PATH-29. GLIOBLASTOMA TUMOR CLASSIFICATION BASED ON SPATIAL ANALYSIS OF ONCOGENIC AMPLIFICATIONS AND PROTEIN EXPRESSION

Heterogeneity of glioblastoma (GBM) has been extensively studied in recent years with identification of oncogenic drivers of GBM cellular subtypes. However, little is known about how these cells interact with each other or with the surrounding tumor microenvironment (TME). We employed spatial protein profiling targeting immune and neuronal markers (79 proteins) coupled with single-cell spatial maps of fluorescence in situ hybridization (FISH) for EGFR, CDK4, and PDGFRA on human GBM tissue sections. Several cores from 20 GBM samples were collected to create a tissue microarray, and 96 regions of interests were profiled with 37,844 nuclei for oncogenic amplification screen. Spatial protein profiling identified strong correlation of certain immune markers, TAU-associated proteins, and oligodendrocyte-enriched protein groups and overall high intratumor heterogeneity of TME. Our single-cell quantification of FISH signals showed differences among tumors based on the prevalence of dual amplification of EGFR and CDK4 within a cell relative to single oncogene amplified cells. High relative frequency of dual amplification was associated with increased expression of immune-related markers and decreased expression of EGFR protein. Moreover, this protein expression signature was associated with survival in another GBM dataset. Here, we present spatial genetic analysis at the single cell level coupled with protein expression profiles associated with tumor microenvironment. Our results suggest that assessment of genetic heterogeneity in GBM could potentially drive improved patient stratification and treatment.

In-situ oxygen-generation nanoplatform with dual amplification effect for combined chemo-photodynamic therapy

Background Photodynamic therapy (PDT) is a promising method for cancer treatment because of its advantages such as easy operation, good targeting, minimal side effects, low systemic toxicity and less invasiveness. However, the hypoxic microenvironment within the tumor significantly inhibited the therapeutic effect of PDT. The development of targeted nanoplatform for regulating hypoxia microenvironment is an important method to give full play to the therapeutic effect of PDT. Methods In this study, we designed and prepared a novel chemo-photodynamic therapy nanoplatform, which can continuously catalyze the decomposition of H2O2 in tumors to generate oxygen (O2) to enhance the therapeutic effect of PDT, resulting in DNA damage, while releasing MTH1 inhibitors in tumor cells to inhibit the repair process of DNA damage caused by PDT. Results In our work, a simple one-step reduction approach was applied to enable platinum nanoparticles (Pt NPs) growth in situ in the nanochannels of mesoporous silica nanoparticles (MSNs). After physical encapsulation of photosensitizer chlorin e6 (Ce6) and MTH1 inhibitor TH588, the drug loading nanoplatform was modified with an arginine-glycine-aspartic acid (RGD) functionalized liposome shell, resulting in the fabrication of multifunctional nanoplatform MSN-Pt@Ce6/TH588@Liposome-RGD (MPCT@Li-R) with dual amplification effect and achieve the purpose of chemo-photodynamic therapy. Conclusions Our study provides a new strategy for PDT to ablation tumor cells by damaging the DNA of tumor nucleus and mitochondria, meanwhile inhibiting the repair process after the damage.

A portable signal-on self-powered aptasensor for ultrasensitive detection of sulfadimethoxine based on dual amplification of capacitor and biphotoelectrodes

A one-compartment photofuel cell with two photoelectrodes was combined with a capacitor to develop a portable self-powered sensor for sulfadimethoxine (SDM) detection. The developed sensor was applied to the assay...