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In the advanced stages of non-small cell lung cancer (non-small-cell lung, NSCLC), brain metastasis occurred in 30%-64% of patients with very poor prognostics.
Beval bead monoantigen is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) and has been approved as a first-line treatment for metastasis non-scale NSCLC in several countries worldwide.
previous studies have suggested that beva bead monoantigen resistance may be effective in patients with NSCLC with brain metastasis, but there is no evidence that beva bead monoantigen has anti-tumor effects on NSCLC metastasis in the brain.
Masamichi Sugimoto of Chugai Pharmaceuticals, Japan, and others conducted studies to assess the efficacy of bevazhu monoantigen anti-brain metastasis by growing brain metastases models in mice with severe combined immunodeficiency (SCID), published in the February 2020 issue of the journal Clinical and Laboratory Metastasis.
methods The authors used simulated clinical blood-brain barrier models to study the effects of beva bead monomorphic osmosis to brain metastasis lesions and anti-tumor microvascular production.
first established a stable expression of "NanoLuc® gene fragment" transplantation capacity, that is, Nluc active NSCLC cell line (Nluc-H1915);
results showed that tumor volume grown under the skin of mice was significantly cored with Nluc activity.
mice with Nluc-H1915 tumors planted under the skin, 5 mg/kg beval bead monoantigen was injected into the abdominal cavity on days 1, 8 and 15 for the treatment group; G), for the control group, on the 22nd day, the TV and Nluc activity of the liquid on the tumor homogenization were determined, and the degree of correlation between the volume of the cortogenic tumor and the activity of Nluc was determined to show that the beva monoantigen inhibited the growth of Nluc-H1915 cells.
, the researchers inoculated Nluc-H1915 cells with the arteries in the neck of SCID mice to form a lung cancer metastasis lesions in the brain and detected human VEGF in the brains of mice (Figure 1).
1. A model of Nluc-H1915 metastasis tumor was established in the brain.
results, HuIgG or bevalt monoantigens were injected into the abdominal cavity of mice every week for 15-17 days after the establishment of the mouse brain metastases model.
found that the activity of Nluc in the brains of mice given bevalgum was significantly lower than that of mice given HuIgG, indicating that beval beads were resistant to brain metastasis tumors in the model.
At the same time, the brains of mice with brain metastasis tumors were observed to have higher concentrations of beva beads than normal mice, and hemorrhagic beval beads in the lesions of brain metastases, indicating that beval beads were resistant to penetration into the lung cancer metastasis site in the brain.
, the study found that the density of microvascular blood vessels in mice injected with beva bead monomorphic tumors was lower than in mice treated with HuIgG (Figure 2).
2. Effects of beva bead monoantion on microvascular density in NSCLC tumor area of brain metastasis.
conclusion The results show that beva bead monoantigen can penetrate into the NSCLC tumor of brain metastasis, and produce anti-angiogenesic activity to inhibit tumor proliferation.
therefore, beval bead monoantin may be a promising treatment option for patients with NSCLC brain metastasis tumors.
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