| Title |
Antitumor effects of minodronate, a third-generation nitrogen-containing bisphosphonate, in synergy with γδT cells in human glioblastoma in vitro and in vivo
|
|---|---|
| Published in |
Journal of Neuro-Oncology, July 2016
|
| DOI | 10.1007/s11060-016-2186-x |
| Pubmed ID | |
| Authors |
Tsutomu Nakazawa, Mitsutoshi Nakamura, Ryosuke Matsuda, Fumihiko Nishimura, Young Soo Park, Yasushi Motoyama, Yasuo Hironaka, Ichiro Nakagawa, Hiroshi Yokota, Shuichi Yamada, Kentaro Tamura, Yasuhiro Takeshima, Kouji Omoto, Yoshitaka Tanaka, Yukiteru Ouji, Masahide Yoshikawa, Takahiro Tsujimura, Hiroyuki Nakase |
| Abstract |
Nitrogen-containing bisphosphonates (N-BPs), which prevent bone resorption, exert direct and γδT cell (GDT)-mediated antitumor effects against several tumor cell types, including glioblastoma (GBM). However, limited information is available regarding the antitumor effects of N-BPs in GBM. Specifically, the antitumor effects of minodronate (MDA), a third-generation N-BP, in GBM are yet unclear. This study aimed to investigate the antitumor effects of MDA in GBM in vitro and in vivo. We performed growth inhibition and apoptosis detection assays using the GBM cell lines U87MG and U138MG. Apoptosis inhibition assays were also conducted. In vivo xenograft assays were performed in highly immunodeficient NOD.Cg-Prkdc(scid) Il2rg(tm1Sug)/Jic mice subcutaneously implanted with U87MG and U138MG cells. Growth inhibition and apoptosis detection assays demonstrated that MDA inhibited GBM cell growth via apoptosis, which was markedly enhanced by ex vivo expanded GDT. A pan-caspase inhibitor, z-VAD-fmk, inhibited MDA-induced U138MG apoptosis and MDA/GDT-induced U87MG and U138MG apoptosis. But z-VAD-fmk increased MDA-induced U87MG apoptosis. MDA/GDT-mediated apoptosis was blocked by the anti-T cell receptor (TCR) Vγ9, mevalonate pathway inhibitor, granzyme B inhibitor, and antitumor necrosis factor (TNF)-α. In vivo xenograft assays showed that combined intraperitoneal administration of MDA/GDT induced antitumor effects on unestablished U87MG-derived subcutaneous tumors. MDA exerted direct and GDT-mediated anti-GBM apoptotic effects in a caspase-dependent manner. GDT recognized MDA-exposed GBM cells via TCRVγ9 and induced apoptosis via granzyme B and TNF-α release. Because MDA elicited anti-GBM effects in synergy with GDT in vivo, a combination of MDA and ex vivo-generated GDT could be an effective treatment in patients with GBM. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 23 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 23 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 17% |
| Student > Master | 3 | 13% |
| Professor > Associate Professor | 2 | 9% |
| Researcher | 2 | 9% |
| Student > Bachelor | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 10 | 43% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 5 | 22% |
| Engineering | 2 | 9% |
| Sports and Recreations | 1 | 4% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
| Neuroscience | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 12 | 52% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 10 July 2016.
All research outputs
#18,465,704
of 22,880,230 outputs
Outputs from Journal of Neuro-Oncology
#2,244
of 2,977 outputs
Outputs of similar age
#270,778
of 354,871 outputs
Outputs of similar age from Journal of Neuro-Oncology
#35
of 54 outputs
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