Journal articles on the topic 'Radiation-induced tissue toxicity'
To see the other types of publications on this topic, follow the link: Radiation-induced tissue toxicity.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Radiation-induced tissue toxicity.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Lombardo, J., A. Shastri, M. Ambelil, T. DeAngelis, Y. Vinogradskiy, and N. L. Simone. "Caloric Restriction Decreases Radiation-Induced Normal Tissue Toxicity." International Journal of Radiation Oncology*Biology*Physics 114, no. 3 (November 2022): S65. http://dx.doi.org/10.1016/j.ijrobp.2022.07.453.
Full text
2
Larrey, Enoch K., and Rupak Pathak. "Radiation-Induced Intestinal Normal Tissue Toxicity: Implications for Altered Proteome Profile." Genes 13, no. 11 (November 2, 2022): 2006. http://dx.doi.org/10.3390/genes13112006.
Full textAbstract:
Radiation-induced toxicity to healthy/normal intestinal tissues, especially during radiotherapy, limits the radiation dose necessary to effectively eradicate tumors of the abdomen and pelvis. Although the pathogenesis of intestinal radiation toxicity is highly complex, understanding post-irradiation alterations in protein profiles can provide crucial insights that make radiotherapy safer and more efficient and allow for increasing the radiation dose during cancer treatment. Recent preclinical and clinical studies have advanced our current understanding of the molecular changes associated with radiation-induced intestinal damage by assessing changes in protein expression with mass spectrometry-based approaches and 2-dimensional difference gel electrophoresis. Studies by various groups have demonstrated that proteins that are involved in the inflammatory response, the apoptotic pathway, reactive oxygen species scavenging, and cell proliferation can be targeted to develop effective radiation countermeasures. Moreover, altered protein profiles serve as a crucial biomarkers for intestinal radiation damage. In this review, we present alterations in protein signatures following intestinal radiation damage as detected by proteomics approaches in preclinical and clinical models with the aim of providing a better understanding of how to accomplish intestinal protection against radiation damage.
3
Schlaak, Rachel A., Gopika SenthilKumar, Marjan Boerma, and Carmen Bergom. "Advances in Preclinical Research Models of Radiation-Induced Cardiac Toxicity." Cancers 12, no. 2 (February 11, 2020): 415. http://dx.doi.org/10.3390/cancers12020415.
Full textAbstract:
Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving RT. As the number of cancer survivors increases, the short- and long-term side effects of cancer therapy are of growing concern. Side effects of RT for thoracic tumors, notably cardiac and pulmonary toxicities, can cause morbidity and mortality in long-term cancer survivors. An understanding of the biological pathways and mechanisms involved in normal tissue toxicity from RT will improve future cancer treatments by reducing the risk of long-term side effects. Many of these mechanistic studies are performed in animal models of radiation exposure. In this area of research, the use of small animal image-guided RT with treatment planning systems that allow more accurate dose determination has the potential to revolutionize knowledge of clinically relevant tumor and normal tissue radiobiology. However, there are still a number of challenges to overcome to optimize such radiation delivery, including dose verification and calibration, determination of doses received by adjacent normal tissues that can affect outcomes, and motion management and identifying variation in doses due to animal heterogeneity. In addition, recent studies have begun to determine how animal strain and sex affect normal tissue radiation injuries. This review article discusses the known and potential benefits and caveats of newer technologies and methods used for small animal radiation delivery, as well as how the choice of animal models, including variables such as species, strain, and age, can alter the severity of cardiac radiation toxicities and impact their clinical relevance.
4
Popanda, Odilia, Jens Uwe Marquardt, Jenny Chang-Claude, and Peter Schmezer. "Genetic variation in normal tissue toxicity induced by ionizing radiation." Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 667, no. 1-2 (July 10, 2009): 58–69. http://dx.doi.org/10.1016/j.mrfmmm.2008.10.014.
Full text
5
Stojanovic-Rundic, Suzana, Vesna Plesinac-Karapandzic, Aleksandar Rankovic, Katarina Obradovic, Marko Dozic, Aleksandar Tomasevic, and Zoran Krivokapic. "Radiation induced toxicity in rectal cancer patients." Acta chirurgica Iugoslavica 63, no. 1 (2016): 33–41. http://dx.doi.org/10.2298/aci1601033s.
Full textAbstract:
Preoperative radiotherapy ? chemotherapy became the standard treatment for locally advanced rectal cancer. Despite better local control with this approach, there was not seen a significant improvement in overall survival and disease free survival, yet. The main disadvantage is toxicity that can be developed, especially concomitantly with chemotherapy. Toxicity can be acute and late. Acute complications are transitory, but late might lead to permanent damage and consequently are more significant for patients. Today, there are technical opportunities in reduction of acute and late radiation toxicity in the treatment of rectal cancer. With the implementation of 3D conformal radiotherapy (3D CRT) and intensity modulated radiation therapy (IMRT) techniques in clinical practice significant accuracy, better dose distribution and safety in the treatment of rectal cancer patients is achieved, with maximal sparing of surrounding normal tissue. Utilization of advanced techniques and new software solutions can keep adverse effects on satisfactory levels with excellent local control.
6
Ko, Dahui, Young Suk Kim, and Yunseon Choi. "Safety of radiotherapy in patients with Behcet’s disease: a case report and review of the literature." Journal of Medicine and Life Science 18, no. 2 (August 31, 2021): 35–39. http://dx.doi.org/10.22730/jmls.2021.18.2.35.
Full textAbstract:
Exaggerated acute and late toxicities following radiotherapy have been reported in patients with pre-existing connective tissue diseases, such as systemic lupus and scleroderma. Behcet’s disease (BD) is a relapsing multisystem connective tissue disease characterized by vasculitis in the mucocutaneous, ocular, gastrointestinal, respiratory, neurologic, urogenital, articular, and cardiovascular systems. Data concerning the relationship between radiotherapy toxicity and BD are limited in the literature. Here, we report a case of lung cancer treated with radiotherapy (60 Gy) in a patient with BD. No severe radiation-induced toxicity was observed. Radiation-induced toxicity in patients with BD has also been discussed.
7
Ivanov, Olivera, Aleksandra Milovančev, Borislava Petrović, Nataša Prvulović Bunović, Jelena Ličina, Marko Bojović, Ivan Koprivica, et al. "Ultra-Hypofractionated vs. Moderate Fractionated Whole Breast Three Dimensional Conformal Radiotherapy during the COVID-19 Pandemic." Medicina 58, no. 6 (May 30, 2022): 745. http://dx.doi.org/10.3390/medicina58060745.
Full textAbstract:
Background and Objectives: Reducing time of treatment during COVID-19 outbreaks has been recommended by the leading Radiation Oncology societies. Still minimizing radiation induced tissue toxicity is one of the most important issues in breast cancer patients. The study aimed to investigate compliance, clinical and dosimetry normal tissue toxicity, and cosmetic results between moderated and ultra-fractionated regimes for breast cancer patients during COVID-19 pandemic. Materials and Methods: This pilot prospective randomized study included 60 patients with early breast cancer after preserving surgery, 27 patients advocated to ultra-hypofractionated whole-breast three dimensional (3D) conformal radiotherapy of 26 Gy in 5 fractions over 1 week and 33 patients with moderate fractionated breast 3D conformal radiotherapy patients between March 2020 and July 2020, during the COVID pandemic outbreak. The compliance to treatment, dosimetric parameters, acute and late skin toxicity, subcutaneous tissue toxicity, cosmetic results and clinical follow up for 18 months for the two regimes were analyzed and compared. Results: When two regimes were compared 5 fraction group had significantly lower prevalence of newly infected cases of SARS-CoV-2 and thus delayed/interrupted treatment (p = 0.05), comparable grade 1 CTCAE v5, acute skin toxicity (p = 0.18), Grade 1 Radiation Morbidity Scoring Scheme (RESS) subcutaneous tissue toxicity (p = 0.18), Grade 1 RESS late skin toxicity (p = 0.88) and cosmetic results (p = 0.46). Dosimetric results reveled that patients in 5 fraction group received significantly lower median ipsilateral lung doses (p < 0.01) in addition to left breast cancer patients that received significantly lower median heart dose (p < 0.01) and median left anterior descending artery (LAD) dose (p < 0.01). Conclusion: Ultra-hypofractionated radiotherapy for breast cancer is comparable to moderate hypofractionation regimen regarding grade 1 acute skin toxicity, grade 1 subcutaneous tissue toxicity, late skin toxicity and cosmetic results. Application of ultra-hypofractionated radiotherapy with significantly lower radiation doses for lung and heart could be crucial in reducing the risk of acute/late pulmonary and heart radiation-induced toxicity.
8
Ghilotti, Marco, Marco Alessandro Pierotti, and Manuela Gariboldi. "Molecular markers for prediction of risk of radiation-related injury to normal tissue." Journal of Nucleic Acids Investigation 1, no. 1 (October 11, 2010): 11. http://dx.doi.org/10.4081/jnai.2010.2055.
Full textAbstract:
Radiotherapy is one of the most effective methods for the treatment of cancer, but occurrence of adverse reactions developing in the co-irradiated normal tissue can be a threat for patients. Identification of individuals at risk of severe reaction is very difficult and considerable efforts have been made to correlate normal tissue toxicity with cellular responses to ionizing radiation. Genetic markers enabling to identify hyper-sensitive patients prior to treatment would considerably improve its outcome. Gene association studies should help to identify such markers. Expression levels of specific transcripts could be putative markers; in fact different studies found associations between gene expression profiles in normal cells and the reaction of normal tissues to radiation therapy. The finding that ionizing radiation induces the deregulation of a high number of genes suggests that also microRNAs that affect the expression of a large number of target genes may be involved. This review briefly introduces the mechanisms of radiation-induced normal tissue toxicity and summarizes clinical research focused on the evaluation of molecular biomarkers for predicting risk of injury to normal tissue, mainly describing gene transcripts alterations.
