CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients

Ozşahin, Mahmut; Crompton, N. E. A.; Gourgou, Sophie; Kramar, Andrew; Li, Ling; Shi, Yu; Sozzi, Wendy Jeanneret; Zouhair, Abderrahim; Mirimanoff, R.O.; Azria, D.

doi:10.1158/1078-0432.ccr-04-2634

Cited by 191 publications

(144 citation statements)

References 38 publications

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“…In addition, it has been hypothesized that individual intrinsic radiosensitivity may influence the development of adverse radiation responses (3). Therefore, efforts have been made to develop assays capable of predicting susceptibility for the development of radiation injury that would allow customization of RT protocols on an individual basis (3,4). By doing so, it has been estimated that a significant improvement in the therapeutic index could be achieved.…”

mentioning

confidence: 99%

Single Nucleotide Polymorphisms, Apoptosis, and the Development of Severe Late Adverse Effects After Radiotherapy

Azria

Ozşahin

Kramar³

et al. 2008

Clinical Cancer Research

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137

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Purpose: Evidence has accumulated in recent years suggestive of a genetic basis for a susceptibility to the development of radiation injury after cancer radiotherapy. The purpose of this study was to assess whether patients with severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0 grade, z3) display both a low capacity of radiation-induced CD8 lymphocyte apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms (SNP) located in candidate genes associated with the response of cells to radiation. Experimental Design: DNA was isolated from blood samples obtained from patients (n = 399) included in the Swiss prospective study evaluating the predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3, TGFB1, and RAD21 genes were screened in patients who experienced severe RIS (group A, n = 16) and control subjects who did not manifest any evidence of RIS (group B, n = 18). Results: Overall, 13 and 21 patients were found to possess a total of <4 and z4 SNPs in the candidate genes. The median (range) RILA in group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the patients (15 of 16) had z4 SNPs. In group B, median (range) RILA was 25.7% (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had z4 SNPs (P < 0.001). Conclusions:The results of this study suggest that patients with severe RIS possess 4 or more SNPs in candidate genes and low radiation-induced CD8 lymphocyte apoptosis in vitro.

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confidence: 99%

Single Nucleotide Polymorphisms, Apoptosis, and the Development of Severe Late Adverse Effects After Radiotherapy

Azria

Ozşahin

Kramar³

et al. 2008

Clinical Cancer Research

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137

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“…Studies point out that low apoptotic response is associated with risk for development of late side effects, which occur around 6 months to many years after exposure and, thus, demanding follow-up relatively long. Besides this, this kind of effect can be irreversible (Erasmus et al 2005, Ozsahin et al 2005, Bordón et al 2009, Schnarr et al 2009, Pinar et al 2010.…”

Section: Discussionmentioning

confidence: 99%

Active caspase-3 expression levels as bioindicator of individual radiosensitivity

Santos

Silva

Pinto

et al. 2017

An. Acad. Bras. Ciênc.

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Several molecules and events involved in cell response to radiation-induced damage have been investigated towards a personalized radiotherapy. Considering the importance of active caspase-3 in the proteolytic cascade that ensures radiation-induced apoptosis execution, this research was designed to evaluate the expression levels of this protein as a bioindicator of individual radiosensitivity. Peripheral blood samples of 10 healthy individuals were gamma-irradiated (cobalt-60 source) with 1, 2 and 4 Gy (control: non-irradiated samples), and active caspase-3 expression levels were measured in lymphocytes, by flow cytometry, ex vivo and after different times of in vitro incubation (24, 48 and 72 hours). Short-term incubation of 24 h was the most adequate condition to evidence correlations between dose radiation and active caspase-3 expression. For each radiation dose, it was observed a significant inter-individual variation in active caspase-3 expression intensity, suggesting that this parameter may be suitable for evidence individual radiosensitivity. The methodology presented and discussed in this work may help to predict healthy tissues response to radiation exposure toward the better patient outcome.

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“…This is because of the impaired genes involved in the repair process in immune-comprised patients or radiosensitive patients and their inability to remove DNA damage after irradiation. The Tlymphocyte apoptosis assay used by Ozsahin et al [101] can predict Grade 2 or Grade 3 late-stage toxicity with a 70% level of accuracy. Sources of variation using the leukocyte apoptosis assay include hereditary factors, cell type and age [100].…”

Section: Radiosensitivitymentioning

confidence: 99%

Deoxyribonucleic acid damage-associated biomarkers of ionising radiation: current status and future relevance for radiology and radiotherapy

Manning

Rothkamm²

2013

BJR

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Diagnostic and therapeutic radiation technology has developed dramatically in recent years, and its use has increased significantly, bringing clinical benefit. The use of diagnostic radiology has become widespread in modern society, particularly in paediatrics where the clinical benefit needs to be balanced with the risk of leukaemia and brain cancer increasing after exposure to low doses of radiation. With improving long-term survival rates of radiotherapy patients and the ever-increasing use of diagnostic and interventional radiology procedures, concern has risen over the long-term risks and side effects from such treatments. Biomarker development in radiology and radiotherapy has progressed significantly in recent years to investigate the effects of such use and optimise treatment. Recent biomarker development has focused on improving the limitations of established techniques by the use of automation, increasing sensitivity and developing novel biomarkers capable of quicker results. The effect of low-dose exposure (0-100 mGy) used in radiology, which is increasingly linked to cancer incidences, is being investigated, as some recent research challenges the linear-no-threshold model. Radiotherapy biomarkers are focused on identifying radiosensitive patients, determining the treatment-associated risk and allowing for a tailored and more successful treatment of cancer patients. For biomarkers in any of these areas to be successfully developed, stringent criteria must be applied in techniques and analysis of data to reduce variation among reports and allow data sets to be accurately compared. Newly developed biomarkers can then be used in combination with the established techniques to better understand and quantify the individual biological response to exposures associated with radiology tests and to personalise treatment plans for patients.

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CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients

Cited by 191 publications

References 38 publications

Single Nucleotide Polymorphisms, Apoptosis, and the Development of Severe Late Adverse Effects After Radiotherapy

Single Nucleotide Polymorphisms, Apoptosis, and the Development of Severe Late Adverse Effects After Radiotherapy

Active caspase-3 expression levels as bioindicator of individual radiosensitivity

Deoxyribonucleic acid damage-associated biomarkers of ionising radiation: current status and future relevance for radiology and radiotherapy

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