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: Oncotarget

Article Title: Drug conjugated nanoparticles activated by cancer cell specific mRNA

doi: 10.18632/oncotarget.9430

Figure Lengend Snippet: A. Percentage of leukemia cells containing DNA Au-NPs covalently labeled with Cy5 (see methods) was assessed by flow cytometry after an overnight incubation. Percentages are the mean±s.e.m. from three independent experiments. K562 cells were mixed with either human bone marrow mononuclear cells B. or murine bone marrow cells C. at the specified ratios and then incubated overnight with DNA Au-NPs covalently labeled with Cy5. Percentages of leukemia cells containing NPs are the mean±s.e.m. from three independent experiments. Flow cytometry histogram D. and quantitation E. of K562 leukemia cells isolated from subcutaneous flanks tumors that were either injected with Cy5 labeled Au-NPs (blue, green, orange) or un-injected (red).

Article Snippet: Either murine bone marrow cells (red cell lysed) or human bone marrow mononuclear cells (Lonza) were mixed at specified ratios with leukemia cells stained with Cell-Trace Violet (Invitrogen).

Techniques: Labeling, Flow Cytometry, Incubation, Quantitation Assay, Isolation, Injection

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