| Title |
Low-dose eribulin mesylate exerts antitumor effects in gastric cancer by inhibiting fibrosis via the suppression of epithelial–mesenchymal transition and acts synergistically with 5-fluorouracil
|
|---|---|
| Published in |
Cancer Management and Research, August 2018
|
| DOI | 10.2147/cmar.s167846 |
| Pubmed ID | |
| Authors |
Toru Kurata, Sachio Fushida, Jun Kinoshita, Katsunobu Oyama, Takahisa Yamaguchi, Mitsuyoshi Okazaki, Tomoharu Miyashita, Hidehiro Tajima, Itasu Ninomiya, Tetsuo Ohta |
| Abstract |
Characterized by aggressive proliferation, extensive stromal fibrosis, and resulting drug resistance, peritoneal dissemination in gastric cancer remains associated with poor prognosis. Interaction between cancer and stromal cells accelerates tumor progression via epithelial-mesenchymal transition (EMT), which is one of the major causes of tissue fibrosis, and human peritoneal mesothelial cells (HPMCs) play important roles as cancer stroma in peritoneal dissemination. Transforming growth factor-β (TGF-β) has a pivotal function in the progression of EMT, and Smad proteins play an important role in the TGF-β signaling pathway. Eribulin mesylate (eribulin), a nontaxane microtubule dynamics inhibitor used for the treatment of advanced breast cancer, inhibits EMT changes in triple-negative breast cancer cells. We examined its ability to inhibit tumor progression and EMT changes resulting from the interaction between gastric cancer cells and HPMCs and to act synergistically with 5-fluorouracil (5-FU), a key drug for gastric cancer. Proliferation of gastric cancer cells and HPMCs isolated from healthy omentum was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Following gastric cancer cell/HPMC coculture, EMT markers were detected by immunofluorescence, immunohistochemistry, and Western blotting; invasion assays were performed; and TGF-β and Smad phosphorylation were assessed by Western blotting and enzyme-linked immunosorbent assay. A mouse fibrotic tumor xenograft model was established using gastric cancer cell/HPMC cocultures. The effect of eribulin and/or 5-FU was tested in each case. Eribulin significantly suppressed gastric cancer cell proliferation and EMT changes in MKN-45 gastric cancer cells and HPMCs induced by their interaction in vitro. Eribulin inhibited EMT at much lower concentrations (≥0.5 nM for MKN-45 and ≥0.1 nM for HPMCs) than its half maximal inhibitory concentrations (2.2 nM for MKN-45 and 8.1 nM for HPMCs), and this resulted, at least partly, from the downregulation of TGF-β/Smad signaling. Eribulin administration of ≥0.1 mg/kg suppressed tumor progression (0.1 mg/kg, p=0.02), and fibrosis was inhibited by lower dose (0.05 mg/kg, p=0.008) in the xenograft model. Furthermore, 0.05 mg/kg administration with 5-FU brought about synergistic antitumor effects (p=0.006). Low-dose eribulin combined with 5-FU might be a promising therapy for peritoneal dissemination in gastric cancer. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 17 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 24% |
| Student > Master | 3 | 18% |
| Student > Bachelor | 2 | 12% |
| Other | 2 | 12% |
| Student > Doctoral Student | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 4 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 5 | 29% |
| Agricultural and Biological Sciences | 3 | 18% |
| Medicine and Dentistry | 2 | 12% |
| Unknown | 7 | 41% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 August 2018.
All research outputs
#14,138,420
of 23,100,534 outputs
Outputs from Cancer Management and Research
#527
of 2,019 outputs
Outputs of similar age
#179,542
of 331,040 outputs
Outputs of similar age from Cancer Management and Research
#30
of 89 outputs
Altmetric has tracked 23,100,534 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,019 research outputs from this source. They receive a mean Attention Score of 3.0. This one has gotten more attention than average, scoring higher than 72% of its peers.
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We're also able to compare this research output to 89 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 66% of its contemporaries.