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Epithelial mesenchymal eribulin

Wataru Goto, Shinichiro Kashiwagi, Yuka Asano, Koji Takada, Tamami Morisaki, Hisakazu Fujita, Tsutomu Takashima, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND/AIM: Several proteins involved in immune regulation and the relationship among these, the tumor microenvironment, and clinical outcomes of eribulin treatment were evaluated in advanced or metastatic breast cancer patients. PATIENTS AND METHODS: This retrospective cohort study comprised 52 eribulin-treated locally advanced or metastatic breast cancer patients. Cancer tissue samples were obtained before and after treatment in 10 patients. Immunohistochemistry was performed to determine programmed death (PD)-1, CD8, and forkhead box P3 (FOXP3) expression by stromal tumor-infiltrating lymphocytes, and PD-ligand (L1) and PD-L2 expression by cancer cells...
May 2018: Anticancer Research
Nicholas F Dybdal-Hargreaves, April L Risinger, Susan L Mooberry
Microtubule targeting agents (MTAs) are some of the most effective anticancer drugs used to treat a wide variety of adult and pediatric cancers. Building evidence suggests that these drugs inhibit interphase signaling events and that this contributes to their anticancer actions. The effects of diverse MTAs were evaluated following a 2 hour incubation with clinically relevant concentrations to test the hypothesis that these drugs rapidly and differentially disrupt epithelial-to-mesenchymal transition (EMT)-related signaling...
January 19, 2018: Oncotarget
Shinichiro Kashiwagi, Yuka Asano, Wataru Goto, Koji Takada, Katsuyuki Takahashi, Takaharu Hatano, Sayaka Tanaka, Tsutomu Takashima, Shuhei Tomita, Hisashi Motomura, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND/AIM: Eribulin mesylate (eribulin) is currently used for the treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress the epithelial-mesenchymal transition (EMT) of cancer cells and promote tumor vascular remodeling. In this study, we investigated the expression of markers for EMT and hypoxia in sets of clinical specimens collected before and after eribulin treatment to verify its unique mechanisms. PATIENTS AND METHODS: The expression of markers for EMT and cellular hypoxia [E-cadherin, N-cadherin, vimentin, and carbonic anhydrase 9 (CA9)] was examined immunohistochemically in MBC tissues collected from 20 patients before and after chemotherapy with either eribulin (n=10) or paclitaxel (n=10)...
January 2018: Anticancer Research
Eva A Ebbing, Anne Steins, Evelyn Fessler, Phylicia Stathi, Willem Joost Lesterhuis, Kausilia K Krishnadath, Louis Vermeulen, Jan Paul Medema, Maarten F Bijlsma, Hanneke W M van Laarhoven
BACKGROUND & AIMS: Drugs that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2) are the standard treatment of patients with different types of cancer, including HER2-overexpressing gastroesophageal tumors. Unfortunately, cancer cells become resistant to these drugs, so overall these drugs provide little benefit to patients with these tumors. We investigated mechanisms that mediate resistance of esophageal adenocarcinoma (EAC) cells and patient-derived xenograft tumors to ERBB inhibitors...
July 2017: Gastroenterology
Gelareh Eslamian, Caroline Wilson, Robin J Young
Eribulin is a novel microtubule-targeting agent that is approved for the treatment of patients with locally advanced or metastatic breast cancer who have previously received treatment with an anthracycline and a taxane in either the adjuvant or metastatic setting. Eribulin induces mitotic catastrophe leading to cell death but has other important antitumor effects, including reversal of epithelial-mesenchymal transition and remodeling of the tumor vasculature. Eribulin was licensed for the treatment of advanced breast cancer based on results from two large randomized Phase III clinical trials...
2017: OncoTargets and Therapy
Shinichiro Kashiwagi, Yuka Asano, Wataru Goto, Koji Takada, Katsuyuki Takahashi, Satoru Noda, Tsutomu Takashima, Naoyoshi Onoda, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: Eribulin mesylate (eribulin) is currently indicated for treatment of locally advanced or metastatic breast cancer (MBC). It is a cytotoxic agent with unique mechanisms that suppress epithelial-mesenchymal transition (EMT) of cancer cells. On the other hand, Tumor-infiltrating lymphocytes (TILs), which are considered indicators of immune response monitoring, have been reported as prognostic factors and predictors of therapeutic efficacy. We thought that eribulin, which has an EMT-inhibiting mechanism, may produce an antitumor effect by improving the immune microenvironment, and in this study investigated the effects of breast cancer eribulin chemotherapy on the immune microenvironment with TILs as a marker...
2017: PloS One
Hiroko Kitahara, Mariko Hirai, Koroku Kato, George Bou-Gharios, Hiroyuki Nakamura, Shuichi Kawashiri
Inhibition of epidermal growth factor receptor (EGFR) signalling has emerged as a new treatment strategy for oral squamous cell carcinoma (OSCC). Previously, we found that loss of EGFR expression in OSCC was associated with epithelial-mesenchymal transition (EMT), and may have functional implications with regard to resistance to cetuximab, a monoclonal anti-EGFR antibody. Eribulin (a microtubule inhibitor) reportedly renders breast cancer less aggressive, and less likely to metastasise, by triggering mesenchymal‑to‑epithelial (MET) transition...
December 2016: Oncology Reports
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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