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      1. Author :
        van der Horst, G.; van der Pluijm, G.
      2. Title :
        Preclinical imaging of the cellular and molecular events in the multistep process of bone metastasis
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Future Oncol
      6. Products :

        OsteoSense

      7. Volume :
        8
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Bone Neoplasms/*diagnosis/*secondary; Diagnostic Imaging/*methods; Disease Models, Animal; Disease Progression; Humans; Molecular Imaging/methods; Neoplasm Metastasis/diagnosis
      12. Abstract :
        Bone metastasis is a complex process that ultimately leads to devastating metastatic bone disease. It is therefore of key interest to unravel the mechanisms underlying the multistep process of skeletal metastasis and cancer-induced bone disease, and to develop better treatment and management of patients with this devastating disease. Fortunately, novel technologies are rapidly emerging that allow real-time imaging of molecules, pathogenic processes, drug delivery and drug response in preclinical in vivo models. The outcome of these experimental studies will facilitate clinical cancer research by improving the detection of cancer cell invasion, metastasis and therapy response.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22515445
      14. Call Number :
        PKI @ kd.modi @ 16
      15. Serial :
        10478
      1. Author :
        Wang, M.; Gartel, A. L.
      2. Title :
        Combination with bortezomib enhances the antitumor effects of nanoparticle-encapsulated thiostrepton
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cancer Biol Ther
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        13
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-luc-D3H2Ln, D3H2Ln, IVIS, Breast cancer, Bioware, Adenocarcinoma/*drug therapy/pathology; Animals; Antineoplastic Combined Chemotherapy; Protocols/pharmacokinetics/pharmacology/*therapeutic use; Apoptosis; Boronic Acids/administration & dosage; Breast Neoplasms/*drug therapy/pathology; Cell Line, Tumor; Drug Synergism; Female; Humans; Male; Mice; Mice, Nude; Nanocapsules/administration & dosage; Proteasome Endopeptidase Complex/metabolism; Pyrazines/administration & dosage; Random Allocation; Thiostrepton/administration & dosage; Tissue Distribution; Tumor Burden/drug effects; Xenograft Model Antitumor Assays
      12. Abstract :
        Bortezomib is well-known for inducing cell death in cancer cells, specifically through the mechanism of proteasome inhibition. Thiostrepton, a thiazole antibiotic, has also been described for its proteasome inhibitory action, although differing slightly to bortezomib in the proteasomal site to which it is active. Previously we had shown the synergic effect of bortezomib and thiostrepton in breast cancer cells in vitro, where sub-apoptotic concentrations of both proteasome inhibitors resulted in synergic increase in cell death when combined as a treatment. Here, we administered such a combination to MDA-MB-231 xenograft tumors in vivo, and found that the effect of complementary proteasome inhibitors reduced tumor growth rates more efficiently than compared with when administered alone. Increased induction of apoptotic activity in tumors was found be associated with the growth inhibitory activity of combination treatment. Further examination additionally revealed that combination-treated tumors exhibited reduced proteasome activity, compared with non-treated and single drug-treated tumors. These data suggest that this drug combination may be useful as a therapy for solid tumors.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22353937
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10510
      1. Author :
        Liu, W.; McDaniel, J.; Li, X.; Asai, D.; Quiroz, F. G.; Schaal, J.; Park, J. S.; Zalutsky, M.; Chilkoti, A.
      2. Title :
        Brachytherapy using injectable seeds that are self-assembled from genetically encoded polypeptides in situ
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Cancer Res
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        72
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        PC-3M-luc2, PC3M-luc2, IVIS, Prostate Cancer, Bioware
      12. Abstract :
        Brachytherapy is a common clinical technique involving implantation of sealed radioactive “seeds” within a tumor to selectively irradiate the tumor mass while minimizing systemic toxicity. To mitigate the disadvantages associated with complex surgical implantation and subsequent device removal procedures, we have developed an alternative approach using a genetically encoded peptide polymer solution composed of a thermally responsive elastin-like polypeptide (ELP) radiolabeled with (131)I that self-assembles into radionuclide seeds upon intratumoral injection. The formation of these nontoxic and biodegradable polymer seeds led to prolonged intratumoral retention (~85% ID/tumor 7 days postinjection) of the radionuclide, elicited a tumor growth delay in 100% of the tumors in two human xenografts (FaDu and PC-3), and cured more than 67% of tumor-bearing animals after a single administration of labeled ELP. These results suggest that in situ self-assembly of biodegradable and injectable radionuclide-containing polypeptide seeds could be a promising therapeutic alternative to conventional brachytherapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23155121
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10487
      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 :
        Frondoside A inhibits human breast cancer cell survival, migration, invasion and the growth of breast tumor xenografts
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Pharmacol
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      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 :
        Rambow-Larsen, Amy A; Rajashekara, Gireesh; Petersen, Erik; Splitter, Gary
      2. Title :
        Putative quorum-sensing regulator BlxR of Brucella melitensis regulates virulence factors including the type IV secretion system and flagella
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Journal of bacteriology
      6. Products :

