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      1. Author :
        Marttila-Ichihara, Fumiko; Auvinen, Kaisa; Elima, Kati; Jalkanen, Sirpa; Salmi, Marko
      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 :
        Amine Oxidase (Copper-Containing); Animals; Antigens, CD11b; B16-F10-luc-G5 cells; Bioware; Cell Adhesion Molecules; Cell Growth Processes; Female; Lymphoma; Male; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myeloid Cells; Neovascularization, Pathologic; Oxidoreductases; Receptors, Chemokine
      12. Abstract :
        Cancer growth is regulated by several nonmalignant cell types, such as leukocytes and endothelial cells, which reside in the stroma of the tumor. Vascular adhesion protein-1 (VAP-1) is an amine oxidase enzyme that is expressed on the surface of endothelial cells. It supports leukocyte traffic into inflamed tissues, but nothing is known about its possible role in cancer biology in vivo. Here, we report that B16 melanoma and EL-4 lymphoma remain smaller in VAP-1-deficient mice than in wild-type controls. We found an unexpected defect in tumor angiogenesis in the absence of VAP-1. VAP-1 also selectively enhanced the recruitment of Gr-1+CD11b+ myeloid cells into the tumors. Generation of mice expressing enzymatically inactive VAP-1 showed that the oxidase activity of VAP-1 was necessary to support neoangiogenesis, myeloid cell recruitment, and tumor growth in vivo. These data describe VAP-1 as the first adhesion molecule known to be involved in the recruitment of Gr-1+CD11b+ myeloid cells into tumors. They also suggest that VAP-1 is a potential new tool for immunotherapy of tumors that could be exploited to reduce tumor burden by controlling the traffic of Gr-1+CD11b+ myeloid cells.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19789345
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8997
      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 :
        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 :
        Motohara, T.; Masuko, S.; Ishimoto, T.; Yae, T.; Onishi, N.; Muraguchi, T.; Hirao, A.; Matsuzaki, Y.; Tashiro, H.; Katabuchi, H.; Saya, H.; Nagano, O.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Carcinogenesis
      6. Products :
      7. Volume :
        32
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Antigens, Neoplasm/genetics/metabolism; Apoptosis; Blotting, Western; Cell Adhesion; Cell Adhesion Molecules/genetics/metabolism; Cell Differentiation; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic/metabolism/*pathology; Female; Flow Cytometry; Immunoenzyme Techniques; Mice; Mice, Inbred C57BL; Neoplastic Stem Cells/metabolism/*pathology; Ovarian Neoplasms/genetics/metabolism/*pathology; Ovary/metabolism/*pathology; Peritoneal Neoplasms/genetics/metabolism/*secondary; Proto-Oncogene Proteins c-myc/genetics/metabolism; Proto-Oncogene Proteins p21(ras)/genetics/metabolism; RNA, Messenger/genetics; RNA, Small Interfering/genetics; Reverse Transcriptase Polymerase Chain Reaction; Tumor Suppressor Protein p53/antagonists & inhibitors/genetics/*metabolism
      12. Abstract :
        Although the existence of tumor-initiating cells (T-ICs) in several types of human cancer has been documented, the contribution of somatic stem cells to the development of T-ICs has remained unclear. Here, we show that normal mouse ovary contains epithelial cell adhesion molecule (EpCAM)-expressing stem-like cells that possess the ability to differentiate into cytokeratin 8 (CK8)-expressing epithelial progeny cells. Furthermore, RNA interference-mediated transient depletion of the tumor suppressor p53 followed by retrovirus-mediated transfer of c-Myc and K-Ras oncogenes in EpCAM-expressing ovarian stem-like cells resulted in the generation of ovarian T-ICs. The established ovarian T-ICs gave rise to hierarchically organized lethal tumors in vivo and were able to undergo peritoneal metastasis. Finally, subsequent RNA interference-mediated knockdown of p53 in tumor cells triggered the expansion of EpCAM-expressing stem-like tumor cells and induced further tumor growth. These data reveal a role for p53 in the development and expansion of ovarian stem-like tumor cells and subsequent malignant progression.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21828057
      14. Call Number :
        PKI @ kd.modi @ 16
      15. Serial :
        10374
      1. Author :
        Noberini, R.; Rubio de la Torre, E.; Pasquale, E. B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cell Adh Migr
      6. Products :
      7. Volume :
        6
      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, Animals; Chromatography, Liquid; Enzyme-Linked Immunosorbent Assay; Ephrins/genetics/*metabolism; Humans; Mass Spectrometry/*methods; Mice; Receptor, EphA1/genetics/*metabolism
      12. Abstract :
        The Eph receptor tyrosine kinase family includes many members, which are often expressed together in various combinations and can promiscuously interact with multiple ephrin ligands, generating intricate networks of intracellular signals that control physiological and pathological processes. Knowing the entire repertoire of Eph receptors and ephrins expressed in a biological sample is important when studying their biological roles. Moreover, given the correlation between Eph receptor/ephrin expression and cancer pathogenesis, their expression patterns could serve important diagnostic and prognostic purposes. However, profiling Eph receptor and ephrin expression has been challenging. Here we describe a novel and straightforward approach to catalog the Eph receptors present in cultured cells and tissues. By measuring the binding of ephrin Fc fusion proteins to Eph receptors in ELISA and pull-down assays, we determined that a mixture of four ephrins is suitable for isolating both EphA and EphB receptors in a single pull-down. We then used mass spectrometry to identify the Eph receptors present in the pull-downs and estimate their relative levels. This approach was validated in cultured human cancer cell lines, human tumor xenograft tissue grown in mice, and mouse brain tissue. The new mass spectrometry approach we have developed represents a useful tool for the identification of the spectrum of Eph receptors present in a biological sample and could also be extended to profiling ephrin expression.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22568954
