title: Antimitotic and Non-mitotic Effects of Eribulin Mesilate in Soft Tissue Sarcoma.
abstract: BACKGROUND
  Eribulin mesilate (eribulin), a first-in-class halichondrin B-based microtubule dynamics inhibitor, has been shown to promote vascular remodeling and reversal of epithelial-mesenchymal transition (EMT) apart from its antimitotic activity in breast cancer models.
  
  
  METHODS
  Anti-proliferative activity of eribulin was examined in vitro and in vivo in several human soft tissue sarcoma (STS) cell lines. To assess tumor blood perfusion and phenotypic changes, eribulin was investigated in a leiomyosarcoma xenograft and in vitro in liposarcoma and leiomyosarcoma cell lines.
  
  
  RESULTS
  Eribulin showed anti-proliferative activity in vitro against all six cell lines investigated, with 50% inhibitory concentration values of around 1 nmol/l, as well as significant antitumor activity against four xenografts in vivo. In addition, eribulin significantly enhanced tumor blood perfusion in xenografts and induced morphological changes and up-regulation of differentiation marker genes.
  
  
  CONCLUSIONS
  In pre-clinical models, eribulin showed anti-proliferative activity against a variety of histopathological subtypes of STS. Eribulin might also cause tumor vasculature remodeling to enhance tumor blood perfusion and induce tumor cell differentiation.
authors.affiliation: Biology Tsukuba, Oncology Product Creation Unit, Eisai Co., Ltd., Tsukuba-shi, Ibaraki, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawano
authors.affiliation: Biology Tsukuba, Oncology Product Creation Unit, Eisai Co., Ltd., Tsukuba-shi, Ibaraki, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Asano
authors.affiliation: Biology Tsukuba, Oncology Product Creation Unit, Eisai Co., Ltd., Tsukuba-shi, Ibaraki, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Adachi
authors.affiliation: Biology Tsukuba, Oncology Product Creation Unit, Eisai Co., Ltd., Tsukuba-shi, Ibaraki, Japan j2-matsui@hhc.eisai.co.jp.
authors.forename: Junji
authors.initials: J
authors.lastname: Matsui
mesh_terms: D000818:Animals; D050256:Antimitotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005663:Furans / Q000494:pharmacology / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007659:Ketones / Q000494:pharmacology / Q000627:therapeutic use*; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000235:genetics; D012509:Sarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000096985:Calponins; D000095662:Polyether Polyketides
chemical_list: D050256:Antimitotic Agents; D002135:Calcium-Binding Proteins; D005663:Furans; D007659:Ketones; D008840:Microfilament Proteins; D000096985:Calponins; C490954:eribulin; D000095662:Polyether Polyketides
keywords: Eribulin; phenotypic change; soft tissue sarcoma; vascular remodeling