E-viri
Recenzirano
Odprti dostop
-
Zhang, Yu; Gao, Xiaomei; Zhu, Ying; Kadel, Dhruba; Sun, Haoran; Chen, Jing; Luo, Qin; Sun, Haoting; Yang, Luyu; Yang, Jing; Sheng, Yuanyuan; Zheng, Yan; Zhu, Kejin; Dong, Qiongzhu; Qin, Lunxiu
Journal of experimental & clinical cancer research, 04/2018, Letnik: 37, Številka: 1Journal Article
The application of VEGF signaling inhibitors have been associated with more invasive or metastatic behavior of cancers including hepatocellular carcinoma (HCC). We explored the contribution of MET pathway to the enhanced HCC invasion and metastasis by VEGF signaling inhibition, and investigated the antitumor effects of NZ001, a novel dual inhibitor of MET and VEGFR2, in HCC. Immunocompetent orthotopic mice model of hepal-6 was established to investigate the effects of either VEGF antibody alone or in combination with the selective MET inhibitor on tumor aggressiveness. The antitumor effects of NZ001 were examined in cultured HCC cells as well as in vivo models. MET gene amplification was determined by SNP 6.0 assay. MET/P-MET expression was detected by IHC. Selective VEGF signaling inhibition by VEGF antibody significantly reduced in vivo tumor growth of the orthotopic mice models, simultaneously also enhanced tumor invasion and metastasis, but inhibiting MET signaling attenuated this side-effect. Further study revealed that hypoxia caused by VEGF signaling inhibition induced HIF-1α nuclear accumulation, subsequently leading to elevated total-MET expression, and synergized with HGF in inducing invasion. NZ001, a novel dual inhibitor of MET and VEGFR2, markedly inhibited both tumor growth and metastasis of HCC, which showed obvious advantages over sorafenib in not inducing more invasive and metastatic behaviors. This effect is more pronounced in HCC with MET amplification and overexpression. The activation of MET is responsible for the metastasis-promoting effects induced by VEGF inhibition. MET and VEGFR2 dual blockade, NZ001, has advantages over sorafenib in not inducing more invasive and metastatic behaviors; MET amplification and overexpression can be used to identify the subgroup of patients most likely to get the optimal benefit from NZ001 treatment.
Avtor
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.