Jean‐Pierre J. Issa
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View article: Reducing Acute Myeloid Leukemia resistance to CAR T cell therapy by epigenetic activation of the tumor inflammasome-pyroptosis signaling
Reducing Acute Myeloid Leukemia resistance to CAR T cell therapy by epigenetic activation of the tumor inflammasome-pyroptosis signaling Open
Acute myeloid leukemia (AML) faces major clinical challenges characterized by high relapse and low cure rates. Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment for B cell malignancies, but it has limited effi…
View article: A Phase I Study of ASTX727 plus Talazoparib in Patients with Triple Negative or Hormone Resistant/HER2-negative Metastatic Breast Cancer
A Phase I Study of ASTX727 plus Talazoparib in Patients with Triple Negative or Hormone Resistant/HER2-negative Metastatic Breast Cancer Open
Background Poly (ADP-ribose) polymerase inhibitors (PARPi) are effective in patients with germline BRCA 1/2 and PALB2 mutations but have been largely ineffective as monotherapy in others. PARP interacts with, and is recruited to, DNA damag…
View article: Assessing Cognition in Kidney Failure Using Virtual Reality Technology: A Clinical Research Protocol
Assessing Cognition in Kidney Failure Using Virtual Reality Technology: A Clinical Research Protocol Open
Background: Cognitive impairment is common in patients receiving dialysis and is associated with morbidity and mortality. Existing approaches to administering face-to-face cognitive screening assessments like the Montreal Cognitive Assessm…
View article: Relationship Between Patient‐Reported Experiences and Treatment Satisfaction Among Men and Women in Residential Substance Use Treatment
Relationship Between Patient‐Reported Experiences and Treatment Satisfaction Among Men and Women in Residential Substance Use Treatment Open
Introduction Understanding the experiences of women participating in residential alcohol and other drug ( AOD ) treatment is important in ensuring treatment effectively meets women's needs. Patient‐reported experience measures aid in asses…
View article: DNA Methylation, Aging, and Cancer
DNA Methylation, Aging, and Cancer Open
Aging and cancer, though distinct biological processes, share overlapping molecular pathways, particularly in epigenetic regulation. Among these, DNA methylation is central to mediating gene expression, maintaining cellular identity, and r…
View article: Data from ZNFX1 Functions as a Master Regulator of Epigenetically Induced Pathogen Mimicry and Inflammasome Signaling in Cancer
Data from ZNFX1 Functions as a Master Regulator of Epigenetically Induced Pathogen Mimicry and Inflammasome Signaling in Cancer Open
DNA methyltransferase (DNMT) and PARP inhibitors induce a stimulator of IFN gene–dependent pathogen mimicry response (PMR) in ovarian and other cancers. In this study, we showed that combining DNMT and PARP inhibitors upregulates expressio…
View article: Supplementary Data from ZNFX1 Functions as a Master Regulator of Epigenetically Induced Pathogen Mimicry and Inflammasome Signaling in Cancer
Supplementary Data from ZNFX1 Functions as a Master Regulator of Epigenetically Induced Pathogen Mimicry and Inflammasome Signaling in Cancer Open
Supplementary Figures
View article: Mollaret's Meningitis: A Case Report of Recurrent Aseptic Meningitis
Mollaret's Meningitis: A Case Report of Recurrent Aseptic Meningitis Open
Benign recurrent meningitis, also known as Mollaret's meningitis, a rare form of recurrent aseptic meningitis, is often associated with herpes simplex virus type 2 (HSV-2) infection, which is characterized by fever, headache, meningeal irr…
View article: CDK9 degradation Inhibits Gastroesophageal Cancer growth and Overcomes Radiation Resistance by Increasing Chromatin Accessibility and Downregulating YAP1/TEAD signaling
CDK9 degradation Inhibits Gastroesophageal Cancer growth and Overcomes Radiation Resistance by Increasing Chromatin Accessibility and Downregulating YAP1/TEAD signaling Open
Background Gastroesophageal cancer (GEAC) remains a major health burden and urgently needs novel therapeutic targets. The inhibition of CDK9’s activity holds the potential to be a highly effective anti-cancer therapeutic. However, the func…
View article: A phase 2 study of decitabine with or without carboplatin and arsenic trioxide in patients with MDS and AML
A phase 2 study of decitabine with or without carboplatin and arsenic trioxide in patients with MDS and AML Open
Although decitabine (DAC) shows activity against myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), patient responses are limited, and prognoses remain poor. Preclinical studies have indicated that arsenic trioxide (ATO) and …
View article: Bone marrow microenvironment signatures associate with patient survival after guadecitabine and atezolizumab therapy in HMA-resistant MDS
Bone marrow microenvironment signatures associate with patient survival after guadecitabine and atezolizumab therapy in HMA-resistant MDS Open
