Manipulating Radiation-Sensitive Z-DNA Conformation for Enhanced Radiotherapy.

DNA double-strand breaks (DSBs) yield highly determines radiotherapy efficacy. However, improving the inherent radiosensitivity of tumor DNA to promote radiation-induced DSBs remains a challenge. Using theoretical and experimental models, the underexplored impact of Z-DNA conformations on radiosensitivity, yielding higher DSBs than other DNA conformations, is discovered. Thereout, a radiosensitization strategy focused on inducing Z-DNA conformation, utilizing CBL@HfO2 nanocapsules loaded with a Z-DNA inducer CBL0137, is proposed. A hollow mesoporous HfO2 (HM-HfO2) acts as a delivery and an energy depositor to promote Z-DNA breakage. The nanocapsule permits the smart DSBs accelerator that triggers its radiosensitization with irradiation stimulation. Impressively, the CBL@HfO2 facilitates the B-Z DNA conformational transition, augmenting DSBs about threefold stronger than irradiation alone, generating significant tumor suppression with a 30% cure rate. The approach enables DSBs augmentation by improving the inherent radiosensitivity of DNA. As such, it opens up an era of Z-DNA conformation manipulation in radiotherapy.

Impact of Practical Online Lessons on Chinese Medical Students' Perception of Radiation Oncology.

Radiotherapy is an essential component of oncology treatment. It is imperative that clinicians and medical students have a fundamental understanding of radiotherapy. However, radiation oncology education is deficient worldwide. This study introduced an hour-long online Massive Open Online Course (MOOC) as a supplement to the basic curriculum for 8-year medical students at Peking Union Medical College and Tsinghua University in China. The students' personal opinions and comprehension of radiation oncology therapy were assessed through pre- and post-test questionnaires before and after the MOOC study. The results indicated that the percentage of students interested in radiotherapy increased, and their knowledge of radiotherapy significantly improved after the online MOOC study, suggesting that short-term MOOC study may stimulate students' interest in learning and improving their knowledge of radiation therapy. The study suggests that the combination of online and offline teaching may be a feasible way to develop radiation oncology education in the future.

Radiotherapy for postoperative vaginal recurrences of cervical squamous cell carcinoma: analysis of dosing and prognosis.

Squamous cell carcinoma (SCC) is the most common type of vaginal recurrence in cervical cancer patients, and the role of salvage radiotherapy on these patients remains unclear. This study aimed to investigate the efficacy of salvage radiotherapy for vaginal recurrence of SCC in patients who previously underwent surgery and to explore prognostic factors associated with survival. Ninety-seven patients with histologically proven SCC who were treated for vaginal recurrence at Peking Union Medical College Hospital were identified. All patients had previously undergone surgery and received salvage radiotherapy. Factors predictive of overall survival (OS), progression-free survival (PFS), and local control (LC) were investigated. The median follow-up time was 42.5 months. The estimated 5-year OS, PFS, and LC rates were 84%, 79%, and 91%. On multivariate analysis, inguinal lymph node metastasis was significantly associated with poor OS; a tumour size ≤4 cm was associated with longer PFS (p < 0.05); the recurrence pattern was an independent predictor of LC (p < 0.05). In the 45 patients with recurrences that were paravaginal or invasive of surrounding organs, biologically equivalent doses in 2 Gy fractions of ≥72.6 Gy were independently predictive of longer LC (p < 0.05). RT is an effective treatment for postoperative vaginal recurrence in patients with cervical SCC. For patients with extravaginal recurrence, a salvage dose of ≥72.6 Gy appears to be optimal.Impact statementWhat is already known on this subject? Radiotherapy plays a critical role in treating recurrent cervical cancer, but the effectiveness of RT for vaginal recurrence in patients who previously underwent surgery remains limited. Few studies have focussed on the effect of RT dose on patient survival.What do the results of this study add? This study investigated the efficacy of RT in patients with cervical squamous cell carcinoma who experienced postoperative recurrence. Lymph node metastasis, tumour size and recurrence pattern were significantly associated with survival. Moreover, an EQD2 ≥ 72.6 Gy was independently predictive of longer LC.What are the implications of these findings for clinical practice and/or further research? RT is an effective treatment for postoperative vaginal recurrence in patients with cervical squamous cell carcinoma. For patients with extravaginal recurrence, a salvage dose of ≥72.6 Gy appears to be optimal.

Radiotherapy for Vaginal Recurrences of Cervical Cancer in Patients After Prior Surgery: Analysis of Effect and Prognostic Factors.

OBJECTIVE: The role of salvage radiotherapy (RT) in the treatment for vaginal recurrence of cervical cancer in patients after prior surgery remains controversial. The aim of this study was to evaluate the efficacy and toxicity of salvage RT and explore prognostic factors associated with the survival after recurrence. METHODS: Patients with cervical cancer, treated for vaginal recurrences at Peking Union Medical College Hospital between July 2011 and November 2019, were identified. All the patients underwent prior surgery for primary tumor and received salvage RT including external beam radiotherapy (EBRT), brachytherapy (BT), or both. The irradiation field and dose depended on the conditions of patients. Recurrence patterns were classified into four categories according to the site of recurrence. Prognostic factors on the overall survival (OS), progression-free survival (PFS), and local control (LC) were analyzed, and late toxicity was evaluated. RESULTS: A total of 141 patients were included in the analysis, with a median follow-up time of 40.8 months. The estimated 5-year OS, PFS, and LC rates were 81%, 75%, and 87%, respectively. In multivariate analysis, endovaginal recurrence and no irradiation history were favorable prognostic factors associated with OS (all p < 0.05), PFS (all p < 0.05), and LC (all p < 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) of the recurrence pattern is larger than the stage of primary tumor (0.734 vs. 0.670). CONCLUSIONS: RT was an effective treatment with tolerable toxicity for vaginal recurrences of cervical cancer in patients with prior surgery. Recurrence pattern and irradiation history were important prognostic factors.

