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  1. Article: Autologous cancer cell vaccination, adoptive T‐cell transfer, and interleukin‐2 administration results in long‐term survival for companion dogs with osteosarcoma

    Flesner, Brian K / Wood, Gary W / Gayheart‐Walsten, Pamela / Sonderegger, F. Lynn / Henry, Carolyn J / Tate, Deborah J / Bechtel, Sandra M / Donnelly, Lindsay L / Johnson, Gayle C / Kim, Dae Young / Wahaus, Tammie A / Bryan, Jeffrey N / Reyes, Noe

    Journal of veterinary internal medicine. 2020 Sept., v. 34, no. 5

    2020  

    Abstract: BACKGROUND: Osteosarcoma (OSA) in dogs is an aggressive bone tumor with frequent chemotherapy failure and translational relevance for human health. HYPOTHESIS/OBJECTIVES: We hypothesized that dogs with OSA could be treated safely by ex vivo activated T‐ ... ...

    Abstract BACKGROUND: Osteosarcoma (OSA) in dogs is an aggressive bone tumor with frequent chemotherapy failure and translational relevance for human health. HYPOTHESIS/OBJECTIVES: We hypothesized that dogs with OSA could be treated safely by ex vivo activated T‐cells that were generated by autologous cancer vaccination and supported by interleukin‐2 (IL‐2) treatment with survival more than twice that reported for amputation alone. ANIMALS: Osteosarcoma‐bearing dogs (n = 14) were enrolled in a single‐arm prospective trial after complete staging before amputation. Four healthy dogs also were treated in a safety study. METHODS: Autologous cancer cell vaccinations were administered intradermally and dogs underwent leukapheresis. Mononuclear cell products were stimulated ex vivo with a T‐cell‐activating agent. Activated product was transfused and 5 SC IL‐2 injections were administered q48h. Dogs were monitored for metastasis by thoracic radiography every 3 months. RESULTS: Autologous cancer cell vaccine and activated cellular therapy (ACT) products were successfully generated. Toxicity was minimal after premedicants were instituted before ACT. With premedication, all toxicities were grade I/II. Median disease‐free interval for all dogs was 213 days. One dog developed cutaneous metastasis but then experienced spontaneous complete remission. Median survival time for all dogs was 415 days. Five dogs survived >730 days. CONCLUSIONS AND CLINICAL IMPORTANCE: This immunotherapy protocol without cytotoxic chemotherapy is safe and tolerable. Compared to historical amputation reports, survival was notably prolonged in this group of patients. Additional prospective studies are warranted to elucidate active immunologic mechanisms and further improve disease response and survival.
    Keywords T-lymphocytes ; amputation ; cytotoxicity ; dogs ; drug therapy ; human health ; interleukin-2 ; metastasis ; neoplasm cells ; osteosarcoma ; radiography ; remission ; vaccination ; vaccines ; veterinary medicine
    Language English
    Dates of publication 2020-09
    Size p. 2056-2067.
    Publishing place John Wiley & Sons, Inc.
    Document type Article
    Note NAL-AP-2-clean ; JOURNAL ARTICLE
    ZDB-ID 92798-3
    ISSN 1939-1676 ; 0891-6640
    ISSN (online) 1939-1676
    ISSN 0891-6640
    DOI 10.1111/jvim.15852
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4095: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: The immune response to picornavirus infection and the effect of immune manipulation on acute seizures.

    DePaula-Silva, Ana Beatriz / Sonderegger, F Lynn / Libbey, Jane E / Doty, Daniel J / Fujinami, Robert S

    Journal of neurovirology

    2018  Volume 24, Issue 4, Page(s) 464–477

    Abstract: Viral infection of the central nervous system can result in encephalitis. About 20% of individuals who develop viral encephalitis go on to develop epilepsy. We have established an experimental model where virus infection of mice with Theiler's murine ... ...

