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      1. Author :
        Zeng, Q.; Yang, Z.; Gao, Y. J.; Yuan, H.; Cui, K.; Shi, Y.; Wang, H.; Huang, X.; Wong, S. T.; Wang, Y.; Kesari, S.; Ji, R. R.; Xu, X.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Eur J Cancer
      6. Products :
      7. Volume :
        46
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-D3H2Ln, IVIS, Bioluminescence, Animals; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use; Cell Hypoxia/physiology; Cell Line, Tumor; Cyclophosphamide/*therapeutic use; Female; Immunohistochemistry; Lung Neoplasms/prevention & control/secondary; Mammary Neoplasms, Experimental/*drug therapy/genetics/pathology; Mice; Mice, Nude; Sirolimus/*therapeutic use; Tumor Burden; Xenograft Model Antitumor Assays
      12. Abstract :
        Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, has been shown to inhibit the growth of oestrogen positive breast cancer. However, triple-negative (TN) breast cancer is resistant to rapamycin treatment in vitro. We set to test a combination treatment of rapamycin with DNA-damage agent, cyclophosphamide, in a TN breast cancer model. By binding to and disrupting cellular DNA, cyclophosphamide kills cells via interfering with their normal functions. We assessed the responses of nude mice bearing tumour xenografts of TN MDA-MB-231 cells to the combination of rapamycin and cyclophosphamide in both orthotopic mammary and lung-metastasis models. We tracked tumour growth and metastasis by bioluminescent imaging and examined the expression of Ki67, CD34 and HIF-1alpha in tumour tissues by immunohistochemistry and apoptosis index with TUNEL assay, and found that MDA-MB-231 cells are sensitive to rapamycin therapy in orthotopic mammary, but not in lung with metastasis. Rapamycin when combined with cyclophosphamide is found to have a more significant effect in reducing tumour volume and metastasis with a much improved survival rate. Our data also show that the sensitivity of TN tumours to rapamycin is associated with the microenvironment of the tumour cells. The data indicate that in a relatively hypoxic environment HIF-1alpha may play a role in mediating the anti-cancer effect of rapamycin and cyclophosphamide may prevent the feedback activation of Akt by rapamycin. Overall our results show that rapamycin plus cyclophosphamide can achieve an improved efficacy in suppressing tumour growth and metastasis, suggesting that the combination therapy can be a promising treatment option for TN cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20156674
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10414
      1. Author :
        Daugimont, L.; Vandermeulen, G.; Defresne, F.; Bouzin, C.; Mir, L. M.; Bouquet, C.; Feron, O.; Preat, V.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Pharm Biopharm
      6. Products :
      7. Volume :
        78
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, IVIS
      12. Abstract :
        BACKGROUND: Despite the discovery of novel inhibitors of tumor angiogenesis, protein-based antiangiogenic cancer therapy suffers some limitations that antiangiogenic gene therapy could overcome. We investigated whether intra-tumoral electrotransfer of three angiogenic plasmids could inhibit tumor growth and metastasis. METHODS: Plasmids encoding recombinant disintegrin domain of ADAM-15 (RDD), thrombospondin 1 (TSP-1), and the soluble isoform of the VEGF receptor 1 (sFlt-1) were injected into B16F10 melanoma-bearing C57BL/6 mice followed by electroporation. Tumor volume was measured daily using a digital caliper. Metastasis was monitored by in vivo bioluminescence after surgical removal of the primary luciferase-encoding B16F10 tumor 5 days after intra-tumoral electrotransfer. Markers of vascularization and cell proliferation were quantified by immunohistochemistry. RESULTS: Intra-tumoral electrotransfer of the antiangiogenic plasmids induced a significant inhibition of tumor growth, doubling of mean survival time and long-term survivors ( approximately 40% vs 0% in control). When the tumor was removed by surgery after intra-tumoral plasmid electrotransfer, a significant decrease in tumor metastasis was observed leading to long-term tumor-free survival especially after treatment with pRDD plasmid (84% vs 0% in control). Unlike pTSP-1 and psFlt-1, pRDD significantly decreased cell proliferation in B16F10 primary tumors which express alphavbeta3 and alpha5beta1 integrins. No effect of antiangiogenic plasmid electrotransfer on normal skin blood flow was detected. CONCLUSION: The intra-tumoral electrotransfer of the three antiangiogenic plasmids is a promising method for the treatment of melanoma. The plasmid encoding RDD seems to be particularly effective due to its direct antitumoral activity combined with angiogenesis suppression, and its marked inhibition of metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21316447
