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| 2. |
- Alevronta, Eleftheria, et al.
(författare)
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Dose-response relationships of the sigmoid for urgency syndrome after gynecological radiotherapy.
- 2018
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X .- 0284-186X. ; 57:10, s. 1352-1358
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Tidskriftsartikel (refereegranskat)abstract
- To find out what organs and doses are most relevant for 'radiation-induced urgency syndrome' in order to derive the corresponding dose-response relationships as an aid for avoiding the syndrome in the future.From a larger group of gynecological cancer survivors followed-up 2-14years, we identified 98 whom had undergone external beam radiation therapy but not brachytherapy and not having a stoma. Of those survivors, 24 developed urgency syndrome. Based on the loading factor from a factor analysis, and symptom frequency, 15 symptoms were weighted together to a score interpreted as the intensity of radiation-induced urgency symptom. On reactivated dose plans, we contoured the small intestine, sigmoid colon and the rectum (separate from the anal-sphincter region) and we exported the dose-volume histograms for each survivor. Dose-response relationships from respective risk organ and urgency syndrome were estimated by fitting the data to the Probit, RS, LKB and gEUD models.The rectum and sigmoid colon have steep dose-response relationships for urgency syndrome for Probit, RS and LKB. The dose-response parameters for the rectum were D50: 51.3, 51.4, and 51.3Gy, γ50=1.19 for all models, s was 7.0e-09 for RS and n was 9.9×107 for LKB. For Sigmoid colon, D50 were 51.6, 51.6, and 51.5Gy, γ50 were 1.20, 1.25, and 1.27, s was 2.8 for RS and n was 0.079 for LKB.Primarily the dose to sigmoid colon as well as the rectum is related to urgency syndrome among gynecological cancer survivors. Separate delineation of the rectum and sigmoid colon in order to incorporate the dose-response results may aid in reduction of the incidence of the urgency syndrome.
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| 3. |
- Boström, Martina, et al.
(författare)
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A role for endothelial cells in radiation-induced inflammation
- 2018
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Ingår i: International Journal of Radiation Biology. - : Informa UK Limited. - 0955-3002 .- 1362-3095. ; 94:3, s. 259-271
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To unravel the role of the vasculature in radiation-induced brain tissue damage.Materials and methods: Postnatal day 14 mice received a single dose of 10Gy cranial irradiation and were sacrificed 6h, 24h or 7 days post-irradiation. Endothelial cells were isolated from the hippocampus and cerebellum using fluorescence-activated cell sorting, followed by cell cycle analysis and gene expression profiling.Results: Flow cytometric analysis revealed that irradiation increased the percentage of endothelial cells, relative to the whole cell population in both the hippocampus and the cerebellum. This change in cell distribution indicates that other cell types are more susceptible to irradiation-induced cell death, compared to endothelial cells. This was supported by data showing that genes involved in endothelial cell-specific apoptosis (e.g. Smpd1) were not induced at any time point investigated but that genes involved in cell-cycle arrest (e.g. Cdkn1a) were upregulated at all investigated time points, indicating endothelial cell repair. Inflammation-related genes, on the other hand, were strongly induced, such as Ccl2, Ccl11 and Il6.Conclusions: We conclude that endothelial cells are relatively resistant to ionizing radiation but that they play an active, hitherto unknown, role in the inflammatory response after irradiation. In the current study, this was shown in both the hippocampus, where neurogenesis and extensive cell death after irradiation occurs, and in the cerebellum, where neurogenesis no longer occurs at this developmental age.
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| 4. |
- Bull, Cecilia, 1977, et al.
(författare)
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A novel mouse model of radiation-induced cancer survivorship diseases of the gut
- 2017
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Ingår i: American journal of physiology. Gastrointestinal and liver physiology. - : American Physiological Society. - 1522-1547 .- 0193-1857. ; 313:5, s. G456-G466
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Tidskriftsartikel (refereegranskat)abstract
- A deeper understanding of the radiation-induced pathophysiological processes that develop in the gut is imperative to prevent, alleviate, or eliminate cancer survivorship diseases after radiotherapy to the pelvic area. Most rodent models of high-dose gastrointestinal radiation injury are limited by high mortality. We therefore established a model that allows for the delivering of radiation in fractions at high doses while maintaining long-term survival. Adult male C57/BL6 mice were exposed to small-field irradiation, restricted to 1.5 cm of the colorectum using a linear accelerator. Each mouse received 6 or 8 Gy, two times daily in 12-h intervals in two, three, or four fractions. Acute cell death was examined at 4.5 h postirradiation and histological changes at 6 wk postirradiation. Another group was given four fractions of 8 Gy and followed over time for development of visible symptoms. Irradiation caused immediate cell death, mainly limited to the colorectum. At 6 wk postirradiation, several crypts displayed signs of radiation-induced degeneration. The degenerating crypts were seen alongside crypts that appeared perfectly healthy. Crypt survival was reduced after the fourth fraction regardless of dose, whereas the number of macrophages increased. Angiogenesis was induced, likely as a compensatory mechanism for hypoxia. Four months postirradiation, mice began to show radiation-induced symptoms, and histological examination revealed an extensive crypt loss and fibrosis. Our model is uniquely suitable for studying the long-term trajectory and underlying mechanisms of radiation-induced gastrointestinal injury. NEW & NOTEWORTHY A novel mouse model for studying the long-term trajectory of radiation-induced gut injury. The method allows for the use of high doses and multiple fractions, with minor impact on animal health for at least 3 mo. Crypt loss and a slow progression of fibrosis is observed. Crypt degeneration is a process restricted to isolated crypts. Crypt degeneration is presented as a convenient proxy endpoint for long-term radiation-induced gut injury.
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| 6. |
- Hedelin, Maria, 1964, et al.
(författare)
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Intake of citrus fruits and vegetables and the intensity of defecation urgency syndrome among gynecological cancer survivors.
- 2019
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite the experimental evidence that certain dietary compounds lower the risk of radiation-induced damage to the intestine, clinical data are missing and dietary advice to irradiated patients is not evidence-based.We have previously identified 28 intestinal health-related symptoms among 623 gynaecological-cancer survivors (three to fifteen years after radiotherapy) and 344 matched population-based controls. The 28 symptoms were grouped into five radiation-induced survivorship syndromes: defecation-urgency syndrome, fecal-leakage syndrome, excessive mucus discharge, excessive gas discharge and blood discharge. The grouping was based on factor scores produced by Exploratory Factor Analysis in combination with the Variable Cutoff Method. Frequency of food intake was measured by a questionnaire. We evaluated the relationship between dietary intake and the intensity of the five syndromes.With the exception of excessive mucus discharge, the intensity of all syndromes declined with increasing intake of citrus fruits. The intensity of defecation-urgency and fecal-leakage syndrome declined with combined intake of vegetables and citrus fruits. The intensity of excessive mucus discharge was increased with increasing intake of gluten.In this observational study, we found an association between a high intake of citrus fruits and vegetables and a lower intensity of the studied radiation-induced cancer survivorship syndromes. Our data suggest it may be worthwhile to continue to search for a role of the diet before, during and after radiotherapy to help the cancer survivor restore her or his intestinal health after irradiation.
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| 7. |
- Malipatlolla, Dilip, 1990, et al.
(författare)
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Long-term mucosal injury and repair in a murine model of pelvic radiotherapy
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Chronic intestinal injury after pelvic radiotherapy affects countless cancer survivors worldwide. A comprehensive understanding of the long-term injury dynamics is prevented in available animal models. With linear accelerators that are used to treat cancer in patients, we irradiated a small volume encompassing the colorectum in mice with four fractions of 8 Gy per fraction. We then determined the long-term dynamics of mucosal injury, repair, and the duration of inflammation. We show that crypt fission, not cell proliferation, is the main long-term mechanism for rescuing crypt density after irradiation, and provides a potentially wide window for clinical interventions. Persisting macrophage aggregations indicate a chronic mucosal inflammation. A better understanding as to how crypt fission is triggered and why it fails to repair fully the mucosa may help restore bowel health after pelvic radiotherapy. Moreover, anti-inflammatory interventions, even if implemented long after completed radiotherapy, could promote bowel health in pelvic cancer survivors.
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| 8. |
- Sjöberg, Fei, et al.
(författare)
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Elastase as a potential biomarker for radiation-induced gut wall injury of the distal bowel in an experimental mouse model
- 2018
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 57:8, s. 1025-1030
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Traditionally, elastase has been used to study exocrine activity of the pancreas in patients with chronic pancreatitis and cystic fibrosis, and calprotectin as a marker for gut-wall inflammation in patients with inflammatory bowel disease. The aim of the study was to find out whether elastase and calprotectin could be used as inflammatory markers for radiation-induced gut wall injury of the distal bowel.Material and methods: Adult male mice were exposed to two, three, or four fractions of 6Gy or 8Gy irradiation to the sigmoid and rectum of the large bowel, using a linear accelerator. Fecal samples were collected from mice at 1, 3, and 6 weeks post-irradiation. The fecal levels of elastase and calprotectin were analyzed using ELISA.Results: Three and 6 weeks after irradiation, we found a dose-effect relationship between dose of ionizing radiation and the fecal level of elastase; that is significantly higher levels of elastase were observed in mice that had received a high irradiation dose. We also found that irradiated mice hosted in the same cage had a comparable level (either high or low) of elastase. No significant differences were observed from the calprotectin data.Conclusions: We found a clear association between the dose of ionizing radiation to the distal colon and the level of elastase in the fecal samples.
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| 9. |
- Steineck, Gunnar, 1952, et al.
(författare)
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Contouring pudendal nerves.
- 2018
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 57:4, s. 438-439
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Steineck, Gunnar, 1952, et al.
(författare)
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Identifying radiation-induced survivorship syndromes affecting bowel health in a cohort of gynecological cancer survivors
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Steineck et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: During radiotherapy unwanted radiation to normal tissue surrounding the tumor triggers survivorship diseases; we lack a nosology for radiation-induced survivorship diseases that decrease bowel health and we do not know which symptoms are related to which diseases. Methods: Gynecological-cancer survivors were followed-up two to 15 years after having undergone radiotherapy; they reported in a postal questionnaire the frequency of 28 different symptoms related to bowel health. Population-based controls gave the same information. With a modified factor analysis, we determined the optimal number of factors, factor loadings for each symptom, factor-specific factor-loading cutoffs and factor scores. Results: Altogether data from 623 survivors and 344 population-based controls were analyzed. Six factors best explain the correlation structure of the symptoms; for five of these a statistically significant difference (P< 0.001, Mann-Whitney U test) was found between survivors and controls concerning factor score quantiles. Taken together these five factors explain 42 percent of the variance of the symptoms. We interpreted these five factors as radiation-induced syndromes that may reflect distinct survivorship diseases. We obtained the following frequencies, defined as survivors having a factor loading above the 95 percent percentile of the controls, urgency syndrome (190 of 623, 30 percent), leakage syndrome (164 of 623, 26 percent), excessive gas discharge (93 of 623, 15 percent), excessive mucus discharge (102 of 623, 16 percent) and blood discharge (63 of 623, 10 percent). Conclusion: Late effects of radiotherapy include five syndromes affecting bowel health; studying them and identifying the underlying survivorship diseases, instead of the approximately 30 long-term symptoms they produce, will simplify the search for prevention, alleviation and elimination.
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