METHODS: Transcriptomic and clinical data pertaining to LUAD were retrieved from open-access databases to establish an association between mRNA expression profiles and the presence of TDP-43. A risk-prognosis model was developed to compare patient survival rates across various groups, and its accuracy was also assessed. Additionally, differences in tumor stemness, mutational profiles, tumor microenvironment (TME) characteristics, immune checkpoints, and immune cell infiltration were analyzed in the different groups. Moreover, the study entailed predicting the potential response to immunotherapy as well as the sensitivity to commonly employed chemotherapeutic agents and targeted drugs for each distinct group.
RESULTS: The TDP-43 Co-expressed Gene Risk Score (TCGRS) model was constructed utilizing four genes: Kinesin Family Member 20A (KIF20A), WD Repeat Domain 4 (WDR4), Proline Rich 11 (PRR11), and Glia Maturation Factor Gamma (GMFG). The value of this model in predicting LUAD patient survival is effectively illustrated by both the Kaplan-Meier (K-M) survival curve and the area under the receiver operating characteristic curve (AUC-ROC). The Gene Set Enrichment Analysis (GSEA) revealed that the high TCGRS group was primarily enriched in biological pathways and functions linked to DNA replication and cell cycle; the low TCGRS group showed primary enrichment in immune-related pathways and functions. The high and low TCGRS groups showed differences in tumor stemness, mutational burden, TME, immune infiltration level, and immune checkpoints. The predictions analysis of immunotherapy indicates that the Tumor Immune Dysfunction and Exclusion (TIDE) score (p
MATERIALS AND METHODS: Thirty-nine formalin-fixed paraffin-embedded ameloblastoma cases comprising unicystic ameloblastoma (n=19) and solid/multicystic ameloblastoma (n=20) were subjected to IHC staining for IL-1α, IL-1β, IL-6 and IL-8. A semi-quantitative method was used to evaluate the expression levels of these cytokines according to cell types in the tumoural parenchyma and stroma.
RESULTS: Major findings were upregulations of IL-1α and IL-6 in SMA compared to UA. Both cytokines were heterogeneously detected in the tumoural parenchyma and stroma. Within the neoplastic epithelial compartment, IL-1α expression was more frequently detected in PA-like cells in UA whereas it was more frequently encountered in SR-like cells in SMA. IL-6 demonstrated higher expression levels in the stromal compartment of SMA. IL-1β and IL-8 were markedly underexpressed in both tumour subsets.
CONCLUSIONS: Overexpression of IL-1α in SMA suggests that this growth factor might play a role in promoting bone resorption and local invasiveness in this subtype. The expression levels of IL-1α and IL-6 in three cellular localizations indicate that parenchymal-stromal components of ameloblastoma interact reciprocally via IL-1α and IL-6 to create a microenvironment conducive for tumour progression.
METHODS: Cell counting kit 8(CCK8), 5-ethynyl-2'-deoxyuridine (EdU), transwell and wound healing assays were conducted to study the influence of ZnC in the proliferating, invading and migrating processes of CRC cell lines (HCT116, LOVO) in vitro. The antitumor activity ZnC as well as its effects on tumor immune microenvironment were then assessed using CRC subcutaneous tumors in the C57BL/6 mouse model.
RESULTS: According to CCK8, EdU, transwell and wound healing assays, ZnC inhibited CRC cell lines in terms of proliferation, invasion and migration. ZnC could inhibit miR-570 for up-regulating PD-L1 expression. In vivo experiments showed that gavage (100 mg/kg, once every day) of ZnC inhibited the tumor growth of CRC, and the combination of ZnC and anti-PD1 therapy significantly improved the efficacy exhibited by anti-PD1 in treating CRC. In addition, mass cytometry results showed that immunosuppressive cells including regulatory T cells (tregs), bone marrow-derived suppressor cells (MDSC), and M2 macrophages decreased whereas CD8+ T cells elevated after adding ZnC.
CONCLUSIONS: The present study reveals that ZnC slows the progression of CRC by inhibiting CRC cells in terms of proliferation, invasion and migration, meanwhile up-regulating PD-L1 expression via inhibiting miR-570. The ZnC-anti-PD1 co-treatment assists in synergically increasing anti-tumor efficacy in CRC therapy.