        Angiogenesis plays a crucial role in cancer progression and metastasis. Thus, blocking tumor angiogenesis is potentially a universal approach to prevent tumor establishment and metastasis. In this study, we used in vivo and ex vivo fluorescence imaging to show that an antihuman vascular endothelial growth factor (VEGF) antibody represses angiogenesis and the growth of primary tumors of human fibrosarcoma HT1080 cells in implanted nude mice. Interestingly, administering the antihuman VEGF antibody reduced the development of new blood vessels and normalized pre-existing tumor vasculature in HT1080 cell tumors. In addition, antihuman VEGF antibody treatment decreased lung metastasis from the primary tumor, whereas it failed to block lung metastasis in a lung colonization experiment in which tumor cells were injected into the tail vein. These results suggest that VEGF produced by primary HT1080 cell tumors has a crucial effect on lung metastasis. The present study indicates that the in vivo fluorescent microscopy system will be useful to investigate the biology of angiogenesis and test the effectiveness of angiogenesis inhibitors.
      13. URL :
        http://onlinelibrary.wiley.com/doi/10.1111/j.1349-7006.2009.01305.x/full
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4495
      1. Author :
        Huang, Yujie; Song, Nan; Ding, Yanping; Yuan, Shaopeng; Li, Xuhui; Cai, Hongchen; Shi, Hubing; Luo, Yongzhang
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Cancer research
      6. Products :
      7. Volume :
        69
      8. Issue :
        19
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Angiopoietin-2; Animals; Bioware; Breast Neoplasms; Capillary Permeability; Female; Gene Expression; Humans; Lung; Lung Neoplasms; Matrix Metalloproteinase 10; Matrix Metalloproteinase 3; MDA-MB-231-D3H1 cells; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, Nude; RNA Interference; Up-Regulation
      12. Abstract :
        Before metastasis, certain organs have already been influenced by primary tumors. However, the exact alterations and regulatory mechanisms of the premetastatic organs remain poorly understood. Here, we report that, in the premetastatic stage, angiopoietin 2 (Angpt2), matrix metalloproteinase (MMP) 3, and MMP10 are up-regulated in the lung by primary B16/F10 tumor, which leads to the increased permeability of pulmonary vasculatures and extravasation of circulating tumor cells. Subsequent studies show that Angpt2, MMP3, and MMP10 have a synergistic effect on disrupting vascular integrity in both in vitro and in vivo models. Lentivirus-based in vivo RNA interference of Angpt2, MMP3, and MMP10 attenuates the pulmonary vascular permeability and suppresses the infiltration of myeloid cells in the premetastatic lung. Moreover, knocking down these factors significantly inhibits the spontaneous lung metastasis in the model by orthotopic implantation of MDA-MB-231-Luc-D3H1 cells in nude mice. Further investigations reveal that the malignancy of tumor cells is positively correlated with their capabilities to induce the expression of Angpt2, MMP3, and MMP10. Luciferase reporter assay and chromatin immunoprecipitation assay also suggest that transforming growth factor-beta1 and tumor necrosis factor-alpha signaling are involved in the regulation of these premetastatic factors. Our study shows that pulmonary vascular destabilization in the premetastatic phase promotes the extravasation of tumor cells and facilitates lung metastasis, which may provide potential targets for clinical prevention of metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19773447
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8989
      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
      1. Author :
        Lee, S.; Vinegoni, C.; Feruglio, P. F.; Fexon, L.; Gorbatov, R.; Pivoravov, M.; Sbarbati, A.; Nahrendorf, M.; Weissleder, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Commun
      6. Products :
      7. Volume :
        3
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense
      12. Abstract :
        Real-time imaging of moving organs and tissues at microscopic resolutions represents a major challenge in studying the complex biology of live animals. Here we present a technique based on a novel stabilizer setup combined with a gating acquisition algorithm for the imaging of a beating murine heart at the single-cell level. The method allows serial in vivo fluorescence imaging of the beating heart in live mice in both confocal and nonlinear modes over the course of several hours. We demonstrate the utility of this technique for in vivo optical sectioning and dual-channel time-lapse fluorescence imaging of cardiac ischaemia. The generic method could be adapted to other moving organs and thus broadly facilitate in vivo microscopic investigations.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22968700
      14. Call Number :
        PKI @ kd.modi @ 7
      15. Serial :
        10436
      1. Author :
        Ackermann, M.; Carvajal, I.M.; Morse, B.A.; Moreta, M.; O'Neil, S.; Kossodo, S.; Peterson, J.D.; Delventhal, V.; Marsh, H.N.; Furfine, E.S.; Konerding, M.A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        International Journal of Oncology
      6. Products :
      7. Volume :
        38
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense 680; anti-angiogenic; anti-tumorigenic; Cancer; FMT1 (VisEn); FMT-Solaris; In vivo imaging (VisEn); intraperitoneal injection; mice
      12. Abstract :
        Antiangiogenesis has become a promising pillar in modern cancer therapy. This study investigates the antiangiogenic effects of the PEGylated Adnectin[TM], CT-322, in a murine Colo-205 xenograft tumor model. CT-322 specifically binds to and blocks vascular endothelial growth factor receptor (VEGFR-2). Adnectins are a novel class of targeted biologics engineered from the 10th domain of human fibronectin. CT-322 treated tumors exhibited a significant reduction in tumor growth of 69%, a 2.8 times lower tumor surface area and fewer necrotic areas. Control tumors showed a 2.36-fold higher microvessel density (MVD) and a 2.42 times higher vessel volume in corrosion casts. The vascular architecture in CT-322-treated tumors was characterized by a strong normalization of vasculature. This was quantified in corrosion casts of CT-322 treated tumors in which the intervascular distance (a reciprocal parameter indicative of vessel density) and the distance between two consecutive branchings were assessed, with these distances being 2.21 times and 2.37 times greater than in controls, respectively. Fluorescence molecular tomography (FMT) equally affirmed the inhibitory effects of CT-322 on tumor vasculature as indicated by a 60% reduction of the vascular probe, AngioSense, accumulating in tumor tissue, as a measurement of vascular permeability. Moreover, AngioSense accumulation was reduced as early as 24 h after starting treatment. The sum of these effects on tumor vasculature illustrates the anti-angiogenic mechanism underlying the antitumor activity of CT-322 and provides support for further evaluation of this Adnectin in combinatorial strategies with standard of care therapies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21109927
      14. Call Number :
        PKI @ user @ 8449
      15. Serial :
        4804
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