Amy J. Johnson
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View article: Enitociclib ( <scp>VIP152</scp> ), venetoclax and prednisone in relapsed or refractory aggressive non‐Hodgkin lymphoma
Enitociclib ( <span>VIP152</span> ), venetoclax and prednisone in relapsed or refractory aggressive non‐Hodgkin lymphoma Open
View article: Targeting CDK9 inhibits the growth of KMT2A-rearranged infant leukemia and demonstrates synergy with menin inhibition
Targeting CDK9 inhibits the growth of KMT2A-rearranged infant leukemia and demonstrates synergy with menin inhibition Open
The KMT2A-rearranged (KMT2A-r) leukemia is one of the most challenging cancers to treat in children, owing to the higher relapse rates and chemoresistance frequently observed in this patient population. At the molecular level, chromosomal …
View article: The prostacyclin receptor PTGIR is a NRF2-dependent regulator of CD8+ T cell exhaustion
The prostacyclin receptor PTGIR is a NRF2-dependent regulator of CD8+ T cell exhaustion Open
View article: Unequal NHS wig provision: toupée or no toupée, that is the question?
Unequal NHS wig provision: toupée or no toupée, that is the question? Open
Wigs are a necessary medical orthotic for some patients with alopecia to participate in society. However, for those with limited incomes, government-funded NHS wig provision is of great help. Recent reports to Alopecia UK, a patient suppor…
View article: Sperm meet the elevated energy demands to attain fertilization competence by increasing flux through aldolase
Sperm meet the elevated energy demands to attain fertilization competence by increasing flux through aldolase Open
Prior to ejaculation, sperm are stored in the epididymis in a ‘resting’ metabolic state. Upon ejaculation, sperm must alter their metabolism to generate the energy needed to support the motility and maturation process known as capacitation…
View article: Enitociclib, a selective CDK9 inhibitor: in vitro and in vivo preclinical studies in multiple myeloma
Enitociclib, a selective CDK9 inhibitor: in vitro and in vivo preclinical studies in multiple myeloma Open
Multiple myeloma (MM) is a cancer of plasma cells that remains incurable despite advances in treatment options. In this study, a library of 216 clinically feasible small-molecule inhibitors was screened to identify agents that selectively …
View article: Data from Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity
Data from Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity Open
The protein arginine methyltransferase 5 (PRMT5) methylates a variety of proteins involved in splicing, multiple signal transduction pathways, epigenetic control of gene expression, and mechanisms leading to protein expression required for…
View article: Supplementary Tables from Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity
Supplementary Tables from Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity Open
Supplementary Tables
View article: Supplementary Figures from Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity
Supplementary Figures from Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity Open
Supplementary Figures
View article: Supplementary Methods from Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity
Supplementary Methods from Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity Open
Materials and Methods
View article: NRF2-dependent regulation of the prostacyclin receptor PTGIR drives CD8 T cell exhaustion
NRF2-dependent regulation of the prostacyclin receptor PTGIR drives CD8 T cell exhaustion Open
The progressive decline of CD8 T cell effector function—also known as terminal exhaustion—is a major contributor to immune evasion in cancer. Yet, the molecular mechanisms that drive CD8 T cell dysfunction remain poorly understood. Here, w…
View article: Highly conserved brain vascular receptor ALPL mediates transport of engineered viral vectors across the blood-brain barrier
Highly conserved brain vascular receptor ALPL mediates transport of engineered viral vectors across the blood-brain barrier Open
Delivery of systemically administered therapeutics to the central nervous system (CNS) is restricted by the blood-brain barrier (BBB). Bioengineered Adeno-Associated Virus (AAV) capsids have been shown to penetrate the BBB with great effic…
View article: Neutrophil elastase as a versatile cleavage enzyme for activation of αvβ3 integrin-targeted small molecule drug conjugates with different payload classes in the tumor microenvironment
Neutrophil elastase as a versatile cleavage enzyme for activation of αvβ3 integrin-targeted small molecule drug conjugates with different payload classes in the tumor microenvironment Open
Introduction: The development of bioconjugates for the targeted delivery of anticancer agents is gaining momentum after recent success of antibody drug conjugates (ADCs) in the clinic. Smaller format conjugates may have several advantages …
View article: Patients' Experiences of Primary Healthcare and Dermatology Provision for Alopecia
Patients' Experiences of Primary Healthcare and Dermatology Provision for Alopecia Open
Background Alopecia describes a group of dermatological conditions characterised by hair loss, which are either non-scarring or scarring in nature, and range from bald patches to complete body hair loss, to general thinning. In the UK, the…
View article: FIGURE 5 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
FIGURE 5 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Comparison of DEGs identified in MYC+ DLBCL cell lines to blood samples from enitociclib-treated patienst with MYC+ NHL. A, Comparison of significant DEGs (Padj ≤ 0.05, fold change ≥2) after at 4 hours pretreatment…
View article: Figure S1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Figure S1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Supplementary Figure 1 shows the principal component analysis of RNA sequencing of either SU-DHL-4 and SU-DHL-10 cell lines as well as that from RNA sequencing of patient blood samples.
