Journal: Blood Advances

Article Title: Copanlisib synergizes with conventional and targeted agents including venetoclax in B- and T-cell lymphoma models

doi: 10.1182/bloodadvances.2019000844

Figure Lengend Snippet: Antitumor activity of copanlisib in lymphoma cell lines other than DLBCL

Article Snippet: Copanlisib, roniciclib (BAY 1000394), bromodomain and extraterminal motif (BET) inhibitor BAY 1238097, positive transcription elongation factor b (PTEFb) inhibitor atuveciclib (BAY 1143572), and AKT inhibitor (BAY 1125976) were provided by Bayer AG.

Techniques: Activity Assay

Journal: Blood Advances

Article Title: Copanlisib synergizes with conventional and targeted agents including venetoclax in B- and T-cell lymphoma models

doi: 10.1182/bloodadvances.2019000844

Figure Lengend Snippet: In vitro and in vivo antiproliferative effects of copanlisib-containing combinations in lymphoma models. (A) In vitro combination in B-cell lymphoma cell lines derived from MCL, MZL, and CLL. (B) In vitro combination in T-cell lymphomas cell lines derived from ALCL, PTCL, and CTCL. (C) Antitumor in vivo activity of copanlisib in combination with venetoclax or lenalidomide in the MZL SSK41 model. Mice were treated with vehicle (IV), copanlisib (14 mg kg IV, 2 days on/5 days off), venetoclax (200 mg/kg, postoperatively, once per day), lenalidomide (50 mg/kg, postoperatively, once per day), copanlisib plus venetoclax (same doses as the single agents), or copanlisib plus lenalidomide (same doses as the single agents). Lines show median values per time point with the corresponding upper interquartile range. The y-axis indicates the tumor volume in millimeters cubed; the x-axis, days of treatment (P values shown in supplemental Table 4).

Article Snippet: Copanlisib, roniciclib (BAY 1000394), bromodomain and extraterminal motif (BET) inhibitor BAY 1238097, positive transcription elongation factor b (PTEFb) inhibitor atuveciclib (BAY 1143572), and AKT inhibitor (BAY 1125976) were provided by Bayer AG.

Techniques: In Vitro, In Vivo, Derivative Assay, Activity Assay

Journal: Blood Advances

Article Title: Copanlisib synergizes with conventional and targeted agents including venetoclax in B- and T-cell lymphoma models

doi: 10.1182/bloodadvances.2019000844

Figure Lengend Snippet: PI3K inhibitor copanlisib and the BCL2 inhibitor venetoclax are cytotoxic for MCL and MZL cells when combined and act via downregulating BCLXL or MCL1. (A) Four cell lines were exposed for 24 hours to copanlisib (30 nM, 300 nM), venetoclax (0.3 μM, 3 μM), or the combination of the 2 agents. (B) Three MCL and 2 MZL primary cells were exposed for 48 hours to copanlisib (100 or 200 nM), venetoclax (100 or 200 nM), or the combination of the 2 agents. The y-axis indicates the percentage of live cells, defined as Annexin V and 7AAD−, compared with dimethyl sulfoxide (DMSO)–treated cells. (C) Two cell lines exposed to copanlisib (30 nM, 300 nM), venetoclax (0.3 μM, 3 μM), or the combination of the 2 agents for 24 hours. cPARP, cleaved PARP; SMZL, splenic MZL.

Article Snippet: Copanlisib, roniciclib (BAY 1000394), bromodomain and extraterminal motif (BET) inhibitor BAY 1238097, positive transcription elongation factor b (PTEFb) inhibitor atuveciclib (BAY 1143572), and AKT inhibitor (BAY 1125976) were provided by Bayer AG.

Techniques:

Journal: Blood Advances

Article Title: Copanlisib synergizes with conventional and targeted agents including venetoclax in B- and T-cell lymphoma models

doi: 10.1182/bloodadvances.2019000844

Figure Lengend Snippet: Combination of the PI3K inhibitor copanlisib with the CDK4/6 inhibitor palbociclib did not induce apoptosis in MCL and MZL cell lines, but did induce G0/G1 arrest with upregulation of PIK3IP1. (A) Four cell lines were exposed for 24 hours to copanlisib (30 nM, 300 nM), palbociclib (0.3 μM, 3 μM), or the combination of the 2 agents. (B) Cell-cycle analysis of 1 MCL (JEKO1) and 1 MZL (SSK41) cell line exposed for 24 hours to copanlisib (30 nM, 300 nM), palbociclib (0.3 μM, 3 μM), or the combination of the 2 agents. (C) RNA changes of PIK3IP1 in 1 MCL (JEKO1) and 1 MZL cell line exposed for 24 hours to copanlisib (30 nM, 300 nM), palbociclib (0.3 μM, 3 μM), or the combination of the 2 agents.

Article Snippet: Copanlisib, roniciclib (BAY 1000394), bromodomain and extraterminal motif (BET) inhibitor BAY 1238097, positive transcription elongation factor b (PTEFb) inhibitor atuveciclib (BAY 1143572), and AKT inhibitor (BAY 1125976) were provided by Bayer AG.