Almost 50% of patients with myelodysplastic syndrome (MDS) are refractory to first-line hypomethylating agents (HMAs), which presents a significant clinical challenge considering the lack of options for salvage. Past work revealed that imm…
View article: Reprogramming T Cell EZH2 to Counteract CAR T Cell Dysfunction during Tumor Control
Reprogramming T Cell EZH2 to Counteract CAR T Cell Dysfunction during Tumor Control Open
T cell dysfunction, including memory loss and exhaustion, is a major limitation of CAR T cell therapy efficacy. Manipulating transcription factor (TF) activity ameliorates their exhaustion and memory loss during tumor control suggests tumo…
View article: ZNFX1 is a Novel Master Regulator in Epigenetically-induced Pathogen Mimicry and Inflammasome Signaling in Cancer
ZNFX1 is a Novel Master Regulator in Epigenetically-induced Pathogen Mimicry and Inflammasome Signaling in Cancer Open
DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon (IFN) genes (STING)-dependent pathogen mimicry response (PMR) in ovarian (OC) and other cancers. We now show that combining…
View article: Figure S11 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S11 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 11: Peripheral immune cells are activated mid-treatment cycle.
View article: Figure S8 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S8 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 8: PD-L1 levels in tumor or tumor microenvironment does not associate with tumor progression or control.
View article: Figure S2 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S2 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 2: Modest treatment-induced DNA methylation changes in UC tumors.
View article: Figure S9 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S9 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 9: CD8 infiltration in tumor is associated with survival.
View article: Supplementary Tables 1 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Supplementary Tables 1 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Tables Supplementary Table 1: Patient and tumor sample information Supplementary Table 2: Tumor mutation burden Supplementary Table 3: Unfiltered whole exome sequencing mutation analysis Supplementary Table 4: Filtered whole …
View article: Figure S10 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S10 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 10: Peripheral immune cell dynamics induced by combination therapy.
View article: Figure S6 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S6 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 6: Gene Set Enrichment Analysis reveals immune-related pathways discriminate PD and SD tumors.
View article: Figure S1 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S1 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 1: Patient recruitment and sample collection overview.
View article: Data from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Data from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Purpose: Based on preclinical evidence of epigenetic contribution to sensitivity and resistance to immune checkpoint inhibitors (ICI), we hypothesized that guadecitabine (hypomethylating agent) and atezolizumab (anti-PD-L1) together would …
View article: Figure S8 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S8 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 8: PD-L1 levels in tumor or tumor microenvironment does not associate with tumor progression or control.
View article: Figure S11 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S11 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 11: Peripheral immune cells are activated mid-treatment cycle.
View article: Figure S10 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S10 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 10: Peripheral immune cell dynamics induced by combination therapy.
View article: Figure S4 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S4 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 4: Weak correlation of TE expression induction with DNA methylation change and viral mimicry activation.
View article: Figure S9 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S9 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 9: CD8 infiltration in tumor is associated with survival.
View article: Figure S2 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S2 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 2: Modest treatment-induced DNA methylation changes in UC tumors.
View article: Figure S6 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S6 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 6: Gene Set Enrichment Analysis reveals immune-related pathways discriminate PD and SD tumors.
View article: Figure S3 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Figure S3 from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy Open
Supplementary Figure 3: Copy number variation detected by SeSAMe from DNA methylation data.