- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Lung Cancer Treatments and Mutations
- Cancer Mechanisms and Therapy
- Ovarian cancer diagnosis and treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Immune Response and Inflammation
- Gastrointestinal Tumor Research and Treatment
- Colorectal Cancer Screening and Detection
- Genomics and Rare Diseases
- Cancer Immunotherapy and Biomarkers
- Gastric Cancer Management and Outcomes
- Cytokine Signaling Pathways and Interactions
- Peptidase Inhibition and Analysis
- Genomics and Chromatin Dynamics
- BRCA gene mutations in cancer
- Reproductive System and Pregnancy
- PARP inhibition in cancer therapy
- Radiomics and Machine Learning in Medical Imaging
- Obesity, Physical Activity, Diet
- Colorectal and Anal Carcinomas
- Immune Cell Function and Interaction
- Protein Degradation and Inhibitors
- Antifungal resistance and susceptibility
The University of Melbourne
2013-2023
Peter MacCallum Cancer Centre
2002-2023
University of Cambridge
2020
Mayo Clinic in Florida
2018
Ventana Research Corporation (United States)
2017
Camden and Campbelltown Hospitals
2016
National Health and Medical Research Council
2000-2016
Royal North Shore Hospital
2016
Medical Research Council
2016
Australian National University
1996-2015
Objective: To assess the effect of plasmafiltration (PF) on biochemical markers inflammation, cytokines, organ dysfunction, and 14-day mortality in human sepsis. Design: Multicenter, prospective, randomized, controlled clinical trial. Setting: Seven university-affiliated intensive care units. Patients: Thirty patients (22 adults, eight children) with new (<24 hrs) evidence infection sepsis syndrome were enrolled. Fourteen 30 (nine five randomized to PF. Interventions: All received...
Abstract Gene expression profiling offers a promising new technique for the diagnosis and prognosis of cancer. We have applied this technology to build clinically robust site origin classifier with ultimate aim applying it determine cancer unknown primary (CUP). A single cDNA microarray platform was used profile 229 metastatic tumors representing 14 tumor types multiple histologic subtypes. This data set subsequently training validation support vector machine (SVM) classifier, demonstrating...
Abstract Genetic alterations that potentiate PI3K signaling are frequent in prostate cancer, yet how different genetic drivers of the cascade contribute to cancer is unclear. Here, we report PIK3CA mutation/amplification correlates with poor survival patients cancer. To interrogate requirement employed a approach mutate Pik3ca mouse epithelium. We show Pik3caH1047R mutation causes p110α-dependent invasive carcinoma vivo. Furthermore, and PTEN loss coexist can cooperate vivo accelerate...
The most common of all activating BRAF mutations (T1799A) leads to a substitution valine (V) glutamic acid (E) at the position 600 amino sequence. major goal this study was compare detection V600E mutation by DNA sequencing with immunohistochemistry (IHC) using anti-BRAF (VE1) antibody. Archival formalin fixed, paraffin embedded tissues from 352 patients colon adenocarcinoma (n = 279) and papillary thyroid carcinoma 73) were evaluated for IHC. discordant cases re-evaluated repeat IHC,...
To identify the physiological role of Hck, a functionally redundant member Src family tyrosine kinases expressed in myelomonocytic cells, we generated Hck(F/F) "knock-in" mice which carry targeted (Y) to phenylalanine (F) substitution COOH-terminal, negative regulatory Y(499)-residue Hck protein. Unlike their Hck(-/-) "loss-of-function" counterparts, "gain-of-function" spontaneously acquired lung pathology characterized by extensive eosinophilic and mononuclear cell infiltration within...
Leukemia inhibitory factor (LIF) has many biological actions which parallel those of IL-1, IL-6 and tumor necrosis factor-alpha, but its role in the pathogenesis human disease is unknown. A specific radioreceptor competition assay capable detecting LIF at concentrations above 1 ng/ml (45 pM) was developed. To identify states might be involved, a cross-sectional survey serum body fluids from approximately 1,500 subjects with variety diseases performed using assay. Serum were transiently...
