A5054196266- Esophageal Cancer Research and Treatment
- Cancer Genomics and Diagnostics
- Receptor Mechanisms and Signaling
- Cancer-related gene regulation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Gastrointestinal Tumor Research and Treatment
- RNA Research and Splicing
- Advanced Breast Cancer Therapies
- Esophageal and GI Pathology
- Pancreatic and Hepatic Oncology Research
- Ferroptosis and cancer prognosis
- Epigenetics and DNA Methylation
- Molecular Biology Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Neuropeptides and Animal Physiology
- Gastric Cancer Management and Outcomes
- Biomedical Text Mining and Ontologies
- Advanced Proteomics Techniques and Applications
- Radiomics and Machine Learning in Medical Imaging
- Genetic factors in colorectal cancer
- Genomics and Rare Diseases
- Lung Cancer Treatments and Mutations
- Breast Cancer Treatment Studies
- RNA modifications and cancer
- Cancer-related Molecular Pathways
Ono Pharmaceutical (United States)
2019-2024
Research & Development Institute
2019-2023
Ontario Institute for Cancer Research
2010-2019
Sunnybrook Health Science Centre
2018
Edinburgh Cancer Research
2018
University of Toronto
2013-2018
Hamilton Health Sciences
2018
Cancer Research UK Clinical Trials Unit
2018
Johannes Gutenberg University Mainz
2018
Athens Medical Center
2018
Reactome ( http://www.reactome.org ) is a collaboration among groups at the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University School of Medicine and The European Bioinformatics Institute, to develop an open source curated bioinformatics database human pathways reactions. Recently, we developed new web site with improved tools pathway browsing data analysis. Pathway Browser Systems Biology Graphical Notation (SBGN)-based visualization system that...
The bicyclam AMD3100 is known as a small synthetic inhibitor of the CXCL12-binding chemokine receptor CXCR4. Here, we show that also binds to alternative CXCL12 CXCR7. or alone activate β-arrestin recruitment CXCR7, which identify previously unreported signaling pathway In addition, increases binding CXCR7 and CXCL12-induced conformational rearrangements in dimer measured by bioluminescence resonance energy transfer. Moreover, but reproducible potency arrestin are observed. Taken together,...
Current protocols for the screening of prostate cancer cannot accurately discriminate clinically indolent tumors from more aggressive ones. One reliable indicator outcome has been determination organ-confined versus nonorgan-confined disease but even this is often only made following prostatectomy. This underscores need to explore alternate avenues enhance prediction patients. Fluids that are proximal prostate, such as expressed prostatic secretions (EPS), attractive sources potential...
The taxanes paclitaxel and docetaxel are widely used in the treatment of breast, ovarian, other cancers. Although their cytotoxicity has been attributed to cell-cycle arrest through stabilization microtubules, mechanisms by which tumor cells die remains unclear. Paclitaxel shown induce soluble necrosis factor alpha (sTNF-α) production macrophages, but involvement TNF taxane or resistance not established. Our study aimed correlate alterations pathway with acquisition resistance.
A key step in cancer genome analysis is the identification of somatic mutations tumor. This typically done by comparing tumor to reference sequence derived from a normal tissue taken same donor. However, there are variety common scenarios which matched not available for comparison. In this work, we describe an algorithm distinguish single nucleotide variants (SNVs) next-generation sequencing data germline polymorphisms absence samples using machine learning approach. Our was evaluated family...
Chromosomal gain at 7q21 is a frequent event in esophageal adenocarcinoma (EAC). However, this has not been mapped with fine resolution large EAC cohort, and its association clinical endpoints functional relevance are unclear.We used cohort of 116 patients to map the amplification using SNP microarrays. Prognostic significance role gene expression were explored.Amplification region was observed 35% tumors focal, minimal amplicon containing six genes. associated poor survival analysis...
Identification of genes that are upregulated during mammary epithelial cell morphogenesis may reveal novel regulators tumorigenesis. We have demonstrated gene expression programs in cells grown monolayer cultures differ significantly from those three-dimensional (3D) cultures. identify a protein tyrosine phosphate, PTPRO, was mature MCF-10A 3D structures but had low to undetectable levels Downregulation PTPRO by RNA interference inhibited proliferation arrest morphogenesis. Low correlated...
Abstract Background Recommendations for perioperative therapy in head and neck cancer are not explicit recurrence occurs frequently. Circulating tumor DNA is an emerging biomarker, but has been extensively explored detection of cancer. Methods Patients diagnosed with squamous cell carcinoma were recruited into the study protocol. Tumors sequenced to identify patient‐specific mutations. Mutations then identified plasma circulating from pre‐treatment blood samples longitudinally during...
Although the G protein-coupled receptors (GPCRs) share a similar seven-transmembrane domain structure, only limited number of amino acid residues is conserved in their protein sequences. One most highly sequences NPXXY motif located at cytosolic end transmembrane region-7 many GPCRs, particularly those belonging to family rhodopsin/beta-adrenergic-like receptors. Exchange Tyr(305) corresponding NPLVY sequence bradykinin B(2) receptor (B(2)R) for Ala resulted mutant, termed Y305A, that...