    Abstract Viral infection of the central nervous system can result in encephalitis. About 20% of individuals who develop viral encephalitis go on to develop epilepsy. We have established an experimental model where virus infection of mice with Theiler's murine encephalomyelitis virus (TMEV) leads to acute seizures, followed by a latent period (no seizures/epileptogenesis phase) and then spontaneous recurrent seizures-epilepsy. Infiltrating macrophages (CD11b
    MeSH term(s) Animals ; Cardiovirus Infections/immunology ; Encephalitis, Viral/immunology ; Encephalitis, Viral/virology ; Mice ; Mice, Inbred C57BL ; Seizures/virology ; Theilovirus/immunology
    Language English
    Publishing date 2018-04-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1283265-0
    ISSN 1538-2443 ; 1355-0284
    ISSN (online) 1538-2443
    ISSN 1355-0284
    DOI 10.1007/s13365-018-0636-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4426: Show issues Location:
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  3. Article ; Online: Autologous cancer cell vaccination, adoptive T-cell transfer, and interleukin-2 administration results in long-term survival for companion dogs with osteosarcoma.

    Flesner, Brian K / Wood, Gary W / Gayheart-Walsten, Pamela / Sonderegger, F Lynn / Henry, Carolyn J / Tate, Deborah J / Bechtel, Sandra M / Donnelly, Lindsay L / Johnson, Gayle C / Kim, Dae Young / Wahaus, Tammie A / Bryan, Jeffrey N / Reyes, Noe

    Journal of veterinary internal medicine

    2020  Volume 34, Issue 5, Page(s) 2056–2067

    Abstract: Background: Osteosarcoma (OSA) in dogs is an aggressive bone tumor with frequent chemotherapy failure and translational relevance for human health.: Hypothesis/objectives: We hypothesized that dogs with OSA could be treated safely by ex vivo ... ...

    Abstract Background: Osteosarcoma (OSA) in dogs is an aggressive bone tumor with frequent chemotherapy failure and translational relevance for human health.
    Hypothesis/objectives: We hypothesized that dogs with OSA could be treated safely by ex vivo activated T-cells that were generated by autologous cancer vaccination and supported by interleukin-2 (IL-2) treatment with survival more than twice that reported for amputation alone.
    Animals: Osteosarcoma-bearing dogs (n = 14) were enrolled in a single-arm prospective trial after complete staging before amputation. Four healthy dogs also were treated in a safety study.
    Methods: Autologous cancer cell vaccinations were administered intradermally and dogs underwent leukapheresis. Mononuclear cell products were stimulated ex vivo with a T-cell-activating agent. Activated product was transfused and 5 SC IL-2 injections were administered q48h. Dogs were monitored for metastasis by thoracic radiography every 3 months.
    Results: Autologous cancer cell vaccine and activated cellular therapy (ACT) products were successfully generated. Toxicity was minimal after premedicants were instituted before ACT. With premedication, all toxicities were grade I/II. Median disease-free interval for all dogs was 213 days. One dog developed cutaneous metastasis but then experienced spontaneous complete remission. Median survival time for all dogs was 415 days. Five dogs survived >730 days.
    Conclusions and clinical importance: This immunotherapy protocol without cytotoxic chemotherapy is safe and tolerable. Compared to historical amputation reports, survival was notably prolonged in this group of patients. Additional prospective studies are warranted to elucidate active immunologic mechanisms and further improve disease response and survival.
    MeSH term(s) Animals ; Bone Neoplasms/drug therapy ; Bone Neoplasms/veterinary ; Dog Diseases/drug therapy ; Dogs ; Interleukin-2/therapeutic use ; Osteosarcoma/drug therapy ; Osteosarcoma/veterinary ; Pets ; Prospective Studies ; T-Lymphocytes ; Treatment Outcome ; Vaccination/veterinary
    Chemical Substances Interleukin-2
    Keywords covid19
    Language English
    Publishing date 2020-07-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 92798-3
    ISSN 1939-1676 ; 0891-6640
    ISSN (online) 1939-1676
    ISSN 0891-6640
    DOI 10.1111/jvim.15852
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4095: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T Cells in Lyme Arthritis.