        Bioware bacteria

      7. Volume :
        190
      8. Issue :
        9
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Amino Acid Sequence; Animals; Bioware; Brucella melitensis; Brucellosis; Disease Models, Animal; Flagella; Gene Deletion; Gene Expression Regulation, Bacterial; Interferon Regulatory Factor-1; Macrophages; Mice; Mice, Mutant Strains; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; pXen-13; Quorum Sensing; Repressor Proteins; Trans-Activators; Virulence Factors
      12. Abstract :
        Brucella melitensis is an intracellular pathogen that establishes a replicative niche within macrophages. While the intracellular lifestyle of Brucella is poorly understood and few virulence factors have been identified, components of a quorum-sensing pathway in Brucella have recently been identified. The LuxR-type regulatory protein, VjbR, and an N-acylhomoserine lactone signaling molecule are both involved in regulating expression of the virB-encoded type IV secretion system. We have identified a second LuxR-type regulatory protein (BlxR) in Brucella. Microarray analysis of a blxR mutant suggests that BlxR regulates the expression of a number of genes, including those encoding the type IV secretion system and flagella. Confirming these results, deletion of blxR in B. melitensis reduced the transcriptional activities of promoters for the virB operon, flagellar genes, and another putative virulence factor gene, bopA. Furthermore, our data suggested that both BlxR and VjbR are positively autoregulated and cross-regulate the expression of each other. The blxR deletion strain exhibited reduced growth in macrophages, similar to that observed for a vjbR deletion strain. However, unlike the vjbR deletion, the blxR deletion did not fully attenuate virulence in mice. More strikingly, bioluminescent imaging revealed that dissemination of the blxR mutant was similar to that of wild-type B. melitensis, while the vjbR mutant was defective for systemic spread in IRF-1(-/-) mice, suggesting that these regulators are not functionally redundant but that they converge in a common pathway regulating bacterial processes.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18310341
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9030
      1. Author :
        Park, H. S.; Cleary, P. P.
      2. Title :
        Active and Passive Intranasal Immunizations with Streptococcal Surface Protein C5a Peptidase Prevent Infection of Murine Nasal Mucosa-Associated Lymphoid Tissue, a Functional Homologue of Human Tonsils
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        Infection and Immunity
      6. Products :

        IVIS Imaging SystemsBioware bacteria

      7. Volume :
        73
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen, Xen20
      12. Abstract :
        C5a peptidase, also called SCPA (surface-bound C5a peptidase), is a surface-bound protein on group A streptococci (GAS), etiologic agents for a variety of human diseases including pharyngitis, impetigo, toxic shock, and necrotizing fasciitis, as well as the postinfection sequelae rheumatic fever and rheumatic heart disease. This protein is highly conserved among different serotypes and is also expressed in human isolates of group B, C, and G streptococci. Human tonsils are the primary reservoirs for GAS, maintaining endemic disease across the globe. We recently reported that GAS preferentially target nasal mucosa-associated lymphoid tissue (NALT) in mice, a tissue functionally analogous to human tonsils. Experiments using a C5a peptidase loss-of-function mutant and an intranasal infection model showed that this protease is required for efficient colonization of NALT. An effective vaccine should prevent infection of this secondary lymphoid tissue; therefore, the potential of anti-SCPA antibodies to protect against streptococcal infection of NALT was investigated. Experiments showed that GAS colonization of NALT was significantly reduced following intranasal immunization of mice with recombinant SCPA protein administered alone or with cholera toxin, whereas a high degree of GAS colonization of NALT was observed in control mice immunized with phosphate-buffered saline only. Moreover, administration of anti-SCPA serum by the intranasal route protected mice against streptococcal infection. These results suggest that intranasal immunization with SCPA would prevent colonization and infection of human tonsils, thereby eliminating potential reservoirs that maintain endemic disease.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16299278
      14. Call Number :
        141964
      15. Serial :
        5327
      1. Author :
        Marttila-Ichihara, Fumiko; Auvinen, Kaisa; Elima, Kati; Jalkanen, Sirpa; Salmi, Marko
      2. Title :
        Vascular adhesion protein-1 enhances tumor growth by supporting recruitment of Gr-1+CD11b+ myeloid cells into tumors
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Cancer research
      6. Products :