Drug resistance in breast cancer is the major obstacle to effective treatment with chemotherapy. While upregulation of multidrug genes an important component drug mechanisms vitro, their clinical relevance remains be determined. Therefore, identifying pathways that could targeted clinic eliminate anthracycline-resistant a challenge. We generated paired native and epirubicin-resistant MDA-MB-231, MCF7, SKBR3 ZR-75-1 cell lines identify contributing anthracycline resistance. Native were...
Abstract Immune Cell Deconvolution methods utilizing gene expression profiling to quantify immune cells in tissues and blood are an appealing alternative flow cytometry. Our objective was investigate the applicability of deconvolution approaches clinical trial settings better mode action drugs for autoimmune diseases. Popular CIBERSORT xCell were validated using from publicly available GSE93777 dataset that has comprehensive matching As shown online tool , ~ 50% signatures show strong...
Objective Activation of endosomal toll‐like receptors (TLRs) is one possible driver inflammation in idiopathic inflammatory myopathies (IIM). We investigated the potential contribution TLR7 and TLR8 to IIM pathogenesis. Methods TLR7/8 healthy donor peripheral blood mononuclear cells (PBMCs) by immune complexes from patients with lupus was tested. Autoantibody profiling patient IgG samples performed using a 1581‐antigen array. and/or activation RNA molecules associated autoantibodies...
RBM10 is an RNA binding protein involved in message stabilization and alternative splicing regulation. The objective of the research described herein was to identify novel targets RBM10-regulated splicing. To accomplish this, we downregulated human cell lines, using small interfering RNAs, then monitored splicing, a reverse transcription-PCR screening platform. knockdown (KD) provoked alterations events 10–20% pre-mRNAs, most which had not been previously identified as targets. Hierarchical...
Purpose: The incidence of esophageal adenocarcinoma (EAC) has increased by 700% in Western countries over the last 30 years. Although clinical guidelines call for endoscopic surveillance EAC among high-risk populations, fewer than 5% new patients are under at time diagnosis. We studied accuracy combined cytopathology and MUC2 immunohistochemistry (IHC) screening Intestinal Metaplasia (IM), dysplasia EAC, using specimens collected from EsophaCap swallowable encapsulated cytology sponge Canada...
Determinants for desensitization and sequestration of G protein-coupled receptors often contain serine or threonine residues located in their C-termini. The sequence context, however, which these have to appear, the receptor specificity motifs are largely unknown. Mutagenesis studies with B(2) bradykinin (B(2)wt), stably expressed HEK 293 cells, identified a distal N338 (NSMGTLRTSI, including I347 but not basally phosphorylated S348) particular TSI therein, as major determinant rapid...
This study aimed to identify pathways and cellular processes that are modulated by exposure of normal esophageal cells bile acid.Barrett's esophagus most likely develops as a response stem the abnormal reflux environment. Although insights into underlying molecular mechanisms slowly emerging, much metaplastic process remains unknown.We performed global analysis gene expression in squamous or acid exposure. Differentially expressed genes were classified major biological functions using...
The DRY motif with the highly conserved R3.50 is a hallmark of family A G protein-coupled receptors (GPCRs). crystal structure rhodopsin revealed salt bridge between R135<sup>3.50</sup> and another residue, E247<sup>6.30</sup>, in helix 6. This ionic lock was shown to maintain its inactive state. Thus far, little information available on how interruption this bond affects signaling properties nonrhodopsin GPCRs, because focus has been mutations R3.50, although residue indispensable for...
New strategies to combat complex human disease require systems approaches biology that integrate experiments from cell lines, primary tissues and model organisms. We have developed Pathprint, a functional approach compares gene expression profiles in set of pathways, networks transcriptionally regulated targets. It can be applied universally across species. Integration large-scale profiling methods curation the public repository overcomes platform, species batch effects yield standard...
Sustained activation of G protein-coupled receptors results in an attenuation cellular responses, a phenomenon termed desensitization. Whereas mechanisms for rapid desensitization ligand-receptor-G protein-effector systems are relatively well characterized, much less is known about long-term adaptation processes that occur the continuous presence agonist. Here we have studied fate endogenously expressed bradykinin B 2 on human fibroblasts during prolonged agonist treatment. Stimulation with...
Transfection of cells with expression vectors is one the most important tools used to assess effects receptor mutations on ligand-induced sequestration. Most transfection methods give rise transiently or stably transfected clones a wide range levels that may also depend made. It is, therefore, determine how regulation receptors depends their numbers per cell. In Chinese hamster ovary (CHO) and human embryonic kidney (HEK)-293 expressing high B 2 kinin receptors, we observed poor...
A functional comparison was made between the wild-type bradykinin B2 receptor (B2wt) and chimera B2eGFP (enhanced green-fluorescent protein fused to C-terminus of B2wt), both stably expressed in HEK 293 cells. There almost no difference terms ligand-inducible phosphorylation internalization, signal transduction (accumulation inositol phosphates) or expression affinity. However, stimulation for up 8 h with 10 microM (BK) resulted a strong decrease surface receptors (by 60% within 5 h) B2wt,...