    Whiteside, Sarah K / Snook, Jeremy P / Ma, Ying / Sonderegger, F Lynn / Fisher, Colleen / Petersen, Charisse / Zachary, James F / Round, June L / Williams, Matthew A / Weis, Janis J

    Journal of immunology (Baltimore, Md. : 1950)

    2018  Volume 200, Issue 4, Page(s) 1457–1470

    Abstract: T cells predominate the immune responses in the synovial fluid of patients with persistent Lyme arthritis; however, their role in Lyme disease remains poorly defined. Using a murine model of persistent Lyme arthritis, we observed that bystander ... ...

    Abstract T cells predominate the immune responses in the synovial fluid of patients with persistent Lyme arthritis; however, their role in Lyme disease remains poorly defined. Using a murine model of persistent Lyme arthritis, we observed that bystander activation of CD4
    MeSH term(s) Animals ; Female ; Interleukin-10/deficiency ; Interleukin-10/immunology ; Lyme Disease/immunology ; Lymphocyte Activation/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; T-Lymphocytes/immunology ; Toll-Like Receptor 2/immunology
    Chemical Substances IL10 protein, mouse ; Tlr2 protein, mouse ; Toll-Like Receptor 2 ; Interleukin-10 (130068-27-8)
    Language English
    Publishing date 2018-01-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1701248
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.37: Show issues Location:
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    Zs.MG 28: Show issues

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  5. Article ; Online: Endothelial cells and fibroblasts amplify the arthritogenic type I IFN response in murine Lyme disease and are major sources of chemokines in Borrelia burgdorferi-infected joint tissue.

    Lochhead, Robert B / Sonderegger, F Lynn / Ma, Ying / Brewster, James E / Cornwall, Doug / Maylor-Hagen, Heather / Miller, Jennifer C / Zachary, James F / Weis, John H / Weis, Janis J

    Journal of immunology (Baltimore, Md. : 1950)

    2012  Volume 189, Issue 5, Page(s) 2488–2501

    Abstract: Localized elevation in type I IFN has been uniquely linked to the severe Lyme arthritis that develops in C3H mice infected with the spirochete Borrelia burgdorferi. In this study, the dynamic interactions that result in generation of these responses were ...

    Abstract Localized elevation in type I IFN has been uniquely linked to the severe Lyme arthritis that develops in C3H mice infected with the spirochete Borrelia burgdorferi. In this study, the dynamic interactions that result in generation of these responses were further examined in C3H mice carrying the type I IFN receptor gene ablation, which effectively blocks all autocrine/paracrine signaling crucial to induction of downstream effectors. Reciprocal radiation chimeras between C3H and IFNAR1⁻/⁻ mice implicated both radiation-sensitive and radiation-resistant cells of the joint tissue in the proarthritic induction of type I IFN. Ex vivo analysis of cells from the naive joint revealed CD45⁺ cells residing in the tissue to be uniquely capable of initiating the type I IFN response to B. burgdorferi. Type I IFN responses were analyzed in real time by lineage sorting of cells from infected joint tissue. This demonstrated that myeloid cells, endothelial cells, and fibroblasts were responsible for propagating the robust IFN response, which peaked at day 7 postinfection and rapidly resolved. Endothelial cells and fibroblasts were the dominant sources of IFN signature transcripts in the joint tissue. Fibroblasts were also the major early source of chemokines associated with polymorphonuclear leukocyte and monocyte/macrophage infiltration, thus providing a focal point for arthritis development. These findings suggest joint-localized interactions among related and unrelated stromal, endothelial, and myeloid cell lineages that may be broadly applicable to understanding the pathogeneses of diseases associated with type I IFN signature, including systemic lupus erythematosus and some rheumatoid arthritides.
    MeSH term(s) Animals ; Ankle Joint/immunology ; Ankle Joint/microbiology ; Ankle Joint/pathology ; Arthritis, Experimental/immunology ; Arthritis, Experimental/metabolism ; Arthritis, Experimental/pathology ; Borrelia burgdorferi/immunology ; Borrelia burgdorferi/pathogenicity ; Cells, Cultured ; Chemokines/biosynthesis ; Chemokines/genetics ; Fibroblasts/immunology ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Interferon Type I/biosynthesis ; Interferon Type I/deficiency ; Interferon Type I/genetics ; Lyme Disease/immunology ; Lyme Disease/metabolism ; Lyme Disease/pathology ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Myeloid Cells/pathology ; Severity of Illness Index ; Signal Transduction/immunology ; Transcription, Genetic/immunology ; Up-Regulation/genetics ; Up-Regulation/immunology
    Chemical Substances Chemokines ; Interferon Type I
    Language English
    Publishing date 2012-07-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1201095
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.37: Show issues Location:
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  6. Article ; Online: Localized production of IL-10 suppresses early inflammatory cell infiltration and subsequent development of IFN-γ-mediated Lyme arthritis.

