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Objective:To investigate the effect of ubiquitin binding enzyme 2T (UBE2T) on the radiosensitivity of lung adenocarcinoma and unravel its possible mechanism.Methods:A total of 45 patients pathologically diagnosed with different stages of lung adenocarcinoma and treated with radiotherapy in the Second Affiliated Hospital of Zunyi Medical University from March, 2019 to December, 2021 were enrolled, and the efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST1.1). All patients were divided into radiosensitive group ( n=25) and radioresistant group ( n=20). Radiosensitive group was complete remission (CR)+partial remission (PR), and radioresistant group was stable disease (SD) + progression disease (PD). Immunohistochemistry (IHC) was used to calculate the score based on the staining intensity and the number of positive cells. Chi-square test was combined to analyze the correlation between the expression level of UBE2T in paraffin specimens of lung adenocarcinoma patients and the radiosensitivity of patients. Lentivirus UBE2T-interfered (UBE2Tsh) A549 and UBE2T-overexpressed SPC-A-1 lung adenocarcinoma cells and their respective controls were constructed for irradiation and colony formation assay. The survivor fraction curve was fitted by single-hit multi-target model. The DNA double-strand break (DSB) marker γH2AX foci were detected by immunofluorescence (IF). The expression levels of UBE2T, γH 2AX and Rad51 proteins were detected by Western blot. Cell cycle and apoptosis rate of A549 were determined by flow cytometry. Binary variables were statistically analyzed by Fisher's exact probability method and measurement data were assessed by t-test. Results:High-expression level of UBE2T was correlated with the radiosensitivity of lung adenocarcinoma patients ( P<0.05). UBE2Tsh improved the radiosensitivity of A549 lung adenocarcinoma cells, and the sensitizing enhancement ratio (SER) was 1.795. UBE2T overexpression decreased the radiosensitivity of SPC-A-1 lung adenocarcinoma cells with an SER of 0.293. γH2AX foci number per cell were significantly increased in UBE2Tsh A549 cells after irradiation ( P<0.01) . Compared with the control group, the expression level of γH2AX protein was up-regulated ( P<0.01)and that of Rad51 protein was down-regulated in UBE2Tsh A549 cells after radiation ( P<0.001). Compared with the control group, the expression level of γH2AX protein was down-regulated ( P<0.05) and that of Rad51 protein was up-regulated in UBE2T overexpressed SPC-A-1 cells ( P<0.001). The proportion of UBE2Tsh A549 cells in G 2 phase was decreased ( P<0.01) and cell apoptosis was increased ( P<0.001). Conclusions:UBE2T might promote the radioresistance of lung adenocarcinoma cells by enhancing DNA DSB repair induced by radiotherapy, inducing cell cycle G 2 phase arrest, and reducing cell apoptosis.
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Radiotherapy is one of the most important methods in the treatment of malignant tumors. However, the decrease of radiosensitivity of tumor cells is the main reason affecting the efficacy of radiotherapy. Epithelial-mesenchymal transition (EMT) is a complex biological process that confers several characteristics necessary for the progression of malignant tumors, such as tumor initiation, aggressiveness, transmissibility, and tolerance to chemotherapy and radiotherapy. In addition, EMT can also be induced by radiation, which endows tumor cells with radiation resistance. Previous studies have shown that inhibition of EMT could enhance the radiosensitivity of tumor cells, but the overall understanding of the molecular mechanisms, key targets and pathways involved are still lacking. In this article, recent studies on the role of EMT in tumor radiation therapy were reviewed, focusing on the signaling pathway, EMT-induced transcription factors, aiming to deepen the understanding of the effect of EMT on the sensitivity of radiotherapy and provide ideas for improving the clinical therapeutic effect of radiotherapy.
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Objective To compare the difference in radiotherapy dose caused by different ways of adding bolus.Methods A total of 20 patients who needed to receive postmastectomy chest wall irradiation from October to December on 2014 were selected.Each patient underwent two CT scans;CT-1 was to perform CT scan directly without bolus, and CT-2 was to perform CT scan after adding bolus to the body surface.An equivalent bolus was added for CT-1 in the radiotherapy planning system, and Plan-1, which met the clinical requirements, was performed.Then Plan-1 was put on CT-2 through image fusion and plan verification to develop Plan-2, which was to develop plans with equivalent boluses at other times and perform radiotherapy with a bolus added to the surface of the body.At last, CT-2 was used to perform radiotherapy Plan-3, which met the clinical requirements.The paired t-test was used for comparison of clinical data between any two plans with SPSS 19.0.Results The V20 of the whole lung, V20 of the diseased lung, V30 of the heart, and Dmax of the healthy breast showed no significant differences across the three plans (P=0.074-0.871).The V50 , V55 , conformity index, and homogeneity index of the planning target showed significant differences across the three plans, and the total number of monitor units showed a significant difference between Plan-1 and Plan-2(P=0.002-0.049).The dose distribution in the target volume and the number of monitor units in each radiation field also showed significant differences.Conclusions When the equivalent bolus is added to the body surface before CT scan, such a plan can accurately reflect the dose distribution of the planning target and the dose to organs at risk.