        Bioware cell lines

      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 :
        Min, Jung-Joon; Nguyen, Vu H.; Gambhir, Sanjiv S.
      2. Title :
        Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Nuclear Medicine and Molecular Imaging
      6. Products :

        Bioware bacteria

      7. Volume :
        44
      8. Issue :
        1
      9. Page Numbers :
        15-24
      10. Research Area :
        N/A
      11. Keywords :
        Cancer; Cardiology; Gene delivery vector; Gene Therapy; Imaging / Radiology; Molecular Imaging; Nuclear Medicine; Oncology; Orthopedics; Xen26
      12. Abstract :
        Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.
      13. URL :
        http://link.springer.com/article/10.1007/s13139-009-0006-3
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        10003
      1. Author :
        Chantry, A. D.; Heath, D.; Mulivor, A. W.; Pearsall, S.; Baud'huin, M.; Coulton, L.; Evans, H.; Abdul, N.; Werner, E. D.; Bouxsein, M. L.; Key, M. L.; Seehra, J.; Arnett, T. R.; Vanderkerken, K.; Croucher, P.
      2. Title :
        Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        J Bone Miner Res
      6. Products :

        Bioware cell linesIVIS Imaging Systems

      7. Volume :
        25
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-D3H2Ln, IVIS, Bioluminescence, Activins/*metabolism; Animals; Bone Neoplasms/*complications/pathology/physiopathology/secondary; Bone Resorption/*etiology/pathology/physiopathology/*prevention & control; Calcification, Physiologic/drug effects; Cell Line, Tumor; HEK293 Cells; Humans; Mice; Multiple Myeloma/complications/pathology/physiopathology; Neoplasm Transplantation; Organ Size/drug effects; Osteoblasts/drug effects/pathology; *Osteogenesis/drug effects; Osteolysis/blood/complications/physiopathology/prevention & control; Paraproteins/metabolism; Recombinant Fusion Proteins/pharmacology; *Signal Transduction/drug effects; Survival Analysis; Tumor Burden/drug effects
      12. Abstract :
        Cancers that grow in bone, such as myeloma and breast cancer metastases, cause devastating osteolytic bone destruction. These cancers hijack bone remodeling by stimulating osteoclastic bone resorption and suppressing bone formation. Currently, treatment is targeted primarily at blocking bone resorption, but this approach has achieved only limited success. Stimulating osteoblastic bone formation to promote repair is a novel alternative approach. We show that a soluble activin receptor type IIA fusion protein (ActRIIA.muFc) stimulates osteoblastogenesis (p < .01), promotes bone formation (p < .01) and increases bone mass in vivo (p < .001). We show that the development of osteolytic bone lesions in mice bearing murine myeloma cells is caused by both increased resorption (p < .05) and suppression of bone formation (p < .01). ActRIIA.muFc treatment stimulates osteoblastogenesis (p < .01), prevents myeloma-induced suppression of bone formation (p < .05), blocks the development of osteolytic bone lesions (p < .05), and increases survival (p < .05). We also show, in a murine model of breast cancer bone metastasis, that ActRIIA.muFc again prevents bone destruction (p < .001) and inhibits bone metastases (p < .05). These findings show that stimulating osteoblastic bone formation with ActRIIA.muFc blocks the formation of osteolytic bone lesions and bone metastases in models of myeloma and breast cancer and paves the way for new approaches to treating this debilitating aspect of cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20533325
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10413