9
Trappetti, Verdiana, Jennifer Fazzari, Cristian Fernandez-Palomo, Lloyd Smyth, Marine Potez, Nahoko Shintani, Bettina de Breuyn Dietler, Olga A. Martin, and Valentin Djonov. "Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner." Biomedicines 10, no. 4 (March 22, 2022): 735. http://dx.doi.org/10.3390/biomedicines10040735.
Full textAbstract:
Radiation therapy (RT) is a vital component of multimodal cancer treatment, and its immunomodulatory effects are a major focus of current therapeutic strategies. Macrophages are some of the first cells recruited to sites of radiation-induced injury where they can aid in tissue repair, propagate radiation-induced fibrogenesis and influence tumour dynamics. Microbeam radiation therapy (MRT) is a unique, spatially fractionated radiation modality that has demonstrated exceptional tumour control and reduction in normal tissue toxicity, including fibrosis. We conducted a morphological analysis of MRT-irradiated normal liver, lung and skin tissues as well as lung and melanoma tumours. MRT induced distinct patterns of DNA damage, reflecting the geometry of the microbeam array. Macrophages infiltrated these regions of peak dose deposition at variable timepoints post-irradiation depending on the tissue type. In normal liver and lung tissue, macrophages clearly demarcated the beam path by 48 h and 7 days post-irradiation, respectively. This was not reflected, however, in normal skin tissue, despite clear DNA damage marking the beam path. Persistent DNA damage was observed in MRT-irradiated lung carcinoma, with an accompanying geometry-specific influx of mixed M1/M2-like macrophage populations. These data indicate the unique potential of MRT as a tool to induce a remarkable accumulation of macrophages in an organ/tissue-specific manner. Further characterization of these macrophage populations is warranted to identify their organ-specific roles in normal tissue sparing and anti-tumour responses.
10
Kim, Jae Ho, Kenneth A. Jenrow, and Stephen L. Brown. "Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials." Radiation Oncology Journal 32, no. 3 (2014): 103. http://dx.doi.org/10.3857/roj.2014.32.3.103.
Full text
11
You, S. H., and S. Kim. "The Effect of Tissue Tension in Radiation-Induced Rectal Toxicity: Apoptosis and Fibrosis." International Journal of Radiation Oncology*Biology*Physics 105, no. 1 (September 2019): E658. http://dx.doi.org/10.1016/j.ijrobp.2019.06.1046.
Full text
12
Bhat, Kruttika, Paul Medina, Ling He, Le Zhang, Mohammad Saki, Angeliki Ioannidis, Nhan T. Nguyen, et al. "1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine treatment after brain irradiation preserves cognitive function in mice." Neuro-Oncology 22, no. 10 (April 15, 2020): 1484–94. http://dx.doi.org/10.1093/neuonc/noaa095.
Full textAbstract:
Abstract Background Normal tissue toxicity is an inevitable consequence of primary or secondary brain tumor radiotherapy. Cranial irradiation commonly leads to neurocognitive deficits that manifest months or years after treatment. Mechanistically, radiation-induced loss of neural stem/progenitor cells, neuroinflammation, and demyelination are contributing factors that lead to progressive cognitive decline. Methods The effects of 1-[(4-nitrophenyl)sulfonyl]-4-phenylpiperazine (NSPP) on irradiated murine neurospheres, microglia cells, and patient-derived gliomaspheres were assessed by sphere-formation assays, flow cytometry, and interleukin (IL)-6 enzyme-linked immunosorbent assay. Activation of the hedgehog pathway was studied by quantitative reverse transcription PCR. The in vivo effects of NSPP were analyzed using flow cytometry, sphere-formation assays, immunohistochemistry, behavioral testing, and an intracranial mouse model of glioblastoma. Results We report that NSPP mitigates radiation-induced normal tissue toxicity in the brains of mice. NSPP treatment significantly increased the number of neural stem/progenitor cells after brain irradiation in female animals, and inhibited radiation-induced microglia activation and expression of the pro-inflammatory cytokine IL-6. Behavioral testing revealed that treatment with NSPP after radiotherapy was able to successfully mitigate radiation-induced decline in memory function of the brain. In mouse models of glioblastoma, NSPP showed no toxicity and did not interfere with the growth-delaying effects of radiation. Conclusions We conclude that NSPP has the potential to mitigate cognitive decline in patients undergoing partial or whole brain irradiation without promoting tumor growth and that the use of this compound as a radiation mitigator of radiation late effects on the central nervous system warrants further investigation.
13
Li, Na, Kun Zhang, Xin Mu, Qiong Tian, Wenli Liu, Tianyuan Gao, Xiaona Ma, and Jian Zhang. "Astragalin Attenuates UVB Radiation-induced Actinic Keratosis Formation." Anti-Cancer Agents in Medicinal Chemistry 18, no. 7 (November 30, 2018): 1001–8. http://dx.doi.org/10.2174/1871520618666171229190835.
Full textAbstract:
Background: Actinic Keratosis (AK), is the most common precancerous skin lesion induced by the excessive Ultraviolet B (UVB) and is a significant threat to the public health. UVB exposure causes oxidative DNA damage and is considered to be a significant contributor to AK and subsequent development of skin cancer. Besides, activation of p38 MAPK also plays a significant role in the development of AK. Objective: This study aimed at the development of a nature compound which can inhibit UVB-induced AK. Method: MTS Cell Proliferation Assay Kit was used to detect the toxicity of astragalin. HE-staining, Immunohistochemical, Western blot and Enzyme Linked Immunosorbent Assay were applied to examine the clinicopathologic feature of AK and the change of p38 MAPK signal pathway treated with astraglin under the condition of UVB in vitro and in vivo. </P><P> Results：In our clinical findings revealed that p38 MAPK, phospho-MSK1, and γ -H2AX were significantly highly expressed in human AK tissue than the normal healthy skin tissue. Moreover, in vitro studies showed that UVB induced the phospho-MSK1 and γ-H2AX in a time- and dose-dependent manner in HaCaT cells. Further, in vitro kinase assay demonstrated that astragalin could directly bind to p38 MAPK and suppress p38 MAPK activity. Furthermore, astragalin exhibited no toxicity and suppressed the UVB-induced expression of phospho- MSK1 and γ -H2AX by suppressing p38 MAPK activity in a time-dependent and dose-dependent manner in HaCaT cells. The in vivo studies with animal UV model demonstrated that astragalin inhibited UVB-induced expression of phospho-MSK1 and γ-H2AX in Babl/c mice. Conclusion: These results suggested that p38 MAPK is a direct valid molecular target of astragalin for the attenuation of UVB-induced AK. Furthermore, astragalin could be a potential promising novel natural therapeutic agent for the prevention and management of UVB-induced AK with high target specificity and low toxicity.
14
Cunningham, Shannon, Shelby McCauley, Kanimozhi Vairamani, Joseph Speth, Swati Girdhani, Eric Abel, Ricky A. Sharma, et al. "FLASH Proton Pencil Beam Scanning Irradiation Minimizes Radiation-Induced Leg Contracture and Skin Toxicity in Mice." Cancers 13, no. 5 (March 1, 2021): 1012. http://dx.doi.org/10.3390/cancers13051012.
Full textAbstract:
Ultra-high dose rate radiation has been reported to produce a more favorable toxicity and tumor control profile compared to conventional dose rates that are used for patient treatment. So far, the so-called FLASH effect has been validated for electron, photon and scattered proton beam, but not yet for proton pencil beam scanning (PBS). Because PBS is the state-of-the-art delivery modality for proton therapy and constitutes a wide and growing installation base, we determined the benefit of FLASH PBS on skin and soft tissue toxicity. Using a pencil beam scanning nozzle and the plateau region of a 250 MeV proton beam, a uniform physical dose of 35 Gy (toxicity study) or 15 Gy (tumor control study) was delivered to the right hind leg of mice at various dose rates: Sham, Conventional (Conv, 1 Gy/s), Flash60 (57 Gy/s) and Flash115 (115 Gy/s). Acute radiation effects were quantified by measurements of plasma and skin levels of TGF-β1 and skin toxicity scoring. Delayed irradiation response was defined by hind leg contracture as a surrogate of irradiation-induced skin and soft tissue toxicity and by plasma levels of 13 different cytokines (CXCL1, CXCL10, Eotaxin, IL1-beta, IL-6, MCP-1, Mip1alpha, TNF-alpha, TNF-beta, VEGF, G-CSF, GM-CSF and TGF- β1). Plasma and skin levels of TGF-β1, skin toxicity and leg contracture were all significantly decreased in FLASH compared to Conv groups of mice. FLASH and Conv PBS had similar efficacy with regards to growth control of MOC1 and MOC2 head and neck cancer cells transplanted into syngeneic, immunocompetent mice. These results demonstrate consistent delivery of FLASH PBS radiation from 1 to 115 Gy/s in a clinical gantry. Radiation response following delivery of 35 Gy indicates potential benefits of FLASH versus conventional PBS that are related to skin and soft tissue toxicity.
15
Dennis-Little, Sarah G., Wilfred Ngwa, Marikki Laiho, Graham Warren, and Michael J. Yost. "Abstract 3319: Purified poloxamer 188 mitigates radiation-induced lung toxicity." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3319. http://dx.doi.org/10.1158/1538-7445.am2022-3319.
Full textAbstract:
Abstract The dose-limiting factor in radiation therapy (RT) is damage to healthy tissues, which presents as radiation-induced lung toxicity (RILT). Acute RILT, pneumonitis, is an early inflammatory-driven toxicity that develops within weeks to months following RT. Purified poloxamer 188 (PP188) is a triblock copolymer that associates with and protects cell membranes from oxidative insult, minimizing secondary inflammatory damage. This study aimed to investigate the effects of PP188 to mitigate the onset of acute radiation pneumonitis in a rat model of RILT, and to test the effect of PP188 on the efficacy of RT on tumor growth of a syngeneic CT26.WT murine colon carcinoma in Balb/c mice. To evaluate the efficacy of PP188 to mitigate RILT in healthy tissues, Sprague Dawley rats were given 200mg/kg PP188 or vehicle via IV 1hr prior to a single dose of partial volume (6mm) 20Gy X-irradiation to the right lung, and then were followed for 6 weeks. To validate PP188 treatment does not interfere with RT efficacy to reduce tumor volume, Balb/c mice were implanted with CT26.WT murine colon adenocarcinoma in the high axilla space, given 5Gy SARRP irradiation, and tumor volume was monitored. Rats were evaluated for histopathological changes indicative of acute RILT, including leakage of proteins into alveolar space, thickening of alveolar septa, and alteration of bronchial epithelium and capillaries; for presence of inflammatory infiltrate (Hanker-Yates Peroxidase Leukocyte kit); and for immunohistochemical expression of alpha-smooth muscle actin (SMA). Without PP188, significant inflammatory infiltrate was observed in all lungs bilaterally (p<0.001) contributing to significant bronchiole epithelium thickening (p<0.001) and alveolar septa thickening (p<0.001). Within the thickened alveoli there was significant SMA expression (p<0.001) indicative of cells undergoing a myofibroblast transition that was not observed in the PP188+RT animals or controls. Morphological assessment demonstrated that PP188 significantly attenuated pathological changes in the functional subunits of the lung, alveoli, as well as the vasculature including bronchiole epithelium and small capillaries, with no significant differences from control animals. Finally, it was shown that PP188 does not abrogate radiation-induced tumor volume reduction. The unique mechanism of PP188 provides radioprotection to healthy tissue without interfering with tumor control, and has the potential to mitigate radiation-induced toxicities in the majority of cancers treated with RT. Citation Format: Sarah G. Dennis-Little, Wilfred Ngwa, Marikki Laiho, Graham Warren, Michael J. Yost. Purified poloxamer 188 mitigates radiation-induced lung toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3319.
16
Ali-Adeeb, Ramie N., Phil Shreeves, Xinchen Deng, Kirsty Milligan, Alex G. Brolo, Jullian J. Lum, Christina Haston, Jeffrey L. Andrews, and Andrew Jirasek. "Raman microspectroscopy and machine learning for use in identifying radiation-induced lung toxicity." PLOS ONE 17, no. 12 (December 30, 2022): e0279739. http://dx.doi.org/10.1371/journal.pone.0279739.
Full textAbstract:
Objective In this work, we explore and develop a method that uses Raman spectroscopy to measure and differentiate radiation induced toxicity in murine lungs with the goal of setting the foundation for a predictive disease model. Methods Analysis of Raman tissue data is achieved through a combination of techniques. We first distinguish between tissue measurements and air pockets in the lung by using group and basis restricted non-negative matrix factorization. We then analyze the tissue spectra using sparse multinomial logistic regression to discriminate between fibrotic gradings. Model validation is achieved by splitting the data into a training set containing 70% of the data and a test set with the remaining 30%; classification accuracy is used as the performance metric. We also explore several other potential classification tasks wherein the response considered is the grade of pneumonitis and fibrosis sickness. Results A classification accuracy of 91.6% is achieved on the test set of fibrotic gradings, illustrating the ability of Raman measurements to detect differing levels of fibrotic disease among the murine lungs. It is also shown via further modeling that coarser consideration of fibrotic grading via binning (ie. ‘Low’, ‘Medium’, ‘High’) does not degrade performance. Finally, we consider preliminary models for pneumonitis discrimination using the same methodologies.
17
Jiang, Yanyan, Jennifer Martin, Maryam Alkadhimi, Kay Shigemori, Paul Kinchesh, Stuart Gilchrist, Veerle Kersemans, et al. "Olaparib increases the therapeutic index of hemithoracic irradiation compared with hemithoracic irradiation alone in a mouse lung cancer model." British Journal of Cancer 124, no. 11 (March 19, 2021): 1809–19. http://dx.doi.org/10.1038/s41416-021-01296-y.
Full textAbstract:
Abstract Background The radiosensitising effect of the poly(ADP-ribose) polymerase inhibitor olaparib on tumours has been reported. However, its effect on normal tissues in combination with radiation has not been well studied. Herein, we investigated the therapeutic index of olaparib combined with hemithoracic radiation in a urethane-induced mouse lung cancer model. Methods To assess tolerability, A/J mice were treated with olaparib plus whole thorax radiation (13 Gy), body weight changes were monitored and normal tissue effects were assessed by histology. In anti-tumour (intervention) studies, A/J mice were injected with urethane to induce lung tumours, and were then treated with olaparib alone, left thorax radiation alone or the combination of olaparib plus left thorax radiation at 8 weeks (early intervention) or 18 weeks (late intervention) after urethane injection. Anti-tumour efficacy and normal tissue effects were assessed by visual inspection, magnetic resonance imaging and histology. Results Enhanced body weight loss and oesophageal toxicity were observed when olaparib was combined with whole thorax but not hemithorax radiation. In both the early and late intervention studies, olaparib increased the anti-tumour effects of hemithoracic irradiation without increasing lung toxicity. Conclusions The addition of olaparib increased the therapeutic index of hemithoracic radiation in a mouse model of lung cancer.
18
Callaghan, Cameron M., M. M. Hasibuzzaman, Samuel N. Rodman, Jessica E. Goetz, Kranti A. Mapuskar, Michael S. Petronek, Emily J. Steinbach, et al. "Neoadjuvant Radiotherapy-Related Wound Morbidity in Soft Tissue Sarcoma: Perspectives for Radioprotective Agents." Cancers 12, no. 8 (August 12, 2020): 2258. http://dx.doi.org/10.3390/cancers12082258.
Full textAbstract:
Historically, patients with localized soft tissue sarcomas (STS) of the extremities would undergo limb amputation. It was subsequently determined that the addition of radiation therapy (RT) delivered prior to (neoadjuvant) or after (adjuvant) a limb-sparing surgical resection yielded equivalent survival outcomes to amputation in appropriate patients. Generally, neoadjuvant radiation offers decreased volume and dose of high-intensity radiation to normal tissue and increased chance of achieving negative surgical margins—but also increases wound healing complications when compared to adjuvant radiotherapy. This review elaborates on the current neoadjuvant/adjuvant RT approaches, wound healing complications in STS, and the potential application of novel radioprotective agents to minimize radiation-induced normal tissue toxicity.
19
Giudici, Stefania, Francesca Maggio, Marco Bertocchi, Maria Rosaria Lucido, Renzo Corvò, and Marco Orsatti. "Topical natural-origin polynucleotides in radiation-induced skin and mucosal toxicity." Folia Medica 64, no. 5 (October 31, 2022): 716–24. http://dx.doi.org/10.3897/folmed.64.e66980.
Full textAbstract:
Seventy to 90 percent of patients who have received radiation treatment struggle with radiation skin and mucosal toxicity. The inflicted damage to progenitor cells and local microcirculation makes it more likely that wounds, infections, and fibrosis may occur; lesions of variable severity often co-exist. Acute erythema, hyperpigmentation, and mild desquamation usually wane in weeks and require only minor treatment. Conversely, the management of persistent radiation dermatitis and telangiectasia remains unsatisfactory; chronic lesions may progress to tissue atrophy and disfiguring fibrosis. Protrophic, natural-origin polynucleotides, formulated as Class III medical devices, have long shown to be a reliable topical option to stop the progression of radiation-related lesions. The present review illustrates the rationale of polynucleotides in skin and mucosal radiodermatitis management. It also illustrates the clinical results in a series of exploratory clinical studies carried out with polynucleotide devices over the last decade. The examined studies open the way to the high-level clinical research program, which will develop over the next years.
20
Schnarr, K., I. Dayes, J. Sathya, N. McFarlane, and D. Boreham. "59 Radiation — Induced apoptosis of lymphocytes to predict normal tissue late toxicity from radiotherapy." Radiotherapy and Oncology 76 (September 2005): S18. http://dx.doi.org/10.1016/s0167-8140(05)80220-8.
Full text
21
Eroglu, Celalettin, Oguz Galip Yildiz, Recep Saraymen, Serdar Soyuer, Eser Kilic, and Servet Ozcan. "Aminoguanidine ameliorates radiation-induced oxidative lung damage in rats." Clinical & Investigative Medicine 31, no. 4 (August 1, 2008): 182. http://dx.doi.org/10.25011/cim.v31i4.4778.
Full textAbstract:
Purpose: To investigate the possible protective effects of aminoguanidine (AG ) on lung damage in whole body irradiated rats. Methods: To evaluate the biological damage of radiation on rat lung tissue, lipid peroxidation products were measured using biochemical parameters. Thirty Wistar albino rats were divided into three subgroups: control (C) , irradiation alone (RT), and RT + AG combined. After sacrificing the rats, antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities and malondiadehyde (MDA), nitric oxide (NO) levels were evaluated in lung tissue. Results: Administration of AG resulted in an increase in the activities of CAT, SOD and GSHPx in the lungs. All were reduced after radiatio. In addition, AG administration resulted in a decrease in both NO and MDA levels in lung compared with the irradiated group. Conclusion: Amnoguanidine increased the endogenous antioxidant defence mechanism in rats and protected the animals from radiation-induced lung toxicity. Moreover, AG may protect against ionizing radiation-induced lung damage because of its antioxidant effect.
22
Konkol, Marek, Maciej Bryl, Marek Fechner, Krzysztof Matuszewski, Paweł Śniatała, and Piotr Milecki. "Normal Lung Tissue CT Density Changes after Volumetric-Arc Radiotherapy (VMAT) for Lung Cancer." Journal of Personalized Medicine 12, no. 3 (March 17, 2022): 485. http://dx.doi.org/10.3390/jpm12030485.
