Journal: Clinical and Experimental Immunology

Article Title: Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft- versus -host-like disease and the role of host major histocompatibility complex

doi: 10.1111/j.1365-2249.2009.03933.x

Figure Lengend Snippet: Infiltration of tissues with human cells in peripheral blood mononuclear cells (PBMC)-engrafted non-obese diabetic (NOD)-severe combined immunedeficient (scid) IL2rγnull mice. (a) Human CD45+ cells were detected in the spleen, lung, liver and small intestine of NOD-scid IL2rγnull mice that were treated with 2Gy irradiation followed by intravenous injection of 5 × 106 human PBMC, 400×. (b) Upper panels: truncal skin from NOD-scid IL2rγnull mice 50 days after treatment with 2 Gy only. The skin shows normal structure. There were no human CD45+ mononuclear cells present. Lower panels: truncal skin from NOD-scid IL2rγnull mouse 63 days after irradiation with 2 Gy, injection with 5 × 106 human PBMC, and repeated doses of etanercept as described in Materials and methods. Infiltrate of lymphocytes is present at the dermal epidermal junction. Arrows point to human cell infiltration.

Article Snippet: Similarly, blocking TNF-α with etanercept (Enbrel®, Immunex Corp., Thousand Oaks, CA, USA; a soluble TNF-α decoy receptor) as part of a GVHD treatment regimen was shown to be efficacious [ 38 ].

Techniques: Irradiation, Injection

Journal: Clinical and Experimental Immunology

Article Title: Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft- versus -host-like disease and the role of host major histocompatibility complex

doi: 10.1111/j.1365-2249.2009.03933.x

Figure Lengend Snippet: Soluble tumour necrosis factor (TNF)-α receptor delays progression of xenogeneic graft-versus-host disease (GVHD). (a) Survival of non-obese diabetic (NOD)-severe combined immunedeficient (scid) IL2rγnull mice that received 20 × 106 peripheral blood mononuclear cells (PBMC) intravenously (i.v.) 4 h after 2 Gy irradiation [solid line, median survival time (MST) = 12 days, n = 18, seven PBMC donors], with etanercept pretreatment of 100 µg/injection on days −3 and −1 prior to injection of PBMC (dashed line, MST = 16 days, n = 18, seven PBMC donors) or etanercept pretreatment plus 100 µg every 3 days (dotted line, MST = 23 days, n = 12, four PBMC donors). (b) The average weight in irradiated mice that received PBMC alone, PBMC plus etanercept pretreatment, or etanercept pretreatment plus 100 µg every 3 days is shown as the percentage of starting weight. The numbers shown correspond with the number of mice that remain alive at each time-point.

Article Snippet: Similarly, blocking TNF-α with etanercept (Enbrel®, Immunex Corp., Thousand Oaks, CA, USA; a soluble TNF-α decoy receptor) as part of a GVHD treatment regimen was shown to be efficacious [ 38 ].

Techniques: Irradiation, Injection

Journal: Clinical and Experimental Immunology

Article Title: Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft- versus -host-like disease and the role of host major histocompatibility complex

doi: 10.1111/j.1365-2249.2009.03933.x

Figure Lengend Snippet: Etanercept-dependent prevention of xenogeneic graft-versus-host disease (GVHD) at lower peripheral blood mononuclear cells (PBMC) cell doses. (a) Survival of non-obese diabetic (NOD)-severe combined immunedeficient (scid) IL2rγnull mice given 5 × 106 PBMC intravenously (i.v.). Four h after 2 Gy irradiation [solid line, median survival time (MST) = 22 days, n = 15, seven PBMC donors], with etanercept pretreatment of 100 µg/injection on days −3 and −1 prior to injection of PBMC (dashed line, MST = 28 days, n = 25, seven PBMC donors) or etanercept pretreatment plus additional 100 µg etanercept injections every 3 days (dotted line, MST = 47 days, n = 24, seven PBMC donors). (b) Mice received 2 Gy irradiation 4 h prior to 5 × 106 PBMC; 14 days later, human CD45+ cell engraftment in the blood (left panel), spleen (middle panel) and bone marrow (right panel) was evaluated by flow cytometry. Etanercept treatment decreased human CD45+ engraftment in all three tissues tested. Horizontal lines represent the median of the values of each group. (c) Levels of human tumour necrosis factor (TNF)-α in plasma samples collected from untreated or etanercept-pretreated mice 1, 4 and 24 h after PBMC injection. All mice received 2 Gy irradiation 4 h prior to intravenous (i.v.) injection of 5 × 106 PBMC from one of two PBMC donors. Each symbol represents an individual mouse.

Article Snippet: Similarly, blocking TNF-α with etanercept (Enbrel®, Immunex Corp., Thousand Oaks, CA, USA; a soluble TNF-α decoy receptor) as part of a GVHD treatment regimen was shown to be efficacious [ 38 ].

Techniques: Irradiation, Injection, Flow Cytometry, Clinical Proteomics

Journal: Cell Death & Disease

Article Title: Withanolide E sensitizes renal carcinoma cells to TRAIL-induced apoptosis by increasing cFLIP degradation

doi: 10.1038/cddis.2015.38

Figure Lengend Snippet: Withanolide E enhances death receptor-induced apoptosis in vivo . Effects of withanolide E and drozitumab (DR5 agonist antibody) on growth of ACHN cell-derived tumors in athymic mice was assessed as described in the text. ( a ) Tumor size at 75 days (intratumor), ( b ) survival up to 150 days (intraperitoneal) – pooled from two separate experiments with similar findings. Numbers of mice were: vehicle control (●, n =10), withanolide E (▴, n =10), drozitumab (▪, n =14), withanolide E plus drozitumab (□, n =16). * P <0.05

Article Snippet: For the generation of subcutaneous tumors, mice were injected subcutaneously with 1 × 10 6 ACHN cells that had been adapted for in vivo passage in a volume of 100 μ l. After tumor volumes reached ~100 mm 3 (~14 days post injection) therapy was initiated - either direct injection of withanolide E and Drozitumab (agonist antibody to TRAIL death receptor DR5, kindly provided by Dr. Avi Ashkenazi, Genentech, South San Francisco, CA, USA , ) into the tumor, or intraperitoneal injection of both agents.

Techniques: In Vivo, Derivative Assay, Control