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ESM1 drives cancer angiogenesis and bevacizumab resistance via trioleate synthesis

Neoplasia. 2026 May;75:101298. doi: 10.1016/j.neo.2026.101298. Epub 2026 Mar 20.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) exhibits high recurrence rates and limited therapeutic options. Endothelial cell-specific molecule 1 (ESM1) and angiopoietin-like 4 (ANGPTL4) are implicated in tumor progression, yet their synergistic role in HCC lipid metabolism and angiogenesis remains unexplored.

METHODS: We integrated multi-omics approaches, including RNA sequencing, metabolomics, and immunoprecipitation-mass spectrometry, in HCC cell lines and patient-derived xenograft models. Key experiments involved Co-IP, Western blotting, tube formation assays, and clinical tissue microarray analysis to validate the ESM1-ANGPTL4-FASN-trioleate axis.

RESULTS: ESM1 and ANGPTL4 formed a positive feedback loop, stabilizing fatty acid synthase (FASN) to promote trioleate synthesis. Trioleate activated the NF-ΞΊB/IL-17 pathway in HCC cells and upregulated CD99 in endothelial cells, driving angiogenesis. In vivo, ESM1/ANGPTL4 knockdown suppressed tumor growth, which was rescued by trioleate supplementation. Clinical data revealed elevated ESM1/ANGPTL4 expression in bevacizumab-resistant HCC, correlating with poor prognosis.

CONCLUSIONS: The ESM1-ANGPTL4-FASN-trioleate axis orchestrates metabolic reprogramming and endothelial activation, representing a promising therapeutic target. Future studies should explore combination therapies targeting this axis and overcoming bevacizumab resistance in HCC.

PMID:41864037 | PMC:PMC13019581 | DOI:10.1016/j.neo.2026.101298

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Top-Down Semantic Refinement for Image Captioning

arXiv:2510.22391v2 Announce Type: replace-cross Abstract: Large Vision-Language Models (VLMs) face an inherent contradiction in image captioning: their powerful single-step generation capabilities often lead to a myopic decision-making process. This makes it difficult to maintain global narrative coherence while capturing rich details, a limitation that is particularly pronounced in tasks that require multi-step and complex scene description. To overcome this fundamental challenge, we redefine image captioning as a goal-oriented hierarchical refinement planning problem, and further propose a novel framework, named Top-Down Semantic Refinement (TDSR), which models the generation process as a Markov Decision Process (MDP). However, planning within the vast state space of a VLM presents a significant computational hurdle. Our core contribution, therefore, is the design of a highly efficient Monte Carlo Tree Search (MCTS) algorithm tailored for VLMs. By incorporating a visual-guided parallel expansion and a lightweight value network, our TDSR reduces the call frequency to the expensive VLM by an order of magnitude without sacrificing planning quality. Furthermore, an adaptive early stopping mechanism dynamically matches computational overhead to the image's complexity. Extensive experiments on multiple benchmarks, including DetailCaps, COMPOSITIONCAP, and POPE, demonstrate that our TDSR, as a plug-and-play module, can significantly enhance the performance of existing VLMs (e.g., LLaVA-1.5, Qwen2.5-VL) by achieving state-of-the-art or highly competitive results in fine-grained description, compositional generalization, and hallucination suppression.
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