徳島大学 教育・研究者情報データベース(EDB)

1. (英) Okada Yasuyuki / (日) 岡田 泰行 / (読) おかだ やすゆき

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2. 木村 哲夫

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3. 中川 忠彦

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4. 岡本 耕一([徳島大学.病院.診療科.内科.消化器内科])

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5. (英) Fukuya Akira / (日) 福家 慧 / (読) ふくや あきら

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6. 郷司 敬洋

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7. (英) Fujimoto Shota / (日) 藤本 将太 / (読) ふじもと しょうた

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8. 曽我部 正弘([徳島大学.キャンパスライフ健康支援センター])

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9. 宮本 弘志([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学]/[徳島大学.病院.診療科.内科.消化器内科])

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10. 六車 直樹

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11. (英) Tsuji Yasushi

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12. 岡久 稔也([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域総合医療学]/[徳島大学.病院.診療科.内科.消化器内科])

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13. 高山 哲治([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.消化器内科学])

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(英) EGFR Down-regulation After anti-EGFR Therapy Predicts the Anti-tumor Effect in Colorectal Cancer.

(英) Anti-EGFR mAb is reported to induce EGFR internalization in colorectal cancer cells. However, the biological relevance of EGFR internalization with anti-EGFR mAb is unknown. Therefore, the relevance of EGFR downregulation with anti-EGFR mAb to antitumor activity in colorectal cancer cells was investigated. Quantification of EGFR on the cell surface before cetuximab treatment was assessed by flow cytometry, and its growth-inhibitory effects were measured by Trypan blue exclusion, in 10 wild-type colorectal cancer cell lines, but there was no significant correlation between EGFR number and its growth-inhibitory effect. However, a significant correlation existed between the percentage decrease in the number of EGFRs after cetuximab treatment and its growth-inhibitory effect in those cell lines. Treatment with TGFα, a ligand for EGFR, induced EGFR internalization in colorectal cancer cells, but most EGFRs subsequently recycled to the cell surface, consistent with previous studies. While cetuximab treatment induced EGFR internalization, most receptors subsequently translocated into the late endosome, leading to lysosomal degradation, as revealed by immunoblotting and double immunofluorescence. Cetuximab-sensitive colorectal cancer cells showed greater EGFR internalization, stronger cell growth inhibition, and more augmented apoptotic signals than nonsensitive cells. IHC for EGFR, performed using an EGFR pharmDx Kit (mouse anti-human EGFR mAb clone 2-18C9), in clinical specimens before and after anti-EGFR mAb therapy in 13 colorectal cancer patients showed a significant correlation between the response to anti-EGFR mAb and decreased staining after therapy. This report clearly demonstrates that anti-EGFR mAb facilitates internalization and subsequent degradation of EGFRs in lysosomes, which is an important determinant of the efficacy of anti-EGFR mAb treatment for colorectal cancer. .

1. (英) Adult
2. (英) Aged
3. (英) Antineoplastic Agents, Immunological
4. (英) Caco-2 Cells
5. (英) Cell Line, Tumor
6. (英) Cell Survival
7. (英) Cetuximab
8. (英) Colorectal Neoplasms
9. (英) Down-Regulation
10. (英) Endosomes
11. (英) Female
12. (英) HCT116 Cells
13. (英) HT29 Cells
14. (英) Humans
15. (英) Male
16. (英) Middle Aged
17. (英) Proto-Oncogene Proteins B-raf
18. (英) Receptor, Epidermal Growth Factor
19. (英) Transforming Growth Factor alpha
20. (英) ras Proteins

1. (英) Article.ELocationID: 10.1158/1541-7786.MCR-16-0383

2. (英) Article.PublicationTypeList.PublicationType: Journal Article