Comprehensive somatic mutational analysis in glioblastoma: Implications for precision medicine approaches.

Glioblastoma multiforme (GBM), a malignant neoplasm originating from glial cells, remains challenging to treat despite the current standard treatment approach that involves maximal safe surgical resection, radiotherapy, and adjuvant temozolomide chemotherapy. This underscores the critical need to identify new molecular targets for improved therapeutic interventions. The current study aimed to explore the somatic mutations and potential therapeutic targets in GBM using somatic mutational information from four distinct GBM datasets including CGGA, TCGA, CPTAC and MAYO-PDX. The analysis included the evaluation of whole exome sequencing (WES) of GBM datasets, tumor mutation burden assessment, survival analysis, drug sensitivity prediction, and examination of domain-specific amino acid changes. The results identified the top ten commonly altered genes in the aforementioned GBM datasets and patients with mutations in OBSCN and AHNAK2 alone or in combination had a more favorable overall survival (OS). Also, the study identified potential drug sensitivity patterns in GBM patients with mutations in OBSCN and AHNAK2, and evaluated the impact of amino acid changes in specific protein domains on the survival of GBM patients. These findings provide important insights into the genetic alterations and somatic interactions in GBM, which could have implications for the development of new therapeutic strategies for this aggressive malignancy.

Development of curcumin-loaded gemini surfactant nanoparticles: Synthesis, characterization and evaluation of anticancer activity against human breast cancer cell lines.

BACKGROUND: Curcumin, the polyphenolic constituent of turmeric, has been recognized as an effective anticancer agent in the treatment of breast cancer. However, the poor bioavailability of curcumin triggers finding of new approaches for elevating its therapeutic efficiency. PURPOSE: We aimed to use gemini surfactant nanocarriers for curcumin in order to overcome its limitations. STUDY DESIGN: We investigated the in vitro characterization of gemini surfactant-curcumin (Gemini-Cur) and examined its antiproliferative & apoptotic activities on breast cancer cell lines. METHODS: Gemini-Cur polymersomes were synthesized through nanoprecipitation method and characterized by dynamic light scattering (DLS), transmission and scanning electron microscopies, HPLC and X-ray diffraction (XRD). The anticancer effect of Gemini-Cur nanoparticles was studied on three different breast cancer cell lines including MCF-7, SkBr-3 and MDA-MB-231 through uptake kinetics, viability & cytotoxicity recordings and apoptotic assays. Furthermore, qRT-PCR was performed to evaluate the expression of apoptotic genes including p16INK4a, p14ARF, Bax and Bcl-2. RESULTS: According to physicochemical analysis, the average particle size, zeta potential value and drug entrapment efficiency for Gemini-Cur compound were recorded as 161 ±â€¯6.2 nm, +5.32 mV and 89.13% ±â€¯0.93, respectively. XRD analysis also confirmed the incorporation of curcumin in gemini surfactant micelles. Regarding the enhanced cellular uptake of sphere shaped Gemini-Cur, our data showed that this nano compound suppresses cancer cell proliferation via induction of apoptosis. Moreover, qRT-PCR analysis revealed that Gemini-Cur could effectively upregulate the expression of p16INK4a, p14ARF and Bax, while significantly decreasing the Bcl-2 expression in these breast cancer cells. CONCLUSION: Our data demonstrates the great potential of gemini surfactants for efficient delivery of curcumin and subsequently, the improvement of its anticancer effect. Therefore, it is sagacious to support the idea that Gemini-Cur nano compound might have the potential to be considered as an anticancer agent.