RESUMEN
Background: Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies. Methods: We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma's growth and motility. Results: ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces γ-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-ß and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs. Conclusions: Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.
RESUMEN
Introduction: Crack formation has become an important issue for endodontists, as it can be decisive for the long-term prognosis of the endodontically treated tooth. Since the applicability of laser in endodontics has become frequent, this systematic review aimed to evaluate the association between laser therapy and the formation of cracks in the dentinal structure of the root canal. Materials and Methods: A search was performed in PubMed, Scopus, Web of Science, and Virtual Health Library, as well as in the gray literature, on September 24, 2021. Studies that evaluated the formation of cracks in human root dentin due to different types of lasers were included. The risk of bias was assessed following the modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist tool. A meta-analysis was performed to evaluate (i) the total number of crack incidences; (ii) complete crack formation; (iii) incomplete crack formation; (iv) intra-dentinal crack formation between ultrasonic tips and laser use. The mean difference was calculated with a 95% confidence interval in a fixed-effect model, the heterogeneity was tested using the I2 index with level of significance of 5%. Results: Of the 22 studies included in this review, 15 have shown that lasers can form cracks in root dentin, including those that performed baseline assessment of samples. The meta-analysis confirmed no difference in crack formation between ultrasonic tips and laser devices. Conclusions: Laser therapy has been gaining prominence in endodontics and that irradiation can form and propagate cracks in the dentinal structure of the root canal assessed by in vitro studies. This is a critical concern for endodontists as it affects the strength and longevity of the tooth. Future research is encouraged to seek the standardization of good methodological practices and achieve establishing parameters to minimize harmful effects of laser on dentin.
