Background: Glioma stem cells (GSCs) are glioma cells with stemness and are responsible for a variety of malignant behaviors of glioma. Evidence has shown that signals from tumor microenvironment (TME) enhance stemness of glioma cells. However, identification of the signaling molecules and underlying mechanisms has not been completely elucidated. Methods: Human samples and glioma cell lines were cultured in vitro to determine the effects of adenovirus (ADV) infection by sphere formation, RT-qPCR, western blotting, FACS and immunofluorescence. For in vivo analysis, mouse intracranial tumor model was applied. Bioinformatics analysis, gene knockdown by siRNA, RT-qPCR and western blotting were applied for further mechanistic studies. Results: Infection of patient-derived glioma cells with ADV increases the formation of tumor spheres. ADV infection upregulated stem cell markers and in turn promoted the capacities of self-renewal and multi-lineage differentiation of the infected tumor spheres. These ADV infected tumor spheres had stronger potential to form xenograft tumors in immune-compromised mice. GSCs formation could be promoted by ADV infection via TLR9, because TLR9 was upregulated after ADV infection, and knockdown of TLR9 reduced ADV-induced GSCs. Consistently, MYD88, as well as total STAT3 and phosphorylated (p-)STAT3, were also upregulated in ADV-induced GSCs. Knockdown of MYD88 or pharmaceutical inhibition of STAT3 attenuated stemness of ADV-induced GSCs. Moreover, we found that ADV infection upregulated lncRNA NEAT1. Knockdown of NEAT1 impaired stemness of ADV-induced GSCs. Lastly, HMGB1, a damage associated molecular pattern (DAMP) that triggers TLR signaling, also upregulated stemness markers in glioma cells. Conclusion: ADV, which has been developed as vectors for gene therapy and oncolytic virus, promotes the formation of GSCs via TLR9/NEAT1/STAT3 signaling.

Background: Postoperative radiotherapy can significantly reduce keloid recurrence. However, consensus on the optimal radiotherapy dose and treatment schedule remains elusive. This study aims to evaluate the effectiveness of surgery followed by a short-course of radiotherapy administered every other day for keloid treatment. Materials/Methods: We conducted a retrospective analysis of 498 patients with keloids treated at our institution between January 2010 and December 2017. All patients underwent electron beam irradiation at a dose of 16 Gy, delivered in four fractions every other day, starting within 24 h post-surgery. The primary endpoint of the study was the local control rate. Results: A total of 130 (26.5%) keloids recurred after a median follow-up of 68.1months (42.6-129.9 months). The local control rates at 1 year, 3 years and 5 years for all patients were 89.5%, 82.5% and 81%, respectively. The highest recurrence rate was observed in keloids located in the chest region (50.8%), followed by the suprapubic (47.8%), head and neck (38.8%), limbs (33.3%) and ear (14%). Both multivariate and univariate analyses identified the presence of pain and or pruritus as an independently prognostic factor for keloid recurrence (p<0.0001). The local control rates at 1-year, 3-years and 5-years for patients with or without symptom of pain or pruritus were 45% vs. 98.8%, 12.5% vs. 95.9%, and 8.8% vs. 95%, respectively (HR:37.829, 95%CI: 24.385–58.686, p<0.001). In the ear keloid subgroup, the 1-year, 3-year and 5-year local control rates for patients with pruritus were significantly lower than those without pain or pruritus (60.0% vs. 97.9%, 26.7% vs. 94.7%, 26.7% vs. 94.3%, HR:30.209, 95% CI:14.793–61.69, p<0.001). The same results were found in other location(p<0.001). During treatment and follow-up, two patients experienced infections, and one patient developed a cutaneous fibroblastoma. Conclusion: This study suggests that a combination of surgery followed by short-course, every-other-day radiotherapy can yield satisfactory local control rates for keloids. Pain and or pruritus symptom was an independently prognostic factors for recurrence of keloid. To further validate these results, a prospective randomized controlled trial is recommended.

