A5026465234- Neuroblastoma Research and Treatments
- Telomeres, Telomerase, and Senescence
- Protein Degradation and Inhibitors
- Acute Myeloid Leukemia Research
- Virus-based gene therapy research
- Cancer, Hypoxia, and Metabolism
- Chronic Myeloid Leukemia Treatments
- Ubiquitin and proteasome pathways
- Acute Lymphoblastic Leukemia research
- Peptidase Inhibition and Analysis
- Cancer-related Molecular Pathways
- Hematopoietic Stem Cell Transplantation
- Epigenetics and DNA Methylation
- Chronic Lymphocytic Leukemia Research
- Histone Deacetylase Inhibitors Research
- IgG4-Related and Inflammatory Diseases
- Genetics, Aging, and Longevity in Model Organisms
- Chromatin Remodeling and Cancer
- Cancer Research and Treatments
- Advanced biosensing and bioanalysis techniques
- Neuroendocrine Tumor Research Advances
- RNA Interference and Gene Delivery
- Cancer-related gene regulation
- Retinoids in leukemia and cellular processes
- Cell death mechanisms and regulation
The University of Sydney
2007-2024
Children's Medical Research Institute
1994-2024
Children's Cancer Institute Australia
2010-2023
UNSW Sydney
2012-2023
Westmead Institute
2022
Cancer Institute of New South Wales
2019
Block Center
2015
Migration Institute of Australia
2015
Cancer Institute (WIA)
2015
Sinclair Pharma
2007
We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique features, clinically significant subtypes, potential therapeutic targets. found 61 somatic copy-number alterations (SCNAs) 46 significantly mutated genes (SMGs). Eleven SCNAs 11 SMGs had not been identified in previous TCGA studies the individual tumor types. functionally estrogen receptor-regulated long non-coding RNAs (lncRNAs)...
The proteome provides unique insights into disease biology beyond the genome and transcriptome. A lack of large proteomic datasets has restricted identification new cancer biomarkers. Here, proteomes 949 cell lines across 28 tissue types are analyzed by mass spectrometry. Deploying a workflow to quantify 8,498 proteins, these data capture evidence cell-type post-transcriptional modifications. Integrating multi-omics, drug response, CRISPR-Cas9 gene essentiality screens with deep...
The identification of recurrent somatic mutations in genes encoding epigenetic enzymes has provided a strong rationale for the development compounds that target epigenome treatment cancer. This notion is supported by biochemical studies demonstrating aberrant recruitment such as histone deacetylases (HDACs) and methyltransferases to promoter regions through association with oncogenic fusion proteins PML-RARα AML1-ETO. HDAC inhibitors (HDACi) are potent inducers tumor cell apoptosis; however,...
The N-Myc oncoprotein is a critical factor in neuroblastoma tumorigenesis which requires additional mechanisms converting low-level to high-level expression. protein stabilized when phosphorylated at Serine 62 by ERK protein. Here we describe novel positive feedback loop whereby directly induced the transcription of class III histone deacetylase SIRT1, turn increased stability. SIRT1 binds Myc Box I domain form transcriptional repressor complex gene promoter mitogen-activated kinase...
Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response manifests after many months treatment transient. reasons underlying AZA resistance unknown, few alternatives exist for non-responders. Here, we show...
Angiosarcomas are rare malignant tumors of vascular origin that represent a genuine therapeutic challenge. Recently, the combination metronomic chemotherapy and drug repositioning has been proposed as an attractive alternative for cancer patients living in developing countries.In vitro experiments with transformed endothelial cells were used to identify synergistic interactions between anti-hypertensive propranolol chemotherapeutics. This led design pilot treatment protocol combining oral...
MYCN gene amplification in neuroblastoma drives a expression program that correlates strongly with aggressive disease. Mechanistically, trimethylation of histone H3 lysine 4 (H3K4) at target promoters is strict prerequisite for this transcriptional to be enacted. WDR5 H3K4 presenter has been found have an essential role trimethylation. For reason, study, we investigated the relationship between WDR5-mediated and N-Myc programs cells. upregulated Gene analysis revealed genes included those...
Before anaplastic lymphoma kinase (ALK) inhibitors, treatment options for ALK-positive inflammatory myofibroblastic tumors (AP-IMTs) were unsatisfactory. We retrospectively analyzed the outcome of patients with AP-IMT treated crizotinib to document response, toxicity, survival, and features associated relapse.The cohort comprised eight surgery. Outcome measures progression-free overall survival after commencing crizotinib, treatment-related toxicities, relapse, ceasing crizotinib.The median...
For pediatric cancers like neuroblastoma, the most common extracranial solid tumor of infancy, p53 mutations are rare at diagnosis, but may be acquired after chemotherapy, suggesting a potential role in drug resistance. Heavy metal-selected neuroblastoma cells were found to acquire an unusually broad multidrug resistance (MDR) phenotype displayed no alterations genes associated with "classic" MDR. These had mutant gene, linking sensitivity neuroblastoma. We therefore generated p53-deficient...
The anti-angiogenic activity of chemotherapy is both dose- and schedule-dependent. While conventional maximum tolerated dose (MTD) exerts only mild reversible effects, low-dose metronomic (LDM) was developed to specifically target tumour angiogenesis. However, the long-term effects either MTD or LDM on vascular endothelial cells have never been investigated. Here, we demonstrated that repeated exposure differentially impact angiogenic potential chemosensitivity immortalized cells. Repeated...
Abstract The RNA-binding protein dyskerin, encoded by the DKC1 gene, functions as a core component of telomerase holoenzyme well ribonuclear complexes involved in RNA processing and ribosome biogenesis. diverse roles dyskerin across many facets biology implicate its potential contribution to malignancy. In this study, we examined expression function neuroblastoma. We show that mRNA levels were elevated relative normal cells panel 15 neuroblastoma cell lines, where both N-Myc c-Myc directly...
Abstract Background Carcinoma of unknown primary (CUP) remains an important tumor entity and a disproportionate cause cancer mortality. Little is known about the contemporary clinical characteristics, treatment patterns, outcomes CUP patients based on updated international classification guidelines. We evaluated cohort to provide insight into current practice impact tissue origin assignment, site‐specific empirical therapy in real‐world setting. Methods conducted retrospective study...