Full textAbstract:
Radiation-induced lung injury remains a significant toxicity in thoracic radiotherapy. Because a precise diagnosis is difficult and commonly used assessment scales are unclear and subjective, there is a need to establish quantitative and sensitive grading methods. The lung tissue density change expressed in Hounsfield units (HUs) derived from CT scans seems a useful numeric surrogate. The study aimed to confirm a dose-response effect on HU value changes (ΔHU), their evolution in time, and the impact of selected clinical and demographic factors. We used dedicated, self-developed software to register and analyze 120 pairs of initial and follow-up CT scans of 47 lung cancer patients treated with dynamic arc radiotherapy. The differences in HU values between CT scans were calculated within discretized dose-bins limited by isodose lines. We have proved the dose-effect relationship, which is well described with a sigmoid model. We found the time evolution of HU changes to suit a typical clinical presentation of radiation-induced toxicity. Some clinical factors were found to correlate with ΔHU degree: planning target volume (PTV), V35 in the lung, patient’s age and a history of arterial hypertension, and initial lung ventilation intensity. Lung density change assessment turned out to be a sensitive and valuable method of grading post-RT lung toxicity.
23
Wirsdörfer, Florian, Simone de Leve, and Verena Jendrossek. "Combining Radiotherapy and Immunotherapy in Lung Cancer: Can We Expect Limitations Due to Altered Normal Tissue Toxicity?" International Journal of Molecular Sciences 20, no. 1 (December 21, 2018): 24. http://dx.doi.org/10.3390/ijms20010024.
Full textAbstract:
In recent decades, technical advances in surgery and radiotherapy, as well as breakthroughs in the knowledge on cancer biology, have helped to substantially improve the standard of cancer care with respect to overall response rates, progression-free survival, and the quality of life of cancer patients. In this context, immunotherapy is thought to have revolutionized the standard of care for cancer patients in the long term. For example, immunotherapy approaches such as immune checkpoint blockade are currently increasingly being used in cancer treatment, either alone or in combination with chemotherapy or radiotherapy, and there is hope from the first clinical trials that the appropriate integration of immunotherapy into standard care will raise the success rates of cancer therapy to a new level. Nevertheless, successful cancer therapy remains a major challenge, particularly in tumors with either pronounced resistance to chemotherapy and radiation treatment, a high risk of normal tissue complications, or both, as in lung cancer. Chemotherapy, radiotherapy and immunotherapy have the capacity to evoke adverse effects in normal tissues when administered alone. However, therapy concepts are usually highly complex, and it is still not clear if combining immunotherapy with radio(chemo)therapy will increase the risk of normal tissue complications, in particular since normal tissue toxicity induced by chemotherapy and radiotherapy can involve immunologic processes. Unfortunately, no reliable biomarkers are available so far that are suited to predict the unique normal tissue sensitivity of a given patient to a given treatment. Consequently, clinical trials combining radiotherapy and immunotherapy are attracting major attention, not only regarding efficacy, but also with regard to safety. In the present review, we summarize the current knowledge of radiation-induced and immunotherapy-induced effects in tumor and normal tissue of the lung, and discuss the potential limitations of combined radio-immunotherapy in lung cancer with a focus on the suspected risk for enhanced acute and chronic normal tissue toxicity.
24
Maines, Lynn W., Randy S. Schrecengost, Yan Zhuang, Staci N. Keller, Ryan A. Smith, Cecelia L. Green, and Charles D. Smith. "Opaganib Protects against Radiation Toxicity: Implications for Homeland Security and Antitumor Radiotherapy." International Journal of Molecular Sciences 23, no. 21 (October 29, 2022): 13191. http://dx.doi.org/10.3390/ijms232113191.
Full textAbstract:
Exposure to ionizing radiation (IR) is a lingering threat from accidental or terroristic nuclear events, but is also widely used in cancer therapy. In both cases, host inflammatory responses to IR damage normal tissue causing morbidity and possibly mortality to the victim/patient. Opaganib, a first-in-class inhibitor of sphingolipid metabolism, has broad anti-inflammatory and anticancer activity. Opaganib elevates ceramide and reduces sphingosine 1-phosphate (S1P) in cells, conditions that increase the antitumor efficacy of radiation while concomitantly suppressing inflammatory damage to normal tissue. Therefore, opaganib may suppress toxicity from unintended IR exposure and improve patient response to chemoradiation. To test these hypotheses, we first examined the effects of opaganib on the toxicity and antitumor activity of radiation in mice exposed to total body irradiation (TBI) or IR with partial bone marrow shielding. Oral treatment with opaganib 2 h before TBI shifted the LD75 from 9.5 Gy to 11.5 Gy, and provided substantial protection against gastrointestinal damage associated with suppression of radiation-induced elevations of S1P and TNFα in the small intestines. In the partially shielded model, opaganib provided dose-dependent survival advantages when administered 4 h before or 24 h after radiation exposure, and was particularly effective when given both prior to and following radiation. Relevant to cancer radiotherapy, opaganib decreased the sensitivity of IEC6 (non-transformed mouse intestinal epithelial) cells to radiation, while sensitizing PAN02 cells to in vitro radiation. Next, the in vivo effects of opaganib in combination with radiation were examined in a syngeneic tumor model consisting of C57BL/6 mice bearing xenografts of PAN02 pancreatic cancer cells and a cross-species xenograft model consisting of nude mice bearing xenografts of human FaDu cells. Mice were treated with opaganib and/or IR (plus cisplatin in the case of FaDu tumors). In both tumor models, the optimal suppression of tumor growth was attained by the combination of opaganib with IR (± cisplatin). Overall, opaganib substantially protects normal tissue from radiation damage that may occur through unintended exposure or cancer radiotherapy.
25
Vinnikov, V. A., and T. V. Rubleva. "Predictors of radiation-induced complications in radiation oncology based on cell survival tests after ex vivo exposure: literature review." Український радіологічний та онкологічний журнал 29, no. 1 (March 29, 2021): 89–118. http://dx.doi.org/10.46879/ukroj.1.2021.89-118.
Full textAbstract:
Background. Among cancer patients receiving radiotherapy about 5–15 % may have adverse reactions in normal tissues and organs that limit their treatment in a full, originally scheduled regimen. The development of biomarkers and assays for radiation oncology allowing the prediction of patients’ normal tissue toxicity requires a lot of resourses, threfore its current status amd potential directions for future research have to be periodically analyzed and re-evaluated.
Purpose – this review summarizes the methodological approaches and developments in the area of functional laboratory assays based on ex vivo cell survival for the prediction of the individual clinical radiosensitivity.
Materials and methods. Data for the analysis and systematization were obtained from the full-text articles published in peer review international scientific journals (in English) in 1990–2020, which were selected by the extensive search in PubMed information database and cross references on the topic “Functional cellular tests for intrinsic radiosensitivity to predict adverse radiation effects and radiotherapy complications”.
Results. In theory, it might be expected that clonogenic cell survival after ex vivo irradiation can surve as the best individual predictor of radiation toxicity, as it is an integral indicator of cell damage and decline of their regenerative potential. Tendentially, fibroblasts, as a test system for such studies, did not show significant advantages over lymphocytes either in detecting inter-individual variations in the intrinsic cellular radiosensitivity or in predicting clinical radiation toxicity, even for that in skin. It was found that clonogenic cell survival assay, being very time consuming and technically demanding, also suffers from the lack of sensitivity and specificity, essential uncertainty and low reproducibility of the results, and thus is not suitable for the sceening for the abnormal intrinsic radiosensitivity. However, this type of assays is applicable for the radiobiological expertise post factum in individual cases with unexpected, extreme radiation lesions. Radiation-induced lymphocyte apoptosis assay seems to be more promising however still requires further fundamental research for better understanding of its background and more validation studies in order to assess the optimum patient groups, radiotherapy regimens and adverse effects for its confident use in clinical practice. Changes in the regulation of cell cycle check-points (radiationinduced delay) ex vivo can have either positive or inverted association, or no correlation with clinical radiation responses in tissues, thus so far cannot be included in the toolbox of applied radiobiological tests.
Conclusions. To date, in the practice of clinical radiobiology, there are no fully validated and standardized functional tests based on the cell survival after ex vivo irradiation, which would allow a sufficiently accurate prediction of adverse radiation effects in normal tissues of radiotherapy patients. In general, ex vivo tests based on the evaluation of only one form of cell death in one cell type are not fully reliable as a “stand alone” assay, because different pathways of cell death probably play different roles and show different dose response within the overal reaction of the irradiated tissue or critical organ. Such tests should become a part of the multiparametric predictive platforms.
26
Alexander, Matthew S., Justin G. Wilkes, Samuel R. Schroeder, Garry R. Buettner, Brett A. Wagner, Juan Du, Katherine Gibson-Corley, et al. "Pharmacologic Ascorbate Reduces Radiation-Induced Normal Tissue Toxicity and Enhances Tumor Radiosensitization in Pancreatic Cancer." Cancer Research 78, no. 24 (September 25, 2018): 6838–51. http://dx.doi.org/10.1158/0008-5472.can-18-1680.
Full text
27
Palma, G., A. Buonanno, S. Monti, R. Pacelli, and L. Cella. "A New Paradigm for Radiation-Induced Toxicity Analysis: Space Based Normal Tissue Complication Probability Modeling." International Journal of Radiation Oncology*Biology*Physics 102, no. 3 (November 2018): S96—S97. http://dx.doi.org/10.1016/j.ijrobp.2018.06.249.
Full text
28
Liu, Tian, Jun Zhou, Emi J. Yoshida, Shermian A. Woodhouse, Peter B. Schiff, Tony J. C. Wang, Zheng Feng Lu, Eliza Pile-Spellman, Pengpeng Zhang, and Gerald J. Kutcher. "Quantitative Ultrasonic Evaluation of Radiation-Induced Late Tissue Toxicity: Pilot Study of Breast Cancer Radiotherapy." International Journal of Radiation Oncology*Biology*Physics 78, no. 3 (November 2010): 811–20. http://dx.doi.org/10.1016/j.ijrobp.2009.08.071.
