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Aoki, Shuichi; Inoue, Koetsu; Klein, Sebastian; Halvorsen, Stefan; Chen, Jiang; Matsui, Aya; Nikmaneshi, Mohammad R; Kitahara, Shuji; Hato, Tai; Chen, Xianfeng; Kawakubo, Kazumichi; Nia, Hadi T; Chen, Ivy; Schanne, Daniel H; Mamessier, Emilie; Shigeta, Kohei; Kikuchi, Hiroto; Ramjiawan, Rakesh R; Schmidt, Tyge Ce; Iwasaki, Masaaki; Yau, Thomas; Hong, Theodore S; Quaas, Alexander; Plum, Patrick S; Dima, Simona; Popescu, Irinel; Bardeesy, Nabeel; Munn, Lance L; Borad, Mitesh J; Sassi, Slim; Jain, Rakesh K; Zhu, Andrew X; Duda, Dan G
Gut, 01/2022, Letnik: 71, Številka: 1Journal Article
Intrahepatic cholangiocarcinoma (ICC)-a rare liver malignancy with limited therapeutic options-is characterised by aggressive progression, desmoplasia and vascular abnormalities. The aim of this study was to determine the role of placental growth factor (PlGF) in ICC progression. We evaluated the expression of PlGF in specimens from ICC patients and assessed the therapeutic effect of genetic or pharmacologic inhibition of PlGF in orthotopically grafted ICC mouse models. We evaluated the impact of PlGF stimulation or blockade in ICC cells and cancer-associated fibroblasts (CAFs) using in vitro 3-D coculture systems. PlGF levels were elevated in human ICC stromal cells and circulating blood plasma and were associated with disease progression. Single-cell RNA sequencing showed that the major impact of PlGF blockade in mice was enrichment of quiescent CAFs, characterised by high gene transcription levels related to the Akt pathway, glycolysis and hypoxia signalling. PlGF blockade suppressed Akt phosphorylation and myofibroblast activation in ICC-derived CAFs. PlGF blockade also reduced desmoplasia and tissue stiffness, which resulted in reopening of collapsed tumour vessels and improved blood perfusion, while reducing ICC cell invasion. Moreover, PlGF blockade enhanced the efficacy of standard chemotherapy in mice-bearing ICC. PlGF blockade leads to a reduction in intratumorous hypoxia and metastatic dissemination, enhanced chemotherapy sensitivity and increased survival in mice-bearing aggressive ICC.
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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 | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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