ArticleCancer cell international2021
The structure of blood-tumor barrier and distribution of chemotherapeutic drugs in non-small cell lung cancer brain metastases.
Article in Cancer cell international, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 29 citations in OpenAlex.
- Revealing the hidden: A systematic review and meta-analysis of FAPI-based tracers imaging for brain metastatic lesions.European journal of nuclear medicine and molecular imaging · 2026Pooled it
- Clinical Management of Patients with Non-Small Cell Lung Cancer, Brain Metastases, and Actionable Genomic Alterations: A Systematic Literature Review.Advances in therapy · 2024Pooled it
- Elevated miR-103b in exosomes derived from brain-metastatic triple-negative breast cancer cells remodels the brain pre-metastatic niche (PMN).Cancer biology & therapy · 2026Article
- Neuro-immune crosstalk in lung cancer brain metastasis: mechanisms, therapeutic targets, and translational opportunities.Medical oncology (Northwood, London, England) · 2026Review
- Trastuzumab deruxtecan efficacy, FcRn-facilitated penetration of the blood-tumor barrier, and distribution to tumor cells in HER2+ brain metastasis model systems.Neuro-oncology · 2026Article
- Amelanotic primary thalamic melanoma: a case report.BMC neurology · 2026Article
- From Cerebrovascular Injury to Brain Cancer: The Role of Blood-Brain Barrier Dysfunction.Biomedicines · 2026Review
- RAP-peptide functionalized biomimetic nanoformulation with pathological ROS/pH-responsive drug release for target immunotherapy in glioma.Journal of nanobiotechnology · 2026Article
- Brain radiotherapy combined with immune checkpoint inhibitors and chemotherapy as first-line treatment for advanced non-small cell lung cancer with brain metastases: a retrospective study.BMC immunology · 2026Article
- Blood-brain barrier alterations as an initiator of brain metastasis from lung cancer: a new take on an old story.Cancer gene therapy · 2025Review
- Regulation of Blood-Brain Barrier Permeability via JNK Signaling Pathway: Mechanisms and Potential Therapeutic Strategies for Ischemic Stroke, Alzheimer's Disease and Brain Tumors.Molecules (Basel, Switzerland) · 2025Review
- Cancer brain metastasis: molecular mechanisms and therapeutic strategies.Molecular biomedicine · 2025Review
- Longitudinal MRI evaluation of the efficacy of non-enhanced lung cancer brain metastases.Scientific reports · 2025Article
- Combination immunotherapy and anti-angiogenic therapy shows promising efficacy in NSCLC patients with recurrent or refractory brain metastases and negative driver genes.Frontiers in immunology · 2025Observational
- Visualizing the vascular-cellular microenvironment in lung cancer brain metastasis via multiparametric fusion of DCE-MRI and DWI.Frontiers in oncology · 2025Article
- Lipid-based nanoparticles as drug delivery carriers for cancer therapy.Frontiers in oncology · 2024Review
- Influence of Exosomes on Astrocytes in the Pre-Metastatic Niche of Lung Cancer Brain Metastases.Biological procedures online · 2023Article
- Osimertinib for EGFR-Mutant Non-Small-Cell Lung Cancer Central Nervous System Metastases: Current Evidence and Future Perspectives on Therapeutic Strategies.Targeted oncology · 2023Review
- Survival and prognostic factors in patients undergoing the resection of solitary brain metastasis from non-small cell lung cancer: a retrospective cohort study.Journal of thoracic disease · 2022Article
- Case report: Brain metastasis necrosis with immune checkpoint inhibitors plus chemotherapy for advanced non-small cell lung cancer.Frontiers in immunology · 2022Article
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundBrain metastasis is an important cause of increased mortality in patients with non-small cell lung cancer (NSCLC). In brain metastasis, the blood-brain barrier (BBB) is frequently impaired, forming blood-tumor barrier (BTB). The efficacy of chemotherapy is usually very poor. However, the characteristics of BTB and the impacts of BTB on chemotherapeutic drug delivery remain unclear. The present study investigated the structure of BTB, as well as the distribution of routine clinical chemotherapeutic drugs in both brain and peripheral tumors.
methodsBioluminescent image was used to monitor the tumor load after intracranial injection of lung cancer Lewis cells in mice. The permeability of BBB and BTB was measured by fluorescent tracers of evans blue and fluorescein sodium. Transmission electron microscopy (TEM), immunohistochemistry and immunofluorescence were performed to analyze structural differences between BBB and BTB. The concentrations of chemotherapeutic drugs (gemcitabine, paclitaxel and pemetrexed) in tissues were assayed by liquid chromatography with tandem mass spectrometry (LC-MS/MS).
resultsBrain metastases exhibited increased BTB permeability compared with normal BBB detected by fluorescence tracers. TEM showed abnormal blood vessels, damaged endothelial cells, thick basement membranes, impaired intercellular endothelial tight junctions, as well as increased fenestrae and pinocytotic vesicles in metastatic lesions. Immunohistochemistry and immunofluorescence revealed that astrocytes were distributed surrounded the blood vessels both in normal brain and the tumor border, but no astrocytes were found in the inner metastatic lesions. By LC-MS/MS analysis, gemcitabine showed higher permeability in brain metastases.
conclusionsBrain metastases of lung cancer disrupted the structure of BBB, and this disruption was heterogeneous. Chemotherapeutic drugs can cross the BTB of brain metastases of lung cancer but have difficulty crossing the normal BBB. Among the three commonly used chemotherapy drugs, gemcitabine has the highest distribution in brain metastases. The permeability of chemotherapeutic agents is related to their molecular weight and liposolubility.
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