Journal: bioRxiv

Article Title: MYC amplifies mitotic perturbations elicited by LXY18 to enable synthetic lethality

doi: 10.1101/2023.11.07.565938

Figure Lengend Snippet: RPE-NEO and RPE-MYC cells were treated with either vehicle control (0.1% DMSO) or indicated mitotic inhibitors for 24 h before immunofluorescent staining for H3Ser10P and staining for DNA with 4’,6-diamidino-2-phenylindole (DAPI). Cells positive for H3Ser10P were scored as mitotic cells and quantified when cells were treated with compounds other than AURKB inhibitors. For cells exposed to AZD1152 and AMG900, mitotic cells were identified based on their condensed chromosomes revealed by DAPI staining. The following mitotic inhibitors were used at minimally effective concentrations that are known to inhibit their respective targets, AZD1152 (200 nM), AMG900 (10 nM), BAY1217389 (20 nM), Centrinone (1 μM), GSK923295 (40 nM), SB743921 HCl (1.25 nM), Sovilnesib (80 nM). (A) Representative immunofluorescent images. (B) The percentage of the mitotic cells. Data are presented as mean ± SD. ****p<0.0001. (C) Histograms show the ratio of the mitotic index (MI) in RPE-MYC cells relative to RPE- NEO cells.

Article Snippet: Other antimitotic agents were obtained from the following commercial sources, AZD1152 (Selleck, CAS: 722544-51-6, Cat. No. S1147), AMG900 (TargetMol, CAS: 945595-80-2, Cat. No. T6380), BAY1217389 (Selleck, CAS: 1554458-53-5, Cat. No. S8215), Centrinone (TargetMol, CAS: 1798871-30-3,Cat.

Techniques: Staining

Journal: eLife

Article Title: BRAF V600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB

doi: 10.7554/eLife.70385

Figure Lengend Snippet: ( A ) Representative image of 15 H&E-stained melanocytic nevus. Border colors indicate two consecutive magnifications. Arrowheads indicate bi- (red) or multi- (blue) nucleation. ( B ) Example images of skin specimen containing a melanocytic nevus (circled) and phase-contrast microscopy of melanocytes isolated from nevus portion. Scale bar=400 µm. ( C ) Images of MLANA (purple) and Hoechst (green) co-staining of melanocytic nevus derived melanocytes in culture. Zoomed images show representative 2 N, 4 N, and 8 N cells. ( D ) Representative images of QPI coupled with fluorescence microscopy to identify adjacent mCherry-expressing and mCherry-negative melanocytes. Individual cells were identified at time zero, tracked, and monitored for division for 96 hr. ( E ) Mean and individual matched data points for the percent of n=3 mCherry-negative or mCherry-positive cells identified at time zero that divided over 96 hr. P value from paired t-test. ( F ) Mean and standard deviation for 48 hr growth rates of indicated cells treated with Barasertib. P values from unpaired t-tests comparing the 30 nM samples of melanoma lines to primary melanocytes (n=3). ( G ) Mean and standard deviation for relative QPI-derived dry mass per 501MEL cell at initial time point (black) compared to 48 hr treatment with Barasertib (gray) (n = 3). P values from unpaired t-tests. QPI, quantitative phase imaging.

Article Snippet: For each experiment, 100,000 melanocytes, 60,000 501Mel cells, or 150,000 HCIMel019 cells were plated per well and media containing indicated concentrations of barasertib (AURKB inhibitor; AZD1152-HQPA | AZD2811, Selleckchem, A1147) was added.

Techniques: Staining, Microscopy, Isolation, Derivative Assay, Fluorescence, Expressing, Standard Deviation, Imaging

Journal: eLife

Article Title: BRAF V600E induces reversible mitotic arrest in human melanocytes via microrna-mediated suppression of AURKB

doi: 10.7554/eLife.70385

Figure Lengend Snippet:

Article Snippet: For each experiment, 100,000 melanocytes, 60,000 501Mel cells, or 150,000 HCIMel019 cells were plated per well and media containing indicated concentrations of barasertib (AURKB inhibitor; AZD1152-HQPA | AZD2811, Selleckchem, A1147) was added.

Techniques: Derivative Assay, Western Blot, Recombinant, Sequencing, Control

Journal: Blood

Article Title: Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia

doi: 10.1182/blood-2011-07-366930

Figure Lengend Snippet: Baseline patient demographics and characteristics, and barasertib treatment cycles

Article Snippet: Similar PK findings have been reported in previous phase 1 studies of barasertib administered by various infusion schedules in patients with solid tumors (AstraZeneca data on file).

Techniques:

Journal: Blood

Article Title: Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia

doi: 10.1182/blood-2011-07-366930

Figure Lengend Snippet: Hematological responses in patients in parts A and B

Article Snippet: Similar PK findings have been reported in previous phase 1 studies of barasertib administered by various infusion schedules in patients with solid tumors (AstraZeneca data on file).

Techniques:

Journal: Blood

Article Title: Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia

doi: 10.1182/blood-2011-07-366930

Figure Lengend Snippet: AEs reported by ≥ 20% of patients overall (in either part A or B) split by maximum grade achieved

Article Snippet: Similar PK findings have been reported in previous phase 1 studies of barasertib administered by various infusion schedules in patients with solid tumors (AstraZeneca data on file).

Techniques:

Journal: Blood

Article Title: Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia

doi: 10.1182/blood-2011-07-366930

Figure Lengend Snippet: Geometric mean plasma concentration-time profiles of barasertib and barasertib-hQPA after a 7-day infusion of barasertib 1200 mg. Error bars indicate SD.

Article Snippet: Similar PK findings have been reported in previous phase 1 studies of barasertib administered by various infusion schedules in patients with solid tumors (AstraZeneca data on file).

Techniques: Clinical Proteomics, Concentration Assay

Journal: Blood

Article Title: Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia

doi: 10.1182/blood-2011-07-366930

Figure Lengend Snippet: PK parameters of barasertib and barasertib-hQPA following a 7-day infusion of barasertib 1200 mg in part B

Article Snippet: Similar PK findings have been reported in previous phase 1 studies of barasertib administered by various infusion schedules in patients with solid tumors (AstraZeneca data on file).

Techniques: