Purpose To examine the possibility of predicting clinical radiosensitivity by quantifying the nuclear forms of autophosphorylated ATM protein (pATM) via a specific enzyme-linked immunosorbent assay (ELISA). Methods and Materials This study was performed on 30 skin fibroblasts from 9 radioresistant patients and 21 patients with adverse tissue reaction events. Patients were divided into 2 groups: radioresistant (toxicity grade Results The pATM ELISA data were in quantitative agreement with the immunofluorescence data. A receiver operating characteristic analysis was applied first to 2 data sets (a training set [n=14] and a validating [n=16] set) and thereafter to all the data with a 2-fold cross-validation method. The assay showed an area under the curve value higher than 0.8, a sensitivity of 0.8, and a specificity ranging from 0.75 to 1, which strongly documents the predictive power of the pATM ELISA. Conclusion This study showed that the assessment of nuclear pATM quantity after 2 Gy via an ELISA technique can be the basis of a predictive assay with the highest statistical performance among the available predictive approaches.
Last. Nicolas Foray(French Institute of Health and Medical Research)H-Index: 30
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The tuberous sclerosis complex (TSC) syndrome is associated with numerous cutaneous pathologies (notably on the face), epilepsy, intellectual disability and developmental retardation and, overall, high occurrence of benign tumors in several organs, like angiofibromas, giant cell astrocytomas, renal angiomyolipomas, and pulmonary lymphangioleiomyomatosis. TSC is caused by mutations of either of the hamartin or tuberin proteins that are mainly cytoplasmic. Some studies published in the 1980s repor...
#1Nicolas Foray(French Institute of Health and Medical Research)H-Index: 30
#2Michel H. Bourguignon(Institut de radioprotection et de sûreté nucléaire)H-Index: 18
Last. Nobuyuki Hamada(CRIEPI: Central Research Institute of Electric Power Industry)H-Index: 33
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Abstract The human response to ionizing radiation (IR) varies among individuals. The first evidence of the individual response to IR was reported in the beginning of the 20th century. Considering nearly one century of observations, we here propose three aspects of individual IR response: radiosensitivity for early or late adverse tissue events after radiotherapy on normal tissues (non-cancer effects attributable to cell death); radiosusceptibility for IR-induced cancers; and radiodegeneration fo...
#1Larry Bodgi(French Institute of Health and Medical Research)H-Index: 8
#2Aurélien Canet(UCBL: Claude Bernard University Lyon 1)H-Index: 3
Last. Nicolas Foray(French Institute of Health and Medical Research)H-Index: 30
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Abstract Cell survival is conventionally defined as the capability of irradiated cells to produce colonies. It is quantified by the clonogenic assays that consist in determining the number of colonies resulting from a known number of irradiated cells. Several mathematical models were proposed to describe the survival curves, notably from the target theory. The Linear-Quadratic (LQ) model, which is to date the most frequently used model in radiobiology and radiotherapy, dominates all the other mo...
Last. Nicolas Foray(French Institute of Health and Medical Research)H-Index: 30
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PURPOSE: Whereas post-radiation therapy overreactions (OR) represent a clinical and societal issue, there is still no consensual radiobiological endpoint to predict clinical radiosensitivity. Since 2003, skin biopsy specimens have been collected from patients treated by radiation therapy against different tumor localizations and showing a wide range of OR. Here, we aimed to establish quantitative links between radiobiological factors and OR severity grades that would be relevant to radioresistan...
#1Larry Bodgi(French Institute of Health and Medical Research)H-Index: 8
#2Nicolas Foray(French Institute of Health and Medical Research)H-Index: 30
AbstractPurpose For 50 years, cellular radiosensitivity has been defined in vitro as the lack of clonogenic capacity of irradiated cells and its mathematical link with dose has been described by the target theory. Among the numerous formulas provided from the target theory, the linear-quadratic (LQ) model empirically describes cell survival as a negative exponential of a second degree polynomial dose-function in which αD is the linear component and βD2 is the quadratic one. The LQ model is exten...
article i nfo Background: Monocentric cohorts suggested that radiation-induced CD8 T-lymphocyte apoptosis (RILA) can predict late toxicity after curative intent radiotherapy (RT). We assessed the role of RILA as a predictor of breast fibrosis (bf+) after adjuvant breast RT in a prospective multicenter trial. Methods: A total of 502 breast-cancer patients (pts) treated by conservative surgery and adjuvant RT were re- cruitedatten centers. RILAwasassessedbeforeRTby flowcytometry.ImpactofRILAonbf+(...
Last. Nicolas Foray(French Institute of Health and Medical Research)H-Index: 30
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Purpose After radiation therapy (RT), various radiation-induced toxicities can develop in about one-fourth of patients. An international interest in using morbidity and mortality rates to monitor the quality of care and integrate morbidity and mortality review (MMR) meetings into organizations' governance processes has arisen. We report the first results of patients included in our MMR procedure that included biological assays for individual intrinsic radiosensitivity (IIRS). Methods and Materia...
Radiomics extracts and mines large number of medical imaging features quantifying tumor phenotypic characteristics. Highly accurate and reliable machine-learning approaches can drive the success of radiomic applications in clinical care. In this radiomic study, fourteen feature selection methods and twelve classification methods were examined in terms of their performance and stability for predicting overall survival. A total of 440 radiomic features were extracted from pretreatment computed tom...
Radiation therapy (RT), either alone or in combination with surgery and/or chemotherapy is a keystone of cancers treatment. Early toxicity is common, sometimes leading to discontinuation of treatment. Recent studies stressed the role of the phosphorylated ATM (pATM) protein in RT-toxicity genesis and its ability in predicting individual radiosensitivity (IRS) in fibroblasts. Here we assessed the reliability of the pATM quantification in lymphocytes to predict IRS. A first retrospective study was...
#2Mélanie L. Ferlazzo(French Institute of Health and Medical Research)H-Index: 7
Last. Nicolas Foray(French Institute of Health and Medical Research)H-Index: 30
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Retinoblastoma (Rb) is a rare form of pediatric cancer that develops from retina cells. Bilateral and some unilateral forms of Rb are associated with heterozygous germline mutations of the (retinob...
MacCune–Albright syndrome (MAS) is a rare autosomal dominant osteo-hormonal disorder. MAS is characterized by a severe form of polyostotic fibrous dysplasia, ‘cafe-au-lait’ pigmentation of the skin...
#1Marina Francis(AUB: American University of Beirut)H-Index: 2
#2Alaa Abou Daher(AUB: American University of Beirut)H-Index: 2
Last. Youssef H. Zeidan(AUB: American University of Beirut)H-Index: 19
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Although once considered as structural components of eukaryotic biological membranes, research in the past few decades hints at a major role of bioactive sphingolipids in mediating an array of physiological processes including cell survival, proliferation, inflammation, senescence, and death. A large body of evidence points to a fundamental role for the sphingolipid metabolic pathway in modulating the DNA damage response (DDR). The interplay between these two elements of cell signaling determine...
Last. Siamak Haghdoost(UNICAEN: University of Caen Lower Normandy)H-Index: 19
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Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival and may appear during or long time after finishing radiotherapy, are depending on the patient radiosensitivity. Currently, there is no assay available that can reliably predict the individual’s response to radiother...
Last. Simon Bouffler(PHE: Public Health England)H-Index: 32
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Tissue reactions and stochastic effects after exposure to ionising radiation are variable between individuals but the factors and mechanisms governing individual responses are not well understood. Individual responses can be measured at different levels of biological organization and using different endpoints following varying doses of radiation, including: cancers, non-cancer diseases and mortality in the whole organism; normal tissue reactions after exposures; and, cellular endpoints such as c...
Last. Sisko Salomaa(University of Eastern Finland)H-Index: 20
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AbstractPurpose: The workshop on ‘Individual Radiosensitivity and Radiosusceptibility’ organized by MELODI and CONCERT on Malta in 2018, evaluated the current state of assays to identify sensitive ...
#1Mélanie L. Ferlazzo(French Institute of Health and Medical Research)H-Index: 7
#2Elise Berthel(French Institute of Health and Medical Research)H-Index: 5
Last. Nicolas Foray(French Institute of Health and Medical Research)H-Index: 30
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AbstractPurpose: Xeroderma Pigmentosum (XP) is a rare, recessive genetic disease associated with photosensitivity, skin cancer proneness, neurological abnormalities and impaired nucleotide excision...