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Epithelial mesenchymal eribulin

Satoshi Kawano, Makoto Asano, Yusuke Adachi, Junji Matsui
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. MATERIALS AND 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...
April 2016: Anticancer Research
Nicholas F Dybdal-Hargreaves, April L Risinger, Susan L Mooberry
Eribulin mesylate (eribulin), an analogue of the marine natural product halichondrin B, is a microtubule-depolymerizing drug that has utility in the treatment of patients with breast cancer. Clinical trial results have demonstrated that eribulin treatment provides a survival advantage to patients with metastatic or locally advanced breast cancer previously treated with an anthracycline and a taxane. Furthermore, a pooled analysis of two pivotal phase III trials has demonstrated that eribulin also improves overall survival in several patient subgroups, including in women with HER2-negative disease and triple-negative breast cancer...
June 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Zoltán Dezső, Judith Oestreicher, Amy Weaver, Stephanie Santiago, Sergei Agoulnik, Jesse Chow, Yoshiya Oda, Yasuhiro Funahashi
OBJECTIVES: Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B. Eribulin is a mechanistically unique inhibitor of microtubule dynamics. In this study, we investigated whether selective signal pathways were associated with eribulin activity compared to paclitaxel, which stabilizes microtubules, based on gene expression profiling of cell line panels of breast, endometrial, and ovarian cancer in vitro. RESULTS: We determined the sets of genes that were differentially altered between eribulin and paclitaxel treatment in breast, endometrial, and ovarian cancer cell line panels...
2014: PloS One
Masato Terashima, Kazuko Sakai, Yosuke Togashi, Hidetoshi Hayashi, Marco A De Velasco, Junji Tsurutani, Kazuto Nishio
Triple-negative breast cancer (TNBC) is associated with a higher incidence of recurrence and distant metastasis and a poor prognosis, whereas effective treatment strategies remain to be established. Finding an effective treatment for TNBC has become imperative. We examined the effect of the combination of S-1 (or 5-FU in an in vitro study) and eribulin in TNBC cell lines. The in vitro effect of the combination was examined in four TNBC cell lines (MDA-MB-231, MDA-MB-468, BT-549 and MX-1) using a combination index and isobolograms...
2014: SpringerPlus
Yasuhiro Funahashi, Kiyoshi Okamoto, Yusuke Adachi, Taro Semba, Mai Uesugi, Yoichi Ozawa, Osamu Tohyama, Taisuke Uehara, Takayuki Kimura, Hideki Watanabe, Makoto Asano, Satoshi Kawano, Xavier Tizon, Paul J McCracken, Junji Matsui, Ken Aoshima, Kenichi Nomoto, Yoshiya Oda
Eribulin mesylate is a synthetic macrocyclic ketone analog of the marine sponge natural product halichondrin B and an inhibitor of microtubule dynamics. Some tubulin-binding drugs are known to have antivascular (antiangiogenesis or vascular-disrupting) activities that can target abnormal tumor vessels. Using dynamic contrast-enhanced MRI analyses, here we show that eribulin induces remodeling of tumor vasculature through a novel antivascular activity in MX-1 and MDA-MB-231 human breast cancer xenograft models...
October 2014: Cancer Science
T Yoshida, Y Ozawa, T Kimura, Y Sato, G Kuznetsov, S Xu, M Uesugi, S Agoulnik, N Taylor, Y Funahashi, J Matsui
BACKGROUND: Eribulin mesilate (eribulin), a non-taxane microtubule dynamics inhibitor, has shown trends towards greater overall survival (OS) compared with progression-free survival in late-stage metastatic breast cancer patients in the clinic. This finding suggests that eribulin may have additional, previously unrecognised antitumour mechanisms beyond its established antimitotic activity. To investigate this possibility, eribulin's effects on the balance between epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) in human breast cancer cells were investigated...
March 18, 2014: British Journal of Cancer
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