      14. Call Number :
        PKI @ kd.modi @ 8
      15. Serial :
        10538
      1. Author :
        Hickson, J; Ackler, S; Klaubert, D; Bouska, J; Ellis, P; Foster, K; Oleksijew, A; Rodriguez, L; Schlessinger, S; Wang, B; Frost, D
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cell death and differentiation
      6. Products :
      7. Volume :
        17
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antineoplastic Agents; Apoptosis; Bioware; Caspase 3; Cell Line, Tumor; Female; Firefly Luciferin; Humans; Luminescent Agents; MDA-MB-231-D3H2LN cells; Mice; Mice, SCID; SKOV3-luc-D3 cells; Molecular Imaging; Neoplasms; Oligopeptides; Taxoids
      12. Abstract :
        Apoptosis is a highly regulated process of programmed cell death essential for normal physiology. Dysregulation of apoptosis contributes to the development and progression of various diseases, including cancer, neurodegenerative disorders, and chronic heart failure. Quantitative noninvasive imaging of apoptosis in preclinical models would allow for dynamic longitudinal screening of compounds and facilitates a more rapid determination of therapeutic efficacy. In this study, we report the in vivo characterization of Z-DEVD-aminoluciferin, a modified firefly luciferase substrate that in apoptotic cells is cleaved by caspase-3 to liberate aminoluciferin, which can be consumed by luciferase to generate a luminescent signal. In two oncology models, namely SKOV3-luc and MDA-MB-231-luc-LN, at 24, 48, and 72 h after treatment with docetaxel, animals were injected with Z-DEVD-aminoluciferin and bioluminescent images were acquired. Significantly more light was detected at 24 (P<0.05), 48 (P<0.01), and 72 h (P<0.01) in the docetaxel-treated group compared with the vehicle-treated group, with caspase-3 activation at these time points confirmed using immunohistochemistry. Importantly, whereas significant differences between groups were detected as early as 24 h after treatment by molecular imaging, caliper measurements were unable to detect a difference for 4-5 additional days. Taken together, these data show that in vivo imaging of apoptosis using Z-DEVD-aminoluciferin could provide a sensitive and rapid method for early detection of drug efficacy, which could potentially be used by numerous therapeutic programs.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20057500
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8950
      1. Author :
        Thomas Christen, Matthias Nahrendorf, Moritz Wildgruber, Filip K. Swirski, Elena Aikawa, Peter Waterman, Koichi Shimizu, Ralph Weissleder and Peter Libby
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Circulation
      6. Products :
      7. Volume :
        119
      8. Issue :
        14
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        In vivo imaging; inflammation; leukocytes; rejection; transplantation; fluorescence molecular tomography; FMT; Prosense
      12. Abstract :
        Background: Clinical detection of transplant rejection by repeated endomyocardial biopsy requires catheterization and entails risks. Recently developed molecular and cellular imaging techniques that visualize macrophage host responses could provide a noninvasive alternative. Yet, which macrophage functions may provide useful markers for detecting parenchymal rejection remains uncertain.

        Methods and Results: We transplanted isografts from B6 mice and allografts from Balb/c mice heterotopically into B6 recipients. In this allograft across major histocompatability barriers, the transplanted heart undergoes predictable progressive rejection, leading to graft failure after 1 week. During rejection, crucial macrophage functions, including phagocytosis and release of proteases, render these abundant innate immune cells attractive imaging targets. Two or 6 days after transplantation, we injected either a fluorescent protease sensor or a magnetofluorescent phagocytosis marker. Histological and flow cytometric analyses established that macrophages function as the major cellular signal source. In vivo, we obtained a 3-dimensional functional map of macrophages showing higher phagocytic uptake of magnetofluorescent nanoparticles during rejection using magnetic resonance imaging and higher protease activity in allografts than in isografts using tomographic fluorescence. We further assessed the sensitivity of imaging to detect the degree of rejection. In vivo imaging of macrophage response correlated closely with gradually increasing allograft rejection and attenuated rejection in recipients with a genetically impaired immune response resulting from a deficiency in recombinase-1 (RAG-1-/-).

        Conclusions: Molecular imaging reporters of either phagocytosis or protease activity can detect cardiac allograft rejection noninvasively, promise to enhance the search for novel tolerance-inducing strategies, and have translational potential.
      13. URL :
        http://circ.ahajournals.org/cgi/content/abstract/circulationaha;119/14/1925
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4640
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