Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up.

OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

Gastrointestinal/genitourinary adverse event after intensity modulated versus three-dimensional primary radiation therapy in the treatment of prostate cancer: systematic review and meta-analysis.

Objective: Prostate cancer (PCa) is one of the most common cancers in the world. The potential benefits of intensity modulated radiation therapy (IMRT) over three-dimensional conformal radiation therapy (3D-CRT) for PCa primary radiation therapy treatment have not yet been clarified. Therefore, this meta-analysis was conducted to assess whether IMRT could improve clinical outcomes in comparison with 3D-CRT in patients diagnosed with PCa. Materials and methods: Relevant studies were identified through searching related databases till December, 2022. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses. Results: The incidence of grade 2 or worse acute adverse gastrointestinal (GI) event was analyzed and the pooled data revealed a clear decreasing trend in the IMRT compared with 3D-CRT (RR=0.62, 95% CI: 0.45-0.84, p=0.002). IMRT slightly increased the grade ≥ 2 acute genitourinary (GU) adverse event in comparison with the 3D-CRT (RR=1.10, 95% CI: 1.02-1.19, p=0.015). The IMRT and the 3D-CRT of patients showed no substantial differences in grade ≥ 2 late GI adverse event (RR =0.62, 95% CI: 0.36-1.09, p=0.1). In those included studies, there was no significant difference between IMRT and 3D-CRT in grade 2-4 late GU adverse event (RR =1.08, 95% CI: 0.77-1.51, p=0.65). There was a significant difference in biochemical control favoring IMRT (RR =1.13, 95% CI: 1.05-1.22, p=0.002). IMRT showed modest increase in biochemical control in comparison with 3D-CRT. Conclusion: In general, based on the above results, IMRT should be considered as a better choice for the treatment of PCa. More randomized controlled trials are needed to determine the subset of patients diagnosed with PCa.

Study on the application of 3D printing head film fixation technology in cranial radiotherapy.

Objective: To investigate the use of 3D printing technology to customize individualized precise radiotherapy head masks for cranial radiotherapy patients. Through the comparison with thermoplastic head film, evaluate the effect of this material on deep dose attenuation and body surface dose, and evaluate its positioning accuracy and repeatability for clinical application. Methods: Thirty patients with head and neck radiotherapy were divided into the control group and the experimental group. The control group used the traditional thermoplastic head film fixation technique for body position fixation, and the experimental group used the 3D printing head film fixation technique. The patient setup was verified by kV-CBCT scanning to obtain the translational setup error and rotational setup error in the X, Y, and Z directions. Results: At a depth of 5 cm, both materials have a radiation attenuation rate of <1%. At the surface location, the body surface dose of control group increased by approximately 27%. With a 3D printing head film, the body surface dose increased by approximately 18%. The positioning of two groups of patients was verified by the kV-CBCT, and a total of 232 data sets were obtained. The average translation positioning errors in the X, Y, and Z direction of control group and experimental group were 1.29 mm, 1.42 mm, 1.38 mm and 1.16 mm, 1.24 mm, 1.16 mm, respectively. The average rotation positioning error in the X, Y, and Z direction of control group and experimental group were 1.29°, 1.02°, 1.01° and 1.08°, 0.96°, 1.00°, respectively. The translational setup errors in the Y and Z directions and rotational setup errors in the X direction significantly differed between the control and experimental groups (all p<0.05), but no statistical significance was found in the other directions (all p>0. 05). Conclusion: Compared to the traditional thermoplastic head membranes, 3D printing head membranes has shown a reliable and reproducible interactional positioning accuracy. Of course, further investigations are needed before the new technology can be used on a regular basis.

EZH2 as a prognostic-related biomarker in lung adenocarcinoma correlating with cell cycle and immune infiltrates.