Techniques: Cell Cycle Assay

Journal: Blood Advances

Article Title: Copanlisib synergizes with conventional and targeted agents including venetoclax in B- and T-cell lymphoma models

doi: 10.1182/bloodadvances.2019000844

Figure Lengend Snippet: In vitro assessment of copanlisib combination with PIM or MCL1 inhibitors

Article Snippet: Copanlisib, roniciclib (BAY 1000394), bromodomain and extraterminal motif (BET) inhibitor BAY 1238097, positive transcription elongation factor b (PTEFb) inhibitor atuveciclib (BAY 1143572), and AKT inhibitor (BAY 1125976) were provided by Bayer AG.

Techniques: In Vitro

Journal: Scientific Reports

Article Title: A c-Myc-regulated stem cell-like signature in high-risk neuroblastoma: A systematic discovery (Target neuroblastoma ESC-like signature)

doi: 10.1038/s41598-017-00122-x

Figure Lengend Snippet: The cyclin-dependent kinase inhibitor Roniciclib induces morphological changes and cell apoptosis in human neuroblastoma cells. ( a ) Roniciclib is the only drug that is commonly over-represented in the ESC-like cancer-activated signature, HR genes, and the MA-dependently expressed MA or MN genes. ( b ) Roniciclib induces apoptotic cell death in SY5Y in a concentration-dependent manner. Proliferating SY5Y cells were exposed to different concentrations of Roniciclib for 72 h. Caspase-3 activity was measured by monitoring Ac-DEVD-R110 fluorescence. The data are represented as the mean ± SD of three independent experiments. ( c ) Morphological changes and cell number decrease in human neuroblastoma cells observed under an inverted microscope (magnification, 20x): Blank control group, dimethyl sulfoxide-treated group (0.1% DMSO, 72 h), and Roniciclib-treated group (1 μmol/L, 72 h).

Article Snippet: Roniciclib was purchased from AdooQ Bioscience (Irvine, CA, USA), dissolved in DMSO at 0.5 mM and 1 mM and stored for later use.

Techniques: Concentration Assay, Activity Assay, Fluorescence, Inverted Microscopy, Control

Journal: Scientific Reports

Article Title: A c-Myc-regulated stem cell-like signature in high-risk neuroblastoma: A systematic discovery (Target neuroblastoma ESC-like signature)

doi: 10.1038/s41598-017-00122-x

Figure Lengend Snippet: Prediction and validation of ESC-like signature genes that interact with Roniciclib, which are used as new biomarkers. ( a ) Venn diagram of the computational prediction of new biomarkers irrespective of MYCN status. Among the ten Roniciclib-interacting genes, four CDKs are inhibited and are underlined. Data resource: DGIdb. The gene symbol colour corresponds to MYCN-dependent over-expression (red: MA, blue: MN; black: NS). ( b ) Roniciclib alters c-Myc and CCND1 protein expression. The SY5Y cells were plated in 60 mm dishes one day before treatment. The cells were treated with or without vehicle control (DMSO) or Roniciclib (1 μM) for the indicated times. Then, 100 μg of protein was loaded and resolved by 10% SDS-PAGE. β-actin was used as a loading control. ( c) Quantitative analysis of mRNA expression in a human HR-NB cell line after Roniciclib treatment for 24, 48, 72 or 96 h. The relative expression levels were normalized to the mean expression level of GAPDH. The data shown are the mean relative expression levels ± SD of replicate experiments after normalization to the non-treated control. The significance (NS > 0.1, . ≤0.1, *<0.05, **<0.01) was estimated by a two-tailed Welch’s corrected t-test that compares Roniciclib with DMSO in each scenario, followed by the number of biological replicates.

Article Snippet: Roniciclib was purchased from AdooQ Bioscience (Irvine, CA, USA), dissolved in DMSO at 0.5 mM and 1 mM and stored for later use.

Techniques: Biomarker Discovery, Over Expression, Expressing, Control, SDS Page, Two Tailed Test

Journal: Scientific Reports

Article Title: A c-Myc-regulated stem cell-like signature in high-risk neuroblastoma: A systematic discovery (Target neuroblastoma ESC-like signature)

doi: 10.1038/s41598-017-00122-x

Figure Lengend Snippet: c-Myc plays a role in the Roniciclib-impacted tumour-initiating cell mechanisms in HR-NB. ( a ) Genomic view of four gene promoters showing chromatin accessibility with c-MYC/MAX occupancy (ENCODE data, hg19 assembly). The view scale of c-MYC/MAX is between 0 and 50, whereas that of DNase is between 0 and 80 in each sub-panel. ( b ) Quantitative analysis of mRNA expression in human HR-NB cells after Roniciclib treatment for 24 h. The relative expression levels were normalized to mean GAPDH expression. The data shown are the mean relative expression levels ± SD of replicate experiments after normalization to the non-treated vehicle. The p-value of a two-tailed Welch’s corrected t-test that compares Roniciclib to DMSO is given in each scenario, followed by the number of biological replicates. ( c ) Proposed model of c-Myc-regulated tumour initiating cell markers that were targeted by Roniciclib in a time-dependent manner in HR-NB. The genes indicated in red are potential neural stem cell markers that are highly expressed, and the genes indicated in blue are neural cell differentiation markers that are repressed in HR-NB compared with LR-NB. The two origin arrows along with each gene indicate the expression changes corresponding to Roniciclib treatment at an early and later phase, respectively.

Article Snippet: Roniciclib was purchased from AdooQ Bioscience (Irvine, CA, USA), dissolved in DMSO at 0.5 mM and 1 mM and stored for later use.

Techniques: Expressing, Two Tailed Test, Cell Differentiation