Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial–mesenchymal transition (EMT) to mesenchymal–epithelial transition (MET) states

Yoshida, Takeshi; Ozawa, Yoichi; Kimura, Takayuki; Sato, Yuki; Kuznetsov, Galina; Xu, Shan; Uesugi, Mai; Agoulnik, Sergei; Taylor, Noel; Funahashi, Yasuhiro; Matsui, Junji

doi:10.1038/bjc.2014.80

Cited by 310 publications

(362 citation statements)

References 30 publications

(40 reference statements)

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“…The survival benefit of eribulin was also apparent in patients with human epidermal growth factor receptor 2 (HER2)-negative or triple-negative breast cancer (15). Interestingly, in a preclinical study, eribulin demonstrated unique effects such as reversed EMT and induced mesenchymal-epithelial transition (MET) (16). This process may explain the clinical observation of prolonged OS in eribulin-treated patients.…”

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confidence: 99%

Eribulin Promotes Antitumor Immune Responses in Patients with Locally Advanced or Metastatic Breast Cancer

Goto

Kashiwagi

Asano

et al. 2018

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confidence: 99%

Eribulin Promotes Antitumor Immune Responses in Patients with Locally Advanced or Metastatic Breast Cancer

Goto

Kashiwagi

Asano

et al. 2018

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“…Among these novel therapeutic armamentariums of soft tissue sarcoma, only eribulin showed the improvement of overall survival in a phase III trial, 3 although angiosarcoma was not included in it. In addition to its antitubulin effect, unique effects of eribulin have been reported on breast cancer in vitro, such as switching the phenotype of cancer cells from mesenchymal to epithelial state, decreasing the capacity of migration and invasion of cancer cells, 4 and improving perfusion in the tumor by vascular remodeling.…”

Section: Case Of Angiosarcoma Of the Scalp Successfully Controlled Bymentioning

confidence: 99%

“…These findings are very rare, because there has been only one report of clear cell sarcoma with intraepidermal nests. 4 It still remains a possibility that nests of tumor cells bordered the epidermis mimicking intraepidermal nests. …”

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confidence: 99%

Case of angiosarcoma of the scalp successfully controlled by eribulin

Wada

Uchi

Furue

2017

The Journal of Dermatology

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sized subcutaneous tumor on his right heel (Fig. 1a). Blue and brown discoloration were observed on the skin surface of the lesion. Magnetic resonance imaging (MRI) revealed a poorly marginated, 3.5 cm 9 6.0 cm 9 2.0 cm tumor with contrast effects within the dermis. T 1 -weighted MRI showed high signal intensity (Fig. 1b), while T 2 -weighted MRI showed low signal intensity (Fig. 1c). Hemangioma with thrombus, hematoma and sarcoma were suspected, and excisional biopsy was performed for diagnosis. Histopathological findings revealed a well-circumscribed nodule (Fig. 1d), composed of epithelioid and spindle cells with clear cytoplasm, and giant cells intermingled with collagen tissues (Fig. 1e). Intraepidermal nests were also observed at the dermoepidermal junction, but limited within small areas of the tips of the rete ridges (Fig. 1f,g). Intraepidermal ascent of tumor cells was not observed. Most of the tumor cells were positive for S100 protein (Fig. 1h), Melan-A (Fig. 1i) and HMB-45 (Fig. 1j) Case of angiosarcoma of the scalp successfully controlled by eribulinDear Editor, Eribulin is a novel microtubule inhibitor recently approved for treatment of soft tissue sarcoma in Japan, which has never been reported to be administrated for angiosarcoma. Here, we report the first case of angiosarcoma successfully controlled by eribulin.A 70-year-old man was referred to our hospital in May 2015 for investigation of refractory erythema on his head. Physical examination revealed erythematous and bruise-like lesions accompanied with a black nodule on the scalp (Fig. 1a). Histopathological examination showed ramifying channels lined by atypical endothelial cells in the dermis (Fig. 1b,c), and immunohistochemically these cells were positive for CD31 (Fig. 1d) and factor VIII (Fig. 1e). He was diagnosed with angiosarcoma of the scalp, and a computed tomography scan did not indicate either lymph node or distant metastasis. 116

