A5079394261- Acute Lymphoblastic Leukemia research
- Estrogen and related hormone effects
- Acute Ischemic Stroke Management
- Epigenetics and DNA Methylation
- Prostate Cancer Treatment and Research
- Reproductive Biology and Fertility
- CRISPR and Genetic Engineering
- Birth, Development, and Health
- CAR-T cell therapy research
- Stroke Rehabilitation and Recovery
- Protein Degradation and Inhibitors
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Hormonal and reproductive studies
- Nuclear Receptors and Signaling
- Renal and related cancers
- Pregnancy and preeclampsia studies
- Acute Myeloid Leukemia Research
- Ovarian cancer diagnosis and treatment
- Genomics and Chromatin Dynamics
- FOXO transcription factor regulation
- Cerebrovascular and Carotid Artery Diseases
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Neurological Disorders and Treatments
Princess Máxima Center
2018-2024
Peter MacCallum Cancer Centre
2019-2023
Cooper Medical School of Rowan University
2022-2023
The University of Melbourne
2023
Radboud Institute for Molecular Life Sciences
2017-2022
Radboud University Medical Center
2015-2022
Radboud University Nijmegen
2015-2022
Cooper University Hospital
2022
Pediatric Oncology Group
2021
UCLA Health
2018
KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate H3K23 exert an oncogenic role in several tumor types including breast cancer where KAT6A is frequently amplified/overexpressed. However, pharmacologic targeting of to achieve therapeutic benefit has been a challenge. Here we describe identification highly potent, selective, orally bioavailable KAT6A/KAT6B inhibitor CTx-648 (PF-9363), derived from benzisoxazole series, which demonstrates anti-tumor...
Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles progression remain poorly characterized. In this study, we define an androgen-repressed gene whose expression elevated during adaptation prostate tumors to androgen-targeted therapies (ATTs), subsequent...
Treatment-induced neuroendocrine transdifferentiation (NEtD) complicates therapies for metastatic prostate cancer (PCa). Based on evidence that PCa cells can transdifferentiate to other neuroectodermally-derived cell lineages in vitro, we proposed NEtD requires first an intermediary reprogramming metastable stem-like (CSCs) of a neural class and demonstrate several different AR+/PSA+ lines were efficiently reprogrammed to, maintained propagated as CSCs by growth androgen-free neural/neural...
Genomic alterations involving translocations of the ETS-related gene ERG occur in approximately half prostate cancer cases. These result aberrant, androgen-regulated production protein variants that directly contribute to disease development and progression. This study describes discovery characterization a new class small molecule antagonists identified through rational silico methods. are designed sterically block DNA binding by ETS domain thereby disrupt transcriptional activity. We...
Drawing on data from a qualitative study of small group physiotherapists, this article explores the meaning hope in neurological physiotherapy practice. Nine female physiotherapists (43.2 +/- 8.5 years) each took part one-off semistructured interview. The most common kinds used and offered by process working with people disease were evident five themes. These are termed 1) Realistic Hope, 2) False 3) Accepting Hope No Need to 4) Faith, 5) Hope. Neurological experience patients provides...
Aims Apolipoprotein D (ApoD) is a protein that regulated by androgen and oestrogen, major constituent of breast cysts. Although ApoD has been reported to be marker cancer, its prognostic importance in invasive cancer unclear. The aim this study was investigate the relationship between expression, oestrogen receptor‐α (ERα) expression receptor (AR) predicting outcome. Methods results levels were measured use immunohistochemistry video image analysis on tissue sections from cohort ( n = 214)....
Abstract Introduction Current approaches to inhibit oestrogen receptor-alpha (ERα) are focused on targeting its hormone-binding pocket and have limitations. Thus, we propose that inhibitors bind a coactivator-binding ERα, called activation function 2 (AF2), might overcome some of these Methods In silico virtual screening was used identify small-molecule ERα AF2 inhibitors. These compounds were screened for inhibition transcriptional activity using stably transfected T47D-KBluc cell line. A...
IKZF1-deletions occur in 10-15% of patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and predict a poor outcome. However, the impact IKZF1-loss on sensitivity to drugs used contemporary treatment protocols has remained underexplored. Here we show experimental models that loss IKZF1 promotes resistance AraC, key component both upfront relapsed protocols. We attribute this resistance, part, diminished import incorporation cytarabine (AraC) due reduced expression solute...
The glycosaminoglycan chondroitin sulfate is significantly increased in the peritumoral stroma of prostate tumors compared with normal and an independent predictor prostate-specific antigen (PSA) relapse following radical prostatectomy. In this study, we determined whether specific alterations sulfation pattern chains clinically organ-confined cancer are associated PSA relapse. Immunoreactivity to distinct disaccharide epitopes was assessed by manually scoring staining intensity tissues from...
Abstract Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) has been implicated as a co-chaperone and regulator of androgen growth hormone receptor (AR, GHR) signalling. We investigated the functional consequences partial full Sgta ablation in vivo using Cre-lox -null mice. +/− breeders generated viable −/− offspring, but at less than Mendelian expectancy. S gta were subfertile with small litters higher neonatal death ( P < 0.02). Body size was significantly...
Abstract KAT6A is a lysine histone acetyltransferase (HAT) of the MYST family HATs. KAT6A, and its paralog KAT6B, have been shown to acetylate H3K23Ac regulate diverse biological processes, including transcription, cell-cycle progression, stem cell maintenance development. Molecular dysregulation has observed in several cancers, amplifications breast, lung, ovarian cancer along with oncogenic fusions AML. In breast cancer, amplified as part 8p11 amplicon 10-15% patient population, which...
Tyrosine kinase 2 (TYK2) is a member of the Janus kinase/signal transducer and activator transcription pathway, which central in cytokine signaling. Previously, germline TYK2 mutations have been described two patients developing de novo T-cell acute lymphoblastic leukemias (T-ALL) or precursor B-ALL. The (P760L G761V) are located within regulatory pseudokinase domain lead to constitutive activation TYK2. We demonstrate transformation capacity P760L hematopoietic cell systems including...
Although long-term survival in pediatric acute lymphoblastic leukemia (ALL) currently exceeds 90%, some subgroups, defined by specific genomic aberrations, respond poorly to treatment. We previously reported that leukemias harboring deletions or mutations affecting the B-cell transcription factor IKZF1 exhibit a tumor cell intrinsic resistance glucocorticoids (GCs), one of cornerstone drugs used treatment ALL. Here, we identified increased activation both AKT and ERK signaling pathways as...
Background: One in 10 ischemic strokes are large hemispheric infarctions (LHI), half of which cause cerebral edema that can lead to significant mortality. Our center implemented a protocol using acute glyburide patients with LHI determine its safety and efficacy reducing formation edema. Methods: Consecutive adult at our (10/2019-08/2021) who met criteria for the CHARM trial were treated per an institutional (2.5mg nasogastric tube twice daily 3 days) multi-disciplinary oversight. Unadjusted...