1. Resources
  2. Citations Library

Citation Details

You are viewing citation details. You can save or export citation(s) below, access an article, or start a new search.

21–30 of 7666 records found matching your query:
Back to Search
Select All  |  Deselect All

Headers act as filters

      1. Author :
        Ahmadi, M.; King, J. W.; Xue, S. A.; Voisine, C.; Holler, A.; Wright, G. P.; Waxman, J.; Morris, E.; Stauss, H. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Blood
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        N/A
      12. Abstract :
        The function of T cell receptor (TCR) gene modified T cells is dependent on efficient surface expression of the introduced TCR alpha/beta heterodimer. We tested whether endogenous CD3 chains are rate-limiting for TCR expression and antigen-specific T cell function. We show that co-transfer of CD3 and TCR genes into primary murine T cells enhanced TCR expression and antigen-specific T cell function in vitro. Peptide titration experiments showed that T cells expressing introduced CD3 and TCR genes recognised lower concentration of antigen than T cells expressing TCR only. In vivo imaging revealed that TCR+CD3 gene modified T cells infiltrated tumors faster and in larger numbers, which resulted in more rapid tumor elimination compared to T cells modified by TCR only. Following tumor clearance, TCR+CD3 engineered T cells persisted in larger numbers than TCR-only T cells and mounted a more effective memory response when re-challenged with antigen. The data demonstrate that provision of additional CD3 molecules is an effective strategy to enhance the avidity, anti-tumor activity and functional memory formation of TCR gene modified T cells in vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21750319
      14. Call Number :
        135769
      15. Serial :
        5654
      1. Author :
        Ahmed, N.; Ratnayake, M.; Savoldo, B.; Perlaky, L.; Dotti, G.; Wels, W. S.; Bhattacharjee, M. B.; Gilbertson, R. J.; Shine, H. D.; Weiss, H. L.; Rooney, C. M.; Heslop, H. E.; Gottschalk, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        67
      8. Issue :
        N/A
      9. Page Numbers :
        5957
      10. Research Area :
        N/A
      11. Keywords :
        Adoptive Transfer, Animals, Brain Neoplasms/immunology/*therapy, Cell Proliferation, Cytokines/biosynthesis, Flow Cytometry, Humans, Immunohistochemistry, Immunotherapy, Adoptive/*methods, Lymphocyte Activation/immunology, Medulloblastoma/immunology/*therapy, Mice, Neoplasms, Experimental/immunology/therapy, Receptor, erbB-2/*immunology, Severe Combined Immunodeficiency, T-Lymphocytes/immunology/*transplantation IVIS, Xenogen
      12. Abstract :
        Medulloblastoma is a common malignant brain tumor of childhood. Human epidermal growth factor receptor 2 (HER2) is expressed by 40% of medulloblastomas and is a risk factor for poor outcome with current aggressive multimodal therapy. In contrast to breast cancer, HER2 is expressed only at low levels in medulloblastomas, rendering monoclonal antibodies ineffective. We determined if T cells grafted with a HER2-specific chimeric antigen receptor (CAR; HER2-specific T cells) recognized and killed HER2-positive medulloblastomas. Ex vivo, stimulation of HER2-specific T cells with HER2-positive medulloblastomas resulted in T-cell proliferation and secretion of IFN-gamma and interleukin 2 (IL-2) in a HER2-dependent manner. HER2-specific T cells killed autologous HER2-positive primary medulloblastoma cells and medulloblastoma cell lines in cytotoxicity assays, whereas HER2-negative tumor cells were not killed. No functional difference was observed between HER2-specific T cells generated from medulloblastoma patients and healthy donors. In vivo, the adoptive transfer of HER2-specific T cells resulted in sustained regression of established medulloblastomas in an orthotopic, xenogenic severe combined immunodeficiency model. In contrast, delivery of nontransduced T cells did not change the tumor growth pattern. Adoptive transfer of HER2-specific T cells may represent a promising immunotherapeutic approach for medulloblastoma.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17575166
      14. Call Number :
        135772
      15. Serial :
        7501
      1. Author :