Efficacy of adjuvant radiotherapy for treatment of adrenocortical carcinoma: a retrospective study and an updated meta-analysis.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy. Surgical resection is the standard treatment for localized ACC, but the local recurrence remains high. Adjuvant radiation (ART) has been proposed as a means to reduce recurrence rates in ACC after surgery with conflicting results from nonrandomized studies. We performed a retrospective study and a meta-analysis to determine the impact of ART on survival outcomes. METHODS: A retrospective study of the adrenocortical cancer database in Peking Union Medical College was conducted. We selected postoperative ACC patients with or without ART. A meta-analysis is also performed to compare the outcomes between ART and only surgical resection in ACC patients. The obtained data were analyzed using SPSS 23.0 and Stata 15.0 statistical software. Differences between two groups were compared using the log-rank test for retrospective analysis and estimated by calculating the odds ratio (OR) and 95% confidence interval (CI) for meta-analysis. RESULTS: Of a total of 75 patients available in the database, 12 patients underwent postoperative ART and were matched one to one to patients with only surgical resection. There was no significant difference on overall survival between ART group and control group (log-rank P = 0.149). Locoregional recurrence was diagnosed in 2 of the ART group, and in 4 of the control group (P = 0.64). A total of 238 participants were selected for the meta-analysis, of which 111 and 127 patients underwent ART after surgical resection and only surgical resection, respectively. Overall survival is significantly higher in ART group, with an odds ratio (OR) of 2.41 (95% CI of 1.33, 4.38; P = 0.004). Besides, meta-analysis significantly favored ART for locoregional recurrence-free survival and disease-free survival, with an OR of 4.08 and 2.27, respectively. CONCLUSIONS: Our results show that compared to only surgical resection, ART is an effective postoperative treatment for ACC.

Combining in Silico Tools with Multicriteria Analysis for Alternatives Assessment of Hazardous Chemicals: A Case Study of Decabromodiphenyl Ether Alternatives.

Alternatives assessment is applied for minimizing the risk of unintentionally replacing a hazardous chemical with another hazardous chemical. Central challenges are the diversity of properties to consider and the lack of high-quality experimental data. To address this, a novel alternatives assessment procedure was developed based on in silico data and multicriteria decision analysis (MCDA) methods. As a case study, 16 alternatives to the flame retardant decabromodiphenyl ether were considered. The hazard properties included persistence (P), bioaccumulation potential (B), toxicities (T), and mobility in water (M). Databases were consulted and 2866 experimental data points were collected for the target chemicals; however, these were mostly replicate data points for some hazard criteria for a subset of alternatives. Therefore, in silico data and three MCDA strategies were tested including heat mapping, multiattribute utility theory (MAUT), and Elimination Et Choix Traduisant la REalité (ELECTRE III). The heat map clearly showed that none of the target chemicals are hazard-free, whereas MAUT and ELECTRE III agreed on ranking the "least worst" choices. This study identified several challenges and the complexity in the alternatives assessment processes motivating more case studies combining in silico and MCDA approaches.

Structure-Dependent Activity of Polybrominated Diphenyl Ethers and Their Hydroxylated Metabolites on Estrogen Related Receptor γ: in Vitro and in Silico Study.

Estrogen-related receptor γ (ERRγ) is an orphan nuclear receptor having functional cross-talk with classical estrogen receptors. Here, we investigated whether ERRγ is a potential target of polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (OH-PBDEs). By using a fluorescence competitive binding method established in our laboratory, the binding potencies of 30 PBDEs/OH-PBDEs with ERRγ were determined for the first time. All of the tested OH-PBDEs and some PBDEs bound to ERRγ with Kd values ranging from 0.13-13.61 µM. The OH-PBDEs showed much higher binding potency than their parent PBDEs. A quantitative structure-activity relationship (QSAR) model was developed to analyze the chemical binding potencies in relation to their structural and chemical characteristics. The QSAR model indicated that the molecular size, relative ratios of aromatic atoms, and hydrogen bond donors and acceptors were crucial factors for PBDEs/OH-PBDEs binding. By using a reporter gene assay, we found that most of the low-brominated PBDEs/OH-PBDEs exerted agonistic activity toward ERRγ, while high-brominated PBDEs/OH-PBDEs had no effect on the basal ERRγ activity. The docking results showed that the low-brominated PBDEs/OH-PBDEs tended to take an agonistic binding mode while the high-brominated ones tended to take an antagonistic binding mode. Overall, our results suggest ERRγ to be a potential novel target for PBDEs/OH-PBDEs.