Low-dose metronomic cisplatin as an antiangiogenic and anti-inflammatory strategy for cancer

Hiroshi Kikuchi, Nako Maishi, Li Yu, Zi Jia, Cong Li, Masumi Sato, Ryo Takeda, Keita Ishizuka, Yasuhiro Hida, Nobuo Shinohara, Kyoko Hida

研究成果: ジャーナルへの寄稿学術論文査読

1 被引用数 (Scopus)

抄録

Background: Conventional chemotherapy is based on the maximum tolerated dose (MTD) and requires treatment-free intervals to restore normal host cells. MTD chemotherapy may induce angiogenesis or immunosuppressive cell infiltration during treatment-free intervals. Low-dose metronomic (LDM) chemotherapy is defined as frequent administration at lower doses and causes less inflammatory change, whereas MTD chemotherapy induces an inflammatory change. Although several LDM regimens have been applied, LDM cisplatin (CDDP) has been rarely reported. This study addressed the efficacy of LDM CDDP on tumour endothelial cell phenotypic alteration compared to MTD CDDP. Methods: Tumour growth and metastasis were assessed in bladder cancer-bearing mice treated with LDM or MTD gemcitabine (GEM) and CDDP. To elucidate the therapeutic effects of LDM CDDP, the change of tumour vasculature, tumour-infiltrating immune cells and inflammatory changes were evaluated by histological analysis and mRNA expression in tumour tissues. Results: Tumour growth and bone metastasis were more suppressed by LDM CDDP + MTD GEM treatment than MTD CDDP + MTD GEM. Myeloid­derived suppressor cell accumulation was reduced by LDM CDDP, whereas inflammatory change was induced in the tumour microenvironment by MTD CDDP. Conclusion: LDM CDDP does not cause inflammatory change unlike MTD CDDP, suggesting that it is a promising strategy in chemotherapy.

本文言語英語
ページ(範囲)336-345
ページ数10
ジャーナルBritish Journal of Cancer
130
2
DOI
出版ステータス出版済み - 10-02-2024

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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