A5042454662- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune cells in cancer
- PARP inhibition in cancer therapy
- Cardiac Arrest and Resuscitation
- Cardiac Imaging and Diagnostics
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Smoking Behavior and Cessation
- Immune Response and Inflammation
- Ultrasound in Clinical Applications
- Air Quality and Health Impacts
- Chronic Lymphocytic Leukemia Research
- Diabetes and associated disorders
- Asthma and respiratory diseases
- Hepatocellular Carcinoma Treatment and Prognosis
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Heart Failure Treatment and Management
- Monoclonal and Polyclonal Antibodies Research
- Trauma Management and Diagnosis
- Tryptophan and brain disorders
- Acute Myocardial Infarction Research
- Inflammatory Biomarkers in Disease Prognosis
- Celiac Disease Research and Management
- T-cell and B-cell Immunology
Roswell Park Comprehensive Cancer Center
2010-2024
Royal Perth Hospital
2016-2022
University of Hawaiʻi at Mānoa
2018
Royal Victoria Infirmary
2013
James Cook University Hospital
2011
McMaster University
2005-2006
McMaster University Medical Centre
2005
Abstract The extent to which T-cell–mediated immune surveillance is impaired in human cancer remains a question of major importance, given its potential impact on the development generalized treatments advanced disease where highest degree heterogeneity exists. Here, we report first global analysis dysfunction patients with hepatocellular carcinoma (HCC). Using multi-parameter fluorescence-activated cell sorting analysis, quantified cumulative frequency regulatory T cells (Treg), exhausted...
Rationale: Previous studies from our laboratory have shown that peripheral blood mononuclear cells (PBMCs) patients with chronic obstructive pulmonary disease (COPD) prone to exacerbations nontypeable Haemophilus influenzae impaired responses lipoprotein P6. We hypothesized an underlying immunosuppressive network could be responsible for the defective antibacterial immunity observed in these patients. evaluated T regulatory (Tregs), myeloid-derived suppressor (MDSC), and exhausted effector...
Rationale Vaping has become a popular method of inhaling various psychoactive substances. While evaluating respiratory effects vaping have primarily focused on nicotine-containing products, cannabidiol (CBD)-vaping is increasingly becoming popular. It currently remains unknown whether the health nicotine and cannabinoids are similar. Objectives This study compares side by pulmonary acute inhalation vaporised CBD versus nicotine. Methods In vivo in mice vitro cytotoxicity experiments with...
Sorafenib is an oral antiangiogenic agent administered in advanced-stage hepatocellular carcinoma (HCC). Based on preclinical and human studies, we hypothesized that, addition to its properties, sorafenib may beneficially reduce the extent of immunosuppressive network HCC patients. To test this hypothesis, examined whether alterations burden patients correlated with clinical outcome.In before after treatment, blood samples collected from 19 advanced HCC, frequency PD-1+ T cells, Tregs,...
BACKGROUNDSorafenib has been shown to reduce the extent of immunosuppression in patients with hepatocellular carcinoma (HCC). The rationale this investigation was identify biomarkers that can predict treatment efficacy sorafenib HCC and unravel mechanism by which impedes immune suppression mediated distinct immunosuppressive cell subsets.METHODSWith informed consent, blood samples were collected from 30 advanced HCC, at baseline 2 time points after initiation treatment. frequency PD-1+ T...
Abstract Despite advocacy to reduce smoking-related diseases, >1 billion people worldwide continue smoke. Smoking is immunosuppressive and an important etiological factor in the development of several human disorders including respiratory diseases like chronic obstructive pulmonary disease. However, there a critical gap knowledge role secondhand smoke (SHS) inflammation immunity. We therefore studied influence SHS on immune responses infection by nontypeable Haemophilus influenzae...
Emerging heated tobacco products (HTPs) were designed to reduce exposure toxicants from cigarette smoke (CS) by avoiding burning and instead heating tobacco. We studied the effects of short-term inhalation aerosols emitted HTP called IQOS, on lung damage immune-cell recruitment lungs in mice.
