A5039483303- Immune cells in cancer
- Tryptophan and brain disorders
- Inflammatory Biomarkers in Disease Prognosis
- Atherosclerosis and Cardiovascular Diseases
- Cancer Immunotherapy and Biomarkers
- Colorectal Cancer Treatments and Studies
- Ferroptosis and cancer prognosis
- Pharmacogenetics and Drug Metabolism
- Cancer Treatment and Pharmacology
- Neutropenia and Cancer Infections
- Adipokines, Inflammation, and Metabolic Diseases
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- Gastric Cancer Management and Outcomes
- Drug Transport and Resistance Mechanisms
- Lung Cancer Treatments and Mutations
- Innovations in Medical Education
- Inflammasome and immune disorders
- Lymphoma Diagnosis and Treatment
- Chemokine receptors and signaling
- Chemical Reactions and Isotopes
- Immune Response and Inflammation
- Reproductive System and Pregnancy
- Macrophage Migration Inhibitory Factor
The University of Sydney
2014-2025
University Hospitals Birmingham NHS Foundation Trust
2023
Queen Elizabeth Hospital
2023
Kamineni Institute of Dental Sciences
2014
Queen Mary University of London
2005-2011
Peter MacCallum Cancer Centre
2011
Edinburgh Cancer Research
2011
University College Dublin
2011
The University of Melbourne
2011
Cancer Research UK
2005-2011
The nuclear factor κB (NF-κB) signaling pathway is important in cancer-related inflammation and malignant progression. Here, we describe a new role for NF-κB cancer maintaining the immunosuppressive phenotype of tumor-associated macrophages (TAMs). We show that are polarized via interleukin (IL)-1R MyD88 to an “alternative” requires IκB kinase β–mediated activation. When inhibited specifically TAMs, they become cytotoxic tumor cells switch “classically” activated phenotype; IL-12high, major...
Advances in the treatment of metastatic colorectal cancer (mCRC) last decade have significantly improved survival; however, simple biomarkers to predict response or toxicity not been identified, which are applicable all community oncology settings worldwide. The use inflammatory markers based on differential white-cell counts, such as neutrophil/lymphocyte ratio (NLR), may be and readily available biomarkers. Clinical information baseline laboratory parameters were for 349 patients, from two...
Abstract Tumor-associated macrophages may influence tumor progression, angiogenesis and invasion. To investigate mechanisms by which interact with cells, we developed an in vitro coculture model. Previously reported that enhanced invasiveness of the cells a TNF-α- matrix metalloprotease-dependent manner. In this report, studied intracellular signaling pathways induction inflammatory genes malignant under macrophage coculture. We report ovarian or breast cancer cell lines led to...
Abstract Tumor-associated macrophages (TAM) may have tumor-promoting activity, but it is not clear how their phenotype achieved. In this study, we demonstrate that ovarian cancer cells switch cocultured to a similar found in tumors. Tumor caused dynamic changes macrophage cytokine, chemokine, and matrix metalloprotease mRNA, protein-inducing mediators are human cancer. Macrophage mannose, mannose receptor, scavenger receptors (SR-As) were also up-regulated by coculture, conditioned medium....
This article is a report on symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics held at Biology 07 meeting in Washington, DC. The presentations discussed phenomenology, clinical consequences, underlying mechanisms of cytochrome P450 drug transporter regulation inflammatory infectious stimuli. Although considerable insights into links between mediators altered hepatic clearance pathways have been gained from previous studies with acute stimuli, this...
Cytokines orchestrate the tumor-promoting interplay between malignant cells and immune system. In many experimental human cancers, cytokine TNF-alpha is an important component of this interplay, but its effects are pleiotropic therefore remain to be completely defined. Using a mouse model ovarian cancer in which either TNF receptor 1 (TNFR1) signaling was manipulated different leukocyte populations or neutralized by antibody treatment, we found that inflammatory maintained TNFR1-dependent...