      14. Call Number :
        PKI @ kd.modi @ 12
      15. Serial :
        10353
      1. Author :
        Al Marzouqi, N.; Iratni, R.; Nemmar, A.; Arafat, K.; Ahmed Al Sultan, M.; Yasin, J.; Collin, P.; Mester, J.; Adrian, T. E.; Attoub, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Pharmacol
      6. Products :
      7. Volume :
        N/A
      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 :
        Breast cancer is a major challenge for pharmacologists to develop new drugs to improve the survival of cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa. It has been demonstrated that Frondoside A inhibited the growth of pancreatic cancer cells in vitro and in vivo. We investigated the impact of Frondoside A on human breast cancer cell survival, migration and invasion in vitro, and on tumor growth in nude mice, using the human estrogen receptor-negative breast cancer cell line MDA-MB-231. The non-tumorigenic MCF10-A cell line derived from normal human mammary epithelium was used as control. Frondoside A (0.01-5muM) decreased the viability of breast cancer cells in a concentration- and time-dependent manner, with 50%-effective concentration (EC50) of 2.5muM at 24h. MCF10-A cells were more resistant to the cytotoxic effect of Frondoside A (EC50 superior to 5muM at 24h). In the MDA-MB-231 cells, Frondoside A effectively increased the sub-G1 (apoptotic) cell fraction through the activation of p53, and subsequently the caspases 9 and 3/7 cell death pathways. In addition, Frondoside A induced a concentration-dependent inhibition of MDA-MB-231 cell migration and invasion. In vivo, Frondoside A (100mug/kg/dayi.p. for 24days) strongly decreased the growth of MDA-MB-231 tumor xenografts in athymic mice, without manifest toxic side-effects. Moreover, we found that Frondoside A could enhance the killing of breast cancer cells induced by the chemotherapeutic agent paclitaxel. These findings identify Frondoside A as a promising novel therapeutic agent for breast cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21741966
      14. Call Number :
        PKI @ kd.modi @ 7
      15. Serial :
        10490
      1. Author :
        Hutteman, M.; Mieog, J. S.; van der Vorst, J. R.; Dijkstra, J.; Kuppen, P. J.; van der Laan, A. M.; Tanke, H. J.; Kaijzel, E. L.; Que, I.; van de Velde, C. J.; Lowik, C. W.; Vahrmeijer, A. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Surg Oncol
      6. Products :
      7. Volume :
        37
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense, Animals; Colorectal Neoplasms/*metabolism/*secondary; Disease Models, Animal; Image Processing, Computer-Assisted; Integrin alphaVbeta3/*metabolism; Intraoperative Period; Liver Neoplasms/*pathology; Male; Neoplasm Transplantation; Rats; Spectroscopy, Near-Infrared/*methods; Tumor Cells, Cultured
      12. Abstract :
        AIM: Near-infrared (NIR) fluorescence optical imaging is a promising technique to assess the extent of colorectal metastases during curative-intended surgery. However, NIR fluorescence imaging of liver metastases is highly challenging due to hepatic uptake and clearance of many fluorescent dyes. In the current study, the biodistribution and the ability to demarcate liver and peritoneal metastases were assessed during surgery in a syngeneic rat model of colorectal cancer using an integrin alpha(v)beta(3)-directed NIR fluorescence probe. METHODS: Liver tumors and peritoneal metastases were induced in 7 male WAG/Rij rats by subcapsular inoculation of 0.5 x 10(6) CC531 colorectal cancer rat cells into three distinct liver lobes. Intraoperative and ex vivo fluorescence measurements were performed 24 (N = 3 rats, 7 tumors) and 48 h (N = 4 rats, 9 tumors) after intravenous administration of the integrin alpha(v)beta(3)-directed NIR fluorescence probe. RESULTS: Colorectal metastases had a