Oncotarget最新文献

The LRIG gene family consists of LRIG1-3. While LRIG2 has been described as a tumor promoter, LRIG1 and LRIG3 have been identified as tumor suppressors in previous literature. Because of these contrasting roles, the expression of LRIG1-3 was examined across different grades of glioma, between primary and secondary glioblastoma and with focus on chemotherapy treatment. Human tumor tissue samples were extracted during neurosurgery and grouped among the WHO classification valid at the time of surgery. Quantitative western blot analysis, qPCR and immunofluorescence staining were performed. LRIG1 was less expressed in glioma compared to peritumoral tissue with additional decrease with ascending tumors grade. Further, secondary glioblastoma expressed more LRIG1 protein than primary. On mRNA level, the same was seen for LRIG2, were low grade glioma expressed significantly more LRIG2 than high grade glioma. And on protein level, secondary glioblastoma showed higher expression than primary. LRIG3 mRNA expression, in contrast, was significantly higher in grade II gliomas compared to surrounding control tissue, whereas chemotherapy did not significantly affect expression levels in glioblastoma. Our results reinforce suggestions that LRIG1-3 could function as diagnostic markers and therapeutic targets in the treatment of gliomas.

In this study, cerium oxide nanoparticles (CeO₂ NPs) were synthesized using a green chemistry approach, utilizing quince fruit (Cydonia oblonga) peel extract as a non-toxic reducing and stabilizing agent. This environmentally friendly technique represents a novel approach to nanoparticle fabrication, emphasizing sustainability in nanotechnology. The surface of the green-synthesized CeO₂ NPs was further functionalized with cidofovir (CDV), an anti-DNA virus agent, to develop a dual-functional therapeutic platform with potential anticancer and antiviral applications. The successful synthesis and modification of CDV-loaded CeO₂ NPs (CDV- CeO₂ NPs) were confirmed through a series of characterizations, including FT-IR, zeta potential, TEM, SEM-EDX, DLS, and UV-Vis analyses. The cytotoxic effects of CDV, CeO₂ NPs, and CDV- CeO₂ NPs were evaluated against the MCF-7 breast cancer cell line using the MTT assay, revealing that the loading of CDV onto CeO₂ NPs significantly enhanced its anticancer efficacy. Furthermore, the interaction of CDV-CeO₂ NPs with nucleic acids (DNA and RNA) was investigated through absorption and fluorescence studies, demonstrating a strong binding affinity and suggesting the potential of these nanoparticles as highly specific chemotherapeutic agents. The novelty of this work lies in the innovative green synthesis method, the dual-functional therapeutic application, and the enhanced biological activity of the CDV-CeO₂ NPs, which collectively position these nanoparticles as promising candidates for future cancer and antiviral therapies.

Contemporary fluorescence-guided surgery has evolved principally based on the uses and limitations of the contrast agent indocyanine green (ICG). A second generation of novel fluorescent agents are under development to target specific molecular markers on tumor cells and/or the tumor micro-environment. Pafolacianine, a molecular agent targeting the folate receptor (FR), is the first of these approved for use in adults, but its potential utility in pediatric cancers is unknown. In this study, we performed immunohistochemistry staining on slides obtained from a range of pediatric patients with solid tumors. Slides were stained with antibodies to FRα and FRβ, and fluorescence was quantified. Separately, publicly available RNA sequencing data were queried for both FRα and FRβ expression in various pediatric tumors.

Background: Intrabuccal administration of amplitude-modulated 27.12 MHz radiofrequency electromagnetic fields (AM RF EMF) resulting in the systemic delivery of low and safe levels of AM RF EMF has shown activity in several forms of cancer.

Methods: Glioblastoma (GB) cell lines were exposed to GB-specific AM RF EMF (GBMF) three hours per day at a level of exposure identical to patients during treatment. Cellular assays and agnostic genomic approaches were used to characterize the mechanism-of-action. One patient with therapy refractory GB received compassionate use treatment with GBMF as well as a second patient with refractory oligodendroglioma.

Results: Treatment with GBMF inhibited the proliferation of several GB cell lines. CACNA1H mediates the effect of GBMF. GBMF modulates the "Mitotic Roles of Polo-Like Kinase" pathway resulting in the disruption of GB mitotic spindle. There was evidence of clinical and radiological benefit in a 38-year-old patient with recurrent GB and evidence of safety and feasibility in a 47-year-old patient with oligodendroglioma.

Conclusions: This is the first report showing in vitro antitumor activity, disruption of the mitotic spindle, activation of the Mitotic Roles of Polo-like kinase pathway in GB. This is also the first report showing feasibility and clinical activity in patients with brain tumor.

STACT is a modular, genetically engineered live attenuated S. Typhimurium bacterial platform that enables tissue-specific localization and cell-targeted delivery of large, multiplexed payloads via systemic administration. It has been engineered to minimize systemic toxicity and to enrich in the tumor microenvironment (TME) via metabolic dependency and showed a decreased systemic inflammatory cytokine profile compared to its parent strain VNP20009. ACTM-838 utilizes the STACT platform to deliver IL-15/IL15Rα and a constitutively active STING to tumor-resident phagocytic antigen-presenting cells. Upon intravenous (IV) dosing to tumor-bearing mice, ACTM-838 distributed and enriched in the TME, exhibited specific uptake in tumor-resident phagocytic cells and led to expression of human IL-15/IL15Rα and murine IFNα in the tumor. ACTM-838 induced comprehensive TME changes to an immune permissive anti-tumor phenotype with a decrease in exhausted T-cells and Tregs and an increase in cytolytic T-cells and MHCII-high proliferating myeloid cells. ACTM-838-treated tumors exhibited upregulated anti-tumor innate and adaptive immunity expression profiles, T-, NK- and B-cell infiltration and downregulated cell cycle, DNA damage and TGFβ responses. Single-cell RNAseq and flow cytometry data confirmed activation and infiltration of both innate and adaptive immune cells. ACTM-838 showed durable anti-tumor efficacy in multiple murine tumor models and synergized with anti-PD1 therapy in combination.

Ovarian high-grade serous carcinoma (HGSC) is an aggressive disease with an urgent need for improved therapies. Immunotherapies have proved useful for some cancers but have failed to provide benefits for HGSC. Improving our understanding of the mechanisms regulating the HGSC tumor microenvironment will facilitate the discovery of novel immunotherapies and help predict patient response. To this end, the development of syngeneic models is imperative to recapitulate immune responses observed in patients with HGSC. Yet, few syngeneic HGSC mouse models exist that accurately reflect the initiation and disease progression of human disease. In this study, we developed a syngeneic model reflecting both the site of origin and the genotype of early HGSC disease by deleting Trp53 in mouse oviductal epithelial (OVE) cells. Orthotopic injection of OVE cells demonstrated advanced disease progression due to loss of Trp53, associated with a less active T cell phenotype. Molecular analyses uncovered altered inflammatory signaling in OVE4-Trp53ko cells. Further analysis on an ascites-derived cell line identified selection for decreased pro-inflammatory signaling. These results highlight potential mechanisms by which loss of p53 function contributes to an immunosuppressive microenvironment in HGSC, and provide insight into the role of ovarian and peritoneal microenvironments in regulating HGSC cell-intrinsic inflammatory signaling.