Journal: Hematology: the American Society of Hematology Education Program

Article Title: The optimal management of relapsed and refractory Hodgkin lymphoma: post–brentuximab and checkpoint inhibitor failure

doi: 10.1182/hematology.2023000450

Figure Lengend Snippet: Clinical trials for relapsed/refractory Hodgkin lymphoma

Article Snippet: AZD4573 , 2 , AZD4573–CDK9 inhibitor , 81 , AstraZeneca , NCT05140382.

Techniques: Clinical Proteomics

Journal: Marine drugs

Article Title: The Polybrominated Diphenyl Ether Bromoxib Disrupts Nuclear Import and Export by Affecting Nucleoporins of the Nuclear Pore Complex.

doi: 10.3390/md23030108

Figure Lengend Snippet: Figure 6. Bromoxib inhibits the expression of the short-lived anti-apoptotic Bcl-2 protein Mcl-1. (A) Schematic illustration of the effect of RNA polymerase II inhibition by the CDK9 inhibitor AZD4573 on the subsequent protein expression of short-lived proteins such as Mcl-1. RNA poly- merase II mediates the transcription of mRNA in the nucleus, which then translocates across the NPC into the cytosol. There, mRNA is translated at the ribosomes into respective proteins. Finally, proteins are degraded by the proteasome. One of the short-lived proteins is the anti-apoptotic Bcl-2 protein Mcl-1. Studies by Cidado et al. have shown that the selective CDK9-inhibitor AZD4573 inhibits the CDK9-mediated activation of RNA polymerase II and induces the downregulation of Mcl-1 mRNA, followed by a rapid downregulation of Mcl-1 at the protein level [25]. (B) Ramos cells were treated with 10 µM or 40 µM of bromoxib, or 0.1 µM of the CDK9 inhibitor AZD4573 in a kinetic for 0 h, 2 h, 4 h, 6 h or 8 h. Treatment with 0.2% w/v DMSO for 8 h served as diluent control. Subsequently, immunoblots for the anti-apoptotic Bcl-2 protein Mcl-1, the caspase substrate poly(ADP-ribose) polymerase-1 (PARP), or vinculin (loading control) were performed. Solid arrowheads indicate the uncleaved form of PARP (p116); open arrowheads indicate the cleaved form (p85). (C) Quantitative analysis of immunoblots (see (B) for representative immunoblots) from three independent biological replicates (n = 3). (D) To avoid caspase-mediated protein degradation, Ramos cells were pretreated with 10 µM of the caspase-inhibitor QVD for 30 min. Subsequently, cells were treated as described in (B). (E) Quantitative analysis of immunoblots (see (D) for representative immunoblots) from three independent biological replicates (n = 3).

Article Snippet: The pan-caspase inhibitor N-(2-Quinolyl)valylaspartyl-(2,6-difluorophenoxy)methyl ketone (Q-VD-OPh, QVD, #S7311) and the selective CDK9-inhibitor AZD4573 (S8719) were obtained from Selleckchem (Houston, TX, USA).

Techniques: Expressing, Inhibition, Activation Assay, Control, Western Blot

Journal: Journal of advanced research

Article Title: An interpretable artificial intelligence framework for designing synthetic lethality-based anti-cancer combination therapies.

doi: 10.1016/j.jare.2023.11.035

Figure Lengend Snippet: Fig. 5. KDDSL can help to develop promising combination therapies based on BP-level induced SL. a Schematic overview of EGFR-related combination therapy and clinical trial validation. The green and purple blocks respectively correspond to EGFR inhibitors and lipid-regulating agents. Clinical Trial Registration Numbers are annotated on the grey line between these blocks.b Schematic overview of mTOR-related combination therapy and clinical trial validation. The green and purple blocks respectively represent mTOR inhibitors and DNA-damaging agents. Clinical Trial Registration Numbers are annotated on the grey line between these blocks.c The impact of Ixabepilone, Veliparib, or Advosertinib (DNA-damaging agents) with Everolimus (mTOR inhibitor) as single agents or drug combinations in A549 cells. Cell viability was measured 72 h after treatment with the indicated doses. Data are means ± SD for triplicate analyses. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Article Snippet: Inhibitors of MDM2 (Idasanutlin, S7205), MAPK12 (BMS-582949, S8124), USP1 (ML323, S7529), CDK9 (AZD-4573, S8719), and RELA (QNZ, S4902) were obtained from Selleck Chemicals (TX, USA).

Techniques: Biomarker Discovery

Journal: Journal of advanced research

Article Title: An interpretable artificial intelligence framework for designing synthetic lethality-based anti-cancer combination therapies.

doi: 10.1016/j.jare.2023.11.035

Figure Lengend Snippet: Fig. 4. KDDSL identifies important SL interaction-related subsystems. a The top subsystems for layers 1–3 were able to differentiate between samples with different labels (top), whereas the bottom subsystems for layers 1–3 were not (bottom). Negative and positive samples are represented by 0 and 1, respectively. b The potential mechanisms underlying SL interactions between ERCC1 and USP1 identified by KDDSL. Evidence supporting this candidate mechanism was derived from the literature.

Article Snippet: Inhibitors of MDM2 (Idasanutlin, S7205), MAPK12 (BMS-582949, S8124), USP1 (ML323, S7529), CDK9 (AZD-4573, S8719), and RELA (QNZ, S4902) were obtained from Selleck Chemicals (TX, USA).

Techniques: Derivative Assay