Conor Mcfadden

Conor Mcfadden
University of Texas Southwestern Medical Center | UT Southwestern · Department of Cell Biology

M.Sc. Carleton University, Ottawa, Canada

About

16
Publications
692
Reads
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92
Citations
Citations since 2017
9 Research Items
90 Citations
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20172018201920202021202220230510152025
20172018201920202021202220230510152025

Publications

Publications (16)
Article
Small molecule inhibitors are currently in preclinical and clinical development for the treatment of selected cancers, particularly those with existing genetic alterations in DNA repair and DNA damage response (DDR) pathways. Keen interest has also been expressed in combining such agents with other targeted antitumor strategies such as radiotherapy...
Article
Purpose/Objective(s) Radiotherapy (RT) controls tumors primarily by inducing DNA damage. However, some tumor cells can repair RT-induced DNA damage and are thus radioresistant. RT could be made more effective by combining it with inhibitors of DNA damage response proteins (DDRi) to selectively render tumor cells more susceptible to RT-induced DNA d...
Article
Purpose/Objective(s) Radiotherapy (RT) has been shown, albeit rarely, to stimulate anti-tumor immune responses. Recent evidence suggests this can, in part, be attributed to the accumulation of cytoplasmic DNA in the form of micronuclei (MN) following RT, which can stimulate IRF3 and NF-κB immune signaling that recruits various immune components to...
Article
Purpose: To show that intrinsic radiosensitivity varies greatly for protons and carbon (C) ions in addition to photons, and that DNA repair capacity remains important in governing this variability. Methods: We measured or obtained from the literature clonogenic survival data for a number of human cancer cell lines exposed to photons, protons (9....
Preprint
Purpose To show that radiation response across cancer cell lines of the same anatomic site and histologic type varies remarkably for protons and carbon (C) ions. Materials and Methods We measured and obtained from the literature clonogenic survival of human cancer cell lines of the lung (n=18), brain (n=10) and pancreas (n=10) exposed to photons,...
Preprint
Purpose To develop an empirical model to predict radiosensitivity and relative biological effectiveness (RBE) after helium (He) and carbon (C) ion irradiation with or without DNA repair inhibitors. Methods We characterized survival in eight human cancer cell lines exposed to 6 MV photons and to He- and C-ions with linear energy transfer (LET) valu...
Article
Purpose: High energetic carbon (C-) ion beams undergo nuclear interactions with tissue producing secondary nuclear fragments. Thus, at depth, C-ion beams are composed of a mixture of different particles with different linear energy transfer (LET) values. We developed a technique to enable isolation of DNA damage response (DDR) in mixed radiation f...
Article
Purpose: This study seeks to identify biological factors that may yield a therapeutic advantage of proton therapy versus photon therapy. Specifically, we address the role of nonhomologous end-joining (NHEJ) and homologous recombination (HR) in the survival of cells in response to clinical photon and proton beams. Methods and materials: We irradi...
Article
Whilst Monte Carlo (MC) simulations of proton energy deposition have been well-validated at the macroscopic level, their microscopic validation remains lacking. Equally, no gold-standard yet exists for experimental metrology of individual proton tracks. In this work we compare the distributions of stochastic proton interactions simulated using the...
Article
Purpose:In order to further understand the interplay between proton physics and radiobiology it is necessary to consider proton energy deposition on the microscopic scale. In this work we used Fluorescent Nuclear Track Detectors (FNTDs) to experimentally investigate proton energy deposition, track-by-track. Methods:We irradiated 8×4×0.5mm3 FNTD chi...
Article
Purpose:To construct a custom and portable fluorescence confocal laser-scanning microscope (FCLSM) that can be placed in the path of therapeutic radiation beams to study real-time radiation-induced damage response in live cells. Methods:We designed and constructed a portable FCLSM with three laser diodes for excitation (405, 488, and 635 nm). An ob...
Article
Purpose:To use confocal microscopy to distinguish cells in different phases of the cell cycle before and after treatment with pegylated gold nanoshells (PEG-AuNSs). Methods:Transfected fibrosarcoma cells (HT1080-EYFP-53BP1-FUCCI) were cultured in T-25 flasks and seeded in glass bottom dishes. These cells express the fluorescent probe AmCyan during...
Article
Purpose: The authors describe a method in which fluorescence nuclear track detectors (FNTDs), novel track detectors with nanoscale spatial resolution, are used to determine the linear energy transfer (LET) of individual proton tracks from proton therapy beams by allowing visualization and 3D reconstruction of such tracks. Methods: FNTDs were exp...
Article
Purpose: Understanding the DNA damage and repair induced by hadron therapy (HT) beams is crucial for developing novel strategies to maximize the use of HT beams to treat cancer patients. However, spatiotemporal studies of DNA damage and repair for beam energies relevant to HT have been challenging. We report a technique that enables spatiotemporal...
Poster
Purpose: To determine the effect of gold-nanoparticles (AuNPs) on energy deposition in water for different irradiation conditions. Methods: TOPAS version B12 Monte Carlo code was used to simulate energy deposition in water from monoenergetic 40 keV and 85 keV photon beams and a 6 MV Varian Clinac photon beam (IAEA phase space file, 10x10 cm2, SSD 1...
Article
Purpose: To construct a custom confocal laser scanning microscope (CLSM) capable of resolving individual proton tracks in the volume of an Al(2)O(3):C,Mg fluorescent nuclear track detector (FNTD). The spatial resolution of the FNTD technique is at the sub-micrometer scale. Therefore the FNTD technique has the potential to perform radiation measurem...

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