ABSTRACT
PURPOSE: To investigate immuno-ethanol ablation using an ethanol and immune adjuvant formulation as a potent immunoablation approach that can achieve an enhanced anticancer effect in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Ethanol concentration- and exposure time-dependent cellular responses were investigated. Curcumin was combined with ethanol as an immunoablation agent. Cellular uptake of curcumin, cancer cell killing, and inflammatory markers of ethanol-curcumin treatment were characterized. To evaluate the potential in vivo anticancer immunity of ethanol-curcumin treatment, each right and left lobe of rat liver was concurrently inoculated with N1S1 HCC cells and a mixture of treated N1S1 cells (ethanol only or ethanol-curcumin) in Sprague Dawley rats (each group: 5 rats; control: nontreated N1S1 cells). Tumor growth and immune response were characterized with 7T magnetic resonance (MR) imaging, flow cytometry analysis, and immunohistology. RESULTS: An optimized ethanol-curcumin (10% ethanol and 0.5% weight/volume (w/v) curcumin solution) treatment contributed to an enhanced cellular uptake of curcumin, increased cancer cell killing, and decreased inflammatory reaction. Ethanol-curcumin-treated N1S1 cell implantation in the rat liver demonstrated N1S1 HCC tumor rejection. The secondary tumor growth by nontreated N1S1 cell inoculation was significantly suppressed at the same time. Activated anticancer immunity was evidenced by significantly increased CD8+ T cell infiltration (3.5-fold) and CD8+-to-regulatory T cell ratio (4.5-fold) in the experimental group compared with those in the control group. CONCLUSIONS: Enhanced anticancer effect of immuno-ethanol ablation could be achieved with ethanol-curcumin agent. The results underscore the importance of optimized immunoablation therapeutic procedures for enhanced therapeutic outcomes.
ABSTRACT
GPT-4 outperformed a radiology domain-specific natural language processing model in classifying imaging findings from chest radiograph reports, both with and without predefined labels. Prompt engineering for context further improved performance. The findings indicate a role for large language models to accelerate artificial intelligence model development in radiology by automating data annotation.
Subject(s)
Natural Language Processing , Radiography, Thoracic , Humans , Radiography, Thoracic/methods , Radiology Information SystemsABSTRACT
With rapid advances in modern imaging, minimally invasive ablative procedures have emerged as popular alternatives to surgical removal of tumors. Tumor ablation modalities currently offered in clinical practice include microwave ablation, radiofrequency ablation, cryoablation, high-intensity focused ultrasound, and irreversible electroporation. Cryoablation, a non-heat-based method of ablation, is increasingly being used for treating various solid tumors. Accumulated comparative data of cryoablation versus heat-based ablation techniques (e.g., radiofrequency and microwave ablation) shows superior tumor response and quicker recovery time. Evolving research has demonstrated that nanocarriers may serves as excellent catalysts for the cryoablation therapy, imaging guidance, and the co-delivery of therapeutics for minimally invasive, precise, and complete treatment of cancer with immune modulation. This review article focuses on the current status of cryoablation in clinical practice, considers opportunities for enhancing therapeutic outcomes from cryoablation, and discusses new research in the field, including theranostic nanoparticles-mediated cryotherapy and combinational cryo-based immunotherapies.
Subject(s)
Ablation Techniques , Catheter Ablation , Cryosurgery , Nanoparticles , Neoplasms , Ablation Techniques/methods , Catheter Ablation/methods , Cryosurgery/methods , Humans , Neoplasms/surgeryABSTRACT
An overlay of local ablation and immunotherapies could be one of the promising approaches to treat solid tumors, but finding the synergistic combination is still challenging with immune tolerance. Herein, electric pulse responsive iron-oxide-nanocube clusters (IONCs) loaded with indoleamine 2,3-dioxygenase inhibitors (IDOi) are prepared for the enhancement of irreversible electroporation (IRE) cell killing and modulation of the tumor immunosuppressive microenvironment (TIM). IDOi-loaded-IONCs (IDOi-IONCs) show highly responsive movement upon the application of IRE electric pulses inducing local magnetic fields. In vitro and in vivo IRE cell-killing efficiency are significantly enhanced by the IDOi-IONCs. The IRE with IDOi-IONCs also triggers IDOi release from IONCs for TIM modulation. The enhanced cell death and local IDOi release of the IRE with IDOi-IONCs demonstrate a synergistic anticancer effect in vivo with overturning the TIM. The increased infiltration of CD8+ T cells and the elevated ratio of CD8+ T cells to regulatory T cells are confirmed after the IRE with IDOi-IONCs. Further, synergistic interaction between IRE and IDOi-modulated TIM resulted in enhanced elimination of primary and secondary tumors. This proof-of-concept work illustrates a robust modality to guide immune-modulating nanoparticle-mediated immuno-ablation cancer therapies that can be easily tailored to improve its therapeutic outcome.
Subject(s)
Electroporation , Enzyme Inhibitors/chemistry , Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors , Magnetic Iron Oxide Nanoparticles/chemistry , Animals , Apoptosis/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cell Line, Tumor , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Humans , Immunotherapy , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Interferon-gamma/metabolism , Magnetic Fields , Mice , Mice, Inbred C57BL , Neoplasms/pathology , Neoplasms/therapy , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Transplantation, Heterologous , Tumor MicroenvironmentABSTRACT
PURPOSE: To develop bile acid-stabilized multimodal magnetic resonance (MR) imaging and computed tomography (CT)-visible doxorubicin eluting lipiodol emulsion for transarterial chemoembolization of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Ferumoxytol, a US Food and Drug Administration-approved iron oxide nanoparticle visible under MR imaging was electrostatically complexed with doxorubicin (DOX). An amphiphilic bile acid, sodium cholate (SC), was used to form a stable dispersion of ferumoxytol-DOX complex in lipiodol emulsion. Properties of the fabricated emulsion were characterized in various component ratios. Release kinetics of DOX were evaluated for the chemoembolization applications. Finally, in vivo multimodal MR imaging/CT imaging properties and potential therapeutic effects upon intra-arterial (IA) infusion bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion were evaluated in orthotopic McA-Rh7777 HCC rat models. RESULTS: DOX complexed with ferumoxytol through electrostatic interaction. Amphiphilic SC bile acid at the interface between the aqueous ferumoxytol-DOX complexes and lipiodol enabled a sustained DOX release (17.2 ± 1.6% at 24 hours) at an optimized component ratio. In McA Rh7777 rat HCC model, IA-infused emulsion showed a significant contrast around tumor in both T2-weighted MR imaging and CT images (P = .044). Hematoxylin and eosin and Prussian blue staining confirmed the local deposition of IA-infused SC bile acid-stabilized emulsion in the tumor. The deposited emulsion induced significant increases in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) stain-positive cancer cell apoptosis compared to those in a group treated with the nonstabilized emulsion. CONCLUSIONS: SC bile acid-stabilized ferumoxytol-DOX-lipiodol emulsion demonstrated sustained drug release and multimodal MR imaging/CT imaging capabilities. The new lipiodol-based formulation may enhance the therapeutic efficacy of chemoembolization in HCC.
