| RRC ID |
61797
|
| 著者 |
Nishidate M, Yamamoto K, Masuda C, Aikawa H, Hayashi M, Kawanishi T, Hamada A.
|
| タイトル |
MALDI mass spectrometry imaging of erlotinib administered in combination with bevacizumab in xenograft mice bearing B901L, EGFR-mutated NSCLC cells.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Combination therapy of erlotinib plus bevacizumab improves progression-free survival of patients with epidermal growth factor receptor-mutated (EGFR-mutated) advanced non-small-cell lung cancer (NSCLC) compared with erlotinib alone. Although improved delivery and distribution of erlotinib to tumours as a result of the normalization of microvessels by bevacizumab is thought to be one of the underlying mechanisms, there is insufficient supporting evidence. B901L cells derived from EGFR-mutated NSCLC were subcutaneously implanted into mice, and mice were treated with bevacizumab or human IgG followed by treatment with erlotinib. The distribution of erlotinib in their tumours at different times after erlotinib administration was analysed by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI). We also analysed the distribution of erlotinib metabolites and the distribution of erlotinib in tumours refractory to erlotinib, which were established by long-term treatment with erlotinib. We found that erlotinib was broadly diffused in the tumours from B901L-implanted xenograft mice, independently of bevacizumab treatment. We also found that erlotinib metabolites were co-localized with erlotinib and that erlotinib in erlotinib-refractory tumours was broadly distributed throughout the tumour tissue. Multivariate imaging approaches using MALDI MSI as applied in this study are of great value for pharmacokinetic studies in drug development.
|
| 巻・号 |
7(1)
|
| ページ |
16763
|
| 公開日 |
2017-12-1
|
| DOI |
10.1038/s41598-017-17211-6
|
| PII |
10.1038/s41598-017-17211-6
|
| PMID |
29196706
|
| PMC |
PMC5711937
|
| MeSH |
Animals
Bevacizumab / administration & dosage
Bevacizumab / pharmacokinetics*
Biomarkers
Carcinoma, Non-Small-Cell Lung / drug therapy
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / pathology
Cell Line, Tumor
Disease Models, Animal
Drug Therapy, Combination
ErbB Receptors / genetics*
Erlotinib Hydrochloride / administration & dosage
Erlotinib Hydrochloride / pharmacokinetics*
Humans
Lung Neoplasms / drug therapy
Lung Neoplasms / genetics*
Lung Neoplasms / pathology
Male
Mice
Mutation*
Neovascularization, Pathologic / drug therapy
Neovascularization, Pathologic / genetics
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization*
Tumor Burden
Xenograft Model Antitumor Assays
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
B901L(RCB3530) |
