A5011692563- Mechanisms of cancer metastasis
- Colorectal Cancer Treatments and Studies
- Gut microbiota and health
- Cancer Research and Treatments
- Cystic Fibrosis Research Advances
- Inflammatory Bowel Disease
- Pediatric health and respiratory diseases
- Immune responses and vaccinations
- Asthma and respiratory diseases
- Neonatal Respiratory Health Research
- Microscopic Colitis
- Cancer-related Molecular Pathways
- Metal complexes synthesis and properties
- Cancer, Lipids, and Metabolism
- DNA Repair Mechanisms
- Molecular Biology Techniques and Applications
- Ferroptosis and cancer prognosis
- Endoplasmic Reticulum Stress and Disease
- Click Chemistry and Applications
- Computational Drug Discovery Methods
- Respiratory Support and Mechanisms
- Vaccine Coverage and Hesitancy
- Cancer Mechanisms and Therapy
- Immunotherapy and Immune Responses
- Inhalation and Respiratory Drug Delivery
McGill University Health Centre
2018
Interface Biologics (Canada)
2017
McGill University
2011-2016
Christie (Canada)
2011-2016
University College Dublin
2012
Abstract Cystic fibrosis transmembrane conductance regulator deficient mouse models develop phenotypes of relevance to clinical cystic (CF) including airway hyperresponsiveness, small intestinal bacterial overgrowth and an altered microbiome. As dysbiosis the microbiota has been recognized as important contributor many systemic diseases, herein we investigated whether altering microbiome BALB/c Cftr tm1UNC mice wild-type littermates, through treatment with antibiotic streptomycin, affects CF...
Abstract BOLD-100 is a first-in-class, ruthenium-based anticancer agent in Phase 2 clinical development for advanced gastrointestinal (GI) cancers combination with FOLFOX. Clinical results have shown that combined FOLFOX improves overall survival (OS) and progression-free (PFS) patients colon, gastric, bile duct cancers. Emerging evidence indicates very well tolerated safety profile While first- or second-line standard-of-care therapy GI cancers, its utility limited by the induction of acute...
Abstract Background Idiopathic pulmonary fibrosis is a disease characterized by alveolar epithelial cell injury, inflammatory infiltration and deposition of extracellular matrix in lung tissue. As mouse models bleomycin-induced display many the same phenotypes observed patients with idiopathic fibrosis, they have been used to study various aspects disease, including altered expression microRNAs. Results In this work, microRNA profiling lungs from treated C57BL/6J mice, relative that...
Background: Current ulcerative colitis (UC) treatments are focused on symptom management primarily via immune suppression. Despite the current arsenal of immunosuppressant treatments, majority patients with UC still experience disease progression. Importantly, aggressive long-term inhibition function comes consequent risk, such as serious infections and malignancy. There is thus a recognized need for new, safe effective treatment strategies people living that work upstream managing symptoms...
Cigarette smoke exposure is the major risk factor for developing COPD. Presently, available COPD treatments focus on suppressing inflammation and providing bronchodilation. However, these options have varying efficacy in controlling symptoms do not reverse or limit progression of Treatments strategies using bacterial-derived products shown promise diseases characterized by immune dysfunction. This study investigated first time whether a novel immunotherapy produced from inactivated...
Triple negative breast cancer (TNBC) represents a subtype of that does not express the three major prognostic receptors human epidermal growth factor receptor 2 (HER2), progesterone (PR), and estrogen (ER). This limits treatment options results in high rate mortality. We have reported previously on efficacy water-soluble, cationic organometallic compound (
BOLD-100 (sodium trans-[tetrachlorobis(1H indazole)ruthenate(III)]) is a ruthenium-based anticancer compound currently in clinical development. The identification of cancer types that show increased sensitivity towards can lead to improved developmental strategies. Sensitivity profiling also identify mechanisms action are pertinent for the bioactivity complex therapeutics. was measured 319-cancer-cell line panel spanning 24 tissues. BOLD-100’s profile showed variation across tissue lineages,...
Acute infection is known to induce strong anti-tumor immune responses, but clinical translation has been hindered by the lack of an effective strategy safely and consistently provoke a therapeutic response. These limitations are overcome with novel treatment approach involving repeated subcutaneous delivery Klebsiella-derived investigational immunotherapeutic, QBKPN. In preclinical models lung cancer, QBKPN administration showed anti-cancer efficacy, which was dependent on Klebsiella...