RAS mutations predict lack of response to epidermal growth factor receptor monoclonal antibody therapy in patients with metastatic colorectal cancer (mCRC), but preclinical studies and retrospective clinical data suggest that tumors harboring the exon 2 KRAS G13D mutation may benefit from cetuximab. We aimed assess cetuximab monotherapy plus irinotecan molecularly selected (G13D mutation) chemotherapy-refractory mCRC a randomized phase II trial this rare molecular subtype.Patients...
The B-type Raf kinase (BRAF) V600E mutation is a well-established biomarker for poor prognosis in metastatic colorectal cancer (mCRC) and highly attractive drug target. A barrier to the development of new therapies targeting BRAF mCRC low prevalence mutations (approximately 10 %) current need access sequencing-based technologies which are not routinely available outside large centres. Availability standardised immunohistochemistry (IHC) test, more suited routine pathology practice, would...
Summary Invasive aspergillosis is a significant cause of death in immunocompromised individuals. The majority strains the main causative agent, Aspergillus fumigatus , produce gliotoxin, secondary metabolite with demonstrated vitro immunosuppressive activity. Pretreatment normally resistant mice single injection sublethal dose gliotoxin was sufficient to make them susceptible infection and subsequent death, after challenge A. spores. Animals infected non‐gliotoxin producing strain survived...
Microsatellite instability (MSI) is a useful marker for risk assessment, prediction of chemotherapy responsiveness and prognosis in patients with colorectal cancer. Here, we describe next generation sequencing approach MSI testing using the MiSeq platform. Different from other capturing strategies that are based on targeted gene capture, utilize "deep resequencing", where focus only microsatellite regions interest. We sequenced series 44 tumours normal controls five loci (BAT25, BAT26,...
Abstract Objective. To examine synovial fluid (SF) from patients with arthritis, for the presence of cytokine leukemia inhibitory factor (LIF). Methods. SF 152 subjects was examined LIF, using a radioreceptor competition assay. Results. LIF present at concentrations 1–43 ng/ml in 23% rheumatoid arthritis (RA) or other inflammatory infectious arthritides but only 1 29 osteoarthritis ( P < 0.01). In RA patients, concentration correlated significantly peripheral blood white cell count (WBC)...
Leukemia inhibitory factor (LIF) has recently been associated with septic shock in humans. In this study we sought to determine, mice, the role of LIF shock. During sublethal endotoxemia, serum levels, as determined by radio-receptor competition assay, peaked at 2 h and were low (3 ng/ml), whereas lethal Escherichia coli levels rose progressively (> 30 ng/ml) premorbid phase coincident development tissue injury. Single i.v. injections high doses (up 50 micrograms per mouse) recombinant...
The in vitro cytotoxicities of a number gold(I), silver(I) and copper(I) complexes containing chiral tertiary phosphine ligands have been examined against the mouse tumour cell lines P815 mastocytoma, B16 melanoma [gold(I) compounds] P388 leukaemia only] with many having IC 50 values comparable to that reference compounds cis ‐diamminedichloroplatinum(ll), cisplatin, bis[1,2‐bis(diphenylphosphino) ethane]gold(I) iodide. used this study include ( R )‐(2‐aminophenyl)methylphenylphosphine; R,R...
Abstract Leukemia‐inhibitory factor (LIF) elicits effects on a broad range of cell types, including cells the monocytic and megakaryocytic series, embryonal stem cells, hepatocytes, adipocytes, osteoblasts. Native recombinant LIF, injected intravenously into adult mice, had an initial half‐life 6‐8 min more prolonged second clearance phase. Clearance 125 I‐LIF from circulation was paralleled by rapid accumulation in kidneys, liver, lungs, spleen gradual thyroid gland. Labeling renal...
Prognostic markers that identify patients with stage II colon cancers who are at the risk of recurrence essential to personalize therapy. We evaluated potential GIV/Girdin as a predictor in such patients.Expression full-length GIV was by IHC using newly developed mAb together mismatch repair (MMR)-specific antibody panel three cancer patient cohorts, is, training (n = 192), test 317), and validation 181) cohort, clinical follow-up data. Recurrence stratification models were established...