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Objective To investigate Feining granule on prevention and treatment of rat with radiation-induced lung injur ( RILI) and its effect on cytokine transforming growth factor-β1(TGF-β1), interleukin-1 (IL-1), interleukin-6 (IL-6).Methods 105 SD female rats were selected, according to random number table, and divided into seven groups: normal group, model group, dexamethasone group(positive drug), Feining granule low-dose group (FN low-dose group), FN medial-dose group, FN high-dose group and FN prevention group, 15 rats in each group.Except for normal group, all remaining groups received the X-ray irradiation of 15Gy, DT30Gy/2f/1w.FN prevention group were intragastric infused with FN granule one week before irradiation, and the other groups 48 h after irradiation.Five rats were sacrificed randomly at 2, 4, 6 weeks respectively, and right lung tissues were taken out.The contents of TGF-β1, IL-1 and IL-6 were detected by immunohistochemical method.ResuIts TGF-β1, IL-1 and IL-6 contents in lung tissue of model group at 2, 4, 6 weeks were higher than those of normal group (P<0.05).The above indicators after treated by Feining granule were lower than those of model group at each time (P<0.05),with a concentration-dependence manner to some extent.The above indicators in FN high-, medial-and low-dose group were higher than those in dexamethasone group (P<0.05), to some extent.However, the above indicators in FN prevention group were lower than those in dexamethasone group ( P<0.05 ) .ConcIusion Feining granule could prevent and cure radiation induced lung injury through decreasing TGF-β1, IL-1 and IL-6 content.The efficacy of dexamethasone is stronger than FN treatment groups, but is weaker than FN prevention.
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Objective To investigate the efficacy and safety of three?dimensional radiotherapy (3DRT) with concurrent chemotherapy for stage IV non?small?cell lung cancer ( NSCLC). Methods A total of 198 eligible patients from 2008 to 2012 were enrolled as subjects. With an age ranging between 18 and 80 years and a Karnofsky Performance Status ( KPS) score of 70 or more, those patients had no contraindication for radiotherapy and chemotherapy, and were newly diagnosed with stage IV NSCLC confirmed by histology or cytology, as well as limited metastatic disease (≤3 organs). Survival rates and acute toxicities in those patients were evaluated. Results The 3?year follow?up rate was 98?? 5% and the 3?year sample size was 165. The median overall survival (OS) and progression?free survival (PFS) were 13?? 0 months (95% CI,11?? 7 ?14?? 3 months) and 9?? 0 months (95% CI,7?? 7 ?10?? 3 months), respectively, while the 1?, 2?, and 3?year OS rates were 53?? 5%, 15?? 8%, and 9?? 2%, respectively. Multivariate analysis showed that a primary tumor volume smaller than 134 cm3 , a stable or increased KPS score after treatment, and a radiation dose of 63 Gy or more were independent prognostic factors for longer survival time ( P=0?? 008;P= 0?? 010;P= 0?? 014). The incidence rates of grade 3?4 neutropenia, thrombocytopenia, anemia, grade 3 radiation esophagitis, and grade 3 radiation pneumonitis were 37?? 9%, 10?? 1%, 6?? 9%, 2?? 5%, and 6?? 6%, respectively. The main cause of death was distant metastasis, and only 10% of the patients died of recurrence alone. Conclusions 3DRT with concurrent chemotherapy achieves satisfactory treatment outcomes with tolerable toxicities for stage IV NSCLC. Primary tumor volume, change in the KPS score after treatment, and radiation dose are independent prognostic factors for OS.Clinical Trial Registry Chinese Clinical Reistry,registration number:ChiCTRC10001026.
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AIM:To investigate the antiemetic effect of preadministration of Banxia Fuling Capsule(Rhizoma Zingiberis recens,Rhizoma Pinelliae,Poria,etc)(BFC)in pigeons and dogs,and to explore the relationship between antiemetic effect of BFC and 5-hydroxytryptamine(5-HT).METHODS:The pigeons and dogs were pretreated with BFC for 3 days.Acute emesis of pigeons and dogs induced by intravenously injecting cisplatin were observed.The concentraction of 5-HT in the serum,small intestine and brainstem of the animals were determined by spectrofluorimetry.RESULTS:The number and incidence of the emesis decreased in the treatment of BFC in dogs and pigeons;The levels of 5-HT in brainstem and small intestine decreased in pigeons,and so was it in the serum of dogs.CONCLUSION:BFC may inhibit emesis induced by cisplatin in dogs and pigeons,the antiemetic effect of BFC may decrease the synthesis and release of 5-HT in brainstem and small intestine.