ABSTRACT
Radiotherapy (RT) is the established noninvasive treatment for glioblastoma (GBM), a highly aggressive malignancy. However, its effectiveness in improving patient survival remains limited due to the radioresistant nature of GBM. Metal-based nanostructures have emerged as promising strategies to enhance RT efficacy. Among them, titanate nanotubes (TNTs) have gained significant attention due to their biocompatibility and cost-effectiveness. This study aimed to synthesize zinc-modified TNTs (ZnTNT) from sodium TNTs (NaTNT), in addition to characterizing the formed nanostructures and evaluating their radiosensitization effects in GBM cells (U87 and U251). Hydrothermal synthesis was employed to fabricate the TNTs, which were characterized using various techniques, including transmission electron microscopy (TEM), energy-dispersive spectroscopy, scanning-transmission mode, Fourier-transform infrared spectroscopy, ICP-MS (inductively coupled plasma mass spectrometry), X-ray photoelectron spectroscopy, and zeta potential analysis. Cytotoxicity was evaluated in healthy (Vero) and GBM (U87 and U251) cells by the MTT assay, while the internalization of TNTs was observed through TEM imaging and ICP-MS. The radiosensitivity of ZnTNT and NaTNT combined with 5 Gy was evaluated using clonogenic assays. Monte Carlo simulations using the MCNP6.2 code were performed to determine the deposited dose in the culture medium for RT scenarios involving TNT clusters and cells. The results demonstrated differences in the dose deposition values between the scenarios with and without TNTs. The study revealed that ZnTNT interfered with clonogenic integrity, suggesting its potential as a powerful tool for GBM treatment.
ABSTRACT
Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by leukocytosis and left shift. The primary molecular alteration is the BCR::ABL1, chimeric oncoprotein with tyrosine kinase activity, responsible for the initial oncogenesis of the disease. Therapy of CML was revolutionized with the advent of tyrosine kinase inhibitors, but it is still not considered curative and may present resistance and serious adverse effects. Discoveries in CML inaugurated a new era in cancer treatment and despite all the advances, a new biomarker is needed to detect resistance and adverse effects. Circular RNAs (circRNAs) are a special type of non-coding RNA formed through a process called backsplicing. The majority of circRNAs are derived from protein-coding genes. CircHIPK3 is formed from the second exon of the HIPK3 gene and has been found in various pathologies, including different types of cancer. New approaches have demonstrated the potential of circular RNAs in cancer research, and circHIPK3 has shown promising results. It is often associated with cellular regulatory pathways, suggesting an important role in the molecular dynamics of tumors. The identification of biomarkers is an important tool for therapeutic improvement; thus we review the role of circHIPK3 and its potential as a biomarker in CML.
