A5075327419- Sarcoma Diagnosis and Treatment
- Gastrointestinal Tumor Research and Treatment
- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Colorectal Cancer Treatments and Studies
- Cancer, Hypoxia, and Metabolism
- Ovarian cancer diagnosis and treatment
- Neurofibromatosis and Schwannoma Cases
- Lung Cancer Research Studies
- Cancer Treatment and Pharmacology
- Glioma Diagnosis and Treatment
- Renal and related cancers
- Lung Cancer Treatments and Mutations
- Pluripotent Stem Cells Research
- Cancer-related Molecular Pathways
- Cancer therapeutics and mechanisms
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Soft tissue tumor case studies
- Neuroblastoma Research and Treatments
- Acute Myeloid Leukemia Research
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- HER2/EGFR in Cancer Research
Frederick National Laboratory for Cancer Research
2015-2024
National Cancer Institute
2009-2024
University of Ottawa
2024
Children's Hospital of Eastern Ontario
2024
McGill University
2019-2023
Jewish General Hospital
2019-2023
Leidos (United States)
2015-2022
Leidos Biomedical Research Inc. (United States)
2016-2022
National Institutes of Health
2017
Science Applications International Corporation (United States)
2007-2011
Data bias is a major concern in biomedical research, especially when evaluating large-scale observational datasets. It leads to imprecise predictions and inconsistent estimates standard regression models. We compare the performance of commonly used bias-mitigating approaches (resampling, algorithmic, post hoc approaches) against synthetic data-augmentation method that utilizes sequential boosted decision trees synthesize under-represented groups. The approach called minority augmentation...
Purpose Desmoid tumors (aggressive fibromatosis) arise from connective tissue cells or fibroblasts. In general, they are slow growing and do not metastasize; however, locally aggressive desmoid can cause severe morbidity loss of function. Disease recurrence after surgery and/or radiation diagnosis multifocal highlight the need to develop effective systemic treatments for this disease. study, we evaluate objective response rate therapy with γ-secretase inhibitor PF-03084014 in patients...
Abstract Background Parkinson's disease (PD) is the most common movement disorder among adults, affecting 2% of world population older than 65 years age. No diagnostic biomarker for routine use in clinical settings currently exists. Dysregulation microRNAs (miRNAs) has been implicated various neurodegenerative conditions, including PD. Distinct miRNAs have demonstrated to be involved regulation α‐synuclein, a key player PD pathogenesis; miR‐153 and miR‐223 are downregulated brain serum...
Abstract Purpose: Hypoxia-inducible factor 1 (HIF-1) α is frequently overexpressed in human tumors and associated with angiogenesis metastasis. Topotecan, a topoisomerase I inhibitor, has been shown to inhibit HIF-1α expression preclinical models. We designed pilot trial measure inhibition tumor biopsies from patients advanced solid overexpressing HIF-1α, after treatment oral topotecan. Experimental Design: Topotecan was administered orally at 1.6 mg/m2 once daily for 5 days/week 2 weeks,...
Abstract Purpose: The Wee1 kinase inhibitor adavosertib abrogates cell-cycle arrest, leading to cell death. Prior testing of twice-daily in patients with advanced solid tumors determined the recommended phase II dose (RPh2D). Here, we report results for once-daily adavosertib. Patients and Methods: A 3 + dose-escalation design was used, given once daily on days 1 5 8 12 21-day cycles. Molecular biomarkers activity, including tyrosine 15–phosphorylated Cdk1/2 (pY15-Cdk), were assessed paired...
Life expectancy has increased globally, leading to a higher proportion of older adults, particularly in developed countries like Canada. This demographic shift strains healthcare systems and is associated with an risk dementia, condition characterised by cognitive decline. Oral health emerged as potential modifiable factor for yet the evidence remains conflicting. study examines association between oral parameters functioning Canadian population, utilizing data from Longitudinal Study on...
The combination of the antiangiogenic agent ziv-aflibercept and heat shock protein 90 inhibitor ganetespib was associated with several serious unexpected adverse events not tolerable on dosing schedule tested.Studies such as these emphasize importance considering overlapping toxicities when designing novel treatment regimens.
Abstract Purpose Following promising responses to the DNA methyltransferase (DNMT) inhibitor 5-fluoro-2′-deoxycytidine (FdCyd) combined with tetrahydrouridine (THU) in phase 1 testing, we initiated a non-randomized 2 study assess response this combination patients advanced solid tumor types for which suppressor gene methylation is potentially prognostic. To obtain pharmacodynamic evidence DNMT inhibition by FdCyd, developed novel method detecting expression of protein p16/INK4A circulating...
// Geraldine O'Sullivan Coyne 1 , Shivaani Kummar 11 Robert S. Meehan Khanh Do Jerry M. Collins 2 Larry Anderson Kazusa Ishii 3 Naoko Takebe Jennifer Zlott Lamin Juwara 4 Richard Piekarz 5 Howard Streicher Elad Sharon Rubinstein 6 Andrea Regier Voth 7 Jay Lozier 8 Angie B. Dull 9 Deborah Wilsker Toshinori Hinoue 10 Peter W. Laird Katherine V. Ferry-Galow J. Kinders Ralph E. Parchment James H. Doroshow 12 and Alice P. Chen Early Clinical Trials Development Program, Division of Cancer...