Background: Randomized controlled study was conducted to evaluate the efficacy of Sanyrene® vs. control intervention (DaBao®, a complex of hyaluronic acid and Vitamin E) for acute radiation dermatitis in patients receiving radiotherapy. Methods: Patients with breast cancer or head and neck cancer undergoing radiotherapy (≥ 50 Gy) were eligible. Participants were randomly assigned to either Sanyrene arm or control intervention arm in a ratio of 1:1. The primary endpoint was incidence rate of ≥ grade 2 radiation induced dermatitis. (Trial Registration: ChiCTR2100050910, registration date: 9/7/2021) Results: A total of 102 eligible patients were randomly assigned into the study. The rate of ≥ grade 2 radiation dermatitis was 22% in Sanyrene group, as compared with 67.3% in the control intervention group (P<0.001). The incidence of grade 3 radiation dermatitis was 20.4% and 8.0% in control intervention group and Sanyrene group, respectively (P = 0.076). Patients in Sanyrene group had a longer median time to reach ≥ grade 2 radiation dermatitis compared to these in control intervention group, with hazard ratio of 0.231 (95%CI:0.116–0.458, p < 0.001). Mean score of SD-16 were much higher in control intervention group than Sanyrene group at end of radiotherapy (25 vs.8.3), 2 weeks after radiotherapy (22.9 vs. 0.5) and 4 weeks after radiotherapy (4.2 vs.0), with significantly statistical difference between two groups. Conclusions: This trial suggests that Sanyrene is effective on preventing serious radiation dermatitis and improving skin related quality of life in patients with breast cancer or head and neck cancer receiving radiotherapy.

The aim of this study is to evaluate the effectiveness of a cervical muscle training intervention in decreasing setup errors in patients head and neck cancer (HNC) undergoing radiotherapy (RT). HNC patients opting for RT at our center. The patients were randomly allocated to either the muscle training group or the control group in a 1:1 ratio. The magnitude of the setup error was measured at the levels of the clivus, C4 and C7 vertebrae respectively. The Van Herk formula was used to determine appropriate planning target volume (PTV) margins. (Trial Registration: ChiCTR2000041009, registration date: 12/16/2020) A total of 221 patients were analyzed, with 109 assigned to the muscle training group and 112 enrolled in the control group. Compared with the control group, the setup errors in the X and Z direction of the clivus and the Z direction of C4 and C7 in the muscle training group were significantly lower (p = 0.031, < 0.001, < 0.001, < 0.001 respectively). The required PTV margins in the Z direction increased from 2.13 mm in the clivus to 3.63 mm in C7 in the muscle training group and from 2.89 mm in the clivus to 4.37 mm in C7 in the control group. Multivariate linear regression analysis demonstrated that the impact of neck muscle training, weight fluctuation, and cervical curvature on the setup error in the Z direction at C7 differed significantly (p = 0.000, 0.001, and 0.008, respectively). Neck muscle training can reduce setup errors and PTV margins in the anterior-posterior direction in patients undergoing RT for HNC.

Objectives: The role of induction chemotherapy (IC) remains ambiguous in a patient with T3-4N0-1 nasopharyngeal carcinoma (NPC) according to data from the endemic area of China. Here, we conducted a multicenter retrospective study to investigate the value of adding IC to concurrent chemoradiotherapy (CCRT) for T3-4N0-1 NPC from Northwest China. Methods: Data were extracted in 3 hospitals from Northwest China between May 1, 2010 and August 30, 2018. The Kaplan-Meier method was used to estimate the endpoints. Survival curves were compared using the log-rank test. Initial propensity matching was conducted with a 1:1 match of IC + CCRT to CCRT. The primary endpoint of this study was overall survival (OS). Results: A total of 108 patients with staging T3-4N0-1 were included in this study. The median follow-up time was 50 months (range: 6 to 118 months). IC followed by CCRT did not significantly improve OS compared with CCRT in the whole cohort (89.5% vs 77.6%, hazard ratio: 0.41, 95% CI: 0.16-1.04, P = 0.100). But significantly better OS was found when a well-balanced propensity score-matched cohort was analyzed. Adjusted 4-year OS was 89.5% for IC followed by CCRT versus 71.1% for CCRT (hazard ratio: 0.30, 95% CI: 0.11-0.80, P = 0.027). No significant differences were detected in side effects between the two groups. Conclusion: This study suggested IC followed by CCRT had the potential to further improve OS in patients with T3-4N0-1M0 NPC from Northwest China compared with CCRT. However, prospective studies with a large sample are warranted to confirm the results.