| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2018-03-01 |
| タイトル |
|
|
タイトル |
Development of a novel analgesic for cancer pain targeting brain-derived neurotrophic factor |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 著者 |
TSUGE, Masatsugu
HAZAMA, Keita
KANZAKI, Hirotaka
ITANO, Yoshitarou
MAESHIMA, Kyoichiro
OUCHIDA, Mamoru
NAKATSUKA, Hideki
|
| 著者所属(英) |
|
|
言語 |
en |
|
値 |
Department of Anesthesiology and Intensive Care Medicine 1, Kawasaki Medical School |
| 著者所属(英) |
|
|
言語 |
en |
|
値 |
Department of Anesthesiology and Intensive Care Medicine 1, Kawasaki Medical School |
| 著者所属(英) |
|
|
言語 |
en |
|
値 |
Department of Pharmacy, Okayama University Hospital |
| 著者所属(英) |
|
|
言語 |
en |
|
値 |
Department of Anesthesiology and Intensive Care Medicine 1, Kawasaki Medical School |
| 著者所属(英) |
|
|
言語 |
en |
|
値 |
Department of Anesthesiology and Intensive Care Medicine 1, Kawasaki Medical School |
| 著者所属(英) |
|
|
言語 |
en |
|
値 |
Department of Molecular Oncology, Graduate School of Medicine,
Dentistry and Pharmaceutical Sciences, Okayama University |
| 著者所属(英) |
|
|
言語 |
en |
|
値 |
Department of Anesthesiology and Intensive Care Medicine 1, Kawasaki Medical School |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
BDNF |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Cancer pain |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
TrkB |
| 抄録(英) |
|
|
言語 |
en |
|
値 |
Brain-derived neurotrophic factor (BDNF) is necessary for nerve growth. BDNF is expressed in the dorsal root ganglion (DRG) and modulates pain transduction from peripheral nociceptors. TrkB, which is a BDNF receptor with a tyrosine kinase domain, acts as a pain modulator on the cell membrane of second neuron. If an exogenous truncated TrkB lacking a tyrosine kinase domain can competitively block the binding of BDNF to endogenous TrkB, inhibitory effects on pain are expected. We constructed two expression vectors coding truncated TrkB-GFP fusion proteins, lacking intracellular tyrosine kinase domain, with and without the transmembrane domain. By transfection of the vectors to HEK293 cells, the expression and localization of the modified receptor proteins were confirmed. The truncated TrkB with the transmembrane domain, TM (+), was localized on cell membrane surface of the transfected cells, and capable of BDNF binding on cell surface. TM (-) without the transmembrane domain was secreted from the transfected cells, and the secreted TrkB protein was confirmed the capability for binding with BDNF by pull-down assay. Furthermore, we developed a rat model of cancerous osteocopic pain for evaluating an analgesic effect of the modified TrkB vectors on cancer pain. Pain-related behavior, as assessed by von Frey tests, indicated hyperalgesia after cancer cell administration. BDNF expression was higher on the affected side of the DRG at the third lumbar vertebra L3 than on the unaffected side. When the modified TrkB vectors were administrated to the cancer pain model rats, both the TM (+) and TM (-) vector administration groups exhibited an analgesic effect. These results suggest that the modified TrkB receptors and their vectors are applicable as molecular targeted drugs for pain control in cancer patients. |
| 書誌情報 |
en : Kawasaki medical journal
巻 43,
号 2,
p. 107-120,
発行日 2017
|
| 出版者 |
|
|
出版者 |
Kawasaki Medical Society |
|
言語 |
en |
| ISSN |
|
|
収録物識別子タイプ |
PISSN |
|
収録物識別子 |
0385-0234 |
| ISSN |
|
|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
2434-3404 |
| 書誌レコードID |
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|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12685295 |
| 書誌レコードID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA12029005 |
| DOI |
|
|
関連タイプ |
isIdenticalTo |
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.11482/KMJ-E43(2)107 |
| 記事種別(英) |
|
|
内容記述 |
Regular Article |
|
言語 |
en |
| 関連サイト |
|
|
|
識別子タイプ |
URI |
|
|
関連識別子 |
http://igakkai.kms-igakkai.com/wp/wp-content/uploads/2017en/KMJ-E43(2)107.pdf |
| 著者版フラグ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
PDF (1.2 MB)