3529 Background: The RAF/MEK/ERK and PI3K/AKT signaling pathways are commonly deregulated in CRC. Each can serve as a compensatory mechanism mediating resistance to single pathway blockade. Combined inhibition with MK-2206 selumetinib (AZD6244) could enhance antitumor activity. Tolerable doses for the combination solid tumors (ASCO 2011, abstr 3004) less than agent MTDs. We conducted biomarker driven trial of at established determine extent pERK pAKT tumor biopsies (bx), using new,...
Heme oxygenase-1 (HO-1), a highly inducible stress protein that degrades heme to biliverdin, carbon monoxide, and free ferrous iron, is increased in blood other biofluids of subjects with various systemic neurological disorders. HO-1 does not contain an N-terminal signal peptide the mechanism responsible for its secretion remains unknown. Extracellular vesicles (EVs) are membrane-bound inclusions transport microRNAs, messenger RNAs, lipids, proteins among diverse cellular extracellular...
Parkinson disease (PD) is the second most common neurodegenerative disease, affecting 2% of population over 65 years age. PD diagnosis based on clinical examination and can only be confirmed during autopsy. In 2018, we reported that heme oxygenase-1 (HO-1), an inducible stress response protein important for catabolism implicated in pathology, was higher saliva relative to healthy controls, suggesting salivary HO-1 may serve as a potential biomarker PD.To ascertain whether levels are elevated...
2558 Background: Indenoisoquinolines (ID) are non-camptothecin inhibitors of topoisomerase (TOP1) identified following a COMPARE analysis the National Cancer Institute’s (NCI) in vitro anticancer drug discovery screen. IDs have improved characteristics over camptothecin top1 inhibitors, with better chemical stability (lacking labile hydroxylactone E-ring) producing stable DNA breaks that resistant to reversal trapped DNA-TOP1 cleavage complex and at different sequence sites camptothecins...
2549 Background: Ataxia-telangiectasia-related (ATR) protein kinase is central to the repair of damaged DNA through homologous recombination (HR) pathway, activating phosphorylation cascades that culminate in cell cycle arrest allow time for damage (DDR). M6620 an ATR inhibitor with antitumor activity across a range lines. Veliparib (ABT-888), oral poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor, plays pivotal role DDR response base excision clinical evidence combination cisplatin BRCA...
Analyses of distributed data networks rare diseases are constrained by legitimate privacy and ethical concerns. Analytical centers (e.g. research institutions) thus confronted with the challenging task obtaining from recruiting sites that often unable or unwilling to share personal records participants. For time-to-event data, recently popularized disclosure techniques guarantees (e.g., Differentially Private Generative Adversarial Networks) generally computationally expensive inaccessible...
3067 Background: M6620 (M), a potent ATR inhibitor, has synergistic activity with cisplatin (C) in multiple preclinical models, resulting DNA damage and antitumor activity. We hypothesize that inhibition of both homologous recombination base excision repair through the combination veliparib (V, inhibitor PARP1/2) would result accumulation lethal double stranded breaks induced by increased initiated phase-1 dose escalation trial this patients (pts) advanced solid tumors (NCT02723864)....
Differential responses to tamoxifen may be due inter-patient variability in metabolism into pharmacologically active Z-endoxifen. Z-endoxifen administration was anticipated bypass these variations, increasing drug levels, and potentially benefitting patients responding sub-optimally tamoxifen.Patients with treatment-refractory gynecologic malignancies, desmoid tumors, or hormone receptor-positive solid tumors took oral daily a 3+3 phase 1 dose escalation format over 8 levels (DLs). Safety,...
14111 Background: Phase 0 trials conducted under the FDA Exploratory IND Guidance involve limited exposures to study drug with no expectation of clinical benefit. We present our experience in recruiting pts a ABT-888, first be at NCI. Methods: Objective: To determine ABT-888 dose that inhibits PARP PBMCs and tumor after single oral administration. Tumor biopsies baseline 3–6 hrs post were planned once activity inhibition or target plasma Cmax was achieved. Protocol approved by NCI scientific...
For a continuous time‐to‐event outcome and an expensive‐to‐measure exposure, we develop pooling design propose likelihood‐based approach to estimate the hazard ratios (HRs) of Cox proportional hazards (PH) model. Our proposed fits PH model based on pooled exposures with individually observed outcomes. The estimation exploits equivalence conditional logistic likelihood functions arising from matched case‐control study partial function riskset‐matched, nested (NCC) subset cohort study. To...
10563 Background: Desmoids are rare, invasive, slow growing soft tissue tumors that sporadic or associated with familial genetic syndromes, such as adenomatous polyposis. characterized by stabilization and abnormal nuclear localization of β-catenin. Mutations in the CTNNB1 gene found 85-90% desmoids. Gamma-secretase cleaves intracellular Notch resulting signaling. PF-030844014 (PF) is an oral reversible γ-secretase inhibitor (GSI) well tolerated. Based on encouraging data from a phase I...