Malignant effusions provide a critical window into metastatic biology. Malignant effusion-derived organoids (ME-PDTOs) hold promise for modeling metastasis and predicting drug response, but the evidence remains fragmented. This systematic review aims to synthesize current evidence on the validity of ME-PDTOs as metastasis models and their concordance with clinical drug responses. We systematically reviewed literature from the past 15 years in strict accordance with PRISMA 2020 guidelines for study identification and selection. Data on genetic, transcriptional, functional, and clinical correlation were extracted. Given sample size limitations and heterogeneity, a descriptive, study-level analysis was performed. Predictive performance (sensitivity, specificity) was calculated with 95
Oral leukoplakia (OLK) is a prevalent oral mucosal disorder and is at risk of malignant transformation. While nanomedicines hold great promise for OLK therapy, their current nanoformulations for topical treatment of OLK typically suffer from poor transmucosal penetration, neglect immunomodulation for suppressing epithelial hyperproliferation, and lack insights into restoration of oral microbiota homeostasis. Herein, we leverage host-guest molecular recognition for the precise construction of an unprecedented molecular spherical nucleic acid (SNA), supramolecular SNA (sSNA). Briefly, β-cyclodextrin (β-CD) and indocyanine green are comodified on the spherical poly-(amidoamine) dendrimer. The β-CD-grafted dendrimers enable high-performance radial arrangement of ferrocene-tagged CpG immunoadjuvant and PD-L1 aptamer through host-guest recognition. The thus-formed sSNA-CpG/AptPD‑L1, when applied topically to OLK lesions, exhibits superior transmucosal penetration through the epithelial barrier. Upon ultrasound irradiation, sSNA-CpG/AptPD‑L1 generates cytotoxic reactive oxygen species (ROS), suppressing the OLK cell hyperproliferation and even triggering immunogenic cell death. Concurrently, ROS-mediated dissociation of the supramolecular assembly releases CpG oligonucleotides, which enhance antigen-presenting function in dendritic cells and potentiate the activation of CD4+/CD8+ T cells. Simultaneously, the released PD-L1 aptamers block PD-1/PD-L1 checkpoint signaling, sustaining T-lymphocyte activation, ultimately inhibiting pathological OLK progression. Importantly, this sonodynamic immunotherapy establishes adaptive immunological memory by expanding central and effector memory T cell populations, which prevents OLK recurrence and impedes malignant transformation. Furthermore, this therapeutic modality remolds the composition and function of oral microbiota, restoring the homeostasis of oral ecosystem. In short, this study proposes an unprecedented sSNA, establishes the first immunotherapeutic approach against OLK, and restores oral microbiota homeostasis during therapy.
Oncolytic bacteria represent a distinct group of microorganisms capable of selectively infecting and colonizing tumor tissues while sparing normal cells. They exert anti-tumor effects primarily by activating the host immune system and eliciting a robust anti-tumor immune response, which ultimately mediates tumor cell killing. According to their distinct mechanisms of action and target specificities, oncolytic bacteria are currently categorized into three main types: direct oncolytic bacteria, indirect oncolytic bacteria, and prophylactic oncolytic bacteria. However, the clinical translation of these therapies faces several challenges, including suboptimal immunogenicity and uneven spatiotemporal distribution in vivo, which hinder their broader application. This review systematically examines the primary bacterial species utilized in cancer therapy and addresses the key obstacles impeding their clinical translation. Our aim is to lay a theoretical foundation and offer a technical perspective for developing safer and more efficacious oncolytic bacterial strategies.
Esophageal squamous cell carcinoma (ESCC) is a highly prevalent malignancy worldwide. Curcumin is a well-known phytochemical with proven anticancer properties. However, it has poor bioavailability and is unstable. Therefore, the purpose of this study was to develop curcumin nanoparticles and explore the antitumour effects of curcumin and nano-curcumin in ESCC. Nano-curcumin was successfully prepared by the thin-film hydration method. The results of MTT assay, colony formation assay, and apoptosis assays demonstrated that both curcumin and nano-curcumin inhibited the proliferation of ESCC cells. Curcumin and nano-curcumin could regulate the expression of BAX, BCL2, and caspase-3 in ESCC cells. We found that curcumin and nano-curcumin could also induce reactive oxygen species production and decrease the mitochondrial membrane potential. The sequencing results indicated that curcumin and nano-curcumin inhibited ESCC proliferation through calcium signalling pathways in KYSE450 cells. Furthermore, curcumin and nano-curcumin increased calcium levels. RT-qPCR and western blot data also demonstrated that both curcumin and nano-curcumin promote endoplasmic reticulum (ER) stress in ESCC cells. By establishing a xenograft tumour model of ESCC, curcumin and nano-curcumin inhibited tumour proliferation and induced apoptosis and ER stress, indicating that curcumin and nano-curcumin exerted antitumour effects in vivo. Therefore, our findings provide a potential lead compound for treating ESCC.
Objectives: This study aims to explore the therapeutic effect and mechanism of stir-roasted deer velvet antler with ghee (ZLR) on Non-Alcoholic Fatty Liver Disease (NAFLD). Methods: This study used proteomics to analyze the protein composition of roasted deer antler velvet. It established a high-fat diet (HFD)-induced NAFLD rat model and evaluated the therapeutic effects of different dosage groups, including liver injury, oxidative stress, glucose metabolism, steatosis, and insulin homeostasis (via fasting glucose tolerance). Transcriptomics explored the mechanism. Gene expression and Western blot detected lipid metabolism-related gene expression. In vivo experiments validated that ZLR-containing serum alleviates NAFLD and reduces reactive oxygen species levels. Results: The results indicated that ZLR could significantly reduce the body weight, liver weight and degree of hepatic steatosis in HFD rats, improve glycolipid metabolism and insulin sensitivity, and alleviate oxidative stress damage. The mechanism involves activating the adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor (AMPK/PPAR) signaling pathway, regulating the expression of lipid metabolism-related genes, promoting fatty acid oxidation, and reducing fat deposition. The results of in vitro experiments show that ZLR-containing serum can effectively reduce lipid droplet production in liver cells and effectively alleviate oxidative stress damage in liver cells. Conclusions: The traditional Chinese medicine processed product ZLR can regulate lipid metabolism in the body and alleviate the degree of NAFLD by activating the AMPK and PPAR signaling pathways. It provides new ideas for the clinical treatment of NAFLD.
