Glioblastoma (GBM) is a highly malignant brain tumor with limited treatment options. While natural killer (NK) cell-based immunotherapy shows promise in cancer treatment, effective tumor targeting remains a challenge. This study investigates the use of folic acid-modified superparamagnetic iron oxide nanoparticles (SPIONs-PEG-FA) to magnetize NK cells, enabling them to accumulate at the tumor site under an external magnetic field while retaining their cytotoxic activity against GBM cells. SPIONs-PEG-FA were synthesized using PEGylation and coprecipitation to ensure efficient NK cell uptake. Their successful synthesis was confirmed through material characterization, including X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and dynamic light scattering. In vitro studies evaluated their safety, cellular uptake, and cytolytic activity, whereas in vivo experiments assessed tumor targeting and therapeutic efficacy in GBM-bearing mice. SPIONs-PEG-FA-loaded NK cells were successfully developed for targeted GBM therapy. In vitro studies confirmed their safety and effectiveness against GBM tumor cells, whereas transmission electron microscopy analysis verified the cellular uptake of SPIONs-PEG-FA by NK cells. In vivo experiments in GBM-bearing mice demonstrated improved tumor targeting, enhanced cytolytic efficiency, and overall safety of SPIONs-PEG-FA-loaded NK cells. SPIONs-PEG-FA-loaded NK cells represent a promising approach for targeted GBM therapy. Their successful synthesis and characterization, coupled with in vitro and in vivo validation, highlight their potential for improved therapeutic outcomes. This magnetic field-guided NK cell therapy offers a promising strategy for overcoming challenges in GBM treatment.

Pharmacological potential of chalepensin from Ruta chalepensis L.: Acute toxicity and in vivo antitumor activity in the L5178Y-R murine model.

Modulating the cytotoxic activity of Titanocene complexes through aliphatic chain modification to optimize albumin affinity.

Plant material dependent synthesis of Dolerophanite/CuO nanoparticles and impact on the antimicrobial and cytotoxic activities

Multimerization approach to improve a cell surface plectin binding cancer stem cell targeted peptoid drug‑lead.

Umbilical cord blood-derived natural killer cells as a viable and potent source for adoptive cell therapy.

Grifolin derivatives from the fruiting bodies of Albatrellus dispansus.

Fragment merging design, synthesis, and biological evaluation of novel methyl Selanyl- And thiazolidinedione-based hybrids as potent anticancer inducing apoptosis and cell cycle arrest.

Indigofera truxillensis Kunth is traditionally used in Brazilian folk medicine as an oral infusion of the aerial parts, taken as one cup several times daily for at least one week, to relieve inflammatory pain and gastrointestinal complaints. To chemically characterize and evaluate the anti-arthritic and analgesic properties of the methanolic extract (MEIT) and indigo obtained from the aerial parts of I. truxillensis. The chemical analysis of MEIT and the identification of indigo were performed by electrospray ionization tandem mass spectrometry and nuclear magnetic resonance. Anti-inflammatory and anti-hyperalgesic activities were assessed in mice using carrageenan-induced pleurisy and paw inflammation, complete Freund's adjuvant (CFA), and zymosan-induced articular inflammation models. Cytotoxicity and phagocytic activity were evaluated in vitro using leukocyte viability (MTT) and neutrophil phagocytosis assays. MEIT and indigo significantly inhibited leukocyte recruitment in carrageenan-induced pleurisy. In the carrageenan paw model, both reduced mechanical hyperalgesia, cold sensitivity, and edema. In CFA-induced inflammation, MEIT and indigo decreased mechanical hyperalgesia, cold response, myeloperoxidase activity, and protein exudation. In the zymosan-induced arthritis model, both treatments reduced knee edema, mechanical hyperalgesia, leukocyte migration, protein extravasation, and nitric oxide levels in synovial fluid. MEIT and indigo did not exhibit cytotoxicity in vitro; MEIT reduced neutrophil phagocytosis at specific concentrations, whereas indigo did not alter phagocytic activity. MEIT and indigo exhibit significant anti-inflammatory, anti-hyperalgesic, and anti-arthritic activities, supporting the traditional use of I. truxillensis for painful and inflammatory conditions and identifying indigo as a key bioactive constituent.

MuTriM: A multiscale deep learning model integrating longitudinal radiomics and pathomic features for predicting recurrence and adjuvant radiation benefit in breast cancer.

Steroid-induced modulation of the tumor immune microenvironment: Implications for cancer progression and immunotherapy outcomes.

Synthesis of 4-chloro-N'-(2-cyanoacetyl)benzohydrazide derivatives, cytotoxicity, VEGFR-2/EGFRT790M bioassays and in silico docking/ADMET studies.

