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Chinami Masuda
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P2.02 - Biology/Pathology (ID 616)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.02-051 - Bevacizumab Prevents Growth of Established Non-Small Cell Lung Cancer Brain Metastases in Hematogenous Brain Metastasis Model (ID 8165)
09:30 - 16:00 | Presenting Author(s): Chinami Masuda
- Abstract
Background:
Patients with non-small cell lung cancer are at high risk of developing brain metastases. The mainstay treatment for patients with brain metastasis is surgical excision, whereas radiation is used for multiple brain metastases. Regardless of the treatment, brain metastasis is associated with poor prognosis and the diminished quality of life. Here, we established experimental brain metastasis model allowed interrogation of the brain-specific requirements for cancer cell metastasis and evaluated antitumor efficacy of bevacizumab (BEV), a humanized monoclonal antibody targeting VEGF.
Method:
To produce brain metastases model, we transfected secreted NanoLuc (Nluc) genetic reporter vectors into NCI-H1915 cell line, which was established from a brain metastasis derived from a primary human lung carcinoma and injected into internal carotid artery of SCID mice with external carotid clamped with microclamp. Mice whose Nluc activities in plasma (Relative Light Unit; RLU/5μl) were detected 16 days after inoculation of NCI-H1915 cells were randomly allocated to control and BEV treatment groups (n=9). HuIgG or BEV (5 mg/kg) was intraperitoneally administered once a week (Day 1, 8, 15). Antitumor activity was evaluated by measuring Nluc activity (RLU/whole brain) in supernatant of brain parenchyma homogenized with cell lysis buffer on Day 22. Statistical analysis was performed using the Wilcoxon test.
Result:
Large metastatic nodules were macroscopically observed in brain on Day 22 in 6/9 mice in the control group, whereas those were not observed in any mice treated with BEV. Nluc activity in brain parenchyma homogenate (RLU, mean ± SD) in the BEV group (3.12E+9 ± 3.04E+9) was significantly lower than that in the control group (1.88E+10 ± 2.03E+10, p<0.05). Meanwhile, the weight of parenchyma (mg, mean ± SD) on Day 22 of control and BEV, was 417 ± 27.5 and 398 ± 15.6, respectively and there was no significant difference between them (p>0.05).
Conclusion:
In the secNluc-transfected H1915 hematogeneous metastasis model, BEV showed remarkable activity in reducing Nluc activity in brain parenchyma as well as emergence of visible legion. These results suggested BEV has efficacy against established hematogenous lung cancer brain metastasis lesions in the xenograft model and it may be one of the treatments for brain metastases from lung cancer.
