Radiation-induced Changes in Levels of Selected Proteins in Peripheral Blood Serum of Breast Cancer Patients as a Potential Triage Biodosimeter for Large-scale Radiological Emergencies

Deperas‐Kaminska, Marta; Bajinskis, Ainars; Marczyk, Michał; Polańska, Joanna; Wersäll, Peter; Lidbrink, Elisabet; Ainsbury, Elizabeth A.; Guipaud, Oliver; Benderitter, Marc; Haghdoost, Siamak; Wójcik, Andrzej

doi:10.1097/hp.0000000000000158

Cited by 11 publications

(10 citation statements)

References 33 publications

(41 reference statements)

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“…It has become clear that RT and RCT do have the potential to change the tumor and its microenvironment (33) and that radiation exposure is reflected locally and systemically (34). Innovative IT approaches should consider the dynamics of radiation-induced immune cell infiltration into tumors since the immune cells should be activated in the modified environment.…”

Section: Discussionmentioning

confidence: 99%

Hypofractionated Irradiation Has Immune Stimulatory Potential and Induces a Timely Restricted Infiltration of Immune Cells in Colon Cancer Tumors

et al. 2017

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In addition to locally controlling the tumor, hypofractionated radiotherapy (RT) particularly aims to activate immune cells in the RT-modified microenvironment. Therefore, we examined whether hypofractionated RT can activate dendritic cells (DCs), induce immune cell infiltration in tumors, and how the chronology of immune cell migration into tumors occurs to gain knowledge for future definition of radiation breaks and inclusion of immunotherapy. Colorectal cancer treatments offer only limited survival benefit, and immunobiological principles for additional therapies need to be explored with preclinical models. The impact of hypofractionated RT on CT26 colon cancer tumor cell death, migration of DCs toward supernatants (SN) of tumor cells, and activation of DCs by SN were analyzed. The subcutaneous tumor of a BALB/c-CT26 mouse model was locally irradiated with 2 × 5 Gy, the tumor volume was monitored, and the infiltration of immune cells in the tumor was determined by flow cytometry daily. Hypofractionated RT induced a mixture of apoptotic and necrotic CT26 cells, which is known to be in particular immunogenic. DCs that migrated toward SN of CT26 cells particularly upregulated the activation markers CD80 and CD86 when in contact with SN of irradiated tumor cells. After hypofractionated RT, the tumor outgrowth was significantly retarded and in the irradiated tumors an increased infiltration of macrophages (CD11bhigh/F4-80+) and DCs (MHC-II+), but only between day 5 and 10 after the first irradiation, takes place. While CD4+ T cells migrated into non-irradiated and irradiated tumors, CD8+ T cells were only found in tumors that had been irradiated and they were highly increased at day 8 after the first irradiation. Myeloid-derived suppressor cells and regulatory T cells show regular turnover in irradiated and non-irradiated tumors. Tumor cell-specific anti-IgM antibodies were enhanced in the serum of animals with irradiated tumors. We conclude that hypofractionated RT suffices to activate DCs and to induce infiltration of innate and adaptive immune cells into solid colorectal tumors. However, the presence of immune cells in the tumor which are beneficial for antitumor immune responses is timely restricted. These findings should be considered when innovative multimodal tumor treatment protocols of distinct RT with immune therapies are designed and clinically implemented.

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Section: Discussionmentioning

confidence: 99%

Hypofractionated Irradiation Has Immune Stimulatory Potential and Induces a Timely Restricted Infiltration of Immune Cells in Colon Cancer Tumors

et al. 2017

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“…found an increased up-regulation of genes involved in the glycolysation in liver and increased serum cytokines, suggesting a systemic response to local irradiation of the skin to 20, 40, and 80 Gy gamma rays. Analysis of three proteins (Apol (please correct spelling should read: Apolipoprotein)ipprotein E, Factor X and Panththenate Kinase 4) in blood samples allowed discrimination up to 1 month following exposure to <2 Gy and >10 Gy in breast cancer patients, although differences at < 2 Gy were subtle [167]. Similarly [168] found that changes in serum amyloid A (SAA) levels permitted a dose prediction model to discriminate ≤1 Gy from ≥2 Gy irradiated mice.…”