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“…Recently, it has been demonstrated that the epithelial-mesenchymal transition (EMT) is a crucial process that is often activated during cancer invasion and metastasis and also induces chemoresistance in cancer treatment (17,18). It has been reported that eribulin mesylate has significant effects on EMT-related pathways, resulting in increased antitumor effects (19,20). The present study clearly shows that eribulin mesylate has antitumor effects, namely reducing cell viability and inducing morphological changes in tumor cells, which could be beneficial in clinical therapy for gemcitabine-refractory advanced pancreatic cancer.…”

Section: Figure 2 Cell Viability In the Aspc-1 (A) And Panc-1 (B) Pamentioning

confidence: 99%

Antitumor Effects of Eribulin Mesylate in Gemcitabine-resistant Pancreatic Cancer Cell Lines

Takezaki

Namikawa

Koyama

et al. 2016

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Abstract. Background respectively), but had no effect on hPE cells. Microscopic examination of Pancreatic cancer is a commonly diagnosed cancer worldwide, with an extremely poor prognosis, and is the fourth leading cause of cancer-related deaths (1). In patients with recurrent, metastatic, or advanced pancreatic cancer, chemotherapy can prolong survival and improve quality of life compared with best supportive care (2, 3). In recent years, gemcitabine, a novel pyrimidine nucleoside analog, has become the standard chemotherapeutic agent used in patients with pancreatic cancer (3). Despite considerable efforts to improve outcomes for these patients, response rates to chemotherapy remain low and the median survival of patients with advanced disease remains in the range of 6 to 10 months (3, 4). Therefore, more effective drugs or combination therapies for pancreatic cancer are needed. and human pancreatic endoderm (hPE) cells were used to evaluate the antitumor effects of gemcitabine and eribulin mesylate. Cell viability after treatment of cells with different concentrations of gemcitabine and eribulin mesylate was evaluated using water-soluble tetrazolium salts (WST) assays; cytotoxic effects were evaluated on the basis of morphological changes to cells. Results: Gemcitabine had no effect on cell viability of AsPC-1 nor Panc-1 cells, whereas gemcitabine reduced cell viability of SUIT-2 cells in a dose-dependent manner. Eribulin mesylate significantly reduced cell viability of bothEribulin mesylate, a completely synthetic macrocyclic ketone analog of halichondrin B, which is a natural large polyether macrolide from a rare marine Japanese sponge, acts as a tubulin-binding agent, interfering with microtubule dynamics and suppressing microtubule polymerization without affecting depolymerization (5, 6). Although eribulin mesylate is a novel drug that has shown significant activity and efficacy in heavily pretreated patients with refractory breast cancer, its efficacy in the treatment of pancreatic cancer in patients with a poor prognosis is not clear (7). In the present study, we investigated the antiproliferative effects of eribulin mesylate in three different pancreatic cancer cell lines. Materials and MethodsMaterials and reagents. The present study was performed on three human pancreatic cancer cell lines (AsPC-1, Panc-1, and SUIT-2) and human pancreatic endoderm (hPE) cells. The AsPC-1 and Panc-1 cell lines were purchased from the European Collection of Authenticated Cell Cultures (Salisbury, Wiltshire, UK), the SUIT-2 cell line was purchased from the Japan Health Sciences Foundation (Tokyo, Japan), and the hPE cell line was purchased from Cell Systems Corporation (Kirkland, WA, USA). Dulbecco's modified Eagle's medium (DMEM) and antibiotics (penicillin, streptomycin) were purchased from Invitrogen Corporation (New York, NY, USA). Co. Ltd, Tokyo, Japan) and gemcitabine (Gemzar powder; Eli Lilly Co. Ltd, Tokyo, Japan) were created by diluting the drugs in water to a concentration of 0.5 μg/μl; stock solutions...

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Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial–mesenchymal transition (EMT) to mesenchymal–epithelial transition (MET) states

Cited by 310 publications

References 30 publications

Eribulin Promotes Antitumor Immune Responses in Patients with Locally Advanced or Metastatic Breast Cancer

Eribulin Promotes Antitumor Immune Responses in Patients with Locally Advanced or Metastatic Breast Cancer

Case of angiosarcoma of the scalp successfully controlled by eribulin

Antitumor Effects of Eribulin Mesylate in Gemcitabine-resistant Pancreatic Cancer Cell Lines

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