Full text
29
Wang, Junru, Christopher Albertson, Huaien Zheng, Louis Fink, Jean-Marc Herbert, and Martin Hauer-Jensen. "Short-Term Inhibition of ADP-Induced Platelet Aggregation by Clopidogrel Ameliorates Radiation-Induced Toxicity in Rat Small Intestine." Thrombosis and Haemostasis 87, no. 01 (2002): 122–28. http://dx.doi.org/10.1055/s-0037-1612954.
Full textAbstract:
SummaryEndothelial dysfunction and increased platelet aggregation may be involved in the pathogenesis of normal tissue radiation toxicity. This study assessed clopidogrel, an inhibitor of ADP-induced platelet aggregation, as a modulator of intestinal radiation injury (radiation enteropathy).Rat small intestine was exposed to 21 Gy X-radiation. Clopidogrel (20 mg/kg/day) or vehicle was administered from 2 days before to 10 days after irradiation. Structural radiation injury, neutrophil infiltration, smooth muscle cell proliferation, collagen content, and TGF-β1 expression were assessed 2 weeks (early phase) and 26 weeks (delayed phase) after irradiation, using quantitative histology and immunohistochemistry, morphometry, and real-time fluorogenic probe RT-PCR.Irradiated intestine exhibited significant histopathologic injury, reduced mucosal surface area, vascular sclerosis, intestinal wall fibrosis, increased collagen content, and increased TGF-β1 expression. Clopidogrel reduced ADP-induced platelet aggregation by 93% and significantly attenuated the severity of post-radiation vascular sclerosis (p = 0.004 and p = 0.02) and the loss of mucosal surface area (p = 0.0008 and p = 0.003) at both 2 and 26 weeks. Clopidogrel also ameliorated overall histopathologic injury (p = 0.02), relative intestinal collagen content (p = 0.03), and collagen III immunoreactivity levels 2 weeks after irradiation, and caused a borderline reduction in the radiation-induced increase in extracellular matrix-associated TGF-β immunoreactivity at 26 weeks (p = 0.04). The effects of clopidogrel on steady-state TGF-β1 mRNA levels and neutrophil infiltration were not statistically significant.Short-term clopidogrel administration affords protection against early and, to a lesser extent, delayed radiation enteropathy. Modulation of platelet aggregation should be subject to further studies as a potential method to increase safety and efficacy of radiation therapy.
30
Kordzińska-Cisek, Izabela, and Ludmiła Grzybowska-Szatkowska. "Complications of radio- and radiochemotherapy in patients undergoing major salivary gland cancer surgery." Otolaryngologia Polska 73, no. 3 (April 5, 2019): 26–31. http://dx.doi.org/10.5604/01.3001.0013.0508.
Full textAbstract:
Purpose: The aim of this retrospective study was to present the prevalence of early and late radiation-induced reaction and factors affecting its formation and severity in patients after adjuvant radio- or radiochemotherapy in salivary gland cancer. Material and methods: A total of 113 patients with early and 91 with late radiation-induced reaction, irradiated in 2006-2016 were enrolled in the study. The frequency of acute mucosal radiation-induced reaction, time of onset, intensity, healing time, as well as the incidence of late radiation-induced reaction from the skin and subcutaneous tissue were analyzed. Factors that could influence the development and intensity of reaction were identified. Results: Acute severity and the presence of late radiation-induced reaction do not affect overall survival. Dosage in the tumor bed site, as well as the dosage in the nodal region, affect the severity of the acute radiation-induced mucosal reaction. The severity of the early radiation-induced reaction is higher in men, more advanced patients (higher T and N+ in TNM classification), irradiated into a larger area, and those in whom two-dimensional planning and complementary chemoradiotherapy were applied. The late reaction of the skin and subcutaneous tissue was dominated by patients irradiated in the nodal regions and those with a higher intensity of early radiation-induced reaction. Conclusions: Supplementary radiotherapy or radiochemotherapy in salivary gland cancer is associated with acceptable toxicity which has no effect on overall survival.
31
Huang, Y., J. Sanz, N. Rodríguez, X. Duran, A. Martínez, X. Li, P. Foro, et al. "Quantitative assessments of late radiation-induced skin and soft tissue toxicity and correlation with RTOG scales and biological equivalent dose in breast cancer." Clinical and Translational Oncology 24, no. 5 (November 18, 2021): 836–45. http://dx.doi.org/10.1007/s12094-021-02729-z.
Full textAbstract:
Abstract Purpose Radiation-induced toxicity (RIT) is usually assessed by inspection and palpation. Due to their subjective and unquantitative nature, objective methods are required. This study aimed to determine whether a quantitative tool is able to assess RIT and establish an underlying BED-response relationship in breast cancer. Methods Patients following seven different breast radiation protocols were recruited to this study for RIT assessment with qualitative and quantitative examination. The biologically equivalent dose (BED) was used to directly compare different radiation regimens. RIT was subjectively evaluated by physicians using the Radiation Therapy Oncology Group (RTOG) late toxicity scores. Simultaneously an objective multiprobe device was also used to quantitatively assess late RIT in terms of erythema, hyperpigmentation, elasticity and skin hydration. Results In 194 patients, in terms of the objective measurements, treated breasts showed higher erythema and hyperpigmentation and lower elasticity and hydration than untreated breasts (p < 0.001, p < 0.001, p < 0.001, p = 0.019, respectively). As the BED increased, Δerythema and Δpigmentation gradually increased as well (p = 0.006 and p = 0.002, respectively). Regarding the clinical assessment, the increase in BED resulted in a higher RTOG toxicity grade (p < 0.001). Quantitative assessments were consistent with RTOG scores. As the RTOG toxicity grade increased, the erythema and pigmentation values increased, and the elasticity index decreased (p < 0.001, p = 0.016, p = 0.005, respectively). Conclusions The multiprobe device can be a sensitive and simple tool for research purpose and quantitatively assessing RIT in patients undergoing radiotherapy for breast cancer. Physician-assessed toxicity scores and objective measurements revealed that the BED was positively associated with the severity of RIT.
32
Hasan, Hesham, Noura Thabet, and Mohamed Abdel-Rafei. "Methanolic extract of Moringa oleifera leaf and low doses of gamma radiation alleviated amiodarone-induced lung toxicity in albino rats." Archives of Biological Sciences 68, no. 1 (2016): 31–39. http://dx.doi.org/10.2298/abs150729005h.
Full textAbstract:
This study aimed to evaluate the effects of methanolic extract of Moringa oleifera (MO) and/or low doses of gamma radiation (LDR) on amiodarone (AMD)-induced lung toxicity in rats. AMD administered to female albino rats (100 mg/kg body weight) for 10 consecutive days. Rats received methanolic extract of MO (250 mg/kg bwt) for 15 successive days and/or were exposed to whole body LDR (0.25Gy on the 1st and 10th days, up to a total dose of 0.5Gy). MO administration induced a significant decrease in serum tumor necrosis factor-alpha (TNF-?) and transforming growth factor-beta (TGF-?) levels as well as lactate dehydrogenase (LDH) activity. Also, the content of malondialdehyde (MDA) and hydroxyproline (HYP) was significantly decreased in lung tissue. Furthermore, MO significantly increased reduced glutathione (GSH) content in lung tissue as compared with AMD. The histopathological investigation of lung tissue revealed the appearance of interstitial pneumonia in rats treated with AMD. The oral administration of MO and/or exposure to LDR reversed the biochemical and histopathological alterations induced by AMD. It can be posited that MO and LDR might have a considerable role in the prevention of lung toxicity induced by AMD.
33
Najafi, Masoud, Mohsen Cheki, Gholamreza Hassanzadeh, Peyman Amini, Dheyauldeen Shabeeb, and Ahmed E. Musa. "Protection from Radiation-induced Damage in Rat’s Ileum and Colon by Combined Regimens of Melatonin and Metformin: A Histopathological Study." Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 19, no. 2 (June 8, 2020): 180–89. http://dx.doi.org/10.2174/1871523018666190718161928.
Full textAbstract:
Background: Radiation-induced enteritis and proctitis are common side effects of abdominopelvic cancers among patients that undergo radiotherapy for prostate, colorectal or urinary cancers. Exposure of these tissues to high doses of radiation leads to damage to villous, inflammation, pain, ulcer and bleeding, which may cause malabsorption and gastrointestinal disorders. To date, several procedures such as pharmaceutical treatment have been proposed for protection and mitigation of gastrointestinal toxicity following radiotherapy. Aims: In the current study, we aimed to investigate the possible radioprotection of ileum and colon in rats using a combination of melatonin and metformin. Methods: In this experimental study, 30 male Wistar rats were randomly assigned to six groups: control, melatonin (100 mg/kg) treatment, melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment, radiation (10 Gy to whole body) group, radiation + melatonin (100 mg/kg) treatment, and radiation + melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment. After 3.5 days, rats were sacrificed and their ileum and colon tissues carefully removed. Histopathological evaluations were conducted on these tissue samples. Results: Histological evaluations reported moderate to severe damages to ileum and colon following whole body irradiation. Melatonin administration was able to protect the ileum remarkably, while the combination of melatonin and metformin was less effective. Interestingly, for the colon, melatonin was less effective while its combination with metformin was able to protect against radiation toxicity completely. Conclusion: For the ileum, melatonin was a more effective radioprotector compared to its combination with metformin. However, the combination of melatonin and metformin can be proposed as an ideal radioprotector for the colon.
34
Kimler, Bruce F., Changnian Liu, Richard G. Evans, and Robert A. Morantz. "Effect of pentobarbital on normal brain protection and on the response of 9L rat brain tumor to radiation therapy." Journal of Neurosurgery 79, no. 4 (October 1993): 577–83. http://dx.doi.org/10.3171/jns.1993.79.4.0577.
