To develop an empirical model to predict carbon ion (C-ion) relative biological effectiveness (RBE).We used published cell survival data comprising 360 cell line/energy combinations to characterize the linear energy transfer (LET) dependence of cell radiosensitivity parameters describing the dose required to achieve a given survival level, e.g.
View Article and Find Full Text PDFAdaptive optics (AO) can restore diffraction-limited performance when imaging beyond superficial cell layers and , and as such, is of interest for advanced 3D microscopy methods such as light-sheet fluorescence microscopy (LSFM). In a typical LSFM system, the illumination and detection paths are separate and subject to different optical aberrations. To achieve optimal microscope performance, it is necessary to sense and correct these aberrations in both light paths, resulting in a complex microscope system.
View Article and Find Full Text PDFAtaxia telangiectasia and Rad3-related protein (ATR) is a key DNA damage response protein that facilitates DNA damage repair and regulates cell cycle progression. As such, ATR is an important component of the cellular response to radiation, particularly in cancer cells, which show altered DNA damage response and aberrant cell cycle checkpoints. Therefore, ATR's pharmacological inhibition could be an effective radiosensitization strategy to improve radiotherapy.
View Article and Find Full Text PDFAdaptive optics (AO) can restore diffraction limited performance when imaging beyond superficial cell layers and , and as such is of interest for advanced 3D microscopy methods such as light-sheet fluorescence microscopy (LSFM). In a typical LSFM system, the illumination and detection paths are separate and subject to different optical aberrations. To achieve optimal microscope performance, it is necessary to sense and correct these aberrations in both light paths, resulting in a complex microscope system.
View Article and Find Full Text PDFis a turnkey, open-source software solution designed to enhance light-sheet fluorescence microscopy (LSFM) by integrating smart microscopy techniques into a user-friendly framework. It enables automated, intelligent imaging with a Python-based control system that supports GUI-reconfigurable acquisition routines and the integration of diverse hardware sets. As a comprehensive package, navigate democratizes access to advanced LSFM capabilities, facilitating the development and implementation of smart microscopy workflows without requiring deep programming knowledge or specialized expertise in light-sheet microscopy.
View Article and Find Full Text PDFSmall 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. Radiotherapy exerts its cytotoxic effects primarily through DNA damage-induced cell death; therefore, inhibiting DNA repair and the DDR should lead to additive and/or synergistic radiosensitizing effects.
View Article and Find Full Text PDFPurpose: 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 (9.9 keV/μm), and C-ions (13.
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 fields using beam line microscopy coupled with fluorescence nuclear track detectors (FNTDs).
View Article and Find Full Text PDFInt J Radiat Oncol Biol Phys
December 2019
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 irradiated HT1080, M059K (DNA-PKcs), and HCC1937 human cancer cell lines and their isogenic counterparts HT1080-shDNA-PKcs, HT1080-shRAD51, M059J (DNA-PKcs), and HCC1937-BRCA1 (BRCA1 complemented) to assess cell clonogenic survival and γ-H2AX radiation-induced foci.
Int J Radiat Oncol Biol Phys
September 2016
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 measurement of radiation-induced damage in live cells and colocalization of this damage with charged particle tracks over a broad range of clinically relevant beam energies.
View Article and Find Full Text PDFPurpose: 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 exposed to proton therapy beams with nominal energies ranging from 100 to 250 MeV. Proton track images were then recorded by confocal microscopy of the FNTDs.