David W. Hedley

ORCID: 0000-0003-1323-2655
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About
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Research Areas
  • Cancer Genomics and Diagnostics
  • Cancer, Hypoxia, and Metabolism
  • Pancreatic and Hepatic Oncology Research
  • Cholangiocarcinoma and Gallbladder Cancer Studies
  • Cancer Cells and Metastasis
  • Cancer Research and Treatments
  • Cancer Mechanisms and Therapy
  • Acute Myeloid Leukemia Research
  • Epigenetics and DNA Methylation
  • Medical Imaging Techniques and Applications
  • Colorectal Cancer Treatments and Studies
  • Lung Cancer Treatments and Mutations
  • Cancer-related Molecular Pathways
  • RNA modifications and cancer
  • Cancer therapeutics and mechanisms
  • Cell death mechanisms and regulation
  • Angiogenesis and VEGF in Cancer
  • Nanoplatforms for cancer theranostics
  • PI3K/AKT/mTOR signaling in cancer
  • Cancer Treatment and Pharmacology
  • Mitochondrial Function and Pathology
  • 3D Printing in Biomedical Research
  • Microtubule and mitosis dynamics
  • Sulfur Compounds in Biology
  • Radiopharmaceutical Chemistry and Applications

University of Toronto
2014-2025

Princess Margaret Cancer Centre
2015-2024

University Health Network
2014-2024

Toronto General Hospital
2012-2024

Ontario Institute for Cancer Research
2009-2020

Institució Catalana de Recerca i Estudis Avançats
2020

Heidelberg University
2020

Occupational Cancer Research Centre
2018

Mount Sinai Hospital
2004-2015

Lunenfeld-Tanenbaum Research Institute
2007-2015

A method has been developed that allows flow cytometry to be used for measuring the cellular DNA content of paraffin-embedded human tumors. Thick (i.e., 30 micron) sections were cut from tissue blocks using a microtome and dewaxed in xylene. The then rehydrated by sequentially immersing them 100, 95, 70, 50% ethanol before finally washing distilled water. Single cell suspensions prepared incubation 0.5% pepsin, pH 1.5, at 37 degrees C min. cells counted, washed, stained with 1 microgram/ml...

10.1177/31.11.6619538 article EN Journal of Histochemistry & Cytochemistry 1983-11-01

Purpose: To perform real-time whole genome sequencing (WGS) and RNA (RNASeq) of advanced pancreatic ductal adenocarcinoma (PDAC) to identify predictive mutational transcriptional features for better treatment selection.Experimental Design: Patients with PDAC were prospectively recruited prior first-line combination chemotherapy. Fresh tumor tissue was acquired by image-guided percutaneous core biopsy WGS RNASeq. Laser capture microdissection performed all cases. Primary endpoint feasibility...

10.1158/1078-0432.ccr-17-2994 article EN Clinical Cancer Research 2017-12-29
Andrea Cossarizza Hyun‐Dong Chang Andreas Radbruch Mübeccel Akdiş Immanuel Andrä and 95 more Francesco Annunziato Petra Bächer Vincenzo Barnaba Luca Battistini Wolfgang Bauer Sabine Baumgart Burkhard Becher Wolfgang Beisker Claudia Berek Alfonso Blanco Giovanna Borsellino Philip E. Boulais Ryan R. Brinkman Martin Büscher Dirk H. Busch Timothy Bushnell Xuetao Cao Andrea Cavani Pratip K. Chattopadhyay Qingyu Cheng Sue Chow Mario Clerici Anne Cooke Antonio Cosma Lorenzo Cosmi Ana Cumano Van Duc Dang Derek Davies Sara De Biasi Genny Del Zotto Silvia Della Bella Paolo Dellabona Günnur Deniz Mark C. Dessing Andreas Diefenbach James P. Di Santo Francesco Dieli Andreas Dolf Vera S. Donnenberg Thomas Dörner Götz R. A. Ehrhardt Elmar Endl Pablo Engel Britta Engelhardt Charlotte Esser Bart Everts Anita Dreher Christine S. Falk Todd A. Fehniger Andrew Filby Simon Fillatreau Marie Follo Irmgard Förster John R. Foster Gemma A. Foulds Paul S. Frenette David W. Galbraith Natalio Garbi Maria Dolores García‐Godoy Jens Geginat Kamran Ghoreschi Lara Gibellini Christoph Goettlinger Carl S. Goodyear Andrea Gori Jane L. Grogan Mor Gross Andreas Grützkau Daryl Grummitt Jonas Hahn Quirin Hammer Anja E. Hauser David L. Haviland David W. Hedley Guadalupe Herrera Martin Herrmann Falk Hiepe Tristan Holland Pleun Hombrink Jessica P. Houston Bimba F. Hoyer Bo Huang Christopher A. Hunter Anna Iannone Hans‐Martin Jäck Beatriz Jávega Stipan Jonjić Kerstin Juelke Steffen Jung Toralf Kaiser Tomáš Kalina Baerbel Keller Srijit Khan Deborah Kienhöfer Thomas Kroneis

The marriage between immunology and cytometry is one of the most stable productive in recent history science. A rapid search PubMed shows that, as July 2017, using "flow immunology" a term yields more than 68 000 articles, first which, interestingly, not about lymphocytes. It might be stated after short engagement, exchange wedding rings officially occurred when idea to link fluorochromes monoclonal antibodies came about. After this, recognizing different types cells became relatively easy...

