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Objective:To identify dose-volume parameters to predict the incidence of acute intestinal toxicity in cervical cancer patients after postoperative adjuvant radiotherapy.Methods:Clinical data of 93 cervical cancer patients who underwent postoperative adjuvant intensity-modulated radiotherapy (IMRT) were retrospectively evaluated. The dose-volume parameters comprised the absolute volume of the bowel receiving 5-45 Gy (5 Gy interval) radiation dose and the total volume of the bowel. The acute radiation-induced intestinal toxicity was evaluated by Radiation Therapy Oncology Group (RTOG) criteria. The association between the irradiated bowel volume and acute intestinal toxicity was analyzed.Results:A total of 26 (28%) patients experienced grade ≥2 acute intestinal toxicity. A strong relationship between grade ≥2 acute intestinal toxicity and the irradiated small bowel volume was observed at the total volume of small bowel, small bowel V 5 Gy, V 10 Gy and V 15 Gy (all P<0.05). Small bowel V 10 Gy ( HR=1.028, 95% CI, 0.993-1.062, P=0.029) and small bowel ?V 15 Gy( HR=0.991, 95% CI, 0.969-1.013, P=0.034)were the independent risk factors for evident acute intestinal toxicity. Conclusion:Dose-volume parameters of the small bowel can be used as predictors for the occurrence of grade ≥2 acute intestinal toxicity in cervical cancer patients undergoing postoperative adjuvant radiotherapy.
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Eigallocatechin gallate (EGCG) is the main component of catechins in green tea. It has many biological functions, such as neuroprotective, hypoglycemic, antioxidant, antibacterial, antiviral and anti-tumor effects, etc. It has been widely used in food additives and health products. Radiotherapy is one of the main methods for the treatment of malignant tumors. However, due to its damage to the normal tissues surrounding tumors, the therapeutic dose of radiotherapy is limited and the local control rate of tumors is affected. Therefore, it is of great practical significance to find a kind of radioprotective agent, which is highly effective and non-toxic and has the ability to limit tumor growth. This review summarizes relevant preclinical studies and clinical trial data to reveal the radiation protective mechanism of EGCG, aiming to provide some reference for EGCG to become a potential clinical radiation protection agent.
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Gut microbiota not only affects the activity of tryptophan metabolism rate limiting enzymes in intestinal cells, but also cooperatively produces a variety of catalytic enzymes, which directly affects the type and quantity of tryptophan metabolites in the intestine. Multiple tryptophan-associated indole compounds originating from the gut microbiome are significantly decreased in the peripheral blood of mice, and negatively correlated with radiation dose ranging from 2 to 10.4 Gy, which might be biomarkers for acute radiation-induced intestinal injury. Recent studies have reported that indole 3-propionic acid (IPA), indole-3-carboxaldehyde (I3A) and kynurenic acid (KYNA), which are tryptophan catabolites derived from gut microbiota, aryl hydrocarbon receptor, which is one of the receptors for tryptophan catabolites, and inhibition of indoleamine 2,3 dioxygenase-1, which is a main rate-limiting enzyme in intestinal tryptophan catabolism, can protect against radiation-induced intestinal toxicity. A more comprehensive understanding of the dynamics of tryptophan catabolites and their roles in acute radiation-induced intestinal injury is needed to deepen the understanding of the pathogenesis in radiation-induced intestinal injury and exploration of effective diagnostic and therapeutic approaches.
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Objective:To investigate the effect and mechanism of lysine acetyltransferase 5(KAT5) on the radio-sensitivity of anaplastic thyroid carcinoma (ATC).Methods:The expression levels of endogenous KAT5 in ATC and normal thyroid cells were detected by Western blot and qRT-PCR. The effect of KAT5 specific inhibitor NU9056 on the radio-sensitivity of human ATC cells and normal thyroid cells was evaluated by colony formation assay. TCGA database, JASPAR database, along with Western blot, microRNA sequencing, qRT-PCR and dual-luciferase reporter assay were conducted to unravel the underlying mechanism.Results:The expression of endogenous KAT5 at the protein and mRNA levels in human ATC cells was significantly higher than that in normal thyroid cells. NU9056 could significantly enhance the radiosensitivity of human ATC cells to 8505C and CAL-62, whereas showed no sensitization effect on normal thyroid cell Nthy-ori 3-1. Knockdown of KAT5 and NU9056 both down-regulated the expression level of miR-210 in the TC cells, while NU9056 decreased the expression level of transcription factor c-Myc. The putative binding sites of c-Myc in the miR-210 promoter region were predicted, and transfection of c-Myc plasmid significantly enhanced the luciferase activity of miR-210 promoter. Elevated miR-210 level was associated with worse survival of patients with thyroid carcinoma. Down-regulated expression of miR-210 decreased the TET2 mRNA level, while inhibition of miR-210 increased the TET2 mRNA level.Conclusion:The aberrantly-activated KAT5/miR-210/TET2 pathway probably causes the radioresistance of ATC, becoming a novel sensitizing target for ATC radiotherapy in clinical practice.
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Radiotherapy is an important component of multidisciplinary comprehensive treatment of malignant tumors. However, the existence of non-neoplastic complications may increase the acute and late adverse reactions of radiotherapy and affect the smooth implementation of radiotherapy. This paper reviews the effects of various common non-neoplastic complications (including diabetes, HIV infection, and inflammatory bowel disease) on radioactive normal tissue damage in tumor patients.