Full textAbstract:
✓ The authors attempted to confirm published reports that pentobarbital protects against radiation-induced damage to normal rat brain, as well as enhances radiotherapeutic efficacy in a rat brain tumor model. They evaluated animal survival in 9L gliosarcoma-burdened rats that received whole-brain radiation therapy (16, 24, 32, or 40 Gy) while under intraperitoneal pentobarbital (60 mg/kg) or intramuscular ketamine (60 mg/kg) sedation. The animals were examined at autopsy to attribute death to either intracranial tumor growth or normal brain toxicity in the absence of discernible tumor. There was no difference between the two anesthesia groups regarding the survival of unirradiated animals. Radiation therapy produced a significant dose-dependent prolongation in animal survival, which was limited by the development of normal tissue toxicity at the higher doses. When compared to ketamine anesthesia, pentobarbital anesthesia appeared to offer some protection (not statistically significant) against early (but not late) toxicity at selected radiation doses. A reduction in the number of deaths from tissue toxicity suggested an increased antitumor effect, but again this was not statistically significant. Only in one case was there even a marginal significant difference (p = 0.045) between overall therapeutic efficacy in rats sedated with pentobarbital versus ketamine. While there may be a radioprotective effect of pentobarbital in rat brains without intracranial tumor, there is no conclusive evidence for either radioprotection or significant improvement of radiotherapeutic efficacy in this 9L rat brain tumor model.
35
Kwak, Seo Young, Sunhoo Park, Hyewon Kim, Sun-Joo Lee, Won-Suk Jang, Min-Jung Kim, SeungBum Lee, et al. "Atorvastatin Inhibits Endothelial PAI-1-Mediated Monocyte Migration and Alleviates Radiation-Induced Enteropathy." International Journal of Molecular Sciences 22, no. 4 (February 12, 2021): 1828. http://dx.doi.org/10.3390/ijms22041828.
Full textAbstract:
Intestinal injury is observed in cancer patients after radiotherapy and in individuals exposed to radiation after a nuclear accident. Radiation disrupts normal vascular homeostasis in the gastrointestinal system by inducing endothelial damage and senescence. Despite advances in medical technology, the toxicity of radiation to healthy tissue remains an issue. To address this issue, we investigated the effect of atorvastatin, a commonly prescribed hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor of cholesterol synthesis, on radiation-induced enteropathy and inflammatory responses. We selected atorvastatin based on its pleiotropic anti-fibrotic and anti-inflammatory effects. We found that atorvastatin mitigated radiation-induced endothelial damage by regulating plasminogen activator inhibitor-1 (PAI-1) using human umbilical vein endothelial cells (HUVECs) and mouse model. PAI-1 secreted by HUVECs contributed to endothelial dysfunction and trans-endothelial monocyte migration after radiation exposure. We observed that PAI-1 production and secretion was inhibited by atorvastatin in irradiated HUVECs and radiation-induced enteropathy mouse model. More specifically, atorvastatin inhibited PAI-1 production following radiation through the JNK/c-Jun signaling pathway. Together, our findings suggest that atorvastatin alleviates radiation-induced enteropathy and supports the investigation of atorvastatin as a radio-mitigator in patients receiving radiotherapy.
36
de Leve, Simone, Florian Wirsdörfer, and Verena Jendrossek. "The CD73/Ado System—A New Player in RT Induced Adverse Late Effects." Cancers 11, no. 10 (October 16, 2019): 1578. http://dx.doi.org/10.3390/cancers11101578.
Full textAbstract:
Radiotherapy (RT) is a central component of standard treatment for many cancer patients. RT alone or in multimodal treatment strategies has a documented contribution to enhanced local control and overall survival of cancer patients, and cancer cure. Clinical RT aims at maximizing tumor control, while minimizing the risk for RT-induced adverse late effects. However, acute and late toxicities of IR in normal tissues are still important biological barriers to successful RT: While curative RT may not be tolerable, sub-optimal tolerable RT doses will lead to fatal outcomes by local recurrence or metastatic disease, even when accepting adverse normal tissue effects that decrease the quality of life of irradiated cancer patients. Technical improvements in treatment planning and the increasing use of particle therapy have allowed for a more accurate delivery of IR to the tumor volume and have thereby helped to improve the safety profile of RT for many solid tumors. With these technical and physical strategies reaching their natural limits, current research for improving the therapeutic gain of RT focuses on innovative biological concepts that either selectively limit the adverse effects of RT in normal tissues without protecting the tumor or specifically increase the radiosensitivity of the tumor tissue without enhancing the risk of normal tissue complications. The biology-based optimization of RT requires the identification of biological factors that are linked to differential radiosensitivity of normal or tumor tissues, and are amenable to therapeutic targeting. Extracellular adenosine is an endogenous mediator critical to the maintenance of homeostasis in various tissues. Adenosine is either released from stressed or injured cells or generated from extracellular adenine nucleotides by the concerted action of the ectoenzymes ectoapyrase (CD39) and 5′ ectonucleotidase (NT5E, CD73) that catabolize ATP to adenosine. Recent work revealed a role of the immunoregulatory CD73/adenosine system in radiation-induced fibrotic disease in normal tissues suggesting a potential use as novel therapeutic target for normal tissue protection. The present review summarizes relevant findings on the pathologic roles of CD73 and adenosine in radiation-induced fibrosis in different organs (lung, skin, gut, and kidney) that have been obtained in preclinical models and proposes a refined model of radiation-induced normal tissue toxicity including the disease-promoting effects of radiation-induced activation of CD73/adenosine signaling in the irradiated tissue environment. However, expression and activity of the CD73/adenosine system in the tumor environment has also been linked to increased tumor growth and tumor immune escape, at least in preclinical models. Therefore, we will discuss the use of pharmacologic inhibition of CD73/adenosine-signaling as a promising strategy for improving the therapeutic gain of RT by targeting both, malignant tumor growth and adverse late effects of RT with a focus on fibrotic disease. The consideration of the therapeutic window is particularly important in view of the increasing use of RT in combination with various molecularly targeted agents and immunotherapy to enhance the tumor radiation response, as such combinations may result in increased or novel toxicities, as well as the increasing number of cancer survivors.
37
Pickler, A., G. Mendes, T. Tanure, L. Serqueira, G. Sena, G. Fidalgo, M. Colaço, et al. "Elemental changes in heart and coronaries after breast cancer radiotherapy assessed by synchrotron radiation soft X-ray spectromicroscopy." Journal of Physics: Conference Series 2340, no. 1 (September 1, 2022): 012001. http://dx.doi.org/10.1088/1742-6596/2340/1/012001.
Full textAbstract:
Abstract Radiotherapy (RT) plays a pivotal role in the treatment of breast cancer (BC) and various thoracic malignancies. Radiation induced heart disease (RIHD) is one such long term toxicity which can offset the improvement in cancer specific mortality. Long term normal tissue toxicity is becoming a bigger concern, as early diagnosis and the improvement in the treatment of these cancers has led to patients surviving longer. Our research group on Physics applied to biomedical sciences has been investigating the side effects of BC treatment (RT and chemotherapy) for more than ten years. The cardiac regeneration has been studied to better understand the damage that occurs following radiation procedures in the heart tissue after many thoracic cancer treatments. One possible complication is coronary artery disease induced by irradiation after radiotherapy in thoracic area. Studies on the structures of cardiac tissue and the distribution of low atomic weight element can help to understand mechanisms associated with damage to healthy tissue, as these are of fundamental importance to metabolism in biological systems. The present study aimed to elucidate how radiotherapy in the thoracic area causes damage in the coronary artery, and to verify the potential use of losartan in reducing, or even preventing, the side effects of irradiation in this artery. To assess elemental and morphological differences in aortic and coronary samples, the Low Energy X-Ray Fluorescence (LEXRF) technique using Synchrotron Radiation was employed. SR- LEXRF and scanning transmission X-ray microscopy measurements were carried out at the beamline TwinMic at Elettra Sincrotrone Triste, Italy.
38
Mokaleng, B. B., and J. M. Akudugu. "Modulation of the sensitivity in Chinese hamster cells to photons and fast neutrons by cisplatin, vinblastine, and bleomycin." Canadian Journal of Physiology and Pharmacology 87, no. 5 (May 2009): 347–52. http://dx.doi.org/10.1139/y09-017.
Full textAbstract:
Normal tissue toxicity resulting from chemoradiotherapy is of significant clinical concern. This study used normal Chinese hamster fibroblasts from lung (V79) and ovary (CHO-K1) to assess the modulation of cellular response to photons and neutrons by cisplatin, vinblastine, and bleomycin. Based on the colony formation assay, the drug concentration corresponding to 50% cell survival (EC50) of V79 cells was 1.50 ± 0.21 µmol/L for cisplatin, 0.97 ± 0.06 nmol/L for vinblastine, and 1.68 ± 0.11 µmol/L for bleomycin. The corresponding values for CHO-K1 cells were significantly lower for vinblastine (0.54 ± 0.02 nmol/L) and bleomycin (0.49 ± 0.13 µmol/L), but not for cisplatin (1.57 ± 0.20 µmol/L). No radiosensitivity enhancement was apparent when cells were exposed to p(66)/Be neutrons or photons (60Co γ-rays) in the presence of these drugs at EC50 concentrations. These data suggest that concurrent use of these drugs with radiation for the treatment of lung and ovarian diseases radiation does not exacerbate radiation-induced normal tissue toxicity, regardless of the quality of radiation. The relatively higher sensitivity of the ovarian cells to vinblastine and bleomycin might constitute a limitation in the use of these drugs for the treatment of lung lesions.
39
Zhao, Jing, Zheng Zhi, Ming Zhang, Qingxia Li, Jing Li, Xiao Wang, and Chunling Ma. "Predictive value of single nucleotide polymorphisms in XRCC1 for radiation-induced normal tissue toxicity." OncoTargets and Therapy Volume 11 (July 2018): 3901–18. http://dx.doi.org/10.2147/ott.s156175.
Full text
40
Zhou, J., P. Zhang, S. Woodhouse, P. Schiff, L. Ballas, G. Kutcher, and T. Liu. "TH-D-AUD C-02: Reliability Study of Ultrasound Tissue Characterization in Quantitative Measurement of Radiation-Induced Breast Tissue Toxicity." Medical Physics 35, no. 6Part27 (June 2008): 2986–87. http://dx.doi.org/10.1118/1.2962914.
Full text
41
Raman Ponna, Dulasi, Yumkhaibam Sobita Devi, Kishalay Baidya, Laishram Jaichand Singh, Ningthoujam Dinita Devi, and Silchang K. Marak. "A COMPARATIVE STUDY ASSESSING THE DIFFERENT PATTERNS OF RADIATION REACTIONS IN HEAD AND NECKCANCER PATIENTS UNDERGOING RADIATION THERAPY AT DIFFERENT TIMES OF THE DAY-IN THE MORNING VERSUS EVENING." International Journal of Advanced Research 9, no. 07 (July 31, 2021): 284–91. http://dx.doi.org/10.21474/ijar01/13127.
Full textAbstract:
Background: Human oral mucosa, is a prime target for radiation induced toxicity in patients undergoing radiotherapy for head and neck cancer. The oral cavity is highly susceptible to direct and indirect toxic effects of cancer chemotherapy and ionizing radiation. In our study we investigated the role of chronotherapy with respect to radiation induced mucositis occurring in the normal oral mucosa and treatment response in tumor tissue in cancer patients undergoing radiation therapy to head and neck region. Materials and Methods: This non-randomized clinical study was done to compare the two different timing schedules in the management of head and neck cancer by external beam radiation therapy by cobalt-60 (Theratron780C). In morning arm (arm A), Patients received external beam radiotherapy (EBRT) by cobalt-60 with SSD of 80cm with daily fractions, five days a week, between 8AM–10 AM whereas in evening arm (arm B), patients received EBRT by cobalt-60 with daily fractions, five days a week, between 3PM–5 PM. Both the arms received same radiation regimen. Results: The study concluded that in the morning arm the onset of oral mucositis was observed to be significantly delayed and the duration of mucositis was also significantly shorter as compared to the evening arm. Statistically significant difference in severity of mucositis was found between the two arms. Conclusion: Since there is no active measure to minimize normal tissue toxicity, chronomodulated radiotherapy would be a feasible and cost effective treatment strategy that can be put into clinical practice.
42
Okunieff, Paul, Elizabeth Augustine, Jeanne E. Hicks, Terri L. Cornelison, Rosemary M. Altemus, Boris G. Naydich, Ivan Ding, et al. "Pentoxifylline in the Treatment of Radiation-Induced Fibrosis." Journal of Clinical Oncology 22, no. 11 (June 1, 2004): 2207–13. http://dx.doi.org/10.1200/jco.2004.09.101.
Full textAbstract:
Purpose Fibrotic sequelae remain the most important dose-limiting toxicity of radiation therapy to soft tissue. Functionally, this is reflected in loss of range of motion and muscle strength and the development of limb edema and pain. Tumor necrosis factor alpha and fibroblast growth factor 2 (FGF2), which are abnormally elevated in irradiated tissues, may mediate radiation fibrovascular injury. Patients and Methods In an open label drug trial, we studied the effects of pentoxifylline (400 mg orally tid for 8 weeks) on 30 patients who displayed late, radiation-induced fibrosis at 1 to 29 years posttreatment (40 to 84 Gy). The primary outcome measurement was change in physical impairments thought to be secondary to radiation, including active and passive range of motion (AROM and PROM), muscle strength, limb edema, and pain. Plasma levels of cytokines (tumor necrosis factor alpha and FGF2) also were measured. Twenty-seven patients completed baseline and 8-week assessments, and 24 patients completed baseline, 8-week, and 16-week assessments. Results After 8 weeks of pentoxifylline intervention, 20 of 23 patients with impaired AROM and 19 of 22 with impaired PROM improved; 11 of 19 patients with muscle weakness showed improved motor strength; five of seven patients with edema had decreased limb girth; and nine of 20 patients had decreased pain. Pretreatment FGF2 levels dropped from an average of 44.9 pg/mL to 24.0 pg/mL after 8 weeks of treatment. Conclusion Patients receiving pentoxifylline demonstrated improved AROM, PROM, and muscle strength and decreased limb edema and pain. Reversal of these delayed radiation effects was associated with a decrease in circulating FGF2.
43
Kilic, Diclehan, Seren Ozenirler, Ibrahim Egehan, and Ayse Dursun. "Sulfasalazine Decreases Acute Gastrointestinal Complications Due to Pelvic Radiotherapy." Annals of Pharmacotherapy 35, no. 7-8 (July 2001): 806–10. http://dx.doi.org/10.1345/aph.10055.
Full textAbstract:
BACKGROUND: Radiation-induced gastrointestinal toxicity is a significant concern for patients who are treated with this modality for pelvic malignancies. Eicosanoids and free radicals are thought to be among the reasons for this effect. Sulfasalazine is an inhibitor of their synthesis in the mucosa. OBJECTIVE: To determine whether sulfasalazine can reduce the radiation-induced acute gastrointestinal complications. METHODS: In this prospective, double-blind study, 31 patients receiving pelvic radiotherapy were randomized to receive two sulfasalazine 500-mg tablets twice daily or placebo, administered orally from the first day of irradiation. Patients were evaluated weekly, and gastrointestinal toxicities were graded according to the Late Effect of Normal Tissue — Subjective Objective Management Analytic (LENT-SOMA) toxicity table during pelvic radiotherapy. On the last day of week 5, the subjects were graded endoscopically, and biopsies taken from the rectum were classified histopathologically. RESULTS: Groups did not differ in age, gender, tumor site, or irradiation procedure. During radiotherapy, grade 2 or higher gastrointestinal toxicity occurred in 20% (3/15) and 63% (10/16) of the sulfasalazine and placebo groups, respectively. This difference was significant (p = 0.017). No statistically significant differences were found in endoscopic and histopathologic evaluations. CONCLUSIONS: Sulfasalazine is effective in decreasing clinically acute gastrointestinal toxicities. Long-term follow-up with the subjects will help to determine the net effect of sulfasalazine on the radiation-induced gastrointestinal injuries.
44
Yildiz, Oguz Galip, Serdar Soyuer, Recep Saraymen, and Celalettin Eroglu. "Protective effects of caffeic acid phenethyl ester on radiation induced lung injury in rats." Clinical & Investigative Medicine 31, no. 5 (October 1, 2008): 242. http://dx.doi.org/10.25011/cim.v31i5.4870.
Full textAbstract:
Purpose: The prevention of radiation-induced pulmonary toxicity may help to improve radiation therapy in the cancer patient. The aim of this study was to investigate the pulmonary protective effects of caffeic acid phenethyl ester (CAPE), an antioxidant, on radiation-induced lung injury in rats. Methods:30 Wistar albino rats were divided into three groups and treated with saline, Radiation (RT) and RT + CAPE respectively. All rats were treated with CAPE (50 ?mol/kg i.p.) or saline. The first dose of CAPE was injected 24 h before radiation and application continued daily, with radiation in second day and 2 days more after the radiation treatment. Radiation dose was 800 cGy for total body. At 72 hr after the last radiation application, under general anesthesia using ip ketamine, the lungs were removed immediately after decapitation. After sacrification, antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) activities and malondiadehyde (MDA) levels were evaluated in lung tissue. Results: The level of malondialdehyde (MDA) was higher in the RT group (233.4±1.5 nmol/g protein) than in both the control (131.8±0.92) and the RT + CAPE (151.4±1.8) groups (P < 0.001). However, CAT activity was decreased in the RT group (7.26±0.27 Umg protein) compared with control (8.49±0.51) and increased again in the RT + CAPE group (8.31±0.56; P < 0.001). In accord with CAT activity, SOD activity in the RT group (0.42±0.07 nmolMDA/g wet tissue) was different from the control (0.78±0.02) and RT + CAPE (0.86±0.06) groups (P < 0.001). Conclusion: CAPE aplication with radiation therapy attenuated radiation induced pulmonary injury in vivo, possibly by its antioxidant effect.
45
Jang, Hyosun, Seo-Young Kwak, Sunhoo Park, Kyuchang Kim, Young-heon Kim, Jiyoung Na, Hyewon Kim, et al. "Pravastatin Alleviates Radiation Proctitis by Regulating Thrombomodulin in Irradiated Endothelial Cells." International Journal of Molecular Sciences 21, no. 5 (March 10, 2020): 1897. http://dx.doi.org/10.3390/ijms21051897.
Full textAbstract:
Although radiotherapy plays a crucial in the management of pelvic tumors, its toxicity on surrounding healthy tissues such as the small intestine, colon, and rectum is one of the major limitations associated with its use. In particular, proctitis is a major clinical complication of pelvic radiotherapy. Recent evidence suggests that endothelial injury significantly affects the initiation of radiation-induced inflammation. The damaged endothelial cells accelerate immune cell recruitment by activating the expression of endothelial adhesive molecules, which participate in the development of tissue damage. Pravastatin, a cholesterol lowering drug, exerts persistent anti-inflammatory and anti-thrombotic effects on irradiated endothelial cells and inhibits the interaction of leukocytes and damaged endothelial cells. Here, we aimed to investigate the effects of pravastatin on radiation-induced endothelial damage in human umbilical vein endothelial cell and a murine proctitis model. Pravastatin attenuated epithelial damage and inflammatory response in irradiated colorectal lesions. In particular, pravastatin improved radiation-induced endothelial damage by regulating thrombomodulin (TM) expression. In addition, exogenous TM inhibited leukocyte adhesion to the irradiated endothelial cells. Thus, pravastatin can inhibit endothelial damage by inducing TM, thereby alleviating radiation proctitis. Therefore, we suggest that pharmacological modulation of endothelial TM may limit intestinal inflammation after irradiation.
46
Miousse, Isabelle R., Laura E. Ewing, Charles M. Skinner, Rupak Pathak, Sarita Garg, Kristy R. Kutanzi, Stepan Melnyk, Martin Hauer-Jensen, and Igor Koturbash. "Methionine dietary supplementation potentiates ionizing radiation-induced gastrointestinal syndrome." American Journal of Physiology-Gastrointestinal and Liver Physiology 318, no. 3 (March 1, 2020): G439—G450. http://dx.doi.org/10.1152/ajpgi.00351.2019.
Full textAbstract:
Methionine is an essential amino acid needed for a variety of processes in living organisms. Ionizing radiation depletes tissue methionine concentrations and leads to the loss of DNA methylation and decreased synthesis of glutathione. In this study, we aimed to investigate the effects of methionine dietary supplementation in CBA/CaJ mice after exposure to doses ranging from 3 to 8.5 Gy of 137Cs of total body irradiation. We report that mice fed a methionine-supplemented diet (MSD; 19.5 vs. 6.5 mg/kg in a methionine-adequate diet, MAD) developed acute radiation toxicity at doses as low as 3 Gy. Partial body irradiation performed with hindlimb shielding resulted in a 50% mortality rate in MSD-fed mice exposed to 8.5 Gy, suggesting prevalence of radiation-induced gastrointestinal syndrome in the development of acute radiation toxicity. Analysis of the intestinal microbiome demonstrated shifts in the gut ecology, observed along with the development of leaky gut syndrome and bacterial translocation into the liver. Normal gut physiology impairment was facilitated by alterations in the one-carbon metabolism pathway and was exhibited as decreases in circulating citrulline levels mirrored by decreased intestinal mucosal surface area and the number of surviving crypts. In conclusion, we demonstrate that a relevant excess of methionine dietary intake exacerbates the detrimental effects of exposure to ionizing radiation in the small intestine. NEW & NOTEWORTHY Methionine supplementation, instead of an anticipated health-promoting effect, sensitizes mice to gastrointestinal radiation syndrome. Mechanistically, excess of methionine negatively affects intestinal ecology, leading to a cascade of physiological, biochemical, and molecular alterations that impair normal gut response to a clinically relevant genotoxic stressor. These findings speak toward increasing the role of registered dietitians during cancer therapy and the necessity of a solid scientific background behind the sales of dietary supplements and claims regarding their benefits.
47
Cargnin, Sarah, Nadia Barizzone, Chiara Basagni, Carla Pisani, Eleonora Ferrara, Laura Masini, Sandra D’Alfonso, Marco Krengli, and Salvatore Terrazzino. "Targeted Next-Generation Sequencing for the Identification of Genetic Predictors of Radiation-Induced Late Skin Toxicity in Breast Cancer Patients: A Preliminary Study." Journal of Personalized Medicine 11, no. 10 (September 27, 2021): 967. http://dx.doi.org/10.3390/jpm11100967.
Full textAbstract:
Normal tissue radiosensitivity is thought to be influenced by an individual’s genetic background. However, the specific genetic variants underlying the risk of late skin reactions following radiotherapy for breast cancer remain elusive. To unravel the genetic basis for radiation-induced late skin toxicity, we carried out targeted next-generation sequencing of germline DNA samples from 48 breast cancer patients with extreme late skin toxicity phenotypes, consisting of 24 cases with grade 2–3 subcutaneous fibrosis and/or grade 2–3 telangiectasia (LENT-SOMA scales) and 24 controls with grade 0 fibrosis and grade 0 telangiectasia. In this exploratory study, a total of five single-nucleotide variants (SNVs) located in three genes (TP53, ERCC2, and LIG1) reached nominal levels of statistical significance (p < 0.05). In the replication study, which consisted of an additional 45 cases and 192 controls, none of the SNVs identified by targeted NGS achieved nominal replication. Nevertheless, TP53 rs1042522 (G > C, Pro72Arg) in the replication cohort had an effect (OR per C allele: 1.52, 95%CI: 0.82–2.83, p = 0.186) in the same direction as in the exploratory cohort (OR per C allele: 4.70, 95%CI: 1.51–14.6, p = 0.007) and was found be nominally associated to the risk of radiation-induced late skin toxicity in the overall combined cohort (OR per C allele: 1.79, 95%CI: 1.06–3.02, p = 0.028). These results raise the possibility of an association between TP53 rs1042522 and risk of radiation-induced late skin toxicity in breast cancer patients; however, large replication studies are warranted for conclusive evidence.
48
Stick, Line Bjerregaard, Maria Fuglsang Jensen, Søren M. Bentzen, Claus Kamby, Anni Young Lundgaard, Maja Vestmø Maraldo, Birgitte Vrou Offersen, Jen Yu, and Ivan Richter Vogelius. "Radiation-Induced Toxicity Risks in Photon Versus Proton Therapy for Synchronous Bilateral Breast Cancer." International Journal of Particle Therapy 8, no. 4 (November 11, 2021): 1–13. http://dx.doi.org/10.14338/ijpt-21-00023.1.
Full textAbstract:
Abstract Purpose This study compares photon and proton therapy plans for patients with synchronous bilateral early breast cancer and estimates risks of early and late radiation-induced toxicities. Materials and Methods Twenty-four patients with synchronous bilateral early breast cancer receiving adjuvant radiation therapy using photons, 3-dimensional conformal radiation therapy or volumetric modulated arc therapy, were included and competing pencil beam scanning proton therapy plans were created. Risks of dermatitis, pneumonitis, acute esophageal toxicity, lung and breast fibrosis, hypothyroidism, secondary lung and esophageal cancer and coronary artery events were estimated using published dose-response relationships and normal tissue complication probability (NTCP) models. Results The primary clinical target volume V95% and/or nodal clinical target volume V90% were less than 95% in 17 photon therapy plans and none of the proton plans. Median NTCP of radiation dermatitis ≥ grade 2 was 18.3% (range, 5.4-41.7) with photon therapy and 58.4% (range, 31.4-69.7) with proton therapy. Median excess absolute risk (EAR) of secondary lung cancer at age 80 for current and former smokers was 4.8% (range, 0.0-17.0) using photons and 2.7% (range, 0.0-13.6) using protons. Median EAR of coronary event at age 80, assuming all patients have preexisting cardiac risk factors, was 1.0% (range, 0.0-5.6) with photons and 0.2% (range, 0.0-1.3) with protons. Conclusion Proton therapy plans improved target coverage and reduced risk of coronary artery event and secondary lung cancer while increasing the risk of radiation dermatitis.
49
Chacko, Tiju, Aditya Menon, Teeju Majeed, Sivaprabha V. Nair, Nithu Sara John, and Cherupally Krishnan Krishnan Nair. "Mitigation of whole-body gamma radiation–induced damages by Clerodendron infortunatum in mammalian organisms." Journal of Radiation Research 58, no. 3 (November 18, 2016): 281–91. http://dx.doi.org/10.1093/jrr/rrw093.
Full textAbstract:
Abstract Several phytoceuticals and extracts of medicinal plants are reported to mitigate deleterious effects of ionizing radiation. The potential of hydro-alcoholic extract of Clerodendron infortunatum (CIE) for providing protection to mice exposed to gamma radiation was investigated. Oral administration of CIE bestowed a survival advantage to mice exposed to lethal doses of gamma radiation. Radiation-induced depletion of the total blood count and bone marrow cellularity were prevented by treatment with CIE. Damage to the cellular DNA (as was evident from the comet assay and the micronucleus index) was also found to be decreased upon CIE administration. Radiation-induced damages to intestinal crypt cells was also reduced by CIE. Studies on gene expression in intestinal cells revealed that there was a marked increase in the Bax/Bcl-2 ratio in mice exposed to whole-body 4 Gy gamma radiation, and that administration of CIE resulted in significant lowering of this ratio, suggestive of reduction of radiation-induced apoptosis. Also, in the intestinal tissue of irradiated animals, following CIE treatment, levels of expression of the DNA repair gene Atm were found to be elevated, and there was reduction in the expression of the inflammatory Cox-2 gene. Thus, our results suggest a beneficial use of Clerodendron infortunatum for mitigating radiation toxicity.
50
Stanić, Jelena, Vesna Stanković, Snežana Voštinić, and Marina Nikitović. "Genetic predictors of radiation-induced morbidity in prostate cancer patients." Medicinski podmladak 73, no. 1 (2022): 1–6. http://dx.doi.org/10.5937/mp73-32951.
Full textAbstract:
Cancer survivors often face adverse effects of treatment, which have a significant impact on morbidity and mortality. Normal-tissue side effects following radiotherapy (RT), as one of therapeutic modalities, are common and may seriously affect quality of life which is especially important in long-term prostate cancer (PC) survivors. Upgrading in our knowledge in radiation biology have led to the better understanding that genetics plays a significant role in determining a patient's predisposition to developing late RT toxicity, leading to the new field of research called "radiogenomics". With the evolution of DNA sequencing technologies and genomic analysis, radiogenomics made an appearance as a state-of-the-art science in the field of personalized medicine with the goal of detection the genetic determinants RT adverse reactions. A single-nucleotide polymorphism (SNPs) - based assay could be used to predict the risk of RT side effects along with clinical features and treatment factors. Several SNPs have been identified that are associated with late radiation-induced morbidity in PC patients. Most importantly, these SNPs make up genes expressed in the tissues that are likely at the root of these symptoms, including the bladder, rectum, and small intestine, which are most exposed in PC RT. Furthermore, genome-wide association studies are likely to lead to an increasing number of genetic polymorphisms that can predict long-term RT complications. Finally, radiogenomics attempts to predict which PC patients will show radiosensitivity, so that radiation oncologists, as well as surgeons, can change treatment accordingly in order to reduce side effects or increase the RT effectiveness.