35 research outputs found
The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen
Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histological progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neo-angiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution towards an IDHwt-like phenotype
Treating glioblastoma often makes a MES
Glioblastoma (GBM) brain tumor cells exhibit
pronounced phenotypic plasticity, but exactly
how this enables GBMs to inevitably resist
standard treatment is not known. A new study
uses multilevel molecular profling of pre- and
post-treatment human GBMs to shed light on
treatment response with single-cell and spatial
resolution
A Combined Smoking Cessation Intervention within a Lung Cancer Screening Trial: A Pilot Observational Study
Electrophoretic Characterization of Bovine Lipoprotein Subfractions Isolated by Agarose Gel Chromatography
Comparative study between transde
Background: This study evaluated the efficacy of transdermal nicotine (TDN) delivery system (15 mg/16 h) or transdermal melatonin (TDM) delivery system (7 mg) 2 h preoperatively for acute postoperative pain after laparoscopic cholecystectomy compared to placebo group (C).
Methods: Sixty female non-smoker patients, aged 18–50 years and ASA I and II undergoing elective laparoscopic cholecystectomy under general anesthesia were included in this randomized controlled double-blind study. Patients were randomly divided into 3 groups 20 each, and C group patients received transdermal placebo patch, TDN group (15 mg/16 h) and TDM group (7 mg/8 h). Assessment of postoperative pain, sedation, hemodynamic variables such as HR and MAP, postoperative monitoring of arterial SpO2 and side effects (e.g. nausea, vomiting, pruritus, respiratory depression and hemodynamic instability) were done 30 min, 1, 2, 6 and 12 h postoperatively. Postoperative Patient’s and Surgeons’ satisfaction, Intraoperative bleeding and plasma cortisol (μg/dl) 2 h postoperatively were also assessed.
Results: There was a significant reduction in the VAS score, total pethidine requirements (mg) and significantly higher patient’s satisfaction in TDN and TDM groups when compared with the C group postoperatively. The sedation score and surgeons’ satisfaction were significantly higher associated with a significant decrease in MAP and Intraoperative bleeding in TDM group compared to C and TDN groups postoperatively. Significant nausea and vomiting in TDN group and significant sedation in TDM group were recorded.
Conclusion: The use of preoperative TDN (15 mg/16 h) or TDM (7 mg/8 h) was an effective and a safe adjuvant for acute pain after surgery