The immune modulatory effect of tivozanib, a tyrosine kinase inhibitor, and the underlying mechanisms impacting survival HCC patients have not been investigated. Pre-clinical studies shown that tivozanib reduces Tregs MDSCs accumulation through inhibition c-Kit/SCF axis. We rationalized axis antagonism by may reverse tumor-induced suppression in patients. frequency circulating Tregs, MDSCs, CTLA-4+Tregs, PD-1+T cells, c-Kit+pERK-2+Tregs, c-Kit+pERK-2+MDSCs were quantified at baseline two...
Abstract Cigarette smoke is a potent proinflammatory trigger contributing to acute lung injury and the development of chronic diseases via mechanisms that include impairment inflammation resolution. We have previously demonstrated secondhand (SHS) exposure exacerbates bacterial infection-induced pulmonary suppresses immune responses. It now recognized resolution bioactive process mediated by lipid-derived specialized proresolving mediators counterregulate signaling promote pathways....
The accumulation of immunosuppressive cells and exhausted effector T highlight an important immune dysfunction in advanced stage hepatocellular carcinoma (HCC) patients. These significantly hamper the efficacy immunotherapies facilitate HCC progression. We have recently demonstrated that multipronged depletion potentially restores T-cell function HCC.
Abstract Tobacco smoke exposure is associated with multiple diseases including, respiratory like asthma and chronic obstructive pulmonary disease. a potent inflammatory trigger immunosuppressive, contributing to increased susceptibility infections in smokers, ex-smokers, vulnerable populations exposed secondhand smoke. also reduces vaccine efficacy. Therefore, mitigating the immunosuppressive effects of improving efficacy vaccinations individuals tobacco smoke, critical unmet clinical...
Sorafenib is an oral anti-angiogenic multi-kinase inhibitor used for systemic therapy in patients with advanced hepatocellular carcinoma (HCC) who are not suitable candidates surgery or liver transplantation. An earlier study conducted HCC tumor tissue suggested that ERK phosphorylation (pERK), a downstream target of sorafenib, may serve as potential biomarker therapeutic efficacy sorafenib. However, no thus far has utilized minimal invasive procedure to predict patient responsiveness We...
Abstract Rationale Due to the relatively short existence of alternative tobacco products, gaps exist in our current understanding their long-term respiratory health effects. We therefore undertook first-ever side-by-side comparison impact chronic inhalation aerosols emitted from electronic cigarettes (EC) and heated products (HTP), combustible (CC) smoke. Objectives To evaluate potential differential effects on lung inflammatory responses efficacy vaccination CC. Methods Mice were exposed...
New approaches in the treatment of chronic B lymphocytic leukemia (B-CLL) have led to improved clinical response rates. In this setting there is a need evaluate novel therapeutic that aim eradicate minimal residual B-CLL cells following an initial favorable response. The use tumor lysate-pulsed dendritic (DC) represents potentially important development field cancer vaccination. ideally suited for DC-based vaccination since are readily available (peripheral blood) and both known (tumor...
Abstract Factitious hypoglycaemia is a challenging diagnosis to confirm. Evaluation of surreptitious human insulin use can be distinguished from endogenous excess by existing biochemical assays. However, the increasing analogues poses challenge because commercially available assays detect these with varying accuracy and precision. Insulin are increasingly used in diabetes management case outlined here highlights variations assay. Initially, local assay (ELISA kit – Dako, Copenhagen) failed...
340 Background: Most patients with high or very risk localized prostate cancer (PCa) experience disease recurrence after radical prostatectomy (RP). A intra-tumoral CD8 + T lymphocyte density is associated improved survival post-RP, 1 suggesting possible clinical benefit from neoadjuvant chemokine modulation (CKM). 2,3 We present the interim results of a three-arm, phase II trial where PCa scheduled to undergo RP were randomized in 1:1:1 ratio 2-week regimen CKM triplet (Arm A: rintatolimod...