ArticleHepatology (Baltimore, Md.)2022
Single-cell biology uncovers apoptotic cell death and its spatial organization as a potential modifier of tumor diversity in HCC.
Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- A machine learning-driven framework integrating cell death and senescence signatures for multi-target drug design and immunotherapy optimization in ovarian cancer.NPJ precision oncology · 2026Article
- Dying cells as architects of the stem cell niche: a conserved mechanism driving tissue regeneration and tumor therapy resistance.Cell communication and signaling : CCS · 2026Review
- What Is Apoptosis and Why Is It Inhibited by the Most Important Tumor Suppressor (p53)?International journal of molecular sciences · 2025Review
- Magnetic Hyperthermia with Iron Oxide Nanoparticles: From Toxicity Challenges to Cancer Applications.Nanomaterials (Basel, Switzerland) · 2025Review
- Anastasis and Other Apoptosis-Related Prosurvival Pathways Call for a Paradigm Shift in Oncology: Significance of Deintensification in Treating Solid Tumors.International journal of molecular sciences · 2025Review
- Global Research Trends and Hotspots in the Role of Cholesterol in Colorectal Cancer: A Bibliometric Analysis.Human mutation · 2025Article
- Characterization of regulated cancer cell death pathways induced by the different modalities of non-thermal plasma treatment.Cell death discovery · 2024Article
- Changing the Landscape of Solid Tumor Therapy from Apoptosis-Promoting to Apoptosis-Inhibiting Strategies.Current issues in molecular biology · 2024Review
- Recent insights into the pathogenesis and therapeutic targets of chronic liver diseases.eGastroenterology · 2023Article
- Intratumor Heterogeneity and Treatment Resistance of Solid Tumors with a Focus on Polyploid/Senescent Giant Cancer Cells (PGCCs).International journal of molecular sciences · 2023Review
- Dissecting intratumor heterogeneity in HCC: new research strategies and clinical implications.Carcinogenesis · 2022Review
- Treacherous apoptosis-Cancer cells sacrifice themselves at the altar of heterogeneity.Hepatology (Baltimore, Md.) · 2022Article
- Schisantherin A inhibits cell proliferation by regulating glucose metabolism pathway in hepatocellular carcinoma.Frontiers in pharmacology · 2022Article
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Abstract
BACKGROUND AND
aimsHCC is a highly aggressive and heterogeneous cancer type with limited treatment options. Identifying drivers of tumor heterogeneity may lead to better therapeutic options and favorable patient outcomes. We investigated whether apoptotic cell death and its spatial architecture is linked to tumor molecular heterogeneity using single-cell in situ hybridization analysis. APPROACH AND
resultsWe analyzed 254 tumor samples from two HCC cohorts using tissue microarrays. We developed a mathematical model to quantify cellular diversity among HCC samples using two tumor markers, cyclin-dependent kinase inhibitor 3 and protein regulator of cytokinesis 1 as surrogates for heterogeneity and caspase 3 (CASP3) as an apoptotic cell death marker. We further explored the impact of potential dying-cell hubs on tumor cell diversity and patient outcome by density contour mapping and spatial proximity analysis. We also developed a selectively controlled in vitro model of cell death using CRISPR/CRISPR-associated 9 to determine therapy response and growth under hypoxic conditions. We found that increasing levels of CASP3
conclusionsThese results are consistent with the hypothesis that increased apoptotic cell death may lead to greater tumor heterogeneity and thus worse patient outcomes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.