Tumor necrosis factor alpha (TNF-alpha) may play a role in renal cell carcinoma (RCC). We performed two sequential phase II studies of infliximab, an anti-TNF-alpha monoclonal antibody, patients with immunotherapy-resistant or refractory RCC.Patients progressing after cytokine therapy were treated intravenous infliximab as follows: study 1 (19 patients), 5 mg/kg at weeks 0, 2, and 6, then every 8 weeks; 2 (18 10 4 weeks. Treatment continued until disease progression (PD). Response was...
Constitutive production of inflammatory cytokines is a characteristic many human malignant cell lines; however, the in vitro and vivo interdependence these cytokines, their significance to cancer microenvironment, are both poorly understood. Here, we describe for first time how three key cytokine/chemokine mediators cancer-related inflammation, TNF, CXCL12, interleukin 6, involved an autocrine cytokine network, "TNF network," ovarian cancer. We show that this network has paracrine actions on...
Abstract In view of our previous findings that tumor cell–derived macrophage migration inhibitory factor (MIF) increased macrophage-mediated ovarian cancer cell invasiveness in vitro, we investigated the wider significance MIF for growth, metastasis, and angiogenesis. We found is expressed borderline malignant tumors, active ascitic fluid. next expression function a syngeneic model. Stable knockdown murine line ID8 decreased vivo burden overall survival. Tumors arising from cells had...
Abstract Purpose: The purpose is to identify the demographic, physiologic, and inheritable factors that influence CYP3A activity in cancer patients Experimental Design: A total of 134 (62 females; age range, 26 83 years) underwent erythromycin breath test as a phenotyping probe CYP3A. Genomic DNA was screened for six variants suspected functional relevance CYP3A4 (CYP3A4*1B, CYP3A4*6, CYP3A4*17, CYP3A4*18) CYP3A5 (CYP3A5*3C CYP3A5*6). Results: (AUC0–40min) varied up 14-fold this population....
Currently there are very few biomarkers to identify head and neck squamous cell carcinoma (HNSCC) cancer patients at a greater risk of recurrence shortened survival. This study aimed investigate whether marker systemic inflammation, the neutrophil-to-lymphocyte ratio (NLR), was predictive clinical outcomes in heterogeneous cohort HNSCC patients. We performed retrospective analysis associations between NLR clinicopathological features free survival (RFS) overall (OS). Univariate used selected...
The CYP3A4*22 allele was recently reported to be associated with reduced CYP3A4 activity. We investigated the impact of this on metabolism CYP3A-phenotyping probes, midazolam (MDZ) and erythromycin.Genomic DNA from 108 cancer patients receiving intravenous MDZ 45 undergoing erythromycin breath test analyzed for (rs35599367 C>T) CYP3A5*3.The metabolic ratio (1´-OH-MDZ:MDZ) 20.7% (95% CI: -36.2 -6.2) lower carriers compared CYP3A4*1/*1 (p = 0.01). Combining CYP3A5*3 genotypes showed a 38.7%...
Many chemotherapeutic drugs have an inherent lack of safety due to interindividual variability hepatic cytochrome P450 (CYP) 3A4 drug metabolism. This reduction in CYP3A4 cancer patients is possibly mediated by cytokines associated with tumor-derived inflammation. We sought examine this link using explant sarcoma a novel transgenic mouse model human regulation.Engelbreth-Holm-Swarm cells were injected into the hindlimb CYP3A4/lacZ mice. Hepatic expression transgene was analyzed direct...
Molecular diagnostic testing of KRAS and BRAF mutations has become critical in the management colorectal cancer (CRC) patients.Some progress been made liquid biopsy detection circulating tumor DNA (ctDNA), which is a fraction cell-free (cfDNA), but slow analysis for sequencing methods limited rapid diagnostics.Other such as quantitative PCR more recently, droplet digital (ddPCR), have limitations multiplexed capacity need expensive specialized equipment.Hence, robust, facile strategy needed...
Fundamental challenges exist in researching complex changes of assessment practice from traditional objective-focused 'assessments learning' towards programmatic 'assessment for learning'. The latter emphasise both the subjective and social collective judgements student progress. Our context was a purposively designed system implemented first year new graduate entry curriculum. We applied critical realist perspectives to unpack underlying causes (mechanisms) that explained experiences...