        Ahmed, N.; Salsman, V. S.; Kew, Y.; Shaffer, D.; Powell, S.; Zhang, Y. J.; Grossman, R. G.; Heslop, H. E.; Gottschalk, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Clin Cancer Res
      6. Products :
      7. Volume :
        16
      8. Issue :
        N/A
      9. Page Numbers :
        474
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen
      12. Abstract :
        PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive human primary brain tumor and is currently incurable. Immunotherapies have the potential to target GBM stem cells, which are resistant to conventional therapies. Human epidermal growth factor receptor 2 (HER2) is a validated immunotherapy target, and we determined if HER2-specific T cells can be generated from GBM patients that will target autologous HER2-positive GBMs and their CD133-positive stem cell compartment. EXPERIMENTAL DESIGN: HER2-specific T cells from 10 consecutive GBM patients were generated by transduction with a retroviral vector encoding a HER2-specific chimeric antigen receptor. The effector function of HER2-specific T cells against autologous GBM cells, including CD133-positive stem cells, was evaluated in vitro and in an orthotopic murine xenograft model. RESULTS: Stimulation of HER2-specific T cells with HER2-positive autologous GBM cells resulted in T-cell proliferation and secretion of IFN-gamma and interleukin-2 in a HER2-dependent manner. Patients' HER2-specific T cells killed CD133-positive and CD133-negative cells derived from primary HER2-positive GBMs, whereas HER2-negative tumor cells were not killed. Injection of HER2-specific T cells induced sustained regression of autologous GBM xenografts established in the brain of severe combined immunodeficient mice. CONCLUSIONS: Gene transfer allows the reliable generation of HER2-specific T cells from GBM patients, which have potent antitumor activity against autologous HER2-positive tumors including their putative stem cells. Hence, the adoptive transfer of HER2-redirected T cells may be a promising immunotherapeutic approach for GBM.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20068073
      14. Call Number :
        135775
      15. Serial :
        6299
      1. Author :
        Ahmed, N.; Salsman, V. S.; Yvon, E.; Louis, C. U.; Perlaky, L.; Wels, W. S.; Dishop, M. K.; Kleinerman, E. E.; Pule, M.; Rooney, C. M.; Heslop, H. E.; Gottschalk, S.
      2. Title :
        Immunotherapy for Osteosarcoma: Genetic Modification of T cells Overcomes Low Levels of Tumor Antigen Expression
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Mol Ther
      6. Products :
      7. Volume :
        17
      8. Issue :
        N/A
      9. Page Numbers :
        1779
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen
      12. Abstract :
        Human epidermal growth factor receptor 2 (HER2) is expressed by the majority of human osteosarcomas and is a risk factor for poor outcome. Unlike breast cancer, osteosarcoma cells express HER2 at too low, a level for patients to benefit from HER2 monoclonal antibodies. We reasoned that this limitation might be overcome by genetically modifying T cells with HER2-specific chimeric antigen receptors (CARs), because even a low frequency of receptor engagement could be sufficient to induce effector cell killing of the tumor. HER2-specific T cells were generated by retroviral transduction with a HER2-specific CAR containing a CD28.? signaling domain. HER2-specific T cells recognized HER2-positive osteosarcoma cells as judged by their ability to proliferate, produce immunostimulatory T helper 1 cytokines, and kill HER2-positive osteosarcoma cell lines in vitro. The adoptive transfer of HER2-specific T cells caused regression of established osteosarcoma xenografts in locoregional as well as metastatic mouse models. In contrast, delivery of nontransduced (NT) T cells did not change the tumor growth pattern. Genetic modification of T cells with CARs specific for target antigens, expressed at too low a level to be effectively recognized by monoclonal antibodies, may allow immunotherapy to be more broadly applicable for human cancer therapy.
      13. URL :
        N/A
      14. Call Number :
        135778
      15. Serial :
        6450
      1. Author :
        Ahonen, M. T.; Diaconu, I.; Pesonen, S.; Kanerva, A.; Baumann, M.; Parviainen, S. T.; Spiller, B.; Cerullo, V.; Hemminki, A.