There is an unmet need for effective new and innovative treatments asthma. It becoming increasingly evident that bacterial stimulation can have beneficial effects at attenuating allergic airway disease through immune modulation. Our aim was to test the ability of a novel inactivated microbe-derived therapeutic based on Klebsiella (KB) in model mice. BALB/c mice were exposed intranasally house dust mite (HDM) two weeks. Mice treated prophylactically via subcutaneous route with either KB or...
Abstract Patients with class I V600EBRAF-mutant (MT) colorectal cancer exhibit a poor prognosis, and their response to combined anti-BRAF/EGFR inhibition remains limited. An unmet need exits for further understanding the biology of V600EBRAFMT cancer. We used differential gene expression BRAFWT MT cells identify pathways underpinning BRAFMT tested panel molecularly/genetically subtyped sensitivity unfolded protein (UPR) activator BOLD-100. To novel combination strategies BOLD-100, we...
Type 2 immunity in the lung is promoted through release of innate cytokines, including TSLP, from structural cells. These cytokines drive part upregulation OX40L on dendritic cells (DCs). DCs expressing are potent inducers Th2 differentiation. We have shown previously that STAT6 inhibitory peptide (STAT6-IP), a cell penetrating designed to inhibit transcription factor, reduces induction adaptive murine models respiratory syncytial virus infection. Here we show intranasal administration...
Site-specific immunomodulators (SSIs) are a novel class of therapeutics made from inactivated bacterial species designed to regulate the innate immune system in targeted organs. QBECO is gut-targeted SSI that being advanced clinically treat and/or prevent inflammatory bowel disease, cancer, and serious infections gastrointestinal (GI) tract proximal organs, QBKPN lung-targeted clinical development for treatment prevention chronic lung cancers respiratory infections. While these SSIs have...
The COVID-19 pandemic has highlighted an urgent need to discover and test new drugs treat patients. Metal-based are known interact with DNA and/or a variety of proteins such as enzymes transcription factors, some which have been shown exhibit anticancer antimicrobial effects. BOLD-100 (sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]dihydrate) is novel ruthenium-based drug currently being evaluated in Phase 1b/2a clinical trial for the treatment advanced gastrointestinal cancer....
Background: Current Crohn’s disease (CD) therapies focus on suppressing immune function and come with consequent risk, such as infection cancer. Notwithstanding, most CD patients still experience progression. There is a need for new treatment strategies that offer better health outcomes patients. Aims: To assess safety, efficacy, tolerability of novel microbial-derived immunotherapy, QBECO, aims to restore rather than suppress in CD. Methods: A randomized, double-blind, placebo-controlled...
We previously observed the lungs of naive BALB/cJ Cftr(tm1UNC) mice to have greater numbers lymphocytes, by immunohistochemical staining, than did BALB wild type littermates or C57BL/6J mice. In present study, we initially investigated whether this mutation in Cftr alters adaptive immunity phenotype measuring lymphocyte populations and spleens FACS evaluating CD3-stimulated cytokine secretion, proliferation, apoptosis responses. Next, assessed a potential influence on lung function through...
Abstract Recent developments in understanding how the functional phenotype of innate immune system is programmed has led to paradigm-shifting views on immunomodulation. These advances have overturned two long-held dogmas: (1) only adaptive immunity confers immunological memory; and, (2) lacks specificity. This work describes observation that effector cells appear be differentially recruited specific pathological sites when mobilized by distinct inactivated bacterial-based stimuli...
<p>Table S5: BOLD-100 Compound Screen</p>
<p>Table S1: Antibodies</p>
<p>Table S3: GSE59857 ssGSEA Hallmarks</p>
<p>BOLD-100 rewires the signaling network of <i>BRAF</i>MT colorectal cancer cells. RNA-seq BOLD-100 treated VACO432 and VT1 cells for 3 24 hours was performed. <b>A,</b> PCA plot displaying separation between <i>BRAF</i>WT clone following treatment with μmol/L hours. <b>B</b> <b>C,</b> Volcano plots show up- downregulated genes at indicated time-points in Dashed lines on <i>x</i> <i>y</i>-axis indicate...
<p>Treatment with BOLD-100 rewires the signalling network of BRAFMT CRC cells.</p>
<p>Table S2: TSG siRNA screen</p>