Section: Biomarkers Related To Changes In Protein Levelsmentioning

confidence: 99%

Ionizing radiation biomarkers in epidemiological studies – An update

Hall

Jeggo

West

et al. 2017

Mutation Research/Reviews in Mutation Research

Self Cite

124

105

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Recent epidemiology studies highlighted the detrimental health effects of exposure to low dose and low dose rate ionizing radiation (IR): nuclear industry workers studies have shown increased leukaemia and solid tumour risks following cumulative doses of <100mSv and dose rates of <10mGy per year; paediatric patients studies have reported increased leukaemia and brain tumours risks after doses of 30-60mGy from computed tomography scans. Questions arise, however, about the impact of even lower doses and dose rates where classical epidemiological studies have limited power but where subsets within the large cohorts are expected to have an increased risk. Further progress requires integration of biomarkers or bioassays of individual exposure, effects and susceptibility to IR. The European DoReMi (Low Dose Research towards Multidisciplinary Integration) consortium previously reviewed biomarkers for potential use in IR epidemiological studies. Given the increased mechanistic understanding of responses to low dose radiation the current review provides an update covering technical advances and recent studies. A key issue identified is deciding which biomarkers to progress. A roadmap is provided for biomarker development from discovery to implementation and used to summarise the current status of proposed biomarkers for epidemiological studies. Most potential biomarkers remain at the discovery stage and for some there is sufficient evidence that further development is not warranted. One biomarker identified in the final stages of development and as a priority for further research is radiation specific mRNA transcript profiles.

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“…78 Serial secondary triage in rearward treatment facilities would focus on clinical, serial hematological and other advanced biological parameters (eg, protein biomarkers for better triage accuracy than one biomarker alone). 78,87 Triage decisions will optimize opportunities for both direct casualty care and mitigation of indirect or preventable mortality and morbidity. Well researched triage tools and cards leading to treatment guidance are readily available.…”

Section: Nuclear Triage Centersmentioning

confidence: 99%

Developing a Nuclear Global Health Workforce Amid the Increasing Threat of a Nuclear Crisis

Burkle

Dallas

2015

Disaster med. public health prep.

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This study argues that any nuclear weapon exchange or major nuclear plant meltdown, in the categories of human systems failure and conflict-based crises, will immediately provoke an unprecedented public health emergency of international concern. Notwithstanding nuclear triage and management plans and technical monitoring standards within the International Atomic Energy Agency and the World Health Organization (WHO), the capacity to rapidly deploy a robust professional workforce with the internal coordination and collaboration capabilities required for large-scale nuclear crises is profoundly lacking. A similar dilemma, evident in the early stages of the Ebola epidemic, was eventually managed by using worldwide infectious disease experts from the Global Outbreak Alert and Response Network and multiple multidisciplinary WHOsupported foreign medical teams. This success has led the WHO to propose the development of a Global Health Workforce. A strategic format is proposed for nuclear preparedness and response that builds and expands on the current model for infectious disease outbreak currently under consideration. This study proposes the inclusion of a nuclear global health workforce under the technical expertise of the International Atomic Energy Agency and WHO's Radiation Emergency Medical Preparedness and Assistance Network leadership and supported by the International Health Regulations Treaty. Rationales are set forth for the development, structure, and function of a nuclear workforce based on health outcomes research that define the unique health, health systems, and public health challenges of a nuclear crisis. Recent research supports that life-saving opportunities are possible, but only if a rapidly deployed and robust multidisciplinary response component exists. (Disaster Med Public Health Preparedness. 2016;10:129-144)

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Radiation-induced Changes in Levels of Selected Proteins in Peripheral Blood Serum of Breast Cancer Patients as a Potential Triage Biodosimeter for Large-scale Radiological Emergencies

Cited by 11 publications

References 33 publications

Hypofractionated Irradiation Has Immune Stimulatory Potential and Induces a Timely Restricted Infiltration of Immune Cells in Colon Cancer Tumors

Hypofractionated Irradiation Has Immune Stimulatory Potential and Induces a Timely Restricted Infiltration of Immune Cells in Colon Cancer Tumors

Ionizing radiation biomarkers in epidemiological studies – An update

Developing a Nuclear Global Health Workforce Amid the Increasing Threat of a Nuclear Crisis

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