| 1. |
- Drobin, Kimi, et al.
(författare)
-
Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer
- 2020
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:3
-
Tidskriftsartikel (refereegranskat)abstract
- 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, may appear during or long time after finishing radiotherapy and depending on the patient's radiosensitivity. Currently, there is no assay available that can reliably predict the individual's response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual's risk of experiencing radiation-induced toxicity.
|
|
| 2. |
- Magnusson, Sven Erik, et al.
(författare)
-
Co-operative Nordic Research
- 1999
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This report has a two-fold objective. -To identify the changing risk management needs in the private and public sectors and the corresponding needs for development of risk analysis methods and related practices. -To list examples of projects where Nordic co-operation between industry, authorities and universities can be effective for increasing the contribution of risk management to industrial growth and a sustainable society. A Nordic expert group, funded by the Nordic Industrial Fund, identified the urgent need for co-operative Nordic risk management research and suggested a structure for co-operation and cross-disciplinary research and for dissemination of knowledge and implementation. The group also specified research areas and project ideas for future development into actual research projects. A workshop with participants from the Nordic countries was one source of ideas. The expert group in addition identified a number of basic resource areas necessary for the development of more efficient risk management industry and which would benefit from Nordic co-operation. A Nordic risk management academy and a Nordic risk management network should be formed. Also a Nordic graduate school on safety and risk management for PhD students should be organized on a Nordic basis in order to ensure competence at all Institutes of Technology, all Business Schools and other education bodies of importance for risk management.
|
|
| 3. |
- McLean, Angela R., et al.
(författare)
-
A restatement of the natural science evidence base concerning the health effects of low-level ionizing radiation
- 2017
-
Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 284:1862
-
Forskningsöversikt (refereegranskat)abstract
- Exposure to ionizing radiation is ubiquitous, and it is well established that moderate and high doses cause ill-health and can be lethal. The health effects of low doses or low dose-rates of ionizing radiation are not so clear. This paper describes a project which sets out to summarize, as a restatement, the natural science evidence base concerning the human health effects of exposure to low-level ionizing radiation. A novel feature, compared to other reviews, is that a series of statements are listed and categorized according to the nature and strength of the evidence that underpins them. The purpose of this restatement is to provide a concise entree into this vibrant field, pointing the interested reader deeper into the literature when more detail is needed. It is not our purpose to reach conclusions on whether the legal limits on radiation exposures are too high, too low or just right. Our aim is to provide an introduction so that non-specialist individuals in this area (be they policy-makers, disputers of policy, health professionals or students) have a straightforward place to start. The summary restatement of the evidence and an extensively annotated bibliography are provided as appendices in the electronic supplementary material.
|
|
| 4. |
|
|
| 5. |
- Skiöld, Sara, et al.
(författare)
-
Radiation-induced stress response in peripheral blood of breast cancer patients differs between patients with severe acute skin reactions and patients with no side effects to radiotherapy
- 2013
-
Ingår i: Mutation research. Genetic toxicology and environmental mutagenesis. - : Elsevier BV. - 1383-5718 .- 1879-3592. ; 756:1-2, s. 152-157
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to compare the radiation-induced oxidative stress response in blood samples from breast cancer patients that developed severe acute skin reactions during the radiotherapy, with the response in blood samples from patients with no side effects. Peripheral blood was collected from 12 breast cancer patients showing no early skin reactions after radiotherapy (RTOG grade 0) and from 14 breast cancer patients who developed acute severe skin reactions (RTOG grade 3-4). Whole blood was irradiated with 0, 5 and 2000 mGy gamma-radiation and serum was isolated. The biomarker for oxidative stress, 8-oxo-dG, was analyzed in the serum by a modified ELISA. While a significant radiation-induced increase of serum 8-oxo-dG levels was observed in serum of the RTOG 0 patients, no increase was seen in serum of the RTOG 3-4 patients. The radiation induced increase in serum 8-oxo-dG levels after 5 mGy did not differ significantly from the increase observed for 2000 mGy in the RTOG 3-4 cohort, thus no dose response relation was observed. A receiver operating characteristic (ROC) value of 0.97 was obtained from the radiation-induced increase in 8-oxo-dG indicating that the assay could be used to identify patients with severe acute adverse reactions to radiotherapy. The results show that samples of whole blood from patients, classified as highly radiosensitive (RTOG 3-4) based on their skin reactions to radiotherapy, differ significantly in their oxidative stress response to ionizing radiation compared to samples of whole blood from patients with no skin reactions (RTOG 0). Extracellular 8-oxo-dG is primarily a biomarker of nucleotide damage and the results indicate that the patients with severe acute skin reactions differ in their cellular response to ionizing radiation at the level of induction of oxidative stress or at the level of repair or both.
|
|
| 6. |
- Skiöld, Sara, et al.
(författare)
-
Unique proteomic signature for radiation sensitive patients : a comparative study between normo-sensitive and radiation sensitive breast cancer patients
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Nearly every fourth person will be diagnosed with a cancer during their lifetime1 and approximately 50 percent of all cancers are treated with radiation therapy2. The therapy is adjusted to the most sensitive patients where 5 percent severe adverse acute healthy tissue effects are accepted. Twenty percent of all patients experience milder adverse effects from radiation therapy and there are indications that the patients with no signs of adverse effects have a higher probability of local reoccurrence of cancer within 5 years, indicating that they would have benefited from a higher dose of ionizing radiation (IR)3,4. If the individual radiation sensitivity could be determined before the start of radiation therapy, the dose could be personalized and the adverse effects reduced in sensitive patients. In addition, the probability to eradicate all cancer cells in normo-sensitive patients would increase. There is no generally accepted method available to diagnose radiation sensitivity before the start of the therapy and several studies on the mechanisms indicate that multifactorial mechanisms are involved.The long-term aim of this study is to identify biomarkers of radiation sensitivity to enable an individualized treatment. We have previously shown that radiation sensitive and normo-sensitive patients differ in their radiation induced 8-oxo-dG levels (a marker of oxidative stress). We hypothesized that this difference is due to different cellular capability to handle oxidative stress, were radiation sensitive patients doesn’t induce an oxidative stress response or are incapable of repairing oxidative stress related damages.To investigate the mechanisms behind radiation sensitivity 8 radiation sensitive (RTOG4) and 9 normo-sensitive (RTOG0) patients from a cohort of 2914 breast cancer patients with known normal tissue reactions after radiation therapy were selected. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 hour post-irradiation incubation at 37°C. The samples in the two groups were pooled to reduce individual variability not associated with radiation sensitivity responses. The protein expression profile of leukocytes was investigated with isotope-coded protein label (ICPL). First the differences in proteomic profiles of leukocytes isolated from normo-sensitive patients (RTOG 0) and extremely sensitive patients (RTOG 4) were investigated. Secondly, we analyzed leukocytes isolated from in vitro irradiated whole blood compared to non-irradiated whole blood within both groups. These two studies were done independent of each other using two different protein labeling methods.Here we show unique proteomic signatures separating the two groups both at the basal level (non-irradiated samples) and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity. Additionally the oxidative stress response can be linked mechanistically to our previous 8-oxo-dG study. Finally this investigation provides unique protein expression profiles which might be useful in future to predict radiation sensitivity.
|
|
| 7. |
- Skiöld, Sara, et al.
(författare)
-
Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients
- 2015
-
Ingår i: Mutation research. - : Elsevier BV. - 0027-5107 .- 1873-135X. ; 776, s. 128-135
-
Tidskriftsartikel (refereegranskat)abstract
- Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 degrees C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy.
|
|