BACKGROUNDS: It has been observed that high levels of enhancer of zeste homolog 2 (EZH2) expression are associated with unsatisfactory prognoses and can be found in a wide range of malignancies. However, the effects of EZH2 on Lung Adenocarcinoma (LUAD) remain elusive. Through the integration of bioinformatic analyses, the present paper sought to ascertain the effects of EZH2 in LUAD. METHODS: The TIMER and UALCAN databases were applied to analyze mRNA and protein expression data for EZH2 in LUAD. The result of immunohistochemistry was obtained from the HPA database, and the survival curve was drawn according to the library provided by the HPA database. The LinkedOmics database was utilized to investigate the co-expressed genes and signal transduction pathways with EZH2. Up- and down-regulated genes from The Linked Omics database were introduced to the CMap database to predict potential drug targets for LUAD using the CMap database. The association between EZH2 and cancer-infiltrating immunocytes was studied through TIMER and TISIDB. In addition, this paper explores the relationship between EZH2 mRNA expression and NSCLC OS using the Kaplan-Meier plotter database to further validate and complement the research. Furthermore, the correlation between EZH2 expression and EGFR genes, KRAS genes, BRAF genes, and smoking from the Cancer Genome Atlas (TCGA) database is analyzed. RESULTS: In contrast to paracancer specimens, the mRNA and protein levels of EZH2 were higher in LUAD tissues. Significantly, high levels of EZH2 were associated with unsatisfactory prognoses in LUAD patients. Additionally, the coexpressed genes of EZH2 were predominantly associated with numerous cell growth-associated pathways, including the cell cycle, DNA replication, RNA transport, and the p53 signaling pathway, according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The results of TCGA database revealed that the expression of EZH2 was lower in normal tissues than in lung cancer tissues (p < 0.05). Smoking was associated with elevated EZH2 expression (p < 0.001). EZH2 was highly expressed in lung cancers with positive KRAS expression, and the correlation was significant in lung adenocarcinoma (r = 0.3129, p < 0.001). CMap was applied to determine the top 15 positively correlated drugs/molecules and the top 15 negatively correlated drugs/molecules. MK-1775, MK-5108, fenbendazole, albendazole, BAY-K8644, evodiamine, purvalanol-a, mycophenolic-acid, PHA-793887, and cyclopamine are potential drugs for patients with lung adenocarcinoma and high EZH2 expression. CONCLUSIONS: Highly expressed EZH2 is a predictor of a suboptimal prognosis in LUAD and may serve as a prognostic marker and target gene for LUAD. The underlying cause may be associated with the synergistic effect of KRAS, immune cell infiltration, and metabolic processes.

Analysis of the correlation between Zeste enhancer homolog 2 (EZH2) mRNA expression and the prognosis of mesothelioma patients and immune infiltration.

Mesothelioma lies one of the most malignant tumors, in which the identification of the corresponding biomarkers is extremely critical. This study aims to investigate the prognostic value of enhancer homolog 2 (EZH2) mRNA expression in mesothelioma patients accompanied with its immune infiltration analysis. Gene expression, clinical information and enrichment analysis were obtained based on the Cancer Genome Atlas (TCGA), the immune infiltration analysis and bioinformatics analysis were performed. Clinical information and gene expression were obtained from 86 patients with mesothelioma based on TCGA database. Survival analysis, GSEA enrichment analysis, and immune infiltration analysis of EZH2 expression were carried out using R (version 3.6.3) (statistical analysis and visualization). The correlation of EZH2 expression with immune cell infiltration in mesothelioma was analyzed according to the TIMER database (Fig. https://cistrome.shinyapps.io/timer/ ). A univariate and multivariate analysis of general data obtained from the TCGA database was performed, involving age, gender, stage, pathological type, and whether they had received radiotherapy, the results indicated the association of high expression of EZH2 with poor prognosis in mesothelioma patients, with the worse prognosis in the High group (HR = 2.75, 95% CI 1.68-4.52, P < 0.010). Moreover, ROC curves showed that EZH2 expression predicted 1-year survival with an AUC of 0.740, 2-year survival with an AUC of 0.756, and 3-year survival with an AUC of 0.692, suggesting a robust predictive effect of EZH2 expression on prognosis. KEGG pathway analysis indicated five pathways showing the strongest positive correlation with EZH2 expression: cell cycle, DNA replication, Cell adhesion molecules cams, Primary immuno deficiency, Tsate transduction, and five pathways showing the strongest negative correlation with EZH2 expression: Glycolysis gluconeogenesis, Drug metabolism, cytochrome P450, retinol metabolism, fatty acid metabolism ribosome. We investigated the correlation between EZH2 expression and the level of immune infiltration in mesothelioma tissues. The results indicated that EZH2 expression played a critical role in immune infiltration, of which the high expression was correlated with the reduced number of NK cells, Mast cells, and Th17 cells. Moreover, mesothelioma patients with high EZH2 expression differ from those with low EZH2 expression in their tumor immune microenvironment. EZH2, as a new prognostic biomarker for mesothelioma, contributes to elucidating how changes in the immune environment promote the development of mesothelioma. Further analysis, EZH2 may serve as a biological test to predict the prognosis of mesothelioma.

