Liver Cancer Model

Indication / Application

Efficacy evaluation of novel targeted therapies (e.g., multikinase inhibitors, ADCs), assessment of immunotherapies (e.g., immune checkpoint inhibitors, cellular therapies) within the hepatic immune microenvironment, and validation of interventional oncology devices (e.g., embolic microspheres, ablation systems).

Modeling Method

1. Subcutaneous Xenograft (CDX) & Syngeneic Models:

• Inoculation of human HCC cell lines (such as HepG2, Huh7, Li7) in immunodeficient rodents, or murine cell lines (such as Hepa1-6) in immunocompetent syngeneic hosts. This setup serves as an efficient screening assay for evaluating the anti-proliferative efficacy of novel drug candidates.

2. Orthotopic Liver Tumor Model:

• Surgical or ultrasound-guided injection of tumor cell suspensions, or direct implantation of donor tumor fragments, into the left lateral lobe of the liver. This system preserves realistic hepatic hemodynamics, vascularization, and local microenvironmental factors.

3. Chemical-Induced Chronic HCC Model:

• Administration of diethylnitrosamine (DEN) in young rodents (e.g., 2-week-old C57BL/6 mice), optionally paired with a high-fat diet (HFD). Over 6 to 9 months, animals develop progressive hepatic pathologies transitioning from steatosis and fibrosis to multifocal HCC, mimicking the clinical development of liver cancer.

4. Large Animal (Porcine) Interventional Model:

• Leveraging the vascular anatomy of Bama mini-pigs, we perform transcatheter arterial chemoembolization (TACE) or thermal ablation (RFA/MWA) under real-time fluoroscopic (DSA) guidance to evaluate advanced interventional oncology devices.

Clinical Relevance

• Microenvironmental Homology: Orthotopic transplantation models accurately simulate human hepatic hemodynamics, local vascular invasion, and metastatic potential, yielding highly translational pharmacokinetics compared to subcutaneous assays.

• Pathological Progression: The DEN/HFD induction model recapitulates the classic clinical sequence of liver injury, chronic inflammation, fibrosis, and eventual malignant transformation, making it suitable for chemoprevention studies.

• Translational Device Validation: The porcine portal and hepatic arterial anatomy allow the use of clinical-grade catheters, embolic agents, and ablation instruments, facilitating regulatory submissions for medical devices.

Key Evaluation Endpoints

In Vivo Tumor Progression & Imaging

• In Vivo Bio-Imaging: High-resolution micro-ultrasound or bioluminescence/fluorescence imaging (using luciferase-labeled cells) to track orthotopic tumor growth and metastasis non-invasively.

• Survival Analysis: Comprehensive tracking of animal clinical scores, body weight dynamics, and long-term survival rates (Kaplan-Meier curves).

Histopathology & Microstructural Analysis (Primary Efficacy Endpoints)

• Standard H&E Staining: Histomorphological scoring of tumor borders, necrotic fraction, cell atypia, and local tissue invasion.

• Immunohistochemistry (IHC) Profiling:

  • Cell Proliferation & Apoptosis: Tracking of Ki-67, PCNA, and TUNEL apoptotic markers.

  • Angiogenesis Quantitation: CD31 or CD34 staining to evaluate tumor microvessel density (MVD).

  • Immune Cell Infiltration: Profiling of CD3+, CD4+, CD8+ (T cells), and F4/80 (macrophages) to evaluate tumor immunogenicity and immunotherapy responses.

Biochemical, Serum & Biomarker Profiling

• Serum Biomarker Monitoring: Quantitative tracking of circulating Alpha-Fetoprotein (AFP) levels.

• Hepatic Function & Systemic Toxicity Panels: Assessment of serum ALT, AST, total bilirubin, and albumin levels to evaluate safety profiles.

• Molecular Expression Profiling: RT-qPCR and Western Blot analysis of tissue-specific oncogenic pathways, angiogenic factors (VEGF, EGFR), and inflammatory cytokines (TNF-alpha, IL-6).