View article: FIGURE 4 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
FIGURE 4 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Enitociclib treatment confers a robust shift in transcriptional activity in MYC+ DLBCL cell lines. A, Comparison of significant DEGs (Padj ≤ 0.05, fold change ≥2) after 4 hours pretreatment of DLBLC cell lin…
View article: TABLE 1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
TABLE 1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Response and pharmacokinetics properties of patients with DH-DLBCL and other patients with MYC+ NHL (n = 15) treated with 30 mg enitociclib i.v. once weekly
View article: Table S2 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Table S2 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Supplementary Table 2 contains the statistical analysis for pSer2 downregulation in SU-DHL-4 and SU-DHL-10 cell lines across CDK9 inhibitor treatments.
View article: Figure S2 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Figure S2 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Supplementary Figure 2: Downregulation of MYC and MCL1 is detected in the whole blood of Enitociclib-treated DH-DLBCL as well as other MYC+ NHL patients
View article: Figure S1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Figure S1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Supplementary Figure 1 shows the principal component analysis of RNA sequencing of either SU-DHL-4 and SU-DHL-10 cell lines as well as that from RNA sequencing of patient blood samples.
View article: Table S3 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Table S3 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Supplementary Table 3 contains the top DEGS from an unbiased analysis of RNAseq from MYC+ DLBCL cell lines treated with CDK9 inhibitors.
View article: FIGURE 4 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
FIGURE 4 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Enitociclib treatment confers a robust shift in transcriptional activity in MYC+ DLBCL cell lines. A, Comparison of significant DEGs (Padj ≤ 0.05, fold change ≥2) after 4 hours pretreatment of DLBLC cell lin…
View article: FIGURE 1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
FIGURE 1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Enitociclib delivers robust inhibition of RNA polymerase II Ser2 phosphorylation for up to 48 hours in cell lines. A, The gene expression of MYC, and MCL1 as determined by RNA-seq expressed as transcripts per million (…
View article: Table S1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Table S1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Supplementary Table 1 shows the enitociclib toxicity in a panel of lymphoma cell lines ranked by IC50
View article: Table S4 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Table S4 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Supplementary Table 4 shows the baseline characteristics of DH-DLBCL and other MYC+ NHL Patients (n=15) treated with 30 mg enitociclib i.v. QW from whom samples were collected for discovery of DEGs.
View article: Data from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Data from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Double-hit diffuse large B-cell lymphoma (DH-DLBCL) is an aggressive, and often refractory, type of B-cell non–Hodgkin lymphoma (NHL) characterized by rearrangements in MYC and BCL2. Cyclin-dependent kinase 9 (CDK9) regulates transcription…
View article: Table S3 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Table S3 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Supplementary Table 3 contains the top DEGS from an unbiased analysis of RNAseq from MYC+ DLBCL cell lines treated with CDK9 inhibitors.
View article: FIGURE 3 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
FIGURE 3 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Enitociclib treatment results in complete regression of MYC-overexpressing SU-DHL-10 lymphoma growth and mechanism of action confirmed in vivo. A, Growth curves where red arrows indicate dosing days and tumor volumes o…
View article: Table S1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Table S1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription Open
Supplementary Table 1 shows the enitociclib toxicity in a panel of lymphoma cell lines ranked by IC50