EPHB4 (EPH receptor B4)

In conclusion, our results highlight that a subset of EPHs and EFNs may be associated with worse clinical outcomes (EPHA4, EPHA5, EPHA7, EPHA8, EPHB2, EFNA2, and EFNB2), and an aggressive histological subtype (EPHA2, EPHA4, EPHA8, EPHB4, EFNA1, EFNA3, EFNA4, and EFNB2). The potential correlation of these genes with clinicopathological parameters of UVM need to be evaluated and validated with bioinformatic and experimental approaches in well-characterized cohorts of UVM patients.

Moreover, this phenotype does not depend on KRAS and BRAF gain-of-function, in contrast to the sporadic form. Given the exceptional nature of the non-syndromic inherited phenotype, this study represents the first evidence of a candidate gene for this rare form of the disease, further suggesting a novel field of investigation for the bAVM pathogenesis.

Finally, in vitro validation confirmed the differential expression of these 5 high-risk genes between normal gastric epithelial cell lines and gastric cancer cell lines. Our study reveals previously unattended high-risk gastric cancer genes, potentially offering new directions and evidence for the molecular diagnosis and treatment of gastric cancer.

Further evaluations in other EphB4-overexpressing cancers and in combination with immune checkpoint inhibitors are warranted. Humanization and tumor-selective engineering may enhance its clinical potential for precision oncology.

The advantage of AP8901 is that it is expected to prevent T cell exhaustion and maintain its anti-tumor effect. This phase 1 study of AP8901 will provide new evidence for the application of this novel CAR-T cell therapy in patients with solid tumors, including Ewing sarcoma.

Most of the primaries and liver metastases may benefit from chimeric antigen receptor-T cell therapy targeting CLDN1, EphB4, and LAT1. Cases with high HLA class I expression may be suitable for vaccine-based and T cell receptor-T cell therapy targeting CLDN1, EphB4, LAT1, FOXM1, HSP105α, ROBO1, and SPARC for primaries and targeting antigens, excluding FOXM1 and SPARC, for liver metastases.

These findings highlight the potential of EphB3 and cMet as biomarkers in CRC, and miR-3168 as a promising minimally-invasive biomarker for monitoring disease progression and therapeutic response. However, further validation in larger cohorts is needed to establish their clinical utility.

In vitro, compared to the human umbilical vein endothelial cells of TNF-α group, the expression levels of interleukin-6, interleukin-1β and p-P65 proteins and messenger RNA of Bcl2, Nos3, Cdk8, Pde2a, Dlg1, Pdpk1, Tnks2, Baz2b, Pparg, Fas, Pde7a and Nampt were significantly lower than dapagliflozin high concentration group (P all<0.05). Dapagliflozin may inhibit endothelial cell inflammatory responses and improve endothelial dysfunction in DCM by regulating key genes such as Dlg1, Bcl2, Nos3, Pde7a and Nampt.

Our results demonstrated that the circRNA in situ hybridization-immunohistochemistry could not only be applied to FFPE-TMAs for high-throughput analysis of circRNA expression in tumors but also suggested a possible role for circ-BRIP1, circ-EPHB4, and their host genes in the progression of GISTs.

Taking reference drugs sorafenib (VEGFR2), NVP-BHG712 (EphB4), pemiganitib (FGFR-1), and DP1919 (TIE-2), three promising natural compounds CNP0003920, CNP0243075, and CNP0211397 were concluded based on their end-point binding energies, binding interactions, molecular dynamics, and optimal pharmacokinetic and toxicity profiles. The density functional theory (DFT) results suggested that the identified compounds bound with protein complexes are stable. Our findings can represent a promising starting point for developing multimodal analogues VEGFR2, EphB4, FGFR-1, and TIE-2 proteins.

P2, N=23, Completed, AIDS Malignancy Consortium | Active, not recruiting --> Completed | Trial completion date: Feb 2026 --> Feb 2025 | Trial primary completion date: Feb 2026 --> Feb 2025

P2, N=23, Active, not recruiting, AIDS Malignancy Consortium | Trial completion date: Jun 2026 --> Feb 2026