      2. Title :
        Calcium Gluconate in Phosphate Buffered Saline Increases Gene Delivery with Adenovirus Type 5
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen
      12. Abstract :
        Background: Adenoviruses are attractive vectors for gene therapy because of their stability in vivo and the possibility of production at high titers. Despite exciting preclinical data with various approaches, there are only a few examples of clear efficacy in clinical trials. Effective gene delivery to target cells remains the key variable determining efficacy and thus enhanced transduction methods are important. Methods/Results: We found that heated serum could enhance adenovirus 5 mediated gene delivery up to twentyfold. A new protein-level interaction was found between fiber knob and serum transthyretin, but this was not responsible for the observed effect. Instead, we found that heating caused the calcium and phosphate present in the serum mix to precipitate, and this was responsible for enhanced gene delivery. This finding could have relevance for designing preclinical experiments with adenoviruses, since calcium and phosphate are present in many solutions. To translate this into an approach potentially testable in patients, we used calcium gluconate in phosphate buffered saline, both of which are clinically approved, to increase adenoviral gene transfer up to 300-fold in vitro. Gene transfer was increased with or without heating and in a manner independent from the coxsackie-adenovirus receptor. In vivo, in mouse studies, gene delivery was increased 2-, 110-, 12- and 13-fold to tumors, lungs, heart and liver and did not result in increased pro-inflammatory cytokine induction. Antitumor efficacy of a replication competent virus was also increased significantly. Conclusion: In summary, adenoviral gene transfer and antitumor efficacy can be enhanced by calcium gluconate in phosphate buffered saline.
      13. URL :
        N/A
      14. Call Number :
        135781
      15. Serial :
        5627
      1. Author :
        Aigner, J.; Staudenmaier, R.; Rotter, N.; Kloppel, M.; Radice, M.; Pavesio, A.; Naumann, A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2000
      5. Publication :
        New Frontiers in Medical Sciences: Redefining Hyaluronan
      6. Products :
      7. Volume :
        1196
      8. Issue :
        N/A
      9. Page Numbers :
        255
      10. Research Area :
        N/A
      11. Keywords :
        bioresorbable materials, cartilage-engineering, dedifferentiation, redifferentiation, tissue-engineering, articular-cartilage, chondrocytes, collagen, gels, alginate, culture, biocompatibility, proliferation, expression, phenotype IVIS, Xenogen
      12. Abstract :
        Background Tissue engineering techniques may offer the means to generate hyaline cartilage for reconstructive surgery and to repair articular defects. Our approach is based on the use of isolated auricular or nasoseptal chondrocytes, which are first expanded and then seeded on bioresorbable cell carriers allowing a three-dimensional (3-D) cell arrangement. While traditional cell culture techniques lead to the dedifferentiation of cells, cells cultured on 3-D scaffolds should reexpress their cartilage-specific phenotype. Methods. Since HA plays an essential role in cartilage matrix organization, our investigations focused on the redifferentiation capability of human and rabbit chondrocytes cultured on HYAFF(R)-11, a nonwoven benzyl esterified hyaluronic acid derivative. Results. Following xenogen implantation of human cells in nude mice, as well as autologous implantation of rabbit cells, chondrocytes regained their phenotype as demonstrated by re-expression of collagen type II. Conclusion. The data show that previously dedifferentiated chondrocytes regain their ability to express cartilage specific molecules when cultured in a 3-D structure on special cell carriers. Longterm studies should clarify the biological effects of the cultured cells with respect to the degradation properties of the nonwoven scaffold. The biomaterial, HYAFF(R)-11, available in versatile forms and structures, provides promising opportunities for the production of custom-designed scaffolds in tissue engineering procedures.
