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Introduction: A spot sign on computed tomography angiography (CTA) scan is a widely recognized radiographic indicator of primary intracerebral hemorrhage (ICH) used to predict early hematoma expansion. Nonetheless, recent multicenter studies have indicated that its predictive value for hematoma expansion is not as significant as previously stated. Therefore, identifying the reasons for the poor performance of these studies is imperative. Case presentation: A 48-year-old man presented with a 9-hour history of alalia and right limb hemiplegia. Noncontrast computed tomography (CT) revealed a hematoma in the left frontal lobe, while CTA showed a spot sign within the hematoma, leading to a diagnosis of frontal lobe hemorrhage. During the surgical procedure, a blood clot was removed, revealing the presence of 3 mm of saccular tissue resembling an aneurysm. The process of exposing its complete form resulted in its rupture and bleeding. The location of this tissue at the top of the hematoma cavity corresponded to the CTA spot sign. Pathological examination confirmed that the characteristics of the tissue wall were consistent with those of a pseudoaneurysm. Conclusion: This case suggests that more stringent identification criteria should be established in studies predicting ICH expansion using the spot sign on CTA to differentiate and exclude pseudoaneurysms, thereby improving the accuracy of predicting early hematoma expansion using the CTA spot sign.
RESUMO
Limited success has been achieved in ferroptosis-induced cancer treatment due to the challenges related to low production of toxic reactive oxygen species (ROS) and inherent ROS resistance in cancer cells. To address this issue, a self-assembled nanodrug have been investigated that enhances ferroptosis therapy by increasing ROS production and reducing ROS inhibition. The nanodrug is constructed by allowing doxorubicin (DOX) to interact with Fe2+ through coordination interactions, forming a stable DOX-Fe2+ chelate, and this chelate further interacts with sorafenib (SRF), resulting in a stable and uniform nanoparticle. In tumor cells, overexpressed glutathione (GSH) triggers the disassembly of nanodrug, thereby activating the drug release. Interestingly, the released DOX not only activates nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) to produce abundant H2O2 production for enhanced ROS production, but also acts as a chemotherapeutics agent, synergizing with ferroptosis. To enhance tumor selectivity and improve the blood clearance, the nanodrug is coated with a related cancer cell membrane, which enhances the selective inhibition of tumor growth and metastasis in a B16F10 mice model. Our findings provide valuable insights into the rational design of self-assembled nanodrug for enhanced ferroptosis therapy in cancer treatment. STATEMENT OF SIGNIFICANCE: Ferroptosis is a non-apoptotic form of cell death induced by the iron-regulated lipid peroxides (LPOs), offering a promising potential for effective and safe anti-cancer treatment. However, two significant challenges hinder its clinical application: 1) The easily oxidized nature of Fe2+ and the low concentration of H2O2 leads to a low efficiency of intracellular Fenton reaction, resulting in poor therapeutic efficacy; 2) The instinctive ROS resistance of cancer cells induce drug resistance. Therefore, we developed a simple and high-efficiency nanodrug composed of self-assembling by Fe2+ sources, H2O2 inducer and ROS resistance inhibitors. This nanodrug can effectively deliver the Fe2+ sources into tumor tissue, enhance intracellular concentration of H2O2, and reduce ROS resistance, achieving a high-efficiency, precise and safe ferroptosis therapy.