A5027301367- Cancer, Hypoxia, and Metabolism
- Angiogenesis and VEGF in Cancer
- MicroRNA in disease regulation
- Ferroptosis and cancer prognosis
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- Amino Acid Enzymes and Metabolism
- Cancer Immunotherapy and Biomarkers
- Enzyme function and inhibition
- Metabolism and Genetic Disorders
- Fibroblast Growth Factor Research
- Kruppel-like factors research
- Synthesis and Catalytic Reactions
- HER2/EGFR in Cancer Research
- Cancer Cells and Metastasis
- Breast Cancer Treatment Studies
- Lymphoma Diagnosis and Treatment
- Immune cells in cancer
- Histone Deacetylase Inhibitors Research
- Cell Adhesion Molecules Research
- Radiopharmaceutical Chemistry and Applications
- Cancer Genomics and Diagnostics
- Arctic and Antarctic ice dynamics
- RNA modifications and cancer
- Estrogen and related hormone effects
Peter MacCallum Cancer Centre
2008-2025
Mater Health Services
2017-2024
John Radcliffe Hospital
2011-2023
Mater Research
2017-2023
Translational Research Institute
2017-2023
The University of Queensland
2017-2023
Mater Adult Hospital
2017-2023
The University of Melbourne
2005-2020
Queensland University of Technology
2020
National Institute of Biomedical Innovation, Health and Nutrition
2020
microRNA expression profiling plays an emerging role in cancer classification and identification of therapeutic strategies. In this study, we have evaluated the benefits a joint microRNA-mRNA analysis breast cancer. Matched mRNA global was conducted well-annotated cohort 207 cases with complete 10-year follow-up. Penalized Cox regression including expression, clinical covariates used to identify microRNAs associated distant relapse-free survival (DRFS) that provide independent prognostic...
Limited clinical benefits derived from anti-VEGF therapy have driven the identification of new targets involved in tumor angiogenesis. Here, we report an integrative meta-analysis to define transcriptional program underlying angiogenesis human cancer. This approach identified ELTD1, orphan G-protein-coupled receptor whose expression is induced by VEGF/bFGF and repressed DLL4 signaling. Extensive analysis multiple cancer types demonstrates significant upregulation ELTD1 tumor-associated...
Bevacizumab, an anti-VEGFA antibody, inhibits the developing vasculature of tumors, but resistance is common. Antiangiogenic therapy induces hypoxia and we observed increased expression hypoxia-regulated genes, including carbonic anhydrase IX (CAIX), in response to bevacizumab treatment xenografts. CAIX correlates with poor prognosis most tumor types worse outcome bevacizumab-treated patients metastatic colorectal cancer, malignant astrocytoma, recurrent glioma.We knocked down by short...
Resistance to VEGF inhibitors is emerging as a major clinical problem. Notch signaling has been implicated in tumor angiogenesis. Therefore, investigate mechanisms of resistance angiogenesis inhibitors, we transduced human glioblastoma cells with retroviruses encoding delta-like ligand 4 (DLL4), grew them xenografts and then treated the murine hosts VEGF-A inhibitor bevacizumab. We found that DLL4-mediated bevacizumab vivo. The large vessels induced by DLL4-Notch increased blood supply were...
Individuals with germline mutations in the BRCA1 gene have an elevated risk of developing breast cancer, and often display characteristic clinicopathological features. We hypothesised that inactivation by promoter methylation could occur as a or early somatic event predisposes to cancer phenotype normally associated mutation.We examined seven cases from breast-ovarian families tumours showed BRCA1-like pathology but did not detectable BRCA2 present. Methylation levels were tested several...
Late-phase clinical trials investigating metformin as a cancer therapy are underway. However, there remains controversy to the mode of action in tumors at doses. We conducted study integrating measurement markers systemic metabolism, dynamic FDG-PET-CT, transcriptomics, and metabolomics paired time points profile bioactivity primary breast cancer. show reduces levels mitochondrial metabolites, activates multiple metabolic pathways, increases 18-FDG flux tumors. Two tumor groups identified...
Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor activated expression carbonic anhydrase IX (CA9), a regulator pH growth. In this study, we investigated the hypothesis that impeding reuptake bicarbonate produced extracellularly by CA9 could exacerbate intracellular acidity hypoxic conditions, perhaps compromising cell growth viability as result. 8 10 cancer lines, found induced at least one transporter. The most robust...
Homozygous mutation of the Csf1r locus ( Csf1rko ) in mice, rats and humans leads to multiple postnatal developmental abnormalities. To enable analysis mechanisms underlying phenotypic impacts mutation, we bred a rat allele inbred dark agouti (DA) genetic background -mApple reporter transgene. The led almost complete loss embryonic macrophages ablation most adult tissue macrophage populations. We extended previous phenotype early development reveal on musculoskeletal proliferation...
Tumour cells can use strategies that make them resistant to nutrient deprivation outcompete their neighbours. A key integrator of the cell's responses starvation and other stresses is amino-acid-dependent mechanistic target rapamycin complex 1 (mTORC1). Activation mTORC1 on late endosomes lysosomes facilitated by amino-acid transporters within solute-linked carrier 36 (SLC36) SLC38 families. Here, we analyse functions SLC36 family member, SLC36A4, otherwise known as proton-assisted...
Enhancement of oligodendrocyte survival through activation leukemia inhibitory factor receptor (LIFR) signaling is a candidate therapeutic strategy for demyelinating disease. However, in other cell types, LIFR under tight negative regulation by the intracellular protein suppressor cytokine 3 (SOCS3). We, therefore, postulated that deletion SOCS3 gene oligodendrocytes would promote beneficial effects limiting demyelination. By studying wild-type and LIF-knockout mice, we established...
Abstract Purpose: Receptor CUB-domain containing- protein 1 (CDCP1) was evaluated as a target for detection and treatment of breast cancer. Experimental Design: CDCP1 expression assessed immunohistochemically in tumors from 423 patients (119 triple-negative cancer (TNBC); 75 HER2+; 229 ER+/HER2- including 228 primary tumors, lymph node 47 distant metastases). Cell cytotoxicity induced vitro by CDCP1-targeting antibody-drug conjugate (ADC), consisting the human/mouse chimeric antibody ch10D7...
Primary cutaneous neoplasms that lack definitive histologic and immunophenotypic evidence of differentiation are a heterogeneous group tumors with diverse prognoses management options. These include undifferentiated dedifferentiated melanoma (UM/DM), atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma (PDS), sarcomatoid squamous cell carcinoma. Diagnosis requires careful correlation between the clinicopathologic molecular features, finding MAPK pathway variant commonly associated may...
The stabilisation of HIF-α is central to the transcriptional response animals hypoxia, regulating expression hundreds genes including those involved in angiogenesis, metabolism and metastasis. degraded under normoxic conditions by proline hydroxylation, which allows for recognition ubiquitination von-Hippel-Lindau (VHL) E3 ligase complex. aim our study was investigate posttranslational modification HIF-1α tumours, assess whether there are additional mechanisms besides reduced hydroxylation...
Background: CUB domain-containing protein 1 (CDCP1) is a cell surface receptor regulating key signalling pathways in malignant cells. CDCP1 has been proposed as molecular target to abrogate oncogenic and specifically deliver anti-cancer agents tumors. However, the development of CDCP1-targeting questioned by its frequent proteolytic processing which was thought result shedding extracellular domain limiting targetability. In this study, we investigated relevance targeting context pancreatic...
Abstract Background Breast cancers acquire aggressive capabilities via epithelial to mesenchymal transition (EMT), in which various integrins/integrin-linked kinase signalling are upregulated. Methods We investigated this two patient-derived xenografts (PDXs) developed from breast-to-bone metastases, and its functional significance a breast cancer cell line system. ED03 EDW01 PDXs were grown subcutaneously immunocompromised SCID mice through 11 passages 7 passages, respectively. Tumour...
Drugs such as gemcitabine that increase replication stress are effective chemotherapeutics in a range of cancer settings. These drugs effectively block and promote DNA damage, triggering cell cycle checkpoint response through the ATR–CHK1 pathway. Inhibiting this signalling pathway sensitises cells to killing by stress‐inducing drugs. Here, we investigated effect low‐level induced low concentrations (> 0.2 m ) reversible ribonucleotide reductase inhibitor hydroxyurea (HU), which slows...
Mammographic density (MD) is a strong and independent factor for breast cancer (BC) risk increasingly associated with BC progression. We have previously shown in mice that high MD, which characterized by the preponderance of fibrous stroma, facilitates xenograft growth metastasis. This stroma rich extracellular matrix (ECM) factors, including heparan sulfate proteoglycans (HSPGs), such as BC-associated syndecan-1 (SDC1). These tether are released heparanase (HPSE). MD positively estrogen...