Journal: Journal of pharmacokinetics and pharmacodynamics

Article Title: A Physiological Model of Granulopoiesis to Predict Clinical Drug Induced Neutropenia from in vitro Bone Marrow Studies: With Application to a Cell Cycle Inhibitor

doi: 10.1007/s10928-020-09680-6

Figure Lengend Snippet: Mechanism of action of palbociclib incorporated in the cell cycle model. Minus sign represents palbociclib inhibition of k1, plus sign represents palbociclib induction of the inactivation process.

Article Snippet: Palbociclib in vitro bone marrow assay Primary human bone marrow mononuclear cells (Lonza) were cultured in stemline II hematopoietic stem cell expansion medium (Sigma Aldrich), supplemented with 5% FBS and under induction by the following cytokines (R&D Systems): 25 ng/mL stem cell factor (SCF), 10 ng/mL G-CSF, 10 ng/mL granulocyte macrophage-colony stimulating factor, 3 U/mL erythropoietin (EPO), 15ng/mL thrombopoietin (TPO), 10ng/mL IL3, 10ng/mL IL6, and 25ng/mL Flt3 ligand.

Techniques: Inhibition

Journal: Journal of pharmacokinetics and pharmacodynamics

Article Title: A Physiological Model of Granulopoiesis to Predict Clinical Drug Induced Neutropenia from in vitro Bone Marrow Studies: With Application to a Cell Cycle Inhibitor

doi: 10.1007/s10928-020-09680-6

Figure Lengend Snippet: Palbociclib PK model parameter values (from [ 49 ]).

Article Snippet: Palbociclib in vitro bone marrow assay Primary human bone marrow mononuclear cells (Lonza) were cultured in stemline II hematopoietic stem cell expansion medium (Sigma Aldrich), supplemented with 5% FBS and under induction by the following cytokines (R&D Systems): 25 ng/mL stem cell factor (SCF), 10 ng/mL G-CSF, 10 ng/mL granulocyte macrophage-colony stimulating factor, 3 U/mL erythropoietin (EPO), 15ng/mL thrombopoietin (TPO), 10ng/mL IL3, 10ng/mL IL6, and 25ng/mL Flt3 ligand.

Techniques:

Journal: Journal of pharmacokinetics and pharmacodynamics

Article Title: A Physiological Model of Granulopoiesis to Predict Clinical Drug Induced Neutropenia from in vitro Bone Marrow Studies: With Application to a Cell Cycle Inhibitor

doi: 10.1007/s10928-020-09680-6

Figure Lengend Snippet: In vitro model results. Time course measurements for control (left panel) and all end-of-assay measurements (right panel) following palbociclib treatment. Symbol: measurements, lines: model predictions. Overall r2=0.94.

Article Snippet: Palbociclib in vitro bone marrow assay Primary human bone marrow mononuclear cells (Lonza) were cultured in stemline II hematopoietic stem cell expansion medium (Sigma Aldrich), supplemented with 5% FBS and under induction by the following cytokines (R&D Systems): 25 ng/mL stem cell factor (SCF), 10 ng/mL G-CSF, 10 ng/mL granulocyte macrophage-colony stimulating factor, 3 U/mL erythropoietin (EPO), 15ng/mL thrombopoietin (TPO), 10ng/mL IL3, 10ng/mL IL6, and 25ng/mL Flt3 ligand.

Techniques: In Vitro

Journal: Journal of pharmacokinetics and pharmacodynamics

Article Title: A Physiological Model of Granulopoiesis to Predict Clinical Drug Induced Neutropenia from in vitro Bone Marrow Studies: With Application to a Cell Cycle Inhibitor

doi: 10.1007/s10928-020-09680-6

Figure Lengend Snippet: Model parameter estimates from palbociclib in vitro bone marrow assay.

Article Snippet: Palbociclib in vitro bone marrow assay Primary human bone marrow mononuclear cells (Lonza) were cultured in stemline II hematopoietic stem cell expansion medium (Sigma Aldrich), supplemented with 5% FBS and under induction by the following cytokines (R&D Systems): 25 ng/mL stem cell factor (SCF), 10 ng/mL G-CSF, 10 ng/mL granulocyte macrophage-colony stimulating factor, 3 U/mL erythropoietin (EPO), 15ng/mL thrombopoietin (TPO), 10ng/mL IL3, 10ng/mL IL6, and 25ng/mL Flt3 ligand.

Techniques: In Vitro, Concentration Assay, Inhibition

Journal: Journal of pharmacokinetics and pharmacodynamics

Article Title: A Physiological Model of Granulopoiesis to Predict Clinical Drug Induced Neutropenia from in vitro Bone Marrow Studies: With Application to a Cell Cycle Inhibitor

doi: 10.1007/s10928-020-09680-6

Figure Lengend Snippet: Overall observed and model predicted number of patients that developed each grade of neutropenia in the palbociclib clinical trials (n=170).

Article Snippet: Palbociclib in vitro bone marrow assay Primary human bone marrow mononuclear cells (Lonza) were cultured in stemline II hematopoietic stem cell expansion medium (Sigma Aldrich), supplemented with 5% FBS and under induction by the following cytokines (R&D Systems): 25 ng/mL stem cell factor (SCF), 10 ng/mL G-CSF, 10 ng/mL granulocyte macrophage-colony stimulating factor, 3 U/mL erythropoietin (EPO), 15ng/mL thrombopoietin (TPO), 10ng/mL IL3, 10ng/mL IL6, and 25ng/mL Flt3 ligand.

Techniques:

Journal: PLoS ONE

Article Title: Virotherapy Using Myxoma Virus Prevents Lethal Graft-versus-Host Disease following Xeno-Transplantation with Primary Human Hematopoietic Stem Cells

doi: 10.1371/journal.pone.0043298

Figure Lengend Snippet: To determine if MYXV can infect CD3 + lymphocytes found in human HCT samples, 1×10 6 whole BM cells ( A ) or 1×10 6 human PBMCs ( B ) were treated with vMyx-GFP at MOI = 10. Twenty-four hours after MYXV exposure, cells were stained with antibodies against CD3 and CD4 and the levels of GFP + cells in each population was determined using flow cytometry.

Article Snippet: Fresh normal human bone marrow aspirate cells and peripheral blood mononuclear cells were obtained commercially from Lonza (Walkersville, Maryland).

Techniques: Staining, Flow Cytometry

Journal: PLoS ONE

Article Title: Virotherapy Using Myxoma Virus Prevents Lethal Graft-versus-Host Disease following Xeno-Transplantation with Primary Human Hematopoietic Stem Cells

doi: 10.1371/journal.pone.0043298

Figure Lengend Snippet: NSG mice were sublethally irradiated and then transplanted with either 5×10 6 primary human PBMCs (n = 6) or 5×10 6 primary human PBMCs pre-treated with MYXV (n = 6). Mice were weighed twice per week to monitor body condition ( A ) and sacrificed either seven weeks after transplant or when their body condition score measured 2 ( B ). Significant differences in survival were determined using the log-rank test (P<0.05). N.S. = not significant. Post-mortem, organs were extracted, fixed in formalin, sectioned and stained for the presence of human CD3 + lymphocytes ( C ). Immunohistochemistry images shown are representative of results observed in three separate mice from the three engrafted cohorts stained for the presence of human CD3 + cells.

Article Snippet: Fresh normal human bone marrow aspirate cells and peripheral blood mononuclear cells were obtained commercially from Lonza (Walkersville, Maryland).

Techniques: Irradiation, Staining, Immunohistochemistry