10.1002/eji.201646632 article EN European Journal of Immunology 2017-10-01

Abstract Purpose: Anticancer drugs gain access to solid tumors via the circulatory system and must penetrate tissue kill cancer cells. Here, we study distribution of doxorubicin in relation blood vessels regions hypoxia mice. Experimental Design: The was quantified by immunofluorescence (recognized CD31) murine 16C EMT6 human prostate PC-3 xenografts. Hypoxic were identified injection EF5. Results: concentration decreases exponentially with distance from tumor vessels, decreasing half its...

10.1158/1078-0432.ccr-05-1664 article EN Clinical Cancer Research 2005-12-15

By using a recently developed flow cytometric method we have analyzed cellular DNA content of paraffin-embedded histological material from cancer patients. This allows the retrospective study tumors patients whose clinical outcome is already known, and applied it to ovarian cancers, stage II breast metastatic adenocarcinoma unknown primary site. In addition knowledge patient survival, comprehensive information was available about other prognostic determinants treatment received, used...

10.1002/cyto.990060409 article EN Cytometry 1985-07-01

The BRCA1/2 proteins are involved in regulation of cellular proliferation by DNA damage repair via homologous recombination. Therefore, mutation carriers with pancreatic cancer may have distinct biologic outcomes. Patients BRCA1/2-associated ductal adenocarcinoma (PDAC) diagnosed between January 1994 and December 2012 were identified from databases at three participating institutions. Clinical data collected. Disease-free survival overall (OS) analysed. Overall, 71 patients PDAC BRCA1...

10.1038/bjc.2014.418 article EN cc-by-nc-sa British Journal of Cancer 2014-07-29

Purpose The main purpose of this study was to determine the prevalence pathogenic BRCA1 and BRCA2 mutations in a consecutively ascertained clinic-based cohort patients with pancreatic ductal adenocarcinoma describe clinical family history characteristics. Patients Methods Unselected, consecutive, incident were recruited at single cancer center over 2-year period. Participants provided blood for DNA analysis history, treatment records reviewed. from all analyzed by Sanger sequencing multiplex...

10.1200/jco.2014.59.7401 article EN Journal of Clinical Oncology 2015-05-05

There is an emerging concept that acquired genetic instability in cancer cells can arise from the dysregulation of critical DNA repair pathways due to cell stresses such as inflammation and hypoxia. Here we report hypoxia specifically down-regulates expression RAD51, a key mediator homologous recombination mammalian cells. Decreased levels Rad51 were observed multiple types during hypoxic exposure not associated with cycle profile or hypoxia-inducible factor. Analyses RAD51 gene promoter...

10.1128/mcb.24.19.8504-8518.2004 article EN Molecular and Cellular Biology 2004-09-14

Standard cytotoxic treatments for neuroendocrine tumours have been associated with limited activity and remarkable toxicity. A phase II study was designed to evaluate the efficacy, safety pharmacodynamics of temsirolimus in patients advanced carcinoma (NEC). Thirty-seven progressive NEC received intravenous weekly doses 25 mg temsirolimus. Patients were evaluated tumour response, time progression (TTP), overall survival (OS) adverse events (AE). Twenty-two archival specimens, as well 13...

10.1038/sj.bjc.6603419 article EN cc-by-nc-sa British Journal of Cancer 2006-10-10

Hypoxia in solid tumors is associated with treatment resistance and increased metastatic potential. Although hypoxia has been reported pancreatic cancer patients, there little direct evidence that this contributes to their overall poor prognosis. To address this, we examined the associations between biological aggression a series of patient-derived xenografts grown orthotopically. Early passage were established from 16 patients undergoing surgery for maintained pancreas immune-deprived mice....

10.1158/0008-5472.can-10-4049 article EN Cancer Research 2011-02-23

<h3>Importance</h3> Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA RNA analysis clinicopathologic data may be crucial step toward personalized treatment strategies this disease. <h3>Objective</h3> To classify PDAC according distinct mutational processes, explore their clinical significance. <h3>Design, Setting, Participants</h3> We performed retrospective...

10.1001/jamaoncol.2016.3916 article EN JAMA Oncology 2016-10-20

Purpose Biliary cancer has a poor prognosis, and chemotherapy had little impact. The objectives of this trial were to determine the response rate, time disease progression, survival, safety profile combination gemcitabine capecitabine (GemCap) in patients with advanced biliary cancer. Patients Methods Eligible pathologically proven, locally or metastatic adenocarcinoma arising from intra- extrahepatic bile ducts gallbladder no prior chemotherapy. treated on 3-week cycle consisting at 650...

10.1200/jco.2005.51.008 article EN Journal of Clinical Oncology 2005-03-30

Abstract The currently available flow cytometric stains for cellular glutathione were evaluated, examining the labelling of both human and rodent cell lines under various conditions concentration, time, temperature. Procedures used that depleted, (GSH) while having a minimal effect on other sulphydryls in order to estimate linearity extent background staining. As previously reported, monochlorobimane was highly specific GSH cells but failed label adequately because its low affinity...

10.1002/cyto.990150411 article EN Cytometry 1994-04-01

PURPOSE: This prospective clinical study was begun in 1994 to validate the independent prognostic impact of tumor hypoxia patients with cervix cancer treated definitive radiation therapy. PATIENTS AND METHODS: Between May and January 1999, 106 eligible epithelial had oxygen pressure (PO 2 ) measured using Eppendorf probe. Oxygenation data are presented as hypoxic proportion, defined percentage PO readings less than 5 mm/Hg (abbreviated HP median . RESULTS: The individual 48%,...

10.1200/jco.2002.20.3.680 article EN Journal of Clinical Oncology 2002-02-01
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