Baseline soluble MICA levels act as a predictive biomarker for the efficacy of regorafenib treatment in colorectal cancer.
Baseline soluble MICA levels act as a predictive biomarker for the efficacy of regorafenib treatment in colorectal cancer.
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DOI：
10.1186/s12885-022-09512-5
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发表时间：
2022-04-20
期刊：
影响因子：
3.8
通讯作者：
Yoshida, Hitoshi
中科院分区：
文献类型：
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作者：
Arai, Jun;Otoyama, Yumi;Fujita, Ken-ichi;Goto, Kaku;Tojo, Masayuki;Katagiri, Atsushi;Nozawa, Hisako;Kubota, Yutaro;Takahashi, Takehiro;Ishida, Hiroo;Tsunoda, Takuya;Matsumoto, Natsumi;Ogawa, Keita;Nakagawa, Ryo;Muroyama, Ryosuke;Kato, Naoya;Yoshida, Hitoshi
评价瑞戈非尼对体外培养的人可溶性MHC I类多肽相关序列A（云母）（sMICA）水平的影响。此外，我们临床检查了其血浆水平是否与瑞戈非尼活性相关，即CRC患者的无进展生存期（PFS）。人CRC细胞系HCT 116和HT 29细胞用与患者血清中浓度相同的瑞戈非尼及其代谢活性代谢产物M2或M5处理。我们还检查了瑞戈非尼、M2和M5的sMICA水平和血药浓度-时间曲线下面积。瑞戈非尼、M2和M5显著抑制人CRC细胞中云母的脱落，而无毒性。这导致sMICA的产生减少。在临床检查中，中位PFS较长（3.7个月）的CRC患者的sMICA水平显著低于中位PFS较短（1.2个月）的患者（p = 0.045）。云母是一种有吸引力的药物，用于控制CRC的免疫控制，基线sMICA水平可能是瑞戈非尼治疗疗效的预测生物标志物。
To evaluate the effect of regorafenib on soluble MHC class I polypeptide-related sequence A (MICA) (sMICA) level in vitro. In addition, we clinically examined whether its plasma levels were associated with regorafenib activity in terms of progression-free survival (PFS) in patients with CRC. Human CRC cell line HCT116 and HT29 cells were treated with regorafenib and its pharmacologically active metabolites, M2 or M5 at the same concentrations as those in sera of patients. We also examined the sMICA levels and the area under the plasma concentration–time curve of regorafenib, M2 and M5. Regorafenib, M2, and M5 significantly suppressed shedding of MICA in human CRC cells without toxicity. This resulted in the reduced production of sMICA. In the clinical examination, patients with CRC who showed long median PFS (3.7 months) had significantly lower sMICA levels than those with shorter median PFS (1.2 months) (p = 0.045). MICA is an attractive agent for manipulating the immunological control of CRC and baseline sMICA levels could be a predictive biomarker for the efficacy of regorafenib treatment.
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DOI：
10.1007/s00262-020-02660-2
发表时间：
2021-01
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Arai J;Goto K;Otoyama Y;Nakajima Y;Sugiura I;Kajiwara A;Tojo M;Ichikawa Y;Uozumi S;Shimozuma Y;Uchikoshi M;Sakaki M;Nozawa H;Nakagawa R;Muroyama R;Kato N;Yoshida H
通讯作者：
Yoshida H
影响因子：
6.4
作者：
Wilhelm, Scott M.;Dumas, Jacques;Zopf, Dieter
通讯作者：
Zopf, Dieter
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T
影响因子：
168.9
作者：
Bruix, Jordi;Qin, Shukui;Han, Guohong
通讯作者：
Han, Guohong
影响因子：
25.7
作者：
Jinushi, M;Takehara, T;Hayashi, N
通讯作者：
Hayashi, N