      13. URL :
        ://000166298900024"">://000166298900024
      14. Call Number :
        135784
      15. Serial :
        5641
      1. Author :
        Akcan, M.; Stroud, M. R.; Hansen, S. J.; Clark, R. J.; Daly, N. L.; Craik, D. J.; Olson, J. M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Journal of medicinal chemistry
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        N/A
      12. Abstract :
        Bioconjugates composed of chlorotoxin and near-infrared fluorescent (NIRF) moieties are being advanced toward human clinical trials as intraoperative imaging agents that will enable surgeons to visualize small foci of cancer. In previous studies, the NIRF molecules were conjugated to chlorotoxin, which results in a mixture of mono-, di-, and trilabeled peptide. Here we report a new chemical entity that bound only a single NIRF molecule. The lysines at positions 15 and 23 were substituted with either alanine or arginine, which resulted in only monolabeled peptide that was functionally equivalent to native chlorotoxin/Cy5.5. We also analyzed the serum stability and serum half-life of cyclized chlorotoxin, which showed an 11 h serum half-life and resulted in a monolabeled product. Based on these data, we propose to advance a monolabeled chlorotoxin to human clinical trials.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21210710
      14. Call Number :
        135790
      15. Serial :
        5701
      1. Author :
        Akens, MK; Hardisty, MR; Wilson, BC; Schwock, J; Whyne, CM; Burch, S; Yee, AJM
      2. Title :
        Defining the therapeutic window of vertebral photodynamic therapy in a murine pre-clinical model of breast cancer metastasis using the photosensitizer BPD-MA (Verteporfin)
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Breast Cancer Research and Treatment
      6. Products :
      7. Volume :
        119
      8. Issue :
        N/A
      9. Page Numbers :
        325
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen
      12. Abstract :
        Breast cancer is known to cause metastatic lesions in the bone, which can lead to skeletal-related events. Currently, radiation therapy and surgery are the treatment of choice, but the success rate varies and additional adjuncts are desirable. Photodynamic therapy (PDT) has been applied successfully as a non-radiative treatment for numerous cancers. Earlier work has shown that the athymic rat model is suitable to investigate the effect of PDT on bone metastasis and benzoporphyrin-derivative monoacid ring A (BPD-MA; verteporfin) has been shown to be a selective photosensitizer. The aim of this study was to define the therapeutic window of photosensitizer with regard to drug and light dose. Human breast carcinoma cells (MT-1)-stable transfected with the luciferase gene-were injected intra-cardiacally into athymic rats. At 14 days, the largest vertebral lesion by bioluminescence imaging was targeted for single treatment PDT. A drug escalating-de-escalating scheme was used (starting drug dose and light energy of 0.2 mg/kg and 50 J, respectively). Outcomes included 48 h post-treatment bioluminescence of remaining viable tumour, histomorphometric assessment of tumour burden, and neurologic evaluation. The region of effect by bioluminescence and histology increased with increasing drug dose and light energy. A safe and effective drug-light dose combination in this model appears to be 0.5 mg/kg BPD-MA and applied light energy of less than 50 J for the thoracic spine and 1.0 mg/kg and 75 J for the lumbar spine. For translation to clinical use, it is an advantage that BPD-MA (verteporfin), a second-generation photosensitizer, is already approved to treat age-related macular degeneration. Overall, PDT represents an exciting potential new minimally-invasive local, safe and effective therapy in the management of patients with spinal metastases.
      13. URL :
        N/A
      14. Call Number :
        135793
      15. Serial :
        5837
      1. Author :
        Akens, M. K.; Yee, A. J.; Wilson, B. C.; Burch, S.; Johnson, C. L.; Lilge, L.; Bisland, S. K.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Photochem Photobiol
      6. Products :
      7. Volume :
        83
      8. Issue :
        N/A
      9. Page Numbers :
        1034
      10. Research Area :
        N/A
      11. Keywords :
        Aminolevulinic Acid/*therapeutic use, Animals, Bone Neoplasms/*drug therapy/secondary, Breast Neoplasms/*pathology, Disease Models, Animal, Female, *Photochemotherapy, Porphyrins/*therapeutic use, Protoporphyrins/*therapeutic use, Rats, Rats, Nude IVIS, Xenogen
      12. Abstract :
        Photodynamic therapy has been successfully applied to numerous cancers. Its potential to treat cancer metastases in the spine has been demonstrated previously in a preclinical animal model. The aim of this study was to test two photosensitizers, benzoporphyrin-derivative monoacid ring A (BPD-MA) and by 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), for their potential use to treat bony metastases. The difference in photosensitizer concentration in the spinal cord and the surrounding tumor-bearing vertebrae was of particular interest to assess the risk of potential collateral damage to the spinal cord. Vertebral metastases in a rat model were generated by intracardiac injection of human breast cancer cells. When tumor growth was confirmed, photosensitizers were injected systemically and the animals were euthanized at different time points. The following tissues were harvested: liver, kidney, ovaries, appendicular bone, spinal cord and lumbar vertebrae. Photosensitizer tissue concentration of BPD-MA or PpIX was determined by fluorescence spectrophotometry. In contrast to BPD-MA, ALA-PpIX did not demonstrate an appreciable difference in the uptake ratio in tumor-bearing vertebrae compared to spinal cord. The highest ratio for BPD-MA concentration was found 15 min after injection, which can be recommended for therapy in this model.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17880497
      14. Call Number :
        135796
      15. Serial :
        7296
Back to Search
Select All  |  Deselect All