minimal two-fold higher NIR fluorescence signal than healthy liver tissue and other abdominal organs (p < 0.001). The tumor-to-background ratio was independent of time of imaging (24 h vs. 48 h post-injection; p = 0.31), which facilitates flexible operation planning in future clinical applications. Total fluorescence intensity was significantly correlated with the size of metastases (R(2) = 0.92 for the 24 h group, R(2) = 0.96 for the 48 h group). CONCLUSION: These results demonstrate that colorectal intra-abdominal metastases can be clearly demarcated during surgery using an integrin alpha(v)beta(3) targeting NIR fluorescence probe. Translating these findings to the clinic will have an excellent potential to substantially improve the quality of cancer surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21215590
      14. Call Number :
        PKI @ kd.modi @ 23
      15. Serial :
        10366
      1. Author :
        Lorenz, U.; Schafer, T.; Ohlsen, K.; Tiurbe, G. C.; Buhler, C.; Germer, C. T.; Kellersmann, R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Vasc Endovasc Surg
      6. Products :
      7. Volume :
        41
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29, Acetates; Animals; *Biofilms; Bioprosthesis; Blood Vessel Prosthesis/*microbiology; Cattle; Colony Count, Microbial; Luminescent Measurements/*methods; Mice; Microbial Viability; Pericardium; *Photons; Polyesters; Polytetrafluoroethylene; Prospective Studies; Prosthesis-Related Infections/*diagnosis; Random Allocation; Silver Compounds; Staphylococcus aureus/isolation & purification/*physiology
      12. Abstract :
        OBJECTIVES: Biophotonic imaging was compared to standard enumeration method both for counting Staphylococcus aureus in biofilm and bacterial susceptibility tests of different graft materials. DESIGN: Prospective, randomized, controlled animal study. MATERIAL AND METHODS: Five types of vascular grafts were placed subcutaneously in 35 mice and challenged with bioluminescent S. aureus. The mice were divided into equal groups as follows: group A (polyester), group B (polytetrafluoroethylene), group C and D (two types of silver acetate-coated polyester) and group E (bovine pericardium). Controls were given only the bacteria. The bioluminescence signal of S. aureus, able to predict number of viable bacteria in biofilm without any manipulation, was measured at different time points. Five days postinfection, regular cultures of adherent bacteria on grafts were obtained. Comparative analyses between bioluminescence activity and culture enumeration were performed. RESULTS: The number of viable bacteria on silver-coated prostheses was the slightest, indicating superior bacterial resistance. The density of bacteria on polytetrafluoroethylene and polyester was comparable, with a non-significant advantage for polytetrafluoroethylene. Moreover, bioluminescence detected the number of viable S. aureus in biofilm more exactly compared to enumeration of bacteria. CONCLUSION: Bioluminescence imaging can be considered a useful tool to characterize susceptibility of any graft material to bacterial biofilm prior to implantation.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20943422
      14. Call Number :
        PKI @ kd.modi @ 12
      15. Serial :
        10453
      1. Author :
        Edinger, M; Cao, Y-a; Hornig, Y S; Jenkins, D E; Verneris, M R; Bachmann, M H; Negrin, R S; Contag, C H
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2002
      5. Publication :
        European journal of cancer (Oxford, England: 1990)
      6. Products :
      7. Volume :
        38
      8. Issue :
        16
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Diagnostic Imaging; Forecasting; Luminescent Measurements; Mice; Models, Animal; Neoplasms; PC-3M-luc; Sensitivity and Specificity
      12. Abstract :
