Exploring Chemovar-Specific Cannabis Extracts Quantification and Evaluation of Cytotoxic Compounds for Targeting Glioblastoma Multiforme

Glioblastoma Multiforme (GBM) represents one of the most aggressive and metastatic brain tumors, with a dismal success rate of less than three percent after five years, particularly in tumors with active immune checkpoints. This necessitates the development of targeted endogenous agents for precise GBM treatment. Previous experiments utilizing Chemovar Specific Cannabis Extractions (CSCEs), fractionated with polar solvents and quantified using Liquid and Gas Column Chromatography combined with Mass Spectrometry (LC/GCMS), have shown reduced viability and motility in human GBM cell lines. However, the complexity of the botanical substance has hindered the personalization of standard cannabis medicines for GBM due to unknown synergistic effects of multiple compounds. To address this limitation, our study focuses on exposing AM251 cells to chemovar fractions extracted using a non-polar solvent, thereby isolating a broader spectrum of constituents. By employing LC/GCMS in conjunction with Nuclear Magnetic Resonance (NMR), we have identified and quantified nine* compounds present in the non-polar CSCE that exhibit significant efficacy (0.1 μM) in inducing cytotoxicity* in GBM tumor cells. Conversely, the polar fraction in our experiment did not demonstrate efficacy against UM251 cells. The quantification of individual compounds within a cannabis extraction that selectively induces cell death in brain tumors holds promise for guiding future research and facilitating the development of a standardized CSCE for GBM therapy.

Limited Margins Using Modern Radiotherapy Techniques Does Not Increase Marginal Failure Rate of Glioblastoma

PURPOSE: We investigate the patterns of failure in the treatment of glioblastoma(GBM) based on clinical target volume(CTV) margin size,dose delivered to the site of initial failure,and the use of temozolomide and intensity-modulated radiotherapy(IMRT).METHODS: Between August 2000 and May 2010,161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide.Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique.Patterns of failure and time to progression and overall survival were compared based on CTV margin,use of temozolomide,and use of IMRT.Kaplan Meier analysis was used to estimate survival times,and χ test was used for comparison of cohorts.RESULTS: For patients treated with 5-,10-,and 15-to 20-mm CTV,79%,77%,and 86% experienced failures in the 60 Gy volume,respectively.Forty-eight percent,55%,and 66% of patients with 5-,10-,and 15-to 20-mm CTV experienced failures in the 46 Gy volume,respectively.There was no statistical difference between patients treated with 5-,10-,15-to 20-mm margins with regard to 60 Gy failure(P=0.76),46 Gy failure(P=0.51),or marginal failure(P=0.73).Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume.There was no increased likelihood of marginal failures in patients receiving IMRT(P =0.97).CONCLUSIONS: Modern treatment techniques including use of concurrent temozolmide,limited CTV margin size,and IMRT have not greatly changed the patterns of failure of GBM.

Characterization of Ablation Thresholds for 3D-Cultured Patient-Derived Glioma Stem Cells in Response to High-Frequency Irreversible Electroporation

High-frequency irreversible electroporation(H-FIRE)is a technique that uses pulsed electric felds that have been shown to ablate malignant cells.In order to evaluate the clinical potential of H-FIRE to treat glioblastoma(GBM),a primary brain tumor,we have studied the efects of high-frequency waveforms on therapy-resistant glioma stem-like cell(GSC)populations.We demonstrate that patient-derived GSCs are more susceptible to H-FIRE damage than primary normal astrocytes.Tis selectivity presents an opportunity for a degree of malignant cell targeting as bulk tumor cells and tumor stem cells are seen to exhibit similar lethal electric feld thresholds,signifcantly lower than that of healthy astrocytes.However,neural stem cell(NSC)populations also exhibit a similar sensitivity to these pulses.Tis observation may suggest that diferent considerations be taken when applying these therapies in younger versus older patients,where the importance of preserving NSC populations may impose diferent restrictions on use.We also demonstrate variability in threshold among the three patient-derived GSC lines studied,suggesting the need for personalized cell-specifc characterization in the development of potential clinical procedures.Future work may provide further useful insights regarding this patient-dependent variability observed that could inform targeted and personalized treatment.