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Acute radiation-induced intestinal injury is the common complication in patients following abdominal and pelvic radiotherapy. However, no effective clinical prevention and treatment interventions are available. As the probiotics and symbiotic bacteria, many species of the genus Lactobacillus are normally present in the gastrointestinal tract and beneficial for the intestinal health. Preclinical studies have reported that the genus Lactobacillus can prevent and treat acute radiation-induced intestinal injury by protecting crypt stem cells, maintaining intestinal barrier and exerting the antioxidant effect, etc. Clinical trials have prompted that oral administration of adequate complex probiotics containing Lactobacillus spp.at one week before radiotherapy contributes to preventing radiation-induced diarrhea. In addition, oral intake of the genus Lactobacillus has the tendency to treat radiation-induced diarrhea and mitigate acute radiation proctitis. At present, no relevant adverse events have been reported.
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Recently,the relationship between intestinal flora and its metabolites and tumorigenesis,inflammatory bowel diseasesas well as radiation-induced intestinal injury has captivated widespread attention from researchers.Accumulated evidence derived from nuclear accident investigation,animal model experiment and clinical research has proven the role of intestinal flora and its metabolites as the biomarkers to evaluate the radiation dose and severity of radiation-induced intestinal injury.This article reviews the relationship between intestinal flora and its metabolites and radiation-induced intestinal injury,aiming to provide theoretical reference for assessing the risk of radiation-induced intestinal injury.
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Objective@#To evaluate the precision of image registration between MRI simulation (MRIsim) and CT simulation compared to diagnostic MRI(MRIdiag) and to provide information for further application of MRIsim.@*Methods@#A total of 24 patients who underwent both MRIsim and MRIdiag were enrolled, including 8 patients with gliomas, 8 with nasopharyngeal carcinomas and 8 with prostate cancers. MRIsim and MRIdiag images of each patient were fused with CT. The OARs were delineated on three modalities of images and targets were delineated on fusion image of MRIsim with CT (F_CTMsim) and fusion image of MRIdiag with CT (F_CTMdiag) respectively. The concordance index (CI), Dice′s similarity coefficient (DSC) between the OARs and image similarity index (S) based on images from MRIsim, MRIdiag and CT were evaluated. IMRT plans were designed based targets on F_CTMsim and OARs on CT images, and differences in dosimetry of targets and OARs were evaluated subsequently.@*Results@#Volumes of most OAR from three modalities of images showed no statistically significant difference(P>0.05). All the CI and DSC between the OARs derived from MRIsim and CT were higher than those corresponding values from MRIdiag, and a statistically significant difference was achieved in 50% of these OARs (t=2.58-5.47, P<0.05). The S values of MRIsim and MRIdiag compared with CT were 0.89 and 0.83 respectively (t=5.77, P<0.05). MRIsim improved the S value by 10% (2%-56%) compared with MRIdiag. No further differences in dosimetry were found on all OARs and all targets(P>0.05).@*Conclusions@#The precision of image registration can be significantly improved by introducing MRIsim into radiotherapy planning design compared with MRIdiag. However, no significant differences in dosimetry were found on targets produced by rigid registration and manual adjustment method .
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Objective@#To investigate the role of p75 neurotrophin receptor (p75NTR) in the irradiation-induced hippocampal neurogenesis impairment.@*Methods@#Thirty Sprague-Dawley rats were subject to whole brain irradiation with a single dose of 10 Gy 4 MeV electron beam. At 1 month after irradiation, the hippocampal tissues of the rats were collected. Western blot was used to detect the changes in the expression level of p75NTR protein. Immunofluorescence confocal laser microscopy was performed to observe the variations in the hippocampal neurogenesis. The stereotatic method was adopted for intra-hippocampal injection of AAV-shp75NTR to specifically knock out p75NTR.The relationship between p75NTR and hippocampal neurogenesis was analyzed.@*Results@#Western blot demonstrated that the expression of p75NTR protein was significantly up-regulated by 43.8% after irradiation (P<0.05). Immunofluorescent staining showed that the quantity of BrdU+ NeuN+ cells in rats was significantly decreased by 81.5% at 1 month after irradiation compared with that in the control group (P<0.01). After the specific knockout of p75NTR, hippocampal neurogenesis was obviously protected.@*Conclusion@#p75NTR plays a pivotal role in the irradiation-induced hippocampal neurogenesis impairment.
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Every stage of tumor initiation and development closely relates to immune regulation as tumor cells tend to evade attacks from immune system by employing the programmed death 1 (PD-1)/ programmed death-ligand 1 (PD-L1) interaction.Therefore,targeting the PD-1/PD-L1 pathway has become an attractive approach for cancer immunotherapy.Radiotherapy has long been considered a local tumor treatment modality and it is immune-inhibitory.However,accumulated evidence has shown that radiotherapy might enhance immune function by eliminating the tumor mass and has become a systemic tumor treatment modality.These observations indicate a strong rationale that the radiotherapy and anti-PD1 and anti-PD-L1 immunotherapy may work synergistically to provide a powerful anti-tumor effect.This review discusses current progresses,challenges and perspectives of this novel combination treatment modality.