        Malignant disease is the final manifestation of complex molecular and cellular events leading to uncontrolled cellular proliferation and eventually tissue destruction and metastases. While the in vitro examination of cultured tumour cells permits the molecular dissection of early pathways in tumorigenesis on cellular and subcellular levels, only interrogation of these processes within the complexity of organ systems of the living animal can reveal the full range of pathophysiological changes that occur in neoplastic disease. Such analyses require technologies that facilitate the study of biological processes in vivo, and several approaches have been developed over the last few years. These strategies, in the nascent field of in vivo molecular and cellular imaging, combine molecular biology with imaging modalities as a means to real-time acquisition of functional information about disease processes in living systems. In this review, we will summarise recent developments in in vivo bioluminescence imaging (BLI) and discuss the potential of this imaging strategy for the future of cancer research.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/12387838
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8983
      1. Author :
        E.A. te Velde; Th. Veerman; V. Subramaniam; Th. Ruers
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        European Journal of Cancer Surgery
      6. Products :
      7. Volume :
        36
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Fluorescent; Sentinel node; Probe; Resection; Oncology; Surgery
      12. Abstract :
        Aims and background: Improved visualization of surgical targets inside of the patient helps to improve radical resection of the tumor while sparing healthy surrounding tissue. In order to achieve an image, optical contrast must be generated by properties intrinsic to the tissue, or require the attachment of special visualization labels to the tumor. In this overview the current status of the clinical use of fluorescent dyes and probes are reviewed.

        Methods: In this review, all experimental and clinical studies concerning fluorescent imaging were included. In addition, in the search for the optimal fluorescent imaging modality, all characteristics of a fluorescent dye were described.

        Findings and conclusions: Although the technique of imaging through fluorescence sounds promising and several animal models show efficacy, official approval of these agents for further clinical evaluation, is eagerly awaited.
      13. URL :
        http://www.ejso.com/article/S0748-7983%2809%2900498-3/abstract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4491
      1. Author :
        Gillrie, Mark R; Zbytnuik, Lori; McAvoy, Erin; Kapadia, Roxna; Lee, Kristine; Waterhouse, Christopher C M; Davis, Shevaun P; Muruve, Daniel A; Kubes, Paul; Ho, May
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        European journal of immunology
      6. Products :
      7. Volume :
        40
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Chemotaxis, Leukocyte; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Humans; Interferon-gamma; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mice, Knockout; Staphylococcal Infections; Staphylococcus aureus; Teichoic Acids; Toll-Like Receptor 2; Transplantation Chimera; Xen29
      12. Abstract :
        The response of leukocytes to lipoteichoic acid (LTA), a TLR2-dependent major cell wall component of Staphylococcus aureus, is linked to the outcome of an infection. In this study we investigated the role of nonhematopoietic TLR2 in response to LTA and S. aureus by creating bone marrow chimeras. Significant leukocyte recruitment in response to LTA required IFN-gamma priming in WT C57BL/6 and TLR2(-/-)-->WT mice, but was not observed in TLR2(-/-) or WT-->TLR2(-/-) animals. LTA also induced a proinflammatory response in IFN-gamma primed primary human microvascular endothelial cells leading to leukocyte recruitment in vitro. When mice were infected with S. aureus, the most profound elevation of TNF-alpha and IL-6 was seen in TLR2(-/-) and TLR2(-/-)-->WT mice. TLR2(-/-), but not chimeric mice, demonstrated increased IL-17, blood leukocytosis and pulmonary neutrophilia compared to WT mice. Collectively, the results suggest an essential role for IFN-gamma and nonhematopoietic TLR2 for leukocyte recruitment in response to LTA. In contrast, TLR2 on both hematopoietic and nonhematopoietic cells appears to orchestrate an inhibitory response to S. aureus such that in complete TLR2 deficiency, there is an exaggerated proinflammatory response and/or skewing of the immune response towards a Th17 phenotype that may contribute to the decreased survival of TLR2(-/-) mice.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20306471
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9036
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