Ameliorative effect of ginsenoside Rg1 on dextran sulfate sodium-induced colitis: involvement of intestinal barrier remodeling in mice.

Background: Ginsenoside Rg1, a major bioactive ingredient of Panax notoginseng, has been shown to reduce gut inflammation and ameliorate experimental colitis in mice. However, it is not yet known whether it affects the intestinal barrier injury of colitis. Methods: This study explored the effect of ginsenoside Rg1 on intestinal barrier injury in dextran sulfate sodium (DSS)-induced colitis mice through an ultrastructure observation of the colonic mucosa and analysis of the expression of colonic cytoplasmatic zonula occludens-1 (ZO-1) protein. Results: Treatment with ginsenoside Rg1, especially high-dose use, significantly ameliorated colonic histopathologic features and the severity of the colitis and reduced colonic tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) levels and increase IL-4 levels in a mouse model of DSS-induced colitis. Its observed efficacy was comparable to that of 5-Aminosalicylic acid (5-ASA), a first-line therapeutic agent for ulcerative colitis. Notably, ginsenoside Rg1 administration was shown to up-regulate the expression of colonic ZO-1 protein, and it repaired the intestinal barrier structure in DSS-induced colitis mice. Conclusions: Taken together, our findings demonstrated that ginsenoside Rg1 treatment can significantly ameliorate the severity of DSS-induced colitis in mice, which involves intestinal barrier structure remodeling through lowering the levels of the colonic pro-inflammatory cytokines TNF-α and IFN-γ and increasing the anti-inflammatory cytokine IL-4. These results suggest the potential therapeutic use of ginsenoside Rg1 as a promising approach for the treatment of inflammatory bowel disease (IBD).

Hypofractionated radiotherapy versus conventional radiotherapy in patients with intermediate- to high-risk localized prostate cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Prostate cancer is one of the most common cancers in the world. The results of treatment after hypofractionated radiotherapy only have been reported from several small randomized clinical trials. Therefore, we conducted a meta-analysis to compare clinical outcomes of hypofractionated radiotherapy versus conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer. METHODS: Relevant studies were identified through searching related databases till August 2018. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses. RESULTS: The meta-analysis results showed that overall survival (HR = 1.12, 95% CI: 0.93-1.35, p = 0.219) and prostate cancer-specific survival (HR = 1.29, 95% CI: 0.42-3.95, p = 0.661) were similar in two groups. The pooled data showed that biochemical failure was RR = 0.90, 95% CI: 0.76-1.07, p = 0.248. The incidence of acute adverse gastrointestinal events (grade ≥ 2) was higher in the hypofractionated radiotherapy (RR = 1.70, 95% CI: 1.12-2.56, p = 0.012); conversely, for late grade ≥ 2 gastrointestinal adverse events, a significant increase in the conventional radiotherapy was found (RR = 0.75, 95% CI: 0.61-0.91, p = 0.003). Acute (RR = 1.01, 95% CI: 0.89-1.15, p = 0.894) and late (RR = 0.98, 95% CI: 0.86-1.10, p = 0.692) genitourinary adverse events (grade ≥ 2) were similar for both treatment groups. CONCLUSION: Results suggest that the efficacy and risk for adverse events are comparable for hypofractionated radiotherapy and conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer.