Comprehensive analysis of EphA2 in pan-cancer: A prognostic biomarker associated with cancer immunity.

BACKGROUND: Several studies have reported a significant relationship between Ephrin receptor A2 (EphA2) and malignant progression in numerous cancers. However, there is a lack of comprehensive pan-cancer analysis on the prognostic value, mutation status, methylation landscape, and potential immunological function of EphA2. METHOD: Using The Cancer Genome Atlas, Genotype Tissue Expression Database and GEO data, we analysed the differences in EphA2 expression between normal and tumour tissues and the effects of EphA2 on the prognosis of different tumours. Furthermore, using GSCALite, cBioPortal, TISDB, ULCLAN and TIMER 2.0 databases or platforms, we comprehensively analysed the potential oncogenic mechanisms or manifestations of EphA2 in 33 different tumour types, including tumour mutation status, DNA methylation status and immune cell infiltration. The correlation of EphA2 with immune checkpoints, tumour mutational burden, DNA microsatellite instability and DNA repair genes was also calculated. Finally, the effects of EphA2 inhibitors on the proliferation of human glioma and lung cancer cells were verified in cellular experiments. RESULTS: EphA2 is differentially expressed in different tumours, and patients with overexpression have poorer overall survival. In addition, gene mutations, gene copy number variation and DNA/RNA methylation of EphA2 have been identified in various tumours. Moreover, EphA2 is positively associated with immune infiltration involving macrophages and CD8+ T cells. Further, EphA2 mRNA expression is significantly associated with immune checkpoint in various cancers, especially programmed death-ligand 1. Finally, the EphA2 inhibitor ALW-II-41-27 shows potent anti-tumour activity. CONCLUSION: Our first pan-cancer study of EphA2 provides insight into the prognostic and immunological roles of EphA2 in different tumours, suggesting that EphA2 might be a potential biomarker for poor prognosis and immune infiltration in cancer.

Panobinostat enhances NK cell cytotoxicity in soft tissue sarcoma.

Sarcoma is a rare and heterogeneous class of mesenchymal malignancies with poor prognosis. Panobinostat (LBH589) as one of histone deacetylase (HDAC) inhibitors has demonstrated anti-tumor activity in patients with sarcoma, but its mechanisms remains unclear. Here, we found that LBH589 alone inhibited the proliferation and colony formation of soft tissue sarcoma (STS) cell lines. Transcriptome analysis showed that treatment with LBH589 augmented the NK cell-mediated cytotoxicity. Quantitative real-time PCR and flow cytometric analysis (FACS) further confirmed that LBH589 increased the expression of NKG2D ligands MICA/MICB. Mechanistically, LBH589 activated the Wnt/ß-catenin pathway by upregulating the histone acetylation in ß-catenin promoter. In vitro co-culture experiments and in vivo animal experiments showed that LBH589 increased the cytotoxicity of natural killer (NK) cells while Wnt/ß-catenin inhibitor decreased the effects. Our findings suggest that LBH589 facilitates the anti-tumor effect of NK cells, highlights LBH589 an effective assistance drug in NK cell-based immunotherapies.

Pyroptosis in Cancer: Friend or Foe?

Pyroptosis is an inflammatory form of programmed cell death that is mediated by pore-forming proteins such as the gasdermin family (GSDMs), including GSDMA-E. Upon cleavage by activated caspases or granzyme proteases, the N-terminal of GSDMs oligomerizes in membranes to form pores, resulting in pyroptosis. Though all the gasdermin proteins have been studied in cancer, the role of pyroptosis in cancer remains mysterious, with conflicting findings. Numerous studies have shown that various stimuli, such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and chemotherapeutic drugs, could trigger pyroptosis when the cells express GSDMs. However, it is not clear whether pyroptosis in cancer induced by chemotherapeutic drugs or CAR T cell therapy is beneficial or harmful for anti-tumor immunity. This review discusses the discovery of pyroptosis as well as its role in inflammatory diseases and cancer, with an emphasis on tumor immunity.

[Preparation and Dissolution Evaluation of Breviscapine Self-microemulsion].

OBJECTIVE: To study the prescription and preparation technology of breviscapine self-microemulsion for oral administration, and to evaluate the quality, stability and in vitro dissolution. METHODS: The prescription and preparation technology were selected and optimized through the solubility experiment, compatibility test, and pseudo-ternary phase diagram method, using the self-emulsifying time, appearance, particle diameter and stability as indexes. The droplet morphous, drug content, stability and dissolution were evaluated. Results:The prescription composition of breviscapine self-microemulsion was caprylic/capric triglyceride(GTCC,40%), Cremophor RH-40(50%), and PEG-400 (10%), with the drug loading of 7. 0 mg/g. The breviscapine self-microemulsion exhibited uniform and transparent,with the particle size of 38. 57 nm,Zeta potential of - 8. 80 mV. The results of dissolution indicated that the accumulative dissolution in 0. 1 mol/L hydrochloric acid was able to reach 90. 30% after 90 min, being 5. 9 times to that of the raw material medicine. The stability result showed that the content of breviscapine self-microemulsion was affected by high temperature, indicating it should be stored at low temperature. CONCLUSION: The preparation of breviscapine self-microemulsion is simple, which can increase the solubility of breviscapine in water and the absorption of breviscapine in the stomach and intestine, and conform to the main indexes of oral drug delivery system. It offers the basis for further research of breviscapine.

[Preparation and quality evaluation of tanshinone IIA microemulsion for parenteral injection].

OBJECTIVE: To study the prescription and preparation technology of tanshinone IIA microemulsion for parenteral injection, and to evaluate its quality. METHODS: The prescription was selected and optimized through single-factor test, compatibility experiment and the pseudo-ternary phase diagram method. The preparation technology was investigated, and the droplet morphous, particle diameter, zeta potential, stability and haemolyticus were evaluated. RESULTS: The prescription composition of tanshinone IIA microemulsion was MCT:Solutol HS-15: fabaceous lecithin: absolute alcohol = 9:10:5:6(m/m), oil phase: aqueous phase = 1:10, with the drug-loaded of 1. 0 mg/g. The acquired microemulsion exhibited salmon pink,uniform and transparent, with the average particle diameter of 16. 04 nm, Zeta potential of -11. 57 mV, and the encapsulation efficiency of 98. 53%. The stability result showed that tanshinone IIA content in microemulsion was influenced by high temperature and illumination, indicating tanshinone IIA microemulsion should to be stored at low temperature and protected from light. The preparation was without hemolytic crisis. CONCLUSION: The preparation of tanshinone IIA micro- emulsion is simple,corresponding to the main index of parenteral injection and offering the basis for new dosage form development of tanshinone IIA.