    Sonderegger, F Lynn / Ma, Ying / Maylor-Hagan, Heather / Brewster, James / Huang, Xiaosong / Spangrude, Gerald J / Zachary, James F / Weis, John H / Weis, Janis J

    Journal of immunology (Baltimore, Md. : 1950)

    2011  Volume 188, Issue 3, Page(s) 1381–1393

    Abstract: IL-10 is a nonredundant inflammatory modulator that suppresses arthritis development in Borrelia burgdorferi-infected mice. Infected C57BL/6 (B6) IL-10(-/-) mice were previously found to have a prolonged IFN-inducible response in joint tissue. Infection ... ...

    Abstract IL-10 is a nonredundant inflammatory modulator that suppresses arthritis development in Borrelia burgdorferi-infected mice. Infected C57BL/6 (B6) IL-10(-/-) mice were previously found to have a prolonged IFN-inducible response in joint tissue. Infection of B6 IL-10 reporter mice identified macrophages and CD4(+) T cells as the primary sources of IL-10 in the infected joint tissue, suggesting that early local production of IL-10 dampened the proarthritic IFN response. Treatment of B6 IL-10(-/-) mice with anti-IFN-γ reduced the increase in arthritis severity and suppressed IFN-inducible transcripts to wild-type levels, thereby linking dysregulation of IFN-γ to disease in the B6 IL-10(-/-) mouse. Arthritis in B6 IL-10(-/-) mice was associated with elevated numbers of NK cell, NKT cell, α/β T cell, and macrophage infiltration of the infected joint. FACS lineage sorting revealed NK cells and CD4(+) T cells as sources of IFN-γ in the joint tissue of B6 IL-10(-/-) mice. These findings suggest the presence of a positive-feedback loop in the joint tissue of infected B6 IL-10(-/-) mice, in which production of inflammatory chemokines, infiltration of IFN-γ-producing cells, and additional production of inflammatory cytokines result in arthritis. This mechanism of arthritis is in contrast to that seen in C3H/He mice, in which arthritis development is linked to transient production of type I IFN and develops independently of IFN-γ. Due to the sustained IFN response driven by NK cells and T cells, we propose the B6 IL-10(-/-) mouse as a potential model to study the persistent arthritis observed in some human Lyme disease patients.
    MeSH term(s) Animals ; Borrelia burgdorferi ; Cell Movement/immunology ; Feedback, Physiological ; Humans ; Inflammation/immunology ; Interferon-gamma/immunology ; Interferon-gamma/pharmacology ; Interleukin-10/biosynthesis ; Interleukin-10/deficiency ; Killer Cells, Natural/immunology ; Lyme Disease/immunology ; Mice ; Mice, Knockout ; T-Lymphocytes/immunology
    Chemical Substances IL10 protein, mouse ; Interleukin-10 (130068-27-8) ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2011-12-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1102359
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ud II Zs.37: Show issues Location:
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