Globally, third leading cause of cancer-related deaths is contributed by Hepatocellular carcinoma (HCC). Chronic hepatitis B virus infection is one of the seminal etiological drivers of HCC. Hepatitis B viral DNA integration, host genomic instability, persistent inflammatory responses and the oncogenic activity of the viral oncoprotein Hepatitis B virus X (HBx), contribute to the hepatocarcinogenesis. Emerging evidences indicate that epigenetic dysregulation plays a seminal role in linking viral persistence in the liver tissue to its malignant transformation. In HBV-infected hepatocytes, aberrant DNA methylation, histone modifications, and dysregulated non-coding RNAs reprogram transcriptional networks that activate oncogenic pathways, promote proliferative signaling, and sustain cancer stem cell-like phenotypes driving HCC progression. The epigenetic modifications in the infected, malignant hepatic cells can influence the tumor microenvironment, contributing to the infiltration of exhausted cytotoxic T lymphocytes with elevated PD-1 and Tim-3 expression. Further, the T lymphocytes exhibit reduced proliferative capacity, impaired cytokine secretion, and diminished cytotoxic activity. In the clinical perspective, long-term nucleotide analogue therapy causes viral suppression and attenuation of inflammation, thereby reducing HCC progression by 40-80%. Despite the extensive T-cell exhaustion, HBV-associated HCC (HBV-HCC) is responsive to immune checkpoint blockade, as highlighted in the CheckMate-040 trial. Emerging therapeutic strategies combine anti-viral agents with immune checkpoint inhibitors, epi-drugs and HBsAg-directed TCR-engineered T cells. These clinical approaches aim to simultaneously restore antitumor immune responses as well as neutralize the viral oncogenic drivers, offering promising avenues for improved management of HBV-induced HCC.

Cytotoxic and oxidative stress-related effects of N2O2-type Ni(II)-thiosemicarbazone complexes: Experimental and computational studies.

Transient tumor exposure induces persistent functional defects in memory CD8+ T cells.

Targeted introduction of T cell receptor genes at the TRAC locus in cytotoxic T lymphocytes regenerated from human iPSCs by genome editing.

Chimeric antigen receptor (CAR) T cells have emerged as an effective immunotherapy for hematologic malignancies. The non-signaling domain of CARs, comprising the spacer and transmembrane regions, is a key structural component that can be engineered to influence CAR expression and function. In this study, we evaluated three non-signaling domain configurations-IgG2.CH3/CD28, IgG2/CD28, and CD8/CD8-within a CD19 CAR construct incorporating 4-1BB and interleukin-7 receptor alpha (IL-7Rα) signaling domains. CARs incorporating the IgG2/CD28 domain exhibited reduced surface expression and diminished functional responses compared with IgG2.CH3/CD28 and CD8/CD8 constructs. The CD8/CD8 configuration supported the highest CAR expression and sustained surface density. In contrast, IgG2.CH3/CD28 CAR T cells displayed increased IL-2 and TNF-α secretion and enhanced CD107α upregulation following antigen stimulation. In a serial tumor cell rechallenge assay, IgG2.CH3/CD28 CAR T cells maintained cytotoxic activity and persistence compared with CD8/CD8 CAR T cells. In a NALM-6 xenograft model, IgG2.CH3/CD28 CAR T cells achieved durable tumor control and were associated with improved survival relative to CD8/CD8 CAR T cells. Collectively, these findings support the IgG2.CH3/CD28 non-signaling domain as a suitable structural component for CD19 CARs incorporating IL-7Rα signaling and provide insight into CAR design strategies aimed at improving T cell persistence and anti-leukemic activity.

In the pathogenesis of hepatocellular carcinoma (HCC), impaired CD8+ T cell function is a critical factor in immune evasion. Although CLCN2 has been implicated in immunomodulation, its role in regulating CD8+ T cell-mediated antitumor immunity in HCC remains unclear. The expression of G2E3 in HCC was analyzed using the TCGA database, qPCR, and western blot. The UbiBrowser database was employed to predict CLCN2 as a downstream substrate of G2E3. Protein interactions were validated via Co-IP and invivo ubiquitination assays. IFN-γ, TNF-α, and Granzyme B levels were measured using ELISA kits, while CD44 and CD134 levels in CD8+ T cells were examined via flow cytometry. The cytotoxic activity of CD8+ T cells against HCC cells was evaluated using an LDH assay. An allograft mouse tumor model was utilized to determine whether the G2E3-CLCN2 axis drove HCC progression by suppressing T cell immunity. We herein discovered that G2E3 was highly expressed in HCC and positively linked with poor prognosis. Mechanistically, G2E3 functioned as an E3 ubiquitin ligase, mediating the ubiquitination and subsequent degradation of CLCN2. Rescue experiments revealed that CLCN2 enhanced the antitumor activity of CD8+ T cells, whereas G2E3 overexpression attenuated this effect. Furthermore, in an allograft mouse tumor model, activation of the G2E3-CLCN2 axis reduced CD8+ T cell infiltration and activity in tumors, thereby driving tumor growth. This investigation elucidates the molecular mechanism by which HCC suppresses CD8+ T cell function to facilitate immune escape, suggesting that targeting the G2E3-CLCN2 axis may represent a potential therapeutic strategy to enhance antitumor immunity.

Antiproliferative Activity and Acute Toxicity of α,β-Bis(diphenylphosphine Oxide)ethanes Obtained by Bisphosphorylation of Acetylenes: Electrosynthesis Under Mild Conditions Versus Improved Superbasic Medium Synthesis.

Discovery of [1,2,4]triazolo[1,5-a]pyrimidine-Imatinib Hybrids With Selective Cytotoxic Activity: A Mechanistically Divergent Series From Direct BCR-ABL1 Inhibition.